A head-to-head comparison of TNF-α inhibitors as the first biologic treatment of rheumatoid arthritis

Abstract

Objectives: TNF-α inhibitors (TNFis) are effective biologic drugs for rheumatoid arthritis (RA), but their comparative efficacy is unclear due to limited direct comparisons. The objective of this work was to compare the efficacy of infliximab (INX), certolizumab pegol (CZP), etanercept (ETN), golimumab (GOM) and adalimumab (ADM) in achieving remission at 3 months in bio-naïve RA patients.

Methods: Using data from the NOR-DMARD study of adult RA patients in Norway starting a TNFi as their first biologic treatment, we employed a target trial emulation approach. TNFi selection is mainly determined by drug prices in annual national tenders, allowing us to use drug cost as an instrumental variable (IV). Applying a novel IV method, causal effects were estimated with remission at 3 months as the end point. Results were compared with standard regression analysis adjusted for baseline variables.

Results: The IV analysis suggested potential differences in efficacy among TNFis, with INX showing higher remission rates compared with CZP, and ETN performing better than GOM. However, confidence intervals were wide, and many comparisons were not statistically significant. Sensitivity analyses confirmed the overall direction of results. Regression analysis adjusting for observed confounders showed no substantial differences, underscoring the importance of addressing unobserved confounding effects.

Conclusion: This hypothesis-generating study provides evidence that TNFis may not be equally effective. The uncertainty in the estimates highlights the need for a pragmatic randomized controlled trial to validate the findings. With decreasing costs of TNFis, such studies are increasingly feasible and critical to guide clinical decision-making.

Keywords: TNF inhibitors; comparative efficacy; instrumental variable analysis; rheumatoid arthritis.