NOVA primary results randomised controlled study of natalizumab Q6W versus continued Q4W treatment for MS

BackgroundNatalizumab every-6-week (Q6W) dosing is associated with lower progressive multifocal leukoencephalopathy risk than every-4-week dosing (Q4W) in retrospective analyses. NOVA is the first randomised trial to assess Q6W efficacy.ObjectiveEvaluate natalizumab Q6W efficacy in patients previously treated with natalizumab Q4W for≥12 months compared with continuation of Q4W over 72 weeks.MethodsNOVA is a randomised, controlled, open-label, rater-blinded phase 3b trial. Included patients were treated with natalizumab Q4W without relapse for ≥12 months. Patients were randomised 1:1 to Q4W (n=248) or Q6W (n=251). The primary endpoint was new/newly enlarging T2 (N/NET2) lesions. Secondary endpoints included clinical and safety outcomes.ResultsProportions of patients with N/NET2 lesions were low in both arms (Q4W:4.1%;Q6W:4.3%). Differ- ences in mean N/NET2 lesions for Q4W and Q6W (primary estimand: 0.05 vs 0.20 [P=0.0755];secondary estimand: 0.06 vs 0.31 [P=0.0437]) were driven by two Q6W patients with extreme (≥25) values. Secondary outcomes were similar for Q4W and Q6W.ConclusionsOverall, NOVA data suggest most patients stable on natalizumab Q4W can switch to Q6W without clinically meaningful loss of efficacy. Support: Biogen. Disclosures on poster.

Risk of COVID-19 infection and severe disease in MS patients on different disease-modifying therapies.

BACKGROUND: The risk of SARS-CoV-2 infection and severity with disease modifying therapies (DMTs) in multiple sclerosis (MS) remains unclear, with some studies demonstrating increased risks of infection with B-cell-depleting (anti-CD20) therapies and severity, while others fail to observe an association. Most existing studies are limited by a reliance on 'numerator' data (i.e., COVID-19 cases) only. OBJECTIVE: To assess the risks of COVID-19 by DMT, this study aimed to assess both 'numerator' (patients with SARS-CoV-2 infection) and 'denominator' data (all patients treated with DMTs of interest) to determine if any DMTs impart an increased risk of SARS-CoV-2 infection or disease severity. METHODS: We systematically reviewed charts and queried patients during clinic encounters in the NYU MS Comprehensive Care Center (MSCCC) for evidence of COVID-19 in all patients who were on the most commonly used DMTs in our clinic (sphingosine-1-phosphate receptor (S1P) modulators (fingolimod/siponimod), rituximab, ocrelizumab, fumarates (dimethyl fumarate/diroximel fumarate), and natalizumab). COVID-19 status was determined by clinical symptoms (CDC case definition) and laboratory testing where available (SARS-CoV-2 PCR, SARS-CoV-2 IgG). Multivariable analyses were conducted to determine predictors of infection and severe disease (hospitalization or death) using SARS-CoV-2 infected individuals per DMT group and all individuals on a given DMT as denominator. RESULTS: We identified 1,439 MS patients on DMTs of interest, of which 230 had lab-confirmed (n = 173; 75.2%) or suspected (n = 57; 24.8%) COVID-19. Infection was most frequent in those on rituximab (35/138; 25.4%), followed by fumarates (39/217; 18.0%), S1P modulators (43/250; 17.2%), natalizumab (36/245; 14.7%), and ocrelizumab (77/589; 13.1%). There were 14 hospitalizations and 2 deaths. No DMT was found to be significantly associated with increased risk of SARS-CoV-2 infection. Rituximab was a predictor of severe SARS-CoV-2 infection among patients with SARS-CoV-2 infection (OR 6.7; 95% CI 1.1-41.7) but did not reach statistical significance when the entire patient population on DMT was used (OR 2.8; 95% CI 0.6-12.2). No other DMT was associated with an increased risk of severe COVID-19. CONCLUSIONS: Analysis of COVID-19 risk among all patients on the commonly used DMTs did not demonstrate increased risk of infection with any DMT. Rituximab was associated with increased risk for severe disease.