Indomethacin in rheumatoid arthritis: an evaluation of its anti-inflammatory and side effects.

Since its introduction in 1963 indomethacin (l-(p-chlorobenzoyl)-5-methoxy-2-methylindol-3-acetic acid) has been reported as an analgesic of value in the treatment of osteoarthitis (Hart and Boardman, 1963 ; Wanka et al., 1964; Percy et al., 1964) and ankylosing spondylitis (Katz et al., 1963 ; Hart and Boardman, 1963 ; Smyth and Godfrey, 1964; Percy et al., 1964; Rothermich, 1964; Michotte and Wauters, 1964; Boland, 1964), and as an agent that effectively reduces joint swelling and inflammation in acute gout (Hart and Boardman, 1963 ; Smyth et al., 1963a, 1963b; Michotte and Wauters, 1964; Percy et al., 1964; Norcross, 1963 ; Kass, 1965). Similar though less striking results have been obtained with indomethacin in rheumatoid arthritis (Hart and Boardman, 1963 ; Norcross, 1963; Wanka et al., 1964; Percy et al., 1964; Catoggio et al., 1964; Clark 1964; Rothermich, 1964; Datey, 1964; Smyth et al., 1964; Thompson, 1964; Smyth, 1965; Thompson and Percy, 1966). Kelly (1964a, 1964b) found the Jenefit " often astonishing," while Boland (1964) was unable to demonstrate conclusively any effect of the drug on patients with rheumatoid arthritis. In the treatment of rheumatic fever Vignau et al. (1965) concluded that the advantages of indomethacin were outweighed by its side-effects. A high incidence of side-effects in proportion to therapeutic effect with this drug in rheumatoid arthritis has been observed (Dixon et al., 1963; Boland, 1964; L6vgren and Allander, 1964 ; Percy et al., 1964 ; Boyle, 1965). Percy et al. (1964) had to withdraw 13 out of 21 patients taking 200 mg. each day, and Katz et al. (1965) withdrew 35 out of 97 patients on doses of 100 to 400 mg. a day, for this reason. Hart and Boardman (1963) reported side-effects in 31 out of 52 patients on a daily dose of 50 to 300 mg. Rubens-Duval and Villiaumey (1964) reported 72% side-effects in patients on a daily dose of over 200 mg., and Robinson (1965) could maintain therapy in less than 50% of patients receiving 125 to 150 mg. a day. On the ither hand, Robecchi et al. (1964), using doses of 75 to 150 mg. each day, had only one withdrawal with 28 patients and found that though side-effects were frequent they were not unduly troublesome. These findings indicate that the therapeutic index Of this drug is low. Hart and Boardman (1963) demonstrated no greater efficiency with the higher range of dose and recommended 50-150 mg. as