Stratification in systemic sclerosis according to autoantibody status versus skin involvement: a study of the prospective EUSTAR cohort

Background The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15middot4%) of 10 709 were male, 9062 (84middot6%) were female, mean age was 54middot4 (SD 13middot8) years, and mean disease duration was 7middot9 (SD 8middot2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0middot82, 95% CI 0middot81-0middot84 for cutaneous only vs 0middot84, 0middot82-0middot85 for antibody only vs 0middot84, 0middot83-0middot86 for combined) or for progression-free survival (0middot70, 0middot69-0middot71 vs 0middot71, 0middot70-0middot72 vs 0middot71, 0middot70-0middot72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0middot57, 0middot46-0middot71 for antibody only vs 0middot29, 0middot19-0middot39 for cutaneous only) and disease progression (0middot36, 0middot29-0middot46 vs 0middot21, 0middot14-0middot28). The antibody -only model did better than the cutaneous-only model in predicting renal crisis (AUC 0middot72, 0middot70-0middot74 for antibody only vs 0middot66, 0middot64-0middot69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0middot76, 0middot75-0middot77 vs 0middot71, 0middot70-0middot72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Copyright (C) 2022 Elsevier Ltd. All rights reserved.Pathophysiology and treatment of rheumatic disease

Stratification in systemic sclerosis according to autoantibody status versus skin involvement: a study of the prospective EUSTAR cohort

Background The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15middot4%) of 10 709 were male, 9062 (84middot6%) were female, mean age was 54middot4 (SD 13middot8) years, and mean disease duration was 7middot9 (SD 8middot2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0middot82, 95% CI 0middot81-0middot84 for cutaneous only vs 0middot84, 0middot82-0middot85 for antibody only vs 0middot84, 0middot83-0middot86 for combined) or for progression-free survival (0middot70, 0middot69-0middot71 vs 0middot71, 0middot70-0middot72 vs 0middot71, 0middot70-0middot72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0middot57, 0middot46-0middot71 for antibody only vs 0middot29, 0middot19-0middot39 for cutaneous only) and disease progression (0middot36, 0middot29-0middot46 vs 0middot21, 0middot14-0middot28). The antibody -only model did better than the cutaneous-only model in predicting renal crisis (AUC 0middot72, 0middot70-0middot74 for antibody only vs 0middot66, 0middot64-0middot69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0middot76, 0middot75-0middot77 vs 0middot71, 0middot70-0middot72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Copyright (C) 2022 Elsevier Ltd. All rights reserved

Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: A prospective cohort study

OBJECTIVE: To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice. METHODS: We performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab. RESULTS: 254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47-5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55-1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56-3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83-9.62]; p=0.019 as compared with controls vs 3 [0.66-5.35]; p=0.012). CONCLUSION: Rituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial