Risk Prediction and Comparative Efficacy of Anti-TNF vs Thiopurines, for Preventing Postoperative Recurrence in Crohn's Disease: A Pooled Analysis of 6 Trials
Evelien Beelen, Daan Nieboer, Jeanine Arkenbosch, Miguel Regueiro, Jack Satsangi, Sandro Ardizzone, Antonio López–Sanromán, Edoardo Savarino, Alessandro Armuzzi, C. Janneke van der Woude, Annemarie C. de Vries
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.