Predictors of Immunogenic Response to the BNT162b2 mRNA COVID-19 Vaccination in Patients with Autoimmune Inflammatory Rheumatic Diseases Treated with Rituximab

Abstract

Treatment with rituximab (RTX) blunts SARS-CoV-2 vaccination-induced humoral re-sponse. We sought to identify predictors of a positive immunogenic response to the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases (AIIRD) treated with RTX (AIIRD-RTX). We analyzed 108 AIIRD-RTX patients and 122 immunocompetent controls vaccinated with BNT162b2 mRNA participating in a multicenter vaccination study. Immunogenic-ity was defined by positive anti-SARS-CoV-2 S1/S2 IgG. We used a stepwise backward multiple logistic regression to identify predicting factors for a positive immunogenic response to vaccination and develop a predicting calculator, further validated in an independent cohort of AIIRD-RTX BNT162b2 mRNA vaccinated patients (n = 48). AIIRD-RTX patients who mounted a seropositive immunogenic response significantly differed from patients who did not by a lower number of RTX courses (median (range) 3 (1–10) vs. 5 (1–15), p = 0.007; lower cumulative RTX dose (mean ± SD) 6943.11 ± 5975.74 vs. 9780.95 ± 7240.12 mg, p = 0.033; higher IgG level prior to last RTX course (mean ± SD), 1189.78 ± 576.28 vs. 884.33 ± 302.31 mg/dL, p = 0.002), and extended interval between RTX treatment and vaccination, 469.82 ± 570.39 vs. 162.08 ± 160.12 days, p = 0.0009, respectively. Patients with ANCA-associated vasculitis and inflammatory myositis had a low likelihood of a seropositive immunogenic response compared to patients with rheumatoid arthritis, odds ratio (OR) 0.209, 95% confidence interval (CI) 0.046–0.96, p = 0.044 and OR 0.189, 95% CI 0.036–0.987, p = 0.048, respectively. Based on these findings, we constructed a calculator predicting the probability of a seropositive immunogenic response following BNT162b2 mRNA vaccination which performed with 90.5% sensitivity, 59.3% specificity, and 63.3% positive and 88.9% negative predictive values. In summary, the predicting calculator could guide clinicians for optimal timing of BNT162b2 mRNA vaccination in AIIRD-RTX patients.