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Observational Study
. 2025 Jul;28(7):e70351.
doi: 10.1111/1756-185X.70351.

Differential Impact of Concomitant Methotrexate and Glucocorticoids Dosages on Biologics and JAK Inhibitors: The ANSWER Cohort Study

Kosuke Ebina  1   2 , Yuki Etani  2 , Yasutaka Okita  3 , Kohei Tsujimoto  3 , Yuichi Maeda  3 , Takaaki Noguchi  1 , Makoto Hirao  4 , Koichi Murata  5 , Takayuki Fujii  5 , Motomu Hashimoto  6 , Tadashi Okano  7 , Takuya Kotani  8 , Koji Nagai  8 , Takaichi Okano  9 , Iku Shirasugi  9 , Ryota Hara  10 , Yonsu Son  11 , Hideki Amuro  11 , Masaki Katayama  12 , Shotaro Tachibana  13 , Shinya Hayashi  13 , Wataru Yamamoto  14 , Atsushi Kumanogoh  3 , Ken Nakata  15 , Seiji Okada  1 , Akira Onishi  5
Affiliations
Observational Study

Differential Impact of Concomitant Methotrexate and Glucocorticoids Dosages on Biologics and JAK Inhibitors: The ANSWER Cohort Study

Kosuke Ebina et al. Int J Rheum Dis. 2025 Jul.

Abstract

Aim: This multicenter retrospective study evaluated the differential impact of concomitant methotrexate (MTX) and glucocorticoids (GCs) administration by dosage on the effectiveness and safety of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) in a real-world cohort of patients with rheumatoid arthritis, adjusting for clinical backgrounds variables.

Methods: The study included 3751 treatment courses (bDMARD- or JAKi-naïve cases, 48.9%; tumor necrosis factor inhibitors: 1668; tocilizumab [TCZ]: 865; abatacept [ABT]: 825; JAKi: 393). Hazard ratios for treatment retention were calculated using multivariate Cox proportional hazards models, adjusted for potential confounders. Improvement in the clinical disease activity index (ΔCDAI) with each formulation was analyzed using mixed-effects models for repeated measures, stratified by concomitant MTX and GCs dosages.

Results: Compared to MTX(-), a lower dose of MTX (< 10 mg/week) was associated with significant improvement in ΔCDAI with golimumab (GLM), TCZ, and JAKi and reduced discontinuation due to ineffectiveness of etanercept (ETN). A higher MTX dose (≥ 10 mg/week) demonstrated a similar trend. Compared to GCs(-), a lower dose of GCs (≤ 5 mg/day; prednisolone equivalent) was associated with a diminished ΔCDAI with GLM and an increased discontinuation due to ineffectiveness of ADA and GLM. A higher dose of GCs (> 5 mg/day) was associated with increased discontinuation due to safety with ETN, CZP, and JAKi.

Conclusions: The effects of concomitant MTX and GCs dosages on the effectiveness and safety of biologics and JAKi vary among agents. MTX did not mitigate safety issues, and GCs did not enhance effectiveness of any agents, regardless of dosage.

Keywords: Janus kinase inhibitors; biological disease‐modifying antirheumatic drugs; glucocorticoids; methotrexate; rheumatoid arthritis.

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References

    1. J. S. Smolen, R. B. M. Landewe, S. A. Bergstra, et al., “EULAR Recommendations for the Management of Rheumatoid Arthritis With Synthetic and Biological Disease‐Modifying Antirheumatic Drugs: 2022 Update,” Annals of the Rheumatic Diseases 82, no. 1 (2023): 3–18, https://doi.org/10.1136/ard‐2022‐223356.
    1. J. L. Nam, K. Takase‐Minegishi, S. Ramiro, et al., “Efficacy of Biological Disease‐Modifying Antirheumatic Drugs: A Systematic Literature Review Informing the 2016 Update of the EULAR Recommendations for the Management of Rheumatoid Arthritis,” Annals of the Rheumatic Diseases 76, no. 6 (2017): 1113–1136, https://doi.org/10.1136/annrheumdis‐2016‐210713.
    1. G. R. Burmester, A. J. Kivitz, H. Kupper, et al., “Efficacy and Safety of Ascending Methotrexate Dose in Combination With Adalimumab: The Randomised CONCERTO Trial,” Annals of the Rheumatic Diseases 74, no. 6 (2015): 1037–1044, https://doi.org/10.1136/annrheumdis‐2013‐204769.
    1. R. N. Maini, F. C. Breedveld, J. R. Kalden, et al., “Therapeutic Efficacy of Multiple Intravenous Infusions of Anti‐Tumor Necrosis Factor Alpha Monoclonal Antibody Combined With Low‐Dose Weekly Methotrexate in Rheumatoid Arthritis,” Arthritis and Rheumatism 41, no. 9 (1998): 1552–1563, https://doi.org/10.1002/1529‐0131(199809)41:9<1552::AID‐ART5>3.0.C....
    1. M. Boers, L. Hartman, D. Opris‐Belinski, et al., “Low Dose, Add‐On Prednisolone in Patients With Rheumatoid Arthritis Aged 65+: The Pragmatic Randomised, Double‐Blind Placebo‐Controlled GLORIA Trial,” Annals of the Rheumatic Diseases 81, no. 7 (2022): 925–936, https://doi.org/10.1136/annrheumdis‐2021‐221957.

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