The Cost of Dose-Escalating TNF Inhibitors

The common practice of dose-escalating tumor necrosis factor (TNF) inhibitors to retain clinical response adds additional costs to the treatment of rheumatoid arthritis, according to a new systematic review. Dose escalation of adalimumab was associated with the highest costs, followed by infliximab, then etanercept. The rationale behind dose escalation comes from evidence suggesting that baseline disease activity is higher among rheumatoid arthritis patients undergoing dose escalation. However, dose escalation is only minimally effective and may only benefit patients who are non-responders or partial responders, according to the researchers. “Dose escalation occurs when patients with high disease activity undergo clinical worsening. However, this improvement may not necessarily be related to a dose increase, but may be a result of the normal course of the disease,” they stated.[[{"type":"media","view_mode":"media_crop","fid":"42982","attributes":{"alt":"©lenetstan/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_4650058578699","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4679","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: 13.008px; line-height: 1.538em; float: right;","title":" ","typeof":"foaf:Image"}}]] In this systematic review of 41 publications, 36 publications reported dose escalation and a weighted proportion of dose escalators were calculated for each drug. The proportion of dose escalators varied widely due to a variety of methods for defining dose escalation. Based on 33 studies, the weighted proportion of dose escalators was adalimumab 14.9%, etanercept 4.9% and infliximab 41.7%. Six studies reported economic data comparing dose escalators with non-dose escalators. Adalimumab drug costs increased 27% to 43%, with total costs increasing 28% to 34%. Total rheumatoid arthritis-related costs were not reported for adalimumab. Infliximab drug costs increased 14% to 71%, rheumatoid arthritis-related costs increased 25% to 54% and total costs increased 14% to 34%.Etanercept drug costs increased 3.2% to 19%, rheumatoid arthritis-related costs increased 4.5% and total costs increased 2.2% to 15%. The review found adalimumab had a higher proportion of switches or discontinuations compared with etanercept or infliximab, suggesting that this is not a major contributor for lower dose escalation with etanercept, they stated. The production of neutralizing anti-infliximab and anti-adalimumab antibodies could also result in the need for dose escalation, the researchers noted. Total TNF inhibitor and rheumatoid arthritis-related costs were higher in dose escalators than non-dose escalators. In general, cost increases were lower with etanercept, and dose escalation of infliximab made it significantly less cost-effective. In conclusion, the researchers stated dose escalation is not the most cost-effective approach to treatment and that patients may benefit from alternative treatment strategies, including switching to a different biologic therapy with a different mode of action. “The need to switch TNF-inhibitors may be higher in those with neutralizing antibodies against a first-line TNF-inhibitor. Concomitant use of methotrexate with TNF-inhibitors may reduce the formation of these antibodies and preserve TNF-inhibitor efficacy,” they stated. 

References:

Moots RJ, Mays R, et al.

"Burden of dose escalation with tumour necrosis factor inhibitors in rheumatoid arthritis: a systematic review of frequency and costs,"

Clinical and Experimental Rheumatology. 2015 Sep-Oct;33(5):737-45. Epub 2015 Jun 8.