ACTRIMS/ECTRIMS 2020 concluded on September 26th with a special session on COVID-19. Presentations and posters attempted to clarify risk factors for COVID-19 in MS patients, and to address the question of whether disease-modifying therapies (DMT) – most specifically anti-CD20 therapies – affect the risk of acquiring SARS-CoV-2 infection or clinical outcomes of COVID-19. Data were provided by large multinational patient registries and individual MS centres.
The largest data set was the MS Global Data Sharing Initiative (n=1540), which includes information from the MS International Federation, the MS Data Alliance, MSBase, COViMS and other sources (Simpson-Yap et al. ACTRIMS/ECTRIMS 2020; SS02.04). Patients were generally younger (63.2% aged < 50 years), with RRMS (75.1%) and with mild-to-moderate disability (77.1% with EDSS 0-6). One-third of patients were receiving anti-CD20 therapies; 11.5% were untreated. To date, there have been 48 deaths (3.12%). Risk factors for COVID-19 hospitalization were older age (PR 1.55 if aged 50-70, 1.70 if aged >70), progressive disease (PR 1.70), and EDSS >6 (PR 1.68). Risk factors for ICU admission were older age (PR 1.92 if aged 50-70) and progressive disease (PR 2.04). Risk factors for death were male sex (PR 0.60 for females vs. males), older age (PR 2.35 if aged 50-70, 3.01 if aged >70) and EDSS >6.0 disease (PR 6.81). Using dimethyl fumarate as the comparator, rituximab was associated with an increased risk of hospitalization (PR 1.58), ICU admission (PR 4.12), and need for ventilation (PR 7.27). Ocrelizumab was associated with an increased risk of ICU admission (PR 3.53), with trends to increased risks of hospitalization (PR 1.19) and ventilation (PR 3.17). There was a trend for worse outcomes in untreated patients. No DMT was associated with increased risk of mortality. A pooled analysis of patients on anti-CD20 therapy (n=343) versus other DMTs (n=492) showed an increased risk for hospitalization (PR 1.49), ICU admission (PR 2.55) and need for ventilation (PR 3.05) with anti-CD20 therapies.
Similar results were reported by the COViMS North American registry of MS patients with COVID-19 (n=734) (Salter et al. ACTRIMS/ECTRIMS 2020; LB1242). Overall mortality was 6.1%. For the combined outcome of mortality, ICU admission and/or hospitalization, there was an increased risk with anti-CD20 therapies (odds ratio 2.53).
In the French COVISEP registry (n=405), the COVID-19 mortality rate among MS patients was 3.0% (Louapre et al. ACTRIMS/ECTRIMS 2020; SS02.06). COVID-19 severity was more common in untreated versus treated MS patients (39.2% vs. 14.4%). No DMT was associated with a greater risk of COVID-19 severity, however, there was a lower risk of severity in patients treated with glatiramer acetate or interferon-β. A Spanish survey of MS patients with COVID-19 (n=93) reported a higher risk of acquiring CoV-2 if treated with an anti-CD20 agent; risk was increased with a longer duration of therapy (Zabalza et al. ACTRIMS/ECTRIMS 2020; LB1168).
A U.S. health claims database analysis identified 170 MS patients with COVID-19 (Kieseier et al. ACTRIMS/ECTRIMS 2020; LB1252). Treatment with anti-CD20 therapies or alemtuzumab appeared to be associated with an increased risk of developing COVID-19 compared to treatment with other DMTs. COVID-19 risk appeared to be lower during treatment with interferon-β compared to a higher-efficacy DMT, which may reflect the severity of patients’ MS. An analysis of U.S. health records identified 47 COVID-19 patients treated with ocrelizumab (Dillon et al. ACTRIMS/ECTRIMS 2020; LB1254). Overall, 25.5% had severe outcomes (hospitalization/ventilation/death).
The New York COVID-19 Consortium of MS clinics (n=349) reported that patient age, obesity, and higher EDSS score were independent predictors of COVID -19 severity; specific DMTs were not associated with a higher risk (Klineova et al. ACTRIMS/ECTRIMS 2020; LB1205). The mortality rate was 3.9%. A separate single-centre study in the U.S. reported on 25 patients with MS and NMOSD with COVID-19; 92% were on treatment with an anti-CD20 agent or DMF (Tremblay et al. ACTRIMS/ECTRIMS 2020; LB1181). One-third required hospitalization; the mortality rate was 12%.
Also noteworthy was a pharmacovigilance update presented by Roche (Hughes et al. ACTRIMS/ECTRIMS 2020; SS02.05). As of 31 July 2020, there were 51 suspected/confirmed COVID-19 cases in the ocrelizumab trial population (1.3%). Cases were more likely to have respiratory, metabolic, vascular and cardiac comorbidities. The rate of severe COVID-19 was 19.6%; the mortality rate was 5.9%. In the post-marketing data set there have been 307 suspected/confirmed COVID-19 cases to date. The overall rate of severe/critical COVID-19 cases was 21.8%; the mortality rate was 5.5%. If the subset with reported outcomes (n=227) is considered, the rates of severe/critical cases and mortality were 29.5% and 7.5%, respectively. When examined by age (n=229), the proportion of patients with severe/critical/fatal disease was 23.9% among ocrelizumab patients aged < 50 years, and 43.7% in patients aged >50 years. Rates of serous outcomes may reflect in part the patient population treated with ocrelizumab, such as those with severe RMS or progressive MS.
Three preliminary case series reported on COVID-19 outcomes in MS patients treated with cladribine. There have been three suspected cases in phase IV participants (Karan et al. ACTRIMS/ECTRIMS 2020; LB1151). Two required hospitalization but have since been discharged. An Italian centre reported two cases of COVID-19 in cladribine-treated patients (Rocca et al. ACTRIMS/ECTRIMS 2020; LB1154). Both had mild, self-limiting disease and did not require hospitalization. A case series in Spain identified 14 patients with COVID-19 during cladribine treatment; mean time on therapy was 7.7 months (Oreja-Guevara et al. ACTRIMS/ECTRIMS 2020; LB1165). Two patients had grade 1 lymphopenia, 5 patients had grade 2 lymphopenia and 1 patient had grade 3 lymphopenia when infected with CoV-2. Of the 14 COVID-19 patients, 2 were asymptomatic, 11 had mild symptoms and 1 had moderate symptoms. One patient required hospitalization.