Indirect comparison of vedolizumab and adalimumab for biologic-naive patients with ulcerative colitis

Abstract

Aim: Indirect comparison of efficacy and safety of vedolizumab with adalimumab in biologic-naïve patients with moderate to severe ulcerative colitis (UC).

Methods: Vedolizumab is a gut-selective medication for moderate to severe UC. Since no comparative trials are available for direct comparison of vedolizumab vs adalimumab in UC, a systematic review of literature databases was conducted to identify randomized, placebo-controlled trials of the two drugs in patients with moderate to severe UC after failure of conventional treatment. Studies were screened for eligibility by two reviewers based on predefined inclusion criteria. Bucher’s adjusted indirect comparison was used to compare vedolizumab and adalimumab indirectly through placebo as common comparator.

Results: One vedolizumab study (GEMINI 1) and three adalimumab studies (ULTRA 1, ULTRA 2 and M10-447) met the eligibility criteria. Baseline characteristics of the included populations were similar in biologic-naïve UC patients across study arms. Although no statistically significant differences between treatments were found for induction efficacy endpoints, there was a trend toward a benefit of vedolizumab over adalimumab. There were also no significant differences between treatments for any maintenance efficacy endpoints, with no clear trend favoring either agent. Vedolizumab exhibited statistically superior maintenance safety compared with adalimumab, with significant reductions in risks of adverse events (relative risk 0.67 [95% confidence interval 0.57–0.80]; p < .0001), serious adverse events (0.20 [0.09–0.42]; p < .0001) and adverse events leading to discontinuation (0.14 [0.05–0.43]; p = .0006).

Conclusion: This analysis indicates that vedolizumab has comparable efficacy to adalimumab with improved safety in biologic-naïve patients with moderate to severe UC.

Trial registration: ClinicalTrials.gov identifier: NCT02497469.

Keywords:

• Vedolizumab
• adalimumab
• α4β7 integrin
• Bucher’s adjusted indirect comparison
• biologic naïve
• ulcerative colitis

Disclosure statement

Axel U. Dignass served as consultant for Boehringer Ingelheim, Celgene, Robarts, Roche/Genentech and Sandoz/Hexal; served as consultant for and received payment for development of educational presentations from Pharmacosmos; served as consultant for, and received payment for development of educational presentations and speaker fees from Falk Foundation; served as consultant for and received manuscript fees from Allergosan and Takeda; served as consultant for and received speaker fees from AbbVie, Ferring, Hospira, Janssen, MSD, Mundipharma, Pfizer, Vifor, Celgene and Takeda; received payment for development of educational presentations and speaker fees from Tillots; received manuscript fees from Thieme and Wiley; received research grants from Institut für Gemeinwohl and Stiftung Leben mit Krebs; and received speaker fees from Immundiagnostik, Med Update GmbH, Medice and Otsuka. Britta Siegmund served as consultant for and received speaker fees from AbbVie, Falk Foundation, Hospira, Janssen, MSD and Takeda; received a research grant from Pfizer; and received speaker fees from Ferring (all payments were made to Charité–Universitätsmedizin Berlin). Ralf Goertz is an employee of AMS Advanced Medical Services GmbH, which received funding from Takeda to perform this meta-analysis. Gundula Schneidewind and Lena Fanter are employees of Takeda.

Data sharing statement

No additional data are available.

Core tip: This adjusted indirect comparison provides initial clinical evidence for the relative efficacy and safety of vedolizumab compared with adalimumab, specifically in biologic-naïve patients with moderate to severe UC after failure of conventional treatment. The results show that vedolizumab treatment offers the benefit of comparable induction and maintenance efficacy, while providing an improved safety profile compared with adalimumab during the first year of therapy. These comparative results between vedolizumab and adalimumab on patient-relevant outcomes in biologic-naïve patients with moderate to severe UC may facilitate treatment decision-making while we await head-to-head clinical trial data.

Additional information

Funding

Medical writing support was provided by BioScience Communications and AMS Advanced Medical Services GmbH, both supported by Takeda Pharmaceuticals International Co. Serap Sankoh (former Takeda employee) was the statistician who provided the post-hoc GEMINI 1 tables.

Notes on contributors

Axel U. Dignass

Dignass AU, Siegmund B, Goertz R, Schneidewind G, Fanter L: substantial contributions to conception and design of the study, acquisition of data and analysis and interpretation of data; drafting the article and making critical revisions related to important intellectual content of the manuscript and final approval of the version of the article to be published.

Britta Siegmund

Dignass AU, Siegmund B, Goertz R, Schneidewind G, Fanter L: substantial contributions to conception and design of the study, acquisition of data and analysis and interpretation of data; drafting the article and making critical revisions related to important intellectual content of the manuscript and final approval of the version of the article to be published.

Ralf Goertz

Dignass AU, Siegmund B, Goertz R, Schneidewind G, Fanter L: substantial contributions to conception and design of the study, acquisition of data and analysis and interpretation of data; drafting the article and making critical revisions related to important intellectual content of the manuscript and final approval of the version of the article to be published.

Gundula Schneidewind

Dignass AU, Siegmund B, Goertz R, Schneidewind G, Fanter L: substantial contributions to conception and design of the study, acquisition of data and analysis and interpretation of data; drafting the article and making critical revisions related to important intellectual content of the manuscript and final approval of the version of the article to be published.

Lena Fanter

Dignass AU, Siegmund B, Goertz R, Schneidewind G, Fanter L: substantial contributions to conception and design of the study, acquisition of data and analysis and interpretation of data; drafting the article and making critical revisions related to important intellectual content of the manuscript and final approval of the version of the article to be published.