The antirheumatoid activity of sulphasalazine and sulphapyridine may result from their antibacterial properties. The second line activity of sulphamethoxazole, in the form of cotrimoxazole (CTZ), has been investigated by treatment of 13 patients with RA for 24 weeks with CTZ (480 mg three times a day). The drug was found to be poorly tolerated, only five of the thirteen patients recruited completing the study. High circulating concentrations of sulphamethoxazole were found, with mean (SD) steady state serum concentrations reaching 54.02 (23.38) micrograms/ml. A significant reduction in serum IgM from 280 to 130 IU/l was observed, but otherwise disease activity remained unchanged or deteriorated throughout the course of the study. In contrast, patients with RA treated with sulphapyridine (1.25 g a day) showed improvement in disease activity. The results argue against an antibacterial mechanism of action for sulphasalazine and sulphapyridine in rheumatoid arthritis, unless this occurs at a site inaccessible to sulphamethoxazole.
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