TNF-alpha Inhibitors Less Effective After RA Patients Discontinue Etanercept

Although switching patients with rheumatoid arthritis (RA) to a second biologic disease-modifying anti-rheumatic drug (DMARD) when their disease has failed to respond to the first agent is generally advocated, no consensus exists on whether the second agent should have the same or a different mechanism of action (ie, a tumor necrosis factor-alpha [TNF-alpha] inhibitor or a non—TNF-alpha biologic). Since TNF-alpha inhibitors are the most frequently prescribed first biologic DMARD, rheumatologists face a dilemma about an ideal switching pattern.

Nanxin Li, PhD, MBA, of Analysis Group Inc, and colleagues recently sought to clarify the issue by analyzing the medical records of patients with RA in the United Kingdom, France, and Germany to assess real-world effectiveness associated with the use of several TNF-alpha inhibitors and non—TNF-alpha biologics after discontinuation of etanercept (Enbrel) treatment. The study, published in the August 2017 issue of Current Therapeutics, found that after patients discontinued treatment with etanercept, TNF-alpha inhibitors were less effective overall as second biologic DMARDs than non—TNF-alpha biologics. The study was funded by AbbVie.

All patients in the study were 18 years or older, had discontinued use of etanercept, and had initiated use of another TNF-alpha inhibitor or a non—TNF-alpha biologic between January 2014 and May 2015.

The TNF-alpha inhibitors used by the patients (n = 296) were adalimumab (n = 137) and other biologics (n = 159): certolizumab pegol, golimumab, and infliximab. The non—TNF-alpha biologics used by patients (n = 276) were abatacept and tocilizumab.

Study outcomes included the European League Against Rheumatism (EULAR) response and change in Clinical Disease Activity Index (CDAI) score. Patient characteristics at the index visit were similar across treatment groups.

Patients’ reasons for discontinuing etanercept and selecting a second biologic DMARD included inadequate response, adverse effects, and patient preference. TNF-alpha inhibitors overall were associated with a significantly lower EULAR good response rate (56.0% versus 64.4%; P <0.05) and smaller CDAI score change (—6.3 versus –7.3; P = .06) than non—TNF-alpha biologics.

A secondary analysis was conducted to compare outcomes among adalimumab, other TNF-alpha inhibitors, and non—TNF-alpha inhibitors. Rituximab was not included in the analysis because of unfavorable reimbursement decisions issued by health technology assessment authorities in the United Kingdom and France.

The proportion of patients achieving a EULAR good response was numerically higher for adalimumab than for other TNF-alpha inhibitors (61.1% versus 51.6%; P = .11) and comparable with non—TNF-alpha biologics (61.1% versus 64.4%; P = .52). Adalimumab was equally or more effective than other TNF-alpha inhibitors and non—TNF-alpha biologics, the authors said, as shown by a CDAI score change that was significantly greater than that of other TNF-alpha inhibitors (–7.1 vs –5.8; P<.05) and comparable with that of non—TNF-alpha biologics (–7.1 versus –7.3; P = .79).

The researchers said their findings were important because switching between TNF-alpha inhibitors is so common. It is important, they note, to help physicians optimize their treatment strategies. More real-world studies that compare different biologic agents used as first and second biologic DMARDs are needed to optimize a treatment algorithm for RA, to maximize clinical outcomes, and to inform policy decisions and clinical guidelines. “Future studies should evaluate and compare the clinical outcomes associated with the switch from other commonly used first-line TNF-alpha inhibitors, such as adalimumab, to another TNF-alpha inhibitor or a non—TNF-alpha biologic,” they write.