TNF-α Inhibitors Show No Increased Risk of Mortality in Rheumatoid Arthritis Patients

Tumor necrosis factor-a (TNF-a) inhibitors are the most widely used first line biologic therapy for the treatment of rheumatoid arthritis, but there have been concerns raised about the safety of these treatments, which have been associated with increased risks of malignancy, infections and other serious adverse events. In an effort to assess the risk of TNF-a inhibitors, researchers from the Université Paris Descartes in Paris, conducted a meta-analysis of 23 trials concluding that TNF-a inhibitors were not associated with increased mortality in rheumatoid arthritis patients.[[{"type":"media","view_mode":"media_crop","fid":"40310","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_3320949045009","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4108","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.0080003738403px; line-height: 1.538em; float: right;","title":" ","typeof":"foaf:Image"}}]] Published in the August 3, 2015 online issue of the American Journal of Medicine, the study included randomized, controlled trials lasting 24 weeks or more, including a total of 10,048 patients, comparing all five available TNF-α inhibitors to placebo or comparator drug, with primary outcome of all-cause mortality. Most of the studies were longer than five years and several were longer than ten years.  The risk of all-cause mortality in patients receiving TNF-α inhibitors was not significantly different from the comparator (odds ratio 1.32, 95% confidence interval 0.76-2.29). Nor was any factor associated with mortality in the subgroup analyses, by individual drug, dose, or quality of evidence of the individual study.  “A recent [2014] meta-analysis has underlined the higher risk of overall serious adverse events in certolizumab pegol-treated patients and the significant increase in the risk of serious infections in patients on adalimumab, certolizumab pegol, and infliximab, which might suggest a potential higher risk of mortality…. This hypothesis has not been confirmed in our meta-analysis, which covered the same time period and compared the 5 currently available TNF-α inhibitors for the risk of mortality, an undisputed hard endpoint. Indeed, the use of TNF-α inhibitors is not associated in our study with an increased risk of medium-term mortality,” reported the group, led by Jérôme Avouac, MD, PhD, Paris Descartes University, Sorbonne Paris Cité, Paris, France.  Several registries have suggested a decrease in mortality in patients with rheumatoid arthritis treated with TNF-α inhibitors. This may be explained by the highly selected patients in randomized controlled trials, and the longer time of drug exposure in registries. “Registries may be more than adequate to address the impact of TNF-α inhibitors on overall mortality,” they write. 

References:

Poiroux L, Allanore Y, Kahan A, Avouac J. All-cause mortality associated with TNF-α Inhibitors in Rheumatoid Arthritis: a Meta-Analysis of Randomized Controlled Trials. American Journal of Medicine. Published Online: August 3, 2015. DOI: http://dx.doi.org/10.1016/j.amjmed.2015.07.020.