Recent systemic sclerosis-related pulmonary hypertension patients show better survival
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Key takeaways:
- A systemic sclerosis-related pulmonary hypertension diagnosis in the last 10 years vs. 10 years prior was linked to improved survival.
- It also showed better baseline hemodynamic characteristics.
Patients diagnosed with systemic sclerosis-related pulmonary hypertension in the last 10 years had better survival than those diagnosed prior, according to results published in American Journal of Respiratory and Critical Care Medicine.
“We believe that with combined therapy, patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) may have much better response and survival now closer to idiopathic PAH (IPAH) in response to the same PAH-targeted drugs,” Paul M. Hassoun, MD, director of the pulmonary hypertension program at Johns Hopkins Medicine, told Healio.
In a single-center retrospective study, Hassoun and colleagues analyzed 504 patients with SSc-PH from the Johns Hopkins Pulmonary Hypertension Center Registry to determine if there have been changes in survival from 1999 to 2021 in this patient population. In addition to survival, researchers also evaluated differences in characteristics of the patients based on when they received their diagnosis.
Of the total cohort, 246 patients received a diagnosis through a right heart catheterization between October 1999 and September 2010 and 258 received a diagnosis between October 2010 and September 2021.
Using the World Symposium on Pulmonary Hypertension (WSPH) disease classification groups, researchers found that 308 patients (61%) fit in group one (precapillary PH with severe remodeling of small pulmonary arteries), 43 (9%) in group two (PH associated with left heart disease such as left ventricular systolic or diastolic dysfunction) and 151 (30%) in group three (associated with parenchymal lung involvement causing hypoxia-induced PH).
Characteristics
Looking at characteristics of patients belonging to WSPH group one, those diagnosed more recently (55%) had several advantages over those diagnosed from 1999 to 2010 (67%).
Compared with patients who received a diagnosis in 1999 to 2010, patients with more recent diagnoses had a higher likelihood of getting upfront combination PAH therapy (38% vs. 10%; P < .01).
Further, patients in group one with a recent diagnosis also showed improved clinical and hemodynamic characteristics when diagnosed, perhaps suggesting earlier disease detection, according to Hassoun. This is demonstrated by patients diagnosed between 1999 and 2010 having greater likelihoods of WHO functional class 3 or 4 limitations (P = .04) and worse right atrial pressure (P < .01), mean pulmonary arterial pressure (mPAP; P < .01), stroke volume index (SVI; P < .01), pulmonary vascular resistance (P = .03), pulmonary arterial compliance (P < .01) and mixed venous oxygen saturation (P < .01).
Moving onto the other disease classification groups, more recently diagnosed patients fell into WSPH group three than earlier diagnosed patients (34% vs. 26%).
When separated according to the time of their diagnosis, patients classified as having WSPH group two or three diseases in both the time cohorts showed comparable baseline clinical and hemodynamic characteristics. Researchers also found that the type of PAH therapy given to 78% of the patients in group three did not differ in the two diagnosis period groups.
Transplant-free survival
Of the total cohort, researchers reported that 250 patients died, and 10 received a lung transplant.
Within the median follow-up period of 2.9 years for patients in WSPH group one, 87 patients diagnosed between 1999 and 2010 died, which was more than the 56 patients diagnosed more recently who died. Two of the patients in the more recent diagnosis cohort also received lung transplantation.
Among WSPH group three patients, the median follow-up was 2 years, during which more patients diagnosed between 2010 and 2021 than patients diagnosed earlier died (59 patients vs. 29 patients) and received a lung transplant (5 patients vs. 2 patients).
When looking at patient survival by disease group in univariable analysis, researchers observed that group one patients diagnosed recently had higher estimated survival rates than those diagnosed between 1999 and 2010 at 1 year (91% vs. 85%), 3 years (74% vs. 62%), 5 years (60% vs. 37%) and 8years (51% vs. 27%). These results translate to almost a 4-year rise in median transplant-free survival for those diagnosed between 2010 and 2021 (P < .01).
Unlike patients with WSPH group one disease, transplant-free survival rates in patients with group two or three diseases were similar between the two diagnosis periods, according to researchers.
In a multivariable analysis of those belonging to WSPH group one that was adjusted for age, sex, WHO functional class, mPAP and SVI, researchers again found that transplant-free survival was higher in patients with a more recent diagnosis vs. patients with an earlier diagnosis (adjusted HR = 0.6; 95% CI, 0.41-0.88; P < .01), which Hassoun said suggests that early disease detection is not the sole reason for improved survival.
“These results were quite surprising to us since scleroderma-associated PAH (ie, WSPH group one) has been known for the past 20 years to have a very poor prognosis (median survival of no more than 4 years), and much worse prognosis compared to IPAH,” Hassoun told Healio. “Further, when reviewing most multicenter large trials for PAH, the response of SSc-PAH was notoriously quite inferior to IPAH.”
Additionally, when WSPH group one patients were divided up according to risk levels at diagnosis using a common risk stratification approach, researchers found that those diagnosed between 2010 and 2021 with low risk (P = .03) and intermediate risk (P = .01) had improved survival. This was not observed in high-risk patients.
“The future for PAH, and particularly SSc-PAH is upfront combination (dual or triple) therapy,” Hassoun told Healio. “The new drug, sotatercept (not yet FDA-approved and therefore not available for this particular cohort), which targets a very different pathway compared to the three classic targeted pathways in PAH (ie, the endothelin, prostacyclin and nitric oxide pathway), offers tremendous promise in this field.”
This study by Hassoun and colleagues demonstrates the importance of screening for PAH when a patient receives a SSc diagnosis, according to an accompanying editorial by Panagiota Xanthouli, MD, of the Centre for Pulmonary Hypertension at Heidelberg University Hospital in Germany.
“These findings have implications for PAH screening, which should start straight away with the first diagnosis of SSc,” Xanthouli wrote. “Screening tools such as DETECT (early detection of PAH in SSc) are established and validated. Although treatment strategies and screening recommendations are widespread and acknowledged, a great number of patients remain undertreated, and screening for PH often starts at later stages of disease, together with greater disability, resulting in impaired survival.”
“Favorable trends in survival observed in this study likewise must be validated in additional SSc–PH cohorts,” Xanthouli concluded. “This is an important step by which to affirm that the remarkable light at the end of the SSc tunnel is real, proving that hope prevails for affected patients.”
For more information:
Paul M. Hassoun, MD, can be reached at phassou1@jhmi.edu.