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Introduction: Limited data are available on the course of Coronavirus disease 2019 (COVID-19) in people with Multiple Sclerosis (MS). More real-world data are needed to help the MS community to manage MS treatment properly. In particular, it is important to understand the impact of immunosuppressive therapies used to treat MS on the outcome of COVID-19. Methods: We retrospectively collected data on all confirmed cases of COVID-19 in MS patients treated with ocrelizumab, followed in two MS Centers based in University Hospitals in Northern Italy from February 2020 to June 2021. Results: We identified 15 MS patients treated with ocrelizumab with confirmed COVID-19 (mean age, 50.47 ± 9.1 years; median EDSS, 3.0; range 1.0-7.0). Of these, 14 were confirmed by nasal swab and 1 was confirmed by a serological test. COVID-19 severity was mild to moderate in the majority of patients (n = 11, 73.3%; mean age, 49.73; median EDSS 3.0). Four patients (26.7%; mean age, 52.5 years; median EDSS, 6) had severe disease and were hospitalized; one of them died (age 50, EDSS 6.0, no other comorbidities). None of them had underlying respiratory comorbidities. Conclusion: This case series highlights the large variability of the course of COVID-19 in ocrelizumab-treated MS patients. The challenges encountered by the healthcare system in the early phase of the COVID-19 pandemic might have contributed to the case fatality ratio observed in this series. Higher MS-related disability was associated with a more severe COVID-19 course.
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IMPORTANCE: The evaluation of therapeutic choices is needed after 24 doses of natalizumab in patients with multiple sclerosis (MS). OBJECTIVE: To evaluate the effect of therapeutic choices on the mean annualized relapse rate and on magnetic resonance imaging MS activity after 24 doses of natalizumab in patients with relapsing-remitting MS. DESIGN, SETTING, AND PARTICIPANTS: The TY-STOP study, which recruited participants between October 22, 2010, and October 22, 2012, at 8 Italian MS centers (secondary care outpatient clinics) among 124 adult patients who demonstrated no clinical or magnetic resonance imaging MS activity after 24 doses of natalizumab. INTERVENTIONS: Natalizumab, no treatment, interferon beta, glatiramer acetate, or fingolimod. MAIN OUTCOMES AND MEASURES: The primary end point was the mean annualized relapse rate. Statistical analyses were performed in 124 patients with complete follow-up data among 130 patients who were recruited and stratified into study groups. In the intent-to-treat group, the decision was made to continue or interrupt natalizumab after 24 doses. In the as-treated group, natalizumab continuers received natalizumab, natalizumab switchers changed to different therapies, and natalizumab quitters discontinued natalizumab during the study year. RESULTS: No significant differences in demographic or baseline clinical characteristics were found among the study participants. In the intent-to-treat group (n = 124), clinical (P = .004) and radiologic (P = .02) MS activity was significantly lower in patients continuing natalizumab (n = 43) than in patients interrupting natalizumab (n = 81), with a protective effect of natalizumab continuation on both outcomes (odds ratio [OR], 0.33; 95% CI, 0.15-0.70 for clinical activity and OR, 0.35; 95% CI, 0.15-0.79 for radiologic activity). In the as-treated group (n = 124), clinical (P = .003) and radiologic (P = .03) MS activity was significantly lower in natalizumab continuers than in natalizumab switchers or quitters, confirming a protective effect of natalizumab on the risk of relapse in natalizumab continuers compared with natalizumab quitters (OR, 4.40; 95% CI, 1.72-11.23) and natalizumab switchers (OR, 3.28; 95% CI, 0.99-10.79). No disease rebound was observed in natalizumab quitters. After natalizumab discontinuation, 1 patient developed progressive multifocal leukoencephalopathy during the observation period, with complete recovery. CONCLUSIONS AND RELEVANCE: This study provides class III evidence of an increased risk of MS activity resumption after natalizumab discontinuation. Therapy discontinuation after 24 doses in natalizumab-responding patients should be considered only if the risk of progressive multifocal leukoencephalopathy is high and outweighs the benefits of continuing the drug. TRIAL REGISTRATION: Osservatorio Nazionale Sulla Sperimentazione Clinica dei Medicinali No. 131/2010.