Efficacy and Safety of IL-23 Inhibitors in the Treatment of Crohn's Disease and Ulcerative Colitis: Systemic Review and Network Meta-Analysis

IntroductionInflammatory Bowel Disease (IBD), which includes Crohns Disease (CD) and Ulcerative Colitis (UC), is a chronic condition that causes inflammation in the gastrointestinal tract and has been steadily increasing in prevalence globally. Traditional therapies for IBD often have limitations in efficacy and long-term safety. In recent years, interleukin-23 (IL-23) inhibitors, such as Ustekinumab, Risankizumab, Guselkumab, and Mirikizumab, have shown promise in treating IBD by targeting immune pathways involved in disease progression. This network meta-analysis (NMA) aims to evaluate the efficacy and safety of these IL-23 inhibitors in treating both Crohns Disease and Ulcerative Colitis. MethodsA comprehensive literature search was conducted across PubMed, Scopus, and the Cochrane Library to identify randomized controlled trials (RCTs) and observational studies published from 2000 to 2023 that assessed the efficacy and safety of IL-23 inhibitors in treating CD and UC. The studies selected focused on clinical outcomes such as remission rates, mucosal healing, and adverse events, comparing Ustekinumab, Risankizumab, Guselkumab, and Mirikizumab to placebo. Data were extracted for adult patients diagnosed with CD and UC, evaluating the results from the induction and maintenance phases. Statistical analysis was conducted using a random-effects model to account for heterogeneity, and I{superscript 2} statistics were used to assess variability across the studies. ResultsA total of 33 studies were included in the analysis, encompassing 19,668 patients, with a male predominance (53.6%). The efficacy of IL-23 inhibitors was compared across both CD and UC induction and maintenance phases. For CD induction, Mirikizumab showed the highest efficacy (OR = 5.19, 95% CI: 1.75 to 16.7), followed by Guselkumab (OR = 3.07, 95% CI: 1.35 to 5.98). In UC induction, Guselkumab demonstrated the most significant benefit (OR = 3.80, 95% CI: 1.10 to 13.3), with Risankizumab closely following (OR = 3.96, 95% CI: 0.685 to 23.0). During maintenance treatment, Guselkumab showed the highest odds ratio for both CD (OR = 10.3, 95% CI: 2.46 to 45.9) and UC (OR = 3.07, 95% CI: 0.698 to 13.4). Regarding safety, Risankizumab and Mirikizumab were associated with the most significant reductions in nausea and infections, while Ustekinumab and Guselkumab showed fewer benefits in these adverse events. Mirikizumab and Risankizumab also demonstrated the most substantial improvements in Quality of Life (QOL) for patients with CD and UC, while Guselkumab had mixed results, and Ustekinumab showed limited improvements in QOL. ConclusionThe results of this network meta-analysis indicate that Mirikizumab and Risankizumab are the most effective IL-23 inhibitors for achieving remission and improving QOL in Crohns Disease and Ulcerative Colitis, with Guselkumab also showing strong efficacy, particularly in UC. Ustekinumab demonstrated more modest effects. Both Risankizumab and Mirikizumab were associated with favorable safety profiles, significantly reducing nausea and infection rates. These findings support the use of Mirikizumab and Risankizumab as potential first-line biologic therapies for patients with moderate to severe IBD.