Survival improves for SSc-PAH patients on combination therapy
Study finding may show 'growing confidence' in strategy's safety, effectiveness
Using combination therapy for pulmonary arterial hypertension (PAH) improves survival in people with systemic sclerosis (SSc), according to the results of a large study in Australia.
The study also demonstrated that the choice between a single medication or a combination of therapies did not vary significantly when comparing participants with more or fewer coexisting conditions, or comorbidities, or individuals with or without heart or lung issues.
“The findings are in line with current recommendations from the [World Symposium of Pulmonary Hypertension] to deploy upfront treatment with combination therapy in PAH, regardless of [a patient’s] comorbidity status,” the researchers wrote. “This prescribing pattern may reflect growing confidence in the safety and efficacy of combination therapy.”
Titled “Impact of Comorbidities on Treatments and Outcomes of Systemic Sclerosis–Associated Pulmonary Arterial Hypertension,” the study was published in the Canadian Respiratory Journal.
SSc, also known as scleroderma, is an autoimmune disease characterized by inflammation and accumulation of scar tissue in the skin and several internal organs. People with SSc may develop pulmonary arterial hypertension, known as PAH for short, which is a condition marked by high blood pressure, or hypertension, in the pulmonary arteries, the blood vessels that supply the lungs.
SSc-PAH patients more likely to have 4 or more coexisting conditions
SSc-PAH treatment may involve a monotherapy, or single medication, or a combination of therapeutic agents. In some cases, clinicians have preferred prescribing a monotherapy when patients have coexisting heart and lung disease, but the use of combination treatment has increased in parallel with data showing that it leads to better outcomes.
“The treatment paradigm for SSc-associated PAH … has undergone significant changes over time,” the researchers wrote, noting that “current guidelines emphasise the importance of comprehensive risk assessment, often using validated tools to guide therapeutic decision-making.”
To learn more about these differing strategies, a research team collected data from participants with SSc recruited to the Australian Scleroderma Cohort Study between 2007 and 2024. A total of 2,004 SSc patients were enrolled, including 238 — about 12% — with SSc-PAH.
The mean age at SSc diagnosis was 46.8 years and most participants were women (85.4%) and Caucasian (91%). Those with SSc-PAH were significantly older at SSc diagnosis than those without PAH (50.3 vs. 46.3 years), and had anticentromere antibodies — a type of self-reactive antibodies found in SSc — more often (53.2% vs. 45.2%).
Additionally, both interstitial lung disease, a condition marked by lung scarring and inflammation (45.7% vs. 26.2%), and difficulty swallowing (72.6% vs. 62.5%) were more frequent in those with SSc-PAH. These patients also reported poorer health-related quality of life in physical component assessments and worse physical function.
The presence of coexisting conditions was assessed using the Charlson Comorbidity Index (CCI), in which higher scores mean a higher burden, with more severe or a greater number of other disorders. Participants with PAH had a significantly higher CCI score (3 vs. 2) and were more likely to have four or more coexisting conditions (30.3% vs. 18.6%) than those without PAH.
People with SSc-PAH also more frequently had hypertension (61.6% vs. 46%), ischemic heart disease (27.6% vs. 12.2%) — heart issues caused by narrowed heart arteries — peripheral vascular disease (15.4% vs. 7.7%), and congestive heart failure (8.6% vs. 5.2%).
In the SSc-PAH group, no significant differences in clinical characteristics were seen between patients with a high comorbidity burden, defined as a CCI of four or more, and those with a lower burden.
40% better survival seen with combination vs. single therapy
Altogether, half of the participants with SSc-PAH received combination therapy, while 44.3% received monotherapy, and 5.7% received no treatment. The use of single therapy or combination regimens was independent of CCI score, or the presence of heart or lung problems.
Among the PAH medication classes used were endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids. All generally promote blood vessel widening and help reduce blood pressure.
A statistical analysis demonstrated that women had a 34% improved survival, while a higher mean pulmonary arterial pressure at diagnosis increased the risk of death by 3%. Patients on combination therapy had a 40% better survival compared to those on monotherapy.
Although a higher CCI score was associated with a poorer prognosis, there were no significant differences compared with lower comorbidity burden, the data showed.
According to the researchers, this study “highlights the significant burden of comorbidities in patients with SSc-PAH and their impact on clinical outcomes.” Particularly, “SSc-PAH patients … with high comorbidity burden tended to have worse survival,” they added.
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