Value-Based Care in Rheumatology

www.ValueBasedRheumatology.com

STAKEHOLDER PERSPECTIVE

CONFERENCE NEWS

Managing Pain After TKA Significantly Lowers Total Hospital Costs And other news from the ISPOR 21st Annual International Meeting

Convergence in Healthcare: Providers, Employers, and Health Plans

By Byron C. Scott, MD, MBA

H

ealthcare in the United States has experienced a tremendous amount of reform and innovation, especially in the past 10 years, with an emphasis on improving value.

Value in healthcare is driven by increasing quality of care while reducing

cost. The evolution of quality measurement has been proactive and voluntary within national organizations, such as the National Quality Forum.1 Reform has been less voluntary through government mandates, such as the Affordable Care Act (ACA).

Continued on page 18

Washington, DC—Significantly lower hospital costs may be incurred by Medicare patients who receive bupivacaine liposome injectable suspension as a way to manage postsurgical pain

after undergoing total knee arthroplasty (TKA), researchers have found.

Data were analyzed from 5 hospitals that are part of the Premier Database. Overall, 3359 Medicare patients Continued on page 5

Usefulness of Vitamin D Supplementation Questioned in Patients with Knee Osteoarthritis

By Phoebe Starr

A

Light Shed on Pain, Pain Care in Veterans

By Sophie Granger

OSTEOARTHRITIS

lthough some observational studies suggest that vitamin D supplementation is beneficial for knee osteoarthritis (OA), a ran-

PAIN MANAGEMENT

domized, placebo-controlled, double-blind study called VIDEO found no benefit for vitamin D supplementation on pain reduction or change on Continued on page 10

P

ainful and expensive to manage, musculoskeletal disorders (MSDs) are among the most common disorders found in veterans and active duty personnel. According to a recent report from researchers behind a cohort designed to shed more light on this patient population, >50% of all veterans receiving care from the Veterans Health

Administration (VHA) have been diagnosed with MSDs, and that the number is increasing annually.

Limited data are available on the characteristics of patients with MSDs, including their comorbidities, and whether rates of non-MSD comorbidities vary by levels of reported pain. In response to a request from the Institute Continued on page 22

INSIDE VALUE PROPOSITIONS. . . . . . . 4 HEALTH & WELLNESS. . . . . . . . 17 Tug-of-War Between Ideal Lifestyle Tocilizumab Effective, Highly Habits and Reality Observed in Retentive in Patients with Patients with RA Rheumatoid Arthritis

Š 2016 Engage Healthcare Communications, LLC

RHEUMATOID ARTHRITIS. . . . 8 PAIN MANAGEMENT. . . . . . . . 21 Baricitinib Effective in Patients with Provider Education Key to Preventing Refractory Rheumatoid Arthritis the Growing Epidemic of Misuse and Abuse in Opioid Prescribing for OSTEOARTHRITIS . . . . . . . . . . 10 Chronic Pain, the FDA Emphasizes Rheumatologists Should Not LUPUS. . . . . . . . . . . . . . . . . . . . . 20 Underestimate the Burden of OA Patient Tip: 5 Tips for Preventing Lupus Flares

ENGAGE

®

HEALTHCARE COMMUNICATIONS, LLC

Heading 30 Senior Vice President/Group Publisher Nicholas Englezos nenglezos@the-lynx-group.com Senior Vice President/Group Publisher

John W. Hennessy

By Author Name

jhennessy2@the-lynx-group.com Publisher Joe Beck jbeck@the-lynx-group.com Editorial Director Frederique H. Evans fevans@the-lynx-group.com Copyeditor Hina Khaliq Editorial Assistant Katharine Brzozowski Senior Production Manager Melissa Lawlor

President/CEO Brian Tyburski Senior Vice President/Group Publisher Russell Hennessy rhennessy@the-lynx-group.com Senior Vice President, Sales & Marketing Philip Pawelko ppawelko@the-lynx-group.com Vice President, Finance Andrea Kelly Senior Financial Assistant Audrey LaBolle Director, Human Resources Jennine Leale Medical Director Julie Strain Director, Strategy & Program Development John Welz Editorial Director Susan Berry Director, Quality Control Barbara Marino Quality Control Assistant Theresa Salerno

Value-Based Care in Rheumatology Editorial Advisory Board Howard B. Blumstein, MD Rheumatology Associates of Long Island Smithtown, NY Scott Breidbart, MD Chief Medical Officer Empire BlueCross BlueShield New York, NY Sheree C. Carter, PhD, RN Assistant Clinical Professor The University of Alabama in Huntsville; President, Rheumatology Nurses Society Gary R. Feldman, MD, FACR Private Practice Pacific Rheumatology Los Angeles, CA Gary L. Johnson, MD, MS, MBA Regional Medical Director Humana, Inc Madison, WI Atheer A. Kaddis, PharmD Vice President Managed Markets Diplomat Specialty Pharmacy Swartz Creek, MI Shelly Kafka, MD Medical Director Rheumatology Medical Affairs Janssen Scientific Affairs, LLC Horsham, PA James T. Kenney, Jr, RPh, MBA Pharmacy Operations Manager Harvard Pilgrim Health Care Wellesley, MA

Muhammad Asim Khan, MD Professor of Medicine Case Western Reserve University Cleveland, OH John Kolstoe, MD Kolstoe Rheumatology Musculoskeletal Medicine East Lansing, MI Randall Krakauer, MD, FACP, FACR National Medical Director Medicare Aetna Princeton, NJ Joel M. Kremer, MD Pfaff Family Professor of Medicine Albany Medical College Director of Research Center for Rheumatology Albany, NY Alan Menter, MD Director, Baylor Psoriasis Research Center Dallas, TX Matthew Mitchell, PharmD, MBA, FAMCP Director, Pharmacy Services SelectHealth Murray, UT

Gary M. Owens, MD President Gary Owens Associates Philadelphia, PA Kim A. Papp, MD, PhD Founder and President Probity Medical Research Waterloo, Ontario, Canada Jeffrey S. Peller, MD Practicing Rheumatologist Harbin Clinic/Rheumatology Rome, GA Edmund J. Pezalla, MD, MPH National Medical Director for Pharmacy Policy and Strategy Aetna Hartford, CT Ronald van Vollenhoven, MD, PhD Associate Professor Karlinska University Hospital Solna Stockholm, Sweden F. Randy Vogenberg, RPh, PhD Principal Institute of Integrated Healthcare Greenville, SC William A. Sunshine, MD, FACR Rheumatology Practice Boca Raton & Delray Beach, FL

Lynn Nishida, RPh Director, Clinical Services Catamaran Center of Excellence Northwest Region Portland, OR

Director, Production & Manufacturing Alaina Pede Director, Creative & Design Robyn Jacobs Design Managers Chris Alpino Lora LaRocca Director, Digital Marketing Samantha Weissman Digital Content Manager Anthony Trevean Digital Editor John Parkinson Digital Media Specialist Charles Easton IV Jr Digital Content Manager Walford Guillaume Junior Digital Developer Christina Bethencourt Sales Operations Manager Margaret Hoffmann Executive Administrative Assistant/Office Manager Dana Rivera Administrative Assistant Colette Puhalski IT Manager Kashif Javaid Office Coordinator Robert Sorensen

President Abigail Adair Account Group Supervisor Karie Gubbins Account Supervisors Alex Charles Deanna Martinez Senior Account Executive Jeremy Shannon Meg Spencer Business Development Advisor Saher Almaita

ASSOCIATION & CONGRESS DIVISION Association Director Patrice Melluso Meeting & Event Planner Linda Mezzacappa Senior Account Executive George Fuller Project Manager Rachael Baranoski Senior Project Coordinator Gretchen Dann Project Administrator Sara Mohamed

Value-Based Care in Rheumatology, ISSN (applied), is published 6 times a year by Engage Healthcare Communications, LLC, 1249 South River Rd, Suite 202A, Cranbury, NJ 08512.

Copyright © 2016 by Engage Healthcare Communications, LLC. All rights reserved.

Value-Based Care in Rheumatology is a trademark of Engage Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher.

Printed in the United States of America.

The ideas and opinions expressed in Value-Based Care in Rheumatology do not necessarily reflect those of the Editorial Board, the Editors, or the Publisher. Publication of an advertisement or other product mentioned in Value-Based Care in Rheumatology should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturers about any features or limitations of products mentioned. Neither the Editors nor the Publisher assume any responsibility for any

injury and/or damage to persons or property arising out of or related to any use of the material mentioned in this publication.

EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, Value-Based Care in Rheumatology, 1249 South River Rd, Suite 202A, Cranbury, NJ 08512. E-mail: editorial@valuebasedcancer. com Phone: 732-992-1880. Correspondence regarding permission to reprint all or part of any article published in this journal should be addressed to REPRINT PERMISSIONS DEPARTMENT, Engage Healthcare Communications, LLC, 1249 South River Rd, Suite 202A, Cranbury, NJ 08512.

POSTMASTER: Correspondence regarding subscriptions or change of address should be directed to CIRCULATION DIRECTOR, Value-Based Care in Rheumatology, 1249 South River Rd, Suite 202A, Cranbury, NJ 08512. Fax: 732-992-1881. YEARLY SUBSCRIPTION RATES: 1 year: $99.00 USD; 2 years: $149.00 USD; 3 years: $199.00 USD.

MISSION STATEMENT Value-Based Care in Rheumatology provides a forum for payers, providers, and the entire rheumatology team to consider the cost-value issues particular to rheumatology treatments. This unique focus is achieved through news coverage from major rheumatology meetings and the rheumatic diseases literature, supplemented with commentaries and perspectives from those involved in evaluating therapies, treating patients, and paying for care.

EHC1064-3

Value Propositions Tocilizumab Effective, Highly Retentive in Patients with Rheumatoid Arthritis

Decernotinib, DMARD Combination Reduces Symptoms, Signs of Rheumatoid Arthritis

According to the results of a recent, 2-year efficacy study, tocilizumab is effective when used as monotherapy or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. Use of the drug has also demonstrated high rates of retention.

Researchers evaluating the efficacy, retention rates, and predictors of response of tocilizumab in patients with rheumatoid arthritis conducted a prospective, longitudinal, open-label study in patients receiving tocilizumab 8 mg/kg every 4 weeks in a clinical practice setting. They used European League Against Rheumatism (EULAR) response criteria to evaluate clinical responses, and also measured low activity and remission rates in accordance with the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28ESR) and Clinical Disease Activity Index (CDAI).

According to the results, and following 6 months of treatment, the EULAR response rate was 86.63% and the DAS28 remission rate was 53.7%. At month 24, rates of low disease activity were 52.9% and 47.1% on CDAI and DAS28, respectively.

No statistically significant differences were observed in the EULAR response rates of low activity and remission on DAS28 between patients receiving tocilizumab monotherapy and as combination therapy, or between patients positive or negative for rheumatoid factor/anti–cyclic citrullinated peptide antibodies.

Remission and low activity rates after 6 months of treatment were better in patients who were naïve to biologic therapy, and, at month 24, the retention rate was 61%. Adverse events were among the most common reasons for treatment discontinuation.

“Tocilizumab is effective in [rheumatoid arthritis], has a similar efficacy when used alone or in combination with synthetic DMARDs and shows high retention rates,” the study authors reported. Notario Ferreira I, Ferrer González MA, Morales Garrido P, et al. Reumatol Clin. 2016 May 9.

Epub ahead of print.

Patients with rheumatoid arthritis and an inadequate response to disease-modifying antirheumatic drug (DMARD) monotherapy may experience a reduction in signs and symptoms of their condition when given decernotinib (VX-509) in combination with stable DMARD therapy, researchers found.

Seeking to examine the early effects of the decernotinib and DMARD combination on joint structures in adults with rheumatoid arthritis, Mark C. Genovese, MD, Professor, Division of Immunology and Rheumatology, Stanford University, Palo Alto, CA, and colleagues conducted a randomized, placebo-controlled, double-blind, dose-ranging study of patients with rheumatoid arthritis and inadequate DMARD response.

Measured outcomes included the rheumatoid arthritis magnetic resonance imaging scoring (RAMRIS) system, American College of Rheumatology scores (ACR20; improvement of ≥20%), and Disease Activity Score 28 (DAS28) using C-reactive protein (CRP). Patients in the study were administered decernotinib 100 mg, 200 mg, or 300 mg, or placebo once daily for 12 weeks.

At 12 weeks, the study authors observed an ACR20 response of 63.6%, 60.0%, and 60.0% in the decernotinib 100-mg, 200-mg, and 300-mg groups, respectively, versus 25.0% in the placebo group. Significant differences were noted between the RAMRIS synovitis scores of the placebo group and all decernotinib dose groups (P <.01), and between the RAMRIS osteitis scores of the placebo and decernotinib 300-mg groups (P <.01). With increasing decernotinib doses, DAS28-CRP scores decreased in a dose-dependent manner. Genovese MC, Yang F, Østergaard M, Kinnman N. Ann Rheum Dis. 2016 Apr 15. Epub ahead of print.

Cardiovascular Screening Cost-Effective in Patients with Rheumatoid Arthritis

Not only does early detection and preemptive treatment play a significant role in reducing excess risk for cardiovascular disease in patients with rheumatoid arthritis, but it is also cost-effective, according to new data.

Using a Markov chain model, a time frame of 10 years, and a variety of scenarios based on different guidelines, Wietske Kievit, PhD, Department of Health Evidence, Radboud University Nijmegen Medical Centre, The Netherlands, and colleagues assessed whether cardiovascular screening is medically cost-effective in this patient population.

Limiting values were obtained primarily from the literature and from patients with rheumatoid arthritis screened for cardiovascular diseases at the Radboud University Nijmegen Medical Centre. Conveyed as costs per quality-adjusted life-year (QALY) gained, the primary outcome measure was incremental cost-effectiveness. Multiple scenarios were devised, and probabilistic sensitivity analysis—which was described using willingness-to-pay curves—was performed.

In 82% of the base-case scenario simulations, screening was more common than no screening. There was a 0.09 mean QALY gain and approximately $1100 in mean cost-savings. Throughout the various scenario simulations, small differences in cost-effectiveness were demonstrated. The study authors also noted that the probability of screenings being more common than no screenings stayed high, with the lowest probability being 50% in a very conservative scenario.

“Screening for cardiovascular events in [rheumatoid arthritis] patients was estimated to be cost-effective with high chances of being less expensive and more effective,” Dr Kievit and colleagues concluded. “These results support endorsement of screening for CV risk in patients with [rheumatoid arthritis].” Kievit W, Maurits JS, Arts EE, et al. Arthritis Care Res (Hoboken). 2016 May 9. Epub ahead of print.

Efficacy of Etanercept, Methotrexate Combination Independent of Methotrexate Dosage

Regardless of the methotrexate dosage, etanercept and methotrexate combination therapy resulted in similar efficacy outcomes at 24 months among patients with rheumatoid arthritis.

“These findings suggest that lower doses of [methotrexate] can be considered in patients who do not tolerate [methotrexate], while maintaining clinical efficacy and [quality of life],” according to the authors.

In an effort to study the impact of methotrexate dosage on clinical, functional, and quality-of-life outcomes in patients with rheumatoid arthritis after 24 months of treatment, investigators conducted a post hoc analysis using data from the etanercept and methotrexate combination treatment arms of the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) and Combination of Methotrexate and Etanercept in Active Early Rheumatoid Arthritis (COMET) studies. Data were stratified by methotrexate dosage at 24 months (ie, low dose, <10.0 mg per week; medium dose, 10.0-17.5 mg per week; and high dose, >17.5 mg per week), and methotrexate monotherapy groups served as controls.

In addition to including descriptive summaries of demographic and disease characteristics of these subgroups at baseline, the study authors evaluated Disease Activity Score 28 (DAS28) low disease activity (LDA) and remission; American College of Rheumatology 20%, 50%, and 70% improvement criteria (ACR20, ACR50, and ACR70) responses; and changes from baseline in DAS28, Health Assessment Questionnaire Disease Index (HAQ-DI), and EuroQol 5-dimensions visual analog scale (EQ-5D VAS).

Aside from disease duration, baseline demographics were similar among the low-, medium-, and high-dose methotrexate groups in the etanercept and methotrexate combination and methotrexate monotherapy arms. At 24 months, and across all methotrexate dosage groups, responses to the etanercept and methotrexate combination therapy were consistently high; rates were very similar in DAS28 LDA and remission, and ACR20, ACR50, and ACR70. In addition, the researchers noted that DAS28, HAQ-DI, and EQ-5D VAS improvements in the combination treatment arm were not dependent on methotrexate dosage. Gallo G, Brock F, Kerkmann U, et al.

RMD Open. 2016;2:e000186.

Conference News

Managing Pain After TKA Significantly Lowers... who received the injectable suspension following primary TKAs between July 1, 2013, and March 31, 2015, were included, along with 5785 controls from the same hospitals who did not receive the injection after their surgeries between January 1, 2011, and March 31, 2015. Patients in both groups were similar with regard to age, sex, and Charlson Comorbidity Index; more whites were included in the experimental group than in the control group.

Mean hospital costs were $823 lower among patients who received the bupiv­ acaine liposome injectable suspension, compared with patients who did not ($16,387 vs $17,210; P <.001). After adjusting for the hospital, age, sex, Charlson Comorbidity Index, and race, use of the injectable was estimated to statistically and significantly reduce total hospital costs (-$1020).

“The Comprehensive Care for Joint Replacement (CJR) program from Medicare will pay hospitals a fixed amount to cover all services from admission to 90 days after discharge for TKA to align incentives to reduce hospital costs for this common and increasingly prevalent surgical procedure,” the researchers explained. These data suggest that managing postsurgical pain with bupivacaine liposomal injectable suspension may alleviate hospital costs under the CJR program.

Dagenais S, Kang, A, Scranton R. A comparison of total hospitals costs for Medicare patients undergoing total knee arthroplasty with or without bupivacaine liposomal injectable suspension. Presented at: International Society for Pharmacoeconomics and Outcomes Research 21st Annual International Meeting; May 21-25, 2016; Washington, DC. Abstract 45745.

New Model Identifies ShortComings in Cost-Effectiveness Treatment Model

Payers should consider implementing a solid framework that addresses subsequent lines of therapy, and the impact of adverse events on mortality, to evaluate the cost-effectiveness of psoriatic arthritis (PsA) treatment, according to recent research.

Using a targeted literature review, investigators sought to propose an improved modeling approach for payers by evaluating existing health technology assessment submissions, and identifying shortcomings of current models. Factors such as proximity to clinical practice, treatment sequencing, as well as adverse events were taken into account during the analysis.

Initial treatment continuation was determined using a model of shortterm response criterion (ie, PsA Response Criteria and/or changes in Psoriasis Area and Severity Index). Al-

though the models allowed withdrawal from treatment because of adverse events or loss of efficacy in the longterm, the investigators identified several shortcomings, which they addressed in their model.

In particular, the proposed model took into account subsequent treatment lines, and the impact of adverse events on mortality, and allowed for inclusion of other factors, such as different population types—based on previous biologic treatment experience and PsA severity—and the ability to model subsequent biologic or conventional treatments.

Graham CN, Gunda P, Miles L, et al. A new cost-effectiveness framework for modeling psoriatic arthritis treatments. Presented at: International Society for Pharmacoeconomics and Outcomes Research 21st Annual International Meeting; May 21-25, 2016; Washington, DC. Abstract 45299.

The proposed model took into account subsequent treatment lines, and the impact of adverse events on mortality.

Long-Term Adherence to Biologics Linked to Treatment Effectiveness Early On

Using an algorithm applied to claims data, investigators were able to determine that adherence to biologics during the second year of treatment may positively correlate with effective treatment in the first year among patients with rheumatoid arthritis (RA).

As part of their research, the investigators evaluated year 2 adherence in patients with RA who were effectively treated, or persistent with, initial biologic therapy during their first year of treatment. To be eligible for study inclusion, patients from the IMS PharMetrics Plus database had to have initiated treatment with a biologic between January 2009 and December 2012, and remain enrolled for 2 continuous years after they started biologic therapy.

Treatment effectiveness and persistence were evaluated in all patients at year 1, whereas adherence was evaluated at year 2 in effectively treated and persistent patients; patients who were nonadherent in year 1 were evaluated separately at year 2.

The patient population eligible for inclusion (10,374) comprised 76.1% women, with a median age of 51 years; 77.9% were receiving a previously given

disease-modifying antirheumatic drug.

At year 1, approximately 30% of patients were effectively treated, whereas approximately 50% were persistent.

Adherence was seen in 46.0% of patients in year 1, and 33.6% in year 2.

Furthermore, the researchers found that patients who were effectively treated during the first year of therapy were significantly more adherent in year 2, compared with patients who were not treated effectively. Similar trends were seen among patients who were persistent in year 1, versus patients who were not.

“Establishing effective treatment in year 1 should result in improved adherence and maintained low disease activity in year 2,” the investigators concluded.

Stolshek B, De AP, Tang D, et al. Adherence of initial biologic during the second year in rheumatoid arthritis patients with one year of effective treatment. Presented at: International Society for Pharmacoeconomics and Outcomes Research 21st Annual International Meeting; May 21-25, 2016; Washington, DC. Abstract 44856.

Abatacept Has Better Cost per Responder Than Adalimumab

From a payer’s perspective, cost per response of abatacept is more favorable than that of adalimumab among patients with rheumatoid arthritis (RA) who are anti-citrullinated protein antibody–positive. Greater cost-savings were seen when more stringent American College of Rheumatology (ACR)70 and ACR90 response criteria were applied, and with increasing anti-citrullinated protein antibody levels, authors of a recent study have found.

“Effective treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) is a significant economic burden in the US healthcare system,” they explained.

Together with data from the AMPLE (Abatacept versus Adalimumab Comparison in Biologic-Naïve RA Subjects with Background Methotrexate) trial, the investigators used a decision tree to compare the costs per response of abatacept and adalimumab in a cohort of patients (N = 1000) with RA who are anti-citrullinated protein antibody– positive.

Overall, the cost per response in this patient population favored abatacept subcutaneous injections versus adalimumab subcutaneous injections for ACR20 ($5514 vs $5619), ACR70 ($10,094 vs $11,237), and ACR90 ($20,187 vs $36,002) responses, as well as Health Assessment Questionnaire Disability Index scores ($6134 vs $6540). In addition, the investigators observed that cost per ACR90— as well as cost per Health Assessment

Continued from page 1

Questionnaire Disability Index score —consistently favored abatacept subcutaneous injections across anticitrullinated protein antibody–positive quartiles, compared with adalimumab subcutaneous injections.

Walsem AV, Patel C, Johnston S, et al. Anti-ccp2 quartile comparison of the cost per response for abatacept compared to adalimumab based on ample in the United States. Presented at: International Society for Pharmacoeconomics and Outcomes Research 21st Annual International Meeting; May 21-25, 2016; Washington, DC. Abstract 45135.

“Effective treatment with bDMARDs is a significant economic burden in the US healthcare system.”

Significant Economic Burden Linked to High Disease Activity in Patients with RA

Rates of healthcare resource use and economic burden are high among patients with rheumatoid arthritis (RA) who have higher disease activity per the Clinical Disease Activity Index, according to recent data.

Adult patients with RA (N = 3749), as defined by the International Classification of Diseases, ninth Edition, were identified from a large claims database and an RA registry between 2006 and 2015.

The mean age of the study population was 57 years, and 76% were women.

Overall, 24.11% of the study participants had high disease activity, 31.93% had moderate disease activity, and 26.91% had low disease activity; 17.04% of the patients were in remission.

Average all-cause total costs were found to be $27,008—including $5262 in costs associated with RA—during the 12-month follow-up period of the study. In addition, the investigators observed that patients with higher disease activity made more frequent office visits (average, 12.31) compared with patients with moderate disease activity (11.79), low disease activity (11.71), and those in remission (11.59). Outpatient costs, as well as pharmacy costs, were found to be the primary cost drivers of all-cause and RA-related costs in patients with high, moderate, and low disease activity, in addition to patients in remission.

Kariburyo MF, Du J, Xie L, Baser O. Assessing the economic burden of rheumatoid arthritis patients with different clinical disease activity index scores: a probabilistic matching study. Presented at: International Society for Pharmacoeconomics and Outcomes Research 21st Annual International Meeting; May 21-25, 2016; Washington, DC. Abstract 45566.

Continued on page 6

Conference News

Ultrasound Not Indicated for Routine Follow-Up in Patients with Early RA

By Alice Goodman London, United Kingdom—Routine ultrasound is not justified for the follow-up of patients with early rheumatoid arthritis (RA) treated with an aggressive treat-to-target strategy, according to results from the ARCTIC trial.

“A treatment strategy based on structured ultrasound assessments aiming for imaging remission does not lead to improved outcomes compared to a conventional strategy based on clinical and laboratory parameters alone,” stated presenting author Espen Haavardsholm, MD, PhD, Senior Researcher and Rheumatologist, Diakonhjemmet Hospital, Oslo, Norway. “Ultrasound is not cost-effective for assessing outcomes and may lead to over treatment. This is an important consideration for optimal use of resources.”

Dr Haavardsholm presented results from the ARCTIC trial at the 2016 European League Against Rheumatism (EULAR) Annual Congress in June.

“The cornerstone of RA care is early initiation of [disease-modifying antirheumatic drug (DMARD)] therapy, tight control of disease, defining response, and treating to target,” he noted. “Although complete remission is achievable in a majority of RA patients, subclinical inflammation [detectable on ultrasound] may be present. It is controversial whether strategies targeting imaging remission are feasible and cost-

Continued from page 5

Greater Disease Burden Seen in Patients with Tophaceous Gout

In an effort to describe patient characteristics and healthcare resource use among patients with and without tophi, researchers systematically assessed data from October 2012 patient chart audits, and identified category, dose of uratelowering therapy, as well as patient characteristics.

Overall, the charts of 125 primary care physicians and 125 rheumatology patients were abstracted for the analysis (N = 1159). Approximately 24% of the patients had tophaceous gout. Compared with patients without tophaceous gout, these patients had gout for a significantly longer period of time (39 months vs 66 months), reported more flares annually (1.8 vs 2.5), and were more likely to have joint damage (6.6% vs 43.6%), the researchers observed.

These patients were also more likely to have higher rates of cardiovascular disease, chronic obstructive pulmonary

effective, and whether this approach improves outcomes.”

ARCTIC was an open-label, randomized, multicenter, controlled trial that included 238 patients with newly diagnosed RA who were naïve to DMARD treatment. Patients were randomized 1:1 to an ultrasound tight control (UTC) strategy that targeted clinical and imaging remission (defined as no ultrasound power-Doppler signal), or conventional tight control (CTC) strategy targeting clinical remission.

Patients in both arms were treated in accordance with a stepwise DMARD escalation strategy, starting with methotrexate, then triple therapy, then biologic DMARDs if the target was not reached. An ultrasound scoring system was used to assess 32 joints. Experienced sonographers performed the ultrasound examinations.

The primary end point was the number of patients who experienced a sustained clinical remission between 16 and 24 months, absence of swollen joints, and no evidence of progression of radiographic joint damage.

Remission was assessed by Disease Activity Score (DAS) <1.6, and radiographic progression was assessed using the Modified Sharp Score, both at 24 months.

Little difference in measured outcomes was seen between the 2 strate-

gies, and patients randomized to UTC were stepped up to the next level of treatment more often than those in the CTC group.

“At the end of the study, 28.8% of those in the UTC group were being treated with biologics versus 17% in the CTC group, despite there being little or no difference in DAS score,” Dr Haavardsholm told listeners at EULAR 2016. “More patients in the UTC group also received more intra-articular injections.”

The primary end point was achieved in 22% of the UTC group, compared with18.8% of the CTC group—a non significant difference. For individual components of the primary end point, no swollen joints were detected in 52.5% versus 54.5% of the UTC and CTC groups, respectively.

In the UTC and CTC groups, DAS remission at 16 to 24 months was observed in 54.2% and 51.8% of patients, respectively. No radiographic progression was observed at 16 to 24 months in 41.5% and 34.8% of patients in the same respective cohorts. At 24 months, the percentage of patients in DAS remission was practically identical (67.8% for UTC, and 67.0% for CTC).

According to EULAR criteria, a good/moderate response was observed at 24 months in 83.1% of the UTC cohort, and 80.4% of the CTC group. In

addition, at 24 months, the Modified Sharp Score was similar between both groups (1 and 1.5 in the UTC and CTC groups, respectively).

At the end of the study, 53.4% of patients in the UTC group were on methotrexate, versus 71.4% in the CTC group (P = .004). Triple therapy was used by 17.8% versus 11.6% of patients in the same respective groups—a nonsignificant difference. Importantly, 28.8% of the UTC group versus 17% of the CTC group were on biologics, the most costly type of therapy (P = .03).

There were no differences in safety outcomes between the 2 groups, even though more biologics were used in the UTC group.

According to Dr Haavardsholm, ultrasounds confirm what clinicians are already aware of, and in the case of this study, inflammation that was detected via ultrasound only impacted the treatment of a small number of patients. He asserted that conventional treatment was good enough for this patient population. n

disease, congestive heart failure, diabetes, depression, hypertension, osteoarthritis, and kidney stones.

Furthermore, the investigators reported that patients with tophaceous

nonsteroidal anti-inflammatory drugs.

“Preventing the development of tophi or resolving crystal burden by treating to guideline targets remains a rarely achieved goal for patients with and without tophi,” the researchers concluded.

”Preventing the development of tophi or resolving crystal burden by treating to guideline targets remains a rarely achieved goal for patients with and without tophi.”

Tafesse E, Khanna P, Kabadi S, et al. The burden of tophaceous and non-tophaceous gout in the United States. Presented at: International Society for Pharmacoeconomics and Outcomes Research 21st Annual International Meeting; May 21-25, 2016; Washington, DC. Abstract 44832.

retrospective study using a large US claims database. Criteria for inclusion included patients who initiated rituximab between March 1, 2006, and March 31, 2011, were preindex exposed to anti–tumor necrosis factor-α therapy, as well as aged ≥18 years, and continuously enrolled for 12 months before and ≥270 days following index.

Of the 594 patients with a mean age of 55 years (women, 81%) who met criteria for inclusion, the researchers observed that oral glucocorticoid use probabilities significantly decreased with time and increasing proportion of days covered. The results suggested that increasing rituximab adherence was associated with statistically significant reduction of oral glucocorticoid use over time. n

gout were more likely to be treated with urate-lowering therapy, and take colchicine and steroids than those without tophi; they were also less likely to take

Better Adherence Linked to Oral Glucocorticoid Use Reduction in Patients with RA

Although there are therapeutic benefits associated with oral glucocorticoid use in patients with rheumatoid arthritis (RA), there are also side effects associated with use of the drug.

To determine whether rituximab adherence was associated with oral glucocorticoid use reduction in this patient population, researchers conducted a

Reference

Haavardsholm EA, Aga AB, Olsen IC, et al. Ultrasound in the management of rheumatoid arthritis: results from the randomized controlled ARCTIC trial. Presented at: 2016 European League Against Rheumatism Annual Congress; June 8-11, 2016; London, United Kingdom. https://b-com.mci-group.com/Abstract/Statistics/ AbstractStatisticsViewPage.aspx?AbstractID=302308.

Accessed June 10, 2016.

Johnston SS, Kamath T, Shi N, et al. Association between rituximab adherence and oral glucocorticoid use in rheumatoid arthritis patients with prior exposure to anti-tumor necrosis factor-alpha therapy. Presented at: International Society for Pharmacoeconomics and Outcomes Research 21st Annual International Meeting; May 21-25, 2016; Washington, DC. Abstract 32604.

Rheumatology Update

Latest Data from the CDC Suggest That 1 in 4 US Adults Are Diagnosed with Arthritis

By Sophie Granger

A

ccording to a recently published analysis of 2014 Behavioral Risk Factor Surveillance System (BRFSS) data, approximately 1 in 4 adults is currently living with physician-diagnosed arthritis in the United States.1,2 A primary cause for disability that affects approximately 52.5 million US adults, arthritis is expected to affect 78.4 million adults in 2040.1 Although national data on the prevalence of physician-diagnosed arthritis has been well-documented, little information has been published on the state and county levels, where interventions are implemented and can have the greatest effect. Seeking to estimate the frequency of physician-diagnosed arthritis among adults, researchers from the Centers for Disease Control and Prevention (CDC) analyzed data from the 2014 BRFSS, an annual, randomized phone survey representative of noninstitutionalized US adults aged ≥18 years.

Notably, respondents to the 2014 BRFSS were classified as having physician-diagnosed arthritis if they responded to, “Have you ever been told by a doctor or other health professional that you have some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia?” with “yes.”

The CDC’s analysis, which used an

age-standardized model to predict the prevalence of physician-diagnosed arthritis by county, summarized data for respondents from all 50 states, the District of Columbia, Puerto Rico, and Guam. Overall, the analysis revealed that, across all 50 states and the District of Columbia, the age-standardized median frequency of physician-diagnosed arthritis was 24% (range, 18.8%35.5%). According to the model, physician-diagnosed arthritis prevalence varied significantly by county, ranging from 15.8% to 38.6%.

“The high prevalence of arthritis in all counties, and the high frequency of arthritis-attributable limitations among adults with arthritis, suggests that states and counties might ben­ efit from expanding underused, evidence-based interventions for arthritis that can reduce arthritis symptoms and improve self-management,” stated lead author Kamil E. Barbour, PhD, Division of Population Health, National Center for Chronic Disease Prevention and Health Promotion, CDC, and colleagues in a published report of the analysis’ results.

A multilevel regression and poststratification approach—including 2014 BRFSS individual-level data on age, sex, and race/ethnicity—was used

to estimate model-predicted arthritis frequency for counties.

A higher prevalence of arthritis was observed in people identifying as American Indians/Alaska Natives or multiracial compared with whites or black non-Hispanics, and a lower frequency of the condition was noted in Hispanics and Asians compared with whites or black non-Hispanics.

Among patients from a combined sampling, arthritis frequency ranged from 8.8% to 53.3% for respondents aged 18 to 44 years and ≥65 years, respectively. Arthritis frequencies standardized for age were higher among women than men, and among people with less versus more education.

Estimated age-standardized arthritis prevalence varied among states and counties. For states and territories, physician-diagnosed arthritis ranged from 18.8% in Hawaii to 35.5% in West Virginia (median, 24.0%). The District of Columbia, Guam, and 47 states had an age-standardized prevalence of doctor-diagnosed arthritis of ≥20% in 2014; 4 states had an arthritis prevalence of ≥30%. Counties along the Appalachian Mountains, Mississippi River, and Ohio River tended to be in the highest quintiles of age-standardized model-predicted arthritis

prevalence, as were the majority of counties in Alabama, Kentucky, Michigan, Tennessee, and West Virginia.

According to the report, physical activity (ie, walking, biking, swimming, and other low-impact activities) can reduce joint pain in patients with arthritis, and community programs, such as EnhanceFitness and Walk With Ease, provide guidance on how to safely remain physically active. Furthermore, confidence in adults with arthritis can be improved when they manage their arthritis symptoms with community self-management education interventions.

“Given the high prevalence of arthritis, health care providers and public health professionals can address arthritis by prioritizing self-management education and appropriate physical activity interventions as effective ways to improve health outcomes,” the authors of the CDC report concluded. n References

1. Barbour KE, Helmick CG, Boring M, et al. Prevalence of doctor-diagnosed arthritis at state and county levels—United States, 2014. MMWR Morb Mortal Wkly Rep. 2016;65:489-494.

2. New CDC Survey Analysis: Nearly One in Four U.S. Adults Now Live with Doctor-Diagnosed Arthritis.

Atlanta, GA: American College of Rehumatology; May 19, 2016. www.rheumatology.org/About-Us/Newsroom/ Press-Releases/ID/747/New-CDC-Survey-AnalysisNearly-One-in-Four-US-Adults-Now-Live-withDoctor-Diagnosed-Arthritis. Accessed May 25, 2016.

Novel Biomarker May Be Useful Indicator for Etanercept Response

By E. K. Charles

P

roviding treatment options for patients with rheumatoid arthritis is paramount to treating the disease. Although existing therapies have been effective, treatment response is still a concern in this patient population.

“Biologic drug therapies represent a huge advance in treatment of rheumatoid arthritis,” Darren Plant, PhD, National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit, Manchester Academy of Health Sciences, United Kingdom, and colleagues explained. “How­ever, very good disease control is achieved in only 30% of patients, making identification of biomarkers of response a research priority.”

Allele Linked to Nonresponse

To determine whether differential DNA methylation patterns are a useful biomarker of tumor necrosis factor inhibitor therapy response, the investigators conducted an epigenome-wide association study to look at differences between good responders and nonresponders treated with etanercept. The data used for this study were based on patients from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate, and included patients aged ≥18 years who were clinically classified with rheumatoid arthritis per the American College of Rheumatology criteria. Thirty-six patients were included in each group, and response at 3 months was the time frame of interest.

Altogether, 5 positions were differently methylated between responders and nonresponders; the top 2 positions mapped to exon 7 of the LRPAP1 gene on chromosome 4. In addition, Dr Plant and colleagues identified a correlation between the A allele of the singlenucleotide polymorphism rs3468 and higher levels of methylation for these 2 positions. That particular allele was also associated with nonresponse, based on criteria from the European League Against Rheumatism.

Treatment Response Multifactorial

These data point to the functional significance of the LRPAP1 gene. The gene itself is highly expressed in mononuclear blood cells, and encodes a

protein that influences transforming growth factor β activity. Targeted ribonucleic acid sequencing of specific cell types in whole blood should be considered in future research, the study authors noted.

Although treatment response is multifactorial, Dr Plant and colleagues concluded, biomarker panels that include serology, and epigenetic, genetic, and transcriptomic factors may help better predict treatment response to therapy in patients with rheumatoid arthritis. n Reference

Plant D, Webster A, Nair N, et al. Differential methylation as a biomarker of response to etanercept in patients with rheumatoid arthritis. Arthritis Rheumatol.

2016;68:1353-1360.

Arthritis

Young Patients with Glenohumeral Arthritis: Etiology, Diagnosis, and Treatment

By E.K. Charles, MBS

A

lthough treatment options are available in elderly patients with shoulder arthritis, they are limited in young patients. In a recent review, Jonathan D. Barlow, MD, Shoulder and Elbow Surgeon, Department of Orthopaedics, The Ohio State University, Columbus, and Joseph Abboud, MD, Shoulder and Elbow Surgeon, Department of Orthopaedic Surgery, Rothman Institute, Philadelphia, PA, discussed ongoing diagnostic and treatment challenges, including surgical options in young patients with glenohumeral arthritis.

“Thorough history, physical, and radiographic analysis is paramount to distinguish possible secondary causes of arthritis, as well as to prepare for potential surgical management,” the study authors explained. “Nonoperative management is the mainstay of treatment of shoulder arthritis in this population.”

A Variety of Population Groups

There are several different populations of young patients with glenohumeral arthritis. In particular, some patients may have an underlying diagnosis of chondrolysis. It is characterized by rapid loss of articular cartilage from the humerus and glenoid, in the absence of osteophyte formation. These cases have been reported at an alarming rate, Dr Barlow and Dr Abboud report, and chondrolysis is cur-

rently the focus of research. Inflammatory arthritis has been reported in the literature as another potential cause of glenohumeral arthritis.

Young patients with glenohumeral arthritis and recurrent shoulder instability are one population of patients that present a challenge. Arthroscopy and open Bankart tend to have better long-term outcomes than other surgical interventions, such as Putti-Platt and Eden-Hybbinette.

The authors also discuss in detail other groups of patients with glenohumeral arthritis who may present with osteonecrosis, glenoid dysplasia, or osteoarthritis.

Considerations When Evaluating Patients

When performing workups in young patients with arthritis, the authors recommend starting with a thorough history of the patient, as well as a physical examination. Focus should also be placed on distinguishing glenohumeral arthritis pain versus other shoulder pains (eg, acromioclavicular joint, rotator cuff, and labral pathology), by asking patients about the quality and timing of the shoulder pain, as well as aggravating factors.

Patients should also be asked about other aspects of their medical history, including previous steroid use, sickle cell disease, and alcohol use.

Radiographic imaging should be a part of patients’ evaluations, including preoperative anterior posteriors with internal and external rotations, and axillary views. The authors also suggest that axial imaging can be helpful in young patients with complex histories and who have had previous operations.

“Nonoperative management is the mainstay of treatment of shoulder arthritis in this population.“ —Jonathan D. Barlow, MD, and Joseph Abboud, MD Ruling out infection in patients with a history of previous surgeries and atypical presentation is critical, and can be done by performing complete blood cell counts, erythrocyte sedimentation rates, and C-reactive protein laboratory studies, Dr Barlow and Dr Abboud emphasized.

Treatment Approaches

In general, the authors of the review recommend nonoperative treatment, such as physical therapy and anti-in-

flammatory medication when indicated, as the initial choice for young patients with glenohumeral arthritis. Corticosteroid injections, hyaluronic acid injections, and platelet-rich plasma may be considered if these treatment modalities are unsuccessful. Arthroscopic debridement, hemiarthroplasty, and total shoulder arthroplasty should be considered in young patients with shoulder arthritis if nonoperative options fail.

Dr Barlow and Dr Abboud discuss in detail the different surgical options for this patient population, one of which is glenohumeral debridement, which is used to preserve the joint, and allows the surgeon to assess the joint surfaces and rotator cuff directly. Arthroscopic resurfacing arthroplasty is another option for young patients with shoulder arthritis. It is considered an intermediate option, between arthroscopic debridement and hemiarthroplasty.

The authors also discuss the use of hemiarthroplasty and resurfacing hemiarthroplasty in specific subpopulations, as well as hemiarthroplasty with glenoid reaming, hemiarthroplasty with biologic interposition, newer resurfacing, and bipolar biologic resurfacing. n Reference

Barlow JD, Abboud J. Surgical options for the young patient with glenohumeral arthritis. Int J Shoulder Surg.

2016;10:28-36.

Rheumatoid Arthritis

Baricitinib Effective in Patients with Refractory Rheumatoid Arthritis

By Phoebe Starr

B

aricitinib, an oral Janus kinase (JAK) inhibitor taken once daily, improved signs and symptoms of rheumatoid arthritis (RA) in patients who were refractory to other treatments, including tumor necrosis factor (TNF) inhibitors, or other biologic disease-modifying antirheumatic drugs (DMARDs), according to investigators in a placebo-controlled, phase 3 trial reported on recently in the New England Journal of Medicine.

“These results provide evidence that

”Selective inhibition of JAK1 and JAK2 with once-daily baricitinib has clinical efficacy in patients with active [RA] that is refractory to aggressive standard-of-care treatments.“ —Marc C. Genovese, MD, and colleagues

selective inhibition of JAK1 and JAK2 with once-daily baricitinib has clinical efficacy in patients with active [RA] that is refractory to aggressive standard-ofcare treatments with both conventional synthetic DMARDs and biologic DMARDs,” observed Marc C. Genovese, MD, Stanford University Medical Center, Palo Alto, CA, and colleagues.

“The treatment benefits were larger with the 4-mg dose than with the 2-mg dose.”

Adverse events included infections and abnormal laboratory test results (eg, Continued on page 9

Treatment Update

Anti-TNF Treatment Makes Inroads in Hand OA

By Alice Goodman London, United Kingdom—The search for effective treatments for osteoarthritis (OA) has been elusive, with little or no progress regarding treatments that can slow disease progression. Two studies presented at the 2016 European League Against Rheumatism Annual Congress suggest that treatment with anti–tumor necrosis factor (TNF) agents may have potential in slowing disease progression in patients with hand OA.1,2 These are still early days, but together, these studies suggest that anti-TNF agents may find a role in slowing disease progression in patients with hand OA. Presence of TNF in Affected Joints

Ruth Wittoek, MD, PhD, Rheumatologist, Department of Rheumatology, Ghent University, Belgium, and lead author of the first study explained that there are no animal models of hand OA, and it is difficult to obtain biopsies or fluid aspiration from small finger joints affected with hand OA.1 Using scintigraphy, Dr Wittoek and her coauthors took static images of both hands of 5 patients with erosive OA <15 minutes after administration of radio labeled certolizumab pegol (early phase), and again 4 to 6 hours posttreatment (late phase).

In the early phase, uptake of the radiolabeled anti-TNF agent was observed in 7 (7.8%) joints, but was quantitated as weak. In the late phase,

uptake was observed in 24 (26.7%) joints, with 5 described as strong and the remaining 19 described as weak.

No uptake of the radiolabeled antiTNF was seen in metacarpophalangeal joints. Uptake of the radiolabeled anti-TNF agent was linked to signs of disease activity, including tender, swollen, and radiographically active joints. Late uptake was present in 12 (36.4%) of 33 tender joints, and 12 (21.1%) of 57 nontender joints. Late uptake was present in 18 (29%) of 62 active joints, but only 6 (21.4%) of 28 noninflamed joints.

“Soft-tissue swelling strongly correlated with uptake of certolizumab pegol, meaning a lot of TNF was present in these joints,” Dr Wittoek explained.

“These data further solidify the rationale for cytokine-directed therapies in OA.”

etanercept was superior to placebo for pain and structural damage assessed by the Ghent University Scoring System (GUSS) in patients who were symptomatic, had inflammatory disease, and completed the study. The drug was particularly effective in joints with signs of inflammation, noted lead author Margreet Kloppenburg, DM, Rheumatology, Clinical Epidemiology, Leiden University Medical Center, The Netherlands.

The beneficial effect of etanercept on bone marrow lesions was more pronounced in joints with synovitis at baseline.

Etanercept Benefits in Hand OA

Results from a multicenter, double-blind, randomized, placebo-controlled trial demonstrated that etanercept has benefits related to pain relief and structural damage in patients with hand OA.2 The study involved 90 patients (mean age, 60 years) randomized to treatment for 1 year with subcutaneous etanercept 50 mg weekly—for 24 weeks, then 25 mg per week for the remainder of the year—versus placebo.

Etanercept did not meet the primary end point of the trial, which was level of OA pain assessed on a visual analog scale (VAS) at 24 weeks. However,

can inhibit bone marrow lesions in patients with hand OA.3 In 20 patients with symptomatic erosive OA and signs of inflammation in ≥1 interphalangeal joints, contrast magnetic resonance images were obtained of joints at baseline and 1 year; images were scored for synovitis and bone marrow lesions. The presence of bone marrow lesions were associated with the erosive and remodeling phases of erosive hand OA. The beneficial effect of etanercept on bone marrow lesions was more pronounced in joints with synovitis at baseline. The study authors theorize that the beneficial effect of etanercept on bone marrow lesions is because of an interaction between synovium and subchondral bone that could be influenced by blocking TNFs. n References

Although the difference between the 2 treatment arms was not statistically significant on the VAS pain scale, an intent-to-treat analysis showed numerical differences favored etanercept. An interaction was observed between soft swelling/erythema and etanercept treatment on GUSS, and the difference favoring etanercept over placebo was statistically significant (P <.05).

Effect on Bone Marrow Lesions

A separate analysis of this study suggested that treatment with etanercept

1. Wittoek R, Carron P, Lanbert B, et al. Immunoscintigraphic detection of TNF by radiolabeled certolizumab pegol in patients with erosive hand osteoarthritis in relation to disease activity and structural progression: a proof of concept study. Presented at: 2016 European League Against Rheumatism Annual Congress; June 8-11, 2016; London, United Kingdom. Abstract OP0097.

2. Kloppenburg M, Ramonda R, Kwok WY, et al.

Randomized, placebo-controlled trial to evaluate clinical efficacy and structure modifying properties of subcutaneous etanercept (ETN) in patients with erosive inflammatory hand osteoarthritis (OA). Presented at: 2016 European League Against Rheumatism Annual Congress; June 8-11, 2016; London, United Kingdom.

Abstract OP0095.

3. Kroon FP, Wittoek R, Verbruggen G, et al. Effect of etanercept on synovitis and bone marrow lesions in the erosive hand osteoarthritis. Presented at: 2016 European League Against Rheumatism Annual Congress; June 8-11, 2016; London, United Kingdom.

Abstract OP0098.

Rheumatoid Arthritis

Baricitinib Effective in Patients with... increases in low-density lipoprotein cholesterol and creatinine levels). “These changes were predominantly minor and did not lead to withdrawal from the study,” according to the investigators.

Previously, phase 2 studies showed that baricitinib reduced disease activity in patients with RA who were naïve to biologic DMARDs. This phase 3 trial included 527 patients who had an inadequate response to—or experienced unacceptable side effects associated with—previous treatment with biologic DMARDs. Patients were randomized in a 1:1:1 ratio to baricitinib 2 mg or 4 mg per day, or placebo, and treated for 24 weeks.

A significantly higher number of pa-

tients treated with a 4-mg dose of bari­ citinib had ≥20% improvement in signs and symptoms of RA—according to American College of Rheumatology criteria—at week 12 versus those who received placebo (55% vs 27%, respectively; P <.001). The 4-mg dose group also had significantly higher scores compared with the placebo group on the Health Assessment Questionnaire-Disability Index, and the 28-joint Disease Activity Score based on C-reactive protein level (P <.001 for both measures).

Baricitinib 4 mg daily was numerically—but not statistically—superior to placebo on the Simplified Disease Activity Index score of ≤3.3 (indicating

remission) at 12 weeks, but the difference between these 2 treatment arms became significant at 24 weeks (P <.01).

A beneficial effect of baricitinib was observed in all analyzed subgroups, regardless of how heavily pretreated with biologic DMARDs they were.

The authors pointed out that the patients enrolled in this trial had particularly refractory disease, having received multiple previous biologic therapies. They wrote that the beneficial treatment effect observed in this study appeared to be favorable compared with historical trials of currently approved therapies for patients with inadequate responses to TNF inhibitors.

This population is growing, and treat-

ment for them represents an unmet need, they wrote.

Limitations of the study include limiting the treatment effect to 24 weeks, and lack of radiographic data showing the effect of treatment on structural joint damage. Other phase 3 trials, however, will address these limitations.

Based on results of this and other studies, Eli Lilly and Incyte filed for US Food and Drug Administration approval for baricitinib in January 2016, and approval is expected to be granted later this year. n Reference

Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374:1243-1252.

Osteoarthritis

Rheumatologists Should Not Underestimate the Burden of OA

By Alice Goodman London, United Kingdom—Rheumatologists are fully aware of the impact of rheumatoid arthritis (RA) on patients’ lives, but underestimate the severity and impact of osteoarthritis (OA), according to the researchers of a study that looked at physician and patient perceptions of global disease status in both conditions.

“Osteoarthritis is a common and debilitating disease. Patients with osteoarthritis have functional disability and the presence of osteoarthritis predicts mortality,” stated Isabel Castrejon, MD, PhD, Assistant Professor, Rush University Medical Center, Chicago, IL, and lead author of the study. “Our study suggests that we are not doing enough for patients with this disease and that we [underestimate] its severity and impact on their lives.”

“The discordance between physician and patient perception of disease severity that we identified is important because of the negative impact it can have on shared decisions concerning the best choice of therapy,” she added.

“This in turn is likely to interfere with treatment compliance and future outcomes.”

RA is generally perceived as a more severe medical condition than OA,

but recent evidence suggests that both diseases have similar burdens, the study authors note. Despite this, OA is still regarded as less severe.

The study was conducted in a routine rheumatology academic setting, where all patients completed a multidimensional health assessment questionnaire (RAPID3) for physical function, pain, and patient global assessment, scoring from 0 to 10 with 10 being the most severe. A fatigue checklist, self-report joint count assessment, and demographic data were also included.

Physician global assessments of each patient were also performed, using the same scoring method.

Patients were then categorized as having the following: patient global assessments worse than physician global assessments, patient and physician assessments that were equal, or physician assessments that were worse than patient assessments.

The study included 216 patients with RA, and 243 patients with OA. Eighteen percent of patients with RA had discordant patient–physician assessments showing that patients rated their disease as more severe than physicians, compared with 34% of patients with OA. Patient and physician assess-

ments were concordant for 67% of patients with RA, and 56% with OA. Physicians rated disease severity as worse than patients’ ratings in 15% and 10% of RA and OA cases, respectively (P <.001).

“We treat RA more aggressively than OA, and we treat-to-target,” explained Dr Castrejon.

In general, orthopedic surgeons are more likely to be empathetic to patients with OA than rheumatologists, because the surgeons see patients at more advanced stages (ie, when they need joint replacement), whereas rheumatologists treat patients from the beginning.

“It is likely orthopedists’ perceptions would be more likely to be concordant with patients’ perceptions,” she suggested.

Although rheumatologists have an array of medications for treatment of RA, there are no medications that target the disease process of OA. In the absence of effective therapy—other than pain control—rheumatologists can communicate with, and show empathy toward, their patients with OA, and encourage weight loss and active exercise that can help their patients, Dr Castrejon commented.

Gerd Burmester, MD, European

League Against Rheumatism President and moderator of the press conference where this study was discussed, has been involved in a study of OA of the hand, a disease that, according to him, has been “completely neglected.”

“This presentation is important because it raises awareness of rheumatologists’ under rating the disease burden of OA for our patients,” Dr Burmester explained. “The rheumatologist has limited treatment options for hand OA. The secret of treating any OA is multidisciplinary team care, comprising physicians, acupuncturists, and physical therapy.”

He also noted the importance of identifying inflammatory destructive OA, and stated that, in such cases, use of cytokines might be helpful.

“We know that physical and occupational therapy work,” Dr Burmester elucidated. “If you take OA seriously and are [empathetic], you can help your patients.” n Reference

Castrejon I, Chua J, Block JA, Pincus T. Physician and patient estimates of global status are more likely to be discordant in osteoarthritis than in rheumatoid arthritis. Presented at: 2016 European League Against Rheumatism Annual Congress; June 8-11, 2016; London, United Kingdom. https://b-com.mci-group. com/Abstract/Statistics/AbstractStatisticsViewPage. aspx?AbstractID=305302. Accessed June 10, 2016.

Usefulness of Vitamin D Supplementation…

Continued from page 1

tibial cartilage volume in patients with symptomatic knee OA and low endogenous vitamin D levels.

“Even among study participants with low vitamin D levels, supplementation did not slow cartilage loss or improve WOMAC [Western Ontario and McMaster Universities Arthritis Index]-assessed pain. These data do not support the use of vitamin D in patients with knee OA,” according to the Xingzhong Jin, MD, Menzies Institute for Medical Research, University of Tasmania, Hobart, and colleagues.

The study included 413 patients with symptomatic knee OA and low vitamin D serum levels who were randomly assigned in a 1:1 ratio to oral vitamin D3 supplementation (50,000 IU) or placebo for 2 years.

All participants had symptomatic knee OA according to American College of Rheumatology criteria for ≥6 months prior to enrollment in the

”Even among study participants with low vitamin D levels, supplementation did not slow cartilage loss or improve WOMAC-assessed pain.“ —Xingzhong Jin, MD, and colleagues study, and pain scores of 20 mm to 80 mm on a 100-mm visual analog scale.

Mean age was 63.2 years, and 50% of participants were women. Of those randomized, 340 (82.3%) participants completed the study.

Serum levels of vitamin D significantly increased in the group assigned to supplementation compared with placebo over 2 years (40.6 nmol/L vs

6.7 nmol/L, respectively; P <.001).

Annual change of tibial cartilage or WOMAC pain score yielded no significant differences between treatment arms. No significant differences were seen between the 2 groups in changes to tibiofemoral cartilage defects or bone marrow lesions.

A total of 56 and 37 patients in the vitamin D supplementation and pla-

cebo groups, respectively, experienced ≥1 adverse events. Four participants in the supplementation group developed hypercalcemia compared with 2 in the placebo group. The study strengths include the randomized controlled design, and restricting enrollment to patients with low vitamin D levels, as they would be the most likely to benefit from vitamin D supplementation. In addition, patients had to fall within a predefined range of knee pain to prevent a ceiling or floor effect in the statistical analysis.

Patients with late-stage knee OA were excluded because they would have little cartilage remaining, and it would be hard to demonstrate effectiveness of supplementation. n Reference

Jin X, Jones G, Cicuttini F, et al. Effect of vitamin D supplementation on tibial cartilage volume and knee pain among patients with symptomatic knee osteoarthritis: a randomized clinical trial. JAMA. 2016;315:1005-1013.

Health & Wellness

Tug-of-War Between Ideal Lifestyle Habits and Reality Observed in Patients with RA

By E. K. Charles

W

ith the ever-present focus on maintaining a healthy lifestyle, patients with established rheumatoid arthritis (RA) struggle between their ideal lifestyle and the limitations inherent to their condition, according to recent research. Patients also described self-regulation when handling lifestyle habits (eg, guilt and motivation), and reported the importance of companionship.

Because little is known about the link between patients’ lifestyle habit experiences and their impact on quality of life in patients with established RA, Karina Malm, PT, PhDc, Department of Clinical Sciences, Section of Rheumatology, Lund University, Sweden, and colleagues conducted a descriptive and exploratory trial using data from the BARFOT (Better AntiRheumaticFarmacOTherapy) study, a multicenter, longitudinal observational analysis of Swedish patients with early RA. The study comprised 2800 patients aged ≥18 years enrolled between 1992 and 2006. The patients received a mailed questionnaire about lifestyle factors, and interviews were conducted with 22 of the patients.

Feelings of Insufficiency and Self-Regulation

Overall, patients described limitations in physical activity, diet, smoking, and alcohol consumption. For example, limitations associated with physical activity were related to joint

ty of life. Patients may experience guilt, for example, if their diet was unbalanced, or when family and friends gave their opinion about the diet they should be following. Motivation was observed among patients who wanted to change their diet and improve their

“Patients experience a struggle to determine the right balance of lifestyle habits in order to enhance quality of life and to try to achieve a normal life, independent of the established RA.” —Karina Malm, PT, PhDc, and colleagues pain, stiffness, and fatigue. These limitations led patients to feel that a sense of insufficiency was affecting their quality of life because they were not able to walk or perform certain activities; however, patients tried to adapt to these situations to continue remaining physically active.

Self-regulation—including guilt and motivation when performing lifestyle habits—also influenced patients’ quali-

quality of life. Similar observations were seen for physical activity, smoking, and alcohol consumption.

The Importance of Companionship and Belonging

Companionship, including the sense of belonging and pleasure when performing lifestyle habits, was another factor that impacted quality of life in patients with established RA. In par-

ticular, patients who smoked got the sense that they belonged with other smokers, and described experiencing pleasure when smoking, which impacted their quality of life. Interestingly, a similar sense of belonging was seen in patients who did not smoke, and who experienced pleasure from not being exposed to smoke, the investigators noted. This was also seen in terms of alcohol consumption, where patients described a feeling of belonging that had an impact on their quality of life, as well as experiencing pleasure by eating and drinking in social situations.

“The patients experience a struggle to determine the right balance of lifestyle habits in order to enhance quality of life and to try to achieve a normal life, independent of the established RA,” Ms Malm and colleagues concluded. “This is important new knowledge for health professionals when discussing lifestyle habits with RA patients.” n Reference

Malm K, Bremander A, Arvidsson B, et al. The influence of lifestyle habits on quality of life in patients with established rheumatoid arthritis-a constant balancing between ideality and reality. Int J Qual Stud Health Wellbeing. 2016;11:30534.

Vaccine Uptake Remains Low in Patients with RA

By Phoebe Starr

P

eople with rheumatoid arthritis (RA) are at increased risk for infection because of inherent immune dysregulation and chronic immunomodulatory therapy. However, uptake of the influenza vaccine (IVX), pneumococcal vaccine (PVX), and herpes zoster vaccine (HZVX) has been suboptimal among this at-risk group.

Researchers who conducted a single-center study found that a concerted effort to mount a system-level intervention made only modest inroads in improving vaccination rates. This disappointing result was attributed in part to flawed interoperability of electronic health records (EHRs), a widespread complaint throughout the US healthcare system; the need to identify a point person within a medical practice who is responsible for vaccination reminders and alerts; and the need for improved education of rheumatologists and other healthcare providers about the safety and efficacy of these vaccines, and what

the current vaccine recommendations are for patients with RA. “We conducted our study to implement and test a system-level intervention that included multiple quality improvement strategies to improve adherence to PVX, annual IVX, and HZVX among patients with RA, including electronic reminders with linked order sets, audit, and feedback to rheumatologists about their vaccination rates and how they compare to their peers, and outreach to patients,” David W. Baker, MD, MPH, Division of General Internal Medicine and Geriatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, and colleagues explained.

The study involved a 12-month, system-level intervention that targeted 1255 eligible patients with RA receiving care at the Northwestern Medical Group, an academic multispecialty practice staffed by faculty from the Feinberg School of Medicine at North-

western University in Chicago, IL. More than 80% were women, mean age was 56 years, and 50.4% were white.

Almost all patients had commercial insurance; 57.8% had commercial insurance, and 37.3% had Medicare or Medicaid. Sixty percent were currently being treated with a biologic, and 38.1% had ≥1 comorbidities.

Following the intervention, there was no change in patients’ self-reported IVX rates; however, the baseline rate was already high, and much higher than what was documented in the EHR. Preintervention, 90.2% of patients had received IVX, and postintervention, 86.1% received IVX. Both preand postintervention, 80% of participants said they received IVX in the previous season. Prior to the intervention, 28.7% of patients received PVX, compared with 45.8% postintervention.

A regression analysis found that the rate of PVX uptake increased annually by 9.4% compared with baseline (P =

.002). The rate of HZVX uptake increased from 2.5% to 4.5% overall (P = .01), and from 3.0% to 6.6% among patients not treated with a biologic therapy that precludes HZVX. “Although the intervention improved pneumococcal and zoster vaccination rates, the improvement in pneumococcal vaccination rate was less than expected, and the zoster vaccination remained low even for ideal candidates,” asserted the researchers.

According to the study authors, future interventions should address the obstacles they cited, including difficulty using EHR reminders and order sets, uncertainty on the part of doctors about the value and safety of recommended vaccines, and issues related to insurance coverage and prior vaccination history. n Reference

Baker DW, Brown T, Lee JY, et al. A multifaceted intervention to improve influenza, pneumococcal, and herpes zoster vaccination among patients with rheumatoid arthritis. J Rheumatol. 2016 Apr 15, Epub ahead of print.

Stakeholder Perspective

Convergence in Healthcare: Providers, Employers, and...

One trend occurring at an accelerated pace right now that will create more changes, and ideally more value for consumers, is convergence. Convergence is not neces­sarily a new trend in healthcare—an industry in which providers, employers, and health plans have typically operated in their unique areas, serving consumers (ie, patients, employees, or members) in a different way, typically without crossing into each other’s domains. The exceptions to this, which is not our focus here, are organizations such as Kaiser Permanente, which has served as a health plan, an employer, and a healthcare provider for more than 60 years.

To give convergence some significance, let us look at its definition. According to the Oxford’s Learner’s Dictionary, convergence is (1) to move toward a place from different directions and meet, (2) to move toward each other and meet at a point, or (3) to become very similar or the same. I propose defining convergence in healthcare as: 1. The collaboration of payers and providers to provide population health management, and 2. Divergent healthcare organizations becoming similar organizations.

For the purpose of this article, providers are defined as physicians and hospitals, unless otherwise noted.

The United States currently has approximately 5600 registered hospitals,2 hundreds of health plans, and thousands of large employers. Convergence can be broken up into many categories, but this article focuses on the 3 areas of: 1. Health systems having their own plans 2. Health plans having their own providers 3. Employers directly contracting with providers.

I have excluded employers that employ their own providers, because many large employers have employed physicians and/or other advanced practice providers in their own clinics to service their employees for many years, so this is not necessarily a new trend. However, methods that bring providers to the workplace, such as primary care onsite healthcare clinics, are expanding as employers look at new ways to keep productivity in the workplace high, with less absenteeism.3 The 3 Convergence Trends

The trend of health systems having

Reprinted with permission from Byron C. Scott.

Convergence in Healthcare: Providers, Employers, and Health Plans. American Health & Drug Benefits.

2016;9:66-67.

their own health plans has become more widespread in the past 2 years.

Since the passage of the ACA, providers are assuming more risk, including health systems acquiring health plans in increasing frequency. Some providers purchase a health plan or acquire a plan through a merger and acquisition.

An estimate by PricewaterhouseCoopers suggests that 50% of health systems have a health plan license or intend to apply for one to create their own plan.4 This trend is not without tension between health plans and providers.

Providers are becoming more concerned about the ability to negotiate reasonable reimbursement rates, especially with several of the largest national health plans merging during the summer of 2015.5

directly contracting with ACOs will likely become more pervasive.9 What Is Driving the Success of Convergence?

Why is convergence occurring, and what are its drivers? The ACA has been a catalyst for convergence, because of the development of new payment models—including ACOs, Medicare Shared Savings Payments, and bundled payments—an increased focus on population health management, and the shift of reimbursement from volume to value. Value-based payment models are suddenly making providers more accountable and innovative in managing their patients.

The further evolution of population health management has been another driver of convergence, as we try to coor-

”Organizations that were historically in silos are now being pushed to create more value for the consumers they serve in a way that will translate to more organizations transforming into other segments of healthcare they were not previously in.“

—Byron C. Scott, MD, MBA

The consolidation of large health plans in itself may continue to push health systems to develop their own health plans. Conversely, some health plans have become owners of providers.

One of the largest examples is Highmark health plan, which owns Allegheny Health Network, a large health system in Pittsburgh, PA.6 More recently, Optum, a subsidiary of UnitedHealth Group, announced that it bought Med­ Express, which operates 141 urgent care clinics in 11 states, to expand its ownership of providers.7 The last convergence trend is employers directly contracting with providers. Although this is not a novel concept in some markets where large employers exist, it is a new trend when a large employer, such as Boeing, directly contracts with 2 accountable care organizations (ACOs; ie, Providence-Swedish Health Alliance and UW Medicine) in its Seattle, WA, market as a healthcare option for employees during its annual open.8 With more than 700 ACOs currently in the United States, the trend of employers

dinate better care, focus on wellness and prevention, and provide better ways for patients to self-manage their healthcare. With the increasing cost of healthcare even before the ACA, providers, employers, and health plans were already trying to find ways to reduce the cost of care for the populations that they serve.

How will various organizations be successful in this convergence movement, and how will patients reap the benefits? The answer is, through data and collaboration. Success will depend on who can assimilate the most accurate information regarding the populations the organizations serve (ie, information about the cost of healthcare, including labor, supply, medical device, and drug cost), and who can better assimilate administrative (claims data) and clinical data (electronic health rec­ords) in meaningful ways to improve the health of the populations they serve, to create value.

Sharing more data across groups in a more transparent approach will become very important, so that even pa-

Continued from page 1

tients will be able to understand the information more clearly. Leadership at the top of every healthcare organization, especially the physician leader, must drive these standards for agreedon data sets of clinical quality and outcomes that are transparent to all.

In the past 20 years, healthcare has witnessed a progression every 5 years— something new and innovative that has occurred to redefine healthcare. We have gone from fee-for-service care to err is human, electronic health records, ACA, and population health to value-­ based care.

One certainty in all this is that organizations that were historically in silos are now being pushed to create more value for the consumers they serve in a way that will translate to more organizations transforming into other segments of healthcare they were not previously in. For those involved in benefit design, these convergence trends will add complexity to their work. Ultimately, however, the beneficiaries of all this will be the patients we all serve in one way or another. n Author Disclosure Statement Dr Scott has no conflicts of interest to report.

References

1. Burstin H, Leatherman S, Goldmann D. The evolution of healthcare quality measurement in the United States. J Intern Med. 2016;279:154-159.

2. American Hospital Association. Fast facts on US hospitals: fast facts 2016. Updated January 2016. www.aha.org/research/rc/stat-studies/fast-facts.shtml.

Accessed January 15, 2016.

3. Shahly V, Kessler RC, Duncan I. Worksite primary care clinics: a systematic review. Popul Health Manag.

2014;17:306-315.

4. Ahlquist G, Javanmardian M, Lathrop P, Porwal A. Several hundred health networks will become payors. June 20, 2014. www.strategyand.pwc.com/reports/ health-networks-become-payors. Accessed March 1, 2016.

5. Abelson R. Health care companies in merger frenzy.

New York Times. October 29, 2015. www.nytimes. com/2015/10/30/business/dealbook/health-care-compa nies-in-merger-frenzy.html?_r=0. Accessed March 1, 2016.

6. Highmark Health. Highmark announces Allegheny Health Network as its new integrated delivery network focused on preserving health care choice and providing high-quality care. Press release. April 29, 2013. www. highmarkhealth.org/hmk/newsroom/2013/pr042913. shtml. Accessed March 1, 2016.

7. Herman B. Optum acquires urgent-care company MedExpress. Mod Healthc. April 9, 2015. www.mod ernhealthcare.com/article/20150409/NEWS/150409897.

Accessed November 1, 2015.

8. Morse S. How two accountable care organizations and Boeing are testing value-based care. Healthcare Finance. February 16, 2015. www.healthcarefinan cenews.com/news/how-two-accountable-care-orga nizations-and-boeing-are-testing-value-based-care.

Accessed March 2, 2016.

9. Muhlestein D. Growth and dispersion of accountable care organizations in 2015. Health Affairs Blog.

March 31, 2015. http://healthaffairs.org/blog/2015/ 03/31/growth-and-dispersion-of-accountable-careorganizations-in-2015-2/. Accessed November 15, 2015.

Adverse Events Watch

TNFi May Not Be Linked to Higher Risk for Ischemic Stroke in Patients with RA

By Leslie Wyatt

A

lthough patients with rheumatoid arthritis (RA) may be at an increased risk for ischemic stroke, researchers in a recent study have concluded that use of tumor necrosis factor inhibitors (TNFis) does not appear to influence the risk of ischemic stroke in this patient population.

Assessing Ischemic Stroke Risk

In an effort to examine this association, Audrey S. L. Low, MRCP, PhD, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester and Salford Royal Hospital NHS Foundation Trust, and colleagues recruited patients from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) from 2001 to 2009. Follow-up analyses were conducted using clinical and patient questionnaires, as well as the national death register. Thirty-day and 1-year mortality postischemic stroke were also evaluated.

Patients eligible to be included in the study were divided into 1 of 2 cohorts. One group of patients consisted of TNFitreated patients who were naïve to bi-

ologics at baseline, and registered in the BSRBR-RA database within ≤6 months of initiating adalimumab, etanercept, or infliximab (n = 11,642).

The second group comprised biologic-naïve patients with active RA who

risk for ischemic stroke between patients receiving only synthetic DMARDs and those ever-exposed to TNFis. Postischemic stroke mortality was compared between the 2 cohorts using age- and sex-adjusted logistic regression.

“The findings of this study indicate that TNFi do not influence the occurrence of ischemic stroke compared to synthetic DMARDs alone in patients with RA.“ —Audrey S. L. Low, MRCP, PhD, and colleagues were receiving synthetic disease-modifying antirheumatic drug (DMARD) therapy (n = 3271). Participants also had to have at least moderate disease activity at baseline, return ≥1 clinical questionnaires to the study coordination center, and no history of prior stroke recorded at baseline.

If brain imaging reports indicated ischemia, or if the ischemic stroke was reported as the underlying cause of death on a death certificate, then the investigators would categorize the incident stroke as ischemic. Cox proportional hazards regression model adjusted for potential confounders were used to compare the

No Link Between TNFi Exposure and Ischemic Stroke

As of April 2010, 127 verified incident ischemic strokes occurred during 61,226 and 11,973 person-years of observa­ tion for TNFiand DMARD-treated patients, respectively; 106 in the TNFi-treated group, and 21 in the synthetic DMARD-treated cohort. Following adjustments for confounders, no association was observed between ever-exposure to TNFi and ischemic stroke (hazard ratio, 0.99; 95% confidence interval [CI], 0.54-1.81). In addition, the study authors did not find an association between TNFi exposure

and mortality 30 days or 1 year following ischemic stroke (odds ratio [OR], 0.18; 95% CI, 0.03-1.21, and OR 0.60; 95% CI, 0.16-2.28, respectively). A total of 13 deaths occurred within 30 days of the 127 ischemic strokes—3 in patients receiving synthetic DMARDs, and 2 in the patients receiving TNFis. Among patients who had past exposure to TNFi at the time of their ischemic stroke, 8 deaths occurred.

“The findings of this study indicate that TNFi do not influence the occurrence of ischemic stroke compared to synthetic DMARDs alone in patients with RA over a period of 4–6 years, which is consistent with the findings of previous studies focusing on the risk over the short term,” Dr Low and colleagues stated. “Although numbers were small, there was a trend toward a reduction in mortality at 30 days and at 1 year following the event among patients who were actively receiving TNFi at the time of their stroke compared to those who had never received biologic therapies.” n Reference

Low AS, Lunt M, Mercer LK, et al. Association between ischemic stroke and tumor necrosis factor inhibitor therapy in patients with rheumatoid arthritis.

Arthritis Rheumatol. 2016;68:1337-1345.

Lupus

Age, Smoking History Are Risk Factors for Early Organ Damage in Patients with SLE

By Phoebe Starr

I

nvestigators behind a longitudinal study at a single center identified several risk factors for organ damage in patients with systemic lupus erythematosus (SLE), and demonstrated that organ damage compromises healthrelated quality of life (HR-QOL) in these patients. Factors such as preexisting damage at baseline, age, immunosuppressive drug use, cigarette smoking, and higher mean erythrocyte sedimentation and C-reactive protein (CRP) levels were associated with earlier organ damage; some of these risk factors are modifiable.

“The negative effect [of organ damage progression] on HR-QOL under-

lines the need to address modifiable risk factors and develop effective prevention and treatment strategies to reduce the risk of organ damage over time,” Alexandra Legge, MD, Depart-

The study included 273 patients with SLE who were followed up for ≤14 years (mean follow-up, 7.3 years).

Patients with newly diagnosed and long-standing SLE were included, and

The relationship between cumulative organ damage and HR-QOL is complex, but it is important to note that organ damage seems to compromise QOL. ment of Medicine, Nova Scotia Health Authority, Dalhousie University, Halifax, and colleagues explained.

may be a limitation of this study.

During follow-up, 126 (46.2%) patients had evidence of organ damage

progression, as reflected by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (SDI).

The researchers evaluated the effect of key disease-related factors, medical therapies, demographic variables, and serologic biomarkers on the rate of damage accrual to identify predictors of damage progression.

As has been shown by other studies, patients with preexisting organ damage at baseline were twice as likely to have earlier organ damage progression. They also examined the relationship between cumulative organ damage and HR-QOL. At baseline, patients were predomiContinued on page 20

Lupus

Patient Tip

5 Tips for Preventing Lupus Flares Lupus is an autoimmune disease that affects multiple parts of the body, and results in the immune system attacking healthy tissues.1 Symptoms of lupus, including painful joints, red rash, and extreme fatigue, differ from person to person, and appear in the form of a flare.

Although symptoms can worsen despite taking medication, certain steps for preventing lupus flares can be beneficial. The following tips include methods for preventing the onset of a flare1-3:

1.

3.

5.

2.

4.

References

Recognize an Oncoming Flare Learning to identify when a flare is coming can assist you in taking steps to cope with the symptoms. Many people feel very tired; experience pain; develop a rash, fever, or headache; and experience stomach discomfort or dizziness right before they have a flare.

Spend Less Time in the Sun Because sunlight can cause rashes and flares, people with lupus should avoid the sun. When you know you will be in the sun, you should wear a hat and sunglasses, and apply a sunscreen with ≥70 SPF all over your body. In addition, you should limit the amount of time you spend in artificial indoor light.

Relax and Make Time for Yourself Having a chronic disease is stressful, and stress is a significant cause of flares. Use yoga and deep breathing exercises to help you de-stress, and make sure that you get enough rest—do not overexert yourself whether at work or home.

Stick to Your Prevention and Treatment Plan It is crucial that you stick to the realistic prevention and treatment plan created especially for you by your rheumatologist.

Medication adherence is important, as is having an open dialogue with your physician and healthcare professionals about which over-the-counter or prescription drugs to avoid because of their risk for inducing flares.

Keep a Healthy Diet In addition to maintaining a healthy diet, you should avoid certain foods that have been shown to aggravate your condition and induce flares, such as garlic and alfalfa sprouts (the latter of which can increase inflammation in people with lupus).

1. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Living with lupus: health information basics for you and your family. www.niams.nih.gov/ health_info/lupus/ living_with_lupus.asp. Published July 2014. Accessed May 23, 2016.

2. S.L.E. Lupus Foundation. Looking out for lupus flares. www.lupusny.org/about-lupus/newsletters/septemberoctober-2006/looking-out-lupus-flares. Accessed May 23, 2016.

3. Johns Hopkins Lupus Center. Things to avoid. www. hopkinslupus.org/lupus-info/lifestyle-additional-informa tion/avoid. Accessed May 23, 2016.

Age, Smoking History Are Risk Factors for... nantly women (87.2%) and white (92%), with a mean age of 44.1 years.

The mean duration of SLE was 7.5 years. Approximately 40% of patients were enrolled ≤1 year of SLE diagnosis.

Approximately 70% had no organ damage at baseline, whereas almost 30% had preexisting damage, as reflected by an SDI score of >1. There were 27 deaths during follow-up, and 37 (13.6%) additional patients were lost to follow-up.

In a multivariate analysis, older age at baseline, fulfilling ≥8 ACR criteria for SLE at baseline, immunosuppressive medication use up to time of first SDI change, mean serum CRP level up to time of first SDI change, and current or past cigarette smoking remained significantly statistically associated with progressive organ damage.

Over time, changes in SDI score were associated with initial declines in the Short Form (SF)-36 medical outcomes study at the time damage oc-

ease increases the likelihood of accumulating organ damage, either because of the disease itself, related to corticosteroid use, or more aggressive immu-

The strong association between cigarette smoking and damage accrual should provide further encouragement to step up smoking cessation efforts in patients with SLE.

curred; SF-36 scores then became comparable to those of SLE patients without damage progression.

The fact that >8 ACR criteria at baseline were identified as a risk factor suggests that having multisystem dis-

nosuppressive therapy leading to drug-related damage.

Cigarette smoking is a modifiable risk factor, and the strong association between cigarette smoking and damage accrual should provide further encour-

Continued from page 19

agement to step up smoking cessation efforts in patients with SLE. The relationship between cumulative organ damage and HR-QOL is complex, but it is important to note that organ damage seems to compromise QOL, according to the authors.

Limitations of the study include the fact that it was conducted at a single site, and among mostly white patients who were followed annually by a single assessment. The study did not evaluate mental health and psychological factors, and included a relatively small sample of patients, so meaningful subgroup analysis was not possible. n Reference

Legge A, Doucette S, Hanly JG. Predictors of organ damage progression and effect on health-related quality of life in systemic lupus erythematosus. J Rheumatol.

2016 Apr 15 Epub ahead of print.

Pain Management

Provider Education Key to Preventing the Growing Epidemic of Misuse and Abuse in Opioid Prescribing for Chronic Pain, the FDA Emphasizes

By Alice Goodman

I

n February 2016, the US Food and Drug Administration (FDA) published a special report in the New England Journal of Medicine, alerting the medical community, including providers, policymakers, and drug manufacturers, about “the growing epidemic of opioid abuse, addiction, and overdose—an epidemic directly related to the increasingly widespread use of powerful opioid pain medications” (Califf RM, et al. N Engl J Med. 2016;374:1480-1485).

In their report, Robert M. Califf, MD, newly appointed Commissioner of the FDA; Janet Woodcock, MD, Director, FDA’s Center for Drug Evaluation and Research; and former FDA Acting Commissioner Stephen Ostroff, MD, highlight the extent of the problem, outlining steps the FDA is taking to address key issues related to overdosing and overprescribing of opioids for pain management.

Abuse of prescription opioids has reached an alarming reality, representing a true medical crisis in the United States. In 2014, an estimated 19,000 deaths resulted from an overdose of prescription opioids, exceeding deaths from motor vehicle–related accidents.

The FDA outlines 10 key issues related to this epidemic of opioid abuse, noting that better education of opioid prescribers is a key weapon to combat the increasing reports of overdosing and deaths in the United States associated with abuse and misuse of prescription opioids. Another key issue is the need for a better evidence base, particularly for the long-term use of prescription opioids.

“Until clinicians stop prescribing opioids far in excess of clinical need, this crisis will continue unabated,” wrote Drs Califf, Woodcock, and Ostroff.

misuse. The FDA Science Board convened in March 2016 to advise on the role of pharmaceuticals in pain management, the development of alternative pain medication, and postmarketing surveillance activities. Future coordinated actions will address the Risk Evaluation and Mitigation Strategy (REMS) programs for extended-release and long-acting opioids (which are funded by pharmaceutical manufacturers); extending prescriber education; and expanding the REMS program to include immediate-release opioids, thereby increasing the number of prescribers being trained on pain management and the safe prescribing of opioids.

“Until clinicians stop prescribing opioids far in excess of clinical need, this crisis will continue unabated.“ —Robert M. Califf, MD, Janet Woodcock, MD, and Stephen Ostroff, MD Labeling and Postmarketing Surveillance

The first issue related to balancing the requirements of individual patients for safe and effective pain medications with the societal and individual risk for opioid abuse and misuse. To address this problem, the FDA plans to consult with partners, including the National Academy of Medicine, to develop a framework for opioid review, approval, and monitoring.

Labeling and postmarketing surveillance requirements for pharmaceutical companies will be reevaluated, and the pharmaceutical companies will be required to generate postmarketing data on the long-term impact of extendedrelease and long-acting opioid use to provide better evidence regarding the serious risks associated with the misuse and abuse of opioids.

Thus far, more than 38,000 prescribers have participated in voluntary REMS education programs that are funded by pharmaceutical manufacturers. These results will be evaluated and inform approaches going forward. At this time, the FDA supports mandatory education for prescribers, as opposed to the current situation, in which prescriber participation in REMS education programs is voluntary.

Need for Timely Action

Abuse-Deterrent Formulations

Individual and Societal Risk

Another issue is the need for flexibility in initiating timely action to address the evolving threat of opioid

The FDA will continue to support abuse-deterrent formulations of opioids and opioid derivatives, and en-

courage the development of more effective abuse-deterrent features. The FDA will also prioritize expanding public access to naloxone, which can reverse overdose and avoid deaths if initiated promptly. Over-the-counter availability of naloxone is under consideration.

Alternatives for Pain Management

The FDA will work closely with the pharmaceutical industry and the National Institutes of Health to develop nonopioid, nonaddictive alternatives for the management of chronic pain.

Developing approaches other than pharmacotherapies to control chronic pain is also an urgent priority, according to the FDA.

New Guidelines on Opioid Use

The Centers for Disease Control and Prevention has drafted clear guidelines for the prescription of opioids to control chronic pain; the FDA supports this process and plans to support the finalized guidelines. In addition, the FDA supports the Surgeon General’s engaging the clinical community in restricting the inappropriate prescribing of opioids, treating opioid addiction, and reinforcing evidence-based approaches to treating chronic pain while sparing the use of opioids.

Managing Chronic Pain in Children

The use of opioids in children with severe and chronic pain is a separate issue that needs immediate attention.

Physicians need high-quality evidence to guide their treatment decisions, and the FDA supports this effort, as well as the need for new pediatric opioid labeling guided by this evidence.

“In some cases, children with serious [pain-related] conditions are being treated with opioids in the absence of adequate knowledge about correct indications and dosing. We must all work together to ensure that all appropriate therapeutic options for pain are available to children,” and that “they are prescribed and handled in an impeccably judicious manner, guided by the best and most current scientific evidence,” Dr Califf and colleagues wrote.

Improving Evidence Base

A better evidence base to guide the treatment of chronic pain is needed, especially regarding the long-term use

FDA Now Requires Boxed Warning for All Opioids

On March 22, 2016, the FDA issued a press release announcing it was requiring a new boxed warning about the risk for abuse, addiction, overdose, and death for all immediate-release opioid drugs prescribed for pain. The FDA will also require other labeling changes related to safety for all opioid medications, across all classes.

“The broad set of actions announced today is reflective of the FDA’s efforts to improve informed prescribing of opioids across the board,” said Dr Woodcock. “We have been and will continue to evaluate all new data to ensure that labels of opioids contain appropriate prescribing information about the benefits and risks of prescription opioids.”

of opioid medications.

The FDA and the US Department of Health & Human Services are mandating industry-funded studies to provide better evidence for opioid use, the biologic phenomenon of pain, and the development of new and alternative approaches to pain prevention and management.

Mandatory Prescribers’ Education

In an accompanying, impassioned editorial by Daniel P. Alford, MD, MPH, Medical Director, Office-Based Opioid Treatment, Boston Medical Center, MA, Dr Alford calls for mandatory—not voluntary—prescriber education regarding opioids (Alford DP. N Engl J Med. 2016;374:301-303).

“Education has the potential to both reduce overprescribing and ensure that patients in need retain access to opioids,” Dr Alford suggested, adding that prescribing opioids has increased dramatically in recent decades, and that has been directly linked to the increasing misuse of and associated deaths from opioids.

He said that mandatory education should go beyond opioid prescribing to include pain management designed for the entire healthcare team, and supported by enhanced clinical systems, including decision-making tools in electronic medical records. n

Psoriatic Arthritis

IL-6 Inhibitor Shows Promise in Patients with PsA

By Phobe Starr

R

esearchers in a phase 2b study of clazakizumab suggest that this drug may become a new option for treatment of the musculoskeletal effects—but not necessarily skin lesions— associated with psoriatic arthritis (PsA).

Treatment for patients with predominant musculoskeletal effects represents an unmet need.

“This is the first clinical trial of an interleukin (IL)-6-targeted therapy in PsA, and the first controlled study to demonstrate a beneficial effect of targeting the IL-6 cytokine in PsA,” Philip Mease, MD, Swedish Medical Center and University of Washington, Seattle, and colleagues stated. Clazakizumab’s efficacy on musculoskeletal measures was of greater magnitude than that observed on measures of skin disease. This suggests nonoverlapping mechanisms of inflammation in the skin and joints of patients with PsA, according to the researchers.

“Thus, clazakizumab may be particularly well suited for patients with PsA in whom skin disease is well controlled with topical agents, ultraviolet therapy, and/or oral systemic therapy such as methotrexate, but whose musculoskeletal manifes-

tations, such as joint signs and symptoms, enthesitis, and dactylitis, require more potent systemic therapy,” the researchers explained. “Furthermore, some PsA patients do not present with skin lesions at diagnosis, and those patients may benefit from clazakizumab treatment.”

nonsteroidal anti-inflammatory drugs in a 1:1:1:1 ratio to subcutaneous placebo or clazakizumab 25 mg, 100 mg, or 200 mg every 4 weeks—with or without methotrexate—for 24 weeks. This was followed by an open-label extension phase. The primary end point was ≥20%

“This is the first clinical trial of an interleukin (IL)-6-targeted therapy in PsA.” —Philip Mease, MD

Clazakizumab is a monoclonal antibody with high affinity and specificity for IL-6. It has been studied in intravenous and subcutaneous formulations as a treatment for rheumatoid arthritis, with encouraging results.

The double-blind, placebo-controlled, dose-ranging study was conducted at 44 sites in 13 countries. The study randomized 165 patients with active PsA and an inadequate response to

improvement, according to American College of Rheumatology (ACR) criteria (ACR20), at week 16; secondary efficacy end points assessed improvement at weeks 16 and 24.

At week 16, clazakizumab 100 mg achieved a significantly higher ACR20 response compared with placebo (52.4% vs 29.3%; P = .039). Other week 16 ACR20 responses for clazakizumab were 46.3% for the 25-mg group, and

39.0% for the 200-mg group.

ACR50/ACR70—representing 50% improvement and 70% improvement, respectively—at weeks 16 and 24 were numerically higher with clazakizumab versus placebo.

Musculoskeletal manifestations of PsA were significantly improved by clazakizumab versus placebo with only minimal improvements in skin.

There were no deaths reported in the study. Only 2 serious adverse events were reported in the clazakizumab 25-mg and 100-mg groups (and also 2 in the placebo arm); 4 patients in the 400-mg arm had a serious adverse event. The overall rate of any adverse event was numerically higher in all treatment groups, with the highest number in the clazakizumab 200mg group. The number of treatment-related discontinuations was small, and comparable to that of placebo for the 25-mg and 100-mg groups. n Reference

Mease P, Gottlieb AB, Berman A, et al. The efficacy and safety of clazakizumab, an anti-interleukin-6 monoclonal antibody, in a phase 2b study of adults with active psoriatic arthritis. Arthritis Rheumatol. 2016 Apr 5. Epub ahead of print.

Pain Management

Light Shed on Pain, Pain Care... of Medicine, and because epidemiologic data on the incidence, prevalence, and consequences of MSDs are scarce, Joseph L. Goulet, PhD, MS, Pain, Research, Informatics, Multi-morbidities, & Education Center, VA Connecticut Healthcare System, West Haven, and colleagues developed the MSD Cohort to improve the existing literature on painful disorders. In this report, the authors provide results of an analysis of the cohort, comparing patient characteristics across cohort entry years.

Three of the primary goals of the MSD Cohort were to generate a comprehensive registry of veterans who have MSD diagnoses and receive care at the VHA, the largest integrated healthcare system in the United States; evaluate variation in pain treatment and outcomes across varying demographic groups, geographic regions, and facilities; and estimate the costs of pain care in this patient population. In describing why the VHA is an ideal resource for data to address concerns in this patient

population, the authors behind the MSD Cohort stated that, in addition to having one of the most comprehensive electronic health record systems in the United States, the VHA keeps numerous disease-specific cohorts and registries that support research and quality improvement initiatives.

“These large, national longitudinal cohorts represent a census of VHA patients that avoids some of the problems of selected samples recruited for research studies or trials, and they provide a wealth of information for understanding chronic illness management,” Dr Goulet and colleagues explained. “Of particular importance, the large size and lengthy follow-up also allows for detection of rare events occurring after years of observation, as well as examination of relationships within small but important subgroups.”

Electronic health records of patients treated at the VHA were explored by the authors of the report to specifically locate those diagnosed with conditions such as

Continued from page 1

joint, back, and neck disorders, and osteoarthritis, per the International Classification of Diseases, Ninth Revision, Clinical Modification. To be included in the cohort, patients had to have ≥2 outpatient visits within 18 months of each other, or 1 outpatient visit with an MSD diagnosis, from 2000 to 2011; the index date was defined by the first diagnosis.

Pain intensity numeric rating scale (NRS) scores, comorbid medical and mental health diagnoses, pain-related treatments, and other characteristics were collected retrospectively and prospectively for the 5,237,763 patients included in the cohort. Six percent of patients were women, 15% identified as black, 18% reported having severe pain (NRS ≥7) on the index date, and the mean age of the cohort was 59 years.

The most common MSD diagnoses were for non traumatic joint (27%), back (25%), and osteoarthritis (21%).

Notably, the authors of the report found that patients entering the cohort in recent years had more simultaneous MSD

diagnoses and higher NRS scores.

“Analyses reported here demonstrate the value of the MSD cohort as an opportunity to study complex interactions among socio-demographic and clinical characteristics of veterans with MSD, including the ability to examine changes over time,” Dr Goulet and colleagues concluded. “Given the large and comprehensive nature of the MSD cohort, there are many additional opportunities to examine, for example, pain among veterans aged ≥85, correlates of specific MSD such as temporomandibular disorders, variation in trajectories of pain by facility, the use of and outcomes associated with nonpharmacologic pain treatments.”

The authors assert that the MSD Cohort is a plentiful resource for collective, health service research relevant to pain. n Reference

Goulet JL, Kerns RD, Bair M, et al. The musculoskeletal diagnosis cohort: examining pain and pain care among veterans. Pain. 2016 Mar 25. Epub ahead of print.