Longer anti-TNF-a treatment duration links to sustained benefit
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.”
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.”
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