Efficacy and safety of Mirikizumab for ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials

Abstract

Ulcerative colitis (UC) is a widespread incurable chronic inflammation of the colon mucosa. Currently, oral small-molecule medications targeting Janus kinase or sphingosine-1-phosphate and monoclonal antibodies to TNF-α,α4β7 integrins and Ustekinumab are the lines of treatment for UC. Up to 50% of patients either do not react to initial treatment or lose response over time, emphasizing the need for innovative treatment. Mirikizumab, a humanized IgG4-variant monoclonal antibody, binds to subunit p19 of interleukin-23. This systematic review aims to evaluate Mirikizumab compared to placebo in treating moderate-to-severe active UC. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and using the Population, Intervention, Comparison, Outcome, Study design (PICOS) model for inclusion and exclusion criteria, we systematically reviewed the literature. Our inclusion criteria encompassed randomized controlled trials assessing Mirikizumab efficacy in treating UC across demographics. We employed the Cochrane Risk of Bias tool (RoB1) to investigate bias within included studies across its seven domains. The statistical analysis was conducted using Review Manager Version 5 software. Four studies were included, comparing patients treated with mirikizumab to placebo groups. All doses of mirikizumab administered intravenously demonstrated clinical remission, specifically, the 200 mg and 300 mg doses showed significant efficacy, with risk ratios of 4.74 (95% CI [1.43, 15.69]) and 1.82 (95% CI [1.33, 2.50]), respectively. During the maintenance phase of extension trials, symptoms subsided with a subcutaneous 200 mg dose (RR = 1.46, 95% CI [0.47, 4.51], P = 0.51). To conclude, mirikizumab demonstrates significant efficacy in treating UC, substaintially improving clinical, endoscopic, and histological outcomes.

Keywords: IL-23 inhibitor; Meta-analysis; Mirikizumab; Ulcerative colitis.

Fig. 1

PRISMA flowchart of the study selection process

Fig. 2

Risk of bias summary and graph of the four included studies based on the Cochrane risk of bias assessment tool (ROB 1 tool)

Fig. 3

Efficacy of different IV Mirikizumab doses on UC clinical remission at 12-week follow-up

Fig. 4

A Efficacy of 200 mg subcutaneous Mirikizumab dose on UC Clinical Remission at 52 Weeks. B Sensitivity analysis excluding Sandborn et al. 2022

Fig. 5

Efficacy of different IV Mirikizumab doses on UC clinical response at 12-week follow-up

Fig. 6

Sensitivity analysis displays the efficacy of Mirkizumab on clinical response outcome after removing D’ Haens 2023

Fig. 7

Efficacy of different IV Mirikizumab doses on UC endoscopic remission after 12-week follow-up

Fig. 8

Forest plot analyzing the Mirkizumab effect on endoscopic remission after the end of the maintenance phase in patients with UC

Fig. 9

Efficacy of different IV Mirkizumab doses on histological remission of patients with UC in the induction phase (12-week follow-up)

Fig. 10

A Forest plot analyzing the effect size of Mirkizumab on histological remission of patients with UC. B Sensitivity analysis excluding Sandborn et al. 2022

Fig. 11

Symptomatic Remission outcome after induction phase of Mirkizumab in patients with UC

Fig. 12

Forest plot analysis showing effect of Mirikizumab on adverse events and drug discontinuation after 52 weeks in UC patients