IBD: Relapse Rate High After Stopping Anti-TNF Treatment

Diana Phillips

April 01, 2016

Approximately one third of patients in remission from inflammatory bowel disease (IBD) with anti-tumor necrosis factor-alpha (anti-TNFα) therapy relapse within 1 year of stopping treatment, and this rate may increase to more than half in the long term, according to the findings of a systematic review and meta-analysis.

"[A]lthough the short-term prognosis after anti-TNF treatment seems favorable, most patients who discontinue these drugs while in clinical remission (and without taking into consideration any other factor) will relapse over time," Javier P. Gisbert, MD, PhD, from the Gastroenterology Unit, La Princesa University Hospital, Madrid, Spain, and colleagues report in an article published online March 22 in the American Journal of Gastroenterology.

The findings suggest that "discontinuation of anti-TNF therapy cannot be considered a globally advisable strategy for all patients in routine clinical practice," the authors write. However, "it seems that some patients may maintain long-term remission after discontinuation of anti-TNF therapy."

For the meta-analysis, the authors included 27 studies that looked at anti-TNFα discontinuation in patients with IBD after clinical remission.

The overall risk for relapse among the combined 1150 patients was 44% (95% confidence interval [CI], 37% - 51%; heterogeneity value [I 2] = 84%) across a follow-up range of 6 to 125 months, the authors report.

When considered by condition, the risk for relapse among patients with Crohn disease (CD) over the same follow-up range was 44% (95% CI, 36% - 51%; I 2 = 79%; 912 patients), whereas the short-term (less than 12 months) relapse rate was 38% (95% CI, 13% - 63%; I 2 = 80%; 126 patients). "If only clinical remission was assessed, the incidence of relapse was higher than that obtained if endoscopic or radiological methods were also used to confirm remission (61% vs. 18%; I 2=0%]," they note.

The medium-term (12 - 24 months) and long-term (25 months or longer) risks for relapse in patients with CD were 40% (95% CI, 33% - 48%; I 2 = 78%; 813 patients) and 49% (95% CI, 31% - 68%; I 2 = 88%; 228 patients), respectively.

In patients with ulcerative colitis (UC), the overall relapse rate was 38% (95% CI, 23% - 52%; I 2 = 82%; 266 patients; follow-up range, 6 - 24 months), whereas the short- and medium-term relapse rates were approximately 40% (I 2 = 22% and 83%, respectfully).

"When patients [with UC] withdrew therapy based exclusively on the achievement of clinical remission (but not on endoscopic remission), the relapse rate in the medium term was 50% (95% CI=37–63%; I 2=26%; 83 patients); if endoscopic remission was included, the relapse rate decreased to 33% (95% CI=18–49%; I 2=43%; 67 patients)," the authors note.

The available data were insufficient to assess long-term relapse rates in patients with UC, according to the authors.

In patients retreated with the same anti-TNF drug, remission rates were high, at 80% (95% CI, 68% - 91%; I 2 = 86%; 290 patients) overall, 82% (95% CI, 70% - 95%; I 2 = 82%; 182 patients) in patients with CD, and 85% (95% CI, 72% - 98%; I 2, 45%; 50 patients) in patients with UC. "When an outlier study was removed from the meta-analysis of CD and UC patients, the efficacy of anti-TNF therapy increased to 92% in both cases and heterogeneity disappeared," the authors report.

The data indicate that "even IBD patients in long-term sustained remission after discontinuing anti-TNF therapy may relapse eventually. In this respect, it should be taken into account that IBD is a relapsing-remitting, chronic disease, and patients would be expected to experience flares, even with excellent disease control and good adherence."

The relationship between relapse rate and time since therapy discontinuation seems to suggest that "most patients in whom anti-TNF therapy has been stopped will relapse," the authors write. "The 'glass half full' perspective, on the other hand, would point out that a subgroup (a minority) of patients could achieve 'indefinite' remission."

There appear to be some differences in relapse/remission rates based on type and subtype of IBD. "Some studies included both CD and UC patients, and found a nonsignificant trend for longer persistence of remission after discontinuation of [infliximab] in patients with UC," the authors write. "Obviously, these differences should be confirmed in adequately controlled studies."

Comparing relapse rates between patients with luminal vs perianal CD, the data point to a higher risk for relapse in perianal compared with luminal disease. However, according to the authors, "adequately controlled studies should be performed to conclude whether perianal and luminal diseases are to be managed differently with respect to the discontinuation of anti-TNF therapy."

With respect to patients with IBD overall, the authors explain that "[c]urrently available data are insufficient to make recommendations on when anti-TNF therapy could be stopped. The decision to continue anti-TNF therapy should be individualized, and potential consequences (risks and benefits) should always be discussed with the patient."

Dr Gisbert and one coauthor have disclosed having served as speakers, consultants, and advisory members for and receiving research funding from MSD and AbbVie. The remaining author has disclosed no relevant financial relationships.

Am J Gastroenterol. Published online March 22, 2016. Abstract


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