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. 2025 Sep 2;35(5):820-829.
doi: 10.1093/mr/roaf029.

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

Yuki Etani  1 , Yasutaka Okita  2 , Yuichi Maeda  2 , Kohei Tsujimoto  2 , Makoto Hirao  3 , Akira Onishi  4 , Hideo Onizawa  4 , Takaichi Okano  5 , Keisuke Nishimura  5 , Ayaka Yoshikawa  6 , Hideyuki Shiba  6 , Hideki Amuro  7 , Yonsu Son  7 , Motomu Hashimoto  8 , Tadashi Okano  9 , Ryota Hara  10 , Wataru Yamamoto  11 , Shotaro Tachibana  12 , Shinya Hayashi  12 , Takaaki Noguchi  13 , Atsushi Kumanogoh  2 , Seiji Okada  13 , Ken Nakata  14 , Kosuke Ebina  1   13
Affiliations

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

Yuki Etani et al. Mod Rheumatol. .

Abstract

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.

Keywords: Anticyclic citrullinated peptide antibody; Janus kinase inhibitors; biological disease-modifying antirheumatic drugs; rheumatoid factor.

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