Immunosuppression use in early systemic sclerosis may be increasing over time

Background: Immunosuppression remains the main treatment for progressing skin involvement, interstitial lung disease and inflammatory joint or muscle disease in systemic sclerosis. This study investigated the pattern and trends in immunosuppressive agents used in early systemic sclerosis (diagnosed before and after 2007) to determine whether the changes in the preferred type, timing and combination of immunosuppression took place over the past decade. Methods: In total, 397 Canadian Scleroderma Research Group database patients (183 diffuse cutaneous systemic sclerosis and 214 limited cutaneous systemic sclerosis) who had baseline and follow-up visits within 3 years (mean: 1.8 ± 0.8) after disease onset were included: 82% females, age at diagnosis 53 ± 13 years. Bivariate, chi-square, analysis of variance and adjusted regression analyses were used. Results: In total, 115 diffuse cutaneous systemic sclerosis patients (63%) and 62 limited cutaneous systemic sclerosis (29%) received immunosuppressive drugs, most commonly methotrexate, followed by mycophenolate mofetil and cyclophosphamide. In diffuse cutaneous systemic sclerosis, immunosuppressants were prescribed after 2007 more often (74% vs 50%, p = 0.001), especially methotrexate ( p = 0.02) and mycophenolate mofetil ( p = 0.04), and earlier (peak at 2 years after onset). Immunosuppressive therapy was associated with male gender, interstitial lung disease, anti-Scl70 positivity, ACA negativity and inflammatory joint disease in limited cutaneous systemic sclerosis and with ACA negativity and a higher modified Rodnan skin score in diffuse cutaneous systemic sclerosis. Multivariate regression analysis showed that the use of immunosuppressants after 2007 was predicted only by ACA negativity in limited cutaneous systemic sclerosis and by younger age in diffuse cutaneous systemic sclerosis. Conclusion: Over the past decade, there has been a trend to prescribe immunosuppressants more often and earlier in diffuse cutaneous systemic sclerosis patients, regardless of modified Rodnan skin score. Methotrexate is being more frequently used, and mycophenolate mofetil has gained favour over cyclophosphamide. Autoantibody status was the most consistent predictor of immunosuppressive therapy.

New Autoantibody Specificities in Systemic Sclerosis and Very Early Systemic Sclerosis

Chemokine (C-X-C motif) ligand 4 (CXCL4) is a biomarker of unfavorable prognosis in Systemic Sclerosis (SSc), a potentially severe autoimmune condition, characterized by vasculitis, fibrosis and interferon (IFN)-I-signature. We recently reported that autoantibodies to CXCL4 circulate in SSc patients and correlate with IFN-α. Here, we used shorter versions of CXCL4 and CXCL4-L1, the CXCL4 non-allelic variant, to search for autoantibodies exclusively reacting to one or the other CXCL4 form. Moreover, to address whether anti-CXCL4/CXCL4-L1 antibodies were present before SSc onset and predicted SSc-progression, we longitudinally studied two VEDOSS (Very Early Diagnosis of Systemic Sclerosis) patient cohorts, separating SSc-progressors from SSc-non-progressors. We found that anti-CXCL4-specific autoantibodies were present in both SSc and VEDOSS patients (both SSc-progressors and SSc-non-progressors). Anti-CXCL4-L1-specific autoantibodies were especially detected in long-standing SSc (lsSSc). Anti-CXCL4/CXCL4-L1 antibodies correlated with IFN-α and with specific SSc-skin features but only in lsSSc and not in early SSc (eaSSc) or VEDOSS. Thus, a broader antibody response, with reactivity spreading to CXCL4-L1, is characteristic of lsSSc. The early anti-CXCL4 autoantibody response seems qualitatively different from, and likely less pathogenic than, that observed in advanced SSc. Lastly, we confirm that anti-CXCL4 autoantibodies are SSc-biomarkers and uncover that also CXCL4-L1 becomes an autoantigen in lsSSc.