Background/Purpose: Skin thickening is the defining manifestation of dcSSc. A dcSSc patient’s assessment of their skin involvement can provide information about how that patient feels and functions in response to treatment. No skin-specific patient-reported outcome (PRO) measure has been prospectively validated in dcSSc in a clinical trial.

Methods: SSPRO is a validated PRO measure that assesses health-related quality of life (HRQOL) related to skin involvement in SSc.  It has 18 items representing 4 HRQOL scales: physical effects, emotional effects, physical function, and social effects.  All items are scored from 0 (better) to 6 (worse). Anabasum is a preferential cannabinoid receptor type 2 agonist that was tested for safety and efficacy in dcSSc in a double-blind randomized placebo-controlled Phase 2 trial (JBT101-SSc-001).  Efficacy outcomes included the SSPRO, Patient Global Assessment (PtGA), HAQ-DI, Physician Global Assessment (MDGA), modified Rodnan Skin Score (mRSS), and FVC % predicted. SSPRO baseline scores were correlated with other baseline outcome scores using Pearson’s Correlation Coefficient.  Internal consistency was estimated using Cronbach’s α.  Effect size (ES, ratio of mean change in SSPRO total score from baseline to 12 weeks, to the standard deviation of the total score at baseline) was calculated to assess the SSPRO’s responsiveness to change.

Results: SSPRO was administered to 41 subjects with dcSSc. Internal consistency was high for the total (0.87) and for all scale scores (0.92). The SSPRO total and scale scores correlated strongly with PtGA, and moderately with HAQ-DI (except for the emotion scale) showing convergent validity.  SSPRO also correlated moderately with MDGA and weakly with mRSS.  As expected, SSPRO total and scale scores did not correlate with FVC % predicted, showing divergent validity.  The SSPRO total mean score showed a significant difference in anabasum-treated (N = 26) compared to placebo-treated subjects (N = 15) at 12 weeks, LS means difference (SE) = -16.9 (6.0), P = 0.004 ANCOVA.  The ES (n = 41) was moderate at -0.51, also demonstrating the SSPRO’s responsiveness to change. 

Table 1.  Correlations of SSPRO with other efficacy outcomes at baseline in a Phase 2 trial of anabasum in dcSSc

¹ P ≤ 0.05; ² P ≤ 0.01; ³P ≤ 0.005; ⁴P ≤ 0.0001

Conclusion: In this clinical trial dcSSc population, SSPRO showed high internal consistency, construct validity, and responsiveness to change.  Moderate and significant correlations of SSPRO scores with PtGA and HAQ-DI scores validate the usefulness of SSPRO as an outcome measure of how the patient with dcSSc feels and functions.  Its weaker but still significant and directionally concordant correlations with mRSS shows that the SSPRO may provide additional information on the patient’s experience of their skin involvement that the mRSS does not assess. This is the first prospective validation of the SSPRO in a clinical trial.