Optimizing 5-aminosalicylate for moderate ulcerative colitis: expert recommendations from the Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition

Abstract

The lack of clear definition and classification for "moderate ulcerative colitis (UC)" creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.

Keywords: 5-Aminosalicylates; Inflammatory bowel diseases; Treatment optimization; Ulcerative colitis.

Fig. 1.

Proposed treatment algorithm for patients with moderate ulcerative colitis (UC). ^aAccording to modified Truelove and Witts criteria: 4–6 bowel movements/day, temperature ≤37.8°C, pulse ≤90 beats/min, hemoglobin ≥10.5 g/dL, and C-reactive protein ≤30 mg/L. Additional assessments to measure disease activity may take into account clinical presentation, patient-reported symptoms, and objective/ laboratory criteria. In the absence of a validated definition for moderate UC, classification of moderate UC is subject to physicians’ preferences and judgement; ^bThe weightage for each predictor varies, and management strategies are determined at the physician’s discretion; ^cRectal 5-aminosalicylate (5-ASA) at a dose of ≥1 g/day at induction is recommended for patients with distal UC, specifically those with proctosigmoiditis or proctitis; ^dIf 5-ASA dose has been maximized to ≥4 g/day, and topical 5-ASA therapy has been added and similarly optimized (e.g., ≥1 g/day rectal 5-ASA), also optimize patient adherence, extend treatment duration, and switch 5-ASA formulation [17]; ^eBudesonide multimatrix (MMX) can be considered before systemic corticosteroids. In some areas, beclomethasone dipropionate is being used instead of budesonide MMX; ^fEarly escalation to immunomodulators such as thiopurine may be required for patients who are intolerant of 5-ASA or with specific strong predictors of aggressive disease; ^gFor patients with predictors of aggressive disease, consider adding 30–40 mg/day oral corticosteroids to 5-ASA. For patients with an inadequate response to 5-ASA therapy, an add-on dose of ≥40 mg/day oral corticosteroids could be considered; ^hInadequate response: failure to achieve ≥50% decrease in rectal bleeding and stool frequency, per an adaptation of STRIDE-II consensus recommendations [49]; ⁱRelapse: failure to achieve rectal bleeding=0, stool frequency=0, or Mayo Endoscopic Subscore <3, per an adaptation of STRIDE-II consensus recommendations [49]; ^jFor maintenance therapy in moderate endoscopic activity: after tapering corticosteroids, an immunomodulator such as thiopurine should be considered in addition to 5-ASA; ^kFor corticosteroid-dependent patients: 5-ASA (particularly topical) can be continued for symptom control until onset of action of treatment, for chemoprotective effects, to meet reimbursement criteria, to control disease activity after de-escalation/treatment holiday, or if patient prefers. IV, intravenous; STRIDE, Selecting Therapeutic Targets in Inflammatory Bowel Disease. Adapted from Le Berre C, et al. Expert Opin Biol Ther 2020;20:363-378, with permission from Taylor & Francis [45].