Smoking and Early Infliximab response in Crohn's disease: a Meta-analysis
BACKGROUND: Infliximab (IFX) is used to treat moderate to severe Crohn's disease (CD), but efficacy varies. Although cigarette smoking worsens CD, its impact on IFX response is unknown. We conducted a systematic review and meta-analysis of clinical trials to determine the effect of smoking on induction response to IFX. METHODS: A systematic search was performed of MEDLINE, EMBASE, CINAHL, Cochrane central register of controlled trials, Cochrane IBD Group Specialized Trials Register for publications and abstracts from major conferences from 1/1996 to 12/2010. Random effects meta-analysis using Mantel-Haenszel method was conducted. Heterogeneity across studies was assessed using Q statistic, I2 statistic, and tau-squared (tau2). RESULTS: We identified 12 articles; 4 were excluded due to use of non-validated scoring systems. The remaining 8 totaled 1,658 patients, with 649 active smokers. Luminal response was assessed by CDAI in 4 studies (3 of which included fistula response), Harvey-Bradshaw Index in 2 (both including fistula response), while 2 studies examined only fistula response. The relative risk (RR) for response to IFX among smokers was 0.99 (95% CI: 0.88 to 1.11) (tau2 = 0.0143). Analysis of the 5 studies examining both inflammatory and fistulizing CD were similar to the analysis of all 8 studies. The pooled RR was 0.92 (95% CI: 0.80 to 1.06) (tau2=0.0154). CONCLUSION: Though smoking worsens CD, this meta-analysis does not show a negative effect of smoking on initial response to IFX. This must be viewed in the proper context, as long term maintenance of response may yet be influenced by smoking status.