Optimism for Interstitial Lung Disease–Associated Pulmonary Hypertension? - nejm.org
Optimism for Interstitial Lung Disease–Associated Pulmonary Hypertension? - nejm.org |
- Optimism for Interstitial Lung Disease–Associated Pulmonary Hypertension? - nejm.org
- Inhaled Treprostinil Shows Promise for ILD-Induced Pulmonary Hypertension - MD Magazine
- Registry highlights 'evolving characteristics' of patients with PAH - Healio
- COVID Vaccine for Patient With Rare Disease? Best Guess Is Yes - MedPage Today
| Optimism for Interstitial Lung Disease–Associated Pulmonary Hypertension? - nejm.org Posted: 13 Jan 2021 12:00 AM PST  Pulmonary hypertension scares us, and for good reason. Pulmonary hypertension may be caused by an intrinsic pulmonary vasculopathy — termed pulmonary arterial hypertension — or it may complicate other, more common problems such as interstitial lung disease, in which it signals the presence of advanced, often end-stage disease.1 Regardless of its cause, without effective therapy, pulmonary hypertension is associated with worsened dyspnea, mobility, quality of life, and short-term survival. Fortunately, remarkable progress in drug development has transformed a diagnosis of pulmonary arterial hypertension from a disease that is uniformly and rapidly fatal into one that in some patients may be . . .  |
| Inhaled Treprostinil Shows Promise for ILD-Induced Pulmonary Hypertension - MD Magazine Posted: 29 Jan 2021 10:09 AM PST  Findings from a new study demonstrated that inhaled treprostinil improved exercise capacity in patients with pulmonary hypertension due to interstitial lung disease (ILD). The drug was further associated with a lower risk of clinical worsening, a reduction in NT-proBNP levels, and fewer exacerbations of underlying lung disease when compared with placebo. Previous research has shown treprostinil to improve exercise capacity after 12 weeks of therapy with group 1 pulmonary hypertension; however, no therapies are currently approved for treatment of pulmonary hypertension in patients with ILD. Led by Aaron Waxman, MD, PhD, Brigham and Women's Hospital, the team of investigators enrolled a total of 326 patients in a multicenter, randomized, double-blind, placebo-controlled INCREASE trial. They sought to evaluate the efficacy and safety of the prostacyclin analogue over the course of 16 weeks. Treprostinil for ILD-Related Pulmonary Hypertension All enrolled patients were randomized 1:1 to receive inhaled treprostinil or placebo. The medication was administered through an ultrasonic, pulsed-delivery nebulizer in up to 12 breaths, 4 times daily. Efficacy was thus evaluated using the 6-minute walk test, which was assessed at baseline, weeks 4, 8, 12, and 16. Tests were performed 10-60 minutes following the most recent dose of the drug or placebo. The investigators then used the difference in this change from baseline to week 16 between the groups as their primary efficacy endpoint. "At week 16, the least-squares mean difference between the treprostinil group and the placebo group in the change from baseline in the 6-minute walk distance was 31.12 m (95% CI, 16.85-45.39; P<0.001)," Waxman and colleagues wrote. They also noted similar effects across subgroups, inclduing disease cause and severity. Such effects were likewise reported across baseline hemodynamic and dosing groups. The team observed a 15% reduction in NT-proBNP levels from baseline with usage of inhaled treprostinial—on the contrary, placebo was associated with a 46% (treatment ratio, 0.58; 95% CI, 0.47-0.72; P<.001). In the treprostinil group, clinical worsening occurred in 37 patients, while worsening in the placebo group occurred in 54 patients (HR, 0.61; 95% CI, 0.40-0.92; P = .04). As for safety, 152 treprostinil-treated patients experienced ≥1 adverse events—compared with 149 placebo-treat patients. The most frequently reported events were cough, headache, dyspnea, nausea, fatigue, and diarrhea. Serious adverse events were reported in 38 patients treated with treprostinil and in 42 who received placebo. And finally, 43 patients in the treprostinil group experienced exacerbations of underlying disease—versus 63 in the placebo group (P = .02). Promise and Limitations The investigators acknowledged that the trial has shown no evidence of worsened oxygenation, given general care concerns surrounding ventilation-perfusion mismatching for those with group 3 pulmonary hypertension. "Inhaled agents have the advantage of preferentially redirecting blood flow to the best-ventilated lung units, thus reducing the risk of ventilation–perfusion mismatching," Waxman and colleagues wrote. As acknowledged by the team, certain limitations surrounding the trial were its overall short duration and the fact that 21% of the patients prematurely discontinued the study. "Finally, the size of the favorable treatment effect on the 6-minute walk distance with inhaled treprostinil is similar to estimates of the minimum clinically important difference for this test in patients with pulmonary disease," they noted. Nevertheless, they expressed optimism of the efficacy and safety of treprostinal for patients with ILD-induced pulmonary hypertension. The study, "Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease," was published online in The New England Journal of Medicine.  |
| Registry highlights 'evolving characteristics' of patients with PAH - Healio Posted: 29 Jan 2021 11:48 AM PST January 29, 2021 2 min read Source/Disclosures Disclosures: Badlam reports no relevant financial disclosures. Please see the study for all other authors' relevant financial disclosures. We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com. The U.S. Pulmonary Hypertension Scientific Registry provides novel insights on patient characteristics, diagnosis delays and treatment trends in adults with pulmonary arterial hypertension. Middle-aged women with idiopathic PAH or associated PAH comprise the majority of patients with group 1 PAH, according to data published in CHEST.  Moreover, delays in diagnosing PAH remain a challenge, and among those with a diagnosis of PAH, use of combinations of PAH-targeted medications is common. "Over the past 4 decades, investigators have described evolving characteristics of patients diagnosed with PAH and improving survival associated with advances in disease management," Jessica B. Badlam, MD, pulmonologist and assistant professor at the University of Vermont, and colleagues wrote. Researchers reported data from the multicenter prospective cohort registry on 499 adults (mean age, 55.8 years; 79% women) diagnosed with group 1 PAH enrolled in the National Biological Sample and Data Repository for PAH within 5 years of a cardiac catheterization demonstrating hemodynamic criteria. Researchers performed a structured interviews and questionnaires to collect exposure and reproductive histories. In the cohort, from 2015 to 2018, 48% had a clinical diagnosis of idiopathic PAH, 51% had familial PAH and 1% had pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. The mean duration between symptom onset and diagnostic catheterization was 1.9 years. Before enrollment, 66% of patients were treated with more than one PAH medication. "Treatment with the combination of an [endothelial receptor antagonist] and a [phosphodiesterase type 5 inhibitor] increased from 12% (REVEAL Registry) to 24% (USPHSR), perhaps reflecting the reported benefit of upfront initiation of an ERA and a PDE5 inhibitor in treatment-naive PAH patients," the researchers wrote. "The proportion of patients with PAH treated with triple combination PAH therapy increased from 8% (REVEAL Registry) to 15% (USPHSR), reflecting both expedient patterns of practice and recent Prostacyclin Receptor Agonist in Pulmonary Hypertension (GRIPHON) trial data showing incremental benefit with the addition of selexipag (Uptravi, Actelion) to background dual therapy." Among women, 37% reported miscarriage, 22.7% premature birth, 18.5% abortion and 4.2% stillbirth. PAH was rarely diagnosed, with only 1.9% diagnosed within 6 months of a pregnancy. Thirteen percent of patients had pathogenic or suspected pathogenic variants, which reclassified 18% of those with idiopathic PAH and 5% of those with associated PAH as having heritable PAH. Prescription use in the past was common, with 16% reporting use of weight-loss drugs, 27% recreational drugs and 77% oral contraception. The most common hormone exposure was oral contraception in 76.9% of all female patients, followed by 19.3% on hormone replacement therapy. Few patients had a history of androgen use (0.8%), diethylstilbestrol treatment (1%) and drugs to induce ovulation (4.4%). "Despite considerable research into understanding how sex hormones may influence the development and progression of PAH, the contribution of estrogens and reproductive factors to the increased susceptibility of women to develop PAH and potentially their improved survival once diagnosed, remains poorly understood," the researchers wrote.  |
| COVID Vaccine for Patient With Rare Disease? Best Guess Is Yes - MedPage Today Posted: 21 Jan 2021 12:00 AM PST Extrapolating from the limited data from the Pfizer/BioNTech and Moderna COVID-19 vaccine trials, clinicians say the products' benefits likely outweigh the risks for people with pulmonary hypertension and other rare diseases. "The reality is folks with rare diseases will never have enough to do the trials out of the gate," said Tom Maddox, MD, MSc, of BJC HealthCare and Washington University School of Medicine in St. Louis. Without hard data, he said, clinicians and researchers can only postulate why COVID vaccines would work differently in people with pulmonary hypertension. "What do we understand about how the disease works? How the infection works? How the vaccine works? Is there anything that can cause the vaccine to worsen the disease? Any side effects?" "The way mRNA vaccines work, the way pulmonary hypertension works, nothing really occurs to us as problematic," Maddox said in an interview. "I'm not seeing any reason to believe [vaccination] would be dangerous to folks with pulmonary hypertension, also no reason to believe it wouldn't be as efficacious." In general, the primary safety events tied to COVID vaccination are transient flu-like symptoms; severe allergic reactions have been seen but only rarely. Accordingly, both Pfizer/BioNTech and Moderna vaccines include known allergy to vaccine components as contraindications -- not pulmonary hypertension, according to Justin Ortiz, MD, MS, of the University of Maryland School of Medicine in Baltimore and chair of the vaccines and immunization working group of the American Thoracic Society. In fact, the CDC includes people with pulmonary hypertension in phase 1c vaccination prioritization given that pulmonary hypertension -- encompassing several diseases that together affect an estimated 1% of the global population -- is recognized as one of the heart conditions that puts people at increased risk of severe illness from SARS-CoV-2 infection. In 2020, U.S. center directors reported hospitalization and mortality rates of 30% and 12%, respectively, among 50 COVID-19 patients with one of two forms of pulmonary hypertension, namely pulmonary arterial hypertension (PAH; WHO group 1) and chronic thromboembolic pulmonary hypertension (WHO group 4). In comparison, the COVID case fatality rate is just 1.7% in the U.S. general population, according to mortality data from Johns Hopkins. "We absolutely believe that PAH patients are a high-risk group" and "we are recommending vaccination for our patients," said Peter Leary, MD, PhD, of the University of Washington Medical Center, in an email to MedPage Today. Nevertheless, the mRNA vaccine data specific to the pulmonary hypertension population are sparse, if not nonexistent. For example, Pfizer/BioNTech's vaccine showed 95% efficacy in preventing COVID-19. The phase III trial enrolled more than 2,900 people with chronic pulmonary disease in the 43,548-person study, according to co-author Stephen Thomas, MD, of SUNY Upstate Medical University in Syracuse. Yet, no participant had pulmonary hypertension, a Pfizer representative confirmed. About 5% of participants in Moderna's 30,000-person trial, which reported 94.1% vaccine efficacy, had significant cardiac disease. Moderna did not clarify how many, if any, pulmonary hypertension patients participated in that trial, though probably no more than a few of those 5%. "In general, it makes sense for pulmonary hypertension patients to get the vaccine, but they certainly should talk to their physicians," Maddox cautioned. "Patients on blood thinning medicines or on medicines that affect their immune system are encouraged to discuss with their healthcare providers before they are vaccinated; however, in my opinion, in the vast majority of situations the benefits of vaccination will greatly outweigh the risks," said Ortiz. Last Updated January 21, 2021  |
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