Comparison of retention of biologics in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study

Sadao Jinno; Akira Onishi; Shuhei Hattori; Maureen Dubreuil; Yo Ueda; Keisuke Nishimura; Takaichi Okano; Hirotaka Yamada; Wataru Yamamoto; Koichi Murata; Hideo Onizawa; Kosuke Ebina; Yuichi Maeda; Yonsu Son; Hideki Amuro; Ryota Hara; Kenichiro Hata; Hideyuki Shiba; Masaki Katayama; Ryu Watanabe; Motomu Hashimoto; Jun Saegusa

doi:10.1093/rheumatology/keae081

Comparison of retention of biologics in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study

Rheumatology (Oxford). 2024 Feb 6:keae081. doi: 10.1093/rheumatology/keae081. Online ahead of print.

Authors

Sadao Jinno^{1

2}, Akira Onishi³, Shuhei Hattori⁴, Maureen Dubreuil^{5

6}, Yo Ueda², Keisuke Nishimura², Takaichi Okano², Hirotaka Yamada², Wataru Yamamoto⁷, Koichi Murata³, Hideo Onizawa³, Kosuke Ebina^{8

9}, Yuichi Maeda¹⁰, Yonsu Son¹¹, Hideki Amuro¹¹, Ryota Hara¹², Kenichiro Hata¹³, Hideyuki Shiba¹³, Masaki Katayama¹⁴, Ryu Watanabe¹⁵, Motomu Hashimoto¹⁵, Jun Saegusa²

Affiliations

¹ Department of Medicine, University of Hawaii, Honolulu, HI, USA.
² Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe, Japan.
³ Department of Advanced Medicine for Rheumatic Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan.
⁴ University of Hawaii Internal Medicine Residency Program, Honolulu, HI, USA.
⁵ Section of Rheumatology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
⁶ VA Boston Healthcare System, Boston, MA, USA.
⁷ Department of Health Information Management, Kurashiki Sweet Hospital, Okayama, Japan.
⁸ Department of Musculoskeletal Regenerative Medicine, Osaka University, Graduate School of Medicine, Osaka, Japan.
⁹ Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
¹⁰ Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
¹¹ First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
¹² Rheumatology Clinic and Department of Orthopaedic Surgery, Nara Medical University, Nara, Japan.
¹³ Department of Internal Medicine IV, Osaka Medical Pharmaceutical University, Osaka, Japan.
¹⁴ Department of Rheumatology, Osaka Red Cross Hospital, Osaka, Japan.
¹⁵ Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.

PMID: 38317442
DOI: 10.1093/rheumatology/keae081

Abstract

Objectives: This multicentre, retrospective study aimed to compare retention and reasons for discontinuation between Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs in patients with elderly-onset rheumatoid arthritis (EORA).

Methods: Patients with RA enrolled in a Japanese multicentre observational registry between 2015 and 2022 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding factors by indication for initiation of tumor necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), cytotoxic T-lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) blockers, or JAKi, a propensity score based on baseline characteristics was used to compare drug retention. To assess the reasons for discontinuation, retention rates for ineffectiveness, adverse events, and remission were analyzed as secondary outcomes.

Results: A total of 572 patients with 835 treatment courses were identified (314 TNFi, 175 IL-6i, 228 CTLA4-Ig, and 118 JAKi). After adjusting for differences in baseline characteristics, drug retention was significantly higher for IL-6i (HR = 0.38, 95%CI = 0.27-0.55, p< 0.01) as compared with TNFi. Discontinuation due to lack of effectiveness was lower with the JAKi (HR = 0.38, 95%CI = 0.22-0.66, p< 0.01) and the IL-6i (HR = 0.29, 95%CI = 0.19-0.46, p< 0.01) as compared with the TNFi although the CTLA4-Ig had a similar HR to TNFi. The adjusted incidence of discontinuation due to adverse event was higher in the JAKi (HR = 2.86, 95%CI = 1.46-5.59, p< 0.01) than the TNFi.

Conclusions: In EORA patients, IL-6i and JAKi had longer retention and less discontinuation due to ineffectiveness than TNFi. The potential risks of JAKi should be approached with an individualized perspective.

Keywords: ANSWER cohort; biologics and targeted-synthetic disease modifying anti-rheumatic drugs; drug retention; elderly onset rheumatoid arthritis.