Is drug discontinuation risk of adalimumab compared with etanercept affected by concomitant methotrexate dose in patients with rheumatoid arthritis?

Hsin-Hua Chen,1–6 Der-Yuan Chen,1–3,6–8 Yi-Ming Chen,1–3 Chao-Hsiun Tang9 1Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; 2School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; 3Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; 4Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taiwan, Republic of China; 5Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan, Republic of China; 6School of Medicine, Chung-Shan Medical University, Taichung, Taiwan, Republic of China; 7Institute of Biomedical Science, Chung-Hsing University, Taichung, Taiwan, Republic of China; 8Department of Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; 9School of Health Care Administration, Taipei Medical University, Taipei, Taiwan, Republic of China Objective: To compare drug discontinuation risk between adalimumab (ADA) and etanercept (ETN) treatment among anti-tumor necrosis factor (anti-TNF)-naïve rheumatoid arthritis (RA) patients, in particular the influence of concomitant dose of methotrexate (MTX).Methods: This retrospective nationwide population-based cohort study identified 4,592 anti-TNF-naïve RA patients in whom ETN (n=2,609) or ADA (n=1,983) was initiated using National Health Insurance claims data. After adjustment for prior medication, concomitant medication, and baseline demographic data, the relative risk of drug discontinuation in ADA users compared with ETN users was quantified by calculating adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) using Cox proportional hazard regression analyses, stratified by the follow-up time (≤1 year, >1 year) and/or concomitant MTX dose (≤10 mg/wk, >10 mg/wk).Results: ADA users had a higher risk of drug discontinuation compared with ETN users during the first year of follow-up (aHR, 1.13; 95% CI, 1.01–1.27), but not during all treatment periods (aHR, 1.06; 95% CI, 0.98–1.16) or after 1 year (aHR, 0.99; 95% CI, 0.87–1.13). However, ADA users had a significantly higher risk of drug discontinuation compared with ETN users among patients on concomitant MTX >10 mg/wk during all treatment periods (aHR, 1.27; 95% CI, 1.10–1.47), during the first year of follow-up (aHR, 1.48; 95% CI, 1.22–1.78), or after 1 year (aHR, 1.42; 95% CI, 1.06–1.90), but not among patients on concomitant MTX 0–10 mg/wk.Conclusion: This population-based cohort study demonstrated a modification effect of concomitant MTX dose on the relative risk of anti-TNF discontinuation for ADA compared with ETN among anti-TNF-naïve RA patients. However, the lack of exact cause of anti-TNF discontinuation limited causal inference of such a concomitant MTX dose-related modification effect. Keywords: adalimumab, etanercept, methotrexate, rheumatoid arthritis, treatment disconti­nuatio