TY - JOUR
T1 - Low protection from breakthrough SARS-CoV-2 infection and mild disease course in ocrelizumab-treated patients with multiple sclerosis after three mRNA vaccine doses
AU - Novak, Frederik
AU - Bajwa, Hamza Mahmood
AU - Coia, John Eugenio
AU - Nilsson, Anna Christine
AU - Nielsen, Christian
AU - Holm, Dorte K
AU - Østergaard, Kamilla
AU - Hvidt, Mathilde Vilhelmine Miller
AU - Byg, Keld-Erik
AU - Johansen, Isik S
AU - Mittl, Kristen
AU - Rowles, William
AU - Zamvil, Scott S
AU - Bove, Riley
AU - Sabatino, Joseph J
AU - Sejbaek, Tobias
N1 - © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023/10
Y1 - 2023/10
N2 - BACKGROUND: Our study investigated the rate of breakthrough SARS-CoV-2 infection and clinical outcomes in a cohort of multiple sclerosis (MS) patients who were treated with the anti-CD20 monoclonal antibody (Ab), ocrelizumab, before first, second and third BNT162b2 mRNA vaccinations. To correlate clinical outcomes with the humoral and cellular response.METHODS: The study was a prospective non-randomised controlled multicentre trial observational study. Participants with a diagnosis of MS who were treated for at least 12 months with ocrelizumab prior to the first BNT162b2 mRNA vaccination were prospectively followed up from January 2021 to June 2022.RESULTS: Out of 54 participants, 32 (59.3%) developed a positive SARS-CoV-2 PCR test in the study period. Mild infection was observed in all infected participants. After the third vaccination, the non-infected participants had higher mean Ab levels compared to the infected participants (54.3 binding antibody unit (BAU)/mL vs 26.5 BAU/mL, p=0.030). The difference in reactivity between spike-specific CD4+ and CD8+ T lymphocytes in the two groups was not significant.CONCLUSION AND RELEVANCE: The study results demonstrate rates of 59% in breakthrough infections after the third SARS-CoV-2 mRNA vaccination in ocrelizumab-treated patients with MS, without resulting in critical disease courses. These findings suggest the need for continuous development of prophylactic treatments when proved important in the protection of severe breakthrough infection.
AB - BACKGROUND: Our study investigated the rate of breakthrough SARS-CoV-2 infection and clinical outcomes in a cohort of multiple sclerosis (MS) patients who were treated with the anti-CD20 monoclonal antibody (Ab), ocrelizumab, before first, second and third BNT162b2 mRNA vaccinations. To correlate clinical outcomes with the humoral and cellular response.METHODS: The study was a prospective non-randomised controlled multicentre trial observational study. Participants with a diagnosis of MS who were treated for at least 12 months with ocrelizumab prior to the first BNT162b2 mRNA vaccination were prospectively followed up from January 2021 to June 2022.RESULTS: Out of 54 participants, 32 (59.3%) developed a positive SARS-CoV-2 PCR test in the study period. Mild infection was observed in all infected participants. After the third vaccination, the non-infected participants had higher mean Ab levels compared to the infected participants (54.3 binding antibody unit (BAU)/mL vs 26.5 BAU/mL, p=0.030). The difference in reactivity between spike-specific CD4+ and CD8+ T lymphocytes in the two groups was not significant.CONCLUSION AND RELEVANCE: The study results demonstrate rates of 59% in breakthrough infections after the third SARS-CoV-2 mRNA vaccination in ocrelizumab-treated patients with MS, without resulting in critical disease courses. These findings suggest the need for continuous development of prophylactic treatments when proved important in the protection of severe breakthrough infection.
U2 - 10.1136/jnnp-2022-330757
DO - 10.1136/jnnp-2022-330757
M3 - Journal article
C2 - 37185261
SN - 0022-3050
VL - 94
SP - 934
EP - 937
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
IS - 11
ER -