Noteworthy and even game-changing new treatments and therapeutic strategies for COPD, cystic fibrosis, and other pulmonary diseases happened in 2019, but the headlines continue to be dominated by a still mysterious outbreak of vaping-related lung injuries.
Few EVALI Answers
In mid-August, health officials with the CDC first announced their investigation of close to 100 cases of severe lung illness related to vaping. A week later the first death attributed to the outbreak was reported in Illinois.
By late October, nearly 1,900 hospitalizations and 37 deaths nationwide had been blamed on the vaping-related collection of illnesses now known by the acronym EVALI (e-cigarette, or vaping, product use associated with lung injury).
In a report released Oct. 28, CDC reaffirmed what had already become apparent: that the vast majority of EVALI cases were occurring in people who vaped cannabis products containing tetrahydrocannabinol (THC).
Among the 19 deceased patients for whom CDC had data on substances used, 84% reported any use of a product containing THC and 63% reported exclusive use of THC vaping products.
The report also confirmed that EVALI patients are mostly young, white, and male. Among patients with available data, 79% were under the age of 35 years, 70% were male, and 78% were non-Hispanic white.
Although most of those who got sick vaped THC, about one in six insisted that they had not; nor were there any other specific features of patients’ vaping history that were present in all cases. Consequently, investigators could not pinpoint a single cause or causes for the vaping illnesses, noting that “the specific chemical exposure(s) causing lung injuries associated with e-cigarette product use, or vaping, remains unknown at this time.”
CDC recently issued interim guidance for health care providers, calling on them to ask patients with respiratory or gastrointestinal symptoms of unknown cause to ask about e-cigarette use or vaping, including what substance was vaped.
The guidance noted that EVALI is considered a diagnosis of exclusion because there is no specific test or marker to confirm it.
Diagnostic procedures suggested by CDC include measuring oxygen saturation, vital signs, a respiratory viral panel, and blood and urine testing — including testing for the presence of THC.
Radiographic findings consistent with EVALI include pulmonary infiltrates on chest x-ray and opacities on chest CT.
“A chest x-ray should be obtained on all patients with a history of e-cigarette, or vaping, product use who have respiratory or gastrointestinal symptoms, particularly when accompanied by decreased O2 saturation (<95%),” the report noted. “Chest CT might be useful when the chest x-ray result does not correlate with clinical findings or to evaluate severe or worsening disease, complications such as pneumothorax or pneumomediastinum, or other illnesses in the differential diagnosis, such as pneumonia or pulmonary embolism.”
FDA Approves First Triple-Drug CF Treatment
Also in October, the FDA approved the first triple-drug therapy for cystic fibrosis (CF), Vertex Pharmaceuticals’ elexacaftor/ivacaftor/tezacaftor (Trikafta).
FDA officials and others hailed the product as a game changer that will greatly expand the population of patients who can be treated.
The treatment was approved for CF patients ages 12 years and older with at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Efficacy was demonstrated in two 24-week clinical trials. Researchers concluded that the combination “has the potential to treat the underlying cause of cystic fibrosis in approximately 90% of patients.”
FDA sped up approval of the drug by granting it priority review, fast track, breakthrough therapy, and orphan drug status.
“(This) landmark approval is a testament to these efforts, making a novel treatment available to most cystic fibrosis patients, including adolescents, who previously had no options and giving others in the cystic fibrosis community access to an additional effective therapy,” acting FDA Commissioner Ned Sharpless, MD, said in a press release.
But a real-world use study of another Vertex Pharmaceuticals combination therapy — also considered revolutionary in CF treatment — raised new questions about how well patients are tolerating the drug.
About 20% of patients who took the lumacaftor-ivacaftor combo Orkambi discontinued the treatment in less than a year, which was more than three times higher than the discontinuation rate reported in phase III clinical trials.
Half of the discontinuations were for adverse breathing events, and 28% were for other types of adverse event, mainly gastrointestinal. In 32 patients who tried to go back on the treatment after discontinuing it, half were able to tolerate the therapy.
LAMA Safe for COPD Patients with Cardio Risk
Concerns that treatment with a long-acting muscarinic antagonist (LAMA) increases cardiovascular risk in at-risk patients with COPD were addressed in a randomized clinical trial published last spring.
Treatment with the LAMA aclidinium bromide (Tudorza Pressair) was not associated with an increase in major adverse cardiac events (MACE) in up to 3 years of follow-up in the study, which included roughly 3,600 COPD patients with established heart disease or multiple cardiovascular risk factors.
Patients taking the LAMA, often along with inhaled corticosteroid or long-acting B2-agonist (LABA), saw a 22% reduction in moderate to severe exacerbations and a 35% reduction in hospitalizations during the first year of treatment, compared to patients in the placebo arm of the study.
A subgroup analysis from the trial found use of the drug to be associated with a similar safety profile in patients with and without a recent history of exacerbations.
Concerns about the safety of beta-blockers in COPD patients were borne out in findings from another recently published study, which was terminated early.
Treatment with the beta-blocker metoprolol failed to increase the time to exacerbations and was associated with an increase in hospitalizations in patients without established cardiovascular indications for use of a beta-blocker.
Researcher Mark Dransfield, MD, of the University of Alabama at Birmingham, told MedPage Today in mid-October that the trial findings confirm that metoprolol is not beneficial, and may be harmful, in COPD patients who do not have indications for beta-blocker use.
“If patients with COPD do not have these indications, they should not be on the drug,” he said.
New analysis of data from prior phase III studies that failed to show a reduction in exacerbations in COPD patients treated with the biologic benralizumab (Fasenra) suggests that certain subgroups of patients may benefit from the treatment.
Among patients with blood eosinophil counts of at least 220 cells/mL taking triple maintenance therapy who experienced three or more exacerbations in the previous year, treatment with benralizumab was associated with a 30% reduction in exacerbations vs placebo.
Patients with a baseline FEV1 of less than 40% of predicted normal after bronchodilator challenge or at least 15% improvement in FEV1 with challenge also appeared to benefit from treatment with the biologic.
Asthma Triple Therapy, Peanut Allergy Drug Coming Soon?
Single-inhaler triple therapy was found to improve lung function and reduce exacerbations in patients whose asthma was not well controlled on standard therapies in the recently published TRIMARAN and TRIGGER trials.
Pooled analysis of the two trials showed treatment with the inhaled corticosteroid (ICS)-LAMA-LABA combo therapy to be associated with a 23% reduction in severe exacerbations, compared to treatment with ICS-LAMA alone.
In the TRIMARAN trial, which compared ICS/LABA/LAMA single inhaler therapy to medium doses of ICS plus LABA, triple therapy was associated with a 15% reduction in the rate of moderate to severe exacerbations (rate ratio 0.85, 95% CI 0.73-0.99, P=0.033).
In the TRIGGER study, in which the LAMA was added to high-dose ICS plus LABA therapy, the exacerbation rate was reduced by 12% (RR 0.88, 95% CI 0.75-1.03, P=0.11).
Other pulmonary medicine headlines of note in the last year: