Controlled trial of penicillamine in severe rheumatoid arthritis

Abstract

A trial of D(-) penicillamine (Distamine) in severe uncontrolled rheumatoid disease was carried out at five different centres; 105 patients with definite or classical rheumatoid arthritis of at least 2 yr duration and meeting additional criteria of disease severity were admitted. Allocation of patients to penicillamine (52) or control (53) groups was randomized after stratification by age, sex and current use of steroids and the trial was double blind. Measurements included erythrocyte sedimentation rate, Hb, differential agglutination test, pain, morning stiffness, articular index, grip strength, functional index, well being, weight, and x radiology of hands and feet. Results were analysed to show mean improvement, percentage improvement, and the number and proportion of persons who were much, moderately, or at all improved in the various measurements after 3, 6, and 12 mth of treatment. There were no significant differences in the mean scores for each of these measurements between the two treatment groups at the start of the trial, but there were differences in almost all, with advantage to penicillamine, at the conclusion of the study, the differences being of statistically significant degree for erythrocyte sedimentation rate, Hb, morning stiffness, pain, articular index, function index, and grip strength. Adverse reactions were more prevalent amongst the penicillamine group during the first 6 mth of the trial but not during the second. Sixteen patients in the penicillamine group were withdrawn because of drug intolerance but none because of increasing rheumatoid activity. Nine of the controls withdrew because of increasing rheumatoid activity and one because of drug intolerance. Adverse reactions which led to withdrawal included rash, thrombocytopenia, albuminuria, and gastrointestinal upset. Recovery was invariable. Among the patients given penicillamine who had improved at 12 mth most of that improvement was already evident at 3 mth. The clinicians' opinion whether the trial treatment had been, with respect to the patient's rheumatoid disease, 'successful', 'of doubtful value', or 'of no value' was recorded whether the course was completed or not. Of the patients who completed the course, 75% of those on penicillamine and 8% of the controls were judged to have received 'successful' treatment. Similar figures are obtained even when the entire patient population is included. It is evident that penicillamine is effective in severe and advanced rheumatoid disease. Controlled studies of its use in early disease are now indicated.