Laura Joszt, MA

's parent company, MJH Life Sciences, since 2011. She has an MA in business and economic reporting from New York University.

Pulmonary arterial hypertension (PAH) is associated with significant morbidity and mortality, including hospitalization. New research presented at AMCP 2021, the annual meeting of the Academy of Managed Care Pharmacy, held virtually April 12-16, evaluated treatment patterns and costs related to hospitalization.

The first abstract reviewed PAH treatment patterns pre- and post hospitalization, as well as treatment modification during the hospital discharge period.

 Although hospitalization is a major morbidity event for patients with PAH, as well as a predictor of survival, there are limited data on therapy management after a hospitalization, the authors explained.

They used Optum’s deidentified Clinformatics Data Mart Database from January 1, 2014, to June 30, 2019, to identify adult patients with PAH. Then they examined treatment patterns in the 30 days prior to and the 90 days after a hospitalization.

In total, 3116 patients with PAH had a hospitalization event. The majority (68%) were female, the mean age was 68 years, the mean Charlson comorbidity index score was 5.1, and the average length of hospitalization was 7 days.

Nearly two-thirds (64.8%) of patients were on monotherapy before their hospitalization compared with just 17.4% on double therapy and 3.1% on triple therapy. In addition, 456 (14.6%) patients had no evidence of PAH therapy prior to their hospitalization.

After the hospitalization, 73.8% had no change in their treatment and 84.6% of the patients who were not on PAH therapy before their hospitalization stayed off treatment after. Patients on monotherapy and double therapy were equally likely to stay on the same type of therapy (72.0% and 72.5%, respectively). Patients only triple therapy were a little less likely to stay with the same type of therapy (69.4%).

“PAH guidelines and risk algorithms other than REVEAL 2.0 do not often include hospitalization as a risk factor for worsening PAH,” the authors concluded. “Further research is required to understand how the new 2019 PAH treatment guideline would impact PAH management in the real-world setting.”

In the second abstract, researchers estimated hospitalization-related cost differences associated with treatment by selexipag (SEL) or oral treprostinil (OT).

They created a comparative cost model to estimate the drug and hospitalization costs (total costs) to a US payer. Then they estimated for a 2-year horizon, which takes into account medication titration followed by maintenance dosing. They used real-world data from the Optum Clinformatics Data Mart Database along with the 2010 US Census and literature to define the population and hospitalization rates for patients (SEL: 0.632l; OT: 1.037).

In a hypothetical plan with 78 patients who have PAH, use of SEL would cost $43,281,212 and use of OT would cost $55,399,134 over 2 years. The SEL patients would have 98 related hospital admissions and the OT patients would have 161 admissions. SEL reduced costs by 21.87% over 2 years, saving $12 million over OT.

For a 1-year time horizon, SEL would save less as there would be less time for patients to receive their full dose strength, but it would still lead to savings of 4.3%.

“SEL is the preferred oral [prostacyclin pathway agent] option since benefits (hospitalization rate) of SEL outweigh those of OT and total costs (1- and 2-year) are lower than OT,” the researchers concluded.

1. Ogbomo A, Tsang Y, Kariburyo F, et al. Real-world analysis of treatment patterns among hospitalized pulmonary arterial hypertension patients. Presented at: AMCP 2021; April 12-16, 2021. Abstract I3.

2. Bilir S, Dufour R, Pruett J, Tsang Y, Panjabi S. Hospitalization-related costs associated with oral agents targeting the prostacyclin pathway for pulmonary arterial hypertension. Presented at: AMCP 2021; April 12-16, 2021. Abstract J8.

Articles

New research presented at AMCP 2021, the annual meeting of the Academy of Managed Care Pharmacy, evaluated treatment patterns and costs related to hospitalization for patients with pulmonary arterial hypertension (PAH).

PAH Treatment Patterns and Costs Related to Hospitalization

Pulmonary arterial hypertension (PAH) has remained a fatal disease with no pharmacological agents available to reverse or halt the disease. As there is no cure, there is an unmet need to understand the genetic etiology of PAH and molecular variants in order to develop better novel therapies.

 identifies potential mutations that are responsible for PAH.

“…A number of potentially causative mutations in genes primarily related to PAH as well as genetic and epigenetic modifiers of disease expression have been discovered via advanced genetic and genomic techniques including but not limited to conventional linkage analysis and next-generation sequencing technologies,” the authors explained.

In familial cases of PAH, not all individuals at risk are affected, and women are preferentially affected in an approximate 2:1 ratio. While 6% of PAH cases are heritable PAH (HPAH), this may be an underestimate, as cases of HPAH may be misclassified as idiopathic PAH (IPAH).

In 75% of HPAH and 20% of IPAH cases, mutations in the gene encoding bone morphogenetic protein receptor type 2 (

) may be responsible. Compared with patients without the mutation, patients with PAH who have the 

 mutation are not only diagnosed and die 10 years earlier, but they also are less likely to benefit from calcium channel blockers.

 mutations are a member of the transforming growth factor-beta (TGF-β) receptor superfamily. The researchers noted that approximately 20% of families with HPAH do not have detectable mutations along this pathway.

“This has led the scientific community to search for additional mutations which may contribute to PAH pathobiology,” they explained. Other genes include:

: This mutation may be a rare genetic cause of HPAH and IPAH. It is highly expressed in human pulmonary artery smooth muscle cells. Loss of its function may result in calcium-mediated vasoconstriction.

: This mutation is also a rare cause of HPAH and IPAH. Although the role of 

 mutations in HPAH and IPAH have been extensively evaluated. 

 may modify TGF-β signaling. Observations “suggest a mechanistic link between 

 mutations in the pathobiology of PAH.”

: These both may be involved in “cell proliferation and viability” and predispose patients to PAH.

: Mice lacking natriuretic peptide receptor type C, which 

 encodes, “exhibit echocardiographic and hemodynamic findings that are similar to those typically seen in humans with PAH.” However, the authors admit the causative genes in mice may not be relevant to humans.

Targeting molecular pathways that may contribute to PAH could provide new approaches to treat the disease. The 6th World Symposium on Pulmonary Hypertension task force recommends genetic screening even though there is no prevention or cure for PAH. However, identifying heritable disease could allow for closer monitoring, earlier disease detection, and earlier initiation of therapy.

“As genetic and other types of inherent biologic variations rarely occur in isolation, major advancements can be expected in the next few years in the identification of additional genes as well as genetic and environmental modifiers for PAH,” the authors concluded. “Larger genetic and biomarkers studies, with a close interplay of animal and human approaches will be necessary to better understand the complex genetic networks and events that promote PAH in genetically at-risk subjects.”

Eroume-A Egom E, Moyou-Somo R, Essame Oyono JL, Kamgang R. Identifying potential mutations responsible for cases of pulmonary arterial hypertension. 

. 2021;14:113-124. doi:10.2147/TACG.S260755

A better understanding of the genetic etiology of pulmonary arterial hypertension and its molecular variants is needed to develop better therapies for the disease, which has no agents available that can reverse or halt it.

Better Understanding of Potential Genetic Mutations May Lead to Improved PAH Diagnosis, Treatment

The FDA and the CDC will pause the use of Johnson & Johnson’s (J&J) single-dose COVID-19 vaccine at federal sites as they investigate safety issues. The agencies have also urged states to follow suit.

There have been reports of cerebral venous sinus thrombosis (CVST) in combination with thrombocytopenia. The disorder causes rare and severe 

 clots that are occurring among individuals within 2 weeks of receiving the J&J dose. There have been 6 reports of women between the ages of 18 and 48 developing the disorder. So far, 1 woman has died and a second has been hospitalized in critical condition.

“Right now, I’d like to stress that these events seem to be extremely rare,” Janet Woodcock, MD, acting FDA commissioner, said in a media briefing. “However, COVID-19 vaccine safety is a top priority for the government.”

The CDC is convening the Advisory Committee on Immunization Practices on Wednesday to review the cases, and the FDA will review the analysis as well as investigate the cases.

“Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” Anne Schuchat, MD, principal deputy director of the CDC, and Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a joint statement. “This is important, in part, to ensure that the health care provider community is aware of the potential for these adverse events and can plan for proper recognition and management due to the unique treatment required with this type of blood clot.”

Marks added in the media briefing that the decision to halt J&J doses at federal sites was made “out of an abundance of caution.”

Typically, blood clots would be treated with the anticoagulant heparin; however, this therapy may be dangerous with CVST, he explained. When doctors see patients with low platelets or blood clots, they need to ask about the history of vaccination in order to not cause more harm.

While they noted that the adverse events “appear to be extremely rare,” they encouraged individuals to contact their health care provider if they develop severe headache, abdominal pain, leg pain, or shortness of breath within 3 weeks of their J&J dose.

Nearly 7 million doses of the J&J vaccine have been administered in the United States. Prior to the CDC and FDA’s announcement, Georgia, Colorado, and North Carolina had all 

 delivering the J&J vaccine after people reported adverse reactions ranging from dizziness and nausea to fainting.

In a statement, Jeff Zients, the White House COVID-19 response coordinator, said that the pause is not expected to have a significant impact on the Biden administration’s vaccination plan since the J&J vaccine was less than 5% of recorded shots in the United States. More than 25 million doses of the Pfizer and Moderna vaccines are available each week.

“This is more than enough supply to continue the current pace of vaccinations of 3 million shots per day and meet the President’s goal of 200 million shots by his 100th day in office—and continue on to reach every adult who wants to be vaccinated,” Zients said.

This isn’t the first setback J&J has faced. A batch of 

 was ruined at a Baltimore plant after a mix-up with ingredients. The plant also produces the AstraZeneca COVID-19 vaccine, and the ingredient mix-up destroyed the J&J doses.

In addition, the European Union is reviewing the J&J vaccine related to the blood clot issue. The European Medicines Agency’s (EMA) safety committee was already looking at how AstraZeneca’s COVID-19 vaccine is associated with rare cases of blood clots. 

 that “unusual blood clots with low blood platelets should be listed as very rare side effects” of the AstraZeneca vaccine. Similar to the J&J vaccine, most of the AstraZeneca cases “have occurred in women under 60 years of age within 2 weeks of vaccination.”

During the FDA and CDC media briefing, Marks emphasized that of the more than 180 million doses of Moderna and Pfizer/BioNTech vaccines administered in the United States, there have not been any reports of CVST with thrombocytopenia.

People who have appointments to receive the other 2 vaccines should continue to get their doses, Schuchat said. For people who were scheduled to get the J&J dose, they are working to reschedule those appointments for one of the other vaccines.

At this time, there is no definitive cause for the condition, but the probable cause is an immune response that occurs rarely after receiving the vaccine and leads to activation of platelets and rare blood clots, Marks said.

Schuchat added that because the pandemic is still severe with cases rising, the CDC wants to make sure that it makes a recommendation quickly.

After cases of rare and severe blood clots led to 1 death and 1 hospitalization, the CDC and FDA will pause the use of Johnson & Johnson's (J&J) COVID-19 vaccine.

CDC, FDA Call for Pause of J&J COVID-19 Vaccine After Safety Concerns Around Clotting

Using the Geriatric Nutritional Risk Index (GNRI) when patients with 

 (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) are hospitalized can help predict their prognosis, according to a study 

PAH and CTEPH are considered precapillary pulmonary hypertension (PH). Among patients with precapillary PH, “undernutrition may trigger or aggravate disease progression. However, it is unclear whether undernutrition at the point of diagnosis is significantly associated with prognoses in patients with precapillary PH,” the authors explained.

The study included 104 patients with either PAH or CTEPH who were treated at the Kagoshima University Hospital in Japan. The majority of patients (84.6%) were female and 68.3% were World Health Organization functional class III or IV; the mean age was 60 years.

A score of < 92 was considered a low GNRI and ≤ 92 was considered a high GNRI. Patients with a low GNRI were more likely to be younger (54 years) compared with the patients with a high GNRI (61 years). Patients in the low-GNRI group also had significantly lower body mass index, serum albumin levels, and hemoglobin.

The median follow-up period was 24 months, during which 16 (15.4%) patients died. The composite outcome of either rehospitalization or all-cause death occurred in nearly half (45.5%) of patients in the low-GNRI group compared with 20.7% of patients in the high-GNRI group. After adjusting for potentially confounding covariates, the researchers still found a higher likelihood of all-cause death or rehospitalization for patients with low GNRI.

“Taken together, these results suggest that undernutrition at the time of diagnosis is a potent prognosticator in patients with PH,” the authors wrote.

They did list a number of limitations, including the relatively small sample size and the retrospective nature of the study. The study only evaluated GNRI scores once, so they could not assess changes in GNRI. In addition, they admitted there may have been unmeasured confounding factors that were not excluded.

The authors suggested that further studies evaluate the effectiveness of nutritional interventions in patients with PAH and CTEPH since undernutrition and weight loss are frequent among them.

“The present study suggests that the GNRI score at first hospitalization may be a simple predictor of prognosis in patients with PAH and CTEPH,” they concluded. “Adjunct nutritional therapies may improve outcomes in such patients.”

Kubota K, Miyanaga S, Iwatani N, et al. Geriatric nutritional risk index is associated with prognosis in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. 

. 2020;2(7):372-377. doi:10.1253/circrep.CR-20-0046

Adjunct nutritional therapies may be a simple way to improve the prognosis for patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension who are hospitalized.

Laura Joszt, MA

Articles

PAH Treatment Patterns and Costs Related to Hospitalization

Better Understanding of Potential Genetic Mutations May Lead to Improved PAH Diagnosis, Treatment

CDC, FDA Call for Pause of J&J COVID-19 Vaccine After Safety Concerns Around Clotting

Assessing Nutritional Risk Can Predict PAH Prognosis at First Hospitalization