[HTML][HTML] Cyclosporine for plaque-type psoriasis: results of a multidose, double-blind trial

CN Ellis, MS Fradin, JM Messana… - … England Journal of …, 1991 - Mass Medical Soc
CN Ellis, MS Fradin, JM Messana, MD Brown, MT Siegel, AH Hartley, LL Rocher, S Wheeler…
New England Journal of Medicine, 1991Mass Medical Soc
Background. Severe plaque-type psoriasis has been successfully treated with orally
administered cyclosporine, but there has been no comparative, controlled evaluation of
various dosages and their efficacy and side effects. Methods. In a 16-week, double-blind
trial, we randomly assigned 85 patients with severe psoriasis to receive 3, 5, or 7.5 mg of
cyclosporine per kilogram of body weight per day or a placebo consisting of the vehicle for
the drug. After eight weeks the dose could be adjusted to improve safety or efficacy while …
Background
Severe plaque-type psoriasis has been successfully treated with orally administered cyclosporine, but there has been no comparative, controlled evaluation of various dosages and their efficacy and side effects.
Methods
In a 16-week, double-blind trial, we randomly assigned 85 patients with severe psoriasis to receive 3, 5, or 7.5 mg of cyclosporine per kilogram of body weight per day or a placebo consisting of the vehicle for the drug. After eight weeks the dose could be adjusted to improve safety or efficacy while maintaining blinding.
Results
The psoriasis improved in a dose-dependent fashion. After eight weeks of fixed-dose therapy, 36, 65, and 80 percent of the patients receiving 3,5, and 7.5 mg of cyclosporine per kilogram per day, respectively, were rated as being clear or almost clear of psoriasis; each group had significant improvement (P<0.0001) as compared with the group receiving vehicle, in which none of the patients were rated as clear or almost clear. The patients who received 5 mg per kilogram were the least likely to require dosage adjustments because of side effects or a lack of efficacy. The glomerular filtration rate, measured in a subgroup of 34 patients receiving cyclosporine, decreased by a median of 16 percent. Higher doses of cyclosporine had greater adverse effects on systolic blood pressure, glomerular filtration rate, and serum levels of creatinine, uric acid, bilirubin, and cholesterol. Delayed-type hypersensitivlty reactions to skin-test antigens were reduced by cyclosporine administration. Cyclosporine appears to become concentrated in skin.
Conclusions
Cyclosporine therapy leads to a rapid and thorough clearing of psoriasis; an initial dose of 5 mg per kilogram per day seems to be appropriate. However, the safety of cyclosporine for the long-term treatment of psoriasis remains to be determined. (N Engl J Med 1991; 324:277–84.)
The New England Journal Of Medicine