The impact of autoantibodies on the efficacy of biological disease-modifying anti-rheumatic drugs in rheumatoid arthritis: meta-analysis of randomized controlled trials

Kaoru Takase-Minegishi; Stefan Böhringer; Jackie L Nam; Yuko Kaneko; Frank Behrens; Saedis Saevarsdottir; Jacqueline Detert; Marjatta Leirisalo-Repo; Désirée van der Heijde; Robert Landewé; Sofia Ramiro; Diane van der Woude

doi:10.1093/rheumatology/keae113

The impact of autoantibodies on the efficacy of biological disease-modifying anti-rheumatic drugs in rheumatoid arthritis: meta-analysis of randomized controlled trials

Rheumatology (Oxford). 2024 Feb 16:keae113. doi: 10.1093/rheumatology/keae113. Online ahead of print.

Affiliations

¹ Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
² Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands.
³ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK.
⁴ Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
⁵ CIRI/Rheumatology and Fraunhofer Institute, Translational Medicine and Pharmacology ITMP, Goethe University, Frankfurt, Germany.
⁶ . Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
⁷ Rheumatological-immunological medical Practice, Templin, Germany.
⁸ Department of Rheumatology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁹ Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.
¹⁰ . Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology Center, Amsterdam, The Netherlands. Department of Rheumatology, Zuyderland Medical Center, Heerlen, the Netherlands.

PMID: 38366945
DOI: 10.1093/rheumatology/keae113

Abstract

Objective: To investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies.

Methods: Previous systematic literature reviews performed by EULAR RA management task forces were searched for qualifying RCTs. RCTs investigating the efficacy of bDMARDs and including both autoantibody-positive (≤80% of total population) and -negative RA patients were eligible. For trials comparing bDMARD+csDMARD vs csDMARD, relative risks (RR) comparing two groups (RF + vs RF-, ACPA+ vs ACPA-) were calculated for efficacy outcomes for each arm. Subsequently, relative risk ratios (RRRs) were computed, as the ratio of RR of the bDMARD-arm and the RR from the non-bDMARD-arm. Pooled effects were obtained with random effect meta-analyses.

Results: Data from 28 eligible RCTs were analyzed, pooling 23 studies in three subgroups: 6 including csDMARD-naïve patients, 14 csDMARD-IR, and 3 TNFi-IR patients. In csDMARD-naïve and csDMARD-IR patients, seropositivity was not associated with a better response to bDMARDs: pooled 6-month ACR20 RRRs 1.02 (0.88-1.18) and 1.09 (0.90-1.32), respectively. Other outcomes showed no difference between groups either. In TNFi-IR patients, based on 3 trials, the 6-month ACR20 RRR was 2.28 (1.31-3.95), favoring efficacy in seropositive patients. Other outcomes mostly showed no significant difference between the groups. Based on the mode of action, efficacy was comparable between RF-positive and RF-negative patients for both TNFi and non-TNFi treatment and also for the individual bDMARDs.

Conclusion: The effect of bDMARDs is generally comparable in patients with and without RF/ACPA, regardless of the patient population, the mechanism of action or individual drug used.

Keywords: anti-citrullinated protein autoantibodies; biological therapies; rheumatoid arthritis; rheumatoid factor.