ABSTRACT
Objective To assess adaptive immunity to SARS-CoV-2 in anti-CD20 treated individuals with mRNA vaccination. Background Anti-CD20 therapies attenuate humoral responses to vaccines. However, their effect on T cell responses is less clear. We examined B and T cell responses following COVID-19 vaccination in patients receiving anti-CD20 therapy for multiple sclerosis (MS) and other autoimmune inflammatory neurologic diseases (AINDs, e.g., autoimmune encephalitis, stiff person syndrome, etc.). Design/Methods MS and AIND patients on anti-CD20 therapies were prospectively enrolled for longitudinal analysis of antibody and T cell responses after a 3rd COVID-19 vaccination. Serum antibodies against the receptorbinding domain of the S1 spike protein (RBD-S1 IgG), neutralizing antibodies, and SARS-CoV-2 CD8 T cell responses, using activationinduced markers (AIM) and INF-gamma release assays (EUROIMMUN, Germany), were measured at various time points including prevaccination, post initial vaccination series, and 4 and 12 weeks after 3rd dose. Results Thirty-four MS and AIND participants are enrolled. Results for these patients (mean age 52 years-old, 79% female, 21 Pfizer, 13 Moderna) demonstrated attenuated RBD IgG antibody responses. However, a robust CD8 T cell response was observed, following a two-dose series, compared to non-immunosuppressed, age-matched vaccinated controls or unvaccinated with severe SARS-CoV-2 infection (p = 0.01). T cell response was sustained long-term (>12 weeks post 3rd dose) in all 11 anti-CD20 patients analyzed thus far. Collections are completed for all participants at 12 weeks and analysis to be completed by 05/15/22. Further analysis includes correlation of the INF- gamma release assay compared to RBD-CD8 T cell response detected by AIM assay. Conclusions Results suggest that patients treated with anti-CD20 therapy generate a robust CD8 T cell response to SARS-CoV-2 mRNA after three doses but remain with attenuated humoral immune responses. Our observational study will provide important data to guide vaccine management in patients on or anticipating anti-CD20 therapy.
ABSTRACT
Introduction: Inebilizumab is approved in the USA and Japan for aquaporin 4 immunoglobulin (Ig)G seropositive neuromyelitis optica spectrum disorder (NMOSD). Objective: Report final safety and efficacy data from the N-MOmentum trial of inebilizumab in NMOSD. Methods: Participants with NMOSD (aged 18+, EDSS score of ≤8, recent history of attacks) were randomized 3:1 to inebilizumab or placebo monotherapy for 28 weeks or up to attack occurrence;the randomized controlled period (RCP). Primary outcome was time to adjudicated attack. Participants could then enter the inebilizumab open label period (OLP). Final study data are presented, including attack risk and safety outcomes. Results: Of the 230 participants randomized and dosed, 216 (93.9%) entered and 174 (80.6%) completed the OLP. In the RCP, 87.0% were attack free with inebilizumab and 59.9% with placebo (72.8% risk reduction, p<0.001). In the OLP, 87.7% were attackfree in those continuing inebilizumab and 83.4% in those switched from placebo. Regardless of randomization, 225 participants received inebilizumab. Mean (SD) treatment duration was 3.2 (1.4) years;36.8% were treated for >4 years (maximum of 5.5 years). Total exposure was 730.36 person-years (py) with an annualized attack rate of 0.092;40/63 (63.5%) attacks occurred in the first year. Treatment-emergent adverse events (AE) were reported by 89 (39.6%) participants, most frequently urinary tract infection (26.2%), nasopharyngitis (20.9%) and arthralgia (17.3%). Infusion-related reactions with inebilizumab occurred in 28 (12.9%) participants (rate per 100-py: whole study, 11.1;RCP, 37.6). The rate (95% confidence interval) of infections per 100-py did not increase with continued treatment: year 1, 116.3 (102.4-131.6);year 2, 68.1 (57.2-80.6);year 3, 61.9 (50.3-75.5);year 4, 55.1 (41.7-71.4). 105 participants had transient low IgG (<700 mg/dL) during treatment, but no correlations were found between the worst IgG, IgM or IgA levels recorded and the occurrence of any infection or an infection ≥ grade 3 (Fisher exact test, all p>0.05). Three trial participants died: one from complications of NMOSD attack, one from a CNS event of unclear etiology and one due to COVID-19, after 9, 224 and 1225 days of inebilizmab treatment, respectively. Conclusions. During the 5.5 years of N-MOmentum, the risk of attack in participants receiving inebilizumab remained low with no evidence of unexpected serious adverse events, including serious infection.