Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS)

Abstract

ObjectivesThe rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches.MethodsThis was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or ‘no immunosuppressant’. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival.ResultsOf 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: −4.0 (−5.2 to −2.7) units for methotrexate, −4.1 (−5.3 to −2.9) for MMF, −3.3 (−4.9 to −1.7) for cyclophosphamide and −2.2 (−4.0 to −0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months.ConclusionsThese findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.Trial registration numberNCT02339441.

A patient‑centered approach to the burden of symptoms in patients with scleroderma treated with Bosentan: A prospective single‑center observational study

“…The latter were more likely to have dyspnea, greater HAQ-DI scores at baseline (P=0.051) and more severe capillaroscopic changes. Recent studies have reported more severe organ manifestations, higher mortality rates in patients with dcSSc compared to lcSSc (45,46). However, the post-treatment disability index scores were not substantially different with respect to disease phenotype in our cohort.…”

Treatment Algorithms for Systemic Sclerosis According to Experts

“…Experts incorporated MMF (as first‐line treatment) and IV CYC (as third‐line treatment) to treat SSc patients with high MRSS scores. There is weak evidence favoring the use of immunosuppression in early diffuse cutaneous SSc (dcSSc) . Experts have incorporated the possibility of performing HSCT .…”

Early trajectories of skin thickening are associated with severity and mortality in systemic sclerosis

“…In addition to lcSSc, there were 20 patients (17%) with dcSSc associated with ATA and whose median baseline mRSS was 9 (IQR 6.5; 9.5). Low mRSS values have already been reported in dcSSc [29][30][31] and some limitations on the current classification have been identified [28,32], especially when the forearms are involved. Their assignation to class 1 was probably related to the modeled trajectory shape of class 1 that was fitter to their individual trajectories than the other modeled trajectories classes.…”

“…Second, we chose to include patients with a disease duration of ≤ 2 years. A longer disease duration might have enabled a larger study size but would have increased the proportion of patients in which the mRSS has already been reached (usually during the first 2-3 years of the disease) [29]. A shorter disease duration could also have been more relevant but would have reduced the sample size preventing a robust modeling.…”