Anti-CD20 Therapy for MS Increases Risk of Severe COVID-19


Age, sex, EDSS score, and recent methylprednisolone use were all identified as risk factors for developing severe COVID-19.

Maria P. Sormani, PhD, professor, biostatistics, University of Genoa, Italy

Maria P. Sormani, PhD

Data from a recent study suggest that, while most disease-modifying therapies (DMTs) for multiple sclerosis (MS) show an acceptable level of safety, therapy with anti‐CD20 agents such as ocrelizumab or rituximab may lead to increased risk of severe COVID‐19.

Researchers found that treatment with ocrelizumab or rituximab led to an odds ratio (OR) of 2.37 (95% CI, 1.18-4.74; P = .015) of developing severe COVID-19. Methylprednisolone treatment within the last month was also associated with a worse outcome (OR, 5.24 [95% CI, 2.20-12.53]; P = .0001).

The COVID-19 pandemic complicates “management of patients who need therapies that impact on the immune system. Data available so far are overall reassuring... however, the robustness of results is not optimal due to the relatively small samples,” wrote first author Maria P. Sormani, PhD, professor, biostatistics, University of Genoa, Italy, and colleagues.

“It is therefore necessary to rely on larger and better characterized case series to improve data quality and relevance. The results will inform clinical decisions that will have a long‐term impact, given the chronicity of the diseases, the duration of therapies, and the long‐lasting effects of some treatments,” they continued.

READ MORE: Older Patients With MS Face Additional Risks With Ocrelizumab Treatment

Sormani and colleagues retrospectively collected data from 844 people with MS from 85 Italian MS centers, 565 with suspected and 279 with confirmed COVID-19. The mean age of participants was 45 years (range, 18-82) and 593 (70.3%) were women. The median expanded disability status scale (EDSS) score was 2 (interquartile range [IQR], 1.50-4). Patients with progressive MS made up 16% of the study and 693 (82%) were treated with a DMT at the time of COVID-19 presumed symptom onset.

Of these patients, 38 (4.5%) were admitted to an intensive care unit (ICU), 99 (11.7%) had radiologically documented pneumonia, and 96 (11.4%) were hospitalized. Fatalities occurred in 13 (1.54%) patients, 11 of which were in a progressive MS phase and 8 of which were not receiving any therapy.

Sormani and colleagues found that patients receiving no therapy were older (mean age, 53.4 years), had a higher EDSS (mean EDSS, 5.5) and had a higher proportion of patients with progressive MS (45.7%) than patients treated with DMTs such as dimethyl fumarate, fingolimod, ocrelizumab, natalizumab, interferon, copaxone, teriflunomide, alemtuzumab, cladribine, azathioprine, rituximab, methotrexate, and mitoxantrone. Patients treated with anti-CD20 therapies also had a higher EDSS of 3.

Researchers found that in multivariate analysis, the risk factors with a significant impact on COVID-19 severity were age (OR, 1.06 [95% CI, 1.03-1.08]; P <.001), sex (OR for female, 0.69 [95%. CI, 0.45-1.04]; P = .076), EDSS (OR, 1.07 [95% CI, 0.93-1.22]; P = .4), recent use of methylprednisolone (OR, 5.24 [95% CI, 2.20-12.53; P = .001) and anti‐CD20 therapy (OR, 2.37 [95% CI, 1.18-4.74]; P = .015).

Sensitivity analyses confirmed these findings. In the subgroup of confirmed cases, anti‐CD20–treated patients had an OR of 2.62 (P = 0.05); in the subgroup of patients with relapsing-remitting MS (RRMS), an OR of 2.87 (P = .03); and using only complete baseline data with no imputation, an OR of 2.69 (P = .026).

Sormani and colleagues also found that 6.1% of patients with RRMS treated with anti-CD20 therapies died or were admitted to ICU compared with 4.2% of untreated patients with RRMS. Similarly, 12.5% of patients with progressive MS died or were admitted to ICU compared to 10.5% of untreated patients or 4.3% of patients treated with other DMTs.

All told, the adjusted OR for anti-CD20 therapy compared to all other therapies was 2.37 (95% CI, 1.36-4.12; P = .002). No associations were seen between COVID-19 severity and time since last anti-CD20 infusion, although associations were seen with treatment duration. Patients on anti-CD20 therapy for less than 6 months had an OR of 1.65 (95% CI, 0.56-4.90; P = .36), patients treated between 6 months and a year had an OR of 2.24 (95% CI, 0.91-5.55; P = .08), and patients treated for over a year had an OR of 2.98 (95% CI, 1.37-6.46; P = .006).

“It will be important to look at other ongoing studies to verify whether they confirm our findings and to compare the new clinical insight in other autoimmune diseases. This may stimulate new laboratory research and shed new light on the biology of SARS‐CoV‐2 infection and on the pathophysiology of the different autoimmune diseases,” Sormani and colleagues concluded.

Sormani MP, Rossi ND, Schiavetti I, et al. Disease‐modifying therapies and coronavirus disease 2019 severity in multiple sclerosis. Ann Neurol. 2021; 89(4). doi: 10.1002/ana.26028 
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