TREATMENT OF SYSTEMIC-SCLEROSIS WITH RECOMBINANT INTERFERON-GAMMA - A PHASE I/II CLINICAL-TRIAL

Objective. A phase I/II trial to examine the safety and efficacy of interferon-gamma (IFNgamma) therapy for patients with systemic sclerosis (SSc). Methods. An 18-week open-label study was performed. Eighteen patients with rapidly progressive SSc were enrolled, 14 of whom completed at least 16 weeks of the study. These 14 patients had a mean age of 40 years and had been diagnosed as having SSc an average of 10.1 months prior to study entry. Recombinant IFNgamma was injected intramuscularly 3 times weekly for 18 weeks. Six patients received a 0.1 mg/m2 dose, while 8 patients received a 0.5 mg/m2 dose. Patients who completed the 18-week trial were offered maintenance therapy at a dose of up to 0.5 mg/m2. The effects of IFNgamma on skin involvement were assessed by 2 methods: 1) evaluation of skin thickness, by scoring 15 zones according to a 0 (normal skin) to 3 (hidebound skin) scale; and 2) determination of the total body surface area involved, by using 2-dimensional body diagrams to indicate areas affected, and then having a second, "blinded," assessor calculate the area score with a planimeter. Results. The mean skin thickness score decreased from a baseline of 25.9 to 19.1 (P < 0.03), and the mean area scores declined from 33.1 to 19.6 (P < 0.02) after 18 weeks of IFNgamma treatment. Ten patients had a > 25% decrease in area score. Five patients had a greater-than-or-equal-to 70% decrease in area score, and 3 of them have not experienced disease recurrence for 6 to 17 months after discontinuation of IFNgamma. Five patients withdrew before the study ended. Three of these patients developed renal crisis, which may reflect the severity of the SSc in the study group, although an adverse effect of IFNgamma in SSc cannot be excluded. Conclusion. IFNgamma was associated with a beneficial effect on the skin involvement in most of this series of patients with rapidly progressive SSc. A placebo-controlled study will be necessary to confirm these results.