Stable Immunity Observed After COVID-19 Infection in Patients With Multiple Sclerosis

Gabriel Bsteh, MD, PhD

Patients with multiple sclerosis (MS) had stable immunity after infection with SARS-CoV-2 but may see reductions depending on whether they are taking an immunosuppressive disease-modifying therapy (DMT), new data suggest. Investigators noted reductions were particularly significant for patients taking anti-CD20 monoclonal antibodies. 

Data was presented by Gabriel Bsteh, MD, PhD, department of neurology, Medical University of Vienna, Austria, at the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), October 13-15. A total of 125 patients with MS were included, with a mean age of 42.4 years (standard deviation, 12.3), 70% of whom were women. 

Antibody testing was performed following a median period of 5.2 months after COVID-19 infection, and investigators found that anti-SARS-CoV-2 antibodies were present in 76% of patients. Data further showed a significantly lower seropositivity in patients treated with immunosuppressant-DMTs (61.4%; P = .001), when compared with patients not treated with a DMT (80.6%) and patients treated with immunomodulatory DMTs (86.0%).¹ 

Lower probability of seropositivity was associated with immunosuppressant DMTs in the multivariate analysis (OR, 0.51 [95% CI, 0.17-0.82]; P <.001). Marked reduction of seropositivity was seen in patients with MS treated with rituximab (Rituxan; Genentech/Biogen) and/or ocrelizumab (Ocrevus; Genentech) in predefined subgroup analyses (OR, 0.15 [95% CI, 0.05-0.56]; P <.001). Comparably, there was no reduction in seropositivity in patients on fingolimod (Gilenya; Novartis) (OR, 0.81 [95% CI, 0.31-1.49]; P = 0.319). Over the course of 6 months, rate of seropositivity did not show significant change in this patient population.

READ MORE: Siponimod Demonstrates Beneficial Effects on Neurodegeneration in Progressive MS

“Knowledge on quality and duration of immunity after SARS-CoV-2 infection in patients with MS, and especially in the role of disease-modifying treatment, is very limited,” Bsteh said during his presentation.¹ “The objective of this study was therefore to test for SARS-CoV-2 antibodies in patients with MS with prior COVID-19 [infection] and to evaluate the degree, duration, and potential predictors of the humoral response.”

Investigators performed antibody testing in the cohort of MS patients who had a confirmed polymerase chain reaction test to confirm diagnosis of symptomatic COVID-19 infection. Data were evaluated from a nationwide Austrian registry, and investigators focused on alemtuzumab (Lemtrada; Sanofi Genzyme), cladribine (Mavenclad; EMD Serono), fingolimod, and rituximab.

“This study provides important evidence for advising patients with MS, especially regarding planning and prioritizing of vaccination,” Bsteh added.¹ 

Also presented at ECTRIMS were data evaluating the safety of the Pfizer/BioNTech COVID-19 mRNA vaccine, BNT162b2, in patients with MS, with investigators concluding that the vaccine was safe but produced varied immune response depending on the DMT patients were treated with. 

According to a presentation from Anat Achiron, MD, PhD, FAAN, professor of neurology, Sackler School of Medicine, Tel-Aviv University; and director and chair, Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Israel, a total of 555 patients with MS in Israel received the first dose of the Pfizer COVID-19 vaccine between December 20, 2020, and January 25, 2021, with 435 patients later receiving the second dose.²

During the median follow up period of 20 days after the first vaccine dose and 38 days after the second dose, investigators found no increased risk of relapse activity for patients with MS and patients with acute relapse rate were comparable to nonvaccinated patients during the follow-up period.

Investigators evaluated differences in humoral SARS-CoV2 immunoglobulin G (IgG) response post-vaccination using anti-spike protein-based serology in patients treated with different high-efficacy DMTs. Investigators found that patients taking fingolimod and ocrelizumab had a significant decrease in protective humoral immune response after vaccination. Also noted was a decrease in SARS-CoV2–specific B-cell and T-cell cellular responses. Comparably, patients who were not treated with a DMT and those treated with cladribine had similar responses in protective humoral and cellular immune responses to healthy subjects after vaccination. 

“Our findings demonstrated that, in patients that are not treated, similar to cladribine-treated MS patients and to healthy subjects, there was a very high percentage—almost 100%—of positive-IgG response at a high level,” Achiron said during her presentation.² “However, looking at fingolimod treated-MS patients, only 1 patient had a very low level of antibodies, and only 22.7% of ocrelizumab-treated patients developed protective immune response. These findings are not surprising, as already it has been reported for ocrelizumab- and fingolimod-treated patients, that they have reduced response to tetanus toxoid and influenza vaccines.”

Anchrion and colleagues also published research in Therapeutic Advances in Neurological Disorders in April 2021 that characterized humoral immunity in patients with MS who had received mRNA-COVID-19 vaccines and were treated with high-efficacy DMT, and finding that cladribine was the only DMT observed to not impair humoral response, displaying a 100% protective humoral immunity rate. Protective humoral immunity was demonstrated in 46 of 47 (97.9%) of healthy subjects (n = 47) and untreated patients with MS (n = 32). All patients (100%) treated with cladribine (n = 23) developed a high level of antibodies post-COVID-19 vaccination (P <.0001).³

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REFERENCE

1. Bsteh G, Dürauer S, Assar H, et al. Humoral immune response after COVID-19 in multiple sclerosis: a nation-wide Austrian study. Presented at ECTRIMS Congress 2021; October 13-15; Virtua. Poster P922. 
2. Achrion A. Treatments in the context of MS: about DMT’s and SARS-CoV2. Presented at ECTRIMS Congress 2021; October 13-15; Virtual. Presentation ID 003.
3. Achiron A, Mandel M, Dreyer-Alster S, et al. Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies. Ther Adv Neurol Disord. 2021;14:17562864211012835. doi:10.1177/17562864211012835