Distinct impact of RF and ACPA titer on the effectiveness and persistency of biologics and JAK inhibitors: The ANSWER cohort study.

Abstract

Objective: We aimed to identify the impact of rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibody (ACPA) titers on the retention of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis.

Methods: We retrospectively analyzed 5312 courses of bDMARDs or JAKi from the ANSWER cohort. To calculate hazard ratios (HRs) for treatment discontinuation, we used multivariate Cox proportional hazards modeling, adjusted for potential confounders.

Results: HRs for discontinuation due to ineffectiveness were calculated based on RF classification, revealing that anti-interleukin-6 receptor antibodies (aIL-6R) exhibited the highest retention rates regardless of RF titer. In the RF-positive group, tumor necrosis factor inhibitors (TNFi) showed lower retention rates, whereas cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig) and JAKi followed aIL-6R in the retention rates. When classified based on ACPA, aIL-6R also exhibited the highest retention rates across all ACPA groups. TNFi showed lower retention rates compared with other agents in the ACPA-positive group, whereas CTLA4-Ig showed lower retention rates in the ACPA-negative group compared with other agents.

Conclusion: Considering effectiveness, aIL-6R showed the highest retention rates regardless of seropositivity. Although CTLA4-Ig and JAKi followed aIL-6R in RF or ACPA-positive cases, CTLA4-Ig showed the lowest retention rates in ACPA-negative cases.