OA42 Impact of immunosuppression on development and outcome of systemic sclerosis-associated pulmonary arterial hypertension

Abstract

Background/Aims Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc). Treatment of SSc-PAH follows the same approach of idiopathic PAH and mainly relies on the combined action of vasodilators. Although immunosuppression might be expected to have a role considering the evidence of autoimmunity and immune dysfunction in the pathogenesis of SSc-PAH, evidence for benefit in prevention or treatment is lacking. The aim of this study was to retrospectively assess whether early immunosuppression impacts development of SSc-PAH or alters survival in patients with an established diagnosis. Methods We included 629 patients meeting the 2013 ACR/EULAR classification criteria for SSc. Early immunosuppression was defined as treatment in the first 5 years since SSc onset with either prednisolone equivalent at a dose ≥10mg daily, conventional synthetic or biologic DMARDs. Pre-capillary pulmonary hypertension (PH) was defined as mean pulmonary artery pressure ≥ 25mmHg, pulmonary vascular resistance >3 WU, pulmonary wedge pressure ≤15mmHg at right-heart catheterization. In case of precapillary-PH and concomitant ILD, we considered it PAH in case of forced vital capacity >70% (i.e. INCREASE trial exclusion criteria for group 3 PH). Outcomes of interest were development of PAH, time from SSc diagnosis to PAH, and survival in patients with PAH. Descriptive statistics, logistic and linear regression, Kaplan-Meier and Cox regression analysis were performed with STATA-18®. 31st December 2023 was chosen as the censorship date for survival analysis. Variables with p value <0.05 in univariate analysis were included in multivariate analysis. P value <0.05 was defined as statistically significant. Results Complete clinical and therapy data were available for analysis in 607 patients, of whom 206 received early immunosuppression. A total of 77 patients received a diagnosis of PAH, among which 11 were in the early immunosuppression group. After adjusting for potentially significant confounding variables, early immunosuppression was not associated to reduced odds of developing PAH (OR 0.74, 95% CI 0.31-1-76; p = 0.495), and time from SSc onset to PAH diagnosis was superimposable between the three treatment groups (i.e. 10.5 years for ‘early immunosuppression’, 11 years for ‘late immunosuppression’, and 11 years for ‘never immunosuppression’; p = 0.581). Survival analysis in patients with PAH included 70 patients. Immunosuppression was associated with a reduced risk of mortality, however, this did not reach statistical significance (HR 0.41, CI 0.16 - 1.04; p = 0.60). When analysing single agents, hydroxychloroquine was associated with reduced mortality risk (HR 0.06, CI 0.01 - 0.52; p = 0.011), while all the other agents did not significantly affect mortality. Conclusion Early immunosuppression does not seem to impact development of PAH or survival in SSc-PAH, however treatment with hydroxychloroquine is associated with reduced mortality in SSc-PAH. Considering the limitations of a retrospective approach, further prospective evidence is warranted. Disclosure S. Rodolfi: None. V.H. Ong: None. C.P. Denton: None.