Factors associated with selection of targeted therapy in patients with rheumatoid arthritis

PLOS ONE RESEARCH ARTICLE Factors associated with selection of targeted therapy in patients with rheumatoid arthritis Yeo-Jin Song1,2, Soo-Kyung Cho1,2, Hyoungyoung Kim1,2, Hye Won Kim2, Eunwoo Nam2, Chan-Bum Choi1,2, Tae-Hwan Kim1,2, Jae-Bum Jun1,2, Sang-Cheol Bae1,2, Dae Hyun Yoo1,2, Yoon Kyoung Sung ID1,2* 1 Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea, 2 Hanyang University Institute for Rheumatology Research, Seoul, Republic of Korea a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 * Abstract Objective OPEN ACCESS Citation: Song Y-J, Cho S-K, Kim H, Kim HW, Nam E, Choi C-B, et al. (2023) Factors associated with selection of targeted therapy in patients with rheumatoid arthritis. PLoS ONE 18(1): e0280234. https://doi.org/10.1371/journal.pone.0280234 Editor: Kazeem Babatunde Yusuff, Qatar University, QATAR Received: May 26, 2022 Deciding which drug to choose for targeted therapy is an important step in sequential treatment for rheumatoid arthritis (RA). This study aimed to identify factors for selecting Janus kinase inhibitors (JAKis) rather than biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with RA in real-world practice. Methods We selected RA patients starting JAKis or bDMARDs from single-center prospective cohorts in Korea. Patients were divided into JAKi, tumor necrosis factor (TNF) inhibitor, and non-TNF inhibitor groups. We performed multinomial logistic regression analyses to identify factors associated with selecting JAKis. Accepted: December 24, 2022 Published: January 10, 2023 Results Copyright: © 2023 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 145, 205, and 89 patients were included in the JAKi, TNF inhibitor, and non-TNF inhibitor groups. In multinomial regression analysis, the JAKi group was older than the TNF inhibitor group (OR 1.03, 95% confidence interval [CI] 1.01–1.05) but younger than the non-TNF inhibitor group (OR 0.97, CI 0.95–1.00). The JAKi group was less likely to have chronic pulmonary diseases compared with the TNF inhibitor group (OR 0.07, CI 0.01–0.56) or the non-TNF inhibitor group (OR 0.06, CI 0.01–0.50). Higher disease activity assessed by physician (OR 1.80, CI 1.51–2.38) and previous tacrolimus use (OR 2.05, CI 1.20–3.51) were factors suggesting selection of JAKis than TNF inhibitors. Data Availability Statement: Data are available upon request as it contains sensitive and potentially identifying patient information. Data access requests may be made to the Section of Pharmacoepidemiology in the Hanyang University Hospital for Rheumatic Diseases. To use the BIORRA and SMIRRA data, investigators should submit a formal application, which will be reviewed by the BIORRA and SMIRRA Scientific committee (). Conclusion Age, pulmonary comorbidities, previous tacrolimus use, and high disease activity assessed by physician were factors influencing the selection of JAKis for RA patients in Korea. Funding: This research was supported by a grant of Patient-Centered Clinical Research Coordinating PLOS ONE | https://doi.org/10.1371/journal.pone.0280234 January 10, 2023 1 / 13 PLOS ONE Center (PACEN) funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI19C0481, HC19C0052). This research was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF2021R1A6A1A03038899). Competing interests: DHY has received research grants from Celltrion, has served as a consultant for Celltrion, and is on the speakers’ bureau of Celltrion and Celltrion Healthcare. YKS has received research grants from Bristol-Myers Squibb, Eisai, Pfizer, and JW Pharmaceutical. There are no patents, and no products in development or being marketed to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Other authors declare no conflicts of interest. Factors for starting JAK inhibitors Introduction The successful introduction of targeted therapy for rheumatoid arthritis (RA) was made possible by improved understanding of the pathogenesis of RA [1], and has increased the attainment of clinical remission or low disease activity in RA [2]. Targeted therapy for RA is classified into use of tumor necrosis factor (TNF) inhibitor, non-TNF inhibitor, and Janus kinase inhibitor (JAKi), the latter of which is the most recently released. Many clinical studies have verified the efficacy and safety of these targeted therapies, followed by studies using real world data for determining long-term safety [3–7]. The drugs used for targeted therapy have different mode of action, but there are no clinically important differences in efficacy [8]. Therefore, JAKis, TNF inhibitors, and non-TNF inhibitors are recommended for RA patients who show inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) through a shared decision-making process between patients and physicians [9,10]. TNF inhibitor was the first biologic agent used for treatment of RA, and adalimumab, etanercept, golimumab, and infliximab are currently approved for use in Korea [11]. These drugs share efficacy and safety profiles, as well as concerns about hematologic malignancy and opportunistic infections such as tuberculosis [12]. Abatacept and tocilizumab are non-TNF inhibitors available for RA, and both have been shown to have similar efficacy as TNF inhibitors [3,13]. However, the efficacies of non-TNF inhibitors and TNF inhibitors as monotherapy were different: abatacept and tocilizumab have been used as monotherapies with similar efficacy as in combination with methotrexate (MTX), while TNF inhibitors have been recommended to be used in combination with MTX [14]. There were no significant differences in overall safety compared to TNF inhibitor [12,15], but abatacept was reported to show a lower risk of hospitalized infection than TNF inhibitor [16]. In addition, abatacept is considered safe for patients with pulmonary comorbidities such as interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD) [17,18]. Though rituximab is another biologic DMARD (bDMARD) available for csDMARD-IR patients with RA, it is not approved as second-line therapy in Korea. Recently, JAKis have been developed for RA treatment: tofacitinib was the first JAKi to be released and approved for RA treatment (in 2015), and baricitinib and upadacitinib are also currently available in Korea [3,19]. JAKis are low-molecular-weight compounds and can be conveniently administered orally, unlike other therapies that require injections. Hence, a great advantage of JAKis is that they are not associated with injection site reactions caused by (...truncated)