Reevaluating aminosalicylates role in maintaining remission in ulcerative colitis: Systematic review and meta-analysis in the era of biologics

Abstract

BACKGROUND

Oral 5-aminosalicylic acid (5-ASA) has been a cornerstone treatment for mild to moderate ulcerative colitis (UC), traditionally used to maintain remission. With the rise of advanced therapies (biologics and small molecules), the role of 5-ASA has come under renewed scrutiny. While earlier systematic reviews affirmed its efficacy compared to placebo, these did not account for the advent of advanced therapies.

AIM

To assess the efficacy and safety of oral 5-ASA in maintaining remission in quiescent UC, compared to placebo, alternative 5-ASA formulations, and advanced therapies, in the era of biologics and small molecules.

METHODS

It was systematically searched MEDLINE, EMBASE, and the Cochrane Library, alongside conference proceedings (European Crohn’s and Colitis Organisation, British Society of Gastroenterology), for randomized controlled trials published between 2003 and 2024 in English. Eligible studies involved oral 5-ASA therapies for quiescent UC with a minimum treatment duration of six months. Outcomes included failure to maintain remission, adverse events, and serious adverse events (SAEs). Data were analyzed using Cochrane methods, with GRADE assessing evidence certainty.

RESULTS

From 44 studies (9967 participants), 5-ASA was superior to placebo in maintaining remission, with 37% of 5-ASA users relapsing at 6-12 months compared to 55% of placebo users [risk ratios (RR): 0.68; 95%CI: 0.61-0.76; high-certainty evidence]. SAEs were rare and comparable between groups (RR: 0.60; 95%CI: 0.19-1.84; low-certainty evidence). Comparative analyses suggested 5-ASA remains a viable option alongside advanced therapies, with notable differences in cost and safety profiles.

CONCLUSION

5-ASA remains effective and safe for maintaining remission in quiescent UC, even in the advanced therapy era. However, tailored approaches are needed to balance efficacy, safety, and cost in clinical practice. This study provides critical insights to guide therapeutic strategies and underscores the enduring relevance of 5-ASA.

Keywords: Colitis ulcerative; Mesalamine; Remission induction; Biological therapy; Sulfasalazine

Core Tip: Oral 5-aminosalicylic acid (5-ASA) has long been a cornerstone treatment for maintaining remission in ulcerative colitis (UC). This systematic review and meta-analysis of 44 randomized controlled trials, involving nearly 10000 patients, demonstrates that 5-ASA is significantly more effective than placebo in sustaining remission in quiescent UC, with a favorable safety profile. Despite the emergence of advanced therapies such as biologics and small molecules, 5-ASA remains a viable and cost-effective option. These findings underscore the enduring relevance of 5-ASA and highlight the need for tailored therapeutic approaches in the modern management of UC.