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

OBJECTIVES: We aimed to identify the impact of rheumatoid factor (RF) or anticyclic citrullinated peptide antibody (ACPA) titres on the retention of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKis) in patients with rheumatoid arthritis. METHODS: We retrospectively analysed 5312 courses of bDMARDs or JAKis from the ANSWER cohort. To calculate hazard ratios (HRs) for treatment discontinuation, we used multivariate Cox proportional hazards modelling, adjusted for potential confounders. RESULTS: HRs for discontinuation due to ineffectiveness were calculated based on RF classification, revealing that anti-interleukin-6 receptor (aIL-6R) antibodies exhibited the highest retention rates regardless of RF titre. In the RF-positive group, tumour necrosis factor inhibitors (TNFis) showed lower retention rates, whereas cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig) and JAKis followed aIL-6R in the retention rates. When classified based on ACPA, aIL-6R also exhibited the highest retention rates across all ACPA groups. TNFis 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. CONCLUSIONS: Considering effectiveness, aIL-6R showed the highest retention rates regardless of seropositivity. Although CTLA4-Ig and JAKis followed aIL-6R in RF or ACPA-positive cases, CTLA4-Ig showed the lowest retention rates in ACPA-negative cases.