September 23, 2021
Livnat Brill, PhD1; Ariel Rechtman, BSc1; Omri Zveik, BMedSc1; et al
Key Points
Question Do patients with multiple sclerosis treated with the B-cell–depleting agent ocrelizumab develop T-cell and humoral responses to the SARS-CoV-2 messenger RNA vaccine?
Findings In this cohort study of 112 participants, those treated with ocrelizumab developed lower serology response compared with untreated patients and healthy controls but showed preserved T-cell response to the SARS-CoV-2 vaccine compared with healthy controls.
Meaning In this study, preserved vaccine-specific T-cell responses in patients with multiple sclerosis treated with ocrelizumab are reassuring and will help to develop therapeutic strategies in patients with multiple sclerosis during the COVID-19 pandemic.
Importance B-cell–depleting therapies may affect the development of a protective immune response following vaccination. Understanding the ability to develop vaccine-specific immunity to COVID-19 in patients with multiple sclerosis (MS) treated with B-cell–depleting therapy is of importance for clinical decisions.
Objective To assess SARS-CoV-2 vaccine-specific humoral and cellular responses in patients treated with ocrelizumab compared with healthy controls.
Design, Setting, and Participants This single-center study performed at Hadassah Medical Center in Jerusalem, Israel, included patients with MS treated with ocrelizumab, healthy controls, and untreated patients with MS. Vaccination occurred between December 2020 and April 2021. Participants donated blood 2 to 4 and 2 to 8 weeks after the second vaccine dose for antibody and T-cell assessments, respectively.
Exposures All participants received 2 doses of BNT162b2 vaccine (Pfizer/BioNTech) and completed the study.
Main Outcomes and Measures Proportion of patients treated with ocrelizumab with SARS-CoV-2–specific serology and/or T-cell responses following vaccination. All participants underwent SARS-CoV-2 antibody testing; 29 patients treated with ocrelizumab and 15 healthy controls had evaluation of SARS-CoV-2–specific T-cell responses.
Results Of 112 participants, 49 (43.8%) had MS and were treated with ocrelizumab (33 [67.3%] female; mean [SD] age, 47.9 [13.3] years), 23 (20.5%) had MS and were not treated with disease-modifying therapies (18 [78.3%] female; mean [SD] age, 49 [13.4] years), and 40 (35.7%) were healthy controls (25 [62.5%] female; mean [SD] age, 45.3 [16] years). Twenty-six of 29 patients (89.7%) treated with ocrelizumab and 15 of 15 healthy controls (100%) had SARS-CoV-2–specific T cells following vaccination at similar levels (mean [SD], 15.4 [7.6] and 14.3 [6.3] spot-forming cells, respectively). Mean antibody titers and positive serology rate were lower in the group of patients treated with ocrelizumab (mean [SD] antibody titers and positive serology rate, 26.2 [49.2] and 376.5 [907.6] AU/mL; 10 of 40 [25%] and 20 of 49 [40.8%] for S1/S2 and receptor-binding domain, respectively) compared with healthy controls (mean [SD] antibody titers and positive serology rate, 283 [100] and 12 712 [9114] AU/mL; 100% S1/S2 and receptor-binding domain) and untreated patients (mean [SD] antibody titers and positive serology rate, 288.3 [113.8] and 10 877 [9476] AU/mL; 100% S1/S2 and receptor-binding domain), with positive association to time from ocrelizumab infusion (S1/S2: r = 0.7, P < .001; receptor-binding domain: r = 0.4, P = .04).
Conclusion and Relevance In this study, patients with MS who were treated with ocrelizumab generated comparable SARS-CoV-2–specific T-cell responses with healthy controls and had lower antibody response following vaccination. Given the potential role of T cells in protection from severe disease, this is reassuring and will help physicians develop consensus guidelines regarding MS treatment in the era of the COVID-19 pandemic.
The SARS-CoV-2 pandemic has presented a clinical concern for patients with multiple sclerosis (MS), whose mainstay treatment are immunosuppressive/immunomodulatory disease-modifying therapies.1 Most approved vaccines, including the messenger RNA vaccines, induce robust humoral and cellular immune responses against the virus spike protein2,3; however, it is still unknown whether SARS-CoV-2 vaccines confer sufficient protection in patients with MS treated with disease-modifying therapies.
In this study, we assessed the potential association of ocrelizumab, a B-cell–depleting agent, with the T-cell and antibody SARS-CoV-2 response following vaccination with the messenger RNA vaccine BNT162b2.
This single-center study was performed at Hadassah Medical Center in Jerusalem, Israel, and was approved by the Hadassah Medical Organization Ethics Committee. Participants were vaccinated between December 2020 and April 2021 and donated blood 2 to 4 and 2 to 8 weeks following their second vaccine dose of BNT162b2 vaccine (Pfizer/BioNTech) for antibody and T-cell assessments, respectively. Five healthy controls who were not vaccinated also participated in the study. All participants provided written informed consent (975-20 HMO). Data on race and ethnicity were not collected. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
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