OP0041 COMPARISON OF b/tsDMARDs ABOUT NON-INFLAMMATORY PAIN IN PATIENTS WITH RHEUMATOID ARTHRITIS–ANSWER LONGITUDINAL COHORT STUDY
Authors: M. Yamashita, T. Okano, I. Shirasugi, H. Yamada, K. Nishimura, S. Sendo, Y. Ueda, T. Maeda, S. Hayashi, W. Yamamoto, A. Onishi, K. Murakami, H. Shiba, K. Hata, K. Tsujimoto, K. Ebina, Y. Son, N. Yoshida, R. Hara, R. Watanabe, M. Hashimoto, R. Kuroda, J. Saegusa
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Recent advances in the treatment have a great effect on the patients of rheumatoid arthritis (RA), but there still remain unsolved problems. Non-inflammatory pain (NIP) is one of such issues, and some previous studies suggest that around 20% of patients of RA remain with NIP even after treatment with biological disease modifying anti rheumatic drugs (bDMARDs). [1] Targeted synthetic DMARDs (tsDMARDs) is reported to improve patient-reported-outcomes including pain [2], further it has been suggested that the effect of tsDMARDs on pain is not only via inflammation control but also via acting on non-inflammatory pathway. [3] However, its effect on NIP is unclear yet. <h3>Objectives:</h3> The aim of this study is to investigate whether tsDMARDs can relieve NIP compared to bDMARDs in RA patients in a longitudinal multicenter cohort study. <h3>Methods:</h3> RA patients started b/tsDMARDs between 2000 to 2022 and continued the same drug for more than 12 months were included in this study. Unacceptable pain (UP) was defined as patient-visual analog scale (VAS) &gt; 40 mm. NIP was defined as UP with C-reactive protein (CRP) level &lt; 10 mg/liter. We also assigned a strict definition for NIP (sNIP) as NIP with swollen joint count ≤1. Inflammatory pain (IP) was defined as UP with CRP level ≥ 10 mg/liter. We examined the association between the choice of b/tsDMARDs and the persistence of NIP at month (Mo) 12 using logistic regression model. This analysis was also conducted between tsDMARDs and each subgroup of bDMARDs (Tumor Necrosis Factor inhibitors, Interleukin-6 Receptor inhibitors and cytotoxic T lymphocyte-associated antigen-4-Ig (CTLA4-Ig)). Confounding factors (age, sex, disease duration, number of previous b/tsDMARDs, smoking status, stage, class, titer of rheumatoid factor and anti-citrullinated protein/peptide antibodies, dose of methotrexate and prednisolone, the use of painkillers and disease activity at baseline) were adjusted with inverse probability of treatment weighting estimated by generalized propensity score. The frequency of NIP, IP and UP at Mo 0, 3, 6, 9 and 12 were also evaluated. Missing data were dealt with multiple imputation to calculate generalized propensity score. <h3>Results:</h3> Of 1880 treatment courses (TCs) included, 1704 TCs were treated with bDMARDs and 176 TCs were treated with tsDMARDs. The rate of UP at baseline was 61.8% in bDMARDs and 63.8% in tsDMARDs. These rates decreased dramatically to 32.2% in bDMARDs and 34.2% in tsDMARDs at Mo 3, respectively, which remained stable at Mo 12. The rates of IP in both bDMARDs and tsDMARDs also declined at Mo 3, and then remained stable at Mo 12. On the other hand, NIP was present in 28.8% of TCs in bDMARDs and 36.2% of TCs in tsDMARDs at baseline, which remained in 25.6% and 26.1% at Mo 12, respectively (Figure 1). Analysis with sNIP did not change the trend. There was no statistically significant difference in frequency of NIP at Mo 12 among b/tsDMARDs in both definitions [NIP: adjusted odds ratio (OR) = 1.47 (95% confidence interval (CI): 0.93-2.34, p = 0.10), sNIP: adjusted OR = 1.58 (95% CI: 0.95-2.62, p = 0.08), (tsDMARDs as a reference)]. Among TCs treated with each subgroup of bDMARDs, only those treated with CTLA4-Ig revealed statistically significant difference in persistence of NIP compared to those treated with tsDMARDs [adjusted odds ratio (OR) = 1.80 (95% CI: 1.01-3.20, p &lt; 0.05)]. This result was similar for the sNIP definition. [adjusted OR = 2.41 (95% CI: 1.26-4.63, p &lt; 0.01)]. <h3>Conclusion:</h3> In RA patients who were able to continue b/tsDMARDs for 12 months, the effect of tsDMARDs against NIP was not different from that of bDMARDs. Persistence of NIP was more frequently observed in RA patients treated with CTLA4-Ig compared to those with tsDMARDs. The frequency of NIP in RA patients treated with b/tsDMARDs for 12 months remained 25%, while that of UP and IP were decreased. <h3>REFERENCES:</h3> [1] Olofsson et al. Arthritis Care Res (Hoboken). 2021; 73: 1312-1321. [2] Toth et al. Int J Mol Sci. 2022; 23:1246. [3] Simon et al. Semin Arthritis Rheum. 2021; 51: 278-284. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Mai Yamashita: None declared, Takaichi Okano: None declared, Iku Shirasugi: None declared, Hirotaka Yamada: None declared, Keisuke Nishimura: None declared, Sho Sendo: None declared, Yo Ueda: None declared, Toshihisa Maeda: None declared, Shinya Hayashi: None declared, Wataru Yamamoto: None declared, Akira Onishi: None declared, Kosaku Murakami: None declared, Hideyuki Shiba: None declared, Kenichiro Hata: None declared, Kohei Tsujimoto: None declared, Kosuke Ebina has received a speaker fee from AbbVie, Amgen, Asahi-Kasei, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Ono Pharmaceutical, Pfizer, Sanofi, Taisho, and UCB Japan., Kosuke Ebina has received research grants from AbbVie, Asahi-Kasei, Eisai, Mitsubishi-Tanabe, and Teijin Pharma. Kosuke Ebina is affiliated with the Department of Musculoskeletal Regenerative Medicine, Osaka University, Graduate School of Medicine, which is supported by Taisho., Yonsu Son has received speaking fees from Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K.,Eisai Co., Ltd., and AbbVie G.K., Naofumi Yoshida: None declared, Ryota Hara has received a speaker fee from AbbVie, Eli Lilly, Eisai and Asahi-Kasei., Ryu Watanabe has received a speaker's fee from Asahi Kasei, Chugai, Eli Lilly, GSK, and Sanofi., Motomu Hashimoto received research grants and/or speaker fee from Abbvie, Asahi Kasei, Astellas, Ayumi, Brystol Meyers, Chugai, EA Pharma, Eisai, Daiichi Sankyo, Eli Lilly, Novartis Pharma, Taisho Toyama, Tanabe Mitsubishi., Ryosuke Kuroda: None declared, Jun Saegusa: None declared.