Efficacy, safety and patient reported outcomes in patients with active relapsing multiple sclerosis treated with ocrelizumab: Final results from the PRO-MSACTIVE study.

BACKGROUND: Ocrelizumab, a humanized anti-CD20 monoclonal antibody, has been approved in Europe for the treatment of adult patients with active relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS), on the basis of previous phase III studies. However, limited data were available on ocrelizumab efficacy in RMS according to the Lublin definition of activity (clinical and/or imaging features) used in the current drug label. The PRO-MSACTIVE study was thus designed to provide additional data on ocrelizumab efficacy according to this definition, and also on safety and patient reported outcomes (PROs). METHODS: PRO-MSACTIVE is a national, multicenter, open-label, single-arm phase IV French study, conducted in patients with active RMS (relapsing-remitting multiple sclerosis, RRMS, or secondary progressive multiple sclerosis, SPMS). The primary endpoint, which was assessed at week (W) 48, was defined as the proportion of patients free of disease activity (defined by no relapses and no T1 gadolinium-enhancing nor new and/or enlarging T2 lesions using brain MRI). Disease activity, disability and PROs using 6 questionnaires for disease severity, quality of life, impact on work productivity, and treatment satisfaction were described at W24 and W48. Adverse events were described until W72. RESULTS: Among the 422 analyzed patients (RRMS: 376, SPMS: 46), 63.3% (95% CI [58.5%; 67.9%]) were free of disease activity at W48 (RRMS: 62.2% [57.1%; 67.2%], SPMS: 71.7% [56.5%; 84.0%]). A total of 358 patients (84.8%; RRMS: 84.6%, SPMS: 87.0%) were relapse-free up to W48, and the overall adjusted annualized relapse rate was 0.14 (RRMS: 0.15, SPMS: 0.09). Overall, 67.8% of patients (RRMS: 66.8%, SPMS: 76.1%) had no evidence of MRI activity (no T1 gadolinium-enhancing lesions [83.4%] and no new/enlarging T2 lesions [75.1%]); 58.5% of patients (RRMS: 57.7%, SPMS: 65.2%) achieved No Evidence of Disease Activity (NEDA: no relapses, no confirmed disability progression, and no MRI activity) at W48. All PRO scores were stable between the first dose of ocrelizumab and W48 and better outcomes were seen for patients having an EDSS score ≥4. Overall, 89.3% of patients reported adverse events, 62.3% adverse events assessed as related to ocrelizumab, and 8.5% serious adverse events. No serious infusion-related reactions, opportunistic infections, progressive multifocal leukoencephalopathy, nor deaths were reported. No new safety signal was identified. CONCLUSION: These data confirm the efficacy of ocrelizumab in a pragmatic setting and its favorable benefit-risk profile in patients with RMS. (ClinicalTrials.gov identifier: NCT03589105; EudraCT identifier: 2018-000780-91).

COVID-19 Lockdown in Patients with Chronic Diseases: A Cross-Sectional Study.

BACKGROUND: We aimed to investigate the impact of the first COVID-19 lockdown on medication adherence, physician access, lifestyle behaviours, and mental health in patients with chronic conditions. METHODS: A cross-sectional phone survey was conducted in 1274 housebound adults recruited from 8 regional chronic disease cohorts (CLEO CD study: NCT04390126). RESULTS: Medication adherence was 97%; 305 (41%) patients declared that at least one scheduled visit with a physician was missed during the first lockdown. The main changes in lifestyle behaviours were deterioration in sleep time (duration and/or quality; 71%), increase in screen time (46%), and decrease in physical activity (46%). Nineteen percent experienced psychological distress (Kessler-6 score ≥ 5). An urban living place (OR, 1.76 vs. rural; 95% CI, 1.32-2.33; p = 10-4), worse self-reported mental health (OR, 1.62 vs. about the same or better; 95% CI, 1.17-2.25; p = 0.003), and a K6 score ≥ 5 (OR, 1.52 vs. <5; 95% CI, 1.05-2.21; p = 0.03) were independent factors associated with at least one unhealthy behaviour. CONCLUSIONS: Encouraging results were observed in terms of medication adherence. Caution is needed in chronic disease patients living in urban places as well as those presenting psychological distress and worse self-reported mental health to reduce unhealthy behaviours.

COVID-19 Lockdown in Patients with Chronic Diseases: A Cross-Sectional Study

Background: We aimed to investigate the impact of the first COVID-19 lockdown on medication adherence, physician access, lifestyle behaviours, and mental health in patients with chronic conditions. Methods: A cross-sectional phone survey was conducted in 1274 housebound adults recruited from 8 regional chronic disease cohorts (CLEO CD study: NCT04390126). Results: Medication adherence was 97%;305 (41%) patients declared that at least one scheduled visit with a physician was missed during the first lockdown. The main changes in lifestyle behaviours were deterioration in sleep time (duration and/or quality;71%), increase in screen time (46%), and decrease in physical activity (46%). Nineteen percent experienced psychological distress (Kessler-6 score ≥5). An urban living place (OR, 1.76 vs. rural;95% CI, 1.32–2.33;p = 10−4), worse self-reported mental health (OR, 1.62 vs. about the same or better;95% CI, 1.17–2.25;p = 0.003), and a K6 score ≥5 (OR, 1.52 vs. <5;95% CI, 1.05–2.21;p = 0.03) were independent factors associated with at least one unhealthy behaviour. Conclusions: Encouraging results were observed in terms of medication adherence. Caution is needed in chronic disease patients living in urban places as well as those presenting psychological distress and worse self-reported mental health to reduce unhealthy behaviours.

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France.

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39-3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18-0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon.