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

Victoria Furer; Tali Eviatar; Devy Zisman; Hagit Peleg; Yolanda Braun-Moscovici; Alexandra Balbir-Gurman; Daphna Paran; David Levartovsky; Michael Zisapel; Ofir Elalouf; Ilana Kaufman; Adi Broyde; Ari Polachek; Joy Feld; Amir Haddad; Tal Gazitt; Muna Elias; Nizar Higazi; Fadi Kharouf; Sara Pel; Sharon Nevo; Ori Elkayam

doi:10.3390/vaccines10060901

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

Vaccines (Basel). 2022 Jun 6;10(6):901. doi: 10.3390/vaccines10060901.

Authors

Victoria Furer¹, Tali Eviatar¹, Devy Zisman², Hagit Peleg³, Yolanda Braun-Moscovici⁴, Alexandra Balbir-Gurman⁴, Daphna Paran¹, David Levartovsky¹, Michael Zisapel¹, Ofir Elalouf¹, Ilana Kaufman¹, Adi Broyde¹, Ari Polachek¹, Joy Feld², Amir Haddad², Tal Gazitt², Muna Elias², Nizar Higazi², Fadi Kharouf³, Sara Pel¹, Sharon Nevo¹, Ori Elkayam¹

Affiliations

¹ Rheumatology Department, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6423906, Israel.
² Rheumatology Unit, Carmel Medical Center, Haifa 3436212, Israel.
³ Rheumatology Unit, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem 9103401, Israel.
⁴ Shine Rheumatology Institute, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3436212, Israel.

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.

Keywords: COVID-19; SARS-CoV-2; immunogenicity; mRNA vaccine; rituximab.

Grants and funding

This research received no external funding.