The PREdictor of MAlnutrition in Systemic Sclerosis (PREMASS) score: the first validated combined index predictive of future weight loss in systemic sclerosis.

Background/Purpose: Malnutrition and severe gastrointestinal dysfunction are the cause of mortality in 4-15% of systemic sclerosis (SSc) patients whereas overall gastrointestinal involvement is observed in 75-90% of cases. There is currently no disease modifying treatment for severe GI involvement and malnutrition in SSc, and their implementation in clinical trials is halted by our current inability to stratify patients with SSc for the risk of progression. Here we set out to identify a combined index predictive of significant weight loss at 12 months employing Malnutrition Universal Screening Tool (MUST) and serum adiponectin to leptin ratio (A/L) both with known value in other conditions. Methods: This was an international, multicentre, longitudinal study employing 180 SSc patients in two independent cohorts: a study cohort (110 consecutive SSc patients) enrolled from University of Messina (60) and University of Padova (50), and a validation cohort (70) at the University of Leeds. Serum A/L ratio was measured by ELISA. MUST score, which includes BMI and weight loss reported by the patient in the last 3-6 months, was calculated as described: 0=no, 1=mild, >2=moderate/severe risk of malnutrition. End point of the study was weight loss ≥10% of baseline weight at 12 months. Results: The two cohorts showed no significant differences in demographic and clinical features. Overall, median BMI decreased over time in both study and validation cohorts (23.5 vs 22.35 and 23.44 vs 22.49, respectively; p<0.0001). A/L ratio correlated significantly with BMI in both cohorts (r2=0.19 for study cohort, r2=0.25 for validation cohort; p<0.0001). MUST score had only low value in predicting weight loss in the study cohort (AUC 0.7; 95% CI: 0.58-0.82). Specifically, 46.5% of SSc patients with “no” or 3 “mild” MUST risk lost ≥10% weight at 12 months. Logistic regression analysis identified the combination of BMI and A/L as the best PREdictor of MAlnutrition in Systemic Sclerosis (PREMASS). The formula 12.18-(0.63*BMI) + (1.51*A/L) predicted the 10% weight loss at 12 months with an AUC=0.91( 95% CI:0.77-0.84). A PREMASS score >0.23 showed 91.3% sensitivity (95% CI:79.79-100) and 80.46% specificity (95% CI:72.13-88.79) for ≥10% weight loss with an overall 55.26% positive predictive value (PPV) (95% CI:39.45-71.07) and 97.22% negative predictive value (NPV) (95% CI:93.43-100) and a relative risk (RR) of 19.90 (95% CI:4.93-80.37). In the validation cohort, PREMASS showed 76.47% sensitivity (95% CI:56.31-96.63) and 75.47% specificity (95% CI:63.89-87.06) with an overall 50% PPV (95% CI:30.78-69.22), 90.91% NPV (95% CI:82.41-99.4) and a RR of 5.5 (95% CI: 2-15.10). Conclusion: Here we propose PREMASS as the first independently validated index for stratification of risk for severe weight loss in the following 12 months in SSc. Prediction of future weight loss in SSc could aid both in clinical management and stratification/enrichment in clinical trials.