Interleukin 12/23 and interleukin 23 inhibitors for moderate-to-severe ulcerative colitis: a systematic review and network meta-analysis

Bisher Sawaf; Mohammad Al Hayek; Ahmad Kassem; Dahham Alsoud; Mulham Alom; Abdelaziz H. Salam; Rana H. Shembesh; Mohammed S. Beshr; Yusuf Hallak; Shahem Abbarh; Elias Batikh; Mosa Shibani; Muhammed Elhadi; Yaseen Alastal; Anita Afzali; Miguel Regueiro

Authors Bisher Sawaf, Mohammad Al Hayek, Ahmad Kassem, Dahham Alsoud, Mulham Alom, Abdelaziz H. Salam, Rana H. Shembesh, Mohammed S. Beshr, Yusuf Hallak, Shahem Abbarh, Elias Batikh, Mosa Shibani, Muhammed Elhadi, Yaseen Alastal, Anita Afzali, Miguel Regueiro.

Abstract

Background Ulcerative colitis (UC) is a chronic inflammatory disease affecting ~1.5 million individuals, causing significant impairment in quality of life, psychological well-being, and healthcare burden. Using indirect meta-analysis, this study compared the efficacy and safety of anti-interleukin (IL)-12/23 and IL-23 agents vs. placebo and each other, during induction and maintenance in moderate-to-severe UC.

Methods A systematic search of PubMed, Cochrane, Scopus, Web of Science, and ClinicalTrials. gov was conducted on October 1, 2024. The randomized controlled trials (RCTs) included evaluated ustekinumab, mirikizumab, risankizumab, and guselkumab. The primary outcomes were clinical remission and endoscopic improvement at both induction and maintenance endpoints. Odds ratios (ORs) with 95% confidence intervals (CIs) and surface under the cumulative ranking (SUCRA) values were used to rank treatment efficacy.

Results Six RCTs (n=3808) were analyzed for induction and 5 RCTs (n=1697) for maintenance. During induction, risankizumab demonstrated the highest clinical remission rates (OR 3.89, 95%CI 2.24- 6.75; SUCRA 80.7%) and endoscopic improvement rates (OR 4.21, 95%CI 2.12-8.35; SUCRA 87.6%) compared to placebo. In maintenance, guselkumab showed the highest clinical remission (OR 4.28, 95%CI 1.58-11.59; SUCRA 81.6%) and endoscopic improvement (OR 4.21, 95%CI 2.12-8.35; SUCRA 93.1%), and was superior to risankizumab (OR 2.05, 95%CI 1.09-3.84) for endoscopic outcomes.

Conclusions Risankizumab was most effective in induction, while guselkumab was more effective in maintenance. Head-to-head trials are warranted.

Keywords Ulcerative colitis, interleukin-12/23 inhibitors, interleukin-23 inhibitors, systematic review, network meta-analysis

Ann Gastroenterol 2025; 38 (6): 648-660