Abstract Background 5-ASA drugs are a cornerstone therapy for patients with mild-to-moderate ulcerative colitis (UC). Despite widespread use, comprehensive analyses of safety and efficacy across oral and rectal (enema) routes, as recommended by ECCO guidelines, remain limited. This systematic literature review (SLR) assessed the safety and efficacy of 5-ASA therapies in adult UC patients based on randomized controlled trials (RCTs) published between 2009 and 2024. Methods Searches were conducted in PubMed, ClinicalTrials.gov, and the European Clinical Trials Registry using AutoLit. Eligible studies were RCTs of drug-based interventions in adult UC patients; non-drug therapies were excluded. Data were extracted for oral and rectal 5-ASA formulations. Efficacy outcomes included clinical remission and quality of life (IBDQ, SF-36). Safety outcomes included overall, serious (SAEs), and treatment-related adverse events (TRAEs), infection rates, and discontinuation due to adverse events. Pooled estimates were calculated using random-effects models. Results Forty-five RCTs met inclusion criteria: 39 evaluating oral and 6 evaluating rectal 5-ASA. Across oral 5-ASA trials, the observed pooled remission rate was 56.2% (4,790/8,213; 95% CI: 49.6–62.5%), with a random-effects pooled estimate of 54.8% (95% CI: 47.1–62.3%). Mean baseline Mayo score was 4.5 (95% CI: 4.3–4.7). For rectal 5-ASA, the remission rate was 68.2% (489/627; 95% CI: 53.9–79.7%) and the pooled estimate was 65.4% (95% CI: 51.2–77.6%), with a mean baseline Mayo score of 3.4. Baseline IBDQ scores were similar (oral: 134.1 95% CI: 129.9–138.3; rectal: 138.1 95% CI: 137.5–138.7). Oral 5-ASA showed a 29-point mean IBDQ improvement (95% CI: 6.6–51.9). SF-36 scores for oral 5-ASA indicated moderate impairment in physical (PCS: 48.5 95% CI: 48.0–49.0) and mental (MCS: 44.5 95% CI: 43.7–45.3) health; SF-36 and IBDQ change data were unavailable for rectal formulations. 5-ASA was well-tolerated across all routes. For oral 5-ASA, random-effects pooled TRAE, SAE, and discontinuation rates were 7.7% (95% CI: 2.3–23.3%), 2.3% (95% CI: 2.0–2.7%), and 3.4% (95% CI: 2.5–4.6%), respectively. Corresponding rectal 5-ASA estimates were 7.6% (95% CI: 1.7–28.3%), 1.2% (95% CI: 0.5–1.7%), and 1.1% (95% CI: 0.4–2.7%). Conclusion Both oral and rectal 5-ASA formulations demonstrate favourable efficacy and safety in mild-to-moderate UC. Random-effects models showed remission rates above 50% and low frequencies of serious adverse events and discontinuations. Oral 5-ASA was associated with meaningful quality-of-life improvements, reinforcing its central role in UC management and the complementary effectiveness of rectal formulations. Conflict of interest: Landeira, Margarita: An employee of Ferring Pharmaceuticals with shares in Novo Nordisk and Jazz Pharmaceuticals. Markert, Marie: Was a Ferring employee at the time of this study and is a current employee of Pharmacosmos. Guedes, Sandra: Was a Ferring employee at the time of this study and is a current employee of Novartis. Sheffels, Erin: A contracted partner of Ferring Pharmaceuticals. Nielsen, Lasse: Was a Ferring employee at the time of this study.
Landeira et al. (2026) studied this question.