Search in the Abstract Database

Abstracts Search 2014

* = Presenting author

P547. Biological agents for moderately-to-severely active ulcerative colitis in adults: a network meta-analysis of randomized controlled trials

S. Danese1, G. Fiorino1, L. Peyrin-Biroulet2, E. Lucenteforte3, G. Virgili4, L. Moja5,6, S. Bonovas7, 1Humanitas Research Hospital, IBD Center, Rozzano, Milan, Italy, 2Nancy University Hospital, Université de Lorraine, Gastroenterology and Hepatology, Vandoeuvre-les-Nancy, France, 3University of Florence, Department of Neurosciences, Psychology, Drug Research and Child Health, Florence, Italy, 4University of Florence, Department of Specialised Surgical Sciences, Florence, Italy, 5IRCCS Galeazzi Orthopedic Institute, Unit of Clinical Epidemiology, Milan, Italy, 6University of Milan, Department of Biomedical Sciences for Health, Milan, Italy, 7IRCCS Mario Negri Institute for Pharmacological Research, Laboratory of Drug Regulatory Policies, Milan, Italy

Background

Biological agents are emerging treatment options for the management of ulcerative colitis (UC). No head-to-head RCT are available to compare efficacy and safety of biologics in UC.

We aimed to assess the comparative efficacy and safety of biologics in naïve adult patients with moderate-to-severe UC.

Methods

We performed a literature research from MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov electronic databases, and the European Medicines Agency and U.S. Food and Drug Administration websites. We selected all randomized, placebo-controlled or head-to-head trials assessing biological agents, which have received regulatory approval for the treatment of UC or are under scrutiny, as induction and/or maintenance therapy for moderate-to-severe UC. Endpoints were clinical response (primary), clinical remission and mucosal healing, at the end of induction and at completion of maintenance phase, and the occurrence of serious adverse events (SAEs). Data specific to naïve patients were extracted. A Bayesian network meta-analysis was performed to compare indirectly efficacy and safety of biologics in UC.

Results

Eight randomized, double-blind, placebo-controlled trials (3 adalimumab, 2 golimumab, 2 infliximab, 1 vedolizumab) were included. Our Bayesian network meta-analysis did show that biologics have superior clinical efficacy compared with placebo (p < 0.05 for all agents, in most outcomes). We found that naïve patients treated with infliximab or vedolizumab are more likely to have a favorable clinical response compared to adalimumab (OR 2.35 and 1.83, respectively, p < 0.05), or golimumab (OR 1.96 and 1.53, respectively, p < 0.05). Subjects treated with infliximab (OR = 2.79), vedolizumab (OR = 2.39), or golimumab (OR = 1.52) are more likely to mantain clinical remission compared to adalimumab (all p < 0.05). Greater mucosal healing was demonstrated for infliximab when compared to adalimumab (OR = 2.02, p < 0.05) or to golimumab (OR = 1.81, p < 0.05). High uncertainity results from the comparison between infliximab and vedolizumab for clinical response and remission (OR = 1.28, 95% CrI: 0.48–3.46 for response, and OR = 1.17, 95% CrI: 0.21–6.22, all p < 0.05) for remission. No significant differences were found between all biologics compared to placebo, and among the biologics themselves.

The estimated probability that either of infliximab or vedolizumab is the most efficacious treatment is 99% for induction, and 83% for maintenance of clinical response. Regarding the occurrence of SAEs, our data did not show significant differences among the four agents.

Conclusion

Among biologics, infliximab or vedolizumab seem to be the most preferable treatment options for UC patients naïve to biologics. All biologics result to be generally safe.