A randomized, double-blind, placebo-controlled trial: intravenous immunoglobulin treatment in patients with diffuse cutaneous systemic sclerosis.

Objectives: This paper aims to investigate the efficacy of intravenous immunoglobulin (IVIG) for skin sclerosis in diffuse cutaneous systemic sclerosis (dcSSc) by a randomised, double-blind, placebo-controlled, multicentre trial (DBT) with subsequent long-term observational and readministration studies.
Methods: In DBT, IVIG (400mg/kg/day for 5 consecutive days: a single course) or placebo (P) was intravenously administered to 63 dcSSc patients of 17 medical institutions in Japan, and changes in the modified Rodnan skin thickness score (MRSS) 12 weeks after administration or at discontinuation were compared as a primary endpoint. Patients with a 5-point or more improvement in the MRSS were continuously observed (long-term observational study), whereas IVIG was administered to those with less than a 5-point improvement (readministration study).
Results: In DBT, changes in the MRSS (mean±SD) were -3.3±4.2 and -4.2±4.6 in IVIG and P groups, respectively, and were not significantly different. Non-responder patients were subsequently subjected to the readministration study, and the change in the MRSS (LS-mean±SEM) at 60 weeks after the first administration was -8.3±1.0 in the IVIG → IVIG (GG) group treated with two courses of IVIG administration and -4.1±1.1 in the P → IVIG (PG) group treated with a single course of IVIG administration. The GG group represented a significant improvement in the MRSS against the PG group (p=0.0040).
Conclusions: Although the primary endpoint was not achieved in DBT, repeated administration of IVIG for two courses may be effective for skin sclerosis in dcSSc. Further investigation by the administration of plural courses will be necessary.