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The article by Ransford and Langman (Gut 2002;51:536–9) on suspected serious adverse drug reactions for sulphasalazine and mesalazine reported in the UK from 1991 to 1998 revealed significant differences between both drugs.
Pancreatitis and interstitial nephritis were reported more frequently for mesalazine in comparison with sulphasalazine. The authors’ conclusion that mesalazine would not offer a safety benefit over sulphasalazine however appears unjustified for several reasons.
Sulphasalazine is an older compound used for the treatment of both rheumatoid arthritis and inflammatory bowel disease (IBD). For 30 years, the adverse event (AE) profile of sulphasalazine has been well known.1 It often induces oligoteratozoospermia in male patients and frequently causes nausea, vomiting, headache, and folic acid deficiency. Although not “serious” AEs, these often lead to low compliance, incorrect use, and early discontinuation. In addition, it is more than likely that the many adverse reactions, identified in the 1970s, were not reported again to the medical authorities in the 1990s. The introduction of mesalazine in the 1980s enabled effective treatment (often at higher doses) without the numerous adverse effects attributed to the sulphapyridine moiety of sulphasalazine.2 Focus on the risk of interstitial nephritis caused by mesalazine preparations in the mid 1990s undoubtedly led to a low threshold for reporting. However, the incidence of renal insufficiency was recently studied in a large cohort of 1449 European IBD patients (more than 70% on mesalazine/sulphasalazine) and did not exceed the expected incidence in the general population.3
Furthermore, pooling the data of all pure mesalazine products (Gut 2002;51:536–9) does not seem appropriate as the different release mechanisms of the various products could bring about different AE profiles. Pentasa has less frequently been associated with interstitial nephritis than other 5-ASAs.4
Unlike Pentasa, Asacol, Claversal, and Salofalk indeed have a relative dose dumping effect with higher peak serum concentrations, allegedly contributing to potential nephrotoxicity.5
In addition, reporting serious AEs in relation to the number of prescriptions is an unusual approach. Dosage and duration of therapy would have been more relevant as the risk of side effects is dose dependent with sulphasalazine but not with mesalazine. Physicians may prefer to prescribe mesalazine to patients who are susceptible to side effects caused by sulphasalazine. For some reason, adverse events with a fatal outcome were not mentioned separately in Ransford and Langman’s report (Gut 2002;51:536–9). Based on the British CSM database, 18 fatal events occurred in patients taking sulphasalazine versus 12 in the pooled pure mesalazine group during the same observation period. Moreover, the mortality rate for Pentasa was zero in an earlier French pharmacovigilance report, revealing an incidence of reported adverse events with this product (the most commonly used mesalazine preparation in France with a market share >70%) of 6–9 per million days of therapy.6
In conclusion, based on all the available data on mortality, serious irreversible adverse events, and tolerability of both drugs, mesalazine should be preferred to sulphalsalzine in the treatment of IBD. Eighty per cent of patients intolerant to sulphasalazine will tolerate mesalazine without problems.7–9
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