Non-steroidal anti-inflammatory drugs and the risk of Clostridium difficile-associated disease

Several case reports have linked diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with Clostridium difficile associated disease (CDAD). We assessed whether NSAID use in general, and diclofenac use in particular, is associated with an increased risk of CDAD.

We used the United Kingdom's General Practice Research Database (GPRD) to conduct a population-based case-control study. All cases of CDAD occurring between 1994 and 2005 were identified and were matched to 10 controls each. Conditional logistic regression was used to estimate the odds ratio of CDAD associated with current NSAID use, adjusting for covariates.

We identified 1360 CDAD cases and 13 072 controls. We found an increased risk of CDAD associated with diclofenac (adjusted odds ratio (RR) 1.35, 95% confidence interval (CI) 1.10, 1.67). We did not observe an increased risk of CDAD with use of any other NSAID. No dose-response for diclofenac exposure was found. When we analyzed only patients who were not hospitalized in the year before the index date, we found diclofenac to have a similar effect on CDAD risk (adjusted RR 1.43, 95% CI 1.11, 1.84).

Diclofenac use is associated with a modest increase in the risk of CDAD. In patients at risk of CDAD, other NSAIDs could be prescribed.