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, multicenter, 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 >or=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.


CONCLUSIONS
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.
Amjadi
Sogol
S
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Maranian
Paul
P
Furst
Daniel E
DE
Clements
Philip J
PJ
Wong
Weng Kee
WK
Postlethwaite
Arnold E
AE
Khanna
Puja P
PP
Khanna
Dinesh
D
D000328:Adult; D017668:Age of Onset; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use; D002417:Cattle; D024042:Collagen Type I / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D010396:Penicillamine / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012065:Relaxin / Q000627:therapeutic use; D012595:Scleroderma, Systemic / Q000188:drug therapy / Q000473:pathology*; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology*
D018501:Antirheumatic Agents; D024042:Collagen Type I; D011994:Recombinant Proteins; D012065:Relaxin; D010396:Penicillamine