Background

The COVID-19 pandemic has raised concerns for increased risk of infection in patients with multiple sclerosis (MS) and disrupted their routine MS care.

Objectives

The aim of this study is to characterize the extent of MS patients’ perceptions of risk and adherence to care during the pandemic.

Methods

A survey was emailed to patients from a large MS center in New York City during the local peak of the pandemic to assess perceptions of infection risk and adherence to MS care including appointments, laboratory studies, MRIs, and taking disease-modifying therapies (DMT).

Results

529 patients from the MS center responded to the survey during two-weeks in April 2020. Patients collectively showed concern about becoming infected with COVID-19 (88%) and perceived a higher infection risk because of having MS (70%) and taking DMTs (68%). Patients frequently postponed appointments (41%), laboratory studies (46%), and MRIs (41%). Noncompliance with DMTs was less common (13%). Decisions to alter usual recommendations for care were made by the patient more often than by the provider regarding adherence to appointments (68%), laboratory studies (70%), MRI (67%), and DMTs (65%). Degree of concern for infection was associated with adherence to appointments (p=0.020) and laboratory studies (p=0.016) but not with adherence to MRI and DMTs. Thirty-five patients reported being tested for COVID-19, of whom fourteen reported a positive test.

Conclusions

Patients with MS were highly concerned about becoming infected during the local peak of the COVID-19 pandemic. Behaviors that deviated from originally recommended MS care were common and often self-initiated, but patients were overall compliant with continuing DMTs.

Background

Teriflunomide is a once-daily oral immunomodulator approved for treating relapsing multiple sclerosis (RMS) and relapsing-remitting MS, depending on the local label. Efficacy and safety of teriflunomide were established in the phase 2 (NCT01487096) and phase 3 trials of patients with RMS (TEMSO [NCT00134563], TOWER [NCT00751881], TENERE [NCT00883337]) and clinically isolated syndrome (TOPIC [NCT00622700]). In post hoc analysis of TEMSO patients stratified by age, structural image evaluation using normalization of atrophy (SIENA) revealed teriflunomide 14 mg significantly reduced the percentage of brain volume change in patients aged >25 to ≤35 years (48%; P=0.0217) and >45 to ≤55 years (35%; P=0.0092) versus placebo over 2 years.

Objectives

To analyze the effect of teriflunomide treatment on MRI lesion activity in TEMSO study patients with RMS stratified by age.

Methods

In TEMSO, patients were randomized 1:1:1 to receive either placebo or teriflunomide 7 mg or 14 mg for ≤108 weeks (Year 2). Through Year 2, MRI lesion activity (unique combined active lesions [UCAL], contrast-enhancing T1 weighted lesions [CEL], and T2 weighted [T2w] lesions) and safety were assessed in the SIENA analysis subgroup; patients were stratified by age at baseline: ≥18 to ≤25 years (n=97 [10%]); >25 to ≤35 years (n=283 [29%]); >35 to ≤45 years (n=388 [40%]); and >45 to ≤55 years (n=201 [21%]). P values between treatment groups were determined for MRI lesions using a Poisson model.

Results

Of 1086 patients in the TEMSO core study, 969 (89%) had scans appropriate for SIENA analysis. Compared with placebo, teriflunomide 14 mg significantly reduced the number of UCAL (0.31–1.44 vs 0.92–6.11 lesions; P≤0.0013) and CEL (0.10–0.46 vs 0.54–3.42 lesions; P≤0.0001) per scan across all age groups. In all age groups except the >45 to ≤55 years group, teriflunomide 14 mg significantly reduced the number of T2w lesions (0.50–0.93 vs 1.07–2.80 lesions; P≤0.001) per scan versus placebo. Similar effects on MRI lesion activity were seen with teriflunomide 7 mg versus placebo. Incidence of adverse events (AEs) generally increased with age, with no deaths reported through Year 2.

Conclusions

Over 2 years in TEMSO RMS patients, teriflunomide reduced the number of new MRI lesions versus placebo across age groups. Significant treatment effects were seen with teriflunomide 14 mg across all age groups for UCAL and CEL. Age-related increases in AEs were observed through Year 2.

STUDY SUPPORT: Sanofi.

Background

ADS-5102, FDA-approved as Gocovri, to treat dyskinesia in Parkinson’s disease, has a unique PK profile, such that once daily bedtime dosing provides higher amantadine concentrations from morning throughout the day and lower at night. Based on results from a 60-subject, 4-week, Phase-2 study, INROADS was designed to confirm benefit of ADS-5102 on walking in MS patients.

Objectives

To evaluate the efficacy and safety of ADS-5102 (amantadine) extended release capsules in patients with multiple sclerosis with walking impairment.

Methods

INROADS comprised a 4-week placebo run-in, followed by a 12-week double-blind period. Five hundred ninety-four MS patients with walking impairment from the US or Canada enrolled, and 560 were randomized, 1:1:1, to 274 mg ADS-5102 (n=185), 137 mg ADS-5102 (n=187), or placebo (n=186). The primary endpoint was the proportion of responders (≥20% improvement from baseline measured in ft/sec) in timed 25-foot walk [T25FW] at Week 16, comparing 274 mg ADS-5012 versus placebo. Subjects who did not have a Week 16 assessment were counted as non-responders. Additional outcomes included timed up and go test, 2-minute walk test, and MS walking scale-12. Prespecified subgroups, including prior dalfampridine use, were analyzed.

Results

Baseline characteristics were similar across treatment arms, with mean time since diagnosis 15.9 years, median EDSS 6.0, and mean T25FW 12.4 seconds; 52.5% reported prior dalfampridine use. At Week 16, 274 mg ADS-5102 demonstrated a statistically significantly greater response rate, 21.1% (P=.01) than placebo (11.3%); the response rate for 137 mg ADS-5102 was 17.6% (P=.08). For subjects who completed the study, the response rates were 28.3% (P< .001) for 274 mg, and 19.6% (P=.049) for 137 mg, vs. 11.9% for placebo. Response rates were consistent for subjects with (20.0%, 15.9%, vs. 11.0%) and without (22.5%, 19.2%, vs. 11.6%) prior dalfampridine use. The most commonly reported (>5%) adverse events (AEs) were peripheral edema, dry mouth, fall, constipation, UTI, and insomnia; AEs led to study drug discontinuation for 20.5% (274 mg), 6.4% (137 mg) and 3.8% (placebo) of subjects.

Conclusions

INROADS met its primary objective of showing clinically meaningful benefit in MS walking speed for 274 mg ADS-5102. A dose-response was seen for both efficacy and tolerability. AEs were consistent with the known safety profile of amantadine. Results suggest a role for ADS-5102 to improve walking in patients with MS, particularly those who have tried and discontinued dalfampridine.

Background

New relapses and magnetic resonance imaging (MRI) abnormalities diminish as people age with multiple sclerosis (MS). Data supporting use of disease modifying therapies (DMTs), from studies with typical inclusion ages of 18-55, suggest diminished benefit in older compared with younger individuals. Whether it is beneficial to continue, or safe to discontinue, DMTs as people age beyond 55 remains unknown. Retrospective studies show those at greatest risk of new inflammatory disease activity upon DMT discontinuation are younger and had recent new relapse and/or MRI scan activity.

Objectives

Present the design and baseline data in our study evaluating whether older individuals with MS who discontinue their DMT have no worse risk of new disease activity compared to those who remain on DMT.

Methods

This is a randomized (1:1), controlled, rater-blinded study in which 260 MS participants aged 55 and older and continuously taking DMTs (at least 5 years, minimum 2 years on current DMT) were enrolled at 19 sites in the United States. They have no evidence of MS relapse for 5+ years or new MRI lesion for 3+ years, and will be followed for up to 2 years, with study visits every 6 months. Primary outcome is either a new MS relapse or T2 brain MRI lesion. Secondary outcomes are 6-month confirmed increase in Extended Disability Status Scores (EDSS), and worsening of Symbol Digit Modality Test or patient-reported outcomes.

Results

Mean age of participants is 63 ± 5 years, and 83.7% are female. Racial/ethnic breakdown is 89.2% White, 9.2% Black or African American, 0.8% Hispanic/Latino, and 0.8% Other. Participants average 22.3 ± 10.5 years since symptom onset, and 13.5 ± 7 years since last relapse. Most have Relapsing-Remitting MS (83.7%), with 13.1% Secondary Progressive and 3.2% Primary Progressive MS. At enrollment, 42.6% were on an interferon, 30.3% on glatiramer acetate, 15.1% dimethyl fumarate, 6.4% fingolimod, 3.2% teriflunomide, 1.6% natalizumab, and 0.8% ocrelizumab. EDSS scores average 3.3 ± 1.8, and 77.8% of participants rate their treatment satisfaction as Satisfied or Very Satisfied at enrollment.

Conclusions

The DISCOMS study is the first controlled trial to address whether it is safe to discontinue DMTs in MS. Enrolled participants represent a unique cohort of stable, older MS patients with relatively low disability. Upon completion, the study will increase our understanding of the utility of MS DMTs throughout the lifespan of MS.

Background

Ocrelizumab (OCR) was approved in 2017 in the United States (US) for the treatment of relapsing and primary progressive forms of multiple sclerosis (MS). Real-world data describing the characteristics of patients initiating OCR are limited. The Corrona MS Registry is a US prospective observational registry that, as of August 2019, encompasses 11 private and academic sites and 781 patients aged ≥18 years, including 631 patients receiving a disease-modifying treatment (DMT) at the time of enrollment.

Objectives

To describe the characteristics of patients enrolled in the Corrona MS Registry who initiated OCR vs other MS DMTs.

Methods

This analysis included patients who initiated a DMT ≤24 months before or at registry enrollment (which began in August 2017) to ensure comparable treatment availability across groups, considering the 2017 approval of OCR. Enrollment visit characteristics were calculated separately for patients initiating OCR, oral/injectable DMTs or other intravenous (IV) DMTs. Patient Global Impression of Change (PGIC) score was reported for patients who started DMT before enrollment.

Results

The analysis population included 326 patients (52% of treated registry patients); 71% initiated OCR (n=233), 16% initiated oral (n=43) or injectable (n=9) DMTs and 13% initiated another IV DMT (n=41). Most patients (n=299) initiated a DMT before enrollment. Compared with patients initiating OCR, those initiating oral/injectable or other IV DMTs were more likely to have a relapsing-remitting disease course (80% vs 89% and 88%, respectively), were younger (mean [SD] age, 51 [11] vs 48 [11] and 44 [12] years, respectively) and had a shorter mean disease duration (13 vs 10 and 8 years, respectively). Fewer patients in the OCR group initiated treatment as a first- or second-line therapy (36%) than in the oral/injectable (67%) or other IV groups (59%). Mild disability (scores ≤1) on the Patient Determined Disease Steps was reported by 49% of patients in the OCR group and 65% and 54% in the oral/injectable and other IV DMT groups, respectively. Improvement on the PGIC was reported by 50%, 27% and 63% in the OCR, oral/injectable and other IV groups, respectively.

Conclusions

In these unadjusted analyses of Corrona registry data, patients initiating ocrelizumab in the 2 years after launch were older and had higher disability levels at the time of enrollment than those initiating other DMTs. Real-world outcomes will continue to be examined as the registry matures.