EFFICACY AND SAFETY OF ADVANCED THERAPIES AS INDUCTION THERAPY FOR ULCERATIVE COLITIS: AN UPDATED SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

Advanced therapies (ATs) are central to the management of moderate-to-severe ulcerative colitis (UC). The expanding therapeutic landscape and limited head-to-head trials necessitate updated comparative effectiveness analyses. We performed a systematic review and network meta-analysis (NMA) to assess the efficacy and safety of ATs as induction therapy for UC.

We searched MEDLINE, Embase, and Cochrane CENTRAL. We included phase 3 randomized controlled trials evaluating approved ATs or agents in late-stage development for induction therapy in moderate-to-severe UC. Pairwise meta-analyses and NMA were conducted using a frequentist random-effects model. Confidence was evaluated using the CINeMA framework. The primary outcome was clinical remission; secondary outcomes included endoscopic improvement, serious adverse events (SAEs), adverse events leading to discontinuation (AELDs), and serious infections. Analyses were stratified by prior exposure to ATs.

Thirty-three induction trials involving 17 therapies, were included. Upadacitinib demonstrated the highest relative efficacy for clinical remission (RR 6.90; 95% CI 3.54-12.45; P-score 0.95; high confidence) and endoscopic improvement (RR 5.29; 95% CI 3.38-8.28; P-score 0.97; moderate confidence). In AT-naïve patients, obefazimod and upadacitinib showed the highest efficacy, whereas in AT-experienced patients, upadacitinib, ustekinumab, and tofacitinib ranked highest. Anti-p19 inhibitors, including risankizumab, subcutaneous guselkumab, and mirikizumab, were associated with the most favorable safety profiles for SAEs and AELDs, although confidence in safety estimates was lower.

Upadacitinib has high efficacy for induction of clinical remission and endoscopic improvement in AT-naïve and AT-experienced patients. Novel therapies, like obefazimod and guselkumab subcutaneous, may represent highly effective alternatives. Anti-p19 inhibitors offer a favorable safety profile.