Abstract
Background
Interleukin-23 (IL-23)p19 inhibitors are an important modality for management of moderate-severe inflammatory bowel disease (IBD), yet intra-class comparative data remains limited with no direct head-to-head trials comparing IL-23p19 inhibitors within class. We conducted a network meta-analysis (NMA) comparing the efficacy and safety of guselkumab, mirikizumab, and risankizumab in Crohn’s disease (CD) and ulcerative colitis (UC).
Aims
To compare induction and maintenance outcomes in IBD across IL-23p19 inhibitors.
Methods
Following PRISMA-NMA guidelines, 5 databases were searched to July 2025 for randomized control trials. Outcomes included clinical response/remission, endoscopic response/remission, and adverse events (AEs). Random-effects NMAs were used to estimate relative risks (RRs) with 95% confidence intervals (CIs). Non-randomized studies were excluded.
Results
Fifteen trials (n = 11,166) formed connected networks including IL-23p19 agents, placebo, and ustekinumab. Across IBD subtypes, all IL-23p19 inhibitors were superior to placebo for clinical and endoscopic outcomes. In CD, guselkumab ranked highest in clinical response among biologic-exposed patients (RR 2.89, 95% CI 1.60-5.21) and achieved the largest effect in endoscopic remission (RR 6.57, 4.04-10.70). However, among biologic-naïve patients, ustekinumab led in clinical response (RR 2.37, 1.44-3.90). In UC, guselkumab showed the greatest efficacy for clinical remission (RR 2.67, 1.92-3.73), and mirikizumab ranked highest for endoscopic response (RR 3.47, 1.45-8.28). Overall AE rates were similar across agents, though serious AEs were lower with mirikizumab (RR 0.56, 0.40-0.77) and guselkumab (RR 0.62, 0.46-0.84).
Conclusions
IL-23p19 inhibitors are effective for both induction and maintenance therapy in IBD. Within this class of biologics, Guselkumab demonstrates the most consistent and robust efficacy across outcomes, while mirikizumab offers a favourable safety profile and the strongest endoscopic healing in UC.
Relative risks (RR) for clinical response to IL-23p19 inhibitors compared to placebo in Crohn’s disease. In head-to-head comparisons, guselkumab was significantly more effective than mirikizumab (1.60 [1.11-2.29]) and risankizumab (1.67 [1.14-2.45]), but comparable to ustekinumab (0.97 [0.73-1.29]).
Funding Agencies
None