Objective While infliximab combined to thiopurines is more effective than infliximab monotherapy in patients with Crohn’s disease (CD) and UC, the impact of adding thiopurines to vedolizumab remains controversial. We emulated two target trials comparing the effectiveness of combination therapy versus vedolizumab monotherapy in CD and UC.
Design Based on two US and the French nationwide healthcare databases, patients with CD and UC who initiated vedolizumab were identified. The study methodology, including confounding adjustment and outcome definitions, were previously validated in successful emulations of the SONIC and SUCCESS trials. Risk ratios for treatment failure based on hospitalisation or surgery related to disease activity, treatment switch, or prolonged corticosteroids use, were estimated after 1:1 propensity score (PS) matching.
Results Among a total of 10 299 vedolizumab users, 804 CD and 1088 UC pairs of combination therapy versus vedolizumab monotherapy users were PS matched. Treatment failure occurred at week 26 in 236 (29.3%) and 376 (34.3%) patients with CD and at week 16 in 236 (21.7%) and 263 (24.2%) patients with UC initiating combination therapy and vedolizumab monotherapy, respectively. The risk of treatment failure was decreased with combination therapy compared with vedolizumab monotherapy in CD (RR 0.85, 95% CI: 0.74 to 0.98) and to a lesser extent in UC (RR 0.90, 95% CI: 0.77 to 1.05). Findings were consistent across databases.
Conclusion Using validated methodologies, combination therapy with vedolizumab and thiopurines was associated with lower treatment failure compared with vedolizumab monotherapy in CD but not UC across the USA and France.
- INFLAMMATORY BOWEL DISEASE
- CROHN'S DISEASE
- ULCERATIVE COLITIS
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information. Not applicable.
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Contributors JK is the guarantor of the article. He had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: JK, SS and SCK. Acquisition, analysis or interpretation of data: All authors. Drafting of the manuscript: JK. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: JK, SS and SCK. Supervision: JK, SS and SCK.
Funding The investigators conducted the research independently through funding from internal sources of the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School. JK received research support (Robert Tournut 2019 grant) from the French National Society of Gastroenterology (SNFGE).
Competing interests JK received research support from the French National Society of Gastroenterology (SNFGE) and has received consulting fees from Roche and Pfizer, and research support from Abbvie for unrelates studies. RJD has received research support to the Brigham and Women’s Hospital from Novartis, Vertex and Bayer for unrelated studies. LB has received consulting fees from Janssen, Pfizer and Allergan, lecture fees from Abbvie, Janssen, MSD, Ferring Pharmaceuticals, Mayoly-Spendler, Takeda and Tillots, and research support from Abbott, Ferring Pharmaceuticals, Hospira-Pfizer, Janssen, MSD, Takeda and Tillots for unrelated studies. SS is participating in investigator-initiated grants to the Brigham and Women’s Hospital from Bayer, Vertex and Boehringer Ingelheim unrelated to the topic of this study. He is a consultant to Aetion, a software manufacturer of which he owns equity. SCK has received research support to the Brigham and Women’s Hospital from Roche, AbbVie and Bristol-Myers Squibb for unrelated studies.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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