Real-world Effectiveness of Biologic Disease-modifying Antirheumatic Drugs for the Treatment of Rheumatoid Arthritis after Etanercept Discontinuation in the United Kingdom, France, and Germany

Clinical Therapeutics. Aug 2017;39(8):1618-1627


The purpose of this study was to assess the real-world effectiveness of patients with rheumatoid arthritis (RA) who discontinued etanercept treatment and subsequently received another tumor necrosis factor α (TNF-α) inhibitor or a non-TNF-α biologic in the UnitedKingdom, France, and Germany.


Medical record data of patients with RA were collected from a panel of rheumatologists in the United Kingdom, France, and Germany. Patients were required to have a diagnosis of RA, be ≥18 years old, and have initiated use of another TNF-α inhibitor (adalimumab, certolizumab pegol, golimumab, or infliximab) or a non-TNF-α biologic (abatacept or tocilizumab) between January 2014 and May 2015 after discontinuing use of etanercept. Reasons for discontinuing use of etanercept and selecting a second biologic disease-modifying antirheumatic drug (DMARD) were described. Study outcomes included European League Against Rheumatism (EULAR) response and change in Clinical Disease Activity Index (CDAI) score. The study outcomes were compared among treatment groups (ie, TNF-α inhibitors and non-TNF-α biologics) using descriptive and multivariable-adjusted analyses. As a secondary analysis, the study outcomes were also descriptively compared between each of the TNF-α inhibitors. Because adalimumab is one of the most commonly used TNF-α inhibitor to treat RA, a secondary analysis was conducted to compare the outcomes among adalimumab, other TNF-α inhibitors, and non-TNF-α inhibitors.


Patient characteristics before initiating treatment with a second DMARD were similar across treatment groups (all TNF-α inhibitors [n = 296] and non-TNF-α biologics [n = 276]). The most common reasons for discontinuing etanercept treatment were inadequate response, adverse effects, and patient preference. After etanercept, TNF-α inhibitors overall were associated with a significantly lower EULAR good response rate (56.0% vs. 64.4%, P < 0.05) and smaller CDAI score change (-6.3 vs -7.3, P = .06) relative to non-TNF-α biologics. However, the proportion of patients achieving an EULAR good response was numerically higher for adalimumab versus other TNF-α inhibitors (61.1% vs 51.6%, P = 0.11) and comparable versus non-TNF-α biologics (61.1% vs 64.4%, P = 0.52). Adalimumab was also associated with a CDAI score change significantly greater than that of other TNF-α inhibitors (-7.1 vs -5.8, P < 0.05) and comparable to that of non-TNF-α biologics (-7.1 vs -7.3, P = 0.79). The results were consistent in the multivariable-adjusted analysis and secondary analysis.


In this retrospective analysis of patients with RA in the United Kingdom, France, and Germany, after discontinuation of etanercept treatment, TNF-α inhibitors as a class were overall less effective as second biologic DMARDs relative to non-TNF-α biologics; however, adalimumab was more or as effective as other TNF-α inhibitors and non-TNF-α biologics.

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Li N, Betts KA, Messali AJ, Skup M, Garg V