Original Article
A Pragmatic Trial of Symptom-Based Inhaled Corticosteroid Use in African-American Children with Mild Asthma

https://doi.org/10.1016/j.jaip.2019.06.030Get rights and content

Background

Symptom-based adjustment (SBA) of inhaled corticosteroids may be an alternative patient-centered approach in which day-to-day inhaled corticosteroid use is adjusted by symptoms and short-acting β-agonist need.

Objective

To evaluate the effectiveness of SBA in the primary care setting.

Methods

We conducted a randomized, open-label, pragmatic equivalence trial in African-American children (6-17 years old) with mild asthma managed by 12 primary care providers (PCPs). A total of 206 participants were randomized to SBA (as-needed beclomethasone 80 μg with rescue short-acting β-agonist) or provider-based guideline-directed adjustment (PBA): maintenance beclomethasone 80 μg/d (6-11 years old), 160 μg/d (12-17 years old), with subsequent guideline-based dose adjustment by PCPs. PCPs implemented both treatment assignments, with outcomes measured by blinded staff. All participants received symptom recognition and albuterol use education from peer educators. Primary outcome was change in asthma control (measured by Asthma Control Test [ACT]/childhood ACT [cACT]) over 12 months.

Results

Participants had adequately controlled asthma (mean ACT or cACT score = 21.6 ± 2.8) at baseline. After 1 year, there was no significant between-group difference in change in ACT scores (SBA − PBA): ACT: −0.88 (95% CI, −2.19 to 0.42), cACT: −0.73 (−2.09 to 0.62), or combined ACT and cACT (P = .10), and was within the predefined statistical clinical equivalence. The proportion with an exacerbation and measures of lung function were similar between groups. Compared with PBA, SBA led to less beclomethasone use (SBA: 526 μg/mo [95% CI, 412-639 μg] vs PBA: 1961 μg/mo [95% CI, 1681-2241]; P < .0001). More parents in the SBA arm felt they were managing their child's asthma.

Conclusions

SBA in African-American children with mild asthma was similar to PBA in asthma control and events when implemented by PCPs with lower inhaled corticosteroid exposure.

Introduction

Asthma guidelines have recommended daily use of inhaled corticosteroids (ICS) for persistent asthma for the past 3 decades.1, 2 However, adherence to daily asthma therapy remains low despite efforts,3 and concerns for side effects from ICS (such as growth effect4 and long-term steroid-induced complications5) negatively affect adherence.6, 7 Moreover, the cost of asthma therapy is a major concern of the urban minority family.7, 8 Reflecting this behavior and belief of the patients and families, primary care providers (PCPs) often elect not to recommend daily ICS to patients with persistent asthma,9 especially those with mild disease.10 These ongoing obstacles to guideline-based asthma management have led to consideration of alternative, nondaily strategies.

Intermittent, symptom-based adjustment (SBA) of ICS is a patient-centered strategy in which the dose of ICS is determined by the patient's rescue inhaler needs. Daily ICS is not used, but rather ICS is delivered whenever a short-acting β-agonist (SABA, albuterol) or a quick-onset long-acting β-agonist (LABA, formoterol) is used to treat symptoms. SBA of ICS with SABA was shown to be effective in controlling asthma and preventing exacerbation both in adults and in children with mild persistent asthma.11, 12, 13 The most recent update of the Global Initiative of Asthma published in April 2019 now recommends this strategy as one of the options for step 1 and step 2 therapy for the first time.14 Similarly, SBA of ICS combined with a LABA (budesonide + formoterol) has been recently shown to deliver better asthma control than SABA alone and resulted in a similar rate of asthma exacerbation compared with daily dose of budesonide + formoterol in patients with mild asthma.15, 16 These studies have consistently shown that patients using SBA were exposed to a lower dose of ICS compared with daily therapy11, 12, 13 and associated with less adverse growth effect.13

However, these previous studies were conducted in a controlled clinical trial setting, which is often different from usual clinical practice. Thus, there is a need to evaluate the SBA in a real-life, primary care setting, especially now that SBA is added to the Global Initiative of Asthma recommendation as a treatment option for mild asthma that is highly prevalent in the primary care practices.

We conducted our study in African-American children, a population in which provider-based guideline-directed adjustment (PBA) asthma care (current standard of care) has been inconsistently implemented.17, 18 Adherence to daily ICS is low,19 and African Americans have concerns regarding the adverse effects of daily ICS.7, 20, 21 We hypothesized that the SBA strategy might be better accepted in this population, because the patient or caregiver can initiate therapy at the onset of symptoms (self-management) without direct guidance by the PCP to adjust the ICS dose. Therefore, we evaluated the effectiveness of ICS use by SBA compared with PBA by a pragmatic trial in African-American children with mild asthma at PCP offices in the community.

Section snippets

Study design and participants

This study was a randomized, open-label, 2-arm, pragmatic trial in African-American children with mild asthma under the care of 12 participating PCPs in Saint Louis, MO (Clinicaltrials.gov: NCT02298205). We included African-American children, aged 6 to 17 years, under the care of the participating PCP with (1) physician-diagnosed asthma by the participant's PCP, (2) prescribed low-dose ICS, leukotriene receptor antagonist, or low-dose ICS plus LABA (for 12- to 17-year-olds), (3)

Demographic characteristics of participants

Of 1825 potential participants, 311 attended the first visit, and 206 participants were randomized (PBA n = 103, SBA n = 103) between March 2015 and October 2016 (Figure 1). There were significantly more females in the SBA group (P = .02). Otherwise, the participant characteristics were similar between groups (Table I). Both groups received similar number of phone-based education calls during run-in (PBA: 3.4 ± 0.6 calls vs SBA: 3.3 ± 0.6 calls; P = .46). A total of 179 participants completed

Discussion

In this pragmatic trial conducted in the primary care setting, SBA of ICS with SABA among African-American children with well-controlled mild asthma at study entry was similar in effectiveness and safety to PBA over 1 year. SBA of ICS resulted in similar level of asthma control as PBA with almost one-fourth of the exposure to ICS. The mean difference in asthma control between groups was much smaller than the reported minimally important difference,27, 29 indicating that there is little

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    Research reported in this work was funded through a Patient-Centered Outcomes Research Institute (PCORI) award (AS-1307-05588). The statements presented in this work are solely the responsibility of the authors and do not necessarily represent the views of the PCORI, its Board of Governors, or its Methodology Committee.

    Conflicts of interest: K. Sumino reports university grant funding from the National Institutes of Health (NIH), the American Lung Association, and the Patient-Centered Outcomes Research Institute (PCORI) and personal fee from Teva. L. B. Bacharier reports grants from the NIH; personal fees from GlaxoSmithKline, Genentech/Novartis, Merck, DBV Technologies, Teva, Boehringer Ingelheim, AstraZeneca, WebMD/Medscape, Sanofi/Regeneron, Vectura, and Circassia; and research support from Sanofi and Vectura. M. Castro receives university grant funding from the NIH, the American Lung Association, and PCORI; receives pharmaceutical grant funding from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, and sanofi-aventis; is a consultant for Aviragen, Boston Scientific, Genentech, Nuvaira, Neutronic, Therabron, Theravance, Vectura, 4D Pharma, VIDA, Mallinckrodt, Teva, and Sanofi-Aventis; is a speaker for Astra-Zeneca, Boehringer Ingelheim, Boston Scientific, Genentech, Regeneron, Sanofi, and Teva; and receives royalties from Elsevier. The rest of the authors declare that they have no relevant conflicts of interest.

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