Efficacy and Safety of Advanced Therapies in Moderately-to-Severely Active Ulcerative Colitis: a Systematic Review and Network Meta-analysis

Abstract

Introduction: This study aimed to compare the efficacy and safety of biologics and small molecules for treatment of adults with moderately-to-severely active ulcerative colitis (UC).

Methods: A systematic literature review was conducted to identify randomised controlled trials evaluating approved and emerging targeted therapies for patients with UC. A Bayesian network meta-analysis (NMA) approach was applied. Outcomes assessed included clinical response and remission, endoscopic mucosal healing, and safety.

Results: Thirty studies were included in the NMA following a feasibility assessment comparing approved induction dosing regimens and 22 studies comparing approved maintenance dosing regimens. In the biologic/Janus kinase inhibitor (JAKi)-naïve population, induction studies showed similar clinical response and remission rates across most interventions, with upadacitinib demonstrating significant improvements versus most other interventions. For maintenance studies, mirikizumab demonstrated significant improvements in clinical response and remission versus most other interventions. In the biologic/JAKi-experienced population, no significant differences were observed between most interventions in induction studies, except for significantly improved clinical response and remission for mirikizumab versus adalimumab, and upadacitinib demonstrated significant improvement versus all other interventions. Few differences between active treatments were observed in maintenance studies. In both populations, all active interventions had similar efficacy in terms of endoscopic mucosal healing in both induction and maintenance studies. Regardless of prior treatment exposure, similar rates of serious adverse events were seen across all active interventions in the induction period.

Conclusion: Among the available interventions, owing to its favourable efficacy and safety profile, mirikizumab has a relevant role in the long-term treatment of UC.

Keywords: Advanced therapies; Biologics; Comparative efficacy; IL-23 inhibitors; Mirikizumab; Small molecules; Ulcerative colitis.

Fig. 1

PRISMA flow diagram: Identification and selection of relevant publications. CENTRAL Cochrane Central Register of Controlled Trials, PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analysis, SLR systematic literature review

Fig. 2

Network plot for clinical response and remission (A) and mucosal healing (B) in the induction period for the biologic/JAKi-naïve population and median ORs (95% credible intervals) versus placebo for clinical response (C), clinical remission (D) and mucosal healing (E). ADA adalimumab, CrI credible interval, FIL filgotinib, GOL golimumab, IFX infliximab, JAKi Janus kinase inhibitor, MIRI mirikizumab, OR odds ratio, OZD ozanimod, PBO placebo, TOF tofacitinib, UPA upadacitinib, UST ustekinumab, VED vedolizumab

Fig. 3

Network plot for clinical response and remission (A) and mucosal healing (B) in the maintenance period for the biologic/JAKi-naïve population and median ORs (95% credible intervals) versus placebo for clinical response (C), clinical remission (D) and mucosal healing (E). ADA adalimumab, CrI credible interval, FIL filgotinib, GOL golimumab, IFX infliximab, JAKi Janus kinase inhibitor, MIRI mirikizumab, OR odds ratio, OZD ozanimod, PBO placebo, TOF tofacitinib, UPA upadacitinib, UST ustekinumab, VED vedolizumab

Fig. 4

All pairwise ORs in the maintenance period for the biologic/JAKi-naïve population for clinical response (A), clinical remission (B) and mucosal healing (C). Median ORs and 95% CrIs (and associated colour shading) correspond to the comparison of row treatment versus column treatment (i.e. an OR > 1 illustrates a result in favour of the row treatment). ADA adalimumab, CrI credible interval, FIL filgotinib, GOL golimumab, IFX infliximab, JAKi Janus kinase inhibitor, MIRI mirikizumab, OR odds ratio, OZD ozanimod, PBO placebo, Q2W every 2 weeks, Q4W every 4 weeks, Q8W every 8 weeks, Q12W every 12 weeks, TOF tofacitinib, UPA upadacitinib, UST ustekinumab, VED vedolizumab

Fig. 4

All pairwise ORs in the maintenance period for the biologic/JAKi-naïve population for clinical response (A), clinical remission (B) and mucosal healing (C). Median ORs and 95% CrIs (and associated colour shading) correspond to the comparison of row treatment versus column treatment (i.e. an OR > 1 illustrates a result in favour of the row treatment). ADA adalimumab, CrI credible interval, FIL filgotinib, GOL golimumab, IFX infliximab, JAKi Janus kinase inhibitor, MIRI mirikizumab, OR odds ratio, OZD ozanimod, PBO placebo, Q2W every 2 weeks, Q4W every 4 weeks, Q8W every 8 weeks, Q12W every 12 weeks, TOF tofacitinib, UPA upadacitinib, UST ustekinumab, VED vedolizumab

Fig. 5

Network plot for clinical response and remission (A) and mucosal healing (B) in the induction period for the biologic/JAKi-experienced population and median ORs (95% credible intervals) versus placebo for clinical response (C), clinical remission (D) and mucosal healing (E). ADA adalimumab, CrI credible interval, FIL filgotinib, GOL golimumab, IFX infliximab, JAKi Janus kinase inhibitor, MIRI mirikizumab, OR odds ratio, OZD ozanimod, PBO placebo, TOF tofacitinib, UPA upadacitinib, UST ustekinumab, VED vedolizumab

Fig. 6

Network plot for clinical response and remission (A) and mucosal healing (B) in the maintenance period for the biologic/JAKi-experienced population and median ORs (95% credible intervals) versus placebo for clinical response (C), clinical remission (D) and mucosal healing (E). ADA adalimumab, CrI credible interval, FIL filgotinib, GOL golimumab, IFX infliximab, JAKi Janus kinase inhibitor, MIRI mirikizumab, OR odds ratio, OZD ozanimod, PBO placebo, TOF tofacitinib, UPA upadacitinib, UST ustekinumab, VED vedolizumab