Specialty Pharmacy Continuum - March / April 2021

Serving managed care, health-system and specialty decision makers Volume 10 • Number 2 • March/April 2021 • specialtypharmacycontinuum.com

OPERATIONS & MGMT Collaboration speeds access to less costly oral oncolytics ....................

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Outsourcing SP model carries some risk ...............

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PAPs Flex Their Muscles During COVID-19

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olitical divisiveness on Capitol Hill and the ongoing push for financial relief for the COVID-19 pandemic so far have caused a slowdown in the Biden administration’s ability to make sweeping changes affecting health care, a policy expert said during Informa’s Hub and SPP Model Optimization 2021 virtual event.

As cabinet positions are filled, more aspects of the Biden plan for public aspe health and the health care environment hea will take clearer shape. Until then, legislative action from Congress is likely islati to be llimited and focused on very particareas, said James Kim, JD, MPH, the ular ar

CLINICAL Managing HCV infection and organ donation ....... 12 Better options for treating resistant HIV ...

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The hidden pandemic of misdosing ......................

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POLICY A single-dose COVID-19 vaccine enters the fray ...................

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TECHNOLOGY Remote monitoring for diabetes, heart disease .................................

REVIEW ARTICLE

The Role of Specialty Pharmacy in

Managing Rheumatoid Arthritis See page 8.

Continued on page 21

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The Year Ahead For Rx Pricing: A Waiting Game

he COVID-19 pandemic continues to have a profound effect on patient access to needed therapies and is shedding light on the care needs of vulnerable patient populaations, speakers said during Informa’s PAP Critical Update 2021 virtual event.

To help ensure medications remained accessible, many patient assistance programs (PAPs), drug manufacturers ers and some payors quickly adapted to a virtual environment, expanding programs and relaxing some requirements.

These stakeholders have responded with a wide range of programs. Independent foundation support, for example, expanded to cover additional areas of need, such as nonmedical day-to-day costs, essential expenses such as utilities and rent, and transportation for patients to get to different locations for their care. Manufacturers, public health organizations and charitable community health clinics donated emergency relief funds and personal protective equipment, and expanded free drug programs to address gaps caused by job loss, furloughs and the loss of health insurance.

PAPs also had to shift quickly to meet patient demand, helping patients stay on therapy because care was disrupted as shelter-in-place orders went into effect last spring, said Emily Gibb, the senior director of public policy at GlaxoSmithKline (GSK) and president of the GSK Patient Access Foundation.

pecialty pharmacists are key stakeholders in the distribution network for rare disease drugs, and they should be considered part of the pharmaceutical manufacturer team in getting patients access to needed therapies, a panel of experts said during Informa’s Hub and SPP Model Optimization 2021 virtual event.

Training and education for specialty pharmacies and their pharmacists around drug products must be ongoing and continual, said Dave MacLeod, the head of patient services and specialty pharmacy operations for Amylyx Pharmaceuticals.

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Continued on page 7

A Call C for More SP SPs on Rare D Disease Teams

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3

Specialty Pharmacy Continuum • March/April 2021

OPERATIONS & MANAGEMENT

Collaborative Ca Agreements Cut Time, Costs A collaborative practice agreement (CPA) for oral oncolytics implemented at St. Luke’s Cancer Institute, in Boise, Idaho, slashed turnaround times for oral oncolytic drug processing and saved thousands in drug costs.

The CPA expanded the scope of pharmacy practice while helping patients and providers, according to Amanda Wright, PharmD, an oncology pharmacist at St. Luke’s. “Implementing a CPA for oral oncolytics has helped our providers devote more time to aspects of patient care they are uniquely skilled to do,” said Wright, “while pharmacists have been able to make sure that treatments are dosed appropriately and that patients initiate and continue their therapy safely and in a timely manner.”

St. Luke’s already had a CPA in place allowing five clinical pharmacists at their oral oncolytic office to help providers individualize antiemetic regimens for patients at the institute’s ambulatory care clinics, she said.

These pharmacists also helped optimize oral oncolytic regimens by ensuring new prescriptions were indication appropriate, reviewing laboratory tests and concurrent medications, providing patient medication counseling, performing follow-ups to complete refills, and assessing adverse effects, adherence issues and new medications.

However, “any changes pharmacists made to a prescription required provider approval, which took between a few hours to a few days to receive,” Wright said. This interrupted pharmacists’ workflow and, “since we needed to check the patient’s electronic medical record to see if the prescriptions had been signed,” she said, “it

also resulted in occasional delays in treatment initiation or continuation.”

Wright and her team decided a CPA could overcome these inefficiencies. They identified a list of clinical activities that pharmacists could perform as part of an oral oncolytic CPA. These activities ranged from dose adjustments based on patient indications, renal and hepatic function, and toxicities; dose rounding to help cut drug costs; signing off on medication renewals; and ordering laboratory tests and examinations.

“We presented these ideas as well as some metrics we would be looking at to our P&T [pharmacy and therapeutics] committee and to the providers and pharmacists that would be involved in a pilot project, and we incorporated their feedback and received approval,” Wright said.

The CPA proved its value in a pilot project conducted between November 2018 and February 2019, said Wright, presenting data on the project during the Association of Community Cancer Centers 2020 Virtual National Oncology Conference. Comparing

‘Not only were we able to improve the pharmacy workflow, we also reduced the time to initiation or continuation of patient treatment.’

—Amanda Wright, PharmD

6 Strategies for Implementing a Successful CPA Amanda Wright, PharmD, an oncology pharmacist at St. Luke’s Cancer Institute, in Boise, Idaho, shared some tips for pharmacists trying to set up collaborative practice agreements (CPAs) at their institutions to help oncology providers and improve patient care.

Develop rapport with the interdisciplinary team. “This is one of the most important steps, because establishing a relationship of trust with nurse practitioners and providers will allow pharmacists to complete their interventions without interruption.”

Identify areas where pharmacy can help providers with oral oncolytics. “Find areas where providers’ medication management workflows are challenging.

The goal is for both pharmacists and providers to complete their tasks in a timely manner.”

Discuss and determine the best approach with the provider team. “Make sure the goals of pharmacists and providers are aligned, with the best interest of patients at heart, and identify provider

champions to review the pharmacist clinical activities and offer feedback on their expectations in the initial stages of creating the CPA.”

Create and present the CPA to the administrative team. “Provide a comprehensive look at the agreement you’ve created, including what goals you have for implementing the CPA. This will help get the buy-in and support you need before going ahead with this.”

Evaluate the CPA to share its impact on the clinic workflow. “A great aspect of how we set up our agreement was that we created data collection goals as part of the CPA. We found ways to evaluate the CPA and its impact within the clinic.”

Request feedback from all members of the team. “Make sure necessary adjustments are made so that patients receive the best care. The great thing about CPAs is that they’re really easy to tailor to the needs of your clinic” to allow you “to provide the best patient care.”

the intervention group of 54 patients treated by four providers with a group to 87 patients managed during the same period by 11 providers not operating under the CPA, they found prescription turnaround times averaged seven minutes in the CPA group and 55 hours in the control group.

Dose-rounding interventions for two patients in the pilot group also led to significant cost savings, with one capecitabine prescription rounded to the nearest tablet size resulting in $547 in savings per treatment cycle ($9,858 annually), and a rounded temozolomide prescription saving $252 per cycle ($3,281 annually).

Most providers were very satisfied with the new oral oncolytic CPA and believed it had a positive impact, saying they would recommend its use across other clinics at St. Luke’s, Wright noted.

Indeed, the CPA was subsequently rolled out across St. Luke’s. Data collected over a three-month period from all 15 providers found the average prescription processing turnaround time was six minutes.

“Not only were we able to improve the pharmacy workflow, we also reduced the time to initiation or continuation of patient treatment,” said Wright, noting that they have not yet found cost savings associated with the CPA since the systemwide rollout.

Jane Rogers, PharmD, a clinical pharmacy specialist at The University of Texas MD Anderson Cancer Center, in Houston, who was not involved with the initiative, said the reductions in prescription turnaround time and cost savings that Wright and her team reported are “striking” and demonstrate the value of pharmacists in cancer care.

“Oncology is an area with a tremendous need for services such as the ones highlighted in this study,” Rogers commented. Management of complex polypharmaceutical cancer regimens and their adverse effects and counseling on use of herbal and vitamin supplements are other important areas where clinical pharmacists can improve patient care, she said, predicting that “more publications like Wright and her team’s will help pave the way to make these services a normal part of everyday practice.”

—David Wild

—D.W. The sources reported no relevant financial disclosures.

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Specialty Pharmacy Continuum • March/April 2021

OPERATIONS & MANAGEMENT

Clinics, Home Rx Spur Chemotherapy Savings With the right mix of people and processes, many chemotherapy treatments can be safely transitioned from inpatient to outpatient settings, reducing inpatient stays and slashing hundreds of thousands of dollars from the drug budget, according to a presentation at the Association of Community Cancer Centers 2020 Virtual National Oncology Conference.

“Institutions can save money they may otherwise lose in the inpatient setting by seeking reimbursement based on a buy-and-bill model, purchasing therapies under 340B if they’re eligible, billing for waste, and gaining access to patient assistance programs,” Ali McBride, PharmD, the clinical coordinator and supervisor of hematology/oncology at the University of Arizona Cancer Center, in Tucson, told attendees.

McBride explained that several years ago, he and his colleagues reviewed some of the highest-cost inpatient chemotherapies administered at their institution and found that some treat-

lists and laboratory tests for any safety concerns, McBride said.

“Another important piece our clinical pharmacists provide is staff and patient clinical education, and they also address adherence to supportive care medications and decrease inpatient drug waste, which has been key to the cost savings aspect of the program,” McBride said.

Staff pharmacists also resolve billing issues, transition eligible

‘More often than not, chemotherapy was being given in the inpatient setting just because it could be given in that setting.’

—Ali McBride, PharmD ments were appropriately being administered in the inpatient setting because of the need for closer monitoring in higher acuity patients, but “more often than not, chemotherapy was being given in the inpatient setting just because it could be given in that setting.”

Building the Right Team To shift some of these therapies to the outpatient setting safely and successfully and champion the program to get buy-in from leadership and physicians, McBride and his colleagues assembled a team that included physicians, advanced practitioners, nurse coordinators, risk management and information technology staff, and others.

Clinical and staff pharmacists have played leading roles on the team and throughout the initiative, he said. Specifically, functions have included screening patients for outpatient chemotherapy eligibility, ensuring individuals have a way of getting to infusion centers, helping arrange after-hours care for patients and caregivers, and securing infusion pumps for home infusion recipients.

They also provide supportive care medications and review patients’ medication

inpatient chemotherapy orders to the outpatient setting, and help reduce drug waste by batch compounding therapies when possible, McBride added.

Starting With Rituximab As McBride reported, his team identified rituximab as a good place to start in their shift to outpatient chemotherapy administration. “While most of our rituximab patients were receiving this drug on the same day as their inpatient chemotherapy, they were also all being given pegfilgrastim in the outpatient setting the day after discharge, so we moved [rituximab] to the day after discharge,” McBride said. He noted that this transition does not affect the safety or efficacy of the drug or the broader regimen.

The team analyzed the use of rituximab for lymphoma patients during a four-year period beginning in 2015, when they implemented the rituximab transition, identifying 35 patients who received rituximab in the inpatient setting and 137 who received it in the outpatient setting. “Some of those who received it as inpatients required other inpatient therapy, while others

Chemotherapy Transition Checklist Is the selected chemotherapy available to be administered on an outpatient basis?

Do you have financial approval, including that for reimbursement for infusion pumps, from insurers?

Do infusion center hours allow for the administration of the chemotherapeutic agents?

Are nursing staff, including nurse coordinators and infusion nurses, trained to provide patient education and monitor side effects for the given agent?

Are pharmacy staff trained to provide patient education on the regimens and supportive care treatments?

may have been admitted as inpatients for their first cycle of chemotherapy,” McBride noted.

Nearing $1 Million in Savings Switching to outpatient administration for the 137 rituximab recipients yielded an estimated savings of $925,000, due to approximately $450,000 in drug cost savings, since patients made use of medication assistance programs, as well as reduced hospital costs from an average nine-hour reduction in inpatient stays.

“We also billed to the nearest milligram, which increased reimbursement for waste,” McBride added. Ultimately, his team hopes to provide 90% of rituximab doses in the outpatient setting and is transitioning several other chemotherapy treatments to outpatient administration.

McBride said modifying order sets and integrating outpatient and inpatient electronic health records led to a “rapid uptick” in physician prescribing of outpatient treatment.

“Physicians really welcomed the shorter inpatient stays,” said McBride, noting that concerns about preserving inpatient resources and keeping patients out of the hospital, when possible, during the COVID-19 pandemic has made the program even more popular.

Karen Fancher, PharmD, an associate professor of pharmacy practice in

oncology acute care at Duquesne University School of Pharmacy, in Pittsburgh, said she was “very impressed by the number of chemotherapy regimens transitioned to the outpatient setting” at the University of Arizona Cancer Center.

“This program provides a lot of tangible evidence that many traditionally inpatient chemotherapy regimens can be safe, feasible and cost-effective to provide in the outpatient setting,” said Fancher, who was not involved with the initiative.

Obtaining Buy-In Although the results of the program are compelling, she said obtaining buy-in from practitioners and creating the workflow changes necessary for a successful outpatient chemotherapy program could make it challenging for others to implement similar initiatives. “Individual institutions would need to spend a lot of time and personnel resources preparing to get this type of program up and running,” Fancher said. “I think it will take a while for this approach to be widely utilized, especially in smaller centers.”

—David Wild McBride reported financial relationships with Coherus and Pfizer. Fancher reported no relevant financial disclosures.

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Specialty Pharmacy Continuum • March/April 2021

OPERATIONS & MANAGEMENT

Data Show the Way to Safer Cancer Care Outpatient chemotherapy clinics are finding innovative ways to better manage patients at the highest risk for hospital admission or emergency department (ED) visits within 30 days of treatment.

Tennessee Oncology and Mercy, a health system with facilities in Arkansas, Kansas, Missouri and Oklahoma, have been have been using technology to improve communication between facilities and help cancer patients get the care they require in the outpatient setting, reducing the need for emergency hospital care.

“Through proactive management, we should be able to avoid many of the treatments outpatient chemotherapy patients are receiving at the hospital or ED,” Michelle Smith, DC, the director of oncology services at one of Mercy’s hospitals (Mercy St. Louis), said at the Association of Community Cancer Centers (ACCC) 2020 Virtual National Oncology Conference.

Smith’s sentiment is in line with recommendations from the Centers for Medicare & Medicaid Services (CMS).

Earlier this year, as part of its Hospital

records from 8,319 of their adult patients with cancer who received at least one outpatient chemotherapy infusion between 2016 and 2018. They found that malnutrition and certain types of chemotherapy were most strongly associated with 30-day inpatient admission, whereas severe pain and social deprivation were strong predictors of ED visits within 30 days of chemotherapy.

Using these and other risk factors, the Mercy team developed a predictive algorithm that pulls data from their electronic health record (EHR) system.

The algorithm identifies patients at high or intermediate risk for a hospital admission or ED visit within 30 days of outpatient chemotherapy and automatically generates a report every night that is added to the system’s oncology dashboard. The report also is sent to the system’s clinics, infusion centers and nurse navigators each day, Smith explained.

Outpatient Quality Reporting Program, CMS rolled out the Admissions and Emergency Department (ED) Visits for Patients Receiving Outpatient Chemotherapy measure (OP-35) (https://cmit. cms.gov/CMIT_public/ReportMeasure? measureRevisionId=672). “Chemotherapy-related admissions and ED visits may be due to outpatient chemotherapy patients having unmet needs and gaps in care,” the agency pointed out.

“Once the clinic receives the report, if a patient on the list has an appointment that day, they will be asked to complete a questionnaire to identify areas of need ahead of their physician appointment, so that the physician has an opportunity to address those needs at the clinic visit,” she said.

Staff at infusion centers act as “a second set of eyes” for patients with an infusion appointment that day, Smith said, explaining that they administer the same questionnaire and identify needs that they can address on their end. These include interventions such as educating patients about medication side effects, reviewing their home medications or, if necessary, alerting the treating physician about any issues they need to address.

Finally, if a patient does not have a

Identifying Risk Factors After finding that Mercy’s 30-day hospital admission rate for outpatient chemotherapy recipients was 15.9%, compared with the CMS benchmark of 12.9%, Smith and her colleagues sought to identify risk factors for admission or ED visits within 30 days of outpatient chemotherapy.

To that end, they analyzed medical

clinic or infusion appointment on the day they are flagged as being at high risk for an ED visit or hospital admission, a nurse navigator will call them and identify areas of need, either addressing them during the call or contacting the physician if needed, Smith said.

“The goal is to get the hospital as much information as we can to make that visit as quick and efficient as possible,” Bilbrey said, adding that the nurse care coordinator also receives a patient discharge alert and follows up with the patient to provide additional care

‘Using these algorithms and managing comorbidities on our end, rather than having patients wait to see their primary care provider … or going to the ED and hospital, can drive costs down and improve patient satisfaction.’

—Larry Bilbrey Tennessee Oncology Tennessee Oncology, an outpatient chemotherapy network with more than 30 locations across that state, also is employing algorithms to reduce rates of hospital admission and ED visits within 30 days of chemotherapy.

“Prior to our project, we had no way of knowing when a patient presented to an ED or hospital or when they were discharged,” said Larry Bilbrey, the network’s care data systems manager, during the ACCC meeting. That was important information for them to have because it would allow them to share information with the hospital to expedite the visit, he said.

Tennessee Oncology now contracts with a data vendor in Tennessee, which alerts a nurse care coordinator at the network when any of their chemotherapy patients have registered at an ED or a hospital admissions desk.

“The coordinator can then log into a portal to identify the patient and call the hospital to find out the reason for their visit or admission,” he explained, noting that direct contact with the hospital is important because hospitals sometimes do not document a diagnosis in their EHR until after admission or discharge.

During the phone call, the nurse care coordinator can share test results or other information on file at Tennessee Oncology, avoiding duplicate testing, and they can also determine whether the patient can receive any of the suggested treatments in the outpatient setting. When appropriate, the nurse care coordinator contacts the patient’s Tennessee Oncology physician for guidance, and the provider can contact the hospital directly to discuss the patient’s management, Bilbrey said.

or schedule a follow-up visit or clinic appointment, if needed.

Proactively Targeting Comorbid Conditions Beyond making their patients’ hospital visits more efficient, Bilbrey and his team also wanted to improve how they manage some of the common comorbidities, such as chronic obstructive pulmonary disease, diabetes mellitus, congestive heart failure and pain, that account for a large number of hospital admissions and ED visits.

“The problem is that many of our patients do not disclose comorbidities to the chemotherapy clinic,” he said.

To overcome this obstacle, information technology experts at Tennessee Oncology developed a management algorithm that draws information from their EHR that points to one of the high-risk comorbid conditions. This includes laboratory values, medications and information from physician notes, which the algorithm incorporates using natural language processing.

When the algorithm identifies a patient as possibly having one of these comorbidities, it alerts a nurse care coordinator, who calls the patient and further employs the algorithm to confirm a diagnosis and provide clinical support, Bilbrey said.

While the Tennessee Oncology team is in the process of studying the impact of the initiative in a subset of patients, Bilbrey said, “it’s hard to imagine that having this data won’t improve our care.” He predicted that “using these algorithms and managing comorbidities on our end, rather than having patients wait to see their primary care provider or specialist or going to the ED and hospital, can drive costs down and improve patient satisfaction.”

—David Wild The sources reported no relevant financial disclosures.

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Specialty Pharmacy Continuum • March/April 2021

OPERATIONS & MANAGEMENT

Outsourcing SP Expertise? Warnings to Heed As more health systems enter the specialty pharmacy space, many are using an outside third-party entity to manage their on-site specialty pharmacies. Although the arrangements offer many benefits, stakeholders need to be ready for state and federal scrutiny surrounding anti-kickback statutes, reimbursement and other compliance issues that could derail these arrangements if they are not managed proactively.

In these partnerships, the pharmacies are still owned by the hospitals, but they’re managed by outside vendors with specific expertise in specialty pharmacy operations—such as Recept, Shields Health Solutions and Trellis Rx—in exchange for fees and, sometimes, a share of the profits.

“There are core competencies that come with running specialty pharmacies, and depending on what expertise a hospital or health system already has on board, the management companies can really help with those, including access to payor networks, access to limited distribution drugs and assistance with accreditation,” said Todd Nova, JD, an attorney with Hall, Render, Killian, Heath & Lyman, an Indianapolis-based firm specializing in health law.

of concern that would raise red flags suggesting a questionable contractracting arrangement, he said said: d: • The owner (the hospispiital or health system) m) expands into a related ted d line of business, which hicch is dependent on referferr rrals from, or other bu busibusi si-si ness generated by, its ts existing business.

• The hospital or health lth system neither operrates the new business itself nor ss it tseellff n orr ccomom o mmits substantial financial, ancial al,, ca ccapital api pita ital orr human resources to tthe venture—in h venture he e—i —in n this case, a specialtyy p pharmacy. harm ha rmac acyy.

Instead, it substantially contracts out virtually all of the new business.

• The third-party contractor is an

‘Summed up, the arrangement needs to be commercially reasonable, at arm’s length and at fair market value. And the hospital has to be at risk.’

—John W. Jones Jr., JD But contracting with a third-party specialty pharmacy management company poses a set of legal and regulatory issues that hospital and health-system compliance departments will have to navigate, said John W. Jones Jr., JD, a partner in the Philadelphia-based firm Troutman Pepper Hamilton Sanders LLP and the chair of its Health Care Transactions and Regulatory Practices of the Health Sciences Department, in a session on compliance issues facing hospital-based specialty pharmacies at the ASHP 2020 Midyear Clinical Meeting and Exposition.

Jones explained that the Department of Health and Human Services Office of Inspector General (OIG) will focus on a number of factors to ensure that the arrangement between the health system and management company is compliant with key statutes.

Anti-kickback regulations are a major focus for HHS OIG, he noted. The regulators have highlighted several areas

established provider of the same services as the new line of business and, absent the contract, would be a competitor, providing items and services in its own right, billing insurers and patients in its own name, and collecting reimbursement.

• The owner and third-party contractor share in the economic benefit (the profits) of the business, in the economic benefit of the owner’s new business.

• Payments to the third-party management company vary by the value or volume of business generated for the specialty pharmacy by the hospital.

“Summed up, the arrangement needs to be commercially reasonable, at arm’s length and at fair market value. And the hospital has to be at risk,” Jones said. “You can’t just have a management company coming in and taking over everything and giving the hospital a fee for this contractual arrangement.”

Pay Attention to Physician Relationships Another key issue, Jones noted, is the relationship between the hospital’s prescribing physicians and the pharmacists in the specialty pharmacy managed by the third-party company.

“What, if anything, is your management company doing for those doctors?” he asked. “You have to evaluate that. Equipment and free services, for example, are a real hot-button item for the OIG with regard to the AntiKickback Statute. I recommend that you make sure everything is at arm’s length and at fair market value, with no free services unless directly blessed by the OIG.” Nova also stressed the need for caution, citing this specific caveat: “The compensation methodology for the third-party management company must not create perverse incentives to overutilize the health care system, such as dispensing higher-cost drugs for no additional therapeutic benefit.”

‘Watch This Space’ To date, Nova said, OIG hasn’t scrutinized these partnerships—but watch this space. “Although there has not been a lot of affirmative movement at this point, I anticipate that will change in the near to midterm. This is care that is funded both directly and indirectly by federal payment programs, and you absolutely have to be aware of that. It’s time for hospitals that are involved in these ventures to be

2015

2018

2019

9%

20%

26%

The Growth of HealthSystem Specialty Pharmacy Source: ASHP 2019 survey of pharmacy practice in hospital settings (Am J Health Syst Pharm 2020;77[13]:1026-1050).

thinking about these issues and making sure that the reimbursement models you implement with these thirdparty companies are cognizant both of federal laws and state laws, particularly as related to percentage-based fee arrangements and joint ventures.”

When scrutinizing contractual arrangements with a third-party specialty pharmacy management company, focus on utilization, costs and outcomes, and what the relationship does with respect to those issues, Jones said. “If you can reduce costs, keep utilization low, improve patient outcomes and not be anticompetitive, then it should be a very good arrangement under the AntiKickback Statute.”

—Gina Shaw The sources reported no relevant financial disclosures other than their stated employment.

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Specialty Pharmacy Continuum • March/April 2021

OPERATIONS & MANAGEMENT

A Rare Opportunity continued from page 1

“The partners I’ve worked with have a hunger for it,” he said. “They don’t want to just get trained at launch around the drug and disease state, and what you want to do. They want ongoing training,” he said. Then as data come in “and you’re making changes to your marketing brand strategy or how you’re going to adapt patient services, they want to be brought along the journey as part of the team.”

Dana Dickens, the director of the specialty pharmacy channel for the biopharmaceutical company Sobi, said when she worked for a specialty pharmacy, she and her colleagues always appreciated any type of education from the manufacturer.

“If you’re launching a new drug, bring in folks to talk to us about the drug, not just talk to our pharmacists on adverse event training, but help us understand your philosophy for the drug, what your overall vision is for the drug, and partner with us to work through the best workflows so that we can streamline the process that meets your vision of the patient’s journey,” she said. “Then we can adapt our capabilities and partner together to enact the best version of that journey.”

Include in that process anyone in the pharmacy who will be part of the patient experience, and let them understand firsthand from the manufacturer what they want, Dickens said. In the rare disease space in particular, she noted, it’s helpful for specialty pharmacists to meet or hear from patient advocates living with the diseases they’re working to treat. “It really goes a long way,” she said.

It’s also important to integrate specialty pharmacists with hub services teams and anyone else involved in patient outreach, said Esther Langer, PMP, MBA, the head of U.S. patient services, trade and distribution for Apellis Pharmaceuticals.

“The pharmacists are talking to patients, and your case manager may be talking to patients, but you don’t want to overwhelm the patient with so many different outreaches,” she said. “You have to think of the whole experience as one workflow and educate all sides on the process.”

Patients these days are in “all types of circumstances,” Langer said, whether trying to work from home with kids in the background or in a job where they may not be able to call a hub during regular business hours. Hub services need to design platforms and solutions, like text messaging services, to meet patients where they are, and partner with pharmacies and distributors who view this as equally important, she said.

Pipeline Keeps Pumping This call to add more specialty pharmacists to the rare diseases care team is timely, because the pipeline for rare

disease therapies just keeps pumping.

Granted, approvals of drugs for rare diseases slowed slightly in 2019, with 25 new drugs approved by the FDA compared with the record-shattering 35 approvals in 2018. But the pipeline remains packed with novel agents for rare diseases that will have a major impact on both therapeutic options and health care economics.

Of drugs currently under review by the FDA, 39% are orphan drugs, as are 35% of drugs in phase 3 clinical trials, said Yuqian Lu, PharmD, the director of specialty clinical solutions for Magellan Rx Management (MRx Pipeline Quarterly Report, July 2020). “Overall, rare diseases affect a very small number of patients, but the spend is super high,” she said in an earlier interview with Specalty Pharmacy Continuum (bit.ly/3tbDrdP). “The top 10 highest-cost medications by annual cost per patient are almost all drugs for rare diseases.”

Lu cited a range of new therapies that are likely to reach the market by the end of 2021, and others that are in the less immediate but still relatively near future.

Perhaps the most imminent is PTCAADC, PTC Therapeutics’ investigational gene therapy for aromatic l-amino acid decarboxylase (AADC) deficiency, an often fatal genetic disease, usually diagnosed in infancy or childhood and caused by mutations in the DDC gene.

“In open-label trials involving 26 children, PTC-AADC lowered the number of oculogyric crises, which involve involuntary upward eye movements that are characteristic of AADC deficiency, as well as recovery of weight and improved ability to sit, walk and talk,” Lu said. (The results were presented at the 2019 annual meeting of the Child Neurology Society; posters P207 and P231). “Those documented benefits lasted at least five years after treatment, which is amazing for a condition like this. We expect approval by the end of this year.”

The anticipated gene therapy pipeline for 2021 also includes Bluebird Bio’s elivaldogene autotemcel (Lenti-D), a treatment for cerebral adrenoleukodystrophy, and betibeglogene autotemcel (LentiGlobin), a one-time gene therapy for patients with transfusion-dependent beta-thalassemia. However, at press-time, there was a pause on betibeglogene autotemcel clinical trials after an announcement that two enrolled sickle cell disease patients developed acute myeloid leukemia and myelodysplastic syndrome, respectively (bit.ly/3bT4Uv1).

“Biomarin’s Valrox [valoctocogene roxaparvovec] was expected to be the first gene therapy for hemophilia to enter the market,” Lu said. “But approval has been delayed until at least 2022 after a

complete response letter from the FDA asked for full completion of the phase 3 study, based on concerns about differences between the phase 1/2 study and early phase 3 regarding durability of effect. More than half a dozen other gene therapies are also in the pipeline for hemophilia, most of them targeted at hemophilia A.” (A complete response letter reflects the FDA’s complete review of the data submitted for a drug in an original application, abbreviated application or resubmission, as well as any amendments that

the agency has reviewed.)

Chimeric antigen receptor (CAR) T-cell therapy is expected to move beyond the cancer sphere in the near future, Lu noted. The near-term non-oncology CAR T-cell pipeline includes metachromatic leukodystrophy gene therapy (OTL-200, Orchard), up for FDA approval this year.

—Karen Blum, Gina Shaw The sources reported no relevant financial disclosures other than their stated employment.

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Specialty Pharmacy Continuum • March/April 2021

CLINICAL

The Role of Specialty Pharmacy in

Managing Rheumatoid Arthritis

RENEE BAIANO, PHARMD, CSP Clinical Program Manager AllianceRx Walgreens Prime Pittsburgh, Pennsylvania

A

lthough rheumatoid arthritis (RA) was once characterized by debilitating deformation, advancing treatment options have improved the outlook for RA patients, shifting the goals of therapy to low disease activity or even remission. Early, aggressive treatment can greatly

improve outcomes, but managing this chronic condition can be a challenge for providers and patients.

Barriers to controlling RA include nonadherence to therapy and the presence of comorbidities.1

Because there is no known cure for RA, the primary goal of therapy is to reach low disease activity or remission,1 which results in improved quality of life, prevention of new joint destruction, and reduced pain and inflammation.2 With the development of new medications and treatment guidelines urging early intervention, outcomes for RA patients have drastically improved. The American College of Rheumatology (ACR) recommends a treat-to-target approach for optimal disease management.3 Specialty pharmacists play a key role in helping patients understand why they should follow prescribed treatment plans. By counseling patients about medication administration, adverse effects (AEs), and disease activity, specialty pharmacists can help patients best manage their disease.

Chronic Inflammatory Disease The most common type of autoimmune arthritis, RA affects approximately 1.3 million US adults, 75% of whom are women.4 Although RA can start at any age, it most frequently begins between the fourth and sixth decades of life.4 In RA, the body’s

immune system mistakenly attacks the synovial tissue lining the joints.

This can lead to irreversible erosion of cartilage and bone, most commonly in the small joints of the hands and feet. This damage can cause pain, stiffness, and swelling, which tend to be worse in the morning, and can last 30 minutes or more after waking up.

Although RA may sound like a disease exclusively of the joints, it is a systemic inflammatory disease. RA also can cause fever, loss of appetite, and fatigue. The disease can manifest in organs including the lungs, blood vessels, eyes, and kidneys.5 One of the most common extra-articular manifestations of RA is the development of nodules under the skin, which present in up to 30% of patients.6 Early and aggressive therapy is the ideal, but this depends on diagnosis, which can be a challenge. RA is diagnosed clinically, and often the symptoms are nonspecific.7 There is no single test to diagnose RA; therefore, diagnosis is based on physical symptoms, blood work results, and various exams. Rheumatoid factor, an antibody found in approximately 80% of RA patients, and antibodies

to cyclic citrullinated peptides, found in approximately 60% to 70% of RA patients, can facilitate the diagnosis.4 In addition, RA patients often present with an elevated erythrocyte sedimentation rate—signaling inflammation—and anemia.4 X-ray, MRI, and ultrasound examinations can help clinicians assess disease progression and measure disease severity.4

Current RA Therapies Although the pathogenesis of RA is not completely understood, recent advances have allowed for targeted therapies that result in improved clinical outcomes. Cytokines, such as tumor necrosis factor (TNF)alpha and various interleukins (ILs), have been found to play a key role in the proliferation of T and B cells and induction of inflammatory responses, which ultimately cause inflammation and joint damage.8 Biologic medications on the market today work to block the activity of these cytokines, as well as other immune response pathways.

The treatment of RA is guided by disease duration and activity, and prognostic features. According to the ACR’s

RA treatment guidelines, patients are categorized as having early or established RA based on whether the disease has been present for less than or greater than 6 months, respectively.3 The guidelines determine disease activity as low, moderate, or high according to a validated patient scale, such as the Patient Activity Score, Disease Activity Score in 28 joints, or Clinical Disease Activity Index. The guidelines also call for evaluation of each patient’s prognostic features, listing extra-articular disease, positive rheumatoid factor, positive anti–cyclic citrullinated peptide antibodies, bony erosions, and functional limitations as poor prognostic features. Tools to quantify functional limitations, such as the Health Assessment Questionnaire, can help clinicians assess a patient’s ability to function in daily life. All these factors help clinicians determine the appropriate treatment plan.

Disease-modifying antirheumatic drugs (DMARDs) are the cornerstone of RA treatment. The ACR guidelines consider leflunomide, hydroxychloroquine, sulfasalazine, minocycline, and methotrexate to be the primary, nonbiologic DMARDs.3 These agents

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often are used first-line as monotherapy or as part of combination therapy, depending on disease activity and prognosis.

Methotrexate, which inhibits dihydrofolate reductase—an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid—often is the DMARD of choice due to its efficacy and ability to slow radiographic progression.9 The entry of biologic DMARDs into the market delivered another treatment option to improve function and decrease disease progression.

These agents target abnormalities of the immune system responsible for inflammation. The ACR guidelines recommend biologics after failure of traditional, nonbiologic DMARDs and as first-line therapy for some patients with more severe disease.3 Biologics often are used in combination with the nonbiologic DMARDs. In fact, the PREMIER study, which compared adalimumab (Humira, AbbVie) and methotrexate combination therapy with adalimumab or methotrexate alone, showed that combination therapy with a biologic significantly decreased disease symptoms and progression.10 The first biologics used in therapy are often TNF-alpha antagonists (Table). Five TNF-alpha antagonists are FDA-approved to treat RA: certolizumab pegol (Cimzia, UCB Pharma), etanercept (Enbrel, Amgen), adalimumab (Humira, AbbVie), infliximab (Remicade, Janssen Biotech), and golimumab (Simponi and Simponi Aria, Janssen Biotech).

Other medications used to treat RA include the IL-6 antagonists tocilizumab (Actemra, Genentech) and sarilumab (Kevzara, Sanofi), the IL-1 antagonist anakinra (Kineret, Sobi), the T-cell modulator abatacept (Orencia, Bristol Myers Squibb), the B-cell modulator rituximab (Rituxan, Genentech), and the oral Janus kinase (JAK) inhibitors tofacitinib (Xeljanz, Pfizer), baricitinib (Olumiant, Lilly), and upadacitinib (Rinvoq, AbbVie).9,11-13 The FDA also has approved several biosimilars to treat RA. These are biologic products that have demonstrated similarities to the reference product with no clinically meaningful difference in safety, purity, and potency.14 It is important to note that biosimilars are not generic medications.

Pharmacists can educate health care professionals and patients about the approved indications and regulations related to biosimilars. Two infliximab biosimilars—infliximab-abda (Renflexis, Merck) and infliximab-dyyb (Inflectra, Pfizer)—are available; several other biosimilars have been approved, but

Table. FDA-Approved Biologic Medications Indicated to Treat RA Mechanism of Action

Medication

Forms

Route and Dosage

TNF-alpha inhibitor

Adalimumab (Humira, AbbVie)

Prefilled syringes, prefilled pens

Subcutaneously: 40 mg every other week

Etanercept (Enbrel, Amgen)

Prefilled syringes, Sureclick pens, vials, cartridges

Subcutaneously: 50 mg every week

Certolizumab pegol (Cimzia, UCB Pharma)

Prefilled syringes, vials

Subcutaneously: Induction: 400 mg weeks 0, 2, and 4 Maintenance: 200 mg every other week, then 400 mg every 4 weeks can be considered

Golimumab (Simponi, Simponi Aria, Janssen Biotech)

Prefilled syringes, SmartJect autoinjector, vials (Simponi Aria)

Subcutaneously: 50 mg every 4 weeks

Infliximab (Remicade, Janssen Biotech)

Vials

Intravenously: Induction: 3 mg/kg 0, 2, and 6 weeks Maintenance: 3 mg/kg every 8 weeks

IL-1 antagonist

Anakinra (Kineret, Sobi)

Prefilled syringes

Subcutaneously: 100 mg daily

IL-6 antagonist

Tocilizumab (Actemra, Genentech)

Prefilled syringes, vials, ACTPen autoinjector

Subcutaneously: Weight <100 kg: 162 mg every other week, then increase to every week based on response; ≥100 kg: 162 mg every week

Intravenously: Induction: 2 mg/kg weeks 0 and 4; Maintenance: 2 mg/kg every 8 weeks

Intravenously: 4 mg/kg every 4 weeks; then increase to 8 mg/kg every 4 weeks based on response

Modulates T-cell activation

Sarilumab (Kevzara, Sanofi)

Prefilled syringes

Subcutaneously: 200 mg every other week

Abatacept (Orencia, Bristol Myers Squibb)

Prefilled syringes, vials

Subcutaneously: 125 mg once weekly; may be initiated with or without an IV loading dose (If initiating with IV loading dose, give single IV loading dose [per body weight] followed by the first 125-mg subcutaneous injection within 1 day of the IV infusion) Intravenously: Induction: Initially, then 2 and 4 weeks after first infusion; maintenance: every 4 weeks (weight <60 kg: 500 mg; 60-100 kg: 750 mg; >100 kg: 1,000 mg)

Binds to CD20, depletes B cells

Rituximab (Rituxan, Genentech)

Vials

Intravenously: Two 1,000-mg infusions separated by 2 weeks; subsequent courses should be administered every 24 weeks or based on clinical evaluation but not sooner than every 16 weeks

Janus kinase inhibitor

Tofacitinib (Xeljanz, Pfizer)

Tablets

Oral: 5 mg by mouth twice daily or 11 mg by mouth once daily (XR formulation)

Baricitinib (Olumiant, Lilly)

Oral: 2 mg by mouth once daily

Upadacitinib (Rinvoq, AbbVie)

Oral: 15 mg by mouth once daily

IL, interleukin; RA, rheumatoid arthritis; TNF, tumor necrosis factor; XR, extended release

ongoing legal challenges have prevented their launch into the market. As more biosimilars come to the market, pharmacists will need to stay current with trials supporting these agents to assist with their use.

AE Risks From Biologics Most patients tolerate biologics well, but AEs are possible.

TNF-alpha antagonists have a boxed warning related to infections, malignancy, and tuberculosis (TB).15 These biologics target components of the immune system to diminish the response, which consequently reduces the patient’s ability to fight infections. The risk for serious infection is increased in the first 6 months of therapy. Some predictors of infection risks

Based on prescribing information.

include glucocorticoid use, older age, and previous history of serious infections.16 Screening the patient before starting biologic therapy can minimize the risk for TB reactivation.17 Specialty pharmacists can educate patients on the importance of TB tests and help them learn how to watch for signs of infection. see SPECIALTY RA, page 10

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SPECIALTY RA continued from page 9

Lymphoma and other malignancies, some fatal, have been reported in some patients taking Janus kinase inhibitors and TNF inhibitors.11-13 In addition, a safety clinical trial show an increased risk of serious heart-related problems and cancer with tofacitinib compared with tumor necrosis factor (TNF) inhibitors.11 Thrombotic events, such as deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions.11-13 It is important for specialty pharmacists to discuss these issues with patients.

Medications in the Pipeline Research is leading to new drug classes and alternative physiologic targets. Gilead Sciences and Galapagos NV are developing a highly selective, oral JAK inhibitor.18 The New Drug Application for filgotinib was submitted in December 2019. If approved, filgotinib would compete with previously approved JAK inhibitors, tofacitinib, baricitinib, and upadacitinib.

Also, the FDA approved the investigational new drug application for ATI-450 (Aclaris Therapeutics), an oral MK2 (mitogen-activated protein kinase–activated protein kinase 2) inhibitor.18 Phase 1 clinical trials started in August 2019.

Improving Quality of Life The CDC has estimated that direct and indirect costs of rheumatic conditions, including RA, total $128 billion per year in the United States.19 Although it is clear that early, aggressive treatment is crucial in preventing irreversible joint damage in patients with RA, medication adherence rates range from 30% to 80%.20 Nonadherence not only negatively affects clinical outcomes, but it also can increase health care costs. When discussing adherence with patients, health care practitioners should be mindful of potential barriers that patients face. It’s common for patients to have improved symptoms and misinterpret this as meaning they no longer need medication. This type of patient-driven undertreatment is one of the most common causes of nonadherence.

Patients tend to be concerned with the current state of their disease

rather than future disease control.1 This perception of a reduced need for medication and the fear of AEs are major factors to consider when counseling on compliance.

AllianceRx Walgreens Prime’s specialty-trained pharmacists take a proactive approach to encourage medication adherence. They conduct monthly outreach assessments to follow up with patients and schedule delivery of medication refills. During these interactions, the pharmacist consults a patient management platform called Connected Care, which assesses patients for missed doses, as well as medication AEs, flares, and worsening of symptoms. Any concern or issue a patient raises leads to a system-generated, algorithmbased clinical escalation. The pharmacist then counsels the patient and provides education and support, with follow-up notification to the patient’s prescriber, if needed. By identifying nonadherence and other concerns, the specialty-trained pharmacist can provide the patient with the required patient-specific, supportive care.

The specialty pharmacist also can play a key role in identifying other opportunities for intervention with RA patients. For example, a pen device

could be more appealing than a prefilled syringe to a patient who has a fear of needles. In addition, pharmacists can help support patients who have comorbid conditions. For example, RA patients are approximately twice as likely to be diagnosed with heart failure as patients who do not have RA, and lung disease, depression, and anemia also are more prevalent in the RA population.21 Whether it’s helping a patient take medication the right way or notifying a prescriber about a new AE, the specialty pharmacist plays a vital role in helping patients manage their conditions. AllianceRx Walgreens Prime offers education on specialty disease states and medications in the form of pharmacist counseling and educational material, including disease-specific educational booklets.

Conclusion The continual interaction between the patient and the specialty pharmacy is fundamental in the continuity of care for RA patients. Specialty pharmacists can improve the quality of life for these patients by providing expert advice and support of treatment regimens, as well as by encouraging medication adherence.

PATIENT CASE

CA

is a 62-year-old woman with a history of RA. Her medical history includes treatment with etanercept (Enbrel, Amgen), abatacept (Orencia, Bristol Myers Squibb), and golimumab (Simponi Aria, Janssen Biotech). In September 2017, CA’s physician prescribed the interleukin-6 inhibitor sarilumab (Kevzara, Sanofi), and she has been receiving monthly medication and supplies from AllianceRx Walgreens Prime.

When the patient began receiving sarilumab, her insurance copay was more than $600 per month. At the initiation of sarilumab therapy with AllianceRx Walgreens Prime, the insurance team researched several options to assist CA with her monthly financial responsibility. Since CA did not have a commercial insurance plan, she did not qualify for the manufacturersponsored copay assistance program. The patient financial services representative at AllianceRx Walgreens Prime found assistance through a nonprofit organization, decreasing CA’s monthly financial responsibility to $10.

Every month before each prescription refill, an AllianceRx Walgreens Prime patient care coordinator (PCC) contacts CA proactively. During the patient outreach process, the PCC uses the disease management

application Connected Care, to obtain information from CA related to any missed doses, disease state flares, or decline in disease activity in the last 30 days, as well as any adverse events. These scheduled monthly patient interactions promote medication adherence and facilitate patient-specific disease management. If the PCC identifies any issues or concerns based on the Connected Care algorithms, a specialty-trained pharmacist consults with the patient.

During a call with CA, the AllianceRx Walgreens Prime PCC, using the Connected Care application, learned that CA was

exper experiencing injection site reactions when self-a self-administering sarilumab. She reported that h her skin became itchy and red for sever several hours after injecting the drug. The Conn Connected Care algorithm prompted the PCC to transfer CA to an AllianceRx Walgreens Prime pharmacist. The pharmacist provided counseling to CA rela related to her injection site reaction, thus puttin putting CA in a position to maintain proper adhe adherence to her prescribed therapy and impro improve her quality of life.

Be Before starting sarilumab, the patient advis advised the AllianceRx Walgreens Prime team that she was experiencing moderate to severe pain related to her RA symptoms, and that the pain negatively affected her ability to perform daily functions. By supporting CA through pharmacist interventions and proactive refill calls, AllianceRx Walgreens Prime improved her chance of having positive outcomes. The patient has been adherent to sarilumab therapy and reported after 2 months of treatment that her disease symptoms had improved and that she was experiencing only mild pain.

This case study demonstrates the key roles that a specialty pharmacy can have in helping RA patients manage their treatment.

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References 1.

Tymms K, Zochling J, Scott J, et al. Barriers to optimal disease control for rheumatoid arthritis patients with moderate and high disease activity. Arthritis Care Res. 2014;66(2):190-196.

2. Tkacz J, Ellis, LA, Meyer R, et al. Quality process measures for rheumatoid arthritis: performance from members enrolled in a national health plan. J Manag Care Spec Pharm. 2015;21(2):135-143.

3. Singh JA, Saag KG, Bridges SL Jr, et al.

2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2016;68(1):1-25.

4. American College of Rheumatology.

Rheumatoid arthritis. Accessed February 19, 2021. www.rheumatology.org/ Practice/Clinical/Patients/Diseases_And_ Conditions/Rheumatoid_Arthritis/ 5. Arthritis Foundation. Rheumatoid arthritis symptoms. Accessed February 19, 2021. www.arthritis.org/about-arthritis/types/ rheumatoid-arthritis/symptoms.php 6. Cojocaru M, Cojocaru IM, Silosi I, et al. Extra-articular manifestations in rheumatoid arthritis. Maedica (Buchar).

2010;5(4):286-291.

7. CDC. Rheumatoid arthritis. July 27, 2020.

Accessed February 19, 2021. https://www. cdc.gov/arthritis/basics/rheumatoidarthritis.html 8. Jung YO, Kim HA. Recent paradigm shifts in the diagnosis and treatment of rheumatoid arthritis. Korean J Intern Med. 2012;27(4):378-387.

9. Kahlenberg JM, Fox DA. Advances in the medical treatment of rheumatoid arthritis.

Hand Clin. 2011;27(1):11-20.

10. Breedveld FC, Weisman MH, Kavanaugh AF, et al. The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment.

Arthritis Rheum. 2006;54(1):26-37.

11. Xeljanz [package insert]. New York, NY: Pfizer Labs; September 2020. Accessed February 19, 2021. http://labeling.pfizer. com/ShowLabeling.aspx?id=959 12. Olumiant [package insert]. Indianapolis, IN: Lilly; July 2020. Accessed February 19, 2021. https://uspl.lilly.com/olumiant/ olumiant.html#pi 13. Rinvoq [package insert]. New York, NY: Pfizer Labs; July 2020. Accessed February 19, 2021.https://www.rxabbvie.com/pdf/ rinvoq_pi.pdf 14. FDA. Biosimilar and interchangeable products. October 23, 2017. Accessed February 19, 2021. https://bit.ly/2HKBqPj 15. Giezen TJ, Mantel-Teeuwisse AK, Straus

SM, et al. Safety-related regulatory actions for biologics approved in the United States and the European Union. JAMA. 2008;300(16):1887-1896.

16. Singh JA. Infections with biologics in rheumatoid arthritis and related conditions: a scoping review of serious or hospitalized infections in observational studies. Curr Rheumatol Rep. 2016;18(10):61.

17. Manno R. Challenges in screening for latent TB in inflammatory arthritis.July 30, 2012. Accessed February 19, 2021. www. hopkinsarthritis.org/arthritis-news/ra-news/ challenges-in-screening-for-latent-tb-ininflammatory-arthritis/ 18. Johanek E. Rheumatoid arthritis drug pipeline at a trickle. Managed Healthcare Executive. March 5, 2020. Accessed

February 19, 2021. https://www. managedhealthcareexecutive.com/view/ rheumatoid-arthritis-drug-pipeline-trickle 19. CDC. National and state medical expenditures and lost earnings attributable to arthritis and other rheumatic conditions– United States, 2003. MMWR Morb Mortal Wkly Rep. 2007;56(1):4-7.

20. Joplin S, Van der Zwan R, Joshua F, et al. Medication adherence in patients with rheumatoid arthritis: the effect of patient education, health literacy, and musculoskeletal ultrasound. Biomed Res Int. 2015;2015:150658.

21. Gabriel SE, Michaud K. Epidemiological studies in incidence, prevalence, mortality and comorbidity of the rheumatic diseases.

Arthritis Res Ther. 2009;11(3):229.

Free Opioid REMS CE/CME

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Medication selection, patient education among skills driving better outcomes

SPs Help Make HCV+ Organ Transplantation Safer Organ transplants from hepatitis C virus (HCV)-positive donors to HCV-negative recipients will continue to increase in frequency as more transplant centers develop protocols for their management, said experts from major transplant programs in a session at the ASHP 2020 Midyear Clinical Meeting and Exposition.

Integrated specialty pharmacies have responded to this trend by playing a key role in assisting with the selection of medication, management of drug interactions, procuring medication (including insurance approval and financial assistance) and patient education.

These are timely efforts, given that the number of transplant centers using HCV-infected kidneys jumped from 11 in 2015 to 39 through the first three months of 2019 (J Am Soc Nephrol 2019;30[10]:1939-1951).

Although direct-acting antiviral (DAA) drugs have had virtually universal success in clearing the virus from these patients in multiple clinical trials over the past several years (Rev Recent Clin Trials 2019;14[3]:173-182), management of these cases can be complex. “Integrated

specialty pharmacy programs can provide the resources necessary to allow these patients to gain access to and remain adherent to DAA therapy,” said Alicia Carver, PharmD, BCPS, a specialty pharmacist in the Digestive Disease Center at Vanderbilt University, in Nashville, Tenn.

More than 110,000 patients were on the waitlist for solid-organ transplants as of late 2020, and more than 5,000 people died while on the waitlist in 2019. Meanwhile, the opioid epidemic has led to an increase in overdoses as well as an increased number of potential organ donors who are HCV-positive.

Beginning with a pioneering clinical trial launched by researchers at Penn Medicine in 2016, a series of trials have demonstrated the safety and efficacy of positive-to-negative transplants for

‘In our program, the inpatient transplant pharmacist provides medication administration teaching upon discharge, with a detailed medication action plan [MAP].’

—Alicia Carver, PharmD

solid organs—including kidney, liver, heart, lung and pancreas—with high rates of sustained virologic response (SVR), low rates of adverse effects and decreased costs, while reducing waitlist time and increasing life expectancy (N Engl J Med 2017;376[24]:2394-2395; Ann Intern Med 2017;166[2]:109-117; [2]:109-117; Am J Kidney Dis 2020;75[6]:857-867; 57-867; N Engl J Med 2019;380[17]:1606-1617; 6-1617; Lancet 2019;4[10]:771-780).

Preemptive Versus Reactive DAA Treatment ment There are two primary ary approaches to treatment nt initiation for patients receiving an HCV-positive organ: preemptive (beginning prior to the transplant) and reactive (after the transplant), each with its own advantages and disadvantages.

“The preemptive strategyy allows for a shorter DAA A course, which patients and providers both may find attracttractive,” said Kristin Beeker, PharmD, MBA, a clinical pharmacyy specialist in the specialty pharmacy at the Medical University of South Carolina (MUSC), ( ) in Charleston, which began transplanting HCV-positive kidneys to HCV-negative recipients in 2018 and expanded the program m to heart, liver, pancreas and lung recipients pients in 2019.

Insurance and Financial Advocacy y

G

etting insurance coverage for direct-acting antiviral (DAA) therapy in transplant patients, particularly in a preemptive situation, can be complex. The involvement of a skilled specialty pharmacy team is essential.

In a report presented at the American Transplant Congress in May 2020, Vanderbilt University specialty pharmacists reported on a series of 91 transplant patients who received DAA therapy. “All of them were able to access coverage,” said Alicia Carver, PharmD, BCPS, a specialty pharmacist in the Digestive Disease Center at Vanderbilt University, in Nashville, Tenn. “Of the 91 patients, 97% were insured; the 3% who were uninsured or underinsured went on to get medications through the manufacturer. For those with insurance, 65% were approved through the prior authorization process, and 35% were approved on appeal. We did not have to move forward with a second level of appeal for any patient.”

The most common reasons for denial were lack of chronicity of the hepatitis C virus diagnosis and a request for more than eight weeks of therapy. The median time to approval was six days, and to first dose, eight days. “To improve your chances for success, be sure to provide all the requested information, including genotype, if it is at all possible to get it,” Carver said. “Most of the insurance providers do require it at this point.”

Other tips to improve the chances of getting a course of DAA therapy approved: • Use a formulary agent if possible.

• Ensure appropriate duration of therapy. Ledipasvir +

“We also can potentially prevent HCV infection from occurring, decrease HCVrelated complications and eliminate the need for genotyping. However, there is an increased risk of clinical instability since the patient is receiving a new

sofosbuvir (Harvoni, Gilead) and glecaprevir + pibrentasvir (Mavyret, AbbVie) may be only approved for eight weeks; if that is insufficient, consider appeal prior to treatment start.

• If denied, cite appropriate studies and clinical documentation.

• Consider a peer-to-peer option if necessary.

Financial assistance options for DAA therapy also can be pursued, including manufacturer copay cards for those patients with commercial insurance. All of the recommended regimens have cards available that reduce patient out-ofpocket costs to $5 and reduce the overall cost of care. Foundations including the Patient Assistance Network Foundation, the Patient Advocate Foundation, Healthwell Foundation, The Assistance Fund and the Good Days Foundation have income-based assistance that can range from $6,000 per year to maximums of $15,000-$30,000, but funds open and close throughout the year depending on available resources.

For patients who are underinsured or uninsured, manufacturers have their own support programs: Gilead’s SupportPath and AbbVie’s MyAbbVie Assist are income-based, and may also assist patients after multiple insurance denials or if insurance coverage is lost while on treatment, Carver said.

—G.S.

organ and we aren’t sure how they will respond to that transplant. That adds another potentially complicating factor iin the early post-transplant recovery period when the patient may not yet be fully stable. There is also an increased risk of drug interactions.

“You also have to have a backup plan if the patient’s insurance doesn’t approve the therapy, since preemptive appr treatment is not FDA approved,” she treat said. “That involves either partnering with the manufacturer to obtain medication through a study, or moving to i reactive therapy post-transplant.”

Reactive therapy has the advantages of clinical stability in the patient as well as a known decrease in drug–drug interactions, treatment failures and resistance.

“Every patient responds differently to transplantation, so it is nice to understand how the patient responds before introducing a new medication with known drug interactions and side effects to potentially complicate the patient’s clinical course,” Beeker said. “But reactive treatment can mean an increased time to DAA initiation, an increased risk for hepatitis C–related complications, and genotyping may or may not be required.”

Studies have demonstrated successful outcomes with both strategies (N Engl J Med 2019;380[17]:1606-1617; Lancet 2019;4[10]:771-780; Am J Transplant

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2019;19[11]:3046-3057; JAMA Cardiol 2020;5[2]:167-174; Hepatology 2020;72[1]: 32-41). The current joint guidelines of the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend early reactive treatment for liver transplant patients, employing a pangenotypic DAA regimen beginning when the patient is clinically stable—with “early” meaning within the first month

after transplant, but preferably within the first week. For nonliver solid organs, the AASLD/IDSA guidelines state that treatment can occur either immediately pretransplant or within the first week posttransplant. “The goal is to undertake DAA therapy as early as clinically possible to avoid the development of acute hepatitis and other complications of HCV infection,” they noted.

Regimen Selection In programs such as Vanderbilt’s and MUSC’s, integrated specialty pharmacists have been effective and involved members of the care team, helping to ensure rapid access to DAA therapy.

One of their main sources of information and guidance on therapy are the AASLD/IDSA guidelines. Whether therapy is initiated preemptively or reactively, the guidelines recommend two options for DAA therapy for recipients of HCV-positive organs: glecaprevir-pibrentasvir (Mavyret, AbbVie) or sofosbuvir-velpatasvir (Epclusa, Gilead).

Treatment is typically 12 weeks. “While the guidelines recommend an eightweek regimen of glecaprevir-pibrentasvir for preemptive therapy in liver transplant recipients, in real-world settings the eight-week duration is not widely practiced at present, because there is not a lot of literature to support the use of

only eight weeks of medication in these patient populations,” Beeker said.

Other regimens that have also been successfully used in clinical trials include 12 to 24 weeks of ledipasvirsofosbuvir (Harvoni, Gilead), elbasvir-grazoprevir (Zepatier, Merck) and sofosbuvir-velpatasvir-voxilaprevir (Vosevi, Gilead), although the latter is typically only used in patients who have already been exposed to another DAA regimen and so not common in transplant patients, Carver said.

Selection of the appropriate DAA treatment is a slightly different process for organ transplant recipients than for traditional chronic HCV patients, Beeker explained. “Factors that we typically would consider for the chronic hepatitis C patient include genotype, cirrhosis status, treatment history, timing of treatment initiation, comorbidities and drug–drug interactions,” she said. “But for patients who are not established with chronic hepatitis C, cirrhosis and treatment history are not a factor and genotype may not be readily available.

So the things we really consider in this population are the timing of treatment initiation, comorbidities and interactions with other drugs [see below] that may negatively impact the outcome of treatment with the DAA regimen.”

What are some of the most common considerations in selecting the appropriate DAA regimen? First, Carver said, absorption concerns are important in these patients, so regimens that can be given either with or without food can be an attractive choice. According to the drug’s prescribing information, ledipasvirsofosbuvir, sofosbuvir-velpatasvir and elbasvir-grazoprevir can be given without regard to food, whereas glecaprevirpibrentasvir and sofosbuvir-velpatasvirvoxilaprevir should be taken with food in order to ensure optimal uptake.

Another issue is alteration of the dosage form. “Many of these patients may be on enteral feeding, which can require crushing of the medication to swallow or deliver via gastrostomy or PEG [percutaneous endoscopic gastrostomy] tubes,” Carver said. “Ledipasvir-sofosbuvir and sofosbuvir-velpatasvir both have a very bitter taste, which can be a deterrent to the patient if they are crushed for swallowing.” She highlighted several studies on crushing and swallowing or delivery via enteral tube, PEG tube and gastrostomy button; although there were varying increases or decreases in absorption, all patients achieved SVR at 12 weeks (J Viral Hepat 2018;25[2]:214-215; Ther Drug Monit 2020;42[2]:163-164; A J Heath Syst Pharm 2020;77[6]:417-148).

“A phase 4 crossover bioequivalence study comparing crushed sofosbuvir-velpatasvir versus the whole tablet, CRUSADE-1, is ongoing,” she said.

Because all DAAs require gastric-

‘The things we really consider in this population are the timing of treatment initiation, comorbidities and interactions with other drugs that may negatively impact the outcome of treatment with the DAA regimen.”

—Kristin Beeker, PharmD, MBA dependent absorption, and stress ulcer prophylaxis is common after transplant, acid-suppressing drug management is a key concern with these therapies, given that acid suppression could potentially decrease DAA absorption and compromise SVR. “The use of proton pump inhibitors [PPIs] is not recommended with sofosbuvir-velpatasvir,” Carver said. “If you absolutely must coadminister them, take the DAA with food and wait four hours before dosing the PPI. Absorption is decreased with the other acid-suppressing agents, but it is not thought to affect SVR.” H2 blockers can be taken simultaneously with ledipasvir-sofosbuvir or sofosbuvir-velpatasvir, or 12 hours apart; there is no guidance on their administration with glecaprevir-pibrentasvir. For antacids, dosing is recommended to be separated from DAA administration by four hours.

Another common drug–drug interaction for DAAs is amiodarone. “Postmarketing studies revealed serious symptomatic bradycardia when administered with sofosbuvir, which was increased with concomitant beta-blockers, cardiac comorbidities and/or advanced liver disease,” Carver said (N Engl J Med 2015;373[19]:1886-1888; also see “warning and precautions” in prescribing information). “Coadministration of these drugs is not recommended; if they must be used together, it requires inpatient cardiac monitoring for 48 hours followed by two weeks of outpatient monitoring.”

Although glecaprevir-pibrentasvir also causes increased amiodarone concentration, “no bradycardia has been reported and only outpatient monitoring is recommended, so that would be a preferred option for these patients,” Carver said.

Even if a transplant patient’s current drug list does not include amiodarone, if their comorbidities suggest that they may have been on the drug in the past, “the specialty pharmacist should investigate further, as the drug has a long half-life,” she added.

Immunosuppressants also can interact with DAAs, causing, for example, increased tacrolimus levels. “Anticonvulsants and antimycobacterials are not commonly used in these patients but it’s important to know that there are serious interactions producing decreased DAA concentrations, and they should not be used together,” Carver said. “It’s important to look at each agent and regimen for

common drug–drug interactions and consider therapeutic alterations. Should we choose another DAA or should we change the drug that interacts with it?”

Communication Is Key Because a transplant patient’s medication list may change, regular ongoing communication about their most current medications is important. “In our program, the inpatient transplant pharmacist provides medication administration teaching upon discharge, with a detailed medication action plan [MAP],” Carver said. “The specialty pharmacist reinforces the MAP during detailed DAA education.” One useful tool for this process: the University of Liverpool HEP Drug Interactions Checker (www.hep-druginteractions.org/checker).

Although patients typically tolerate DAA regimens well with few side effects, the specialty pharmacist plays an important role in ensuring that the observed side effects—typically fatigue, headaches, nausea and vomiting, diarrhea and insomnia—do not interfere with adherence. “Mitigation strategies could include changing the timing of the DAAs to minimize these symptoms. For example, if the patient is experiencing headaches an hour or two after taking their medication, it may be beneficial to move dosing to right before bedtime so that the side effect isn’t noticed as much,” she said.

Acetaminophen also can be used for headaches, she added, noting that nonsteroidal anti-inflammatory drugs are not recommended in a transplant population because they can interact with antirejection medications. Additionally, “antiemetics can be taken prophylactically for nausea, melatonin and diphenhydramine for insomnia, and it’s important to ensure that patients stay hydrated.”

“An integrated specialty pharmacy approach helps optimize treatment outcomes in hepatitis C–negative transplant patients receiving hepatitis C–positive organs,” Beeker said. “We are able to improve drug–drug interaction management while improving patient satisfaction, achieving decreased time to treatment and insurance approval, and, at the same time, increasing revenue and margin.”

—Gina Shaw The sources reported no relevant financial disclosures.

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Specialty Pharmacy Continuum • March/April 2021

CLINICAL

Better Options Available for Resistant HIV Patients with multidrug-resistant (MDR) HIV currently make up a smaller but still challenging part of the population living with HIV. With careful monitoring and new drugs coming, providers can still help their patients.

“It’s really great that we have a relatively low number of patients with this issue,” said Milena Murray, PharmD, BCIDP, AAHIVP, an associate professor of pharmacy practice at Midwestern University-Chicago College of Pharmacy, and an HIV/ID clinical pharmacist at Northwestern Memorial Hospital, in Chicago. “Patients can have one or two mutations and still have plenty of options at this point.”

About 3% to 7% of the HIV population are considered MDR and need additional new agents, according to Michael Kozal, MD, a professor of medicine at the Yale School of Medicine, in New Haven, Conn., and the chief of staff at the VA Connecticut Healthcare System.

He has studied HIV multidrug resistance since 1991.

People can develop resistance to multiple drugs for several reasons, experts said.

Children who acquire HIV perinatally often have problems adhering to medicacation, and can burn through several drugs ugs by the time they reach adolescence and young adulthood. Some patients are less ess adherent to medication because they’re re in and out of the criminal justice sys-tem, have substance use issues or forr other reasons, and develop viral muta-tions that render the drugs ineffective. e.

Some patients also experience toxicities ties or cannot tolerate some of the existing ing drug classes, or are long-term survivors ors initially diagnosed in the late 1980s to early 1990s who have gone through a myriad of drugs over time.

“We have had a number of great agents over six different drug classes, but some people develop drug resistance,” Kozal said. “It sounds like a lot—six classes— but as patients have reactions, it limits the drugs they can take, and some patients are infected with drug-resistant virus. There is a need for new agents that have different mechanisms of action.”

Until the past couple of years, there were a limited number of targets on HIV that could be hit by available medications, said Jonathan Appelbaum, MD, FACP, AAHIVS, a professor and the chair of the Department of Clinical Sciences at Florida State University College of Medicine, in Tallahassee.

Recently, several new targets have emerged, including drugs designed to inhibit the maturation of the virus inside cells or prevent its entry into immune system T cells.

“The good thing about these new drugs is they don’t show cross-resistance to the

existing drugs, because their mechanisms of action are different,” Appelbaum said.

“If you’re resistant to the older drugs, you are not automatically resistant to these.”

New Medication Help One of the newer medications is an attachment inhibitor, ibalizumabuiyk (Trogarzo, Theratechnologies), approved by the FDA in 2018. The drug has a novel mechanism of action.

A monoclonal antibody that binds to the surface of immune cells, ibalizumab blocks the steps required for viral entry into cells. Multiple centers participated in the pivotal study the FDA considered for approval, enrolling 40 patients with MDR HIV. Patients received a dose of IV ibalizumab-uiyk in addition to their failing regimen for one week. After that period, they received ibalizumab-uiyk with optimized treatment regimens

After one week on ibalizumab-uiyk, 83% of patients experienced a decrease in viral load.

Source: N Engl J Med 2018;379(7):645-654.

for six months. After one week on ibalizumab-uiyk, most patients (83%) experienced a decrease in viral load (N Engl J Med 2018;379[7]:645-654).

After 25 weeks, nearly half saw their viral load fall below the level of detection. The researchers also reported an increase in CD4 T cells, which are a marker of immunity.

“This is a great drug that has worked well,” Appelbaum noted, but because it is given intravenously, it’s not used early in HIV treatment.

The FDA recently approved fostemsavir (Rukobia, ViiV Healthcare), which was developed specifically for patients with MDR HIV and works by a novel mechanism of action, said Kozal, the lead author on a recent article (N Engl J Med 2020;382[13]:1232-1243)

‘Sometimes we need to have patients on four to five medications, but that regimen is able to get them to an undetectable viral load.’

—Milena Murray, PharmD describing phase 3 trial results.

Fostemsavir is a prodrug whose active metabolite, temsavir, is an attachment inhibitor that prevents viral entry into host immune cells by binding to a glycoprotein on the surface of the virus. In the ongoing BRIGHTE trial in 23 countries, tries 371 patients with MDR HIV-1 infection were given fostemsavir along infec with wit their failing HIV regimen. After 48 4 weeks of therapy, 54% of randomized and 38% of nonrandomd iized patients who took the drug had undetectable viral RNA levh eels. The most common side effects included diarrhea, nausea and upper inc respiratory tract infections. resp “The data were very promising in that “T load stayed nondetectable in a the viral v llarge number of patients out to week 48,” Kozal said. “There’s no cross-resistance to other classes, so we think it’s going to be helpful for people who have exhausted other drug classes or can’t take other drug classes because [of intolerance].”

Current management of patients still comes down to individual resistance profiles, Murray said. Protease inhibitors are good options for some patients with drug resistance. Maraviroc can be helpful but requires a tropism assay. Enfuvirtide (Fuzeon, Genentech) is an injectable that may cause painful injection site reactions and is usually used as a last resort.

At times, adding an integrase inhibitor to the regimen will be enough if there are no mutations to this class.

“Sometimes we need to have patients on four to five medications, but that regimen is able to get them to an undetectable viral load,” Murray said, while other times medications are not enough to get to undetectable but can keep the viral load at a lower point. Ibalizumab can be a good option for patients who are extensively drug-resistant, she added.

“One of the caveats of HIV treatment is you never want to add on or substitute just one drug if patients have resistance to multiple drugs,” Appelbaum noted.

“You want to have two, and ideally three, active medications.”

When monitoring patients, Murray said, always check the viral load. “If patients are undetectable, that’s the bestcase scenario,” she said. “But if we can’t get them to undetectable, we want to make sure their viral load isn’t continuing to increase.”

Don’t Forget CD4 Counts In addition, monitor CD4 counts to make sure they’re not decreasing.

Check for any signs or symptoms of opportunistic infections and make sure any comorbid conditions are being addressed. Follow all guideline recommendations for screenings.

T-cell count also is important, “because if you don’t have the virus under control, the immune system is being constantly attacked by the virus, and so the patient is at risk for opportunistic infections and malignancies,” Appelbaum said.

Be mindful that as patients get older and need to add statins or antihypertensives to their regimens, drug interactions can occur with their HIV medications, Murray said. Then you can run into the issue of not being able to change the antiretroviral therapy to mitigate drug interactions because there aren’t any other options to treat the drug-resistant HIV. Overall, have good encouragement and support for your patients, Kozal advised: “You’ve got to take the drugs in order for them to work.”

—Karen Blum Appelbaum reported a financial relationship with Merck and ViiV Healthcare. Murray reported a financial relationship with Merck.

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Specialty Pharmacy Continuum • March/April 2021

CLINICAL

Study Sees Vast Treatment Gap for Hepatitis B Nearly half of all eligible patients infected with chronic hepatitis B do not receive treatment for the disease, a new study has found.

The investigators said the research was bolstered by the large, ethnically diverse multicenter cohort that formed the foundation of the analysis.

“We know that hepatitis B is predominantly a disease affecting ethnic minorities, as well as underserved and vulnerable populations,” said Robert Wong, MD, MS, of the Veterans Affairs Palo Alto Health Care System and Stanford University School of Medicine, in Stanford, Calif. “Many data show that hepatitis B remains underdiagnosed due to suboptimal awareness, screening, diagnosis and linkage [to care].”

Wong’s study focused on patients who had already been diagnosed with hepatitis B. “This is sort of considered the lowhanging fruit, because these are patients who have already been diagnosed, yet continue to experience delays in progressing through the cascade of care to receive antiviral treatment,” he said.

The researchers evaluated 5,157 adults with chronic hepatitis B who presented to four urban safety-net heath systems between Jan. 1, 2010, and Dec. 31, 2015, and who had at least two years of follow-up. The disease was confirmed with laboratory data. Criteria from the American Association for the Study of Liver Diseases were used to determine treatment eligibility.

“The diversity of the group was definitely a strong point, because many previous hepatitis B studies were predominantly Asian,” Wong told Specialty

Pharmacy Continuum. “But we actually captured a very diverse hepatitis B population: 34.6% were African American, 35.7% non-Hispanic white and 7.7% Hispanic.”

Of the patients, 46.8% were eligible for treatment, with significantly higher rates of treatment eligibility among men than women (58.2% vs. 32.9%; P<0.001). Similar rates of eligibility were found across race and ethnicity.

In a study presented at the 2020 International Liver Congress (abstract FRI404), the investigators reported that only 55.7% of treatment-eligible patients received treatment for chronic hepatitis B. Of that group, only 17.5% received treatment within six months of becoming eligible.

Women with treatment-eligible disease were significantly less likely than men to receive therapy (41.2% vs. 62.5%; P<0.01), according to the researchers. Asians were significantly more likely to be treated than whites (49.5% vs. 39.1%; P<0.01).

“This highlights a missed opportunity and a gap in our delivery of care for hepatitis B patients,” Wong said. “We believe this identifies areas where we can develop targeted quality improvement programs to try to address these shortcomings.”

Such efforts include improved linkage to care in at-risk populations, increased patient and provider awareness regarding treatment guidelines, and general hepatitis B educational efforts targeted at patients, he said.

Poor adherence to treatment can be

‘I think these low numbers really scream that we need to invest more resources in addressing the low rates of hepatitis B treatment in safety-net and vulnerable populations.’

—Robert Wong, MD, MS another barrier to comprehensive care.

“That’s where taking a comprehensive approach can help—one that targets providers, disease and health systems, and also invests in patient-centered education and engagement,” Wong said. “We used this approach in previous work and found it actually led to better follow-up and improved treatment rates.”

Future efforts, according to Wong, likely will include prospective quality improvement studies. “Now that we’ve identified the problem, we want to evaluate how we can improve this going forward,” he said. “So, we and others are planning prospective studies to see how we can better identify, engage and improve treatment rates for these hepatitis B patients. I think these low numbers really scream that we need to invest more resources in addressing the low rates of hepatitis B treatment in safety-net and vulnerable populations.”

Sammy Saab, MD, MPH, a professor of medicine and surgery at the David Geffen School of Medicine at the University of California, Los Angeles, said the results are a call to action to identify barriers to therapy and develop protocols that extend treatment to a broader range of patients with chronic hepatitis B. “We need to improve education. People need to understand that hepatitis B is a carcinogen, and a major reason for cirrhosis and liver cancer,” Saab said.

“We also need to educate them that we have great therapies that are safe, effective and tolerable. We need more studies to find out where these barriers exist, whether it be at the patient level, office level, pharmacy level, insurance level or physician level.”

—Michael Vlessides The study was supported by a grant from Gilead Sciences. Saab reported a financial relationship with Gilead Sciences.

Opioid Crisis Also Affects HAV and HBV Rates Thanks to direct-acting antivirals, hepatitis C virus (HCV) has gotten a lot of attention, but infectious disease experts are starting to hear more about hepatitis A and B viruses because cases are increasing due to the opioid crisis.

For the last 15 years, hepatitis A virus (HAV) had been associated mostly with international travel to countries where the virus is endemic, and with contaminated food, but current U.S. outbreaks of HAV are now primarily spread by person-to-person contact.

“We’re seeing really large person-toperson outbreaks of hepatitis A among persons who report drug use and homelessness,” said Monique Foster, MD, MPH, a medical epidemiologist in the CDC’s Division of Viral Hepatitis. She said 30 states have reported HAV outbreaks, 34,297 cases had occurred by

September, with more than 21,067 hospitalizations and 333 deaths.

The spike in infections can be attributed to factors associated with homelessness and drug use, as well as low vaccination rates among groups at risk for infection, according to Foster.

“Since hepatitis is spread by fecal–oral transmission, access to clean, sanitary facilities is really important, along with vaccination of populations at highest risk,” she said.

“Public health authorities have been trying to address the outbreak with temporary facilities” that include

restrooms with handwashing facilities, as well as mobile vans that bring vaccines to those at risk, said Ravi Jhaveri, MD, a professor of pediatrics at Northwestern University Feinberg School of Medicine, in Chicago.

People with HBV and/or HCV are at higher risk for adverse outcomes when infected with HAV—notably liver failure, and possibly death, according to Foster.

The Advisory Committee on Immunization Practices (ACIP) of the CDC recommends certain at-risk populations of adults be vaccinated against HAV, including: • people experiencing homelessness; • people who use drugs; • men who have sex with men; • travelers to countries with medium to high rates of endemic HAV;

• people in close personal contact with an international adoptee in the first 60 days after arrival from a country with endemic HAV; • people who work with HAV in laboratories or with infected nonhuman primates; and • people with chronic liver disease or clotting factor disorders.

Additionally, incarcerated people and, in some cases, those who work in close contact with them are also at high risk. People who have sex with someone with HAV should be vaccinated “within the 14-day window of being exposed,” Foster said.

Vaccine coverage for at-risk adults is wanting. According to the 2017 National Health Interview Survey, 10.9% of adults aged 19 years or older see OPIOIDs/HAV/HBV, page 17

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Specialty Pharmacy Continuum • March/April 2021

CLINICAL

The Hidden Pandemic of Misdosing Rachel Eyler, PharmD, BCPS Project Clinical Lead Lexicomp Reference Content at Clinical Effectiveness Wolters Kluwer Health Ann Arbor, Michigan

Bruce Mueller, PharmD, FCCP, FASN, FNKF Interim Dean and Professor of Clinical Pharmacy University of Michigan College of Pharmacy Senior Editor Lexicomp Reference Content at Clinical Effectiveness Wolters Kluwer Health Ann Arbor, Michigan

P

harmacists and clinicians adjust drug doses for patients every day.

Yet determining the correct dosage is one of the most difficult aspects of the prescribing process. This is due in part to the complexity involved in tailoring dosage to an individual patient’s condition, age, organ function, comorbidities, and concurrent medications.

Kidney dysfunction, in particular, presents unique challenges that clinicians calculating medication dosages.

Renal Dosing: A Common Yet Complex Task About 14% of the world’s population has chronic kidney disease (CKD)1 and almost one-fourth of hospitalized patients develop acute kidney injury (AKI).2 The risk is even greater in the ICU, where more than half of patients develop AKI.3 Accurate dosing and monitoring in these patients is complex and crucial.

Dosing of anticoagulants provides a clear example. Anticoagulants are high-risk medications. Clinicians must carefully balance the risks for causing bleeding associated with higher doses with the potentially catastrophic consequence of the patient suffering a clot or stroke if the dose is too low.4 Estimating a patient’s kidney function and subsequent drug clearance is the first step in the renal dose adjustment process and can be quite difficult. Several equations are available for estimation, but there are strengths and weaknesses in each formula and limited applicability to certain populations (eg, those with AKI, hepatic dysfunction, and other conditions).5-7 Hospitalized patients may experience dynamic changes in their kidney function, making dose estimation even more difficult. For patients who require renal replacement therapy, each type of therapy (intermittent hemodialysis, peritoneal dialysis, continuous renal replacement therapy) can affect drug removal.8 Once kidney function and drug removal are evaluated, the next step is tailoring

dose adjustments to kidney function. This step also is lacking in good references to assist pharmacists and clinicians in making the proper dose recommendations. Khanal et al highlighted this dynamic in their study that pulled 5 different renal dosing guides and compared recommendations for 61 commonly adjusted medications.9 According to their review, many of the sources offered ambiguous recommendations, such as “increase dosing interval” or “seek specialist advice in severe impairment,” and often disagreed on the reported availability of clinical trials.

The variability in drug dosing recommendations is not surprising. Before 1998, the United States did not provide structured regulatory guidance to pharmaceutical companies about how, and for which drugs, such renal dosing evaluations should be conducted.10 This has improved somewhat with guidance from the FDA. One ongoing problem is the lack of pharmacokinetic trials and studies that thoroughly evaluate dosing implications for patients with kidney dysfunction.

Many dose recommendations are based on single-dose pharmacokinetic trials and studies to quantify the impact of renal replacement therapies that were conducted for only 21.6% of the 194 new chemical entities for which new drug applications were approved by the FDA between 1999 and 2010. Only 4 of those studies evaluated patients on peritoneal dialysis and 1 evaluated patients receiving continuous renal replacement therapy.10 That means that for some medications, there are no data or only case reports available to advise clinicians about how to dose these drugs. For other medications, the various pharmacokinetic studies draw different conclusions based on the population studied. Some references have not been updated in over a decade.

For example, the last edition of the oftencited Drug Prescribing in Renal Failure,

by Aronoff et al, was published in 2007.11

Addressing the Critical Information Gap There is a clear need to improve the quality of renal dosing recommendations in clinical drug references that clinicians consult every day at the point of care. Teams behind evidence-based

References 1. US Department of Health and Human Services.

Office of Disease Prevention and Health Promotion. National Action Plan for Adverse Drug Event Prevention. 2014. Accessed January 29, 2021. http://bit.ly/3pAnn3Y 2. Hill NR, Fatoba ST, Oke JL, et al. Global prevalence of chronic kidney disease—a systematic review and meta-analysis. PLoS One. 2016;11(7):e0158765.

medicine tools should consist of a panel of consultants that include experts specialized in reading and interpreting pharmacokinetic literature, experts in caring for patients with kidney disease, and others who know how to use the medication in question in clinical practice. These teams should review and debate gray areas in the literature to develop concise, clinically helpful recommendations, so overworked clinicians at the bedside can provide safe, effective, patient-centered care.

Regulatory agencies also need to continue to push for well-designed studies of patients with CKD, AKI, and those receiving renal replacement therapies.

Rigorous studies should be mandated as part of the approval process, and postmarketing drug optimization research should be encouraged to include patients with altered kidney function.

The FDA has signaled its intention to address some of these concerns. In September 2020, the FDA issued a draft guidance on the evaluation of pharmacokinetics in patients with impaired renal function.12 The guidance includes advice on how to use population pharmacokinetics and phase 2 and 3 trials to inform dosing in patients with kidney dysfunction and how to conduct studies in patients receiving continuous renal replacement therapy.

Addressing the challenges in proper renal dose adjustments will require regulatory changes and new approaches to scientific research to include access to real-time data. Once this is achieved, our clinicians will be equipped with the tools they need to truly individualize care for their patients.

3. Wang HE, Muntner P, Chertow GM, et al.

Acute kidney injury and mortality in hospitalized patients. Am J Nephrol. 2012;35(4):349-355.

4. Hoste EA, Bagshaw SM, Bellomo R, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study.

Intensive Care Med. 2015;41(8):1411-1423.

5. Jones GR. Estimating renal function for drug dosing decisions. Clin Biochem Rev. 2011;32(2):81-88.

6. Raman M, Middleton RJ, Kalra PA, et al. Estimating renal function in old people: an in-depth review. Int Urol Nephrol.

2017;49(11):1979-1988.

7. Sherman D, Fish DN, Teitelbaum I. Assessing renal function in cirrhotic patients: problems and pitfalls. Am J Kidney Dis. 2003;41(2):269-278.

8. Mueller BA, Smoyer WE. Challenges in developing evidence-based drug dosing guidelines for adults and children receiving renal replacement therapy. Clin Pharmacol Ther. 2009;86(5):479-482.

9. Khanal A, Castelino RL, Peterson GM, et al.

Dose adjustment guidelines for medications in patients with renal impairment: how consistent are drug information sources? Int Med J. 2014;44(1):77-85.

10. Matzke GR, Dowling TC, Marks SA, et al.

Influence of kidney disease on drug disposition: an assessment of industry studies submitted to the FDA for new chemical entities 19992010. J Clin Pharmacol. 2016;56(4):390-398.

11. Aronoff GR, Brier ME. Drug Prescribing in Renal Failure. 5th ed. American College of Physicians; 2007.

12. FDA. Pharmacokinetics in patients with impaired renal function—study design, data analysis, and impact on dosing and labeling.

September 2020. Accessed January 29, 2021. http://bit.ly/3otVxFa The authors thank Jason Roberts, PhD, BPharm (Hons), B App Sc, University of Queensland, Australia, and Michael Heung, MD, MS, University of Michigan, for reviewing this article. Drs Eyler and Mueller reported no financial disclosures other than their stated employment.

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Specialty Pharmacy Continuum • March/April 2021

CLINICAL

OPIOIDS/HAV/HBV continued from page 15

have had two or more doses of HAV vaccine, as have 17.7% of international travelers and 20.8% of adults with chronic liver disease.

Can’t Blame the Kids Anymore Children used to drive outbreaks of HAV, but in 2007, recommendations from ACIP to vaccinate children were implemented. “We don’t see a lot of cases among children anymore,” Foster said.

until just after delivery. The real deficit is many women don’t get the additional testing they need to identify them as higher risk for transmitting to the baby,” Jhaveri said, adding that the CDC, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America are pushing to get the systems in place to ensure automatic follow-up testing. He also said Kaiser Permanente in Northern California has put such systems in place.

Worldwide, vaccines are becoming routine throughout much of Asia.

Southern Africa has high rates of HBV,

Sign up @ PharmacyPracticeNews.com/eNews Get the latest news from the most widely read hospital pharmacy publication in the United States, including multimedia and web-only content, delivered directly to your inbox!

Hepatitis D can ‘cause a severe worsening of symptoms if you already have chronic hepatitis B.’ Ravi Jhaveri, MD Vaccination coverage for children is around 86% for one dose, and 60% for the required two doses, he said.

Treatment “is mainly supportive care,” Foster said. Most people with healthy immune systems expunge the virus, and antibodies provide lifelong protection.

In rare cases, fulminant hepatic failure requires transplantation.

Hepatitis B Like HAV, HBV has been increasing, due to many of the same risk factors, notably from injecting opioids. “One thing we should be doing that we don’t do enough is treating pregnant women with chronic hepatitis B,” Jhaveri said.

“The literature has shown that if [such women] meet criteria for high replication of the virus, we providers should treat those women with an antiviral through the middle of their pregnancy

but little routine vaccination at birth, according to Jhaveri.

Hepatitis D Hepatitis D requires machinery from HBV to cause infection, Jhaveri noted.

Hepatitis D, although uncommon in the United States, can “cause a severe worsening of symptoms if you already have chronic hepatitis B,” he said. Hepatitis D is spread by contact with infected blood or other bodily fluids. There is no vaccine for hepatitis D; hepatitis B vaccine is the best protection. Protection is given because only people infected with HBV can become infected with hepatitis D virus, according to the CDC. —David C. Holzman The sources reported no relevant financial disclosures.

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Specialty Pharmacy Continuum • March/April 2021

CLINICAL

Glucarpidase Keeps CNS Lymphoma Rx on Track A new outpatient treatment regimen allowed patients with central nervous system (CNS) lymphoma to continue infusions during the height of the COVID-19 pandemic, and could change the way patients receive care after the current crisis subsides.

Researchers at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City found methotrexate could be coupled with repeated doses of glucarpidase (Voraxaze, BTG International), and patients could safely receive the two treatments in an outpatient setting, according to a study presented at the 2020 Society for Neuro-Oncology virtual annual meeting.

While the pandemic was surging in New York last spring, many patients with CNS lymphoma canceled treatments because they were afraid to come to the hospital, missing potentiallyy cura curative infusions, said Lauren Schaff, ff, MD, a neuro-oncologist and neurologist gist at MSKCC and lead investigator on the research. “We just felt like that was not in the best interest of our patients ts and really not acceptable,” she said.

Before the pandemic began, an, Schaff and her team had started ed examining the safety and efficacy cy of low-dose glucarpidase to clear ear methotrexate from patients who received both medications in the he hospital (abstract CTNI-61). Schaff ff and her team wanted to see whether er glucarpidase could be given multiplee times and stay effective for patients with th new or recurrent CNS lymphoma without systemic involvement and renal failure.

In the study, 12 patients received i d a total of 65 doses of methotrexate (28 doses of 3 g/m2, 26 doses of 6 g/m2 and 11 doses of 8 g/m2). Twenty-four hours after each methotrexate infusion, patients received glucarpidase, at 1,000 (20 doses) and 2,000 units (45 doses).

The researchers found that glucarpidase led to a more than 95% reduction in serum methotrexate levels within 15 minutes 97.7% of the time after administration of 2,000 units of glucarpidase and 75% of the time after administration of 1,000 units.

Four of 11 analyzed patients had anti-glucarpidase antibodies that were associated with reduced methotrexate clearance and methotrexate rebound.

The researchers also analyzed the cerebrospinal fluid of seven patients and found potentially cytotoxic methotrexate concentrations remained in the fluid one hour and six hours after patients received glucarpidase. No glucarpidase was detected in the cerebrospinal fluid of the seven patients tested.

To Schaff and her team, these findings demonstrated the glucarpidase treatment was safe and did not cross the blood–brain barrier to interfere with the methotrexate response. They also noticed that patients who received glu-

‘It’s very interesting and exciting to see what researchers and clinicians are doing to try to move patients from an inpatient setting to an outpatient setting in a way that’s safe.’

—Lisa Holle, PharmD, BCOP glucarpidase and additional hydration.

None of the patients required hospitalization, and in each case, methotrexate levels dropped to less than 100 nmol/L 48 hours after the dose. Two patients experienced grade 1 elevation of aspartate aminotransferase/alanine aminotransferase levels over three treatments, and one had a grade 2 creatinine increase that was remedied with additional hydration.

an outpatient setting likely will involve surmounting some logistical hurdles, Holle said. Many smaller institutions don’t have the laboratory capacity to process their own methotrexate, she noted. In addition, a new treatment like this could require additional training for infusion center staff, and the costs and cost-effectiveness of the treatment also need to be determined, she added.

Glucarpidase yielded

95%+ reduction in serum methotrexate

97.7% of time after dose of 2,000 units;

75% after 1,000 units Source: MSKCC

carpidase could go home earlier than they would have been able to otherwise, Schaff said.

When COVID-19 hit in March and April 2020, Schaff and her team quickly reconceived a follow-up study already in the works to accommodate patients who were unable to continue their inpatient treatment because of the pandemic.

They opened the study to patients who had isolated CNS lymphoma and previously tolerated high-dose methotrexate. The study enrolled four patients who received a total of 10 methotrexate treatments (3.5 g/m2) in the outpatient setting with hydration. Patients came back 24 hours later for 2,000 units of

Patients really appreciated the outpatient option, Schaff said. “Every patient who received this treatment opted to continue the outpatient treatment as long as feasible.”

Some Centers Likely to Face Logistical Hurdles “It’s very interesting and exciting to see what researchers and clinicians are doing to try to move patients from an inpatient setting to an outpatient setting in a way that’s safe,” said Lisa Holle, PharmD, BCOP, an associate clinical professor at the University of Connecticut School of Pharmacy, in Storrs.

However, moving these treatments to

For now, the MSKCC researchers are continuing to study the safety and efficacy of this approach. They are treating patients who need access to outpatient treatment as a result of the continuing pandemic and have started enrolling patients into a prospective study of this treatment approach in the outpatient setting. Schaff predicted, “I think certainly there’s going to be a place for this post-pandemic.”

—Jillian Mock Holle reported no relevant financial disclosures. Schaff has her name on a patent pending for a lower dose of glucarpidase.

BTG Specialty Pharmaceuticals provided the glucarpidase for this study.

If you missed any recent issues of Specialty Pharmacy Continuum, visit www.specialtypharmacycontinuum.com.

19

Specialty Pharmacy Continuum • March/April 2021

POLICY

FDA Grants EUA for Third COVID-19 Vaccine February ended in a flurry for the FDA and the Janssen COVID-19 vaccine. In the space of three days, an FDA advisory committee unanimously recommended an emergency use authorization (EUA) for the vaccine, which the agency then granted, followed by the Advisory Committee on Immunization Practices (ACIP) endorsing the safety and effectiveness of the vaccine for people aged 18 years and older.

“This third safe, effective COVID-19 vaccine comes at a potentially pivotal time. CDC’s latest data suggest that recent declines in COVID-19 cases may be stalling and potentially leveling off at still very high numbers. That is why it is so critical that we remain vigilant and consistently take all of the mitigation steps we know work to stop the spread of COVID-19 while we work our way toward mass vaccination,” said CDC Director Rochelle P. Walensky, MD, MPH, on signing the ACIP’s recommendation.

“As vaccination scales up, so too does our nation’s overall protection from serious outcomes due to COVID-19,” she explained.

Calling the vaccine an “important tool in our toolbox,” Walensky said the vaccine has some advantages over the Pfizer/BioNTech and Moderna vaccines.

Because it is a one-dose vaccine, “people do not have to return for a second dose to be protected. In addition, this vaccine does not need to be kept in a freezer and can be stored at refrigerated temperatures—so it is easy to transport and store and allows for expanded availability in most community settings and mobile sites, as supply scales up,” she said.

The FDA determined that the Janssen COVID-19 vaccine met the statutory criteria for issuance of an EUA. The totality of the available data provides clear evidence that the Janssen vaccine may be effective in preventing COVID-19.

The data also show that the vaccine’s known and potential benefits outweigh its known and potential risks, supporting the company’s request for the vaccine’s use in people 18 years of age and older, the FDA said in a statement.

The Janssen COVID-19 vaccine is manufactured using an adenovirus type 26 (Ad26) to deliver a piece of the DNA that is used to make the distinctive “spike” protein of the SARS-CoV-2 virus. While adenoviruses are relatively common, Ad26, which can cause cold symptoms and pink eye, has been attenuated for the vaccine so that it cannot replicate in the human body to cause illness.

After a person receives this vaccine, the body can temporarily make the spike protein, which does not cause disease, but triggers the immune system to

learn to react defensively, producing an immune response against SARS-CoV-2.

A Pivotal Multicenter Trial The decision to grant the EUA was based in part on an analysis of 43,783 participants enrolled in the ongoing ENSEMBLE trial, a randomized, placebo-controlled study being conducted in South Africa, certain countries in South America, Mexico and the United States. The participants, 21,895 of whom received the vaccine and 21,888 of whom received saline placebo, were followed for a median of eight weeks after vaccination.

Overall, the vaccine was approximately 67% effective in preventing moderate to severe/critical COVID-19 occurring at least 14 days after vaccination and 66% effective in preventing moderate to severe/critical COVID-19 occurring at least 28 days after vaccination. Additionally, the vaccine was approximately 77% effective in preventing severe/critical COVID-19 occurring at least 14 days after vaccination and 85% effective in preventing severe/ critical COVID-19 occurring at least 28 days after vaccination.

There were 116 cases of COVID-19 in the vaccine group that occurred at least 14 days after vaccination, and 348 cases of COVID-19 in the placebo group during this time. There were 66 cases of COVID-19 in the vaccine group that occurred at least 28 days after vaccination and 193 cases in the placebo group during this time period. Starting 14 days after vaccination, there were 14 severe/critical cases in the vaccinated group versus 60 in the placebo group, and starting 28 days after vaccination, there were five severe/ critical in the vaccine group versus 34 cases in the placebo group.

Data are not available to determine how long the vaccine will provide protection, nor is there evidence that the vaccine prevents transmission of SARS-CoV-2 from person to person, the FDA said.

The most commonly reported side

effects were pain at the injection site, headache, fatigue, muscle aches and nausea. Most of these side effects were mild to moderate in severity and lasted one to two days. As part of the authorization, Janssen Biotech Inc. and vaccination providers must report serious adverse events following administration to the Vaccine Adverse Event Reporting System (VAERS) for the Janssen COVID-19 vaccine. Those include serious adverse events, cases of multisystem inflammatory syndrome and cases of COVID-19 that result in hospitalization or death.

Strength in Numbers Public health experts applauded the availability of the new COVID-19 vaccine. “Having different types of vaccines The Janssen COVID-19 vaccine is

67% effective overall in preventing moderate to severe COVID-19 occurring at least 14 days after vaccination and

66% effective at least 28 days after vaccination.

available for use, especially ones with different dosing recommendations and storage and handling requirements, can offer more options and flexibility for the public, jurisdictions and vaccine providers,” Walensky said. “Getting vaccinated with the first vaccine available to you will help protect all of us from COVID-19.”

“The authorization of this vaccine expands the availability of vaccines, the best medical prevention method for COVID-19, to help us in the fight against this pandemic, which has claimed over half a million lives in the United States,” added acting FDA Commissioner Janet Woodcock, MD.

Johnson & Johnson said it was committed to making its COVID-19 vaccine available on a not-for-profit basis for emergency pandemic use. The company has begun shipping its COVID-19 vaccine and expected to deliver enough single-shot vaccines by the end of March to enable the full vaccination of more than 20 million Americans.

In March, President Joe Biden called on state, local and tribal governments to enable access to all American adults eligible to sign up for COVID-19 vaccines

by May 1.

What About Pharmacists?

In related news, the first public meeting of the COVID-19 Health Equity Task Force was held on Feb. 26, and although several initiatives were announced, including addressing inequities related to COVID-19 vaccination, there was one glaring error: not having pharmacists involved in potential solutions, according to a letter ASHP sent to the Biden administration.

In the letter, ASHP asked the administration to add pharmacists to the group charged with addressing health inequities caused or exacerbated by the COVID-19 pandemic. “I am greatly concerned that despite the role pharmacists are playing in COVID-19 vaccination and treatment, and the relative accessibility of pharmacists in otherwise underserved communities, this task force does not have a single pharmacist among its members,” said ASHP CEO Paul Abramowitz, PharmD, ScD (Hon).

“This deprives the task force of insights from medication use experts and the most accessible providers in underserved communities.”

Other sectors of the government seem to better grasp the value pharmacists bring to vaccination efforts. In March, the Department of Health and Human Services expanded its guidance on clinicians who can administer COVID-19 vaccines to include recently inactive pharmacists (active and in good standing within the last five years) and pharmacy interns.

—Marie Rosenthal, David Bronstein The sources reported no relevant financial disclosures.

20

Specialty Pharmacy Continuum • March/April 2021

POLICY

PAPs Flex Muscles continued from page 1

Call centers shifted from office-based to remote operations, and companies put information about their COVID-19 response on their patient support websites. The GSK program adapted some of its emergency management protocols typically used for fires or floods in certain municipalities, allowing for spouses or legal agents to sign paperwork on behalf of patients who were in quarantine, Gibb said. In some cases, she noted, they looked to alternate therapies, such as an injection patients could self-administer at home with telehealth-based training versus an office-based infusion.

Some PAPs turned to bridge programs to cover therapy for patients with rare diseases whose physician specialists closed their offices for several weeks, halting the prior authorization process, added Emily Phillips, the executive director of reimbursement strategy and patient access for Pharming Healthcare Inc. Several payor partners also extended authorizations as typical follow-up and check-in appointments were canceled, she said. “I was happy to see that patients understood there were struggles all the way around,” Phillips said. “They knew there wasn’t a way for doctors to fight for authorizations if

they couldn’t get into the office.”

Gaps Remain Despite all of these actions, there are some gaps that remain in care, panelists said. One is in the isolationism patients are experiencing, affecting anything from the ability to access social services face to face, to exercising at senior centers, said Meenakshi Datta, JD, a partner with Sidley Austin LLP in Chicago. This could contribute to other problems in the health care system, she said.

“While many of us try to do the best we can, our services always have to have the ‘why’; they have to be needs-based, and have to be medically appropriate within the criteria depending on the program,” Phillips said. “I think we still see, unfortunately, a fear among some patients of being able to access therapies or even get transported to facilities or be seen in a timely manner to make sure they continue to receive therapies.” Her programs and others look to partner with other advocacy organizations where appropriate. (For a listing of more PAP providers, see Table.)

Last year saw a steep drop-off in people undergoing preventative screenings and routine immunizations that has continued, Gibb added. And, even

‘Last year was historic in its focus on social determinants of health, and health equity, and [it underscored] that different populations are impacted differently by disease.’

—Emily Gibb

THE MCMAHON GROUP, LLC McMAHON PUBLISHING McMAHONMED.COM Sales, Production and Editorial Offices: 545 West 45th Street, 8th Floor, New York, NY 10036 Telephone: (212) 957-5300 CT Office: 83 Peaceable Street, Redding, CT 06896 Copyright © 2021 McMahon Publishing, New York, NY 10036. All rights reserved. Specialty Pharmacy Continuum is published bimonthly by McMahon Publishing. POSTMASTER: Send address changes to

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Table. Top 10 Patient Assistance Programs In the United States Program

Total Giving, $

URL

The AbbVie Patient Assistance Foundation

853,356,401

bit.ly/3bvnhWx

Johnson & Johnson Patient Assistance Foundation Inc.

787,776,687

bit.ly/2PGfjkT

The Bristol Myers Squibb Patient Assistance Foundation Inc.

619,573,888

bit.ly/3rBFA23

Sanofi Foundation for North America

617,927,313

bit.ly/3cgNsQ1

Merck Patient Assistance Program Inc.

566,675,598

bit.ly/2Ol7gJV

Novartis Patient Assistance Foundation 542,136,898

bit.ly/2OcWpSy

Genentech Access to Care Foundation

495,979,664

bit.ly/3co8X1v

Pfizer Patient Assistance Foundation Inc.

446,674,762

bit.ly/3bwIq2y

Lilly Cares Foundation Inc.

408,239,166

bit.ly/3cdNok0

GSK Patient Access Programs Foundation

386,459,002

bit.ly/3ceSFYy

Source: Patients Rising Now.

though there was progress in the use of telehealth and being able to reach patients in new digital ways, some gaps remain in electronic health record integration, and new ways to leverage digital technologies to make processes smoother for patients, she said.

Looking forward, Gibb noted two areas for consideration for research and development.

“Last year was historic in its focus on social determinants of health, and health equity, and [it underscored] that different populations are impacted differently by disease,” she said.

“Some of the statistics around “S COVID-19 and how it has C affected minority communities [are] really sobering.

As we look toward the R&D pipeline, thinking about p considerations for clinical trial tr diversity and making sure we have the data on different populations is really critical.”

PAPs also need to keep tabs on ongoing in development programs for COVID-19 vaccines and therapies, and determine v how to remove any access barriers, Gibb h said.

The government has allocated funds s

for the uninsured, but as people’s employment status can change even into 2021 and 2022, PAPs may need to evolve programs to meet the needs of uninsured and underinsured persons.

The employment picture even before COVID-19 had not been encouraging. Between March and April 2019, the United States lost 20.6 million jobs, Datta noted, resulting in an unemployment rate of 14.7%—a level not seen since the Great Depression. Certain populations faced rising rates of being uninsured, including Black Americans, 26% of whom were uninsured as of September 2020, and people without a high school diploma, 27% of whom were uninsured as of September 2020.

In addition, 19 rural hospitals closed in 2020, and urban hospitals were squeezed due to economic pressures inflicted by the pandemic, which also affected cities and states that subsidize these providers.

All these factors, she stressed, exerted a “tremendous impact on patient access.”

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—Karen Blum The sources reported no relevant financial disclosures other than their stated employment.

Founded in 1972, McMahon Publishing is a family-owned medical publisher of clinical newspapers and specialty periodicals, and creates continuing medical education programs and custom publications. As the second largest publisher of medical newspapers, McMahon produces Anesthesiology News, Gastroenterology & Endoscopy News, General Surgery News, Infectious Disease Special Edition, Pain Medicine News, Pharmacy Practice News and Specialty Pharmacy Continuum.

21

Specialty Pharmacy Continuum • March/April 2021

POLICY

Waiting for Relief continued from page 1

lead partner of the law firm McDermott, Will and Emery, in Washington, D.C.

The Year Ahead There are a few issues to watch this year, Kim said. They include: International Reference Pricing/ Most Favored Nation Drugs. Court injunctions put the previous administration’s “Most Favored Nation” (MFN) interim final rule aimed at lowering prescription drug prices in limbo, but experts said this probably isn’t the last we’ll see of international drug reference pricing. The rule, which was set to take effect Jan. 1, proposed to restrict costs for the top 50 physician-administered Medicare Part B drugs—which account for almost 80% of Part B spending—to no more than the lowest price that drug manufacturers receive in other similar countries, as reported in Specialty Pharmacy Continuum (bit.ly/ 38LkbMn).

However, there are indications that the Biden administration is interested in looking to foreign pricing of certain products in the pharmaceutical sector as a way to negotiate lower prices for U.S. beneficiaries, Kim said. But the use of such a pricing model has significant legal and policy considerations, he stressed, and drugs elsewhere are regulated under d i f f e re n t e nv i r o n m e n t s . Adoption of MFN-like pricing in the United States also may have unintended consequences for the overall global community—something that has to be examined carefully, Kim said.

340B Drug Pricing. Significant debates abound in the legal community regarding 340B drug pricing. One contentious issue is the use of third-party contract pharmacies by institutions that qualify for 340B drug pricing but do not have in-house pharmacies. The use of contract pharmacies can yield significant cost savings for these hospitals, but the practice has drawn the ire of drug manufacturers, many of which have sought to block these arrangements over the past year. The conflict has resulted in an administrative ruling by the Department of Health and Human Services to uphold the rights of contract pharmacies to access 340B prices.

The HHS summarized its ruling in a Dec. 30, 2020, statement: “HHS has become aware of drug manufacturers refusing to provide 340B discounts to covered entities when covered entities order the drugs themselves but then

have the drug physically delivered to patients through contract pharmacies.” Based on its advisory opinion, “HHS has clarified that drug manufacturers must provide 340B discounts when a contract pharmacy is acting as an agent of a covered entity, providing services on behalf of the covered entity.”

“There does need to be a resolution of this issue,” Kim said, because it is now affecting beneficiaries. Xavier Becerra, the attorney general of California and one of those lawyers leading the charge against manufacturers’ refusal to allow contract pharmacy access to 340B

‘[Authorizing Medicare to negotiate drug prices] will not be an easy question to answer, but this is a very serious lever … that the Biden administration intends to utilize as much as possible.’

—James Kim, JD, MPH

drugs, is President Joe Biden’s pick to head HHS. If he takes over leadership, there is likely to be a resolution of this issue sooner than later, Kim said. But he stressed that it will require an enormous amount of effort and discussion among providers, distributors and pharmacies.

Medicare Drug Price Negotiation.

A big part of Biden’s plan to control drug prices and access to drugs is to authorize Medicare to negotiate the prices of its reimbursed drugs. The factors that will go into the negotiations are extraordinarily complex, Kim said. “It will not be an easy question to answer, but this is a very serious lever on control of drug prices and access that the Biden administration intends to utilize as much as possible.”

Prescription Drug Importation. Several states and the FDA have authorized rules examining importing prescription drugs, particularly from Canada, but none have seen major success, Kim said. The FDA is concerned with safety and efficacy of those products as well as appropriate regulation, but the Canadian government already has created legislative actions

to prohibit such programs from moving forward. Like international reference pricing, any changes have to account for impacts to the global economy, he said.

Title X Federal Family Planning Program. In response to the Trump administration’s 2019 issued rules banning providers that receive Title X funds from referring people for abortions, on Jan. 28, the Biden administration issued a memorandum on protecting women’s health at home and abroad. It states the secretary of HHS shall review the Title X Rule and any other regulations governing the Title X program that impose “undue restrictions on the use of federal funds or women’s access to complete medical information,” and will consider whether to suspend, revise or rescind them. The memorandum does not change the rule, Kim said, but it does make clear of an intent to modify the Title X program rulings substantially, if not rescind them entirely. The Supreme Court announced in February it would hear a case brought by the American Medical Association, Planned Parenthood and others arguing that former President Trump’s changes violate federal law and harm patient care.

Meanwhile, division among political parties “limits the ability for real substantive changes to occur,” Kim said. “I am hopeful over the course of the year that some issues that have bipartisan support, such as drug pricing issues,

can have some sort of effective change.

The key question is how we are going to come to a single model that all parties can at least agree to disagree on. No one’s going to be happy with the result from all perspectives, but there is common ground to be met on these issues.”

‘Important to Listen’ Dave MacLeod, a co-chair of the conference and the head of patient services and specialty pharmacy operations for Amylyx Pharmaceuticals, said Kim’s presentation was informative and timely with the administration crossover.

“I think it’s important for our industry to listen to what’s going on with legislation and the government, and how things are moving forward,” he said.

One issue that MacLeod said keeps him up at night is drug importation.

“We do see patients who may not have coverage under insurance for a particular product, so they may go out of their way to become cash-paying patients in Canada, Europe or somewhere else to get their hands on that drug, and that’s hard to regulate,” he said. “It’s tough because if they’re getting their drug outside the country, as a manufacturer there’s not much you can to do to support that because it’s considered offlabel. That’s a key concern.”

—Karen Blum The sources reported no relevant financial disclosures.

22

Specialty Pharmacy Continuum • March/April 2021

TECHNOLOGY

Devices improve arrhythmia detection, glycemic control

Remote Monitoring for Diabetes, Heart Disease Two studies presented at the American College of Clinical Pharmacy 2020 virtual annual meeting point to the power of mobile technology in helping patients with medication-induced heart problems and with diabetes.

The first project demonstrated that community pharmacists can make use of mobile ECG monitors to detect heart conduction abnormalities in their patients and alert prescribing physicians.

In a pilot study of 53 patients enrolled at three community pharmacies in Iowa, pharmacists used 30-second ECG measures recorded on a mobile device to study patients’ QTc intervals.

All patients were taking medications known to be associated with prolonging the QTc interval, which can cause arrhythmia and result in fainting, seizures or sudden death. Based on QTc interval length calculated from the recordings, pharmacists contacted prescribers about potential drug-induced long QT syndrome in six patients (11% of the study sample). In three cases, prescribers made a medication change.

The technology could help “fill a big void” for pharmacists, said lead study author James Hoehns, PharmD, a clinical associate professor at the University of Iowa College of Pharmacy, in Iowa City, and the research director at the Northeast Iowa Medical Education Foundation, in Waterloo.

“Pharmacists have been working with these prescriptions, and making judgments about when to try and intervene and get somebody off of a medication, without actually knowing what their QTc interval is at that moment in time, which is really one of the elephants in the room,” Hoehns said. “Now, with this easy technology, we’ve got the ability for a pharmacist in 30 seconds to determine somebody’s QTc interval at the time they are processing this prescription. It’s put a totally new tool in the pocket of the pharmacist to help them with their professional judgment.”

More than 100 FDA-approved medications have a known ability to cause drug-induced long QT syndrome, he said, including commonly used drugs such as azithromycin, fluconazole, ciprofloxacin and escitalopram.

The study was conducted from July 2019 through March 2020. Patients’ mean age was 55.1 years, 38 (72%) were female, and 19 (36%) received newly prescribed medications that could prolong the QTc interval. The ECG measures were recorded on a personal ECG monitor made

by KardiaMobile, for which patients place their fingers on a small device that uploads readings to a smartphone.

Researchers found no statistically significant differences between the community pharmacists’ calculations of QTc intervals and those done by family medicine physicians and cardiologists, using five sample recordings. In addition, Hoehns said, study participants responded well to the intervention. In a survey of 19 subjects, all said they agreed or strongly agreed that they were comfortable with the pharmacist obtaining their ECG recordings; that the pharmacist explained the test in a manner that was easy for them to understand; and that after talking with the pharmacist about the test, they felt safer taking a medication that could affect their heart.

The Livongo remote diabetes monitoring program employs cellular-enabled glucose meters, test strips and coach interactions to help patients with glycemic control.

‘Pharmacists have been working with these prescriptions, and making judgments about when to try and intervene and get somebody off of a medication, without actually knowing what their QTc interval is at that moment in time, which is really one of the elephants in the room.’

The KardiaMobile personal ECG monitor yields readings that can be uploaded to a smartphone and accessed by a caregiver for signs of arrhythmia.

The next step would be to conduct a randomized clinical trial to better measure the effectiveness of this tool against sites that don’t have it, Hoehns said.

Diabetes Monitoring In the other study, researchers with Teladoc Health Inc. found that Livongo’s remote diabetes monitoring program (RDMP) with cellular-enabled glucose meters, test strips and coach interactions can improve both medication adherence and glycemic control.

Investigators noted that during two years of participation, medication adherence (measured as proportion of days covered) increased from 77% to 80% among 870 patients with diabetes enrolled in the program, but decreased from 78% to 69% among 479 matched controls not enrolled. Among RDMP members, each 10-day increase in days covered resulted in a 1-mg/dL decrease in blood glucose per month.

“We were pretty astonished to see this

—James Hoehns, PharmD real difference at two years of medication adherence,” said Bimal Shah, MD, MBA, the chief medical officer of product and analytics at the company and a cardiologist with Duke University School of Medicine, in Durham, N.C. Previous studies showed that people with diabetes who are adherent to medications not only improve clinical outcomes but also save on health care costs over time because they are less likely to have major events such as heart attack, stroke or kidney disease, he said.

Patients enrolled in the RDMP program, usually offered through employer, national and regional health plans, are given a two-way cellular glucometer and unlimited testing strips, Shah said.

Once a person takes a blood glucose reading, the information is sent to the program’s cloud-based analytics engine and is processed by a computerized algorithm that takes into account the person’s historical readings, medication list and other characteristics. Digital messages are then returned to the patient with tips to help them better manage blood glucose levels.

In addition, participants can set up oneon-one coaching appointments at any time with certified diabetes educators, through their glucometer, a web portal or a mobile app, Shah said. If any member registers an unusually high or low glucose reading for their history, one of the company’s diabetes response specialists will call within 90 seconds to walk through American Diabetes Association– recommended steps to get their blood glucose quickly back to a safe range. The program’s digital and human coaching features use member information to send reminders to take prescribed medications.

“We know that only about a third of people with diabetes are adherent to their medications on an ongoing basis,” Shah said. “This is a huge opportunity to promote better glucose control and better diabetes management.”

—Karen Blum The University of Iowa College of Pharmacy study was sponsored by the Iowa Pharmacy Association Foundation. Hoehns reported no relevant financial disclosures. Shah reported no relevant financial disclosures other than his stated employment.

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