Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn's disease (PISA-II): a patient preference randomised trial.

Autor:	Meima-van Praag EM; Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands., van Rijn KL; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands., Wasmann KATGM; Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands., Snijder HJ; Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands., Stoker J; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands., D'Haens GR; Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands., Gecse KB; Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands., Gerhards MF; Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands., Jansen JM; Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands., Dijkgraaf MGW; Department of Epidemiology and Data Science, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands., van der Bilt JDW; Department of Surgery, Flevoziekenhuis, Almere, Netherlands., Mundt MW; Department of Gastroenterology and Hepatology, Flevoziekenhuis, Almere, Netherlands., Spinelli A; Department of Biomedical Sciences, Humanitas University, IRCCS Humanitas Research Hospital, Milan, Italy., Danese S; Department of Gastroenterology and Endoscopy, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy., Bemelman WA; Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands; Department of Gastroenterology and Endoscopy, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy., Buskens CJ; Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands. Electronic address: c.j.buskens@amsterdamumc.nl.
Jazyk:	angličtina
Zdroj:	The lancet. Gastroenterology & hepatology [Lancet Gastroenterol Hepatol] 2022 Jul; Vol. 7 (7), pp. 617-626. Date of Electronic Publication: 2022 Apr 12.
DOI:	10.1016/S2468-1253(22)00088-7
Abstrakt:	Background: Guidelines on Crohn's perianal fistulas recommend anti-tumour necrosis factor (TNF) treatment and suggest considering surgical closure for patients with surgically amenable disease. However, long-term outcomes following these two strategies have not been directly compared. The aim of this study was to assess radiological healing in patients who received short-term anti-TNF treatment and surgical closure compared with those who received anti-TNF treatment alone. Methods: The PISA-II trial was a multicentre, patient preference study done in nine hospitals in the Netherlands and one hospital in Italy. Adult patients with Crohn's disease and an active high perianal fistula with a single internal opening were eligible for inclusion. After counselling, patients with no treatment preference were randomly assigned (1:1) using random block randomisation (block sizes of six without statification), to 4-month anti-TNF therapy and surgical closure or anti-TNF therapy for 1 year, after seton insertion. Patients with a treatment preference received their preferred therapy. The primary outcome was radiological healing assessed by MRI at 18 months, defined as a complete fibrotic tract or a MAGNIFI-CD (Magnetic Resonance Index for Fistula Imaging in Crohn's Disease) score of 0, assessed according to the intention-to-treat principle. Secondary outcomes included clinical closure, number of patients undergoing surgical reintervention and number of reinterventions, recurrences, and impact on quality of life measured by the Perianal Disease Activity Index (PDAI). Analyses were performed on an intention-to-treat basis and additionally an as-treated analysis for radiological healing and clinical closure. This study was registered at the Dutch Trial Registry, NL7625, and with EudraCT, 2018-002064-15, and is closed to accrual due to completion. Findings: Between Sept 14, 2013, and Dec 7, 2019, 94 patients were enrolled onto the trial, of whom 32 (34%) were randomly assigned and 62 (66%) chose a specific treatment. 38 (40%) patients were assigned to the surgical closure group and 56 (60%) patients to the anti-TNF group. At 18 months, radiological healing was significantly more common in the surgical closure group (12 [32%] patients) than in the anti-TNF group (five [9%] patients; p=0·005). By contrast, clinical closure was not significantly different between the two treatment groups (26 [68%] patients in the surgical closure group vs 29 [52%] patients in the anti-TNF group; p=0·076). Significantly fewer patients required a reintervention in the surgical closure group than in the anti-TNF therapy group (five [13%] patients in the surgical closure group, median one reintervention [IQR one to three] vs 24 [43%] patients in the anti-TNF group, median two reinterventions [one to two]; p=0·005). Among patients who reached clinical closure during follow-up, four (14%) of 29 in the surgical closure group and five (16%) of 31 in the anti-TNF therapy group had a recurrence, which occurred only in patients without radiological healing. PDAI was significantly lower in the surgical closure group than in the anti-TNF group after 18 months (p=0·031). Adverse events and serious adverse events were similar in both treatment groups and mostly entailed reinterventions. Ten (11%) patients had side-effects associated with anti-TNF treatment. Two serious adverse events unrelated to study treatment occurred (appendicitis and myocardial infarction). One patient died from a tongue base carcinoma, unrelated to study treatment. Interpretation: Short-term anti-TNF treatment combined with surgical closure induces long-term MRI healing more frequently than anti-TNF therapy in patients with Crohn's perianal fistulas. These data suggest that patients with Crohn's perianal fistula amenable for surgical closure should be counselled for this therapeutic approach. Funding: Netherlands Organisation for Health Research and Development and Broad Medical Research Program. Competing Interests: Declaration of interests GRD'H reports grants from Arena Pharmaceuticals, Bristol Myers Squibb, Celltrion, Eli Lilly, Galapagos, Pfizer, Johnson & Johnson, Procise Diagnostics, Prometheus laboratories, Prometheus Biosciences, and Progenity; consulting fees from AbbVie, Agomab, AstraZeneca, AM Pharma, AMT, Arena Pharmaceuticals, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Exo Biologics, Galapagos, Index Pharmaceuticals, Kaleido, Roche, Gilead, GlaxoSmithKline, Gossamerbio, Pfizer, Immunic, Johnson & Johnson, Origo, Polpharma, Procise Diagnostics, Prometheus Laboratories, Prometheus Biosciences, Progenity, Protagonist; and speaker's honoraria from AbbVie, Merck Sharp & Dohme, Tillotts, Janssen, Takeda, Pfizer, and Bristol Myers Squibb. GRD'H participated on a Data Safety Monitoring Board or Advisory Board for Galapagos, Astrazeneca, and AbbVie. KBG reports grants from Pfizer, Galapagos, and Celltrion; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, ImmunicTherapeutics, Janssen Pharmaceuticals, Novartis, Pfizer, Samsung Bioepis, and Takeda; consulting fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Novartis, Pfizer, Samsung Bioepis, and Takeda; and speaker's honoraria from Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer, Samsung Bioepis, Takeda, and Tillotts. SD reports consulting fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZaneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, and Vifor. WAB has served as speaker for Takeda, Johnson & Johnson, and Braun; and reports research grants from Braun and Vifor. CJB has an unrestricted grant from Boehringer Ingelheim and Roche; reports consultancy fees or speaker's honoraria from AbbVie, Merck Sharp & Dohme, Tillotts, Janssen, and Takeda. All other authors declared no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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