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.Keywords : Crohn's Disease ; Ulcerative Colitis ; Patient Management ; Cessation.Abbreviations used in this paper : anti-TNF, anti-tumor necrosis factor therapy ; CD, Crohn's disease ; CRP, C-reactive protein ; FC, fecal calprotectin ; IBD, inflammatory bowel disease ; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses ; RCT, randomized controlled trial ; TNF, tumor necrosis factor ; UC, ulcerative colitis.Therapeutic strategies in inflammatory bowel disease (IBD) have evolved considerably in the past few decades. The acknowledgment that subclinical and undertreated inflammation can lead to poor outcomes has underpinned a shift in treatment goals from symptomatic control to sustained clinical and endoscopic remission.1 Treatment strategies have changed accordingly, including the ear...

Outcomes 7 Years After Infliximab Withdrawal for Patients With Crohn’s Disease in Sustained Remission

“…9,10,[13][14][15] Few studies reported on the long-term outcome of patients after IFX withdrawal when in clinical remission. A Danish retrospective observational study reported a low rate of remission (12%) ten years after the last IFX infusion.…”

“…longer-term data are still missing. 10 The aim of the present study was to describe the long-term results of the STORI trial and to identify predictors of poor outcomes.…”

Stopping 5-aminosalicylates in patients with ulcerative colitis starting biologic therapy does not increase the risk of adverse clinical outcomes: analysis of two nationwide population-based cohorts

“…In patients who are refractory to conventional treatments, anti-tumour necrosis factor-alpha (anti-TNF)  biologics are effective at inducing clinical response, clinical remission and endoscopic remission 4. There has been a significant amount of research conducted on the impact of discontinuing immunomodulators (ie, azathioprine, 6-mercaptopurine) and biologics on clinical outcomes in IBD due to their cost and side effects 5. However, after a patient with UC requires escalation to biologics, the benefit of continuing or withdrawing 5-ASA is currently unknown.…”

Considerations, challenges and future of anti-TNF therapy in treating inflammatory bowel disease

“…Other trials outlined the role of concomitant therapy in reducing immunogenicity [68,72]. The decision to withdraw a drug should be made on individual basis, balancing several factors [73,74]. A summary of the key aspects of de-escalating therapy in patients treated with anti-TNF is shown in table 4.…”