Patients with ulcerative colitis (UC) and Crohn disease (CD) are frequently treated with immunosuppressive agents including immunomodulators and biologics. Over the years, more biologic classes have been developed, including inhibitors of tumor necrosis factor-alpha (TNF-α), integrin, and interleukin (IL)-12/23. Depending on the type, prognosis, and severity of inflammatory bowel disease (IBD), physicians and patients may opt to follow a “top-down” (which favors early use of biologics) or “bottom-up” (starting with corticosteroids and agents such as 5-aminosalicylic acids [5-ASAs]) approach to treatment.

Treatment Goals

Although the definition of remission varies across the literature, the goal of treatment for IBD is to achieve and sustain remission. A frequent question asked by patients when discussing treatment options and goals is if and when IBD medications can be de-escalated or discontinued overall.

This decision is typically multifactorial, with safety outcomes, relapse rates, and costs being frequently voiced concerns. Because many IBD medications affect the patient’s immune system, patients often express concern about infection and malignancy risk.

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Looking at the SToRi Study

The Study of Infliximab (IFX) Discontinuation in Crohn Disease Patients in Stable Remission on Combined Therapy with Immunosuppressors (STORI) was conducted by Louis et al and published in Gastroenterology in 2012.1 This prospective multicenter study conducted in 20 centers in France and Belgium included 115 patients with CD who were treated for at least 1 year with IFX and an antimetabolite and were in corticosteroid-free remission for at least 6 months. After stopping IFX, the 1-year relapse rate was 43.9%±5.0%.

Some of the risk factors associated with relapse were found to be male sex, absence of prior surgical resection, C-reactive protein (CRP) level 5.0 mg/L or greater, and fecal calprotectin level 300 µg/g or greater. Patients with 1 or 2 of these risk factors had comparatively lower rates of relapse (15%). Of patients who experienced a relapse, 88% were successfully re-treated with IFX.

Torres et al Continue the Work

A subsequent study was conducted by Torres et al and published in Gastroenterology in 2015.2 This systematic review included 69 studies with a total of 4672 patients. Of patients with CD on immunomodulator-only therapy who stopped their medication after remission, 75% had a relapse within 5 years. Of patients with CD receiving combination therapy with a biologic therapy and an immunomodulator, 55% to 60% had relapses 24 months after they stopped their immunomodulator, which is similar to that experienced by patients who continued on their immunomodulator.

When evaluating UC and CD together, approximately 40% to 50% of patients who discontinued treatment with an anti-TNF agent experienced a relapse within 2 years. Remission rates continued to decline as time progressed, with rates of 35% and 12% at 7 and 10 years postdiscontinuation, respectively. Predictors of relapse included poor prognostic features (eg, ileal disease location, perianal disease, and younger age), prior disease course, and/or markers of subclinical disease activity.

De-escalating Instead of Discontinuing Therapy

Although complete discontinuation of a patient’s IBD medications is an option, some physicians may consider dose de-escalation as an alternative. To further evaluate this option, Little et al conducted a systematic review evaluating the loss of clinical remission in patients with IBD who had their biologic dose de-escalated instead of discontinued.3

The authors included a total of 20 studies with 995 patients with IBD. Clinical relapse occurred in 0% to 54% of patients who de-escalated their biologic therapy, with 1-year clinical relapse rates of 7% to 50%.

Concerns About De-escalating

Unfortunately, many of the studies included were at high risk for bias, mostly because of a lack of a control group. Lower rates of relapse (10%-25%) were found in studies in which patients had endoscopic and/or histologic remission. Similarly, patients with higher trough levels before de-escalation also had lower rates of clinical relapse (0%-10%). These rates appear to be similar to the relapse rates after complete discontinuation of biologic therapy as discussed in the prior studies.

Risk factors identified for relapse after dose de-escalation included lack of concomitant immunomodulator therapy, shorter duration of biologic therapy before de-escalation, elevated CRP level, active disease on endoscopy and/or magnetic resonance imaging, and not using trough-based de-escalation strategies.

Typically, more than 50% of patients who de-escalated treatment and experienced relapse and for whom biologic treatment was subsequently re-started were able to achieve clinical remission or clinical response, although not all studies included these data. Many studies also did not include mucosal healing data. It is important to note the heterogeneity among the studies included in this systematic review as well as the overall patient population.

The authors concluded that, based on their findings, the lowest risk of relapse was for patients in clinical, biologic, and endoscopic remission while on combination therapy with an immunomodulator for a duration of remission of 6 to 12 months. However, a patient who meets all of these criteria is difficult to find in the real world.

A Complicated Decision

As these studies have noted, deciding whether or not to de-escalate or discontinue a patient’s biologic treatment for their IBD is a complicated decision and requires a detailed evaluation and discussion with the patient. At the time of diagnosis, it is important to classify the severity and prognosis of the patient’s IBD because this may help guide future decisions. It may be useful to perform an ileocolonoscopy before making any substantial medication decisions.

As medications with new mechanisms of action continue to be developed, additional data on their dose de-escalation and discontinuation will have to be evaluated, because much of the current data has focused on anti-TNF agents. Therapeutic drug monitoring is increasingly being used to help guide IBD medication changes; however, many real-world hurdles must be overcome to obtain coverage of these tests for both reactive and proactive monitoring indications.

Although many of the studies included relapse rates, complication rates after de-escalation or discontinuation such as fistulas, abscesses, infections, antibody formation, and need for surgery were not specified often. Even if the decision to de-escalate is made, there is a lack of data to support the best dosing algorithm to follow, which may significantly affect outcomes.


  1. Louis E, Mary JY, Vernier-Massouille G, et al; Groupe D’etudes Thérapeutiques Des Affections Inflammatoires Digestives. Maintenance of remission among patients with Crohn’s disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology. 2012;142(1):63-70.e5. doi:10.1053/j.gastro.2011.09.034
  2. Torres J, Boyapati RK, Kennedy NA, Louis E, Colombel JF, Satsangi J. Systematic review of effects of withdrawal of immunomodulators or biologic agents from patients with inflammatory bowel disease. Gastroenterology. 2015;149(7):1716-1730. doi:10.1053/j.gastro.2015.08.055
  3. Little DHW, Tabatabavakili S, Shaffer SR, Nguyen GC, Weizman AV, Targownik LE. Effectiveness of dose de-escalation of biologic therapy in inflammatory bowel disease: a systematic review. Am J Gastroenterol. 2020;115(11):1768-1774. doi:10.14309/ajg.0000000000000783

This article originally appeared on Gastroenterology Advisor