Evidence-Based Approach to the Discontinuation of Immunomodulators or Biologics in Inflammatory Bowel Disease

Abstract

<b><i>Background:</i></b> Biologics and immunomodulators are key drugs in the long-term treatment of inflammatory bowel diseases, while they may negatively impact patients’ quality of life due to concerns of adverse events, need for frequent hospital visits, and medical expenses. The basic concept of drug withdrawal should be based on the risk of relapse and the efficacy of re-treatment. Considering a number of patients may relapse even if treatment is continued, the disadvantage of discontinuation should be recognized not by all relapse after discontinuation, but by the increase in relapse. <b><i>Summary:</i></b> Discontinuation of immunomodulator monotherapy is associated with an increased risk of relapse. However, prolonged remission might be an indication of withdrawal, concerning the long-term adverse effect including lymphoma and nonmelanoma skin cancers. When considering discontinuation from combination therapy of anti-tumor necrosis factor (TNF) agents with immunomodulators, therapeutic drug monitoring may be useful to understand the pharmacokinetic effect. However, recent randomized controlled trials, as well as large-scale observational studies, demonstrated that discontinuation of anti-TNF agents, but not of immunomodulators, resulted in a significantly higher risk of relapse even in deep remission. Therefore, discontinuation of anti-TNF agents should be considered with caution and close monitoring combined with fecal calprotectin may be necessary. On the other hand, evidence of not only short-term relapse rate but of the true long-term influence on the patient’s quality of life should be clarified by a multidimensional approach. <b><i>Key Messages:</i></b> Discontinuation of treatment should be implemented based on shared decision-making with careful interpretation of evidence and the condition.

Krill Oil and Its Bioactive Components as a Potential Therapy for Inflammatory Bowel Disease: Insights from In Vivo and In Vitro Studies

“…While corticosteroids are highly effective for inducing remission, they demonstrate toxicity effects and a loss of response over time, and contribute to major infection [14,129,130]. Therapy with immunomodulators is the mainstay treatment for moderate-to-severe CD and active UC where 5-ASA or corticosteroid treatments have failed; however, the associated toxicity is highly variable and unpredictable among patients and long-term use is correlated with an increased rate of infection and cancer risk [130][131][132]. Biological therapies are demonstrated to be highly efficacious for moderate-to-severe IBD; nonetheless, many patients either do not respond to initial treatment or lose responsiveness over time [1,[20][21][22][23].…”

APE1/Ref-1 as a Therapeutic Target for Inflammatory Bowel Disease

“…Thus, the toxicity of thiopurine therapy is highly variable and unpredictable among individuals. While the efficacy of immunomodulators to maintain remission has been established, long-term use is associated with an increased rate of infection and risk of cancer [37,39]. Additionally, the onset of action for anti-metabolites is slow, which is not ideal given these drugs are most effective when the IBD is moderate to severe [40].…”

Discontinuation of therapy in inflammatory bowel disease: Current views

“…In particular, the actual disadvantage of withdrawal should not be recognized by the rate of relapse after discontinuation itself, but by the increase in the rate of relapse over the rate of relapse with continued therapy, because a considerable number of patients may still relapse even if therapy is continued[ 15 ].…”