5-Aminosalicylates for non-surgical patients with active or quiescent Crohn’s disease: an overview of systematic reviews (umbrella review)

Background: 5-aminosalicylates (5-ASAs) are commonly used in non-surgical patients with Crohn’s disease (CD), especially in mild-to-moderate disease, despite current guidelines against their use. Despite this, the evidence regarding their efficacy is mixed, with conflicting findings in systematic reviews (SRs). Aims: We conducted an overview of reviews (umbrella review) to consolidate existing knowledge from published SRs on using 5-ASAs in patients with active or quiescent CD. Methods: We systematically searched for relevant SRs published in English until July 6, 2024, summarizing data on 5-ASAs used in induction, maintenance, or withdrawal trials of CD. We also searched for placebo-controlled RCTs of 5-ASAs published after 2015. Results: Eight SRs met our inclusion criteria, with the number of included RCTs of 5-ASAs in CD ranging from 2 to 22. Two were network meta-analyses (NMA); 4 were Cochrane SRs. SRs found no evidence of benefit for oral 5-ASAs over placebo for maintaining medically induced remission. The latest NMA in 2017, including 22 RCTs for induction of remission, suggested that high-dose mesalamine (≥ 2.4 g) was more effective than placebo, though ranking lower than systemic corticosteroid and high-dose budesonide. No placebo-controlled RCT of 5-ASAs was published after 2015, only the ongoing STATIC trial is investigating the withdrawal of 5-ASAs in patients with quiescent CD. Conclusion: This overview of SRs suggests that the evidence does not support the use of 5-ASAs for maintaining medically induced remission. However, high-dose mesalamine may be considered for inducing remission in selected patients with mild luminal CD who prefer to avoid steroids.