New data presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2022 Annual Meeting, and simultaneously published in the New England Journal of Medicine, offer evidence supporting an easy-to-implement, effective, and low-cost strategy for reducing the burden of asthma in Black and Latinx adults with moderate-to-severe asthma.
Black and Latinx adults with asthma bear a disproportionate burden of the disease compared with white adults. While many have attempted to reduce this burden, efforts have been resource-intensive and, unfortunately, mostly unsuccessful. The PeRson-Empowered Asthma RElief (PREPARE) study showed that simply having patients use an inhaled corticosteroid (ICS) any time they use an inhaled or nebulized quick-reliever for asthma symptoms can reduce asthma exacerbations and improve asthma control and quality of life in the underserved populations who suffer a disproportionate burden of asthma.
PREPARE was an open-label, real-world study of over 1,200 Black and Latinx adults with moderate-to-severe asthma. As opposed to efficacy studies with interventions such as SMART (single maintenance and reliever therapy), this study did not require an exacerbation in the prior year or bronchodilator responsiveness and did not exclude patients using nebulizers. Participants who were on an ICS and had poorly controlled asthma or an asthma exacerbation in the prior year were randomized to either continue their usual asthma care or to add a Patient-Activated, Reliever-Triggered Inhaled CorticoSteroid (PARTICS) to their usual asthma care. At the only study visit, they were instructed to use one puff of ICS for every puff of inhaled quick-reliever or five puffs of ICS for every quick-reliever nebulization. Importantly, their existing asthma therapies were unchanged.
The PARTICS intervention reduced asthma exacerbations by 15% (0.13 exacerbations per patient per year) versus usual care alone. In addition, the PARTICS intervention led to improved asthma control (exceeding the minimal clinically important difference [MCID] of the Asthma Control Test), improved quality of life (exceeding the MCID of the Asthma Symptom Utility Index), and a reduced number of missed work/school/activity days. These effects were accompanied by an 18% lower incidence of quick-reliever inhaler refills and by 32% fewer months of quick-reliever nebulizer use with the PARTICS intervention than usual care. These results were achieved with one-time instruction and a total additional ICS-containing inhaler use of only 1.1 canisters per year, thus representing minimal burden to clinicians and low cost to the health care system.
It is important to consider these results in the context of the studies of SMART therapy in moderate-to-severe asthma. By comparison, the reduction of 0.13 exacerbations/patient/year seen in PREPARE is equal to or greater than the reduction seen in studies of SMART therapy which prompted the paradigm-shifting guideline updates detailed above (0.12 exacerbations/patient/year, weighted by sample size and duration).
There are several gaps in understanding the efficacy of SMART therapy. SMART has not been well-studied in Black or Latinx adults or in real-world settings in the United States, in which many patients use nebulizers to administer their quick-reliever (45% of PREPARE participants reported using a nebulizer at least once per week). In addition, as mentioned above, relevant SMART trials enrolled only patients with an asthma exacerbation history and demonstrated bronchodilator response.
There are also barriers to implementation which may limit the broad uptake of SMART in the United States. The National Asthma Education and Prevention Program (NAEPP) 2020 guidelines specifically recommend ICS/formoterol as the ICS/long-acting β2-agonist (LABA) of choice for SMART, so patients using an ICS/LABA other than ICS/formoterol would need to switch products. However, despite the NAEPP endorsement of SMART therapy, as-needed use of ICS/formoterol is not currently approved by the United States Food and Drug Administration. Thus, access to SMART therapy and insurance coverage for this approach may pose significant challenges.
A unique aspect of the PREPARE trial was the degree of patient involvement in study design and implementation. The investigators focused exclusively on patient populations facing significant asthma disparities, and they included those very patients as partners in designing the study, optimizing its structure and methods, and interpreting the results.
Limitations include that the trial was open-label, and participants in the PARTICS arm had access to free study ICS with refills upon request. However, PARTICS participants used only 1.1 additional canisters of ICS-containing inhalers per year compared to those in the Usual Care group. In addition, the PREPARE population included individuals of many different Black and Latinx ethnicities, who may vary in their response to PARTICS. Women account for two-thirds of adult patients with asthma but were overrepresented in PREPARE.
In summary, the results of the PREPARE trial show us that we can reduce the disproportionate impact of moderate-to-severe asthma in underserved populations through the simple, patient-centered intervention of having patients use ICS along with their quick-reliever inhaler or nebulizer. This intervention is easy to use, low-cost, effective, does not require changing a patient’s underlying medications, faces no regulatory barriers, and results in less additional ICS use than other strategies. The PARTICS strategy could be quickly and easily implemented while we continue to assess the effectiveness of SMART and other asthma management strategies. Head-to-head studies of this strategy vs. SMART in real-world populations may be worthwhile.
Dr. Israel is employed by Brigham and Women's Hospital. He has received grants and/or consulting fees from AstraZeneca Destination, Avillion Mandala/Denali, Circassia, Gossamer Bio, NIH, Novartis, PCORI, Allergy and Asthma Network, Amgen, GlaxoSmithKline, Merck, NHLBI, Novartis, Pneuma Respiratory, Regeneron, Sanofi Genzyme, Teva, and Cowen. Lastly, he has received payment for writing for Teva, Cowen, and Westchester Medical Center.
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