(08) Identification of factors associated with severe SARS-Cov2 infection for patients treated with MS-specific disease-modifying therapies

Introduction: Multiple Sclerosis (MS)-specific and non-MS-specific risk factors of severe SARS-Cov2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection have been previously identified. However, published studies are more controversial regarding the association between infection severity and MS-specific disease-modifying therapies (1-3). The objective was to identify the association between severe SARS-Cov2 infection occurrence and different Disease-Modifying Therapies among MS treated patients in a dynamic exposed-non-exposed cohort.

Material and methods: We identified, from the French health insurance database, MS patients with SARS-Cov2 infection between February 15, 2020, and March 31, 2021. Patients had at least one reimbursement for a specific MS disease-modifying therapy, i.e., glatiramer acetate, teriflunomide, fingolimod, dimethyl fumarate, pegylated or non-pegylated beta-interferons, ocrelizumab and natalizumab, 6 months before the date of first infection with SARS-Cov2, defined as the index date. The exposure group was defined according to the last two reimbursements before infection. The interest event was severe infection occurrence characterized by hospitalization of at least 24 hours. For each patient, socio-demographic, MS characteristics and general health condition (consultations and hospitalizations preceding the index date, comorbidities) were described, and their associations with severe SARS-Cov2 infection occurrence and drug exposure were assessed using logistic regression. Confounding factors were those associated with exposure drugs and SARS-Cov2 infection severity. Confounding by exposure drug indication was studied with interest covariates adjustment and IPTW (Inverse Probability of Treatment Weighting) method.

Results: Among 2924 patients identified with SARS-Cov2 infection and MS-specific disease-modifying therapy, 6 months before the index date, 2660 (92.0%) had a non-hospitalized SARS-Cov2 infection, and 234 (8.0%) were hospitalized. The occurrence of SARS-Cov2 infection requiring hospitalization was significantly associated with an increase of age, MS severity and an increase of the number of medical consultations or hospitalizations the year before the index date. Overall, drug exposure was associated with age, MS severity and patient general health condition. With an adjustment on confounding factors, only exposure to ocrelizumab was associated with severe SARS-Cov2 infection occurrence, compared with interferons [OR = 2.4 (1.5; 4.1)]. Exposure to other disease-modifying therapies was not associated with this risk. Results with IPTW method were similar.

Discussion / conclusion: The severe infection risk increased with ocrelizumab exposure compared to other disease-modifying therapies for MS. It may be explained by pharmacological action mechanism of ocrelizumab. It is a CD20 receptor inhibitor that conducts to a decrease in B cells (2). Although health insurance database is exhaustive, some MS characteristics could not be identified such as the MS disability. Therefore, residual confusion in our study is possible. It might be interesting to assess this association for patients with SARS-Cov2 vaccine exposure.

Bibliography :

1. Louapre C. et al. Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis. JAMA Neurol. 2020;77(9): 1–10.

2. Sormani P.M. et al. Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis. Ann Neurol. 2021;89(4):780-789. 

3. Zabalza A. et al. COVID-19 in multiple sclerosis patients: susceptibility, severity risk factors and serological response. Eur J Neurol. 2021;28(10):3384-3395.

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