Several studies presented at the ACTRIMS Forum 2022 provided some additional details on the COVID-19 vaccine response among MS patients treated with anti-CD20 therapies. The data suggest that vaccine response may differ somewhat among anti-CD20 agents, which may be related to the depth and/or duration of B cell suppression, the timing of vaccination and patient factors such as age.
A large series in Spain (N=162) found that mean antibody titres were lower among patients on ocrelizumab and rituximab (Oreja-Guevara et al. ACTRIMS 2022;P136). Only 3 of 20 ocrelizumab-treated patients developed vaccine antibodies; 0 of 6 rituximab patients developed antibodies. For the three vaccine responders in the ocrelizumab group, two had not received a dose of ocrelizumab for >12 months, and one was hospitalized with COVID-19 infection. The authors also noted that the antibody response was less robust in patients receiving the AstraZeneca vaccine rather than an mRNA vaccine.
A study in Greece similarly reported an impaired vaccine response in patients treated with anti-CD20 therapy (n=38) (Akrivaki et al. ACTRIMS 2022;P135). Factors that improved the vaccine antibody response were longer duration from last anti-CD20 dose and the CD19+ absolute count at the time of vaccination. Also noteworthy was a U.S. study that found that patients with a detectable CD19+ count at the time of vaccination were more likely to have a positive humoral response (Abboud et al. ACTRIMS 2022;P149).
A University of California-San Francisco study looked at humoral and cellular immunity following a third (booster) vaccination in anti-CD20-treated MS patients and healthy controls (n=47) (Sabatino et al. ACTRIMS 2022;P141). Mean age was 36 years for controls, 44 years for the ocrelizumab group and 48 years for the ofatumumab group. Using IgG reactivity to the spike receptor binding domain (RBD) (a surrogate for neutralizing antibodies), the vaccine responder rate was 62.5% for ofatumumab, 50.0% for ocrelizumab and 100% for healthy controls. All patients treated with an anti-CD20 agent appeared to have an adequate T cell response (CD4+ and CD8+). A previous study reported an augmented CD8+ response to vaccination with ocrelizumab although the follicular T cell response was attenuated (Apostolidis et al. Nat Med 2021;27:1990-2001). For the ofatumumab group in the UCSF study, the antibody response was poorer in patients previously treated with ocrelizumab or an S1PR agent. There were high antibody titres after booster injection in the ofatumumab group when the first two vaccinations were administered prior to treatment start.
An ongoing phase IV study is currently evaluating response to mRNA vaccination in ofatumumab patients (Cross et al. ACTRIMS 2022;P101). For the interim analysis (n=26), mean age was 42 years; 80.8% were female; and 34.6% were Hispanic/Latino. Median time on ofatumumab was 239 days. A total of 61.5% received two vaccine doses, and 38.5% received three vaccine doses. Overall, 56% were vaccine responders at 14 days post-vaccination. The response after two vaccine doses was 70% in patients aged <50 years who had not received prior ocrelizumab. Vaccine response was greater following a booster shot. In the subgroup receiving a third vaccination, the overall response was 77.8%; the response rate was 85.7% in patients with no prior ocrelizumab and 100% in patients <50 years. These results are consistent with the interim findings from the ALITHIOS study, which reported that 94% of ofatumumab-treated patients who contracted COVID-19 had mild-to-moderate outcomes (Cross et al. ECTRIMS 2021;P982).