Prevalence and Impact of Antibodies Against TNF Alpha Inhibitors inRheumatoid Arthritis and Spondyloarthritis: Systematic Review and Meta-Analysis with Subgroup Analysis

Abstract

OBJECTIVES: We aimed to estimate the global prevalence of anti-drug antibodies (ADAb), their impact on response, and associated factors in adults with rheumatoid arthritis (RA) and spondyloarthritis (SpA) treated by TNF alpha inhibitors (TNF-i). METHODS: We searched PubMed, MEDLINE, Cochrane, Web of Science, and Scopus for observational, population-based studies published between Jan 2010 and Sept 2021. We included studies that reported the prevalence of ADAb (our main outcome) and examined their impact on treatment efficacy in adults treated with TNF-i (secondary outcome). To investigate heterogeneity, we used a Q-test and predictive interval. RESULTS: The overall global prevalence of ADAb in RA was 20.8% (95%CI,6.8-25.5) (95%PI,6.12-51.42) and in SpA 24.8% (95%CI,19.1-31.5) (95%PI,7.31-57.98). There was no significant difference in the prevalence of ADAb between infliximab (IFX) and adalimumab (ADA) in RA (p=0.21) nor in SpA (p=0.46). There was a statistically significant difference between IFX and etanercept (ETN) in RA (p<0.0001) as well as in SpA (p=0.001) and, likewise, between ADA and ETN in RA (p<0.0001) and in SpA (p=0.002). Study by subgroups of the impact of immunogenicity on response, according to the type of TNF-i, showed that the mean OR for ADA was 0.152 (CI 95%, 0.054 to 0.427) and for IFX was 0.144 (CI 95%, 0.055 to 0.378). The pairwise comparison of ADA vs IFX was not statistically significant (p=0.94). In subgroup analysis, according to the disease, the mean OR for RA was 0.149 (IC 95% 0.064 to 0.347) and for SpA was 0.303 (IC95% 0.103 to 0.890). The pairwise comparison of RA vs SpA was not statistically significant. The use of methotrexate tends to reduce the development of ADAb in RA and SpA with an OR=0.472 (CI95%,0.324-0.689) (PI95%,0.16-1.39). CONCLUSION: ADAb were equally prevalent in RA and SpA treated with TNF-i. Immunogenicity was associated with response to treatment and influenced by concomitant use of methotrexate.