The Significance of Databases for PAH - MD Magazine

The Significance of Databases for PAH - MD Magazine
Validating REVEAL: Can Scores Accurately Predict Survival in SSc-PAH? - Rheumatology Advisor
Owlstone, Actelion Team to Develop Breath-based Test for Diagnosing PH - Pulmonary Hypertension News

Posted: 30 May 2019 05:30 AM PDT

Patients who present with symptoms of pulmonary arterial hypertension could land on any spot of a spectrum which indicates minimal to significant risk of comorbidities, and even mortality. The uncommon, burdensome condition often requires that patients are receiving optimized therapy early and aggressively following diagnosis.

That puts pressure on investigators to broaden their access to clinical data. In an interview with MD Magazine®, Rich Channick, MD, director of the Acute and Thromboembolic Disease Program at the UCLA Medical Center, and Prof. Sean Gaine, director of the National Pulmonary Hypertension Unit in Ireland, explained the utility of national, international registries of PAH patients, and how it influences their ability to identify low- and high-risk patients.

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MD Mag: How critical are broad database in assessing care of patients with a rare, chronic condition such as PAH?

Channick: Yeah, I mean there's a lot of creative ways to get data. A lot of people are using claims data, insurance claims, instead of getting a big data. You can find a lot of patience. And now with coding, diagnostic codes, you look at pulmonary hypertension as a code for an insurance claim.

Obviously, there's a lot of different insurance companies. It's different in other countries, but you can really then look at different testing that has been done, what drugs are getting used, and patterns of use. You often can't get very granular, as we say, a higher view. But you can look at it a lot of patients.

Gaine: Yeah, in fact, we saw it at our session today, that we were presenting the GRIPHON data from the VA (Veterans Affairs). So the VA is an enormous database, and patients who attend VA have pulmonary hypertension—some of them—and you can gather data from there. So there are those are national registries that we pour through, not just registries from drug trials and seeing how patients are using them, but the national registries. And we learn a lot from them.

We've learned in the last few years that PAH as a disease seems to be sort of shifting—or at least what we're seeing is older patients that we wouldn't have seen previously. So we have to reset where to look for the disease. We used to say, "Oh, this is a disease of idiopathaty from the arterial hypertension." Formerly, primary pulmonary hypertension was a disease in young women in their mid-30s. So you knew where to look, in the sense of when a young woman arrived in breathless. You thought, this is unusual, maybe it's primary pulmonary hypertension, maybe it's idiopathic pulmonary hypertension.

Now we've learned from these registries that it's not necessarily always the case. You may have a 55 year old person who comes in says, "I'm breathless." You're thinking, well you're not doing any exercise, that's why you're breathless. But, in fact—normal pulmonary function, normal chest, X-ray, ECG. They need to go for an echo, and the echo is the number 1 screening tool to see if a person has problems with the right ventricle. So again, in primary care, someone comes in and it just doesn't fit, think of an echo as a really valuable screening tool.

Channick: Yeah, the last thing I'd say about registries—especially all the registries in Europe and elsewhere—is they have allowed us to start to look at things like risk stratification. One of the big mantras in pulmonary hypertension is determining what risk category are patients in, based on composite parameters—coming up with scores where we can actually profile a patient.

And when you treat a patient with these therapies, they determine whether they are into what we call the low-risk category, meaning they'll have a good prognosis. We quantify that. So, these registries have really allowed us both to develop some of these scores, and then validate them to show that it actually are predictive.

And that's really how we're treating. We have the GRIPHON subgroup to really look at the ability of the agent to lower risk, to put people into a low-risk category—that's really important in our treatment.

Validating REVEAL: Can Scores Accurately Predict Survival in SSc-PAH? - Rheumatology Advisor

Posted: 30 May 2019 01:00 AM PDT

When predicting 1-year survival for patients with newly diagnosed systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH), REVEAL prediction scores should be interpreted with caution, particularly in patients with a higher predicted risk, according to research published in Arthritis and Rheumatology.

The recently developed Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL Registry) prognostic equation and risk score calculator can be used to predict 1-year survival in patients with PAH. For this particular study, researchers sought to evaluate the predictive accuracy of the equation and risk score calculator in patients with incident SSc-PAH.

Patients participating in the validation cohort were drawn from 2 different cohorts: the Johns Hopkins Pulmonary Hypertension Program (JHPHP) Registry and the multicenter Pulmonary Hypertension Assessment and Recognition of Outcome in Scleroderma (PHAROS) Registry.

Patients from the JHPHP registry were consecutive patients with SSc, who were newly diagnosed with PAH via right heart catheterization between January 1, 2000 and July 1, 2015. Exclusions were applied to patients with evidence of obstructive or interstitial lung disease, rheumatologic overlap syndrome, previous treatment with active drugs for pulmonary hypertension, or inclusion in the initial REVEAL Registry.

Patients from the PHAROS Registry had established SSc and either a diagnosis of pulmonary hypertension within the previous 6 months or a classification of increased risk of developing PAH. Researchers noted that because Johns Hopkins is a PHAROS site, Johns Hopkins patients were removed from the PHAROS cohort because the JHPHP Registry included more complete patient information.

Investigators assessed 19 parameters and predicted the probability of 1-year survival for each patient. Patients were assigned points values and were then stratified into 5 risk groups: low (1-7 points), average (8 points), moderately high (9 points), high (10-11 points), and very high (≥12 points).

In total, the validation cohort included 292 patients (n = 117 from JHPHO and n = 176 from PHAROS); patients were primarily white women, age ≥60 years, with World Health Organization Functional Class II or III; however, patients in the JHPHP cohort were younger and were more likely to present with limited SSc, worse functional class, shorter distance on 6-minute walk test, lower reduced lung diffusion capacity, and worse hemodynamics.

Mean REVEAL risk score was higher in patients in the JHPHP Registry vs the PHAROS registry (9±2 vs 8±2; P =.005), although researchers noted that the PHAROS Registry does not record several data points recorded by the JHPHP Registry, so patients could not receive those points.

In total, 36 patients died and overall survival was 87.4% (95% CI, 82.9%-90.7%). C-indices for the REVEAL prognostic equation (0.73; 95% CI, 0.65-0.82) and risk score calculator (0.74, 95% CI: 0.66-0.82, respectively) showed "good discrimination," according to investigators. Slope of calibration was 0.71 (95% CI, 0.4-1.01), indicating a marginal overall fit.

According to hazard ratios, researchers found that patients classified as high risk had the worst survival.

"This suggests that while overall discrimination was good, discrimination for those at higher risk may not be as accurate," the researchers noted.

One important limitation of the study included concerns with missing data, including right atrial pressure, heart rate, and systolic blood pressure in the PHAROS cohort. Because these variables are included with increased risks, their absence "may have biased predictions toward a lower predicted mortality in the PHAROS cohort," according to the researchers.

"Our results show that when applied to a cohort of patients with newly diagnosed SSc-PAH, the REVEAL prognostic equation and risk score offer similar measures of overall discrimination as they did in the original model development cohort," the researchers wrote. "However, discrimination and calibration appear to be less accurate in patients in the highest risk groups, indicating that the REVEAL prediction model may not perform adequately in separating and predicting survival in newly diagnosed [patients with SSc-PAH] with high risk features and the lowest predicted probabilities of 1-year survival."

Reference

Mullin CJ, Khair RM, Damico RL, et al; PHAROS investigators. Validation of the REVEAL prognostic equation and risk score calculator in incident systemic sclerosis-associated pulmonary arterial hypertension [published online May 8, 2019]. Arthritis Rheumatol. doi:10.1002/art.40918

Topics:

Scleroderma Systemic Sclerosis

Owlstone, Actelion Team to Develop Breath-based Test for Diagnosing PH - Pulmonary Hypertension News

Posted: 30 May 2019 05:00 AM PDT

Owlstone Medical has established a strategic collaboration with Actelion Pharmaceuticals to develop and validate a breath-based diagnostic test for different types of pulmonary hypertension (PH).

Actelion Pharmaceuticals will solely fund this discovery and development program.

The test will be based on Owlstone's non-invasive method called Breath Biopsy, in which the patient's breath is sampled to identify PH-specific volatile organic compounds (VOC) that can serve as diagnostic markers.

"Owlstone Medical was founded with the objective of improving the early diagnosis of disease in order to save lives through the application of Breath Biopsy. This strategic collaboration with Actelion, which is focused on improving the lives of those suffering from PH and PAH [pulmonary arterial hypertension], represents a tremendous opportunity to do just that," Billy Boyle, co-founder, and CEO at Owlstone Medical, said in a press release.

"This is particularly true in underdiagnosed areas such as PH, where early diagnosis is difficult and so screening has to be simple, reliable, and cost effective," Boyle added.

PH is a progressive condition caused by the narrowing of blood vessels, which restricts blood flow, causing an excessive increase in blood pressure in vessels and added strain on the heart. Routine physical exams do not detect the early signs of PH, and the symptoms of advanced PH are very similar to those of other heart and lung conditions, thereby increasing the chances of misdiagnosis.

Also, diagnosing the type of PH is critical because it determines the course of treatment. That is why early screening and proper detection are crucial in the management of PH, emphasizing the need for efficient tests that are simple, specific, reliable, and cost-effective.

Of note, VOCs are the result of metabolic processes within the body, meaning that changes in metabolic activity can be associated with particular VOC patterns characteristic of specific diseases.

As part of this collaboration, exhaled breath samples containing VOCs will be collected from more than 1,000 patients from the United States, the United Kingdom, and other counties in the European Union.

ReCIVA, Owlstone Medical's proprietary VOC sampling device, will be used to collect the samples. The samples then will be analyzed by Owlstone Medical to identify PH-specific signatures that can be developed as biomarkers to help in early PH detection.

"We believe Breath Biopsy will deliver a program from discovery through to the launch of a test to the market, and this novel approach will make a real difference for the healthcare of patients suffering from PH," Boyle said.

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