Abstract
Background & Aims: The superiority of anti-TNF-α agents to thiopurines for the prevention of postoperative recurrence of Crohn's disease (CD) after ileocolonic resection remains controversial. In this meta-analysis of individual participant data (IPD), the effect of both strategies was compared and assessed after risk stratification. Methods: After a systematic literature search, IPD were requested from randomized controlled trials investigating thiopurines and/or anti-TNF-α agents after ileocolonic resection. Primary outcome was endoscopic recurrence (ER) (Rutgeerts score ≥i2) and secondary outcomes were clinical recurrence (Harvey-Bradshaw Index/Crohn's Disease Activity Index score) and severe ER (Rutgeerts score ≥i3). A fixed effect network meta-analysis was performed. Subgroup effects were assessed and a prediction model was established using Poisson regression models, including sex, smoking, Montreal classification, CD duration, history of prior resection and previous exposure to anti-TNF-α or thiopurines. Results: In the meta-analysis of IPD, 645 participants from 6 studies were included. In the total population, a superior effect was demonstrated for anti-TNF-α compared with thiopurine prophylaxis for ER (relative risk [RR], 0.52; 95% confidence interval [CI], 0.33–0.80), clinical recurrence (RR, 0.50; 95% CI, 0.26–0.96), and severe ER (RR, 0.41; 95% CI, 0.21–0.79). No differential subgroup effects were found for ER. In Poisson regression analysis, previous exposure to anti-TNF-α and penetrating disease behavior were associated with ER risk. The advantage of anti-TNF-α agents as compared with thiopurines was observed in low- and high-risk groups. Conclusions: Anti-TNF-α is superior to thiopurine prophylaxis for the prevention of endoscopic and clinical postoperative CD recurrence after ileocolonic resection. The advantage of anti-TNF-α agents was confirmed in subgroup analysis and after risk stratification.
Original language | English |
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Pages (from-to) | 2741-2752 |
Journal | Clinical Gastroenterology and Hepatology |
Volume | 20 |
Issue number | 12 |
Early online date | 19 Oct 2021 |
DOIs | |
Publication status | Published - Dec 2022 |
Bibliographical note
Funding Information:Conflicts of Interest These authors disclose the following: Annemarie C. de Vries has received research funding from MLDS, and Tramedico; and has served in the advisory board for Jansen, Takeda, and AbbVie, all outside the submitted work. C. Janneke van der Woude has served on the advisory board for Celltrion, AbbVie, and Takeda, outside the submitted work. Antonio López-Sanromán has lectured for AbbVie, Pfizer, MSD, and Janssen; and has received research grants from AbbVie, MSD, and Janssen. Alessandro Armuzzi has received research grants from MSD, Takeda, and Pfizer; and served on the advisory board for and/or received lecture fees from AbbVie, Allergan, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, and Tigenix. Sandro Ardizzone has served as a speaker, consultant, and/or advisory board member for AbbVie, MSD, Takeda, Janssen, Pfizer, Sandoz, Biogen, and Enthera. Miguel D. Regueiro has served on the advisory board and as a consultant for AbbVie, Janssen, UCB, Takeda, Pfizer, Miraca Labs, Amgen, Celgene, Seres, Allergan, Genentech, Gilead, Salix, Prometheus, Lilly, TARGET Pharma Solutions, ALFASIGMA, S.p.A., and Bristol-Myers Squibb. Edoardo Savarino has received lecture or consultancy fees from AbbVie, Alfasigma, Amgen, Bristol-Myers Squibb, Fresenius Kabi, Grifols, Janssen, Johnson & Johnson, Innovamedica, Merck & Co, Novartis, Reckitt Benckiser, Sandoz, Shire, SILA, Sofar, Takeda, and Unifarco, all outside the submitted work. The remaining authors disclose no conflicts.
Funding Information:
Raw data from this meta-analysis are not publicly available because the data belong to the original studies. Upon request, contact details of the data holders can be shared. Analytical methods can be shared upon reasonable request to the corresponding author. The authors of this meta-analysis would like to acknowledge the contribution of Wichor Bramer, biomedical information specialist of the Erasmus University Medical Center, for performing the systematic literature search. Furthermore, the authors acknowledge the contributions of Giovanni Maconi and Gianluca Sampietro (University Hospital Milan) and Carla Felice (Catholic University of Rome) for their effort and participation in the original studies that are part of the final dataset of this meta-analysis. This study used data from the TOPPIC trial, obtained via the Edinburgh Clinical Trials Unit, situated in the University Court of the University of Edinburgh. This study, carried out under YODA Project #2018-3236, used data obtained from the Yale University Open Data Access Project, which has an agreement with Janssen Research & Development. The interpretation and reporting of research using this data are solely the responsibility of the authors and does not necessarily represent the official views of the Yale University Open Data Access Project or Janssen Research & Development.
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