Efficacy and Safety of Biological Therapy for Treating Adults With Moderate-Severe Crohn's Disease: A Systematic Review and Network Meta-Analysis

OBJECTIVES: The initial therapeutic approach for Crohn's, a chronic inflammatory bowel disease, typically involves immunosuppressants, aminosalicylates, corticosteroids. However, 30-45% cases are resistant to first-line treatments, thus requiring the use of add-on biologics (e.g., infliximab, adalimumab, certolizumab, vedolizumab, ustekinumab). Our aim was to synthesize the evidence on the efficacy and safety of these drugs in Crohn's disease.

METHODS: A systematic review was perfomed with searches in PubMed, Scopus, Web of Science (February-2024). Randomized controlled trials evaluating biological drugs for the induction of remission in adult patients with moderate to severe Crohn's disease were included. For each outcome of interest [disease remission and serious adverse events (SAE)], data were pooled using network meta-analysis with p-score analysis. The results were presented as risk ratio with 95% credibility intervals (NMAstudio-v.2). The certainty of evidence was rated using CINeMA.

RESULTS: Overall, 39 trials (n=10,561) (1997-2023) assessing 23 biologic drugs across 79 different dosages were included. Alongside infliximab 5mg/kg (p-score probabilities of 95%) and 10mg/kg (85%), recently approved drugs such as mirikizumab 600mg (90%), guselkumab 200mg (87%) and 600mg (86%) presented higher probabilities of disease remission. Adalimumab 80-160mg (81%), vedolizumab 300mg (72%) and ustekizumab 6mg/kg (69%) presented an intermediate effect. Certolizumab 200 mg (25%) and 400 mg (44%), and fontolizumab 0.1mg/kg (11%) ranked last for this outcome. Certolizumab also presented a worse safety profile with high probabilities of causing SAE (around 75%), while mirikizumab 600mg (45%) and guselkmab 200 mg (41%) and 60mg (51%) were considered safer alternatives. Vedolizumab 300mg (53%) and ustekizumab 6 mg/kg (45%) presented moderate rates of SAE.

CONCLUSIONS: Moderate-to-high quality evidence highlight new inhibitors of interleukin-23 as more promising alternatives for the treatment of Crohn's disease. Given their safety profile, some anti-TNF drugs should be avoided in clinical practice. Other important factors, such as drugs’ access and costs, should be considered for this decision.