Effect of acetylator phenotype on efficacy and toxicity of sulphasalazine in rheumatoid arthritis.

A group of 54 patients with rheumatoid arthritis (31 fast, 23 slow acetylators) treated with sulphasalazine 3 g/day were studied retrospectively. At 24 weeks no difference in the efficacy of the drug could be shown between fast and slow acetylators. In a second prospective study 40 fast acetylators were allocated to 3 g/day and 20 slow acetylators to 1.5 g/day. At 24 weeks marked improvement was seen in the fast acetylators given high dose but not the slow acetylators given low dose. It was also noted in this study that the usual ratio of fast : slow acetylators was reversed, and there is some suggestion that fast acetylators may be predisposed to more severe rheumatoid arthritis. The toxicity pattern in a total of 149 patients (83 fast, 66 slow acetylators) was also studied. Significantly more slow acetylators stopped treatment because of nausea or vomiting, or both, but serious toxicity was not confined to either group. Acetylator phenotype therefore appears important in determining the incidence of nausea and/or vomiting associated with sulphasalazine therapy in patients with rheumatoid arthritis but has no effect on the occurrence of potentially serious toxicity or efficacy. Thus prior measurement of acetylator phenotype in patients with rheumatoid arthritis confers little practical benefit in their management.