Abstract
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.
Supplementary materials
Table S1 The adjusted HRs with 95% CIs of drug discontinuation for adalimumab compared with etanercept on concomitant MTX >10 mg/wk during all treatment periods, ≤1 year or >1 year, stratified by other covariates with the significance of their modification effects
Table S2 The adjusted HRs with 95% CIs of drug discontinuation followed by antibiotics prescription for adalimumab compared with etanercept on concomitant MTX >10 mg/wk during all treatment periods, ≤1 year or >1 year, stratified by other covariates with the significance of their modification effects
Acknowledgments
The authors would like to thank the Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China, for assistance with statistical analysis. The authors thank the members of the Bureau of National Health Insurance, Department of Health, and the National Health Research Institutes for providing and managing, respectively, the National Health Insurance Research Database.
Disclosure
Hsin-Hua Chen and Chao-Hsiun Tang received funding from Pfizer Limited, Taiwan, Republic of China. The authors report no other conflicts of interest in this work.