Background/Purpose:

Diffuse systemic sclerosis (dcSSc) is a devastating multi-organ disease where the mainstay of treatment is immunosuppression. Data on these therapies are mostly based on skin or organ specific outcomes such as lung involvement. However, a new composite response index in dcSSc (CRISS) was proposed to improve assessment of treatment interventions¹. Our aim is to examine the effect of current immunosuppressive therapy on the CRISS in an observational dcSSc cohort.

Methods:

Adult dcSSc patients without prior immunosuppression followed in the Canadian Scleroderma Research Group (CSRG) registry between 2005 and 2017 were included. Patients newly treated with methotrexate, azathioprine, mycophenolate and/or cyclophosphamide for ≥2 years were the exposed group and untreated patients with at least the same follow up duration were controls. To account for disparity between treated and untreated patients, inverse probability of treatment weighting (IPTW) was performed to balance potential confounders: age, sex, disease duration and CRISS variables (modified Rodnan skin score, forced vital capacity, patient and physician global assessments, and HAQ-DI). Overall disease evolution after 1 year was qualified using CRISS which defines improvement as a score ≥0.6. Missing data were multiply imputed and logistic regression was used to obtain pooled odds ratios and confidence intervals.

Results:

301 dcSSc patients were analyzed. Of these, 47 (15.7%) were treated and 254 (84.4%) were untreated. At baseline, treated compared to untreated patients were younger (50.1±10.4 vs. 55.1±12.3 years respectively, p=0.008), had significantly shorter disease duration (5.5±7.4 vs. 11.7±9.3 years respectively, p<0.001) and higher mean physician global assessment scores (4.2±2.3 vs. 2.5±1.9 points respectively, p<0.001). IPTW used to correct for the different treatment probabilities and confounders showed excellent balance between the two groups. Prior to IPTW, treated patients trended towards more improvement after 1 year. However, after IPTW correction, treated patients were significantly more likely than untreated patients to have improved disease, regardless of age, sex, or disease duration (Table 1).

Conclusion:

Assessing the effects of treatment in an observational cohort is intrinsically biased as treated patients will likely have more severe disease.  After balancing using IPTW to reduce these confounders, we demonstrated that patients on immunosuppression are more likely to experience substantial improvement than untreated patients after 1 year using the CRISS score, a newly proposed global measure of disease severity.

1. Khanna D, Berrocal VJ, Giannini EH, et al. The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis. Arthritis Rheumatol 2016;68(2):299-311.