Highest Risk Of Pulmonary Arterial Hypertension Observed In Patients With Systemic Scleroderma

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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scleroderma and PAH

Scleroderma has often been associated with a higher risk of pulmonary arterial hypertension (PAH) in previous research. This is because in patients with scleroderma, there is progressive blood vessel contraction (narrowing) that often leads to an increase in blood pressure in the lungs, which can in turn develop into PAH. This progression from scleroderma into pulmonary arterial hypertension was recently discussed by renowned PH expert Harrison Farber, MD, at the American College of Rheumatology’s State-of-the-Art Clinical Symposium in Chicago.

According to Dr. Farber, people with scleroderma are at the highest risk of developing PAH, which is why clinical trials involving PAH patients typically recruit around 60% (systemic) scleroderma-affected patients. Comparatively, patients with systemic lupus erythematosus (a chronic, autoimmune connective tissue disease) are at a much lower risk of developing PAH – around 17% of these patients develop PAH, according to Dr. Faber.

The most common diagnostic methods for PAH include echocardiogram and right heart catheterization (mainly because cardio-pulmonary hemodynamics need to be measured in these cases for proper treatment). RHC is considered to be a steadier form of diagnosis with fewer false positives and more accuracy.

“As we know, the [American College of Rheumatology] recommends that anyone who is newly diagnosed with scleroderma and / or is diagnosed should have an [echocardiogram], or sooner if their symptoms change,” Farber said.

While the prospect of developing PAH is concerning for those with scleroderma, Dr. Farber notes that, thanks to modern-day research, the life expectancy of patients with PAH has increased over the last few decades, thanks to new FDA-approved therapies as well as promising experimental treatments in the drug development pipeline. Earlier in the year, Dr. Farber commented on Reata Pharmaceuticals’ investigational PAH therapy based on an antioxidant inflammation modulator called bardoxolone methyl, noting that, “If Bardoxolone works in PAH without untoward effects on the immune system, then potentially it will be disease changing and not another vasodilator.”

However, despite progress, PAH and interstitial lung disease (ILD) are still the leading causes of death in patients with scleroderma. Patients with scleroderma who do not have any symptoms of cardio-pulmonary complications have a better prognosis, as do patients affected by both ILD and scleroderma.

Some of the other risk factors in people with scleroderma pertaining to development of PAH and related complications include increasing age, pericardial effusion and liver disease.

Another cause of concern is the fact that diagnosis of patients with PAH might be difficult and may take up to as many as two years. Symptoms are not easily detectable until and unless a patient takes the 6 minute treadmill test. Due to slow diagnoses, a delay in initiation of treatment measures leads to poorer prognosis.

“If you look at the way [these patients] are treated, they are less frequently put on prostacyclin, which is considered the most-potent classification of drugs we can use, and … although they don’t typically respond to calcium channel blockers, typically, they are taking them,” Farber said, adding that earlier intervention with prostacyclin therapy can lead to better outcomes.

Faber concluded by stating that he has been involved in a clinical trial with patients with PAH where the drug rituximab is being tested on PAH patients receiving other background therapies, the results of which would be published later this year.

A Conversation With Rare Disease Advocates