Little is known about the optimal
duration of therapy with an anti-
tumor necrosis factor (TNF) agent and/or an
immunomodulator for patients with
inflammatory bowel disease (IBD). We performed a systematic search of the literature to identify studies reporting after de-escalation (
drug cessation or
dose reduction) of anti-TNF agents and/or
immunomodulators in patients in remission from IBD. Studies were reviewed according to the type of IBD and
drug. Rates of relapse, factors associated with relapse, and response to re-treatment were determined. Our search yielded 6315 unique citations; we analyzed findings from 69 studies (18 on de-escalation [
drug cessation or
dose reduction] of
immunomodulator monotherapy, 8 on
immunomodulator de-escalation from combination
therapy, and 43 on de-escalation of anti-TNF agents, including 3 during pregnancy) comprising 4672 patients. Stopping
immunomodulator monotherapy after a period of remission was associated with high rates of relapse in patients with
Crohn's disease or
ulcerative colitis (approximately 75% of patients experienced a relapse within 5 years after
therapy was stopped). Most studies of patients with
Crohn's disease who discontinued an
immunomodulator after combination
therapy found that rates of relapse did not differ from those of patients who continued taking the
drug (55%-60% had disease relapse 24 months after they stopped taking the
immunomodulator). The only study in patients with
ulcerative colitis supported continued
immunomodulator use. Approximately 50% of patients who discontinued anti-TNF agents after combination
therapy maintained remission 24 months later, but the proportion in remission decreased with time. Markers of disease activity, poor prognostic factors, and complicated or relapsing disease course were associated with future relapse. In conclusion, based on a systematic review, 50% or more of patients with IBD who cease
therapy have a disease relapse. Further studies are required to accurately identify subgroups of patients who are good candidates for discontinuation of treatment. The decision to withdraw a
drug should be made for each individual based on patient preference, disease markers, consequences of relapse, safety, and cost.