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 response. 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. Immunogenicity 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.

Breakthrough SARS-CoV-2 infections and prediction of moderate-to-severe outcomes during rituximab therapy in patients with rheumatic and musculoskeletal diseases in the UK: a single-centre cohort study

“…This finding is concordant with a cohort study that identified lower IgG concentrations as a predictor of poor immunogenicity after vaccination with the BNT162b2 vaccine in patients with rheumatic and musculoskeletal diseases. 29 We and others have shown that a low IgG concentration is an established predictor of severe infection events within the first 12 months of rituximab therapy and in repeated cycles in patients with rheumatic and musculoskeletal diseases. 27 , 30 Thus, immunoglobulin concentrations should be monitored at baseline and before each rituximab cycle, particularly in patients with comorbidities, to discern those at an increased risk of severe infection.…”

Detection of viable SARS-CoV-2 in deep respiratory specimens despite negative nasopharyngeal SARS-CoV-2 RT-PCR: Occult COVID-19 as an unsuspected cause of pulmonary infiltrates in immunocompromised patients

“…While both cases had received BNT162b2 mRNA vaccine prior to infection, none produced detectable antibodies against SARS-CoV-2, possibly contributing to viral persistence. Patients treated with rituximab may have discordant humoral and cellular immune responses to COVID-19 vaccination; immunogenic non-response to mRNA vaccination is not uncommon in this patient population [10] , [11] . Seroconversion rates of 17.5-40% have been reported in the literature [10] , [11] .…”

“…Patients treated with rituximab may have discordant humoral and cellular immune responses to COVID-19 vaccination; immunogenic non-response to mRNA vaccination is not uncommon in this patient population [10] , [11] . Seroconversion rates of 17.5-40% have been reported in the literature [10] , [11] . Similarly, other cases of occult COVID-19 reported in the literature occurred in individuals who received anti-CD20 treatment and were unable to produce neutralising antibodies to SARS-CoV-2 [5] , [12] .…”

Clinical and Molecular Characterization of a Rare Case of BNT162b2 mRNA COVID-19 Vaccine-Associated Myositis

“…Several cases of mild autoimmune reactions followed by BNT162b2 vaccine administration were reported where the requirement for hospital care was rare [ 8 , 9 ]. However, recent studies showed that in autoimmune inflammatory rheumatic diseases (AIIRD), the BNTb262 vaccine could generate immunogenic response in the majority of patients, which raised safety concerns for patients with AIIRDs [ 10 , 11 , 12 ]. Some evidence demonstrated that BNT162b2 could induce the development of Guillain-Barre syndrome (GBS), which is a rare neurological autoimmune disorder of the peripheral nervous system [ 13 , 14 , 15 , 16 , 17 ].…”