Comparative Efficacy of TNF-α Inhibitors Evaluated in AS

The efficacy and safety of tumor necrosis factor (TNF)-α inhibitors adalimumab, etanercept, golimumab, and infliximab were similar among patients with ankylosing spondylitis (AS), according to a meta-analysis published in Nature Scientific Reports.

TNF-α inhibitors have been shown to be effective at reducing inflammation and AS symptoms in clinical trials, although measures of efficacy and safety varied among the studies. In order to provide guidance regarding optimal TNF-α inhibitor selection in AS, the authors compared the published data on TNF-α inhibitors currently used to treat AS—adalimumab, etanercept, golimumab, and infliximab—in this meta-analysis.

A total of 16 studies and data from 2574 patients with AS were examined. The traditional meta-analysis, which evaluated studies that directly compared TNF-α inhibitors with placebo, found that each TNF-α inhibitor was significantly more effective than placebo at achieving Assessment of SpondyloArthritis international Society (ASAS) 20, ASAS40, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50% responses. 

In addition, no differences in all-cause drug withdrawals were found between any of the TNF-α inhibitors and placebo.

Individual TNF-α inhibitors were then indirectly compared with each other via network meta-analyses. No significant differences in efficacy or safety (serious adverse events or all-cause withdrawals) were found between any of the TNF-α inhibitors.

In the network meta-analyses, each TNF-α inhibitor again demonstrated greater efficacy than placebo in all measures except for etanercept, which achieved a nonsignificant increase in ASAS40 response compared with placebo.

Although no significant differences between the TNF-α inhibitors were found, the researchers ranked the TNF-α inhibitors by efficacy and safety measures in a secondary analysis. While infliximab ranked highest with regards to response measures, it also had the greatest risk for serious adverse events and drug withdrawal. Golimumab and adalimumab had the lowest probability for serious adverse events and drug withdrawal, respectively.

Summary and Clinical Applicability

TNF-α inhibitors have demonstrated efficacy in AS, but the optimal TNF-α inhibitor for treating AS is unclear since head-to-head comparisons are lacking. In this meta-analysis, the researchers found that all TNF-α inhibitors were more effective at treating AS than placebo in direct comparisons, but no differences in efficacy or safety were found between individual TNF-α inhibitors in indirect comparisons.

“In summary, the four TNF-α inhibitors [adalimumab, etanercept, golimumab, and infliximab] have superior clinical performance for managing AS patients when compared with placebo. However, we were unable to conclude the optimal TNF-α inhibitor and this issue should be solved by future researchers,” the authors stated.

Limitations and Disclosures

• Only 2 randomized controlled trials for golimumab were included in this analysis and may not have provided sufficient data to detect a clinical difference

• The study design did not account for differences in treatment duration, dose, or route of administration among the studies analyzed, which may have affected efficacy and safety outcomes

Reference

Liu W, Wu YH, Zhang L, et al. Efficacy and safety of TNF-α inhibitors for active ankylosing spondylitis patients: Multiple treatment comparisons in a network meta-analysis. Sci Rep. 2016;6:32768. doi: 10.1038/srep32768.

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