Etanercept Again Found Safest TNF Inhibitor for RA

July 1, 2014
Norman Bauman

Combining results from studies involving nearly 12,000 rheumatoid arthritis patients finds the fusion protein etanercept less likely than other TNF inhibitors to be discontinued due to infections.

Michaud TL, Rho YH, Tatyana Shamliyan T, et al.The Comparative Safety of TNF Inhibitors in Rheumatoid Arthritis - A Meta-Analysis Update of 44 Randomized Controlled Trials. Am J Med (2014) Published online: June 17, 2014. doi: 10.1016/j.amjmed.2014.06.012

Etanercept has a lower rate of discontinuation than adalimumab, certolizumab pegol, or infliximab, and a lower rate of serious infection. That’s the result of this meta-analysis of studies testing tumor necrosis factor (TNF) inhibitors for rheumatoid arthritis, intended to update earlier assessments. The review was supported by the National Institute of Health.

The authors assessed 44 randomized controlled trials with altogether 11,700 subjects receiving TNF inhibitors and 5,901 subjects receiving either placebo or conventional treatment. Although as a group, users of TNF inhibitors showed no increased risk of serious adverse events (consistent with earlier meta-analyses), these drugs were associated with a higher risk of serious infection (odds ratio 1.42) and treatment discontinuation due to adverse events (OR 1.23).

Pointing out that averages can "mask" differences between the drugs, the authors observed that the adalimumab, certolizumab pegol, and infliximab seem to drive this class of drugs toward discontinuation due to adverse events. These three monoclonal antibodies had increased risks for serious infection (OR 1.69) and discontinuation (OR 1.38) compared to placebo or other treatments, while etanercept, which is a fusion protein, actually had a decreased risk for discontinuation due to adverse events (OR 0.72).

The relative safety of etanercept echoes the results of previous meta-analyses, leading the authors to conclude that "among available TNFis, etanercept stands out as a potentially safer option with regard to the risk of serious infection."

Golimumab was also included in the analysis, but the only noteworthy finding was a trend toward an increase in serious infections when it was used in combination with methotrexate.

There were increased ORs for cancer, but none reached statistical significance.