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September 27, 2021
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Longer anti-TNF-a treatment duration links to sustained benefit

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Loss of response to anti-tumor necrosis factor-alpha among patients with inflammatory bowel disease decreased in incidence following two years of treatment, according to research published in Alimentary Pharmacology & Therapeutics.

“Anti-TNF-a agents are widely used as maintenance treatment for patients with IBD. After successful induction of remission, the risk of a subsequent loss of response to anti-TNF-a has been estimated to be as high as 13% to 21% per patient-year,” Johannes P.D. Schultheiss, MD, of the department of gastroenterology and hepatology at the University Medical Centre Utrecht in the Netherlands, and colleagues wrote. “In clinical practice, however, anti-TNF-a treatment is frequently continued much longer with, anecdotally, favorable long-term outcomes. Quantitative characterization of long-term efficacy might help to balance the benefits of prolonged treatment against the risks of infections and malignancies as well as treatment costs.”

 Loss of treatment response incidence to anti-TNF-a in IBD:

To characterize the association between loss of treatment response and anti-TNF-a treatment duration, researchers retrospectively analyzed 708 patients (mean age, 26.1; 53.4% women) with either Crohn’s disease (n = 532) or ulcerative colitis (n = 176) who received maintenance therapy for at least four months. Studied endpoints included incidence of anti-TNF-a loss of response, overall anti-TNF-a rates of discontinuation and dose escalation. Cox regression analyses identified loss of response predictors.

Among a total of 844 identified treatment episodes and 2,270 patient-years of follow-up, discontinuation due to loss of response occurred in 25% of treatment episodes with anti-drug antibodies detected in 31.3%. Compared with the first year of treatment, incidence of loss of response declined more than threefold following four years of treatment (17.2% per patient-year; 95% CI, 13.7-21.2 vs. 4.8% per patient-year; 95% CI, 3.1-7.2) with an overall incidence of loss of response of 9.3% per patient-year (95% CI, 8.1%-10.6%). Discontinuation (28.6% vs. 14% per patient-year) and dose escalation (38% vs. 6.8% per patient-year) also decreased from the first year to after four years. While immunomodulators were protective against loss of response with anti-drug antibodies (adjusted HR = 0.42; 95% CI, 0.24-0.74), UC (aHR = 1.53; 95% CI, 1.1-2.15) predicted loss of response as well as stricturing or penetrating disease (aHR = 1.68; 95% CI, 1.15-2.46) and male sex (aHR = 0.55; 95% CI, 0.38-0.78) among patients with CD.

“The therapeutic armamentarium for IBD is rapidly expanding with alternatives for anti-TNF-a, including non-anti-TNF-a biologicals and small molecules," Schultheiss and colleagues concluded. "For a chronic, life-long disease such as IBD, it is essential to not only characterize the initial treatment response but also to examine long-term outcomes. Our results coming from a 9 year retrospective analysis indicate that patients on long-term anti-TNF-a treatment represent a distinct population with high clinical benefit and tolerability of maintenance treatment.”