Chair of the Digestive Disease & Surgery Institute
Cleveland Clinic, Cleveland
One of the first questions patients often ask before beginning a new therapy is, “How long will I have to take this?” Or perhaps, “Will I have to take this for the rest of my life?” That’s human nature, and these questions are perfectly understandable.
The trouble, however, is that these can be hard questions to answer when people living with Crohn’s disease begin an anti–tumor necrosis factor therapy. Our goal in these cases, of course, is to bring about a full remission. When this happens, it can seem hard to justify the risk of removing people from a therapy that works. On the other hand, a lifetime of therapy that can have side effects and potentially may not be needed isn’t ideal either.
The question of when to stop therapy, and for whom, has been active since biologic treatments for inflammatory bowel disease emerged in the late 1990s. At that time, there was hope that short courses of these biologics would be sufficient to reverse disease course, and therapy was often stopped after a few infusions. However, this led to painful flares in selected patients, surgeries in some cases, and unanticipated reactions or ineffective response when therapy was reintroduced.
This early experience led to understandable caution about stopping anti-TNF therapy, resulting in the concept of maintaining therapy long term. Now, the pendulum is swinging back, and we are dipping our toes into the water of identifying which people with IBD could possibly stop maintenance therapy.
My opinion is that this is true for perhaps only about 20% of the people with IBD we treat, especially if they responded well to just one biologic and did not require multiple agents to reach remission and have been in “deep remission” for years with normal testing, colonoscopies and histology. That is an educated guess. The field needs further research to help us identify the patients who will not need therapy indefinitely. Until then, I recommend continuing therapy for those in remission, not stopping.
The two studies discussed this month shed important light on this question. The first, the STOP IT study, strikes appropriate caution about stopping anti-TNF therapy too readily. The study participants who ceased taking infliximab relapsed much more often than those who maintained treatment. The second, the CEASE study, provides a clinical algorithm for determining which patients could most safely and productively cease anti-TNF therapy.
Discontinuation of Infliximab Therapy in Patients With Crohn’s Disease Results in Relapse
(BMJ Open 2014;4:e005887)
The multicenter, double-blind, placebo controlled STOP-IT study included 115 people in endoscopic, clinical and biochemical remission from Crohn’s disease who had taken infliximab for at least one year. Over 48 weeks, approximately half of the participants (n=59) continued their anti-TNF therapy as usual while the others (n=56) received matching placebo. None of the 59 participants who maintained therapy relapsed, whereas 23 of the 56 who stopped therapy altogether relapsed. Time to relapse was significantly shorter among patients who discontinued infliximab than those who continued it (hazard ratio, 0.080; 95% CI, 0.035-0.186; P<0.001). There were no adverse events. The authors advised caution when considering whether to discontinue anti-TNF therapy.
Predicting Relapse After Anti–Tumor Necrosis Factor Cessation in Crohn’s Disease
(Clin Gastroenterol Hepatol 2022;20[8]:1671-1686.e16)
The CEASE trial is a prognostic study to identify the highest risk factors for relapse of Crohn’s disease after cessation of anti-TNF therapy. This meta-analysis of 1,317 patients in 14 studies showed that a lower age at initial diagnosis of Crohn’s disease (=16 years of age), a disease course of greater than five years, upper gastrointestinal symptoms and being on a second-line anti-TNF therapy predict greater relapse risk after cessation of their anti-TNF therapy. The researchers suggested that, pending further validation, their model could be useful for guiding therapy cessation decisions.
—Written and compiled by Marcus A. Banks
This article is from the January 2023 print issue.