Low-dose intravenous immunoglobulin as an adjunctive therapy for systemic sclerosis: real-world evidence from a single center

Abstract Background Intravenous immunoglobulin (IVIG) has shown potential benefits for systemic sclerosis (SSc), but its high cost and supply instability may restrict the use of the 2 g/kg monthly regimen most commonly used in previous studies. We therefore evaluated the potential benefits of low-dose IVIG as an adjunctive therapy in patients with SSc using real-world data. Methods A single-center retrospective observational study was conducted in adults with SSc treated with at least two cycles of IVIG between 2014 and 2025. Patients with SSc who had never received IVIG served as controls. Propensity score matching was performed at a 1:3 ratio using age, sex, SSc-specific antibody profile, and rituximab or cyclophosphamide treatment history. The primary outcome was the 6-month change in modified Rodnan skin score (mRSS). Clinical outcomes were also compared between the first and last IVIG cycles in the IVIG group. Results Among 20 patients treated with IVIG, 19 were matched with 44 controls. At 6 months, mRSS decreased by 5.5 ± 6.9 in the IVIG group and by 1.8 ± 7.3 in the control group; however, the between-group difference was not statistically significant after multivariable adjustment (adjusted β = 2.436, 95% CI − 1.428 to 6.300, p = 0.224). In the IVIG group, mRSS decreased from 17.6 ± 9.7 at the first IVIG cycle to 12.0 ± 8.9 at the last IVIG cycle (p = 0.002), and the median glucocorticoid dose decreased from 7.5 [5.0–10.0] to 5.0 [3.4–7.5] mg/day (p = 0.013). Gastrointestinal improvement was observed in 9 of 16 patients (56%) with gastrointestinal involvement. Conclusions Low-dose IVIG did not significantly improve mRSS compared with matched controls. In the within-group analysis, gastrointestinal improvement was observed in more than half of IVIG-treated patients with gastrointestinal involvement, and IVIG was generally well tolerated. These findings suggest that low-dose IVIG may have potential as an adjunctive treatment for gastrointestinal involvement in SSc