Mirikizumab 300mg/15ml solution for infusion vials

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.

Abstract licence: CC BY-NC-ND 4.0

First-line therapeutic approaches for Crohn's disease include immunosuppressants, aminosalicylates, and corticosteroids. However, more than one-third of patients are resistant to these treatments and require second-line therapies. Our goal was to synthesize the evidence on the efficacy and safety of biologics and small molecules for inducing remission in patients with moderate-to-severe Crohn's disease. A systematic review was conducted by searching for randomized controlled trials on the target population in PubMed, Scopus, and Web of Science (March 2025). Data synthesis for the outcomes of remission, health-related quality of life (HRQoL), and safety was performed using network meta-analyses and surface under the cumulative rating curve (SUCRA) analyses. The results were presented as risk ratios with 95% credible intervals. We included 55 trials (n = 16,113 patients) evaluating 26 biological drugs across 83 doses and six small molecules across 15 doses. Similar results were obtained in the sensitivity analyses conducted across different measurement time points. Alongside infliximab 5 mg/kg (SUCRA 98.6%), 10 mg/kg (92%), and 20 mg/kg intravenous (91.8%), the recently approved drugs guselkumab 1200 mg (83.2%), 600 mg (89.2%), and 200 mg intravenous (90.1%), as well as mirikizumab 600 mg (91.5%) and 1000 mg intravenous (82.4%) presented higher probabilities of disease remission and were associated with increased HRQoL. Drugs such as certolizumab, andecaliximab, fontolizumab, abatacept, and etanercept ranked low for remission (SUCRA < 40%) and presented high probabilities of serious adverse events (over 60%). Small molecules presented an intermediate profile. Inhibitors of interleukin-23 appear to be promising alternatives for the treatment of moderate-to-severe Crohn's disease. Given their safety profile, some anti-TNF drugs should be avoided in practice. Trial Registration: PROSPERO: CRD42024519150.

Abstract licence: CC BY

Background and Aim: The therapeutic landscape for ulcerative colitis (UC) is rapidly evolving, with an increasing number of biologic agents available. This systematic review and meta-analysis synthesized randomized controlled trials (RCTs) data on biologic therapies for achieving key endoscopic and histologic endpoints in moderate to severe UC. Methods: A systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science and grey literature was conducted through November 2024. Separate meta-analyses were performed for induction and maintenance. A random-effects model was used to estimate relative risks (RR), with 95% confidence intervals (CI), and confidence in estimates was evaluated with the GRADE approach (Grading of Recommendation Assessment, Development and Evaluation). Results: We included 40 RCTs (13 therapies, 14,369 patients). Thirty-two trials provided data in induction and twenty-eight in maintenance. During induction, all biologic therapies, except mirikizumab and filgotinib 100 mg, demonstrated superiority over placebo (RR 2.02, 95% CI: 1.76-2.31, I2 = 72%) for endoscopic improvement. Upadacitinib showed the highest efficacy (RR 5.53, 95% CI: 3.78-8.09). For mucosal healing, all interventions were superior to placebo (RR 2.95, 95% CI: 2.11-4.13, I2 = 61%), except filgotinib 100 mg. Risankizumab showed the highest efficacy (RR 10.25, 95% CI: 2.49-42.11). In maintenance, all therapies showed superiority over placebo for endoscopic improvement. For mucosal healing all therapies were superior to placebo, except risankizumab. Upadacitinib 30 mg showed the highest efficacy (RR 4.01, 95% CI: 1.81-8.87). Conclusions: Biologic and small-molecule therapies demonstrated substantial efficacy in achieving key endpoints. Standardized outcome definitions and further head-to-head RCTs are essential to strengthen confidence in our findings.

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IntroductionInterleukin (IL)-12/23 and IL-23 inhibitors have emerged as promising therapeutic options for moderate-to-severe Crohn's disease (CD), but comparative data between agents remain limited. This study aimed to assess and rank the efficacy of IL-12/23 and IL-23 inhibitors across key clinical and endoscopic outcomes using network meta-analysis.MethodsWe included randomized controlled trials (RCTs) evaluating IL-12/23 (ustekinumab) and IL-23 inhibitors (risankizumab, mirikizumab, guselkumab, briakinumab, and MEDI2070) versus placebo or each other in adult patients with moderate-to-severe CD. Primary outcomes included clinical and endoscopic remission (assessed at the end of the induction and maintenance phases) and corticosteroid-free clinical remission (assessed at the end of the maintenance phase). Risk ratios (RRs) were estimated using a random-effects model. All analyses were conducted in R using the netmeta package. Surface under the cumulative ranking curve (SUCRA) analysis was used to rank treatments across these endpoints.ResultsFourteen RCTs involving 4,464 patients during the induction phase and 2,601 patients during the maintenance phase were included. Guselkumab achieved the highest clinical remission rate compared to placebo at the end of both the induction phase (RR = 2.62; 95% confidence interval [CI], 2.03-3.39; SUCRA: 91%) and the maintenance phase (RR = 2.37; 95% CI, 1.64-3.42; SUCRA: 85%). In addition, guselkumab was superior to mirikizumab in terms of clinical remission at the end of the induction phase (RR = 1.66; 95% CI, 1.16-2.37). Guselkumab was also the most effective agent for achieving corticosteroid-free clinical remission compared to placebo (RR = 3.06; 95% CI, 1.52-6.16; SUCRA: 78%) at the end of the maintenance phase. Mirikizumab achieved the highest endoscopic remission rate compared to placebo at the end of both the induction phase (RR = 3.52; 95% CI, 1.50-8.27; SUCRA: 78%) and the maintenance phase (RR = 5.84; 95% CI, 2.76-12.37; SUCRA: 88%). Furthermore, mirikizumab, guselkumab, and risankizumab were superior to ustekinumab in terms of endoscopic remission at the end of the maintenance phase.ConclusionsThese findings suggest that guselkumab may be a potential first-line therapy for patients presenting with predominant clinical symptoms, offering the additional benefit of reducing corticosteroid use and its associated long-term risks. Conversely, mirikizumab may be the preferred option for patients with persistent mucosal inflammation, owing to its superior efficacy in achieving endoscopic remission.

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