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

Yuki Etani; Yasutaka Okita; Yuichi Maeda; Kohei Tsujimoto; Makoto Hirao; Akira Onishi; Hideo Onizawa; Takaichi Okano; Keisuke Nishimura; Ayaka Yoshikawa; Hideyuki Shiba; Hideki Amuro; Yonsu Son; Motomu Hashimoto; Tadashi Okano; Ryota Hara; Wataru Yamamoto; Shotaro Tachibana; Shinya Hayashi; Takaaki Noguchi; Atsushi Kumanogoh; Seiji Okada; Ken Nakata; Kosuke Ebina

doi:10.1093/mr/roaf029

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

Mod Rheumatol. 2025 Mar 19:roaf029. doi: 10.1093/mr/roaf029. Online ahead of print.

Authors

Yuki Etani¹, Yasutaka Okita², Yuichi Maeda², Kohei Tsujimoto², Makoto Hirao³, Akira Onishi⁴, Hideo Onizawa⁴, Takaichi Okano⁵, Keisuke Nishimura⁵, Ayaka Yoshikawa⁶, Hideyuki Shiba⁶, Hideki Amuro⁷, Yonsu Son⁷, Motomu Hashimoto⁸, Tadashi Okano⁹, Ryota Hara¹⁰, Wataru Yamamoto¹¹, Shotaro Tachibana¹², Shinya Hayashi¹², Takaaki Noguchi¹³, Atsushi Kumanogoh², Seiji Okada¹³, Ken Nakata¹⁴, Kosuke Ebina^{1

13}

Affiliations

¹ Department of Sports Medical Biomechanics, Osaka University Graduate School of Medicine, Suita, Japan.
² Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan.
³ Department of Orthopedic Surgery, Osaka Minami Medical Center, Kawachi-Nagano, Japan.
⁴ Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁵ Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe Japan.
⁶ Department of Internal Medicine (Ⅳ), Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
⁷ First Department of Internal Medicine, Kansai Medical University, Osaka, Hirakata, Japan.
⁸ Department of Clinical Immunology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
⁹ Center for Senile Degenerative Disorders (CSDD), Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
¹⁰ Department of Orthopedic Surgery, Nara Medical University, Nara, Japan.
¹¹ Department of Health Information Management, Kurashiki Sweet Hospital, Kurashiki, Japan.
¹² Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
¹³ Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
¹⁴ Department of Health and Sport Sciences, Osaka University Graduate School of Medicine, Suita, Japan.

PMID: 40103318
DOI: 10.1093/mr/roaf029

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.

Keywords: Anti-cyclic citrullinated peptide antibody; Biological disease-modifying antirheumatic drugs; Janus kinase inhibitors; Rheumatoid factor.

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