Tiotropium is just as good as steroid add-on and perhaps safer
by Roger Sergel
Senior Executive Editor, MedPage Today Video
Asthma exacerbations were not reduced in black adults when a long acting beta-agonist (LABA) was added to treatment with inhaled corticosteroids (ICS), a randomized trial concluded.
The mean number of exacerbations was 0.42 exacerbations per person-year for LABA plus ICS, versus 0.37 exacerbations per person year for tiotropium plus ICS (rate ratio [RR] 0.90, 95% CI 0.73 to 1.11, log-rank P=0.31), Elliot Israel, MD,director of clinical research in the pulmonary and critical care division at Brigham and Women's Hospital, in Boston, and colleagues wrote in the Oct. 27 issue of the Journal of the American Medical Association.
The probability of being free of exacerbation at 1 year was 74.0% for LABA plus ICS versus 75.7% for tiotropium plus ICS (hazard ratio [HR] 0.91, 95% CI 0.70 to 1.18, P=0.47), they said.
"Blacks represent a group that bears a disproportionate burden of asthma morbidity (2 times the rates of emergency room visits and hospitalizations and 2-3 times the death rate)," Israel wrote in an email to MedPage Today. "Differences persist even after correction for socioeconomic disparities."
In addition, "Increasing evidence supports the therapeutic utility of anti-cholinergic agents for asthma, particularly for patients with airway obstruction or signs of higher cholinergic tone (e.g., lower resting heart rate)," David Lang, MD, chair of allergy and clinical immunology at the Cleveland Clinic, said in an email.
Researchers say asthma inhalers containing a long-acting beta-agonist (LABA) and an inhaled corticosteroid have become the most prescribed category of controller medication for asthma. Current treatment guidelines call for increasing inhaled corticosteroid (ICS) dose or adding a long- acting beta-agonist to patients poorly controlled on low dose ICS.
"Several studies have suggested that the long-acting beta-agonist may exert adverse effects related to asthma deteriorations in blacks," Israel noted. "Some of this has been thought to be related to genetic differences in the receptor for the beta-agonist."
And Stanley Fineman MD, MBA, past president of American College of Allergy, Asthma, and Immunology, said that "This concern about worsening asthma in black patients predisposed to have the Arg/Arg locus is a reason to use LAMA [a long-acting muscarinic anticholinergic] instead of LABA for all black patients with asthma."
The BELT randomized trial was done at 20 sites in an open-label parallel group from March 2011 through July 2013. The trial enrolled 1,070 black adults with moderate to severe asthma.
The primary outcome was time to asthma exacerbation, defined as a worsening asthma event requiring oral or parenteral corticosteroids.
The study found that "LAMA with ICS does not have added benefit over using LABA with ICS in this black adult population," Fineman said.
The clinical implications were clear, according to both Israel and Fineman. "Despite fears about LABAs in Blacks, LABA/ICS appears to be no worse than Tio/ICS for Blacks. Conversely, Tio/ICS seems as good," Israel said.
The study "is reassuring to physicians that there does not need to be a switch in asthma controller medications (for) all black patients," Fineman said.
Even though he found the study "reassuring," Fineman added that "The conclusions were somewhat 'underwhelming' since the results show 'non-superiority' of added LABA compared with LAMA."
Lang does not believe the results should be taken too far. "This study does not provide evidence to overturn recommendations from the Third Expert Panel Report guidelines: prescribing ICS+LABA for African-Americans with asthma remains a reasonable therapeutic option," he said.
There were some safety concerns about tiotropium. Israel said, "In a post-hoc analysis, we did find that tiotropium, which was just licensed by the FDA to treat asthma, was associated with a higher rate of hospitalizations than LABA." Therefore, "we need to keep an eye out for the issue of hospitalizations."
And Fineman found some limitations with the study, "particularly the patient selection -- 74% were female and the mean BMI was 34. Another problem was the high discontinuation rate and poor adherence to maintenance controller medications."
The study raises questions about the disproportionate burden of asthma among blacks. This burden has been linked "in some pre-clinical in vitro studies to a greater intensity of inflammation expressed in the airways and to a relative corticosteroid resistance," according to Michael Foggs, MD, immediate past president of the American College of Allergy, Asthma, & Immunology.
Foggs, who is chief of allergy and immunology at the Advocate Medical Group in Chicago, said in an email that some in vitro studies have suggested that there is a corticosteroid resistance among individuals with Vitamin D insufficiency. "Since up to 90% of African Americans have low vitamin D levels, double jeopardy may be at play if the intrinsic airways inflammation in blacks with asthma is further intensified if they also have low vitamin D levels."
And he cites the importance of socioeconomic status and education. "There are far more modifiable risk factors that drive asthma in indigent communities than in affluent ones. Inability to promptly impact such factors, (e.g., violence, other social stresses, indoor and outdoor pollution, pests) undoubtedly increases the burden of asthma in these communities."
LAST UPDATED 10.27.2015