2022 October AANnews

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22 Tips Your Colleagues Use in Their Efficient Practices

There’s still time to gather with your neurology colleagues this October 28 to 30 at Caesars Palace in Las Vegas—or virtually from your home or office—for a weekend of timely updates on the hottest topics in the world of neurology, practical issues in practice management, the most innovative science, long-awaited networking, and the chance to earn up to 51.5 valuable end-of-year CME credits. Visit AAN.com/Fall today to learn more and to register.

Optimizing efficiency can increase patient access, enhance the patient experience, and decrease clinician burden. As the Medical Economics and Practice Committee continues its work supporting practices looking to improve their efficiency, it asked AAN members for their “most obvious” efficiency tips. In this article, your peers share solutions they’ve implemented successfully. These obvious tips are meant to be low-hangingfruit solutions: easy to execute with a high impact on your efficiency. Additional efficiency tips and best practices can be found at AAN.com/practice/neurology-practice-efficiencies

FOR PATIENTS WITH RELAPSING FORMS OF MS

WITHPLAYING FEWER RELAPSES

• The efficacy of VUMERITY® (diroximel fumarate) is based upon bioavailability studies in patients with relapsing forms of multiple sclerosis and healthy subjects comparing dimethyl fumarate to VUMERITY1

• Study 1: A 2-year, randomized, double-blind, placebo-controlled study in 1234 patients with RRMS. Primary endpoint: PPR1

• Study 2: A 2-year, multicenter, randomized, double-blind, placebo-controlled study in 1417 patients with RRMS. Primary endpoint: ARR1

VUMERITY offers the efficacy demonstrated by dimethyl fumarate across 2 pivotal trials1

of treated patients were relapse-free at 2 years1

Based on ARR, treated patients experienced RELAPSE every 2 years1

• Dimethyl fumarate demonstrated a 49% and 34% relative risk reduction in PPR vs placebo, respectively (27% vs 46%; P <0.0001), (29% vs 41%; P =0.0020)

• Dimethyl fumarate demonstrated a 53% and 44% relative reduction in ARR vs placebo, respectively (0.172 vs 0.364; P <0.0001), (0.224 vs 0.401; P <0.0001)

Visit www.vumerityhcp.com

Indication

VUMERITY® (diroximel fumarate) is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Important Safety Information

CONTRAINDICATIONS

VUMERITY is contraindicated in patients

• With known hypersensitivity to diroximel fumarate, dimethyl fumarate, or to any of the excipients of VUMERITY. Reactions may include anaphylaxis and angioedema

• Taking dimethyl fumarate WARNINGS AND PRECAUTIONS

Anaphylaxis and Angioedema

• VUMERITY can cause anaphylaxis and angioedema after the first dose or at any time during treatment. Signs and symptoms in patients taking dimethyl fumarate (which has the same active metabolite as VUMERITY) have included difficulty breathing, urticaria, and swelling of the throat and tongue. Patients should be instructed to discontinue VUMERITY and seek immediate medical care should they experience signs and symptoms of anaphylaxis or angioedema

Progressive Multifocal Leukoencephalopathy

• Progressive multifocal leukoencephalopathy (PML) has occurred in patients with MS treated with dimethyl fumarate (which has the same active metabolite as VUMERITY). PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. A fatal case of PML occurred in a patient who received dimethyl fumarate for 4 years while enrolled in a clinical trial

• PML has occurred in patients taking dimethyl fumarate in the postmarketing setting in the presence of lymphopenia (<0.9 × 10 9/L). While the role of lymphopenia in these cases is uncertain, the PML cases have occurred predominantly in patients with lymphocyte counts <0.8×10 9/L persisting for more than 6 months

• At the first sign or symptom suggestive of PML, withhold VUMERITY and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes

Important Safety Information (cont'd)

WARNINGS AND PRECAUTIONS (CONT'D)

Progressive Multifocal Leukoencephalopathy (cont'd)

• Magnetic resonance imaging (MRI) findings may be apparent before clinical signs or symptoms. Monitoring with MRI for signs consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present

Herpes Zoster and Other Serious Opportunistic Infections

• Serious cases of herpes zoster have occurred in patients treated with dimethyl fumarate (which has the same active metabolite as VUMERITY), including disseminated herpes zoster, herpes zoster ophthalmicus, herpes zoster meningoencephalitis, and herpes zoster meningomyelitis. These events may occur at any time during treatment. Monitor patients on VUMERITY for signs and symptoms of herpes zoster. If herpes zoster occurs, appropriate treatment for herpes zoster should be administered

• Other serious opportunistic infections have occurred with dimethyl fumarate, including cases of serious viral (herpes simplex virus, West Nile virus, cytomegalovirus), fungal (Candida and Aspergillus), and bacterial (Nocardia, Listeria monocytogenes, Mycobacterium tuberculosis) infections. These infections have been reported in patients with reduced absolute lymphocyte counts (ALC) as well as in patients with normal ALC. These infections have affected the brain, meninges, spinal cord, gastrointestinal tract, lungs, skin, eye, and ear. Patients with symptoms and signs consistent with any of these infections should undergo prompt diagnostic evaluation and receive appropriate treatment

• Consider withholding VUMERITY treatment in patients with herpes zoster or other serious infections until the infection has resolved

Lymphopenia

• VUMERITY may decrease lymphocyte counts. In the MS placebo-controlled trials with dimethyl fumarate (which has the same active metabolite as VUMERITY), mean lymphocyte counts decreased by approximately 30% during the first year of treatment with dimethyl fumarate and then remained stable. Four weeks after stopping dimethyl fumarate, mean lymphocyte counts increased but did not return to baseline. The incidence of infections and serious infections was similar in patients treated with dimethyl fumarate or placebo. There was no increased incidence of serious infections observed in patients with lymphocyte counts <0.8 x 10 9/L or ≤0.5 x 10 9/L in controlled trials, although one patient in an extension study developed PML in the setting of prolonged lymphopenia (lymphocyte counts predominantly <0.5 x 10 9/L for 3.5 years)

• In controlled and uncontrolled clinical trials with dimethyl fumarate, 2% of patients experienced lymphocyte counts <0.5 x 10 9/L for at least six months, and in this group the majority of lymphocyte counts remained <0.5 x 109/L with continued therapy. Neither VUMERITY nor dimethyl fumarate have been studied in patients with preexisting low lymphocyte counts

• Obtain a complete blood count (CBC), including lymphocyte count, before initiating treatment with VUMERITY, 6 months after starting treatment, and then every 6 to 12 months thereafter, and as clinically indicated. Consider interruption of VUMERITY in patients with lymphocyte counts less than 0.5 x 10 9/L persisting for more than six months. Given the potential for delayed recovery of lymphocyte counts, continue to obtain lymphocyte counts until their recovery if VUMERITY is discontinued or interrupted because of lymphopenia. Consider withholding treatment from patients with serious infections until resolution

Liver Injury

• Clinically signifi cant cases of liver injury have been reported in patients treated with dimethyl fumarate (which has the same active metabolite as VUMERITY) in the postmarketing setting. The onset has ranged from a few days to several months after initiation of treatment with dimethyl fumarate. Signs and symptoms of liver injury, including elevation of serum aminotransferases to greater than 5-fold the upper limit of normal and elevation of total bilirubin to greater than 2-fold the upper limit of normal have been observed. These abnormalities

resolved upon treatment discontinuation. Some cases required hospitalization. None of the reported cases resulted in liver failure, liver transplant, or death. However, the combination of new serum aminotransferase elevations with increased levels of bilirubin caused by drug-induced hepatocellular injury is an important predictor of serious liver injury that may lead to acute liver failure, liver transplant, or death in some patients

• Elevations of hepatic transaminases (most no greater than 3 times the upper limit of normal) were observed during controlled trials with dimethyl fumarate

• Obtain serum aminotransferase, alkaline phosphatase (ALP), and total bilirubin levels prior to treatment with VUMERITY and during treatment as clinically indicated. Discontinue VUMERITY if clinically signifi cant liver injury induced by VUMERITY is suspected

Flushing

• VUMERITY may cause flushing (e.g., warmth, redness, itching, and/or burning sensation). In clinical trials of dimethyl fumarate (which has the same active metabolite as VUMERITY), 40% of dimethyl fumarate-treated patients experienced flushing. Flushing symptoms generally began soon after initiating dimethyl fumarate and usually improved or resolved over time. In the majority of patients who experienced flushing, it was mild or moderate in severity. Three percent (3%) of patients discontinued dimethyl fumarate for flushing and <1% had serious flushing symptoms that were not life-threatening but led to hospitalization

ADVERSE REACTIONS

• The most common adverse reactions (incidence ≥10% and ≥2% more than placebo) for dimethyl fumarate (which has the same active metabolite as VUMERITY) were flushing, abdominal pain, diarrhea, and nausea

• Gastrointestinal adverse reactions: Dimethyl fumarate caused GI events (e.g., nausea, vomiting, diarrhea, abdominal pain, and dyspepsia). The incidence of GI events was higher early in the course of treatment (primarily in month 1) and usually decreased over time in patients treated with dimethyl fumarate compared with placebo. Four percent (4%) of patients treated with dimethyl fumarate and less than 1% of placebo patients discontinued due to gastrointestinal events. The incidence of serious GI events was 1% in patients treated with dimethyl fumarate

• Hepatic transaminases: An increased incidence of elevations of hepatic transaminases in patients treated with dimethyl fumarate was seen primarily during the first six months of treatment and most patients with elevations had levels <3 times the upper limit of normal (ULN) during controlled trials. There were no elevations in transaminases ≥ 3 times the ULN with concomitant elevations in total bilirubin >2 times the ULN. Discontinuations due to elevated hepatic transaminases were <1% and were similar in patients treated with dimethyl fumarate or placebo

• Eosinophilia adverse reactions: A transient increase in mean eosinophil counts was seen during the first 2 months of therapy

USE IN SPECIFIC POPULATIONS Renal Impairment

• No dosage adjustment is necessary in patients with mild renal impairment. Because of an increase in the exposure of a major metabolite, use of VUMERITY is not recommended in patients with moderate or severe renal impairment

Please see following pages for Brief Summary of full Prescribing Information.

PPR=proportion of patients relapsed; ARR=annualized relapse rate.

Reference: 1. VUMERITY Prescribing Information, Biogen, Cambridge, MA.

1. INDICATIONS AND USAGE

VUMERITY is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsingremitting disease, and active secondary progressive disease, in adults.

2. DOSAGE AND ADMINISTRATION

2.1 Blood Tests Prior to Initiation of VUMERITY

Obtain the following prior to treatment with VUMERITY:

• A complete blood cell count (CBC), including lymphocyte count [see Warnings and Precautions (5.4)]

• Serum aminotransferase, alkaline phosphatase, and total bilirubin levels [see Warnings and Precautions (5.5)]

2.2 Dosing Information

The starting dosage for VUMERITY is 231 mg twice a day orally. After 7 days, the dosage should be increased to the maintenance dosage of 462 mg (administered as two 231 mg capsules) twice a day orally.

Temporary dosage reductions to 231 mg twice a day may be considered for individuals who do not tolerate the maintenance dosage. Within 4 weeks, the recommended dosage of 462 mg twice a day should be resumed. Discontinuation of VUMERITY should be considered for patients unable to tolerate return to the maintenance dosage.

Administration of non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to VUMERITY dosing may reduce the incidence or severity of flushing [see Clinical Pharmacology (12.3)]

2.3 Administration Instructions

Swallow VUMERITY capsules whole and intact. Do not crush or chew, or sprinkle the capsule contents on food.

If taken with food, avoid a high-fat, high-calorie meal/snack; the meal/snack should contain no more than 700 calories and no more than 30 g fat [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)]

Avoid co-administration of VUMERITY with alcohol [see Clinical Pharmacology (12.3)]

2.4 Blood Tests to Assess Safety After Initiation of VUMERITY

Obtain a complete blood cell count (CBC), including lymphocyte count, 6 months after initiation of VUMERITY and then every 6 to 12 months thereafter, as clinically indicated [see Warnings and Precautions (5.4)].

Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels during treatment with VUMERITY, as clinically indicated [see Warnings and Precautions (5.5)]

2.5 Patients With Renal Impairment

No dosing adjustment is recommended in patients with mild renal impairment.

VUMERITY is not recommended in patients with moderate or severe renal impairment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)]

3. DOSAGE FORMS AND STRENGTHS

VUMERITY is available as hard, delayed-release capsules containing 231 mg of diroximel fumarate. The capsules have a white cap and a white body, printed with “DRF 231 mg” in black ink on the body.

4. CONTRAINDICATIONS

VUMERITY is contraindicated in patients

• With known hypersensitivity to diroximel fumarate, dimethyl fumarate, or to any of the excipients of VUMERITY. Reactions may include anaphylaxis and angioedema [see Warnings and Precautions (5.1)]

• Taking dimethyl fumarate [see Drug Interactions (7.1)].

5. WARNINGS AND PRECAUTIONS

5.1 Anaphylaxis and Angioedema

VUMERITY can cause anaphylaxis and angioedema after the first dose or at any time during treatment. Signs and symptoms in patients taking dimethyl fumarate (which has the same active metabolite as VUMERITY) have included difficulty breathing, urticaria, and swelling of the throat and tongue. Patients should be instructed to discontinue VUMERITY and seek immediate medical care should they experience signs and symptoms of anaphylaxis or angioedema.

5.2 Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) has occurred in patients with MS treated with dimethyl fumarate (which has the same active metabolite as VUMERITY). PML is an opportunistic viral infection

of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. A fatal case of PML occurred in a patient who received dimethyl fumarate for 4 years while enrolled in a clinical trial.

During the clinical trial, the patient experienced prolonged lymphopenia (lymphocyte counts predominantly <0.5 × 109/L for 3.5 years) while taking dimethyl fumarate [see Warnings and Precautions (5.4)]. The patient had no other identified systemic medical conditions resulting in compromised immune system function and had not previously been treated with natalizumab, which has a known association with PML. The patient was also not taking any immunosuppressive or immunomodulatory medications concomitantly.

PML has also occurred in patients taking dimethyl fumarate in the postmarketing setting in the presence of lymphopenia (<0.9 × 109/L). While the role of lymphopenia in these cases is uncertain, the PML cases have occurred predominantly in patients with lymphocyte counts <0.8×109/L persisting for more than 6 months.

At the first sign or symptom suggestive of PML, withhold VUMERITY and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.

Magnetic resonance imaging (MRI) findings may be apparent before clinical signs or symptoms. Cases of PML diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported in patients treated with other MS medications associated with PML. Many of these patients subsequently became symptomatic with PML. Therefore, monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Lower PML-related mortality and morbidity have been reported following discontinuation of another MS medication associated with PML in patients with PML who were initially asymptomatic compared to patients with PML who had characteristic clinical signs and symptoms at diagnosis. It is not known whether these differences are due to early detection and discontinuation of MS treatment or due to differences in disease in these patients.

5.3 Herpes Zoster and Other Serious Opportunistic Infections

Serious cases of herpes zoster have occurred in patients treated with dimethyl fumarate (which has the same active metabolite as VUMERITY) including disseminated herpes zoster, herpes zoster ophthalmicus, herpes zoster meningoencephalitis, and herpes zoster meningomyelitis. These events may occur at any time during treatment. Monitor patients on VUMERITY for signs and symptoms of herpes zoster. If herpes zoster occurs, appropriate treatment for herpes zoster should be administered.

Other serious opportunistic infections have occurred with dimethyl fumarate, including cases of serious viral (herpes simplex virus, West Nile virus, cytomegalovirus), fungal (Candida and Aspergillus), and bacterial (Nocardia, Listeria monocytogenes, Mycobacterium tuberculosis) infections. These infections have been reported in patients with reduced absolute lymphocyte counts (ALC) as well as in patients with normal ALC. These infections have affected the brain, meninges, spinal cord, gastrointestinal tract, lungs, skin, eye, and ear. Patients with symptoms and signs consistent with any of these infections should undergo prompt diagnostic evaluation and receive appropriate treatment.

Consider withholding VUMERITY treatment in patients with herpes zoster or other serious infections until the infection has resolved [see Adverse Reactions (6.2)]

5.4 Lymphopenia

VUMERITY may decrease lymphocyte counts. In the MS placebocontrolled trials with dimethyl fumarate (which has the same active metabolite as VUMERITY), mean lymphocyte counts decreased by approximately 30% during the first year of treatment with dimethyl fumarate and then remained stable. Four weeks after stopping dimethyl fumarate, mean lymphocyte counts increased but did not return to baseline. Six percent (6%) of dimethyl fumarate patients and <1% of placebo patients experienced lymphocyte counts <0.5 × 109/L (lower limit of normal 0.91 × 109/L). The incidence of infections (60% vs 58%) and serious infections (2% vs 2%) was similar in patients treated with dimethyl fumarate or placebo, respectively. There was no increased incidence of serious infections observed in patients with lymphocyte counts <0.8 × 109/L or ≤0.5 × 109/L in controlled trials, although one

patient in an extension study developed PML in the setting of prolonged lymphopenia (lymphocyte counts predominantly <0.5 × 109/L for 3.5 years) [see Warnings and Precautions (5.2)]

In controlled and uncontrolled clinical trials with dimethyl fumarate, 2% of patients experienced lymphocyte counts <0.5 × 109/L for at least six months, and in this group the majority of lymphocyte counts remained <0.5 × 109/L with continued therapy. Neither VUMERITY® (diroximel fumarate) nor dimethyl fumarate have been studied in patients with preexisting low lymphocyte counts.

Obtain a complete blood count (CBC), including lymphocyte count, before initiating treatment with VUMERITY, 6 months after starting treatment, and then every 6 to 12 months thereafter, and as clinically indicated. Consider interruption of VUMERITY in patients with lymphocyte counts less than 0.5 × 109/L persisting for more than six months. Given the potential for delayed recovery of lymphocyte counts, continue to obtain lymphocyte counts until their recovery if VUMERITY is discontinued or interrupted because of lymphopenia. Consider withholding treatment from patients with serious infections until resolution. Decisions about whether or not to restart VUMERITY should be individualized based on clinical circumstances.

5.5 Liver Injury

Clinically significant cases of liver injury have been reported in patients treated with dimethyl fumarate (which has the same active metabolite as VUMERITY) in the postmarketing setting. The onset has ranged from a few days to several months after initiation of treatment with dimethyl fumarate. Signs and symptoms of liver injury, including elevation of serum aminotransferases to greater than 5-fold the upper limit of normal and elevation of total bilirubin to greater than 2-fold the upper limit of normal have been observed. These abnormalities resolved upon treatment discontinuation. Some cases required hospitalization. None of the reported cases resulted in liver failure, liver transplant, or death. However, the combination of new serum aminotransferase elevations with increased levels of bilirubin caused by drug-induced hepatocellular injury is an important predictor of serious liver injury that may lead to acute liver failure, liver transplant, or death in some patients.

Elevations of hepatic transaminases (most no greater than 3 times the upper limit of normal) were observed during controlled trials with dimethyl fumarate [see Adverse Reactions (6.1)]

Obtain serum aminotransferase, alkaline phosphatase (ALP), and total bilirubin levels prior to treatment with VUMERITY and during treatment, as clinically indicated. Discontinue VUMERITY if clinically significant liver injury induced by VUMERITY is suspected.

5.6 Flushing

VUMERITY may cause flushing (e.g., warmth, redness, itching, and/ or burning sensation). In clinical trials of dimethyl fumarate (which has the same active metabolite as VUMERITY), 40% of dimethyl fumaratetreated patients experienced flushing. Flushing symptoms generally began soon after initiating dimethyl fumarate and usually improved or resolved over time. In the majority of patients who experienced flushing, it was mild or moderate in severity. Three percent (3%) of patients discontinued dimethyl fumarate for flushing and <1% had serious flushing symptoms that were not life-threatening but led to hospitalization.

Administration of VUMERITY with food may reduce the incidence of flushing [see Dosage and Administration (2.3)]. Studies with dimethyl fumarate show that administration of non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to dosing may reduce the incidence or severity of flushing [see Clinical Pharmacology (12.3)]

6. ADVERSE REACTIONS

The following important adverse reactions are described elsewhere in labeling:

• Anaphylaxis and Angioedema [see Warnings and Precautions (5.1)]

• Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions Section (5.2)]

• Herpes Zoster and Other Serious Opportunistic Infections [see Warnings and Precautions (5.3)]

• Lymphopenia [see Warnings and Precautions (5.4)]

• Liver Injury [see Warnings and Precautions (5.5)]

• Flushing [see Warnings and Precautions (5.6)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The data described in the following sections were obtained using dimethyl fumarate delayed-release capsules, which has the same active metabolite as VUMERITY.

Adverse Reactions in Placebo-Controlled Trials with Dimethyl Fumarate

In the two well-controlled studies demonstrating effectiveness, 1529 patients received dimethyl fumarate with an overall exposure of 2244 person-years [see Clinical Studies (14)]

The adverse reactions presented in Table 1 below are based on safety information from 769 patients treated with dimethyl fumarate 240 mg twice a day and 771 placebo-treated patients. The most common adverse reactions (incidence ≥10% and ≥2% more than placebo) for dimethyl fumarate were flushing, abdominal pain, diarrhea, and nausea.

Table 1: Adverse Reactions in Study 1 and 2 Reported for Dimethyl Fumarate at ≥2% Higher Incidence than Placebo

Adverse Reactions

Flushing

Abdominal pain

Diarrhea

Nausea

Vomiting

Pruritus

Albumin urine present

Erythema

Dyspepsia

Aspartate aminotransferase increased

Lymphopenia

Dimethyl Fumarate 240 mg Twice Daily (N=769) %

Placebo (N=771)%

6

10

11

9

5

4

3

4

1

3

2

<1

Gastrointestinal Dimethyl fumarate caused GI events (e.g., nausea, vomiting, diarrhea, abdominal pain, and dyspepsia). The incidence of GI events was higher early in the course of treatment (primarily in month 1) and usually decreased over time in patients treated with dimethyl fumarate compared with placebo. Four percent (4%) of patients treated with dimethyl fumarate and less than 1% of placebo patients discontinued due to gastrointestinal events. The incidence of serious GI events was 1% in patients treated with dimethyl fumarate.

Hepatic Transaminases

An increased incidence of elevations of hepatic transaminases in patients treated with dimethyl fumarate was seen primarily during the first six months of treatment, and most patients with elevations had levels <3 times the upper limit of normal (ULN) during controlled trials. Elevations of alanine aminotransferase and aspartate aminotransferase to ≥3 times the ULN occurred in a small number of patients treated with both dimethyl fumarate and placebo and were balanced between groups. There were no elevations in transaminases ≥3 times the ULN with concomitant elevations in total bilirubin >2 times the ULN. Discontinuations due to elevated hepatic transaminases were <1% and were similar in patients treated with dimethyl fumarate or placebo.

Eosinophilia

A transient increase in mean eosinophil counts was seen during the first 2 months of therapy.

Adverse Reactions in Clinical Studies with VUMERITY

In clinical studies assessing safety in patients with RRMS, approximately 700 patients were treated with VUMERITY and approximately 490 patients received more than 1 year of treatment with VUMERITY. The adverse reaction profile of VUMERITY was consistent with the experience in the placebo-controlled clinical trials with dimethyl fumarate.

6.2 Postmarketing Experience

The following adverse reaction has been identified during post approval use

of dimethyl fumarate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hepatobiliary Disorders: Liver function abnormalities (elevations in transaminases ≥3 times ULN with concomitant elevations in total bilirubin >2 times ULN) [see Warnings and Precautions (5.5)]

Infections and Infestations: Herpes zoster infection and other serious opportunistic infections [see Warnings and Precautions (5.3)]

Respiratory, Thoracic, and Mediastinal Disorders: Rhinorrhea

Skin and Subcutaneous: Alopecia

8. USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no adequate data on the developmental risk associated with the use of VUMERITY® (diroximel fumarate) or dimethyl fumarate (which has the same active metabolite as VUMERITY) in pregnant women. In animal studies, administration of diroximel fumarate during pregnancy or throughout pregnancy and lactation resulted in adverse effects on embryofetal and offspring development (increased incidences of skeletal abnormalities, increased mortality, decreased body weights, neurobehavioral impairment) at clinically relevant drug exposures [see Data]

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Data Animal Data

Oral administration of diroximel fumarate (0, 40, 100, or 400 mg/kg/ day) to pregnant rats throughout organogenesis resulted in a decrease in fetal body weight and an increase in fetal skeletal variations at the highest dose tested, which was associated with maternal toxicity. Plasma exposures (AUC) for MMF and HES (the major circulating drugrelated compound in humans) at the no-effect dose (100 mg/kg/day) for adverse effects on embryofetal development were approximately 2 times those in humans at the recommended human dose (RHD) of 924 mg/day.

Oral administration of diroximel fumarate (0, 50, 150, or 350 mg/kg/ day) to pregnant rabbits throughout organogenesis resulted in an increase in fetal skeletal malformations at the mid and high doses and reduced fetal body weight and increases in embryofetal death and fetal skeletal variations at the highest dose tested. The high dose was associated with maternal toxicity. Plasma exposures (AUC) for MMF and HES at the no-effect dose (50 mg/kg/day) for adverse effects on embryofetal development were similar to (MMF) or less than (HES) those in humans at the RHD.

Oral administration of diroximel fumarate (0, 40, 100, or 400 mg/kg/day) to rats throughout gestation and lactation resulted in reduced weight, which persisted into adulthood, and adverse effects on neurobehavioral function in offspring at the highest dose tested. Plasma exposures (AUC) for MMF and HES at the no-effect dose for adverse effects on postnatal development (100 mg/kg/day) were approximately 3 times (MMF) or similar to (HES) those in humans at the RHD.

8.2 Lactation Risk Summary

There are no data on the presence of diroximel fumarate or metabolites (MMF, HES) in human milk. The effects on the breastfed infant and on milk production are unknown.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VUMERITY and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of dimethyl fumarate and VUMERITY did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients.

8.6 Renal Impairment

No dosage adjustment is necessary in patients with mild renal impairment. Because of an increase in the exposure of a major metabolite [2-hydroxyethyl succinimide (HES)], use of VUMERITY is not recommended in patients with moderate or severe renal impairment [see Clinical Pharmacology (12.3)].

17. PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Dosage and Administration

Inform patients that they will be provided a starter dose bottle: one capsule twice a day for the first 7 days and then two capsules twice a day thereafter. Advise patients to take VUMERITY as instructed. Inform patients to swallow VUMERITY capsules whole and intact. Inform patients to not crush, chew, or sprinkle capsule contents on food. Inform patients that they should avoid a high-fat, high-calorie meal/snack at the time they take VUMERITY. If taken with food, the meal/snack should contain no more than 700 calories and no more than 30 g fat. Advise patients to avoid co-administration of VUMERITY with alcohol [see Dosage and Administration (2.2)]

Anaphylaxis and Angioedema

Advise patients to discontinue VUMERITY and seek medical care if they develop signs and symptoms of anaphylaxis or angioedema [see Warnings and Precautions (5.1)]

Progressive Multifocal Leukoencephalopathy

Inform patients that progressive multifocal leukoencephalopathy (PML) has occurred in patients who received dimethyl fumarate, and therefore may occur with VUMERITY. Inform the patient that PML is characterized by a progression of deficits and usually leads to death or severe disability over weeks or months. Inform the patient of the importance of contacting their healthcare provider if they develop any symptoms suggestive of PML. Inform the patient that typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes [see Warnings and Precautions (5.2)]

Herpes Zoster and Other Serious Opportunistic Infections

Inform patients that herpes zoster and other serious opportunistic infections have occurred in patients who received dimethyl fumarate and therefore may occur with VUMERITY. Instruct the patient of the importance of contacting their doctor if they develop any signs or symptoms associated with herpes zoster or other serious opportunistic infections [see Warnings and Precautions (5.3)]

Lymphocyte Counts

Inform patients that VUMERITY may decrease lymphocyte counts. A blood test should be obtained before they start therapy. Blood tests are also recommended after 6 months of treatment, every 6 to 12 months thereafter, and as clinically indicated [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)]

Liver Injury

Inform patients that VUMERITY may cause liver injury. Instruct patients treated with VUMERITY to report promptly to their healthcare provider any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. A blood test should be obtained before patients start therapy and during treatment, as clinically indicated [see Warnings and Precautions (5.5)]

Flushing and Gastrointestinal (GI) Reactions

Flushing and GI reactions (abdominal pain, diarrhea, and nausea) are the most common reactions, especially at the initiation of therapy, and may decrease over time. Advise patients to contact their healthcare provider if they experience persistent and/or severe flushing or GI reactions. Advise patients experiencing flushing that taking VUMERITY with food (avoid high-fat, high-calorie meal or snack) or taking a nonenteric coated aspirin prior to taking VUMERITY may help [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]

Pregnancy

Instruct patients that if they are pregnant or plan to become pregnant while taking VUMERITY they should inform their healthcare provider [see Use in Specific Populations (8.1)]

Manufactured for: Biogen Inc. Cambridge, MA 02142

VUMERITY is a registered trademark of Biogen.

Biogen

The Mission of the AAN is to promote the highest quality patient-centered neurologic care and enhance member career satisfaction.

The Vision of the AAN is to be indispensable to our members.

Contact Information

American Academy of Neurology

201 Chicago Avenue

Minneapolis, MN 55415

Phone: (800) 879-1960 (toll free) (612) 928-6000 (international)

Email: memberservices@ aan.com Website: AAN.com

For advertising rates, contact: Michael J. O’Brien II

Account/Relationship Manager

Wolters Kluwer

Phone: (978) 578-4514

Email: Michael.Obrien @ wolterskluwer.com

October Highlights 9

Shooting Victim Gabby Giffords Shares Insights on Aphasia, Gun Safety

In the latest issue of Brain & Life®, former US Representative Gabby Giffords talks about her experience with aphasia and her advocacy work, which includes gun safety and speaking up for others with aphasia.

12November 2 Is Deadline to Apply for 2023 AAN Awards

Apply or nominate a deserving colleague for a variety of prestigious AAN awards to be celebrated in person during the 75th AAN Annual Meeting in Boston next April 22–27.

22

Transforming Leaders Graduate Breaks Down Barriers to Become a Guiding Star

AAN Chief Executive Officer: Mary E. Post, MBA, CAE Editor-in-Chief: Melissa W. Ko, MD, MBA, CPE, FAAN

Managing Editor: Angela M. Babb, MS, CAE, APR

Editor: Tim Streeter

Writers: Ryan Knoke and Sarah Parsons

Designer: Siu Lee

Email: aannews@ aan.com

AANnews® is published monthly by the American Academy of Neurology for its 38,000 members worldwide. Access this magazine and other AAN publications online at AAN.com.

The American Academy of Neurology ’s registered trademarks and service marks are registered in the United States and various other countries around the world.

“American Brain Foundation” is a registered service mark of the American Brain Foundation and is registered in the United States.

The inclusion of advertisements and/or promotions of Sponsors and other Internet sites or resources that offer content, goods, or services on the Website does not imply endorsement of the advertised/promoted products or services by AAN.

Since graduating from the Transforming Leaders Program in 2021, Sonika Agarwal, MBBS, MD, has catapulted to national leadership roles outside her unique expertise in fetal-neonatal neurology, clinical excellence, and educational achievements.

Apply for 2023 Neurology on the Hill

Next year’s Neurology on the Hill will take place March 5–7, in Washington, DC. Applications for this premier AAN advocacy event will be open from October 10 to November 21, 2022. Learn more about how you can represent crucial neurology issues to your members of Congress at AAN.com/NOH

The Brain Health Summit: An Evolution of a Long Tradition of Public Education at the AAN

On September 15, the American Academy of Neurology convened its first Brain Health Summit in Washington, DC. It was the culmination of decades of commitment to take on the responsibility of public education about neurologic health, stretching back to the founding era of the Academy when Mabel G. Marston, MD—the first woman to become a full professor at the University of Wisconsin Medical School in 1950 and eventual chair of its Department of Neuro-psychiatry—chaired the AAN Committee for Public Relations in 1949.

In those earlier years, most of the AAN’s external focus was on promoting public education through press releases on the latest brain research, often in conjunction with the Annual Meetings. Today, our robust press release program shares exciting scientific results published in Neurology ® at least six times per month, with each release reaching millions upon millions of readers and viewers through local, national, and international print and electronic media.

The AAN’s capable advocacy efforts resulted in the 1990s being deemed “The Decade of the Brain” by an act of Congress, and a subsequent supplement in USA Today furthered our public education outreach. Soon, members asked for education materials they could share with their patients in their offices, and the Academy responded with disease-specific brochures with concise, easy-to-understand information and visual aids. There has been ongoing public education through our AAN patient guideline summaries and sports concussion resources, as well as projects to promote acute stroke treatment and the signs of stroke, disease-specific videos and guidebooks, and public service announcements.

A great leap forward occurred in late 2001, when former President Theodore L. Munsat, MD, FAAN, was asked by then-President Stanley Fahn, MD, FAAN, to take part in the creation of a series of educational books for people with neurologic disease. He, in turn, recruited my friends former President Steven P. Ringel, MD, FAAN, and future President Terrence L. Cascino, MD, FAAN, (who was co-chair of the AAN Education Committee at the time), and thus began an effort to create material that will “serve as a recognized authoritative source of information” for patients and the public. Others joined on and in a written proposal dated February 22, 2002, Dr. Munsat, a cofounder of Continuum® ,

concluded, “I view this an exciting challenge with great potential to provide patients with much needed educational material and simultaneously address the mission of the AAN.” There were subsequent financial and logistical challenges to overcome as the tactics evolved beyond the creation of a book series to include a patient and caregiver magazine, and in April of 2005 the first issue of Neurology Now® (now called Brain & Life® magazine) was published.

More than two decades subsequent to that meeting of the minds, the AAN’s suite of public educational products now includes Brain & Life® en Espanol, the website BrainandLife.org, the Brain & Life® Book Series, and the Brain & Life Podcast—resources that reach millions of people throughout the world. Today, these Brain & Life products cover a broad spectrum of brain health including exercise and nutrition, wellness, preventive care, lifestyle improvements, and assistance in living well with neurologic conditions.

The AAN has also presented a variety of free Brain Health Fairs for the residents of cities hosting our Annual Meetings and free bike helmet giveaways in conjunction with a police-sponsored bike safety program in the city of Minneapolis, where the AAN headquarters is located.

It was at a Brain Health Fair in 2013 that I was first introduced to Natalia S. Rost, MD, MPH, FAHA, FAAN, who serves as the chief of the stroke division at the Massachusetts General Hospital and as Science Committee chair. We were both helping people get free bicycle helmets at a booth at the San Diego Convention Center. Attendees of all ages loved it, and we did as well! As crowds of people rushed our table to get properly fitted, we chatted, and over the subsequent years serving together on the AAN Board of Directors I learned about her commitment to preventive care.

When the newly established Committee on Public Engagement (COPE) launched during my term as president, under the direction of the Board of Directors—which had set brain health as one of the organization’s top priorities—I asked Dr. Rost to serve as its vice chair together with policy expert David A. Evans, MBA, as its chair. Over the past year, they have led COPE in developing a strategic plan prioritizing brain health

Natalia S. Rost, MD, MPH, FAHA, FAAN; Avitzur; and Evans.

Avitzur

Sen. Ben Ray Luján (D–NM); AAN CEO Mary E. Post, MBA, CAE; David A. Evans, MBA; and Avitzur.

as a key aspect of public engagement and developing the AAN’s Brain Health Initiative, with Dr. Rost being instrumental in planning the Brain Health Summit and promoting it to key neurologists, educators, and thought leaders in and outside our profession.

Designed as a call to action to raise awareness and improve understanding of brain diseases and the importance of maintaining a healthy brain, the summit is intended to set the stage to enable the public to become better educated in brain health during every stage of life. Despite a growing number of local, national, and global brain health initiatives created to promote disease prevention and advance research, no singular medical or allied profession has ever been able to curate whole brain health. I believe that neurology, bolstered by the vast experience of the AAN in public education, is the ideal profession to lead this effort. Toward that end, the US House of Representatives granted our request to designate September 15 as National Brain Health Day.

A highlight of the event was the surprise appearance of New Mexico Sen. Ben Ray Luján, a recent stroke survivor, who shared his experience with attendees and expressed his ongoing commitment to brain health. He is already a leader on the ENACT Act (S. 1548), a bill to increase the participation of underrepresented populations in research and clinical trials for Alzheimer's disease and related dementias, and the Neuroscience Center of Excellence Act (S. 3427), which would establish a Neuroscience Center of Excellence at the Food and Drug Administration.

Just hours before the September 15 Brain Health Summit convened, the Neurology journal published a special editorial I had

PRACTICE

asked Dr. Rost, and Mr. Evans to write with me. It goes into greater detail about the need and purpose of the Brain Health Initiative and the goals of this initial meeting, which brought together 100 of the brightest minds in American neurology. As I finish composing this column the day after, I am still energized by the enthusiasm our colleagues brought to this event and the torrent of creative ideas they shared.

I wish to thank the National Institute on Aging, Healthy Brain Global Initiative, Center for BrainHealth, American Heart Association, the Health Metrics and Evaluation, Feil Family Brain and Mind Research, and AARP, among others who were represented at the summit and shared their work in brain health. I’d also like to recognize other international neurology associations, such as the European Academy of Neurology and the World Federation of Neurology, on their brain health efforts and look forward to future collaboration with all of them.

I’d like to believe that Drs. Marston and Munsat and their colleagues would be proud to learn how far their vision to reach the public has come. The bold steps we take now with this new initiative will have a tremendous impact on the brain health of America for decades to come.

Orly Avitzur, MD, MBA, FAAN President, AAN oavitzur@aan.com @OrlyA on Twitter

Shooting Victim Gabby Giffords Shares Insights on Aphasia, Gun Safety

In the latest issue of Brain & Life®, former US Representative Gabby Giffords talks about her experience with aphasia and her advocacy work, which includes gun safety and speaking up for others with aphasia. The feature includes a sidebar on understanding aphasia, including the importance of speech therapy and recent research on the use of brain stimulation to treat the disorder.

With the Senate passing a bill to make daylight saving time permanent, sleep experts caution against it, noting several health risks. Brain & Life looks at the evidence and offers advice on how to protect sleep in any situation.

Seeking a second opinion makes good sense but how do patients resolve conflicting perspectives? This article provides various examples (a general neurologist’s diagnosis differs from a specialist’s; one doctor recommends surgery, another says it isn’t necessary, etc.) and provides tips for making informed decisions.

Brain & Life magazine is free for AAN members in the United States to distribute to patients, who also can subscribe for free. If you would like to adjust the number of copies you receive for your patients or update your clinic address, email BeGreen @ WasteFreeMail.com. All members have online access to the magazine articles and additional resources at BrainandLife.org and are encouraged to share the website with their patients.

AAN members, patients, and caregivers also can listen to the new Brain & Life podcast, an entertaining weekly podcast featuring neurology experts, celebrity advocates, and people whose lives are affected by brain conditions. Follow and subscribe wherever you get your podcasts. Learn more at BrainandLife.org/podcast

doesn’tAphasiachange whoyou

Put Compensation and Productivity Data to Work for You—Soon!

If you completed the 2021 Neurology Compensation and Productivity Survey, your free access to the dashboard is available only until December 31, 2022. With more than 4,000 AAN participants in the latest survey, this is the largest and most robust source of neurology data anywhere. Use the dashboard that has been created for you to filter the data by subspecialty, practice setting, region, and more. Visit AAN.com/Benchmark today to start changing your practice for the better.

The Academy again thanks all members who participated in the 2021 survey

looks forward to your continued contributions to the new survey coming in 2023.

Patients of Axon Registry Participants Eligible for Data-driven Clinical Trials

The AAN’s strategic data and technology partner for the Axon Registry®, Verana Health, is focused on elevating data quality and the value practices derive from their registry participation. A new participant benefit supported by Verana Health is data-driven trial opportunities, which may help you refer patients with limited treatment options to innovative studies.

One open study is for patients with frontotemporal dementia (FTD), a rare neurodegenerative disease but the most common form of dementia for people under 60. It can change a person’s

behavior and personality and limit their verbal and physical abilities. It also can be challenging to diagnose, and current treatment options are limited.

Verana Health is supporting a Phase III Study sponsored by Alector Therapeutics by using de-identified Axon Registry data to find and alert neurology practices

with patients who may qualify for study participation. Patients who are referred for this trial and meet key criteria may be offered no-cost genetic testing and counseling services.

Learn more at info.veranahealth.com/ aan-trials.

Neurology: Clinical Practice Serves up Latest Brain Research

Research published in the new Neurology® Clinical Practice spans a range of neurologic topics, including “A Review of Practices Around Determination of Death by Neurologic Criteria by an Organ Procurement Organization in the WAMI Region,” by Abhijit Vijay Lele, MD, MBBS, MS, FNCS, et al.; “Discordance Between Perceptions and Experience of Lumbar Puncture: A Prospective Study,” by Adrienne Boire, MD, PhD, et al.; “Objective Neurophysiological Markers of Cognition After Pediatric Brain Injury,” by Sudhin A. Shah, PhD, et al.; “Creating a Patient-based Diagnostic Checklist for Functional Tics During the COVID-19 Pandemic,” by Steven Patrick Trau, MD, et al.; and “Clinicopathologic Correlations of Jaw Tremor in a Longitudinal Aging Study,” by Sana Aslam, DO, et al.

Published continuously online and in print six times a year, Neurology: Clinical Practice is free to AAN members via the website (and available in print for US members only) who have a current subscription to Neurology® Visit Neurology.org/cp for more information.

22 Tips Your Colleagues Use in Their Efficient Practices continued from cover

EHR Efficiency

Electronic health record (EHR) software tools can be an easy way to increase efficiency. These tools can simplify documentation, maximize billing, and improve communication with your patients.

Consider adjusting the outline of user notes or note templates to reflect the 2021 outpatient E/M guidelines. Learn more at AAN.com/EM

Use any onboarding or development time with clinicians to equip them with EHR tools for easier, faster, and better documentation.

Leverage the EHR’s custom dictionary or autocorrect function using unique codes or acronyms that automatically spell out the whole word. This gives the user the speed for which the acronym was developed yet spells out the word to avoid confusion by the reader (e.g., sz = seizure, emu = epilepsy monitoring unit).

Ensure all forms and questionnaires are electronically available through the patient portal for efficient integration and utilization in patient charts.

Technology Efficiency

There are many technology tools that can increase efficiency. Using technology can make tasks easier, improve accuracy, and streamline business processes.

Consider incorporating and becoming proficient in using speech recognition software in your documentation workflow.

A secure text messaging system to communicate with patients (e.g., sending appointment reminders) can help reduce staff time needed to make patient phone calls.

Send patient questionnaires via a portal or other secure third-party web application to patients, and caregivers when appropriate, in advance of the

appointment to capture reported outcome measures.

Use telehealth software that integrates into the EHR system to streamline the patient touchpoints such as check-in.

Consider having support staff send telehealth appointment links in advance to confirm connectivity. Develop a backup plan for synchronous audio/visual connectivity challenges, e.g., confirming the best way to connect with the patient via audio only.

Connect the entire care team via telehealth to enhance the patient experience, e.g., connecting with the ICU pharmacist when doing medicine reconciliation, or including the patient’s rehab nurse when seeing a patient at a rehab facility.

Staffing Efficiency

Optimizing staffing and their workflows is one of the best ways to improve clinician efficiency. It can ensure clinicians are practicing to the top of their license and increase access by enabling the clinician to spend more time with patients.

Invest in training support staff to ensure accurate work.

Use team-based huddles to plan for the upcoming day and week.

Consider having the medical assistant bring the after-visit summary and patient instructions into the exam room to review with the patient prior to checking out. This allows the clinician to move to the next room more quickly while still allowing the patient to ask final questions with a member of the team.

Have your rooming staff prepare patients by asking them for any specific questions in advance of the physician’s arrival into the room.

Consider increasing medical assistants’ mobility by assigning them a laptop each day. Using a secure messaging system to allow for real-time updates

and communication with support staff (e.g., if an exam is taking longer than expected so staff can communicate with patients) can increase efficiency and patient experience by having a coordinated team.

Workflow Efficiency

Building in workflow efficiencies can reduce burden across the organization, improve the health of the business, and establish best practices to deliver exceptional patient care.

Create a separate “short notice” cancellation list that indicates when patients can be available to fill an opening on short notice, either by coming in person or connecting via telehealth. This can reduce staff moving through a long cancellation list to fill an unexpected opening, such as a no-show.

Create a list at the start of each day that shows scheduled patients’ balances to make it easier for administrative staff to collect the outstanding balances during check-in. Consider offering incentives for collecting a certain percentage of the balances.

As much as possible, set up all exam rooms the same way so restocking is easy, and everyone knows where everything is kept. This will minimize “looking around” for supplies, forms, equipment, etc.

Minimize phone calls by scheduling outpatient follow-up appointments prior to discharge from the hospital.

Ask all patients at check-in if they need refills or forms completed and establish a workflow to communicate and complete these tasks with the team.

Be sure the patient has enough refills to get them to the next visit to reduce patient phone calls and refill requests.

Consider a nurse triage call system to differentiate emergent, urgent, and routine requests with common language.

Registration Still Available for This Month’s Fall Conference continued from cover

Conference highlights include:

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New programming based on updates and progress made in the field of neurology over the past six months

ƒ The latest innovative science through the Neuroscience in the Clinic and Plenary Sessions

ƒ

Insights on practice management ranging from coding, building service lines, value-based care, and productivity to telemedicine and HR/staffing

ƒ Leadership University with four sessions focused on professional development

ƒ Interactive Experiential Learning Areas with one-onone Curbside Consults where you can bring your most challenging cases for discussion with an expert or learn about neuro exam tips and tricks.

ƒ Opportunities to learn about the latest industry innovations in the Exhibit Hall

Can’t Join Us in Las Vegas?

You can still register for the convenient online option and join us from anywhere you have an internet connection to watch sessions live and participate in Q/A opportunities with presenters, catch exclusive online-only content, connect with others with similar interests, and view session recordings at your leisure through November 14, 2022. Add On Demand for access to conference sessions through August 1, 2023. 

Come a Day Early for One of These In-person Pre-conferences!

Attend either of these inperson-only pre-conferences on Thursday, October 27, as a stand-alone, or bundle with the full Fall Conference to save! Visit AAN.com/Fall to learn more.

Advanced Practice Provider Pre-conference

This pre-conference provides a full day of programming that includes neurology fundamentals and clinical case studies on several topics such as dementia, epilepsy, movement disorders; a deeper dive on techniques and skills for lumbar punctures, deep brain stimulation, nerve blocks, and botulinum toxin use in treatment of migraine; as well as special networking opportunities.

Sports Concussion Pre-conference

A full day of sports concussion programming designed especially for residents, medical students, and general neurologists. The curriculum will focus on the physical exam, TBI, special populations, brain health, and updated concussion guidelines for the general neurologist. 

November 2 Is Deadline to Apply for 2023 AAN Awards

The November 2 deadline to apply for the 2023 AAN awards is quickly approaching. Apply or nominate a deserving colleague for a variety of prestigious AAN awards to be celebrated in person during the 75th AAN Annual Meeting in Boston next April 22–27.

The AAN values unique contributions to the field of neurology and AAN awards recognize individuals across all career levels for their outstanding achievements. Recipients will be honored during conferences and may receive travel stipends, or have the opportunity to present their work to their colleagues.

Visit AAN.com/Awards to learn more and apply or nominate. 

AAN Urges Congress to Help Expand Neurology Workforce

The US is on the precipice of a “perfect storm” that could severely swamp neurologic care for decades. And the AAN is working hard to convince Congress that it can help prevent health care from capsizing.

It’s no secret that the population of the United States is rapidly aging. It is expected to grow by 10.6 percent by 2034, with a 42.4-percent increase of individuals aged 65 years and older, and a 74-percent increase of individuals aged 75 years and older. As life expectancy continues to rise, more Americans will develop chronic neurologic conditions that require specialized care.

Second, the country faces a shortage of between 37,800 and 124,000 physicians by 2034, according to a 2021 study by the Association of American Medical Colleges. The workforce will likely be depleted further by rising rates of physician burnout and early retirement due to the COVID-19 pandemic. Several years ago, the AAN estimated the current shortage of neurologists at 11 percent, reaching as high as 19 percent by the end of this decade.

The latest high-pressure front is long COVID-19, with concerns that as many as millions of Americans may be suffering from long-term neurologic effects of the coronavirus and its variants. According to one study in the April 2021 Lancet Psychiatry, one-third of patients diagnosed with COVID-19 may develop psychiatric or neurologic disorders within six months, including depression, anxiety, strokes, and dementia. That same study found that among COVID-19 patients admitted to an intensive care unit, the incidence of developing a psychiatric or neurologic disorder increased to 46 percent. Given the magnitude of COVID-19 cases across the US, the impact of neurologic symptoms is likely enormous, and long-term care will be essential.

To address this problem, the AAN has lobbied members of Congress to pass two bills that will expand graduate medical education and reauthorize and strengthen the important Conrad 30 program.

Expand Graduate Medical Education: the Resident Physician Shortage Act of 2021 (S. 834/H.R. 2256)

Congress increased the number of Medicare-supported graduate medical education positions by 1,000 in 2021, the

first increase in nearly 25 years. Building on these new positions, the Resident Physician Shortage Reduction Act of 2021 would increase the number of Medicaresupported direct graduate medical education and indirect medical education medical resident training positions by 14,000 over seven years. The bill has bipartisan congressional support and is widely supported by the medical community, said Umer Najib, MD, FAAN, a member of the AAN Health Policy Subcommittee and the neurology department at West Virginia University Hospitals, who has closely followed this issue.

“These positions are targeted to teaching hospitals with diverse needs,” said Najib, “including those that are rural, are already training over their Medicare caps, are in states with new medical schools or branch campuses, and are serving patients in health professional shortage areas.” The bill also requires a report to look at ways to create a more diverse clinical workforce.

Reauthorize and Strengthen: the Conrad State 30 and Physician Access Reauthorization Act (S. 1810/H.R. 3541)

With communities across the country facing physician shortages, the Conrad 30 program provides 30 waivers per state to non-US international medical graduates (IMGs) with a J-1 visa, allowing them to continue practicing in the US if they agree to work in a medically underserved area for three years. Currently IMGs, who make up 31.5 percent of the US neurology workforce, are required to return to their home country for two years after residency before applying for a work visa or green card. The Conrad 30 program is also at perpetual risk of expiring without reauthorization.

How Do We Increase the Number of Neurologists?

“The Conrad State 30 and Physician Access Reauthorization Act would reauthorize the Conrad 30 program for an additional three years,” said Najib. “It would make several key improvements to the program, including a process to gradually increase the number of waivers up to 45 per state and requiring additional employment protections.” 

Better access to neurologic patient care

Najib

2022 APP Neurology Education Series Now Available

Advanced practice providers (APPs) play an important role in the provision of clinical care for neurology patients in the outpatient and inpatient settings. APPs looking for a convenient, online opportunity to get overviews, updates, and resources on a variety of core topics in neurology won’t want to miss this year’s Advanced Practice Provider Neurology Education Series, now available in its entirety in a self-paced format, with all video presentations, slides, and resources accessible immediately upon purchase.

“The Advanced Practice Provider Neurology Education Series provides ongoing professional development and helps lay the foundation for neurological practice for neurology APPs wherever they are in their careers,” said series Co-director Calli Leighann Cook, DNP, FNP-C, FAANP.

Available online-only via video presentations, slides, and other virtual resources, the series was created by physicians and APPs to help neurology APPs keep current on best practices for evaluating and managing:

ƒ

Neuro-ophthalmology: sudden monocular vision loss

Neuro-infectious disease

Functional movement disorders

Epilepsy

Stroke

MS

Chronic daily headache, cluster, and headache syndromes

What’s new in critical care neurology

“For the many neurologists who work closely with APPs in their clinical practice of neurology, the series provides a superb education tool for

RITE Registration Opens This Month

Registration for the AAN’s RITE® (Residency In-service Training Examination) opens October 13. The exam will be administered February 14 through 20, 2023, and offers a chance for neurology residents to assess their current level of knowledge in neurology and neuroscience, identify areas for potential growth, and track their progression throughout their residency. Each exam question is accompanied by discussions and references for additional study.

APPs, assisting in the orientation of new APPs, and also providing an educational resource for experienced APPs who are looking to continue to expand their fund of knowledge in clinical neurology,” said series Co-director Robert D. Brown, Jr., MD, MPH, FAAN.

Added Cook, “I love that the product is a partnership; we use a team-based approach to teaching aiming to be inclusive to all learners.”

The series also offers up to eight CME credits. Learn more and enroll today at AAN.com/APP

Program directors/coordinators will receive an email when registration opens, along with a custom link to the program’s registration page, which lists program and resident information, registration information, and a program resident roster. Be sure to verify your correct email address is listed in your member profile to ensure receipt of this important information.

The deadline to apply is December 9, 2022. Visit AAN.com/RITE to learn more.

Deadline Approaching to Complete 2022 Continuous Certification Requirements

UCNS diplomates should complete their continuous certification (C-cert) activities by no later than December 1. The UCNS C-cert annual requirements provide diplomates with a relevant, effective, timely, and convenient way to meet the needs of lifelong learning and self-assessment.

Diplomates can earn up to 15 ABPN SA credits in addition to up to 15 AMA PRA Category 1 CreditsTM for meeting the 2022 UCNS C-cert requirements. The total credits earned are based on the actual time spent completing the 2022 C-cert activities, up to a maximum of 15 credit hours contingent on passing the C-cert quiz. Confirmation of the credits earned

is emailed to diplomates within 10 business days of passing the 2022 C-cert subspecialty quiz(zes).

The American Board of Psychiatry and Neurology (ABPN) approved the 2022 C-cert program as a part of a comprehensive self-assessment (SA) program, which is mandated

by the American Board of Medical Specialties as a necessary component of maintenance of certification.

Visit UCNS.org/C-cert for more information or contact Bryan Hagerla, Continuous Certification Manager, at bhagerla @ucns.org or (612) 928-6326.

New Continuum Examines Movement Disorders

The October issue of Continuum: Lifelong Learning in Neurology ® offers the latest information on movement disorders. Guest Editor Kathleen L. Poston, MD, MS, shared, “For so many movement disorders, accurate diagnosis hinges on the physical examination. We hope readers will feel more comfortable with the movement disorders examination and will understand when to use supportive biological and genetic markers when making difficult diagnoses. Neurologists will be surprised by some of the newer therapeutic options for people with movement disorders as well as how important palliative care is in the overall therapeutic approach."

Content for this issue includes:

ƒ Prodromal α-Synucleinopathies

Lana M. Chahine, MD, FAAN

ƒ Diagnosis and Medical Management of Parkinson Disease

Avner Thaler, MD, PhD; Roy N. Alcalay, MD, MS

ƒ Surgical Therapies for Parkinson Disease

Ashley E. Rawls, MD, MS

ƒ Diagnosis and Treatment of Cognitive and Neuropsychiatric Symptoms in Parkinson Disease

and Dementia with Lewy Bodies

Daniel Weintraub, MD; David Irwin, MD

ƒ Diagnosis and Treatment of Essential Tremor

Aparna Wagle Shukla, MD

ƒ Multiple System Atrophy

Daniel O. Claassen, MD, MS, FAAN

ƒ Progressive Supranuclear Palsy and Corticobasal Syndrome

Alexander Pantelyat, MD, FAAN

ƒ Chorea

Erin Furr Stimming, MD, FAAN; Danny Bega, MD

MEMBERSHIP

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Neurodegenerative Cerebellar Ataxia

Liana S. Rosenthal, MD, PhD

ƒ The Dystonias

Christopher D. Stephen, MB ChB, FRCP, MS

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Diagnosing Common Movement Disorders in Children

Jennifer A. O’Malley, MD, PhD

ƒ Palliative Care and Movement Disorders

Maya Katz, MD

The issue includes a postreading self-assessment and test with the opportunity to earn up to 20 AMA PRA Category 1 Credits™ toward Self-assessment CME.

AAN members pay only $399 per year for a subscription to Continuum® and Continuum® Audio. Subscribe now by contacting Wolters Kluwer at (800) 361-0633 or (301) 223-2300 (international) or visit shop.lww.com/continuum. AAN Junior members who are transitioning to neurologist memberships are eligible to receive a 60-percent discount on the already low member rate for the Continuum and Continuum Audio subscription.

New Resource Helps Put IDEAS into Practice—in Your Practice

Inclusion is the reason the AAN was founded. To be an organization that is the home for all neurologists. It is what makes us stronger. To support our goal of being a fully inclusive, deliberately diverse, and anti-racist organization and our core values of Inclusion, Diversity, Equity, Anti-racism, and Social Justice (IDEAS), we are excited to share progress and updates with you.

The AAN has developed a new microlearning series on using data to drive IDEAS efforts in your practice. The three-part series is called “Building Inclusion, Diversity, Equity, Anti-racism, and Social Justice in Our Practices.” It is available free to members and takes a total of 15 minutes to view.

“This series is three short, yet thoughtprovoking, videos that encourage the learner to think about practical ways they can build a more inclusive practice,” said Amy E. Martens, MBA, a business administrator member who serves

on the Telehealth Subcommittee, the Academic Business Administrators Work Group, and Neurology Compensation and Productivity Work Group. She participated in developing the resources as a subject matter expert on the topic of recruitment and retention and an advocate of practicing IDEAS principles. “Central to this approach is segmenting materials into bite-size installments with the aim of reducing unnecessary cognitive load as an impediment to learning. This, in turn, allows the learner to prioritize the most

essential skills and content.”

The learning objectives are:

ƒ Use data to develop IDEAS initiatives in your neurology practice

ƒ Learn about intentional and inclusive staff recruitment and retention in the COVID era

ƒ Implement intentional hiring practices

The series is available in the Online Learning Center. For more information, email practice @aan.com.

Poston

FOR PATIENTS WITH CERTAIN VHL-ASSOCIATED TUMORS

DISCOVER WELIREG TM THE FIRST AND ONLY SYSTEMIC TREATMENT 1,2

WELIREG is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

Simple, once-daily, oral dosing

• The recommended dosage is 120 mg once daily until progression of disease or unacceptable toxicity. WELIREG may be taken with or without food.

Not actual size.

1x daily

SELECTED SAFETY INFORMATION

WARNING: EMBRYO-FETAL TOXICITY

• Exposure to WELIREG during pregnancy can cause embryo-fetal harm.

• Verify pregnancy status prior to the initiation of WELIREG.

• Advise patients of these risks and the need for effective non-hormonal contraception as WELIREG can render some hormonal contraceptives ineffective.

Before prescribing WELIREG, please read the additional Selected Safety Information on the following pages and the adjacent Brief Summary of the Prescribing Information, including the Boxed Warning about embryo-fetal toxicity.

WELIREG

TUMOR SHRINKAGE ACROSS CERTAIN TUMORS IN PATIENTS WITH VHL DISEASE

49%

ORRa

(95% CI, 36–62) (n=30/61)b

All responses were partial responses (complete response, 0%)b

Median DOR was not reached (range of ongoing responses: 2.8+ to 22+ months)

56% of patients who responded (n=17/30) maintained a response that lasted ≥12 months

Patient Subgroups

With CNS hemangioblastomas (n=24)

63%

ORRa (95% CI, 41–81) (n=15/24)c

Complete response, 4%; partial response, 58%

Median DOR was not reached (range of ongoing responses: 3.7+ to 22+ months)

73% of patients who responded (n=11/15) maintained a response that lasted ≥12 months

With pNET (n=12)

83%

ORRa (95% CI, 52–98) (n=10/12)c

Complete response, 17%; partial response, 67%

Median DOR was not reached (range of ongoing responses: 11+ to 19+ months)

50% of patients who responded (n=5/10) maintained a response that lasted ≥12 months

Complete response defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response defined as ≥30% decrease in the sum of the longest diameters of target lesions compared with baseline.3

Median DOR could not be estimatedd since the majority of patients who responded to treatment maintained their response (did not experience disease progression per RECIST v1.1) at the time of data cutoff.4

aMeasured by radiology assessment using RECIST v1.1 as assessed by IRC.

bAll patients with a response were followed for a minimum of 18 months from the start of treatment.

cNumber of patients with measurable solid lesions, based on IRC assessment. dBy Kaplan-Meier method.

+ Denotes ongoing response.

DOR = duration of response; RECIST v1.1 = Response Evaluation Criteria

In Solid Tumors v1.1; ORR = objective response rate; CI = confidence interval.

STUDY DESIGN: Patients (N=61) had VHL-associated RCC diagnosed based on a VHL germline alteration and with at least 1 measurable solid tumor (as defined by RECIST v1.1) localized to the kidney. Patients had other VHL-associated tumors, including CNS hemangioblastomas and pNET. CNS hemangioblastomas and pNET in these patients were diagnosed based on the presence of at least 1 measurable solid tumor in brain/spine or pancreas, respectively, as defined by RECIST v1.1 and identified by central independent review committee (IRC). The study excluded patients with metastatic disease. Patients received WELIREG 120 mg once daily until progression of disease or unacceptable toxicity. Median age of patients was 41 years (range 19 to 66 years). Of the 61 patients included in the study, 3.3% were age 65 years or older, and 53% were male. Ninety percent were White, 3.3% were Black or African-American, 1.6% were Asian, and 1.6% were Native Hawaiian or other Pacific Islander. Eighty-two percent had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 16% had an ECOG PS of 1, and 1.6% had an ECOG PS of 2; and 84% had VHL Type I Disease. The median diameter of RCC target lesions per IRC was 2.2 cm. Median time from initial radiographic diagnosis of VHL-associated RCC tumors that led to enrollment to the time of treatment with WELIREG was 17.9 months (range: 2.8 to 96.7 months). Seventy-seven percent of patients had prior surgical procedures for RCC. The major efficacy end point for the treatment of VHL-associated RCC was ORR measured by radiology assessment using RECIST v1.1 as assessed by IRC. Additional efficacy end points included DOR and time to response (TTR).

Learn more at www.welireghcp.com

SAFETY

Anemia

• WELIREG can cause severe anemia that can require blood transfusion. In Study 004, anemia occurred in 90% of patients and 7% had Grade 3 anemia. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months). In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, anemia occurred in 76% of patients and 28% had Grade 3 anemia.

• Monitor for anemia before initiation of and periodically throughout treatment. Closely monitor patients who are dual UGT2B17 and CYP2C19 poor metabolizers due to potential increases in exposure that may increase the incidence or severity of anemia.

• Transfuse patients as clinically indicated. For patients with hemoglobin (Hb) <9 g/dL, withhold WELIREG until Hb ≥9 g/dL, then resume at reduced dose or permanently discontinue depending on the severity of anemia. For life-threatening anemia or when urgent intervention is indicated, withhold WELIREG until Hb ≥9 g/dL, then resume at a reduced dose or permanently discontinue.

• The use of erythropoiesis stimulating agents (ESAs) for treatment of anemia is not recommended in patients treated with WELIREG.

Hypoxia

• WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. In Study 004, hypoxia occurred in 1.6% of patients. In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, hypoxia occurred in 29% of patients; 16% were Grade 3 hypoxia.

• Monitor oxygen saturation before initiation of and periodically throughout treatment. For decreased oxygen saturation with exercise (eg, pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same or a reduced dose. For decreased oxygen saturation at rest (eg, pulse oximeter <88% or PaO2 ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a health care provider.

Embryo-Fetal Toxicity

• Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman.

• Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Adverse Reactions

• In Study 004, serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).

• WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each).

• Dosage interruptions due to an adverse reaction occurred in 39% of patients. Those which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness.

• Dose reductions due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%).

• The most common adverse reactions (≥25%) were decreased hemoglobin (93%), anemia (90%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%).

• In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, the following additional adverse reactions have been reported: edema, cough, musculoskeletal pain, vomiting, diarrhea, and dehydration.

Drug Interactions

• Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended.

• Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A4 substrates, which may reduce the efficacy of these substrates or lead to therapeutic failures. Avoid coadministration with sensitive CYP3A4 substrates. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information. Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding.

Lactation

• Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose.

Females and Males of Reproductive Potential

• WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG.

• Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

• Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential and the reversibility of this effect is unknown.

Pediatric Use

• Safety and effectiveness of WELIREG in pediatric patients under 18 years of age have not been established.

Before prescribing WELIREG, please see the adjacent Brief Summary of the Prescribing Information, including the Boxed Warning about embryo-fetal toxicity.

Summary

the

Information for

40 mg tablets, for oral use

WARNING: EMBRYO-FETAL TOXICITY

• Exposure to WELIREG during pregnancy can cause embryo-fetal harm.

• Verify pregnancy status prior to the initiation of WELIREG.

• Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective.

INDICATIONS AND USAGE

WELIREG is indicated for treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

DOSAGE AND ADMINISTRATION

Recommended Dosing

The recommended dose of WELIREG is 120 mg administered orally once daily until disease progression or unacceptable toxicity. WELIREG should be taken at the same time each day and may be taken with or without food.

Advise patients to swallow tablets whole. Do not chew, crush, or split WELIREG prior to swallowing.

If a dose of WELIREG is missed, it can be taken as soon as possible on the same day.

Resume the regular daily dose schedule for WELIREG the next day. Do not take extra tablets to make up for the missed dose.

If vomiting occurs any time after taking WELIREG, do not retake the dose. Take the next dose on the next day.

Dosage Modifications for Adverse Reactions

Dosage modifications for WELIREG for adverse reactions are summarized in Table 1.

The recommended dose reductions are:

• First dose reduction: WELIREG 80 mg orally once daily

• Second dose reduction: WELIREG 40 mg orally once daily

• Third dose reduction: Permanently discontinue Table 1: Recommended Dosage Modifications for Adverse Reactions

Adverse ReactionSeverity

Hemoglobin <9 g/dL or transfusion indicated

Dosage Modification

• Withhold until hemoglobin ≥9g/dL.

• Resume at reduced dose or discontinue depending on the severity of anemia.

Anemia

Life-threatening or urgent intervention indicated

Decreased oxygen saturation with exercise (e.g., pulse oximeter <88%)

• Withhold until hemoglobin ≥9g/dL.

• Resume at a reduced dose or permanently discontinue.

• Consider withholding until resolved.

• Resume at the same dose or at a reduced dose depending on the severity of hypoxia.

The use of erythropoiesis stimulating agents (ESAs) for treatment of anemia is not recommended in patients treated with WELIREG. For patients treated with WELIREG who develop anemia, the safety and effectiveness for use of ESAs have not been established. Randomized controlled trials in patients with cancer receiving myelosuppressive chemotherapy with ESAs have shown that ESAs increased the risks of death and serious cardiovascular reactions, and decreased progressionfree survival and/or overall survival. See the prescribing information for ESAs for more information.

Hypoxia

WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization.

In Study 004, hypoxia occurred in 1.6% of patients. In another clinical trial [Study 001 (n=58)] in patients with advanced solid tumors who received the same dosage of WELIREG, hypoxia occurred in 29% of patients, including Grade 3 hypoxia in 16%.

Monitor oxygen saturation before initiation of, and periodically throughout, treatment with WELIREG. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same dose or at a reduced dose.

For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or urgent intervention indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening hypoxia or for recurrent symptomatic hypoxia, permanently discontinue WELIREG.

Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider.

Embryo-Fetal Toxicity

Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman. In an animal reproduction study, oral administration of belzutifan to pregnant rats during the period of organogenesis caused embryo-fetal lethality, reduced fetal body weight, and fetal skeletal malformations at maternal exposures ≥0.2 times the human exposures (AUC) at the recommended dose of 120 mg daily. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective nonhormonal contraception during treatment with WELIREG and for 1 week after the last dose, since WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

ADVERSE REACTIONS

The following clinically significant adverse reactions are discussed elsewhere in the labeling:

• Anemia

• Hypoxia

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of WELIREG was evaluated in an open-label clinical trial (Study-004) in 61 patients with VHL disease who had at least one measurable solid tumor localized to the kidney. Patients received WELIREG 120 mg orally once daily. The median duration of exposure to WELIREG was 68 weeks (range: 8.4 to 104.7 weeks).

Hypoxia

Decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or urgent intervention indicated

Life-threatening or recurrent symptomatic hypoxia

Other Adverse Reactions Grade 3

Grade 4

CONTRAINDICATIONS

None.

WARNINGS AND PRECAUTIONS

Anemia

• Withhold until resolved.

• Resume at reduced dose or discontinue depending on the severity of hypoxia.

• Permanently discontinue.

• Withhold dosing until resolved to ≤ Grade 2.

• Consider resuming at a reduced dose (reduce by 40 mg).

• Permanently discontinue upon recurrence of Grade 3.

• Permanently discontinue.

Serious adverse reactions occurred in 15% of patients who received WELIREG, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).

Permanent discontinuation of WELIREG due to adverse reactions occurred in 3.3% of patients. Adverse reactions which resulted in permanent discontinuation of WELIREG were dizziness and opioid overdose (1.6% each).

Dosage interruptions of WELIREG due to an adverse reaction occurred in 39% of patients. Adverse reactions which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness.

Dose reductions of WELIREG due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, that occurred in patients who received WELIREG were decreased hemoglobin, anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea.

WELIREG can cause severe anemia that can require blood transfusion. In Study 004, anemia occurred in 90% of patients and 7% had Grade 3 anemia. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months). In another clinical trial [Study 001 (n=58)] in patients with advanced solid tumors who received the same dosage of WELIREG, anemia occurred in 76% of patients and 28% had Grade 3 anemia. Monitor for anemia before initiation of, and periodically throughout, treatment with WELIREG. Closely monitor patients who are dual UGT2B17 and CYP2C19 poor metabolizers due to potential increases in exposure that may increase the incidence or severity of anemia.

Transfuse patients as clinically indicated. For patients with hemoglobin <9g/dL, withhold WELIREG until ≥9g/dL, then resume at reduced dose or permanently discontinue WELIREG, depending on the severity of anemia. For life threatening anemia or when urgent intervention is indicated, withhold WELIREG until hemoglobin ≥9g/dL, then resume at a reduced dose or permanently discontinue WELIREG.

Brief Summary of the Prescribing Information for WELIREG™ (belzutifan)

mg tablets,

oral use

2 summarizes the adverse reactions reported in patients treated with WELIREG in Study 004.

Table 2: Adverse Reactions Occurring in ≥10% of Patients Who Received WELIREG in Study 004 Adverse Reaction

WELIREG N=61

Grades*

Blood and Lymphatic

Anemia

General

Fatigue†

System

Gastrointestinal

Nausea

Eye Disorders

impairment#

Infections

Upper respiratory tract infectionÞ

Thoracic and Mediastinal

Musculoskeletal and Connective Tissue

Arthralgia

Vascular

Hypertension

and Nutrition

increased

per

CTCAE

and asthenia

headache and migraine

dizziness and vertigo

3-4

Hormonal Contraceptives

Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding.

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk Summary

Based on findings in animal studies, WELIREG can cause fetal harm when administered to a pregnant woman. There are no available data on the use of WELIREG in pregnant women to inform the drug-associated risk. In an animal reproduction study, oral administration of belzutifan to pregnant rats during the period of organogenesis caused embryo-fetal lethality, reduced fetal body weight, and fetal skeletal malformations at maternal exposures ≥0.2 times the human exposure (AUC) at the recommended dose of 120 mg daily (see Data). Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.

Data

Animal Data

In a pilot embryo-fetal development study, pregnant rats received oral doses of 6, 60, or 200 mg/kg/day of belzutifan during the period of organogenesis. Belzutifan caused embryo-fetal lethality at doses ≥60 mg/kg/day (approximately 1 time the human exposure at the recommended dose based on AUC). Reduced fetal body weights, fetal rib malformations, and reduced skeletal ossification occurred at doses of 6 and 60 mg/kg/day (approximately ≥0.2 times the human exposure at the recommended dose based on AUC).

Lactation

Risk Summary

There are no data on the presence of belzutifan or its metabolites in human milk or their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose.

Females and Males of Reproductive Potential

WELIREG can cause fetal harm when administered to a pregnant woman.

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG.

Contraception

Females

abdominal discomfort, abdominal pain, abdominal pain upper and abdominal pain

visual impairment, vision blurred, central retinal

occlusion and retinal

bronchitis, sinusitis, upper respiratory tract infection, and viral upper respiratory infection

3 summarizes the laboratory abnormalities in Study 004.

Table 3: Select Laboratory Abnormalities (≥10%) That Worsened from Baseline in Patients Who Received WELIREG in Study 004

Laboratory Abnormality*

Chemistry

Increased creatinine

Grades 1-4

Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective.

Males

Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

WELIREG (n=61)

Infertility

Grades 3-4

Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential. The reversibility of the effect on fertility is unknown.

Pediatric Use

glucose

4.9 Increased ALT

0 Increased AST

calcium (corrected)

phosphate

Hematology

0

Safety and effectiveness of WELIREG have not been established in pediatric patients. Geriatric Use

Of the patients who received WELIREG in Study 004, 3.3% were ≥65 years old. Clinical trials of WELIREG did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger patients.

Renal Impairment

Decreased hemoglobin

7 Decreased leukocytes

denominator used to calculate

Other Clinical Trials Experience

0

In Study 001 (NCT02974738), a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose in which the median age of enrollment was 62.5 years (range 39-75) and the median number of prior therapies for cancer was 3 (range 1-9), the following additional adverse reactions have been reported following administration of WELIREG at the recommended dosage: edema, cough, musculoskeletal pain, vomiting, diarrhea, and dehydration.

DRUG INTERACTIONS

Effects of Other Drugs on WELIREG UGT2B17 or CYP2C19 Inhibitors

Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions of WELIREG. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended.

Effect of WELIREG on Other Drugs

Sensitive CYP3A4 Substrates

Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A substrates, which may reduce the efficacy of these substrates. The magnitude of this decrease may be more pronounced in patients who are dual UGT2B17 and CYP2C19 poor metabolizers. Avoid coadministration of WELIREG with sensitive CYP3A4 substrates, for which minimal decrease in concentration may lead to therapeutic failures of the substrate. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information.

No dosage modification of WELIREG is recommended in patients with mild (eGFR 60-89 mL/min/1.73 m2 estimated by MDRD) and moderate (eGFR 30-59 mL/min/1.73 m2) renal impairment. WELIREG has not been studied in patients with severe (eGFR 15-29 mL/min/1.73 m2) renal impairment.

Hepatic Impairment

No dosage modification of WELIREG is recommended in patients with mild [total bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN or total bilirubin >1 to 1.5 x ULN and any AST] hepatic impairment. WELIREG has not been studied in patients with moderate or severe hepatic impairment (total bilirubin >1.5 x ULN and any AST).

Dual UGT2B17 and CYP2C19 Poor Metabolizers

Patients who are dual UGT2B17 and CYP2C19 poor metabolizers have higher belzutifan exposures, which may increase the incidence and severity of adverse reactions of WELIREG. Closely monitor for adverse reactions in patients who are dual UGT2B17 and CYP2C19 poor metabolizers.

OVERDOSAGE

There is no specific treatment for WELIREG overdose. In cases of suspected overdose, withhold WELIREG and institute supportive care. Grade 3 hypoxia occurred at dosages of 120 mg twice a day and Grade 4 thrombocytopenia occurred at dosages of 240 mg once daily (approximately 2 times the recommended dosage).

For more detailed information, please read the Prescribing Information. uspi-mk6482-t-2108r000 Revised: 08/2021

Copyright © 2022 Merck & Co., Inc., Kenilworth, NJ, USA and its affiliates All rights reserved.

Transforming Leaders Graduate Breaks Down Barriers to Become a Guiding Star

Since graduating from the Transforming Leaders Program (TLP) in 2021, Sonika Agarwal, MBBS, MD, has catapulted to national leadership roles outside her unique expertise in fetal-neonatal neurology, clinical excellence, and educational achievements at Children’s Hospital of Philadelphia/Perelman School of Medicine at the University of Pennsylvania (PENN/CHOP), where she has been since 2018.

Agarwal originally trained in India as a maternal fetal medicine specialist where she had a rich career path in academic medicine prior to her move to the US. “I wrote an article for Child Neurology Open that highlights the perseverance that was required for the arduous residency match process,” she explained. “The article’s title—'The Guiding Star’—refers to each person I crossed paths with who guided and mentored me in my journey. It symbolizes the Hindu astrology belief that the stars and planets have a powerful influence on our lives and future directions.”

One of the most important things Agarwal says she learned from her earliest mentors—her parents, who are both physicians in India—was to “never give up and be persistent in your work until you succeed.” Her career path as an immigrant

development curriculum. “I applied wishing to excel even further and looking for national mentors and leaders to connect with; those who could help build a network for me to grow in the field of fetal-neonatal neurology and child neurology,” she said.

While in the TLP, she was paired with mentors Ann H. Tilton, MD, FAAN, and Mark Scher, MD, who helped her crystalize her vision, mission, and goals and focus on her work on expanding national initiatives in fetal-neonatal neurology focusing on early origins of neurologic disorders and care in “the first thousand days” interval from conception until two years of age, during which developmental neuroplasticity establishes lifelong brain connectivity. “Dr. Tilton was a wonderful guide and advisor, very approachable, and extremely invested in my personal and professional development,” said Agarwal. “She showed me the path to break walls and barriers for professional growth—including connecting me with other national leaders and organizations—and has continued to guide through various steps with commitment on a long-term basis.”

physician has been only one of many personal challenges she’s had to overcome in her lifetime and “raising a son with cerebral palsy added further resilience and the attitude of persistent determination,” she said—an experience that also helped steer her toward child neurology and fetal-neonatal neurology. “I’m particularly grateful for my mentors Tim Lotze, MD, and Gary Clark, MD, from Texas Children’s HospitalBaylor College of Medicine who brought me in to the world of child neurology,” she said.

In fact, having experienced so many life-changing mentors was one of the primary things that inspired Agarwal to apply for the AAN’s TLP, which is highly regarded as being unmatched in its caliber of training that incorporates executive-level coaching, mentoring, and a fully customized intensive leadership

Indeed, in the last year Agarwal’s national visibility and success have been amplified. Since graduating, she has taken on several national leadership roles, serving as an associate editor to the Fetal-Neonatal Neurology Section and director of the Residents and Fellows Board of Journal of Child Neurology/Child Neurology Open. She is on work groups with the AAN and the Child Neurology Society (CNS). Agarwal collaborated to develop the fetal-neonatal neurology webinars and online publications for the Child Neurology Foundation. She created a series of podcasts in fetal-neonatal neurology for SAGE Neuroscience & Neurology and Journal of Child Neurology/Child Neurology Open. As a culminating project in the TLP, she launched an innovative Fetal Neurology Consortium and Registry Workgroup with collaborations with leaders of well-established fetal-neonatal neurology programs. The consortium develops applicable educational curricula to apply to multicenter research projects, educational partnerships, and family resources. Agarwal’s national leadership at the multicenter consortium led to partnering with Child Neurology Society to launch the first unique Fetal Neurology Special Interest Group in June 2022 to foster an interdisciplinary collaborative network of specialists and expand the work of the consortium on an international platform.

Agarwal was also selected to serve on the Board of Directors for the Child Neurology Foundation, a non-profit organization committed to advocating for children and families who are

Agarwal

Agarwal with mentor Ann H. Tilton, MD, FAAN.

challenged by a neurologic condition. She serves on the Steering Committee of the Global Pregnancy Collaborative (CoLab), an international professional organization that explores improved global maternal care. In recognition of her excellence in education, she was awarded the AAN’s A.B. Baker Teacher Recognition Award, and PENN/CHOP Resident’s Award for Excellence in Teaching in 2020.

Agarwal’s ongoing efforts are focused on enhancing her institution’s national and global commitments to improved maternal, pediatric, and family health through service, education, and research collaborations. “I was honored to participate on the Pennsylvania team of neurologists at the AAN’s 2022 Neurology of the Hill. One long-term goal would be to create collaborative national and global initiatives to advocate for life-course brain health worldwide starting from the first thousand days,” she said.

Having experienced such life-changing mentorship, Agarwal is also paying it forward by working to inspire the next generation of child neurologists, including those in the AAN’s Leadership Development Programs to which she credits so much of her success. “At the completion of TLP, I was selected as the project advisor for the 2022 Transforming Leaders Program to guide a new diverse group of future leaders,” she said.

As she quotes in her career path essay: “As I wrote of my own story of challenges, hope, and persistence, it gave me a personal perspective of the American dream, reinforcing my belief in the Indian philosophy of karma, and the importance

guiding stars that illuminate our paths. In my journey as a clinician and educator I am committed to connect the dots through my experience, and mentor and inspire the next generation of child neurologists to serve as an advocate for women and children while considering the developmental origins of brain health and disease across the lifespan. I am grateful every day that I now get to be a guiding star for so many children and families and other young medical

October 19 is the deadline to apply for the upcoming

Leaders and Women Leading in Neurology Programs. Learn more at AAN.com/Lead

Thank you to the organizations supporting this program in part:

AstraZeneca Rare Disease

AMERICAN BRAIN FOUNDATION

Support Research with a Donation to the American Brain Foundation When You Renew Your AAN Membership

have funded research across a broad spectrum of brain and nervous system disorders in pursuit of our goal. To date, Foundation funding—through your support—has provided more than $34 million to aid more than 300 researchers.

We believe that by curing one disease, we will cure many. To this end, we are more committed than ever in 2023 to

It’s that time of year to start thinking about renewing your membership to the American Academy of Neurology for 2023. While renewing, consider making a difference for neurology researchers with a gift to the American Brain Foundation. The American Brain Foundation was founded by the AAN more than 30 years ago as the premier foundation that promotes and invests in brain disease research. It’s with the ongoing support of AAN members like you that we can continue our relentless pursuit of discovery research that will lead to improvements in prevention, treatments, and—ultimately—cures for brain diseases. For three decades we

raising awareness of brain disease and the need for research. Your gift to the Foundation will help fund the Academy’s research program, including Clinical Research Training Scholarships.

Visit AmericanBrainFoundation.org to learn more about the Foundation’s work—and be sure and select the option to give a gift while renewing your AAN membership this fall! 

OCTOBER

October 10

Applications Open: 2023 Neurology on the Hill AAN.com/NOH

October 11

Submission Deadline: 2023 Annual Meeting Abstracts AAN.com/AMAbstracts

October 13

Registration Opens: RITE® (Residency In-service Training Exam)

AAN.com/RITE

October 19

Application Deadline: Transforming Leaders and Women Leading in Neurology Programs AAN.com/Lead

October 24–28

Neurology Career Week Careers.aan.com

October 26–27

Virtual Career Fair Careers.aan.com

October 27

AAN Fall Pre-conferences: APP and Sports Concussion AAN.com/Fall

October 28–30

AAN Fall Conference AAN.com/Fall

Academic General and Subspecialty Neurology Opportunities in Northeast Florida—UF Jacksonville Physicians, Inc— Jacksonville, Florida

The Department of Neurology at the University of Florida College of Medicine-Jacksonville, seeks full time faculty members at the non-tenure accruing level of Assistant/Associate/Full Professor. The successful candidates will be BC/BE adult neurologists with or without specialty training (stroke, epilepsy, neuromuscular, movement disorder, neuroimmunology, neurocritical care) who will join the Jacksonville and Flagler campuses. There are opportunities to modify patient-mix to subspecialty interests. The successful candidate is expected to participate in shared departmental clinical and teaching responsibilities. There are also opportunities to engage in scholarly research and advance in academic rank. This position will report to the Chairman of the Department of Neurology at the University of Florida College of MedicineJacksonville. Enjoy the benefits of a healthy work-life balance, a competitive salary, a collegial environment, all while living in one of the most sought-after areas of the country. The University of Florida College of Medicine-Jacksonville is the largest of the three UF colleges—medicine, nursing and pharmacy—located on the approximately

110-acre UF Health Jacksonville campus. The college's 16 clinical science departments house more than 400 faculty members and 300 residents and fellows. The college offers 32 accredited graduate medical education programs. In addition to graduate medical education, clinical rotations in all the major disciplines are provided for students from the UF College of Medicine in Gainesville. For practicing physicians, the college offers a continuing medical education program that recruits national and international speakers who are well known and respected in their fields. The campus' faculty, residents and fellows are active in clinical research. Residents and fellows regularly present their findings at locations across the country and publish their projects in well-known publications. Residents in Northeast Florida and Southeast Georgia are offered all the benefits of an academic health center by combining our strengths with that of the UF Health Jacksonville. Together, the University of Florida Health Science Center–Jacksonville and UF Health Jacksonville form the region’s premier academic health center–UF Health, a leader in the education of health professionals, a hub for clinical research and a unique provider of high-quality patient care. With more than 5,000 faculty and staff, the academic health center in Jacksonville is the largest UF campus outside of Gainesville, offering nearly 100 specialty services, including: Cancer services; Cardiovascular; Neuroscience; Orthopaedic; Pediatrics; Poison Center; Trauma and Critical Care; and Women and Families services. At 37 clinical sites throughout Northeast Florida, UF physicians tally more than 600,000 outpatient visits and more than 34,000 inpatient admissions annually. Located in North Jacksonville is UF Health North, the only full-service hospital in North Jacksonville. The state-of-the-art hospital at UF Health North offers conveniently located, high-quality health care to patients across Northeast Florida and Southeast Georgia. It offers a wide range of inpatient and outpatient services unavailable anywhere else in North Jacksonville, provided by UF Health and community physicians. The hospital features all-private rooms, which studies show promote healing and improve the patient experience. Patient engagement technology in patient suites allows for easy meal ordering, TV control and access to nurses. The hospital is adjacent to the existing medical office building, where UF Health providers offer more than 20 specialties, including pediatrics and women’s health services. The campus is located on Max Leggett Parkway close to Jacksonville International Airport, approximately 15 minutes from Nassau

NOVEMBER

November 2

Application Deadline: AAN Awards

AAN.com/Awards

November 21

Application Deadline: 2023 Neurology on the Hill

AAN.com/NOH

DECEMBER

December 9

Registration Deadline: RITE® (Residency In-service Training Exam) AAN.com/RITE

„ Careers.AAN.com

County and less than 30 minutes from Georgia. For more information, visit http://north.ufhealthjax.org/. Located on Florida's First Coast, Jacksonville is one of the largest in land area, and among the fastest growing cities in the United States. The city provides an eclectic combination of southern hospitality, business and recreational paradise. More than 1 million people live in the five-county area known as Florida's First Coast. The area offers something for everyone, with a temperate climate incorporating seasonal changes, miles of beautiful waterways and beaches, and a myriad of public facilities for work and play. For more information contact Camberlee Evers; camberlee. evers@jax.ufl.edu.

Vascular Neurologist—Ascension Saint Agnes— Saint Agnes Hospital—Baltimore, MD

Seeking Fellowship trained Vascular neurologist to direct our dual certified Primary Stroke Program by The Joint Commission (TJC) and Maryland Institute for Emergency Medical Services System (MIEMSS). Working with four other multi sub-specialty trained neurologists for inpatient consultations and outpatient clinical activities. Program includes our well-established cerebrovascular service with gold and elite plus status. The program infrastructure includes our dedicated Nurse Practitioner and Stroke coordinators. Current director is planning retirement. Please contact Susan Counselman; scounsel@ ascension.org for more information.

AANnews® Classified Advertising

The AAN offers a complete package of print, online, and in-person recruitment advertising opportunities. Visit careers.AAN.com for all AAN options, rates, and deadlines.

Ad copy for the December 2022 print edition of AANnews must be submitted by November 1, 2022.

The same deadline applies to changes/cancellations.

The American Academy of Neurology reserves the right to decline, withdraw, or edit advertisements at its discretion. Every care is taken to avoid mistakes, but the responsibility for clerical or printer errors does not exceed the cost of the ad.

„ Visit the AAN’s Neurology Career Center to view hundreds of additional jobs and sign up for customized, confidential notifications when positions of interest are added.