Toxicity of antirheumatic and anti-inflammatory drugs in children

The aim of the study was to describe the longterm toxicity of antirheumatic and anti-inflammatory drugs in a paediatric rheumatology clinic population. One hundred and seventeen children were studied on first admission to a paediatric rheumatology clinic and after a mean of 8.6 +/- 0.4 years of follow-up. Medical records from the intermediate period were reviewed. The patients had 155 exposures to non-steroidal antiinflammatory drugs (NSAIDs), 88 exposures to disease-modifying antirheumatic drugs (DMARDs) and 12 exposures of prednisolone during a total of 682 patient years. Drug toxicity was measured in terms of the number of toxic events, number of drug discontinuations due to toxicity, number of side-effects per patient year of drug exposure and as a toxicity index. Side-effects were seen in 69 (27%) of the drug exposures, corresponding to 0.10 toxic events per patient year of exposure. Abdominal pain was the most common side-effect, and was reported in 21 (14%) of the exposures to NSAIDs. Five severely toxic events, all leading to hospitalisation, occurred. The toxicity of NSAIDs was not significantly different from that of DMARDs with regard to the number of toxic events (21% and 31%, respectively, NS) and drug discontinuations due to toxicity (17% and 14%, respectively, NS). Piroxicam tended to be more toxic than ibuprofen (46% versus 18% toxic events, p<0.05; 36% versus 16% discontinuations due to toxicity, NS; 0.33 versus 0.05 side-effects per patient year and a toxicity index of 1.45 versus 0.20 units per patient year). Gold tended to be more toxic than antimalarials (41% versus 15% toxic events, p<0.05; 24% versus 12% discontinuations, NS; 0.37 versus 0.08 side-effects per patient year and a toxicity index of 1.56 versus 0.23 units per patient year). It was concluded that antirheumatic and anti-inflammatory drugs led to side-effects in 27% of the exposed children during 9 years of follow-up. There was an overlap of the toxicity of certain NSAIDs and the most commonly employed DMARDs.