M Pascua1, C Su, J D Lewis, C Brensinger, G R Lichtenstein. 1. Division of Gastroenterology, Department of Medicine, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. monina.pascua@uphs.upenn.edu
Abstract
BACKGROUND: The use of placebo in randomized clinical trials (PC-RCTs) is often required to evaluate drug efficacy in maintenance of Crohn's disease (CD). AIM: To determine pooled estimates of placebo rates of maintaining clinical remission and endoscopic recurrence following surgery for CD and identify factors that influenced placebo outcomes. METHODS: We performed a systematic review and meta-analysis of PC-RCTs evaluating post-operative maintenance therapies for CD identified from MEDLINE from 1966 to 2005. RESULTS: Twelve studies met our inclusion criteria. The pooled placebo rate of maintaining clinical remission was 56% (95% CI 47-64%; range 34-89%) during a median follow-up of 52 weeks (range 12-156 weeks), but significant heterogeneity existed among the studies (P < 0.001). Prior steroid therapy was the only factor found to be associated with maintaining remission (P = 0.04). The pooled placebo endoscopic recurrence rate was 58% (95% CI 51-65%; range 36-80%) during a median follow-up of 52 weeks (range 12-156 weeks), with significant heterogeneity noted (P = 0.0003). Prior surgery, concomitant small bowel and colonic disease, fistulizing phenotype, or prior immunomodulator therapy influenced endoscopic recurrence (P < 0.05). CONCLUSION: Placebo rates in PC-RCTs evaluating post-operative clinical and endoscopic recurrence demonstrate significant variability, which is influenced by specific study characteristics.
BACKGROUND: The use of placebo in randomized clinical trials (PC-RCTs) is often required to evaluate drug efficacy in maintenance of Crohn's disease (CD). AIM: To determine pooled estimates of placebo rates of maintaining clinical remission and endoscopic recurrence following surgery for CD and identify factors that influenced placebo outcomes. METHODS: We performed a systematic review and meta-analysis of PC-RCTs evaluating post-operative maintenance therapies for CD identified from MEDLINE from 1966 to 2005. RESULTS: Twelve studies met our inclusion criteria. The pooled placebo rate of maintaining clinical remission was 56% (95% CI 47-64%; range 34-89%) during a median follow-up of 52 weeks (range 12-156 weeks), but significant heterogeneity existed among the studies (P < 0.001). Prior steroid therapy was the only factor found to be associated with maintaining remission (P = 0.04). The pooled placebo endoscopic recurrence rate was 58% (95% CI 51-65%; range 36-80%) during a median follow-up of 52 weeks (range 12-156 weeks), with significant heterogeneity noted (P = 0.0003). Prior surgery, concomitant small bowel and colonic disease, fistulizing phenotype, or prior immunomodulator therapy influenced endoscopic recurrence (P < 0.05). CONCLUSION: Placebo rates in PC-RCTs evaluating post-operative clinical and endoscopic recurrence demonstrate significant variability, which is influenced by specific study characteristics.
Authors: Christopher Andrew Lamb; Nicholas A Kennedy; Tim Raine; Philip Anthony Hendy; Philip J Smith; Jimmy K Limdi; Bu'Hussain Hayee; Miranda C E Lomer; Gareth C Parkes; Christian Selinger; Kevin J Barrett; R Justin Davies; Cathy Bennett; Stuart Gittens; Malcolm G Dunlop; Omar Faiz; Aileen Fraser; Vikki Garrick; Paul D Johnston; Miles Parkes; Jeremy Sanderson; Helen Terry; Daniel R Gaya; Tariq H Iqbal; Stuart A Taylor; Melissa Smith; Matthew Brookes; Richard Hansen; A Barney Hawthorne Journal: Gut Date: 2019-09-27 Impact factor: 23.059
Authors: Maryam Alkhatry; Ahmad Al-Rifai; Vito Annese; Filippos Georgopoulos; Ahmad N Jazzar; Ahmed M Khassouan; Zaher Koutoubi; Rahul Nathwani; Mazen S Taha; Jimmy K Limdi Journal: World J Gastroenterol Date: 2020-11-21 Impact factor: 5.742