High-intensity immunosuppression versus modern standard care in poor-prognosis diffuse cutaneous systemic sclerosis: A propensity-matched study.

BACKGROUND

Purpose: The 2023 EULAR update recommends autologous hematopoietic stem-cell transplantation preceded by high-intensity immunosuppression (HI-IS/HSCT) for selected poor-prognosis early diffuse cutaneous systemic sclerosis (dcSSc). As real-world data remain scarce, we compared 5-year outcomes of HI-IS/HSCT recipients with propensity-matched controls receiving standard care. Because undergoing HI-IS/HSCT identifies poor-prognosis systemic sclerosis (SSc), we compared their 5-year outcomes with those of propensity-matched dcSSc controls receiving standard care.

METHODS

This retrospective multicenter study analyzed ACR/EULAR-2013 dcSSc patients treated after 2013 from the Greater Paris University Hospitals and French national registry. Patients had poor-prognosis SSc defined by early disease and rapid skin progression or organ involvement. HI-IS/HSCT recipients were matched 1:1 with conventional immunosuppression controls using nearest-neighbor 20-variable propensity scores (covering demographics, antibodies, organ involvement, and prior treatments). Outcomes included overall survival (OS), event-free survival (EFS), progression-free survival (PFS), and toxicities at 60 months. Exploratory multivariable logistic regression identified predictors of EFS.

RESULTS

We analyzed 100 patients, equally divided between the HI-IS/HSCT and control groups. Five-year OS was similar (90%) in both groups. However, HI-IS/HSCT was associated with significantly improved 5-year event-free survival (76% vs 46%, p = 0.021) and progression-free survival (82% vs 40%, p = 0.001), a more favorable Global Rank Composite Score (p = 0.001), greater skin improvement (p < 0.001), and stabilization of FVC (p = 0.034) compared with controls. Prior DMARD burden was significantly lower in the transplant group (median 1 vs 2, p < 0.0001). Conditioning containing fludarabine/rituximab showed a non-significant trend towards higher EFS compared to CYC + ATG alone (82.6% vs 66.7%, p = 0.33). HI-IS/HSCT caused higher grade ≥4 toxicities (36% vs 8%, p < 0.001), with a 2% procedure-related mortality. Older age and pre-existing cardiac involvement were independently associated with worse EFS after transplant.

CONCLUSION

In patients with poor-prognosis dcSSc, 5-year overall survival was high and similar between HI-IS/HSCT and modern conventional care. However, HI-IS/HSCT provided significantly superior event-free and progression-free survival, skin improvement, and pulmonary stabilization. These findings support early HSCT as a highly effective disease-stabilizing therapy in carefully selected patients, provided they undergo rigorous cardiac screening.