title: Systematic Review of Effects of Withdrawal of Immunomodulators or Biologic Agents From Patients With Inflammatory Bowel Disease.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: joana.torres@mssm.edu.
authors.forename: Joana
authors.initials: J
authors.lastname: Torres
authors.affiliation: Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland. Electronic address: ray.boyapati@ed.ac.uk.
authors.forename: Ray K
authors.initials: RK
authors.lastname: Boyapati
authors.affiliation: Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kennedy
authors.affiliation: Department of Gastroenterology, University Hospital CHU of Liège, Liège, Belgium.
authors.forename: Edouard
authors.initials: E
authors.lastname: Louis
authors.affiliation: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland.
authors.forename: Jack
authors.initials: J
authors.lastname: Satsangi
mesh_terms: D001688:Biological Products / Q000008:administration & dosage* / Q000009:adverse effects; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D003424:Crohn Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D001688:Biological Products; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha
keywords: Cessation; Crohn's Disease; Patient Management; Ulcerative Colitis