Eighty-one patients with SSc-PAH (median age 61 years, IQR 54–67years, 84% females) were enrolled.
Baseline characteristics are shown in Table 1. Non-invasive data were recorded 22 days (IQR 5.3–58.8 days), while invasive data were recorded 99 days (IQR 36–249 days) before the initiation of i.v. prostanoids.
Response to i.v. Prostanoid Therapy
Follow-up characteristics after the initiation of i.v. prostanoids are shown in Table 2. Non-invasive data were recorded 6.5 months (IQR 5.4–8 months), while invasive data were recorded 6.5 months (IQR 3.9–8.6 months), after the initiation of i.v. prostanoids. A total of 16 SSc-PAH patients died before the first assessment; in addition, one patient developed manifest PVOD and four patients were unable to tolerate prostanoid side-effects and discontinued intravenous prostanoids early (Supplementary Figure S1A, available at Rheumatology online), leaving 60 patients on i.v. therapy at the time of reassessment. The baseline and the follow-up characteristics after initiation of intravenous prostanoids in SSc-PAH patients are shown in Table 2.
On i.v. prostanoids, SSc-PAH patients improved WHO-FC (13.3% achieved FC II, 3.3% fewer FC i.v., P =0.041), had a reduction in mean pulmonary arterial pressure (mPAP) [52.5 mmHg (IQR 43.3–56.8) vs 46 mmHg (IQR40-54), P =0.036], and in PVR [9.9 Wood Units (IQR 7.7–12.3) vs 7.3 Wood Units (IQR 5.2–10.9) vs, P =0.012], an increase in cardiac index [3 l/min/m2 (IQR 2–3.5) vs 2.3 l/min/m2 IQR (2–3), P =0.003] and SvO2 [65% (IQR 58–71) vs 62% (IQR 52–67), P =0.036], associated with an improvement in ESC score (P < 0.05) and a reduction in REVEAL score (P <0.03). Median trerostinil dose at the time of first follow-up right heart catheterization was 46 (IQR 38–54) ng/kg/min, and mean epoprostenol dose was 18.1 ± 5.7.ng/kg/min. Mean maximum dose of trerostinil achieved was 91.4 ± 47.4 ng/kg/min, and mean maximum dose of epoprostenol dose achieved was 25.2 ± 11 ng/kg/min. Changes in ESC and REVEAL score in SSc-PAH patients before and at first formal assessment after the initiation of i.v. prostanoids are presented in Supplementary Figure S2, available at Rheumatology online.
Baseline Parameters Associated With 5-year Survival
The estimated survival for CTD-PAH patients on i.v. prostanoids was 64%, 31% and 18% at 1 year, 3 years and 5 years, respectively (Figure 1). Of the original 81 patients, 60 did not survive 5 years, including nine of the 13 patients that stopped i.v. prostanoids (nine patients due to intolerance and four patients developed manifest PVOD) (Supplementary Figure S1b, available at Rheumatology online).
Kaplan–Meier estimates of survival in the whole cohort
SSc-PAH: systemic sclerosis-associated pulmonary arterial hypertension.
On univariable analysis of baseline data, older age, higher NT-proBNP levels and lower SvO2 levels were associated with increased 5-year mortality (Table 3). On multivariable analysis, older age, higher NT-proBNP levels, and lower SvO2 levels remained the baseline parameters that were associated with increased 5-year mortality (Table 3).
Risk Scores and Outcome
Patients with a high ESC risk score at the time of i.v. treatment initiation had a lower estimated 5-year survival, compared with patients with a low/intermediate ESC risk score (Figure 2A, P =0.003), and patients with a high ESC risk score at first formal reassessment had a very adverse estimated 2-year survival [16% if worsened to high risk, 13% if persistent high risk, (Supplementary Figure S3, available at Rheumatology online)], and significantly worse 5-year survival than patients with a low (P =0.001) and intermediate (P <0.001) ESC risk score (Figure 3A).
Kaplan–Meier estimates of survival according to (A) ESC Score, (B) REVEAL score, at baseline, prior to initiation of intravenous prostanoids
Kaplan–Meier estimates of survival according to (A) ESC Score, (B) REVEAL score, at first formal reassessment, after the initiation of intravenous prostanoids
High/very high REVEAL score, at the time of i.v. treatment initiation and at first formal reassessment, was associated with a lower 5-year survival, compared with patients with a low and average REVEAL score (P =0.025 at baseline, P <0.001 at follow up), and compared with patients with moderate REVEAL score (P =0.046 at baseline, P <0.001 at follow-up) (Figures 2B and 3B).
SSc-PAH patients in whom the ESC score deteriorated from intermediate to high or remained high at the first reassessment after the initiation of intravenous prostanoids had a worse prognosis compared with the other groups of patients (Supplementary Figure S3, available at Rheumatology online).
Similarly, SSc-PAH patients in whom the REVEAL score remained high/very high at the first reassessment after the initiation of intravenous prostanoids had a poor prognosis (15%, 2-year survival) (Supplementary Figure S4, available at Rheumatology online). While numbers prevent analysis, patients that improved their ESC or REVEAL score from high/very high exhibited a trend toward improved survival (Supplementary Figures S3 and S4, available at Rheumatology online).
Finally, though numbers prevent formal analysis, a trend towards improved survival was noted in patients enrolled after January 2011 (30 SSc-PAH patients were commenced on i.v. prostanoids from January 2006 to December 2010, 51 SSc-PAH patients were commenced on i.v. prostanoids from January 2011 to November 2020), when the option for upfront combination therapy became available in the UK (Supplementary Figure S5, available at Rheumatology online).
Rheumatology. 2022;61(3):1106-1114. © 2022 Oxford University Press