Table 2:
β2 agonist studies reporting only clinical effectiveness or harms (no genetic findings)
| Author, Year Country |
Study Type Age group(s) Race/ethnicity (N) |
Operational definition for Black subgroup |
Condition(s)/ Drug(s) Studied |
Findings | Outcome type and relative directionality of effect among Blacks |
|---|---|---|---|---|---|
| SABA Efficacy | |||||
| McGarry 201526 USA, Puerto Rico SAGE II and GALA II studies |
Cross-sectional Children and adolescents Black (864) Mexican (687) Puerto Rican (974) Mixed/other Latino (435) |
Self-report; participant and all parents and grandparents self-identified as Black or African American | Asthma SABA (Albuterol) |
Blacks were less likely to be unresponsive to bronchodilator (BD) (positive BD response defined as ≥12% increase and a ≥200 mL increase in FEV1) as compared with Mexican Americans (OR:0.71, 95%CI: 0.50 to 0.99, p=0.04) | ↑ Efficacy |
| Wechsler 201122 USA Asthma Clinical Research Network |
Secondary analysis of data from 10 trials Adolescents and adults Black (233) White (795) |
Self-report | Asthma SABA (Agent not specified) |
No statistically significant difference observed in response between Blacks and Whites during short-acting β agonist therapy. | = Efficacy |
| Naqvi 2008;27 Naqvi 200728 USA, Mexico, Puerto Rico GALA and SAGE studies |
Cross-sectional Children, adolescents, and adults 199/200 Black (163/216) Mexican (106/294) Puerto Rican (246/365) |
Self-report; participant and all parents and grandparents self-identified as Black or African American | Asthma SABA (Albuterol) |
Puerto Ricans had lower bronchodilator responsiveness (% change in FEV1) as compared with Mexicans (p<0.001) and Blacks (p<0.001); the same signals were detected in the subset of asthmatics with FEV1 80% of predicted. Puerto Ricans of all ages and Black children with moderate-to-severe asthma demonstrated the lowest bronchodilator responsiveness overall. ICS use was associated with augmented bronchodilator responsiveness in Mexican Americans and Puerto Ricans (both p<0.05), but not in Blacks; these signals remained after excluding those who used long-acting β2 agonists |
↑ Efficacy (compared with Puerto Ricans) ↓ Efficacy (among Blacks with moderate-to-severe asthma) |
| Hardie 200720 | Cross-sectional Adults Black (16) White (16) |
NR | Asthma SABA (albuterol) |
FEV1 (in liters) before and after bronchodilator administration in Blacks and Whites, respectively, was 1.94±0.39 and 2.13±0.70 at baseline, 2.66±0.49 and 3.06±0.86 at 180 mcg albuterol, 2.88±0.48 and 3.37±0.91 at 360 mcg, and 2.42±1.29 and 3.47±0.95 at 540 mcg. The differences between Blacks and Whites in responsiveness were significant at 360 mcg (p<0.05) and 540 mcg (p<0.01). Visual Analog Scale and Borg score results for breathing discomfort did not differ significantly by group at all doses of albuterol. While words used by participants to describe asthma symptoms at 540 mcg of albuterol indicated a reduction in symptoms among Whites, 80% of Black participants used words indicating persistent upper airway symptoms. |
↓ Efficacy |
| El-Ekiaby 200623 | Cross-sectional Adults Blacks (155) Whites (140) |
Self-report | Asthma SABA (albuterol) |
There were no significant differences between Blacks and Whites in response to standard doses of albuterol, with mean peak expiratory flow rates increasing significantly in both groups. Further subgroup comparisons did not find any significant differences between Blacks and Whites with mild, severe, or life-threatening pretreatment obstruction. | = Efficacy |
| Lima 200013 USA |
Cross sectional Adults Black (15) White (18) |
NR | Asthma SABA (Albuterol) |
No difference in albuterol-induced change in FEV1 or percent predicted FEV1 between Blacks and Whites | = Efficacy |
| LABA Efficacy | |||||
| Murphy 201221 USA |
Secondary analysis of data from 4 RCTs Adolescents/Adults (12 years or older) Black (356) White (392) Other, including Hispanic (352) |
Self-report | Asthma LABA (Formoterol + Budesonide) |
Asthma event rates were significantly lower for participants receiving budesonide+formoterol as compared with participants treated with budesonide alone, regardless of race/ethnicity. | = Efficacy |
| Lemanske 201014 USA |
Randomized crossover trial Children and adolescents Black (45) White (67) Hispanic (39) Other (12) |
NR | Asthma LABA (Salmeterol) |
Race/ethnicity significantly associated with patterns of differential response to treatment (based on comparison of the need for treatment with oral prednisone for acute asthma exacerbation, number of asthma-control days, and FEV1) (p=0.005) Hispanic and non-Hispanic White participants most likely to have best response to LABA step-up, least likely to have best response to ICS step-up Black patients equally likely to have a best response to LABA or ICS step up therapy and less likely to have a best response to LTRA step-up. |
= Efficacy |
| LABA Safety | |||||
| Weinstein 201924 | RCT Adolescents and adults Black (705) Multiracial (968) Asian (550) American Indian or Alaska Native (440) Native Hawaiian or other Pacific Islander (9) Unknown (1) White (9056) |
Self-report Patients who selected Black plus another group were analyzed as part of a Black subgroup in the safety analysis (total revised N 1116) |
Asthma LABA (formoterol + mometasone furoate vs. mometasone furoate alone) |
Asthma exacerbations were more frequent among Black patients compared with non-Blacks in both treatment groups. Fewer asthma exacerbations occurred in Black patients in the mometasone furoate + formoterol group as compared with Blacks in the mometasone furoate only group (17.0% vs. 21.2%). Among non-Blacks, these frequencies were 11.5% in the combined treatment group and 12.5% in the mometasone-only group. Incidence of serious asthma outcomes (composite end point including asthma-related hospitalizations, intubations, and deaths) among Blacks were 1.2% in the combined group and 0.4% in the mometasone only group; among non-Blacks the frequency of hospitalization was 0.6% in both the combined treatment group and the mometasone only group. Adherence was lower in the Black subgroup; Black participants had a greater rate of treatment discontinuation as compared with non-Black |
= Safety (asthma exacerbations) ↓ Safety (composite of serious asthma outcomes) |
| Peters 201625 | RCT Adolescents and adults Black (401) White (4003) Asian (907) Other (536) |
Self-report | Asthma LABA (budesonide + formoterol vs. budesonide only) |
Risk of asthma exacerbation hazard ratios (95% CI, p) for comparison of the combined treatment group to the budesonide only group was 0.851 (0.608-1.192, p=0.348) among Blacks, 0.827 (0.720-0.950, p=0.007) among Whites, 0.776 (0.565-1.067, p=0.119) among Asians, and 1.026 (0.662-1.591, p=0.908) among participants of other race/ethnicity. | = Safety |
| Stempel 201616 AUSTRI trial Multiple countries |
RCT Adolescents and adults Black (1726) White (8783) Other (1170) |
NR | Asthma LABA (salmeterol+fl uticasone vs. fluticasone alone) |
No significant difference in rate of asthma-related hospitalization by race; investigators note that the trial was not powered to detect noninferiority in race/ethnicity subgroups. | = Safety |
| Stempel 201615 VESTRI trial Multiple countries |
RCT Children Black (1050) White (4030) Other (1128) |
NR | Asthma LABA (salmeterol+fl uticasone vs. fluticasone alone) |
Serious asthma-related event rates were less than 2% of the defined populations in all race subgroups. Time to event analysis of the first severe asthma exacerbation was not statistically significant between the fluticasone alone vs. salmeterol+fluticasone groups in the overall cohort or in the Black subgroup. Investigators note that the safety analyses were not powered to detect noninferiority in subgroups. |
= Safety |
| Wechsler 201122 USA Asthma Clinical Research Network |
Secondary analysis of data from 10 trials Adolescents and adults Black (233) White (795) |
Self-report | Asthma LABA, SABA (Specific agents not specified) |
Increased risk of treatment failures (asthma exacerbation, worsening lung function, increased use of asthma medication, or physician clinical judgment) in Blacks compared to Whites during treatment with long acting β agonists (LABA) (OR: 2.36, 95% CI 1.38-4.02, p=0.002), with or without other medications There was also an increased risk of treatment failure among Blacks as compared with Whites in the subgroup of patients receiving LABA plus a leukotriene receptor antagonist (OR 5.81 95% CI 2.11-16.02, p=0.0007). |
↓ Efficacy |
| Price 201017 Multinational UK/Sweden |
Pooled analysis of 41 trials Children and adolescents Black (369) White (8,947) Asian (1,043) Other or unknown (1,490) |
NR | Asthma LABA (Formoterol) |
No difference in hospital admission rates between formoterol treated and non-LABA-treated patients when analyzed by race/ethnicity. In general, Black participants tended to have higher hospital admission rates than Whites in both the formoterol (1.57% vs 0.65%) and the non-LABA treated (2.63% vs. 0.67%) groups. There was a decreased risk in asthma-related adverse events in the formoterol group (RR 0.67, 95% CI 0.46 to 0.98) and no effect of formoterol by gender or race. |
= Safety |
| Nelson 200618 USA SMART study Note: study terminated after interim analysis due to findings in Blacks and difficulties in enrollment Note: A Cochrane review by Walters et al. 200719 evaluated safety of LABA therapy in children; the subgroup analysis by race and ethnicity in this systematic review was limited to the SMART study, with slightly altered analytic approach. |
RCT Adolescents and adults Black (4,685) White (18,642) Hispanic (1,995) Asian (322) Other (454) |
NR | Asthma LABA (Salmeterol) |
Significant differences between salmeterol and placebo groups among Blacks for a combined outcome of respiratory related death or life threatening experience (20 vs. 5; RR: 4.1; 95% CI: 1.54 to 10.9), a combined outcome of asthma-related death or life threatening experience (19 vs. 4; RR: 4.92; 95% CI: 1.68 to 14.45), and combined all-cause death or life-threatening experience (24 vs 11, RR 2.17, 95% CI 1.06-4.41); no similar increases in risk observed among Whites. The subset of Blacks not using ICS at baseline experienced increased risk of combined respiratory-related death or life-threatening experience (RR 5.61, 95%CI 1.25-25.26) and of combined asthma-related death or life-threatening experience (RR 10.45 (1.34-81.58) with use of salmeterol as compared with placebo, as compared with those using ICS at baseline; no similar increases in risk observed among Whites. As calculated separately in the Cochrane review, Blacks were at particular risk for the respiratory related death and life-threatening asthma event (i.e. intubation, mechanical ventilation) as compared with Whites (RR: 3.9 (95% CI: 1.29 to 11.84). There was no significant difference between the two groups in asthma related deaths after LABA. |
↓ Safety |
Key: ↑ Efficacy=increased efficacy; ↑ Safety=increased safety; ↓ Efficacy=decreased efficacy; ↓ Safety=decreased safety; = Efficacy=equal efficacy; = Safety=equal safety; CI= confidence interval; ICS= inhaled corticosteroids; SABA = short acting β2 agonist; LABA= long-acting β2-agonist; LTRA= leukotriene receptor antagonists; OR=odds ratio; RCT=randomized controlled trial; relative risk; CI confidence interval; SAGE Study of African Americans, Asthma, Genes, and Environments; GALA Genes-environments and Admixture in Latino Americans; SMART Salmeterol Multicenter Asthma Research Trial
Legend: This table summarizes data from included studies evaluating safety and effectiveness of beta-agonists in Blacks as compared with other groups, including directionality of effects and focusing on the subset of studies that did not include any genetic data.