Is there room for immunomodulators in ulcerative colitis?

ABSTRACT

Introduction: The management of patients with ulcerative colitis (UC) has evolved over the past few decades. While aminosalicylates remain the mainstay of induction and maintenance therapy in patients with mild-to-moderate UC, the advent of biologic agents and novel oral small molecules has substantively changed the treatment landscape for patients with moderate-to-severe disease and confounded the role of traditional immunomodulators (IMMs) such as thiopurines and methotrexate in the UC management algorithm.

Areas covered: We summarize the mechanism of action of thiopurines and methotrexate, identify clinical parameters for their use, and appraise the evidence supporting the efficacy and safety of IMMs in UC as both monotherapy and in combination with other therapies, emphasizing on prospective, controlled data.

Expert opinion: With the advent of several classes of highly effective treatments for UC, emergence of data demonstrating no benefit of IMMs over placebo, and concerns about the relative safety profile of long-term IMM exposure, we propose that the role of thiopurines or methotrexate be restricted to patients with milder disease failing to maintain corticosteroid-free remission on aminosalicylates alone or in combination therapy with tumor necrosis factor antagonists in patients with moderate-to-severe UC.

KEYWORDS:

• Azathioprine
• inflammatory bowel disease
• mercaptopurine
• methotrexate
• thiopurine
• ulcerative colitis

Article Highlights

• The role of traditional immunomodulators such as thiopurines and methotrexate in the management algorithm for UC is unclear

• Pooled data suggest that thiopurines may provide some benefit for maintaining corticosteroid-free remission in UC, although this must be weighed against potentially serious treatment-related adverse events

• Prospective controlled data have not consistently demonstrated a benefit of methotrexate over placebo for induction or maintenance of remission in patients with UC

• Combination azathioprine and infliximab is more effective than either therapy alone for inducing corticosteroid-free remission in patients with moderate-to-severe UC although the efficacy of this strategy for maintaining remission is unclear

• As more effective and safer treatment options for UC emerge, the role of traditional IMMs may be restricted to patients with mild UC intolerant to or failing to maintain corticosteroid-free remission on aminosalicylates alone or as combination therapy with tumor necrosis factor antagonists

This box summarizes the key points contained in the article.

Declaration of interest

C Ma has received consulting fees from Janssen, AbbVie, Pfizer, and Robarts Clinical Trials, Inc; speaking fees from Janssen and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

One of the reviewers on the manuscript has served as an advisory board member for Janssen and AbbVie. Two additional peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.