CONQUER Scleroderma: association of gastrointestinal tract symptoms in early disease with resource utilization.

OBJECTIVES: SSc is associated with increased health-care resource utilization and economic burden. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative that collects longitudinal follow-up data on SSc patients with <5 years of disease duration enrolled at scleroderma centres in the USA. The objective of this study was to investigate the relationship between gastrointestinal tract symptoms and self-reported resource utilization in CONQUER participants. METHODS: CONQUER participants who had completed a baseline and 12-month Gastrointestinal Tract Questionnaire (GIT 2.0) and a Resource Utilization Questionnaire (RUQ) were included in this analysis. Patients were categorized by total GIT 2.0 severity: none-to-mild (0-0.49); moderate (0.50-1.00), and severe-to-very severe (1.01-3.00). Clinical features and medication exposures were examined in each of these categories. The 12-month RUQ responses were summarized by GIT 2.0 score categories at 12 months. RESULTS: Among the 211 CONQUER participants who met the inclusion criteria, most (64%) had mild GIT symptoms, 26% had moderate symptoms, and 10% severe GIT symptoms at 12 months. The categorization of GIT total severity score by RUQ showed that more upper endoscopy procedures and inpatient hospitalization occurred in the CONQUER participants with severe GIT symptoms. These patients with severe GIT symptoms also reported the use of more adaptive equipment. CONCLUSION: This report from the CONQUER cohort suggests that severe GIT symptoms result in more resource utilization. It is especially important to understand resource utilization in early disease cohorts when disease activity, rather than damage, primarily contributes to health-related costs of SSc.

Thirty-day hospital readmission in systemic sclerosis associated pulmonary hypertension: A nationwide study.

OBJECTIVE: To identify risk-factors for 30-day hospital readmission in systemic sclerosis pulmonary hypertension (SSc-PH) and to compare trends and characteristics of 30-day readmissions in SSc-PH versus non-SSc pulmonary arterial hypertension (non-SSc PAH). METHODS: In this retrospective study, we identified SSc-PH and non-SSc PAH hospitalizations using ICD-9 codes within the Healthcare Cost and Utilization Project-National Readmission Database. Thirty-day readmission rates were calculated between 2010 and 2015. Characteristics were compared using chi-square, Wilcoxon rank-sum, or two-sample t-tests between (A) SSc-PH patients with versus without readmission and (B) patients with ≥1 readmission with SSc-PH versus non-SSc PAH. Adjusted logistic regression models were generated for readmission in SSc-PH. RESULTS: 4,846 of 22,420 (22%) with SSc-PH and 10,573 of 49,254 (21%) with non-SSc PAH had ≥1 30-day readmission. Between 2010-2015, readmission rate decreased in non-SSc PAH (23% to 20%; p<0.001) and was unchanged in SSc-PH (23% to 23%; p = 0.77). In SSc-PH, independent predictors of 30-day readmission include male sex, age <60, Medicare or Medicaid, higher Charlson/Deyo comorbidity index, and congestive heart failure (CHF). A higher proportion of patients with SSc-PH (vs. non-SSc PAH) died during index hospitalizations (p = 0.001) and readmissions (p <0.001). Readmitted patients with SSc-PH (vs. non-SSc PAH) were younger and less often had CHF. In SSc-PH, the most common readmission primary diagnosis was infection, followed by respiratory and heart failure. CONCLUSION: In SSc-PH, 30-day readmission is frequent, and in-hospital deaths occur at a higher rate compared to those with non-SSc PAH. This study identifies factors that may characterize those with SSc-PH at highest risk for readmission.

Assessment of skin disease in scleroderma: Practices and opinions of investigators studying scleroderma.

Background: The modified Rodnan skin score is a common primary outcome measurement tool in clinical trials of systemic sclerosis (scleroderma). However, it is unknown how often physicians perform the modified Rodnan skin score in clinical practice or what precise approach is most often used when assessing each of the 17 sites included in the modified Rodnan skin score (i.e. "maximizing," "averaging," "representative area"). This study assessed the experiences, perceptions, training, and practices of individuals studying scleroderma with regard to modified Rodnan skin score. Methods: An invitation with an online survey link was sent electronically to 282 individuals who are part of the Scleroderma Clinical Trials Consortium. The 46-item survey included three sections: participant demographics, modified Rodnan skin score background/training, and modified Rodnan skin score assessment practices. The survey was accessible for 5 weeks (October-November 2019). Results: The response rate was 41% (116 of 282 individuals). The majority of participants perform the modified Rodnan skin score in clinical care (>99%) and practice at academic institutions (90%) in North America (41%) or Europe (40%). Nearly all participants felt that the modified Rodnan skin score is either "somewhat important" (43%) or "essential" (56%) to the care of patients with systemic sclerosis. In total, 91% of participants reported having received modified Rodnan skin score training. The majority (60%) of those who had not received training were interested in receiving modified Rodnan skin score training, and 39% of participants felt either "uncomfortable" or only "somewhat comfortable" performing the modified Rodnan skin score. The modified Rodnan skin score approach varied: 44% used "maximizing," 28% used "averaging," and 18% used "representative area." Conclusion: A majority of participants feel that the modified Rodnan skin score is "essential" to the care of patients with systemic sclerosis; however, the method used to measure modified Rodnan skin score varies greatly among systemic sclerosis investigators. These results indicate a continued role of modified Rodnan skin score for care and research in systemic sclerosis, support ongoing efforts to increase opportunities for modified Rodnan skin score training, and highlight a potential need to harmonize the technical approach to measuring the modified Rodnan skin score.

Utility of B-type natriuretic peptides in the assessment of patients with systemic sclerosis-associated pulmonary hypertension in the PHAROS registry.

OBJECTIVES: To assess the utility of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) in detecting and monitoring pulmonary hypertension (PH) in systemic sclerosis (SSc). METHODS: PHAROS is a multicenter prospective cohort of SSc patients at high risk for developing pulmonary arterial hypertension (SSc-AR-PAH) or with a definitive diagnosis of SSc-PH. We evaluated 1) the sensitivity and specificity of BNP≥64 and NT-proBNP≥210 pg/mL for the detection of SSc-PAH and/ or SSc-PH in the SSc-AR-PAH population; 2) baseline and longitudinal BNP and NT-proBNP levels as predictors of progression to SSc-PAH and/or SSc-PH; 3) baseline BNP≥180, NT-proBNP≥553 pg/mL, and longitudinal changes in BNP and NT-proBNP as predictors of mortality in SSc-PH diagnosed patients. RESULTS: 172 SSc-PH and 157 SSc-AR- PAH patients had natriuretic peptide levels available. Median BNP and NT-proBNP were significantly higher in the SSc-PH versus SSc-AR-PAH group. The sensitivity and specificity for SSc-PAH detection using baseline BNP≥64 pg/mL was 71% and 59%; and for NT-proBNP≥210 pg/mL, 73% and 78%. NT-proBNP showed stronger correlations with haemodynamic indicators of right ventricular dysfunction than BNP. Baseline creatinine, RVSP > 40 mmHg, and FVC%:DLco% ratio ≥1.8 were associated with progression from SSc-AR-PAH to SSc-PH but no association with individual or combined baseline BNP and NT-proBNP levels was observed. Baseline and follow-up BNP or NT-proBNP levels were not predictive of death, however, a composite BNP/NT-proBNP group predicted mortality (HR 3.81 (2.08-6.99), p<.0001). CONCLUSIONS: NT-proBNP may be more useful than BNP in the detection and monitoring of PAH in SSc patients, but additional studies are necessary.

Musculoskeletal Involvement in SSc Is Associated with Worse Scores on Short Form-36 and Scleroderma Health Assessment Questionnaire and Lower Tumor Necrosis Factor-α Gene Expression in Peripheral Blood Mononuclear Cells.

BACKGROUND: Systemic sclerosis (SSc) is characterized by a wide variety of symptoms and disease manifestations including joint pain, gastrointestinal dysfunction, interstitial lung disease, and cardiomyopathy. QUESTIONS/PURPOSES: Using the Scleroderma Health Assessment Questionnaire (SHAQ) and Short Form-36 (SF-36) we explored how patient-reported physical health, mental health, and functional status related to these clinical characteristics and to cytokine levels utilizing the Hospital for Special Surgery Scleroderma Registry. METHODS: In a cross-sectional study of 185 patients meeting the 2013 ACR/EULAR criteria for SSc, we compared disease features and patient-reported outcomes (PROs). Interleukin-6 (IL-6), interleukin-1ß (IL1ß), and tumor necrosis factor-α (TNFα) levels were assessed by luminex and ELISA assays in a subset of 32 patients. The Pearson correlation coefficient, Spearman correlation coefficient, two-sample t test or Wilcoxon rank sum test, ANOVA or Kuskal-Wallis test, and Pearson chi-squared or Fisher's exact test were performed as applicable to detect the association between disease manifestations, PROs, and blood biomarkers. RESULTS: The modified Rodnan skin score (MRSS) was positively correlated with SHAQ scores. Patients who had musculoskeletal involvement scored worse on both the SHAQ and SF-36. Lower levels of TNFα expression in PBMCs were also correlated with musculoskeletal involvement. No other significant correlations were found between clinical factors, PROs, and cytokine data. CONCLUSION: Musculoskeletal outcomes are a major determinant of quality of life and function in patients with SSc. These results emphasize the importance of musculoskeletal outcomes in clinical studies of SSc.

African American race associated with body image dissatisfaction among patients with systemic sclerosis.

OBJECTIVES: Studies have shown a high degree of body image dissatisfaction among patients with systemic sclerosis (SSc). We aimed to identify demographic and phenotypic characteristics that correlate with body image dissatisfaction. METHODS: Ninety-eight patients with SSc were recruited from Georgetown University Medical Center 2003-2004. Anonymous surveys collected demographic information (age, race, gender, duration/type of SSc) and assessed degree of body image dissatisfaction on a scale of 0-3 in relation to phenotypic features of SSc (hand contractures, finger ulcers, pigmentation changes, lip wrinkling/thinning, telangiectasias). A composite total distress score was derived. Parametric and nonparametric T tests were used to compare groups. RESULTS: Of 98 patients, 86 were female and 12 male. The majority of patients were 30-60 years old. The sample was 62% Caucasian, 27% African American, and the rest identified as "other". Twenty-seven percent had limited SSc, 48% diffuse, and 25% "other". African American patients had greater total body image dissatisfaction (p=0.002), specifically with respect to digital ulcers, pruritus, and pigmentation changes, than Caucasian participants. Patients with diffuse SSc had greater body image dissatisfaction than those with limited disease (p=0.002). CONCLUSIONS: Our results suggest that African American patients with SSc and those with diffuse subtype suffer a higher degree of body image dissatisfaction. Screening for and addressing this issue in SSc patients is prudent. Further study is needed to understand racial differences in body image dissatisfaction among patients with SSc.

Survival and predictors of mortality in systemic sclerosis-associated pulmonary arterial hypertension: outcomes from the pulmonary hypertension assessment and recognition of outcomes in scleroderma registry.

OBJECTIVE: To assess cumulative survival rates and identify independent predictors of mortality in patients with incident systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) who had undergone routine screening for PAH at SSc centers in the US. METHODS: The Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma registry is a prospective registry of SSc patients at high risk for PAH or with definite pulmonary hypertension diagnosed by right-sided heart catheterization within 6 months of enrollment. Only patients with World Health Organization group I PAH (mean pulmonary artery pressure >25 mm Hg and pulmonary capillary wedge pressure <15 mm Hg without significant interstitial lung disease) were included in these analyses. RESULTS: In total, 131 SSc patients with incident PAH were followed for a mean ± SD of 2.0 ± 1.4 years. The 1-, 2-, and 3-year cumulative survival rates were 93%, 88%, and 75%, respectively. On multivariate analysis, age >60 years (hazard ratio [HR] 3.0, 95% confidence interval [95% CI] 1.1- 8.4), male sex (HR 3.9, 95% CI 1.1-13.9), functional class (FC) IV status (HR 6.5, 95% CI 1.8 -22.8), and diffusing capacity for carbon monoxide (DLCO) <39% predicted (HR 4.2, 95% CI 1.3-13.8) were significant predictors of mortality. CONCLUSION: This is the largest study describing survival in patients with incident SSc-associated PAH followed up at multiple SSc centers in the US who had undergone routine screening for PAH. The survival rates were better than those reported in other recently described SSc-associated PAH cohorts. Severely reduced DLCO and FC IV status at the time of PAH diagnosis portended a poor prognosis in these patients.