PO:34:204 | Impact of anti-centromere antibodies on immunosuppressive therapy persistence in systemic sclerosis: a single-center case-control study

Martina Salerno¹, Marius Cadar¹, Ilaria Bisconti¹, Francesca Romana Di Ciommo¹, Elena Platania¹, Jacopo Landro¹, Beatrice De Girolamo¹, Davide Mohammad Reza Beigi^1|2, Simona Truglia¹, Fabrizio Conti¹, Valeria Riccieri¹ | ¹Rheumatology unit, AOU and Università di Cagliari; ²Asl Biella, Ospedale degli Infermi, Ponderano (BI), Italy

Background. Although in Systemic Sclerosis (SSc) the autoantibody profile is associated with different clinical and therapeutic phenotypes, it remains unclear whether it also affects patients’ persistence in immunosuppressive (IS) therapy. Through a case-control study, we aimed to evaluate whether the presence of specific autoantibodies is associated with a greater tendency to discontinue IS therapy in SSc patients.

Materials and Methods. We conducted a retrospective analysis on a single-center cohort of 90 patients (M/F 4/86) affected by SSc, classified according to the 2013 ACR/EULAR criteria and treated with immunosuppressive drugs (IS). Thirty ACA-positive (ACA+) patients were identified and compared with 60 ACA-negative (ACA–) patients, including anti-Scl-70+, anti-RNAP III+, and non-specific ANA+ subjects, matched 1:2 for sex and age. A descriptive analysis of clinical, demographic, and instrumental characteristics was performed at the time of IS initiation (T0). Data regarding the first IS introduced and its clinical indications were also collected. During follow-up, conducted for up to 10 years or until the last documented visit, tolerability and causes of therapy discontinuation were evaluated. Persistence was analyzed using Kaplan–Meier curves, log-rank test, and Cox regression.

Results. Table 1 reports the clinical, demographic, and instrumental characteristics of the 90 patients at T0. Table 2 describes, at baseline, IS use and clinical indications in the two groups. During follow-up, 8 ACA+ patients (27%) discontinued therapy compared to 7 ACA– patients (12%). Among ACA+ patients, the main reasons were clinical stability (25%) and gastrointestinal intolerance (25%) (Figure 1). In the ACA– group, discontinuation mainly occurred due to malignancy (28.5%), with no cases related to clinical stability. Persistence was significantly lower in ACA+ patients compared to ACA– (log-rank test, p = 0.0163), with a marked divergence between the 2nd and 6th year (Figure 2). In Cox regression analysis, ACA positivity was significantly associated with IS discontinuation (HR 12.26; 95% CI 1.65–133.4; p = 0.014), whereas no other variable (age, disease duration, mRSS, FVC%) was significantly associated with the outcome.

Conclusions. In ACA+ SSc patients, persistence in immunosuppressive therapy was significantly lower than in ACA– patients, mainly due to clinical stability. ACA positivity confirmed to be an independent factor associated with early IS discontinuation. This finding suggests that in some patient subgroups, disease management may be feasible even without IS therapy, as treatment proved to have limited influence on the symptoms for which it was prescribed. These results support the potential role of serology not only in phenotypic definition but also in guiding more personalized therapeutic strategies. These preliminary data need to be validated in studies with larger sample sizes.