A number of case series have reported a negative SARS-CoV-2 antibody response to COVID-19 vaccination or vaccine failure in patients treated with ocrelizumab. While the results are preliminary, they do lend support to the findings from a recent study in Israel (Achiron et al. Ther Adv Neurol Disord 2021;14:1-8). (See Few vaccine responders with fingolimod, ocrelizumab, NeuroSens, April 23, 2021).
An Italian case series compared anti-Spike IgG titres in four MS patients on ocrelizumab versus 55 healthy controls (Gallo et al. Neurol Sci 2021; epub 15 June 2021). Serum samples were collected at 0, 14 and 21 days after the first dose of Pfizer vaccine and 7 days after the second vaccine dose. Anti-spike IgG titres were expressed in Binding Antibody Units (BAU). At one week after the second vaccine dose, all healthy controls showed a significant antibody response (mean 2010.4 BAU/mL). IgG titres were substantially lower in all ocrelizumab-treated patients (range 4.81 to 175 BAU/mL). All vaccinations were administered >3 months (range 97-184) after the last ocrelizumab dose.
A separate Italian case series reported that a 46-year-old female patient failed to produce a protective antibody response when vaccinated two months after the last ocrelizumab infusion (Buttari et al. Mult Scler Relat Disord 2021;52:102983). However, a second patient aged 64 years did mount a response when vaccinated three months after her ocrelizumab infusion, suggesting a minimum three-month gap between ocrelizumab dosing and vaccination is needed. Two other patients receiving either the AstraZeneca or Pfizer vaccines did mount a response when vaccinated 3 months after the second cycle of cladribine, a finding that was similar to that reported by Achiron et al.
A separate case report described a 44-year-old male who received two doses of the Pfizer vaccine 21 days apart; vaccination occurred five months after his last ocrelizumab infusion (Khayat‑Khoei et al. J Neurol 2021; epub 27 February 2021). The next ocrelizumab infusion was given 9 days after the last vaccination. A Spike antibody assay (Roche Elecsys Anti-SARS-CoV-2 S assay) at 27 days post-vaccination showed no demonstrable vaccine immunity. The authors speculated that the blunted vaccine response shown with ocrelizumab may have been further impaired by administering the next ocrelizumab dose soon after vaccination.
A case of COVID vaccine failure was reported by clinicians in New York (Chilimuri et al. Vaccines 2021;9:219). The patient, a 52-year-old male, received a dose of ocrelizumab in the first week of December 2020. He then received two doses of the Pfizer vaccine approximately 2 and 5 weeks later. He subsequently developed COVID-19 symptoms 19 days after the last vaccine dose. Antibody testing (Roche Cobas Elecsys Anti-SARS-CoV2 assay) was negative for IgG and IgM to the nucleocapsid (N) antigen, indicating no seroconversion following vaccination.
These preliminary findings suggest that the current National MS Society recommendations regarding the timing of ocrelizumab dosing and vaccination may not be optimal (www.nationalmssociety.org/coronavirus-covid-19-information/multiple-sclerosis-and-coronavirus/covid-19-vaccine-guidance/Timing-MS-Medications-with-COVID-19-Vaccines). It is unclear why the recommendations state that ocrelizumab initiation may be considered 2-4 weeks after vaccination, whereas >4 weeks is recommended between vaccination and a resumption of ocrelizumab dosing. In addition, the recommendation to consider vaccination >12 weeks after the last ocrelizumab dose would appear to be the minimum duration; a longer delay (4-6 months) may be preferable, in line with the most recent recommendations (31 January) from the Canadian Network of MS Clinics (https://cnmsc.ca/Covid19VaccineGuidance).