ABSTRACT
Introduction: The approval of ocrelizumab (OCR) for the treatment of primary progressive MS (PPMS) showed that the course of progressive MS (PMS) can be altered with effective treatment;however, direct evidence across the spectrum of PMS, including secondary progressive MS (SPMS), is still lacking. Objective(s): CONSONANCE (NCT03523858) is a single-arm, phase 3b, 4-year study designed to evaluate for the first time the effectiveness and safety of OCR in patients with SPMS or PPMS. Year 2 results are reported. Method(s): Patients with active or non-active PMS but showing disability progression in the past 2 years were enrolled. Primary outcomes are (1) proportion of patients with no evidence of progression (NEP) defined as no progression confirmed for >=24 weeks on Expanded Disability Status Scale (EDSS), no >=20% increase in timed 25-foot walk test (T25FWT), no >=20% increase in nine-hole peg test (9HPT) time, and no MS-related death or treatment discontinuation due to efficacy failure;(2) proportion of patients with no evidence of progression and no active disease (NEPAD) defined as NEP plus no protocol-defined relapse, no new/enlarging T2 lesions (N/E-T2, re-baselined at week 24), and no T1 gadolinium-enhanced lesions. Result(s): Patients (n=629;SPMS n=324, PPMS n=305) had mean (SD) age of 48.5 (9.2) years and 52.3% were female. At baseline (BL), median (IQR)/mean (SD) EDSS scores were 6.0 (4.5- 6.0)/5.3 (1.3) for patients with SPMS and 5.0 (4.0-6.0)/4.8 (1.3) for PPMS. Overall median times for 9HPT and T25FWT were 27.9 and 9.4 seconds, respectively. Over 2 years, 311/586 (53.1%) patients had NEP (SPMS 55.8%;PPMS 50.2%;progression was mostly driven by increases in T25FWT) and 283/588 (48.1%) had NEPAD (SPMS 49.5%;PPMS 46.7%;acute activity predominantly driven by N/E-T2 lesions). Overall EDSS remained stable from BL to year 2 (mean [SD] change of +0.07 (0.79) points). In patients with EDSS >=2.0 at BL (n=526), 24-week confirmed disability improvement in any of the components (EDSS, T25FWT, 9HPT) was observed in 29.8% of cases. Rates of serious AEs and serious infections were 7.6/100PY and 3.2/100PY, respectively. Eight deaths were reported (COVID=6, pulmonary embolism=1, non-small cell lung cancer=1). Conclusion(s): Over a 2-year period, treatment with OCR was associated with comparable rates of NEP and NEPAD in patients with SPMS and PPMS, and with functional improvement in about one-third of patients. Safety outcomes were consistent with known safety profile.
ABSTRACT
Introduction: SARS-CoV-2 seroconversion rate after COVID-19 may be influenced by disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMO-SD). Objectives: To investigate the seroprevalence and the quantity of SARS-CoV-2 antibodies in a cohort of patients with MS or NMO-SD. Aims: To improve our knowledge of the impact of different DMTs on the immune response to SARS-COV2. Methods: Blood samples were collected in patients diagnosed with COVID-19 between February 19, 2020 and February 26, 2021. SARS-CoV-2 antibody positivity rates and Ig levels (anti-S IgG titer, anti-S IgA index, anti-N IgG index) were compared between DMTs groups. Multivariate logistic and linear regression models were used to estimate the influence of DMTs and other confounding variables on SARS-CoV-2 serological outcomes. Results: 119 patients (115 MS, 4 NMO, mean age: 43.0 years) were analyzed. Overall seroconversion rate was 80.6% within 5.0 (SD 3.4) months after infection. 20/21 (95.2%) patients without DMT and 66/77 (85.7%) patients on DMTs other than anti-CD20 had at least one SARS-CoV-2 Ig positivity, while this rate decreased to only 10/21 (47.6%) for patients on anti-CD20 (p < 0.001). Patients on anti-CD20 had a lower anti-S IgG titer (mean [SD], 1.4 [1.6]) relative to patients on other DMTs (2.4 [1.1]) or no DMT (2.7 [0.8] (p<0.001 by ANOVA). Being on anti-CD20 was associated with a decreased odd of positive serology (OR, 0.06 [95%CI, 0.01-0.59], p=0.01) independently from time to COVID-19, total IgG level, age, sex and COVID-19 severity. Time between last anti-CD20 infusion and COVID-19 was longer (mean [SD], 3.7 [2.0] months) in seropositive patients compared to seronegative patients (mean [SD], 1.9 [1.5] months, p=0.04). Serological data at 6 months follow-up after inclusion will be available and presented during the congress. Conclusions: SARS-CoV-2 antibody response was decreased in patients with MS or NMO-SD treated with anti-CD20 therapies. Monitoring long-term risk of reinfection and specific vaccination strategies in this population may be warranted.
ABSTRACT
Background: Risk factors associated with the severity of COVID- 19 in patients with multiple sclerosis (MS) begin to be identified from several cohort studies. Disease modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities. Objectives: The objective was to describe the clinical characteristics and outcomes in patients with COVID-19 and to identify the factors associated with COVID-19 severity. Methods: This multicenter, retrospective, observational cohort study (COVISEP registry, NCT04355611) included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020 and July 14, 2020. The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1: not hospitalized, no limitations on activities, to 7: death;cutoff at 3: hospitalized, not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Score (EDSS), comorbidities, COVID-19 characteristics and outcome. Univariate and multivariate logistic regression models were used to estimate the influence of collected variables on COVID-19 outcome. Results: A total of 405 patients (mean age: 44.7 years, female/male: 293/112, mean disease duration: 13.4 years) were analyzed. Seventy-eight patients (19.3%) had a COVID-19 severity score ≥ 3, and 12 patients (3.0%) died from COVID-19. Median EDSS was 2.0 (range: 0-9.5), 326 patients (80.5%) were on DMT. There was a higher proportion of patients with COVID-19 severity score ≥ 3 among patients with no DMT relative to patients on DMTs (39.2% versus 14.4%, p<0.001). Multivariate logistic regression models determined that age (OR for 10 years: 1.8, 95% CI: 1.4-2.4), EDSS (OR for EDSS ≥ 6: 4.5, 95% CI: 2.0-10.0) were independent risk factors for COVID-19 severity score ≥ 3 (hospitalization or higher severity) while immunomodulatory treatment (interferon or glatiramer acetate) was associated with lower risk of COVID-19 severity score ≥ 3 (OR: 0.2, 95% CI: 0.05-0.8). EDSS was associated with the highest variability of COVID-19 severe outcome (R2= 0.18), followed by age (R2= 0.06) and immunomodulatory treatment (R2= 0.02). Conclusions: EDSS and age were independent risk factors of severe COVID-19, while exposure to immunomodulatory DMTs (interferon and glatiramer acetate) were independently associated with lower COVID-19 severity. We did not find an association between other DMTs exposure (including immunosuppressive therapies) and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of MS patients during the COVID- 19 pandemic.