P3325 - Comparative Efficacy of IL-12/23 and IL-23 Inhibitors for Maintenance Therapy in Ulcerative Colitis: A Systematic Review and Network Meta-Analysis

Bisher Sawaf, MD¹, Mulham Alom, MD², Mohammad Al Hayek, MD³, Ahmad Kasem, MSc⁴, Yusuf Omar Hallak, MD⁵, Amine Rakab, MD⁶, Mohammed S. Beshr, MBBS⁷, Shahem Abbarh, MD⁸, Miguel Regueiro, MD⁹, Yaseen Alastal, MD¹⁰
1University of Toledo Medical Center, Toledo, OH; 2Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL; 3Damascus University, Dimashq, Dimashq, Syria; 4David Geffen School of Medicine at UCLA, Los Angeles, CA; 5The University of Toledo, Toledo, OH; 6Division of Medical Education, Weill Cornell Medicine, Doha, Ad Dawhah, Qatar; 7Sana’a University, Faculty of Medicine and Health Sciences, Sana'a, Hadramawt, Yemen; 8Georgetown University MedStar Health, Baltimore, WA; 9Cleveland Clinic, Cleveland, OH; 10University of Toledo, Toledo, OH

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurrent flares and the need for long-term maintenance therapy to sustain remission and prevent mucosal damage. Biologic agents targeting the interleukin (IL)-12/23 and IL-23 pathways have shown promise in managing moderate to severe UC. However, the lack of direct comparative data between individual IL-12/23 and IL-23 inhibitors poses challenges in determining their relative therapeutic efficacy.

Methods: We systematically searched PubMed, Scopus, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and ClinicalTrials.gov for randomized controlled trials (RCTs) evaluating IL-12/23 and IL-23 inhibitors for maintenance therapy in UC. A Bayesian network meta-analysis was conducted to allow indirect comparisons between agents. The primary outcomes were clinical remission and endoscopic improvement. Odds ratios (ORs), 95% confidence intervals (CIs), and surface under the cumulative ranking (SUCRA) probabilities were calculated to estimate and rank the comparative efficacy of treatments.

Results: The maintenance phase analysis included a total of 1,697 patients from five randomized controlled trials (RCTs). Patient allocation was as follows: 179 received risankizumab, 412 were treated with mirikizumab, 190 received guselkumab, 176 received ustekinumab, and 740 were assigned to the placebo group. Among the treatments evaluated, guselkumab achieved the highest rate of clinical remission (OR: 4.28, 95% CI: 1.58–11.59) with a SUCRA score of 81.6%. It also provided the most substantial improvement in endoscopic outcomes compared to placebo, with an OR of 4.21 (95% CI: 2.12–8.35) and a SUCRA value of 93.1%. Furthermore, guselkumab demonstrated a significantly greater rate of endoscopic improvement than risankizumab (OR: 2.05, 95% CI: 1.09–3.84).

Discussion: While all IL-12/23 and IL-23 inhibitors showed higher efficacy than placebo in achieving clinical and endoscopic outcomes, guselkumab ranked highest in both domains based on SUCRA probabilities and demonstrated statistically significant advantages over risankizumab for endoscopic improvement. These findings suggest a potential therapeutic edge for guselkumab in UC maintenance therapy and highlight the need for head-to-head trials to validate these comparative outcomes.


Figure: Figure 1 A - Network plot of clinical remission at the end of the maintenance phase
Figure 1 B - Network plot of endoscopic improvemeent at the end of the maintenance phase


Figure: Table 1 - Clinical remission & Endoscopic improvement at the end of the maintenance phase

Disclosures:
Bisher Sawaf indicated no relevant financial relationships.
Mulham Alom indicated no relevant financial relationships.
Mohammad Al Hayek indicated no relevant financial relationships.
Ahmad Kasem indicated no relevant financial relationships.
Yusuf Omar Hallak indicated no relevant financial relationships.
Amine Rakab indicated no relevant financial relationships.
Mohammed Beshr indicated no relevant financial relationships.
Shahem Abbarh indicated no relevant financial relationships.
Miguel Regueiro: AbbVie – Advisory Committee/Board Member, Consultant. Amgen – Advisory Committee/Board Member, Consultant. BMS – Advisory Committee/Board Member, Consultant. Boehringer Ingelheim Pharmaceuticals Inc. – Advisory Committee/Board Member, Consultant. Celegene – Advisory Committee/Board Member, Consultant. Eli Lilly and Company – Advisory Committee/Board Member, Consultant. Genentech – Advisory Committee/Board Member, Consultant. Gilead – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant. Organon – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Prometheus – Advisory Committee/Board Member, Consultant. Salix – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant. UCB – Advisory Committee/Board Member, Consultant.
Yaseen Alastal indicated no relevant financial relationships.

Bisher Sawaf, MD¹, Mulham Alom, MD², Mohammad Al Hayek, MD³, Ahmad Kasem, MSc⁴, Yusuf Omar Hallak, MD⁵, Amine Rakab, MD⁶, Mohammed S. Beshr, MBBS⁷, Shahem Abbarh, MD⁸, Miguel Regueiro, MD⁹, Yaseen Alastal, MD¹⁰. P3325 - Comparative Efficacy of IL-12/23 and IL-23 Inhibitors for Maintenance Therapy in Ulcerative Colitis: A Systematic Review and Network Meta-Analysis, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.