A combined clinical and immunological assessment of four cyclophosphamide regimes in rheumatoid arthritis.

Four dosage regimes of cyclophosphamide have been compared in patients with late rheumatoid arthritis, in an attempt to separate toxicity from efficacy. Joint inflammation was assessed clinically and objectively by quantitative thermography. Delayed hypersensitivity in vitro was assessed using leucocyte migration inhibition (L.M.T.) to a standard antigen, Streptokinase. There was no significant difference in clinical response or side-effects between a continuous oral regime (1 mg/kg/day) and the same total dose given as an intermittent oral regime. Responders and non-responders were seen in both groups and there was a significant relationship between clinical response and fall in platelet count, suggesting a variable threshold. The same total dose given as an intermittent intravenous regime caused considerable side-effects but these could be avoided by the addition of methylprednisolone. Both intravenous regimes induced a much more rapid fall in the Thermographic Index (T.I.) than the oral regimes. Indeed many patients receiving oral cyclophosphamide showed an increase in joint inflammation in the first three weeks of treatment. Immunological studies demonstrated a corresponding increase in reactivity to Streptokinase over this period. There was a highly significant correlation between changes in L.M.T. and T.I. both early in treatment and, in the oral groups, over a period of six months.