Treatment of Perianal Fistulas in Crohn's Disease, Seton Versus Anti-TNF Versus Surgical Closure Following Anti-TNF [PISA]: A Randomised Controlled Trial

Autor: Apollo Pronk, Merel E. Stellingwerf, Karlien F. Bruin, Antonino Spinelli, Silvio Danese, David D. E. Zimmerman, Sebastiaan A.C. van Tuyl, Marcel G. W. Dijkgraaf, Cyriel Y. Ponsioen, Geert R. D'Haens, Jarmila D. W. van der Bilt, Karin A. T. G. M. Wasmann, Christianne J. Buskens, Krisztina B Gecse, E. Joline de Groof, Michael F. Gerhards, Willem A Bemelman, M.W. Mundt, Jeroen M. Jansen
Přispěvatelé: Graduate School, Surgery, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Epidemiology and Data Science, APH - Methodology, Wasmann, Katgm, de Groof, Ej, Stellingwerf, Me, D'Haens, Gr, Ponsioen, Cy, Gecse, Kb, Dijkgraaf, Mgw, Gerhards, Mf, Jansen, Jm, Pronk, A, van Tuyl, Sac, Zimmerman, Dde, Bruin, Kf, Spinelli, A, Danese, S, van der Bilt, Jdw, Mundt, Mw, Bemelman, Wa, Buskens, Cj
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Crohn’s disease
Fistula
Perianal fistula
law.invention
Anti-TNF
Primary outcome
0302 clinical medicine
Crohn Disease
Quality of life
Randomized controlled trial
law
Data monitoring committee
Crohn's disease
Medical treatment
Gastroenterology
General Medicine
Combined Modality Therapy
Outcome and Process Assessment
Health Care
030220 oncology & carcinogenesis
Early Termination of Clinical Trials
Cohort
Drainage
Female
030211 gastroenterology & hepatology
Medical Futility
Adult
Reoperation
medicine.medical_specialty
Randomization
03 medical and health sciences
medicine
Humans
Rectal Fistula
Trial registration
AcademicSubjects/MED00260
Wound Closure Techniques
business.industry
General surgery
Adalimumab
Patient Acuity
Consolidated Standards of Reporting Trials
Original Articles
medicine.disease
Infliximab
Surgery
Clinical trial
Good clinical practice
Quality of Life
Tumor Necrosis Factor Inhibitors
business
Zdroj: Journal of Crohn's & Colitis
Journal of Crohn's & colitis, 14(8), 1049-1056. Elsevier
ISSN: 1873-9946
DOI: 10.1093/ecco-jcc/jjaa004
Popis: Background: Most patients with perianal Crohn's disease fistulas receive medical treatment with anti-TNF. So far, outcomes of anti-TNF have not been directly compared to chronic seton drainage or surgical closure. We hypothesized that chronic seton drainage would result in fewer re-interventions compared to anti-TNF and surgical closure. Methods: This multicentre, randomised trial was performed in 19 European centres. Patients with high perianal Crohn's fistulas with a single internal opening were randomly assigned in a 1:1:1 ratio to chronic seton drainage, long-term anti-TNF therapy, or surgical closure using a central web-based system without stratification. Patients were analysed according to the intention-to-treat principle. The primary outcome was the cumulative number of patients with fistula-related re-intervention(s) at 1.5 year. Patients refusing randomisation due to a specific treatment preference were included in a parallel prospective PISA registry cohort. Findings: Between September 14, 2013 and November 20, 2017, 44 of the 126 planned patients were randomised. The study was stopped by the data safety monitoring board because of futility. Seton treatment was associated with the highest re-intervention rate (10/15, versus 6/15 anti-TNF and 3/14 surgical closure patients, P = 0·02). No substantial differences in perianal disease activity and quality of life between the three treatment groups were observed. Interestingly, in the PISA prospective registry (n = 50), inferiority of chronic seton treatment was not observed for any outcome measure. Interpretation: The results imply that chronic seton treatment should not be recommended as the sole or superior treatment for perianal Crohn's fistulas. However, the statistical inferiority of seton treatment should be interpreted with caution, due to the crucial aspects of small numbers and as this inferiority could not be confirmed in the PISA registry data. Trial Registration Number: The trial is registered with the Dutch Trialregister.nl number NTR4137. Funding Statement: The Netherlands Organization for Health Research and Development and the Crohn and Colitis Foundation. Declaration of Interests: KAW, EJdG, MES, MGD, MFG, JMJ, AP, SAvT, DDZ, KFB, JvdB, MWM, WAB, and CJB have no conflicts of interests to declare. GRD’H has served as advisor for Abbvie, Ablynx, Allergan, Amakem, Amgen, AM Pharma, Arena Pharmaceuticals, AstraZeneca, Avaxia, Biogen, Bristol Meiers Squibb, Boerhinger Ingelheim, Celgene/Receptos, Celltrion, Cosmo, Covidien/Medtronics, Echo Pharmaceuticals, Eli Lilly, Engene, Ferring, DrFALK Pharma, Galapagos, Genentech/Roche, Gilead, Glaxo Smith Kline, Gossamerbio, Hospira/Pfizer, Immunic, Johnson and Johnson, Lycera, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Pfizer/Hospira, Photopill, Prometheus laboratories/Nestle, Progenity, Protagonist, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Seres/Nestle, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant and Vifor; received speaker fees from Abbvie, Biogen, Ferring, Johnson and Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millenium/Takeda, Tillotts and Vifor. CYP has served as adviser for Abbvie, Takeda, and Pliant, declares a grant from Takeda, and received speaker’s fees from Abbvie, Tillotts, and Takeda. KBG has served as speaker and/or advisor for Amgen, AbbVie, Biogen, Boehringer Ingelheim, Ferring, Hospira, MSD, Pfizer, Samsung Bioepis, Sandoz, Takeda and Tigenix. AS has served as speaker and/or advisor for Takeda. SD has served as a speaker, a consultant and an advisory board member for Abbvie, Ferring, Hospira, Johnson & Johnson, Merck, Millennium Takeda, Mundipharma, Pfizer, Tigenix, UCB Pharma, and Vifor. Ethics Approval Statement: The study was performed in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines, and is reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines. The trial received central approval from the medical ethics committee at the Amsterdam UMC, location AMC, and from the corresponding committees in all participating centres.
Databáze: OpenAIRE
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