Course of the Modified Rodnan Skin Thickness Score in Systemic Sclerosis Clinical Trials Analysis of Three Large Multicenter, Double-Blind, Randomized Controlled Trials

Objective. To assess the course of the modified Rodnan skin thickness score (MRSS) in 3 large, multi-center, double-blind, randomized controlled trials (RCTs) of patients with diffuse cutaneous systemic sclerosis (dcSSc) with different baseline disease durations, as defined from the date of onset of the first dcSSc symptom (excluding Raynaud's phenomenon) or from the date of onset of the first dcSSc-related symptom (including Raynaud's phenomenon). Methods. Data from 3 RCTs examining high-dose versus low-dose D-penicillamine (D-Pen Trial), recombinant human relaxin versus placebo (Relaxin Trial), and oral bovine type I collagen versus placebo (Collagen Trial) treatment in patients with dcSSc were pooled and analyzed. Patients were divided into 5 groups according to their disease duration at baseline. The linear mixed model for correlated data was used to model the 2 predictors of MRSS: time in study (expressed in months after baseline) and baseline disease duration (expressed in months, calculated from the date of onset of the first symptom characteristic of dcSSc with and without Raynaud's phenomenon). Results. At study entry, the mean MRSS value was 21.0 in the D-Pen Trial cohort, 27.3 in the Relaxin Trial cohort, and 26.1 in the Collagen Trial cohort. Time in study was a significant predictor of improvement in MRSS regardless of the disease duration at baseline (P < 0.0001). Patients with a disease duration of >= 24 months showed a greater rate of decline as compared with patients with a disease duration of <24 months (P < 0.05). Similar results were obtained when disease duration was reclassified by including the time of the first Raynaud's phenomenon symptom in the definition. Conclusion. Our study confirms recent findings that in patients entered into these 3 RCTs, skin thickening did not follow the same trend in natural history as that seen in the dcSSc populations entered into early, open longitudinal studies previously reported. These findings have important implications for study design, in which "prevention of worsening" is the main objective.