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• Antibiotic use and the development of Crohn's disease - Methodological issues
  Samy Suissa
  Published on: 18 April 2016

• Published on: 18 April 2016

  Antibiotic use and the development of Crohn's disease - Methodological issues

  • Samy Suissa, Professor and Director
  • Other Contributors:
    • Verena Schneider

  Dear Editor

  Card et al.[1] report that the use of antibiotics could increase the risk of Crohn's disease, particularly those prescribed 2 to 5 years prior to the diagnosis (OR= 1.32; 95% CI 1.05-1.65). As the use of drugs acting on the central nervous system and of other prescription drugs such as oral contraceptives was also associated with the diagnosis of Crohn's disease, the authors concluded that this...

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  Dear Editor

  Card et al.[1] report that the use of antibiotics could increase the risk of Crohn's disease, particularly those prescribed 2 to 5 years prior to the diagnosis (OR= 1.32; 95% CI 1.05-1.65). As the use of drugs acting on the central nervous system and of other prescription drugs such as oral contraceptives was also associated with the diagnosis of Crohn's disease, the authors concluded that this association is nonspecific. Nevertheless, some methodological issues could have had an important impact on the results.

  One methodological aspect of the study design that could have biased the findings is that calendar time was not accounted for properly. This is highlighted by the fact that the median time available prior to the index date, the period during which exposure to antibiotics is measured, was 6.4 years for the cases compared with 8.2 years for the controls. This difference of almost 2 years is due to the fact that the index date was correctly taken to be the date of diagnosis of Crohn’s disease for the cases, but was taken to be the date of the end of data for the controls. Consequently, a case diagnosed in 1992 could potentially be compared with a control whose date of end of data was in 1998. As a result, the odds ratio based on the comparison of cases and controls for exposure to antibiotics may be biased by comparing exposures to antibiotics that may have changed over calendar time. Thus, any trends over time in the patterns of use of antibiotics during the calendar time span of the study, namely the 1990s, would bias the estimate. Such bias cannot be excluded, particularly for an odds ratio as small as 1.32, because neither did the design match the index date on calendar time nor did the data analysis adjust for calendar time. In fact, such widely changing patterns have been observed in this population for oral contraceptive usage after a pill scare in the mid-1990s.[2]

  A second limitation of the study is the unclear accounting of age. On the one hand, there is the issue of matching on age of cases and controls, while on the other there is the issue of adjustment for age in the analysis. First, it is not clear at what time these two ages are measured, and particularly whether age is taken at the index date. We suspect this choice because cases are 2.1 years younger than the controls, which is similar to the difference of almost 2 years in the index dates of cases and controls. Second, the age matching is based on 20-year age bands, which may be too wide to control fully for confounding, unless the precise age was used in adjustment.

  References

  1. Card T, Logan RFA, Rodrigues LC, et al. Antibiotic use and the development of Crohn's disease. Gut 2004; 53:246-50.

  2. Spitzer WO, Lewis MA, Heinemann LAJ, et al. Transnational Research Group on Oral Contraception and the Health of Young Women. Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study. BMJ 1996; 312:83-88.

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  Conflict of Interest:
  None declared.

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