Meta-analysis: factors predicting post-operative recurrence with placebo therapy in patients with Crohn's disease.
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).


OBJECTIVE
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).


CONCLUSIONS
Placebo rates in PC-RCTs evaluating post-operative clinical and endoscopic recurrence demonstrate significant variability, which is influenced by specific study characteristics.
Pascua
M
M
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
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Lewis
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Brensinger
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Lichtenstein
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GR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003424:Crohn Disease / Q000601:surgery*; D003627:Data Interpretation, Statistical; D004724:Endoscopy / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012074:Remission Induction / Q000379:methods; D012720:Severity of Illness Index; D016896:Treatment Outcome
D010919:Placebos