Intravenous Prostanoids in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

A Single-Centre Experience

Maria Vlachou; Hossam Fayed; Adele Dawson; Sally Reddecliffe; Alexander Stevenson; Ross J Thomson; Benjamin Emmanuel Schreiber; J. Gerry Coghlan


Rheumatology. 2022;61(3):1106-1114. 

In This Article


Our study shows that in the UK, the estimated 5-year survival in SSc- PAH patients on i.v. prostanoids remains poor. We also report for the first time evidence that ESC and REVEAL scoring, before the initiation of i.v. prostanoids and at the first formal reassessment, identifies SSc-PAH patients with a particularly poor prognosis in need for urgent consideration for lung transplantation, or palliation.

Published series on parenteral prostanoids in CTD-PAH are inconsistent, with 5-year survival ranging between 19% and 50% (Supplementary Table S1, available at Rheumatology online).[9,11–13] Our data sits at the lower end of this scale but focuses only on SSc-PAH patients. During the period 2006–2017, 321 patients were diagnosed with SSc-PAH in Royal Free Hospital, 69 (21.5%) of the above patients were transitioned to i.v. prostanoids and are included in this report. Ramjug et al. recently reported an overall expected 1-, 3- and 5-year survival of 64%, 26% and 21%, in a smaller heterogeneous CTD-PAH cohort using low dose iloprost.[11] Survival in the UK has, therefore, not improved compared with the outcome reported by Badesch et al. two decades ago.[9] By contrast, Bartolome et al. reported a 5-year survival of 50% in 61 CTD-PAH patients, the average age of CTD patients in that study was 10 years younger, suggesting a high proportion of lupus patients.[12] This explanation does not however explain the lower survival compared with Olsson et al..[13] From Supplementary Table S1, available at Rheumatology online, we can see that age, functional class, treatment intensity achieved and CTD subtype do not provide an adequate explanation for the worse survival reported in UK populations. The proportion of patients in high-risk groups at the time of initiation of i.v. therapy, or under treatment remain as possible explanations. While 77.8% of our population were on combination therapy at the time of initiating i.v. therapy, commissioning rules forced us to stop endothelin receptor antagonist therapy in the majority of patients after starting i.v. therapy until the last three years. If the latter is relevant, we should see improvement over the next couple of years; if the former, then a change in strategy is required.

Improvement of non-invasive and haemodynamic parameters after initiation of i.v. prostanoids in PAH patients has been reported.[6,11,25–27] Here we report an improvement in WHO FC in short-term, a trend toward improvement in NT-proBNP levels, 6MWD and haemodynamics (improved mPAP, PVR, cardiac index and SvO2).

Despite more aggressive uptitration, the change in WHO FC is lower than reported by Ramjug et al. (improved in 35% of patients at 6 months).[11] Badesch et al. reported improvement in 6MWD, improvement in right atrial pressure, mPAP, PVR, SvO2, 12 weeks after initiation of i.v. epoprostenol in CTD-PAH patients, compared with the conventional therapy arm.[8]

Multiparameter risk assessment using either the ESC or REVEAL score has an essential role in prognostication, monitoring treatment response and disease progression.[1,23] In the current study, we demonstrated that, in SSc-PAH patients, ESC and REVEAL score improved at the first formal reassessment, after initiation of i.v. prostanoids, while remaining high or intermediate risk or worsening to ESC high score and REVEAL high/very high score were associated with a very poor outcome.

ESC and REVEAL risk assessment have not previously been reported in CTD-PAH patients treated with i.v. prostanoids. Olsson et al. demonstrated that achievement of a low ESC risk score, 6–12 months after initiation of i.v. treprostinil in 126 PAH patients was associated with superior survival compared with patients who remained at intermediate or high ESC risk (5-year estimated survival was >90% survival for low-risk patients vs 28% for intermediate and high-risk patients, P <0.001).[13] However, only 16 CTD-PAH patients were included in their study population, and only one of them achieved the low-risk profile.[13] Bartolome et al. studied 195 PAH patients (61 of whom had CTD-PAH) treated with continuous prostanoids, and they demonstrated that the 2-year survival rate was <50% for PAH patients with no low-risk ESC parameters and with two or more higher risk ESC parameters at follow-up; however, ESC parameters and their impact on survival was not reported separately on the CTD-PAH subpopulation.[12]

We found that unchanged high/very high risk SSc-PAH patients, 6.5 months after initiation of i.v. prostanoids had a poor prognosis based on either the original REVEAL score or the ESC score. Both scores showed improvement after initiation of i.v. prostanoids. Patients who remained at or deteriorated to high risk had a very adverse prognosis, while a trend toward improved outcome among those whose risk profile improved at follow-up is evident (SSupplementary Figures S4 and S5, available at Rheumatology online).