Comparative efficacy of pharmacologic interventions in ulcerative colitis: a network meta analysis
Atta Ullah Khan1, Maria Ali2, Muhammad Aamir Wahab3
1Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy. attaullah.khan@unicampania.it.
Introduction:
Ulcerative colitis is chronic inflammatory condition affecting the colon, necessitating remission inducing therapeutic interventions. With the emergence of newer more advanced options, their relative effectiveness remains unclear. This network meta-analysis (NMA) will compare the effectiveness of presently available biologics and small molecules in achieving and maintaining remission among patients of moderate-to-severe ulcerative colitis as part of induction and maintenance therapy.
Methods:
A systematic search was conducted up to 21st February 2025, including only phase 2b/3 or 3 randomized controlled trials. The primary outcome was induction and maintenance of clinical remission (Full Mayo Score (FMS) ≤ 2, with no individual subscore > 1). Secondary outcomes assessed were clinical response, endoscopic improvement (Mayo Endoscopic Score (MES) ≤ 1 either with or without friability) and steroid free remission.
Results:
Across 22 studies (7,683 patients), upadacitinib had the highest likelihood of inducing clinical remission (99.08%), clinical response (97.44%) and endoscopic improvement (99.32%), followed by Infliximab and guselkumab following close by for specific outcomes. In maintenance of clinical remission and endoscopic improvement upadacitinib again ranked highest (95.60%) and (99.46%). Tofacitinib (92.43%) has the highest probability with upadacitinib (87.73%) following behind in achieving steroid free remission.
Conclusion:
Upadacitinib displayed high efficacy across multiple outcomes in both induction and maintenance therapy with Infliximab, guselkumab, and filgotinib following closely behind. For achieving steroid free remission tofacitinib has the highest probability of doing so. Overall small molecules and selective IL-23 inhibitors seems promising alternative to older biologics though additional head-to-head trial are warranted along with more real-world data.
Insights
Upadacitinib shows high efficacy for inducing and maintaining remission in ulcerative colitis. Tofacitinib is most effective for steroid-free remission, suggesting small molecules are promising alternatives.
Area of Science:
- Gastroenterology
- Clinical Pharmacology
- Immunology
Background:
- Ulcerative colitis (UC) is a chronic inflammatory colon condition requiring effective treatments.
- Numerous biologics and small molecules are available, but their comparative effectiveness is unclear.
- This study addresses the need for comparative data on UC therapies.
Purpose of the Study:
- To compare the effectiveness of current biologics and small molecules for UC.
- To evaluate induction and maintenance of remission in moderate-to-severe UC patients.
- To assess clinical response, endoscopic improvement, and steroid-free remission.
Main Methods:
- A network meta-analysis (NMA) of phase 2b/3 or 3 randomized controlled trials.
- Systematic literature search conducted up to February 21, 2025.
- Primary outcome: clinical remission (Full Mayo Score ≤ 2). Secondary outcomes: clinical response, endoscopic improvement, steroid-free remission.
Main Results:
- Upadacitinib demonstrated the highest likelihood for inducing clinical remission (99.08%), response (97.44%), and endoscopic improvement (99.32%).
- Upadacitinib also ranked highest for maintaining clinical remission (95.60%) and endoscopic improvement (99.46%).
- Tofacitinib showed the highest probability for steroid-free remission (92.43%).
Conclusions:
- Upadacitinib exhibits high efficacy in both induction and maintenance therapy for UC.
- Infliximab, guselkumab, and filgotinib are also effective, with tofacitinib leading in steroid-free remission.
- Small molecules and IL-23 inhibitors offer promising alternatives to older biologics, warranting further trials.
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