University of Michigan Ann arbor, Michigan, United States
Disclosure(s): No financial relationships with ineligible companies to disclose
Background/Purpose: Systemic sclerosis (SSc) is a rare autoimmune disease with high mortality. Early stratification by autoantibody (SSc-Ab) profile may inform prognosis and management, but data in early SSc remain limited. This study evaluated clinical features, treatment, and outcomes by SSc-Ab subtype in early SSc. Methods: We analyzed data from 116 patients (pts) enrolled in a prospective registry at a scleroderma center who had diffuse cutaneous SSc (dcSSc) or at-risk for progression based on serologic and clinical features. The at-risk group included those with swollen hands or sclerodactyly with anti-Scl-70 (Scl70) or anti-RNA polymerase 3 (RNAP3) Abs, and/or tendon friction rubs(1). Patients were classified into three groups: RNAP3, Scl70, or Triple Negative (negative for RNAP3, Scl70, and anti-centromere). We analyzed longitudinal data including change in modified Rodnan skin score (mRSS), forced vital capacity (FVC), HAQ-DI, organ complications, and mortality. Time-to-event analyses stratified by SSc-Ab group were conducted using cumulative incidence curves and the log-rank test. Results: A total of 116 pts had a median follow-up of 5.3 years (IQR: 2.1, 6.7); 109 (93.9%) had SSc-Ab data available (Table 1). The mean age was 51.1 years and 65.1% were female. Median disease duration from non-Raynaud phenomenon was 1.0 year . Of the 109, 38.5% were RNAP3+, 26.6% were Scl70+,and 34.8% were Triple Negative. dcSSc was present in 85.3%; 14.7% had at-risk features. RNAP3+ were older (mean 56 years), had the highest mRSS (mean 24.9 units), and the highest predicted FVC (mean 86.2%). At baseline, 61.5% of patients were receiving DMARDs, most commonly mycophenolate mofetil (40.4%), followed by methotrexate (12.8%) and cyclophosphamide (4.6%), while prednisone was used in 22.9%. During follow-up, immunosuppressive therapy was initiated or continued in 92.7% of patients, with variation across Ab subtypes (100% in Triple Negative, 85.7% in RNAP3+, and 93.1% in Scl70+; p=0.03). Mycophenolate mofetil remained the most frequently used agent (78.9%), followed by methotrexate (19.3%).
Of 109 pts, 17 had an event before registry entry and were not included in the time to composite event analysis. Overall, 55.4% experienced ≥1 new clinical event (Table 2), with the majority having mRSS worsening (13%), FVC decline ≥10% (13%), and HAQ-DI worsening (16.3%) as the first event; mortality occurred in 4 (4.3%) pts.
Cumulative incidence curves (Figure Panels A and B) show a trend toward a lower incidence of first events over time in the Triple Negative. mRSS worsening happened predominantly in the first 2 years, whereas FVC decline, HAQ-DI disability, and mortality continued over several years. Panels C-D show a trend toward higher incidence for mRSS worsening in pts with SCL70 and FVC decline in both RNAP3 and SCL70. Panel E-F show the impact of different SSc-Ab on HAQ-DI worsening and mortality. None of these trends were statistically significant. Conclusion: Distinct SSc-Ab in early SSc are linked to distinct organ involvement and clinical trajectories. Pts continue to have progressive organ involvement and high mortality despite current management strategies.
