Asthma is a disease with high morbidity. In the United States, about 26 million individuals have asthma, accounting for 1.7 million emergency department visits and 440,000 hospitalizations annually.1Centers for Disease Control and PreventionAsthma surveillance data.https://www.cdc.gov/asthma/asthmadata.htmDate accessed: April 23, 2019Google Scholar Most patients with severe asthma respond to inhaled corticosteroid (ICS) therapy combined with short-acting beta-agonists or long-acting beta-agonists (LABAs); however, about 3.6% to 10% of subjects with asthma have severe disease refractory to maintenance therapy with ICS, and account for a disproportionate percentage of asthma-related costs.2Chung K.F. Wenzel S.E. Brozek J.L. Bush A. Castro M. Sterk P.J. et al.International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma.Eur Respir J. 2014; 43: 343-373Crossref PubMed Scopus (2433) Google Scholar,3Hekking P.P. Wener R.R. Amelink M. Zwinderman A.H. Bouvy M.L. Bel E.H. The prevalence of severe refractory asthma.J Allergy Clin Immunol. 2015; 135: 896-902Abstract Full Text Full Text PDF PubMed Scopus (459) Google Scholar The development of mAbs for the treatment of asthma has revolutionized the care of these patients with severe asthma. At the time of this writing, the Food and Drug Administration has approved 5 biologics for the treatment of severe asthma. These are omalizumab, an anti-IgE antibody for allergic asthma; 3 anti–IL-5 or receptor antagonists (anti–IL-5; mepolizumab, reslizumab, and benralizumab) for severe eosinophilic asthma; and dupilumab, an IL-4 receptor alpha antagonist approved for the treatment of moderate to severe eosinophilic asthma or corticosteroid-dependent asthma.4Hambly N. Nair P. Monoclonal antibodies for the treatment of refractory asthma.Curr Opin Pulm Med. 2014; 20: 87-94Crossref PubMed Scopus (63) Google Scholar Our goal was to evaluate the percentage of patients with asthma in the United States who met criteria for eligibility for any of these mAbs and to assess the degree of overlap of participants eligible for these biologics. We identified participants with severe asthma from the 2005-2012 National Health and Nutrition Examination Survey (NHANES) to generate a nationally representative sample. Participants with severe asthma were 6 years or older with current asthma; on ICS combined with LABA or an anticholinergic for at least a year, or on oral corticosteroids for at least 3 months at the time of interview; and had 1 or more exacerbation in the previous year requiring an emergency room or urgent care center visit. We determined whether subjects were eligible for a biologic on the basis of Food and Drug Administration–approved indications. For omalizumab, this included age, weight, IgE, and perennial sensitivity. Because only NHANES 2005-2006 had IgE and perennial sensitivity data available, we imputed these for the period 2007 to 2012. For the anti–IL-5s and dupilumab, eligibility included age and eosinophil count. For dupilumab, eligibility also included patients on oral steroid for at least 90 days at the time of the interview. We conducted sensitivity analyses to evaluate the impact of varying duration of ICS/LABA use and oral corticosteroid use on proportion of patients classified as having severe asthma. Full details of methods can be found in this article’s Methods section in the Online Repository at www.jacionline.org. There were 3039 survey participants with current asthma. There was a female preponderance (63% [60-66]). Almost a quarter (22% [19-27]) had an emergency room or urgent care visit for asthma in the previous year. Ninety-nine (3.1% [2.3-4.2]) participants met criteria for severe asthma (see Table E1 and Fig E1 in this article’s Online Repository at www.jacionline.org). This proportion was robust to various definitions of severity based on duration of ICS/LABA or oral corticosteroid use (see Fig E2 in this article’s Online Repository at www.jacionline.org). Seventy-six percent of participants younger than 18 years had eosinophil counts of greater than 150 cells/mm3, and 40% of these participants had eosinophil counts of greater than or equal to 400 cells/mm3, compared with 67% and 25%, respectively, of those 18 years or older (Table I). Table E2 in this article’s Online Repository at www.jacionline.org presents results of imputation of IgE and perennial sensitivity.Table IProportion of participants with asthma and severe asthma eligible for mAb therapymAb eligibilityWeighted % (95% CI)∗NHANES sample weights based on the complex sampling survey design were used in constructing estimates.Overall≤18 y>18 yEligible for at least 1 biologic All asthma (n = 3039)2.8 (1.9-3.7)2.6 (1.4-3.9)2.8 (1.8-3.8) Severe asthma (n = 104)84.7 (73.0-96.4)89.7 (74.1-97.9)83.9 (70.4-97.4)Eligible for all the 5 biologics All asthma0.2 (0.0-0.5)00.2 (0.0-0.6) Severe asthma6.4 (3.1-15.9)07.4 (3.5-18.3)Anti–IL-5 therapy MepolizumabAll asthma2.2 (1.5-3.1)2.5 (1.5-3.1)2.1 (1.5-3.1)Severe asthma72.1 (59.6-81.8)88.5 (62.9-97.2)66.9 (53.3-78.2) BenralizumabAll asthma1.3 (0.8-2.1)1.9 (1.0-3.5)1.1 (0.6-1.9)Severe asthma40.2 (26.7-55.4)62.8 (42.8-82.6)32.3 (18.7-49.7) ReslizumabAll asthma0.5 (0.3-1.0)00.7 (0.4-1.4)Severe asthma14.8 (7.1-28.4)019.5 (9.4-36.0)Anti–IL-4/13 receptor alpha DupilumabAll asthma2.4 (1.7-3.3)1.9 (1.0-3.5)2.5 (1.8-3.5)Severe asthma73.4 (63.4-81.4)67.8 (46.2-83.7)75.1 (64.0-83.7)Anti-IgE†Original data are from the period 2005-2006. IgE and sensitivity to perennial allergens for the period 2007-2012 imputed. Only 8 participants were eligible for omalizumab from 2005 to 2006, and only 20 had “severe” asthma. OmalizumabAll asthma1.4 (0.6-2.1)1.3 (0.2-2.4)1.4 (0.5-2.2)Severe asthma41.4 (22.8-60.1)42.5 (10.1-75.0)41.3 (19.5-63.2) Original dataAll asthma1.6 (0.7-3.8)QNSQNSSevere asthma58.5 (30.7-81.8)QNSQNSQNS, Insufficient sample.∗ NHANES sample weights based on the complex sampling survey design were used in constructing estimates.† Original data are from the period 2005-2006. IgE and sensitivity to perennial allergens for the period 2007-2012 imputed. Only 8 participants were eligible for omalizumab from 2005 to 2006, and only 20 had “severe” asthma. Open table in a new tab QNS, Insufficient sample. Of those with asthma, 2.4% were dupilumab-eligible, 2.2% mepolizumab-eligible, 1.6% omalizumab-eligible, 1.3% benralizumab-eligible, and 0.5% reslizumab-eligible. Among those with severe asthma, 73% were dupilumab-eligible, 72% mepolizumab-eligible, 41% omalizumab-eligible, 40% benralizumab-eligible, and 15% reslizumab-eligible (Table I). About 2.8% of participants with asthma and 85% of those with severe asthma were eligible for at least 1 biologic. Every participant eligible for anti–IL-5 was also eligible for dupilumab except for participants aged 6 to 11 years who were eligible for mepolizumab (7% of mepolizumab-eligible participants) but not for dupilumab. Ninety-one percent, 55%, and 22% of dupilumab-eligible participants were eligible for mepolizumab, benralizumab, and reslizumab, respectively. More than 70% of omalizumab-eligible participants were dupilumab- or mepolizumab-eligible. Conversely, about 40% of participants eligible for dupilumab- or anti–IL-5 were eligible for omalizumab (Fig 1, A and B). Overall, on the basis of these eligibility criteria, 702,000 (95% CI, 468,000-962,000) people in the United States would be eligible for at least 1 biologic as a treatment for asthma. In a nationally representative sample of the US population, we found that more than 80% of participants with severe asthma and 2.8% of participants with asthma may be eligible for 1 of the currently available biologics. To our knowledge, this is the first study to date providing an estimate of Americans eligible for asthma biologics. These levels of eligibility are similar to the levels in a study of 69 patients with uncontrolled asthma, in which 43.5% were eligible for omalizumab, but higher than levels in a retrospective study of mepolizumab eligibility among patients referred to a tertiary center for severe asthma, which found that 49% were eligible for mepolizumab.5Lee J. Tay T.R. Radhakrishna N. Hore-Lacy F. Mackay A. Hoy R. et al.Nonadherence in the era of severe asthma biologics and thermoplasty.Eur Respir J. 2018; 51: 1701836Crossref PubMed Scopus (78) Google Scholar,6Comberiati P. McCormack K. Malka-Rais J. Spahn J.D. Proportion of severe asthma patients eligible for mepolizumab therapy by age and age of onset of asthma.J Allergy Clin Immunol Pract. 2019; 7: 2689-2696Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar These results are also consistent with previous studies on asthma phenotypes including a study using NHANES to generate clusters of asthma phenotype,7Tran T.N. Zeiger R.S. Peters S.P. Colice G. Newbold P. Goldman M. et al.Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma.Ann Allergy Asthma Immunol. 2016; 116: 37-42Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar which showed that 78% of children and 69% of adults had eosinophilic asthma. This distribution of eosinophilic asthma is likely related to the percentage of participants we have found as eligible to 1 of these biologics given that 4 of the 5 currently available biologics are indicated for eosinophilic asthma. The proportion of omalizumab-eligible participants eligible for mepolizumab in this study is slightly higher than previously reported. The Identification and Description of sEvere Asthma patients in a cross-sectionaL study, IDEAL,8Albers F.C. Mullerova H. Gunsoy N.B. Shin J.Y. Nelsen L.M. Bradford E.S. et al.Biologic treatment eligibility for real-world patients with severe asthma: the IDEAL study.J Asthma. 2018; 55: 152-160Crossref PubMed Scopus (73) Google Scholar an observational study of patients with severe asthma, showed that 53% of omalizumab-eligible patients from Australia and North America were eligible for anti–IL-5. Another study showed that 47% of omalizumab-eligible patients were eligible for anti–IL-5.5Lee J. Tay T.R. Radhakrishna N. Hore-Lacy F. Mackay A. Hoy R. et al.Nonadherence in the era of severe asthma biologics and thermoplasty.Eur Respir J. 2018; 51: 1701836Crossref PubMed Scopus (78) Google Scholar However, our results of the proportion of patients eligible for anti–IL-5 or mepolizumab who were eligible for omalizumab are similar to the 37% and 36% reported by IDEAL8Albers F.C. Mullerova H. Gunsoy N.B. Shin J.Y. Nelsen L.M. Bradford E.S. et al.Biologic treatment eligibility for real-world patients with severe asthma: the IDEAL study.J Asthma. 2018; 55: 152-160Crossref PubMed Scopus (73) Google Scholar and Lee et al,5Lee J. Tay T.R. Radhakrishna N. Hore-Lacy F. Mackay A. Hoy R. et al.Nonadherence in the era of severe asthma biologics and thermoplasty.Eur Respir J. 2018; 51: 1701836Crossref PubMed Scopus (78) Google Scholar respectively. Switches between these biologics are possible due to the overlap although the proportion of eligible participants dropped significantly as eligibility criteria became stricter based on age and eosinophil count. This was most notable for reslizumab, approved for those 18 years or older and with eosinophil counts of greater than 400 cells/mm3 (see Table E3 in this article’s Online Repository at www.jacionline.org). Only a quarter of adults with severe asthma in this study had eosinophil count of greater than or equal to 400 cells/mm3 and just 2 of 10 mepolizumab-eligible participants were reslizumab-eligible. This is similar to the 18% of mepolizumab-eligible patients eligible for reslizumab in IDEAL.8Albers F.C. Mullerova H. Gunsoy N.B. Shin J.Y. Nelsen L.M. Bradford E.S. et al.Biologic treatment eligibility for real-world patients with severe asthma: the IDEAL study.J Asthma. 2018; 55: 152-160Crossref PubMed Scopus (73) Google Scholar Because the study design was cross-sectional, we are unable to make inferences about how disease severity or treatment changed over time. We could have also misclassified participants’ disease severity. Our estimates of omalizumab eligibility are imprecise because of the small number of subjects with IgE data. Questionnaire data are self-reported, and the definition of asthma severity may be influenced by health care utilization patterns and medication adherence. However, these are real-life challenges that clinicians face when defining asthma severity in practice. Also, we have not addressed comparative effectiveness or costs of these biologics and this will be important for future research. Regardless of eligibility, providers may need to incorporate other factors such as insurance, costs, and route of administration into their decision to prescribe these biologics. For instance, dupilumab and mepolizumab are approved for home administration, whereas reslizumab is given intravenously. Furthermore, annual costs of these biologics, the wholesale acquisition costs, range from $27,950 for reslizumab to $48,472 for the first year on benralizumab.9Mauger D. Apter A.J. Indirect treatment comparisons and biologics.J Allergy Clin Immunol. 2019; 143: 84-86Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Despite these limitations, however, this study provides important insights into available treatments options for patients with severe asthma for clinicians in real-world settings. In summary, using a nationally representative sample, we were able to show that 80% of participants with severe asthma, and about 700,000 Americans, would meet criteria for 1 of the currently available biologics. These results could help inform therapeutic choices for providers caring for patients with asthma who may be considering initiating therapy with a biologic agent or switching to an alternative agent. Data for analysis were obtained from 4 pooled cycles (2005-2012) of the NHANES. The National Center for Health Statistics of the Centers for Disease Control and Prevention conducts the NHANES as a continuous publicly available US population–based cross-sectional survey of the noninstitutionalized civilian population.E1Centers for Disease Control and PreventionNational Center for Health Statistics (NCHS). National Health and Nutrition Examination Survey Data. 2016.http://www.cdc.gov/nchs/nhanes/imdex.htmDate accessed: March 30, 2019Google Scholar NHANES has been conducted continuously in biennial blocks since 1999. About 10,000 individuals of all ages are sampled per biennial cycle. Sampling procedures are designed such that estimates are representative of the general noninstitutionalized US population. NHANES has 2 phases of information gathering. The initial phase is an interview conducted in homes and subsequently, a health examination component in a mobile examination center where physical examination and laboratory evaluation take place. Response rate for the 4 pooled survey cycles ranged from 71% to 81% for the interview portion and from 69% to 78% for the examination portion. In NHANES 2005-2006, low-income persons, adolescents 12 to 19 years, pregnant persons, persons 60 years and older, blacks, and Mexican Americans were oversampled. NHANES 2007-2008 and NHANES 2009-2010 oversampled all Hispanics, persons 60 years and older, blacks, and low-income persons, whereas adolescents and pregnant people were no longer oversampled. In addition, for each of the race/ethnicity domains, the 12- to 15-year and 16- to 19-year age domains were combined whereas the 40- to 59-year age domains were split into 10-year age domains: 40 to 49 years and 50 to 59 years. Thus, there has been an increase in the number of participants aged 40 years and older and a decrease in the 12 to 19 year age group in comparison to previous cycles. In NHANES 2011-2012 and 2013-2014, non-Hispanic Asians were oversampled in addition to Hispanics, non-Hispanic blacks, older adults, and low-income whites/others. Given this complex sample design, sample weights are assigned and analysis needs to use appropriate survey analysis methods. Participants aged 6 years and older were eligible. We considered a subject as having current asthma if the subject answered the following questions in the affirmative: “Has a doctor or health professional ever told [you/study participant] that [you/s/he had] asthma?” and “Do you still have asthma?” We considered asthma to be severe if the participant was on ICS therapy in combination with a LABA or long-acting muscarinic antagonist for 1 or more year, or oral corticosteroids for 3 or more months at the time of interview, and had 1 or more exacerbations in the previous year requiring a visit to an emergency room or urgent care center. For each of the biologics, we determined whether subjects with severe disease were eligible for a biologic based on the Food and Drug Administration–approved indications per the drug labels. Although some post-hoc studies have identified benefits of some of these biologics regardless of peripheral eosinophil counts, for the anti-IL5s and dupilumab, we defined eosinophil cut offs per the primary endpoint cut offs in the pivotal phase 3 trials used to grant approval. We defined subjects as eligible for omalizumab if they were aged 6 to 11 years, had IgE levels between 30 and 1300 kU/L, weighed 44 to 330 lb, and had an IgE level greater than or equal to 0.35 kU/L to 1 of the following perennial allergens: Dermatophagoides farinae, Dermatophagoides pteronyssinus, cat, dog, roach, alternaria, aspergillus, mouse, and rat. For patients 12 years or older, eligible subjects had IgE levels between 30 and 700 kU/L, weighed 66 to 330 lb, and had an IgE level greater than or equal to 0.35 kU/L to 1 of the perennial allergens outlined above. Subjects were eligible for mepolizumab if aged 6 years or more with eosinophil count greater than or equal to 150 cells/μL; for benralizumab, if aged 12 years or older with eosinophil count greater than or equal to 300 cells/μL; and for reslizumab, if 18 years or older with eosinophil count greater than or equal to 400 cells/μL. Subjects eligible for dupilumab were 12 years or older with eosinophil count greater than or equal to 150 cells/μL or oral corticosteroid use. We included only those patients who had been on oral steroids for at least 30 days at the time of the interview for the oral corticosteroid criterion. Data on age, sex, race/ethnicity, insurance status, and income were from self-report. Weight, body mass index, eosinophil counts, and IgE levels were objectively measured. Only NHANES 2005-2006 included serum total IgE and specific IgE levels to perennial allergens. Smoking history was available for participants 20 years or older. A participant was considered a current smoker if they (1) had smoked at least 100 cigarettes in life and (2) reported currently smoking. A nonsmoker was one who had smoked fewer than 100 cigarettes in life and reported not smoking at the time of the interview. A former smoker was one who had smoked at least 100 cigarettes in life but was not currently smoking. We report weighted proportions or means. SEs and CIs are used as appropriate. P values for differences in proportions or means were calculated using chi-square test for categorical variables and Student t test for continuous variables. To determine omalizumab eligibility for subjects with asthma in the 2007-2012 surveys, we imputed serum IgE levels and sensitivity to perennial allergens because data on serum or perennial allergen IgE levels were not collected during those years. A total of 659 (88%) and 750 (100%) of the 750 eligible participants with asthma from the 2005-2006 cycle had complete serum IgE and perennial allergen testing data, respectively. We used multiple imputation techniques.E2Rubin D.B. Multiple imputation for nonresponse in surveys. Wiley, New York1987Crossref Google Scholar, E3Liu B. Yu M. Graubard B.I. Troiano R.P. Schenker N. Multiple imputation of completely missing repeated measures data within person from a complex sample: application to accelerometer data in the National Health and Nutrition Examination Survey.Stat Med. 2016; 35: 5170-5188Crossref PubMed Scopus (12) Google Scholar, E4Schafer J.L. Multiple imputation: a primer.Stat Methods Med Res. 1999; 8: 3-15Crossref PubMed Scopus (2441) Google Scholar, E5Schafer J.L. Ezzati-Rice T.M. Johnson W. Khare M. Little R.J.A. Rubin D.B. The NHANES III multiple imputation project.in: Proceedings of the Survey Research Methods Section. American Statistical Association, 1998Google Scholar We proceeded with fully conditional specification to decrease confounding in our estimates.E6Lee K.J. Carlin J.B. Multiple imputation for missing data: fully conditional specification versus multivariate normal imputation.Am J Epidemiol. 2010; 171: 624-632Crossref PubMed Scopus (491) Google Scholar, E7Liu Y. De A. Multiple imputation by fully conditional specification for dealing with missing data in a large epidemiologic study.Int J Stat Med Res. 2015; 4: 287-295Crossref PubMed Google Scholar Thus, we included age, sex, race/ethnicity, weight, insurance status, and family to poverty level in all imputation models. Eosinophil count was also included as a possible auxiliary variable. Ten imputed data sets were developed. All analyses were done as per multiple imputation and survey data analyses in STATA (version 15.1, STATCorp, College Station, Tex). NHANES sample weights were used in all analyses to obtain unbiased national estimates. SEs, CIs, and P values were developed as appropriate for the complex survey design by using Taylor series linearization methods. P values of less than .05 were considered statistically significant. We sought to evaluate the impact of using different cutoffs of duration on medication use on proportion of participants classified as having severe asthma. We assessed this proportion across varying durations of reported ICS/LABA or long-acting muscarinic antagonist use (≥3, 6, 9, 12, 24, and 48 months) with varying oral steroid durations (≥3, 6, and 12 months). Fig E2Percentage of participants with severe asthma (by varying durations of medication use). Percentage of participants with severe asthma was approximately 3% regardless of duration of medication use.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Table E1Baseline characteristics of survey participants with current asthmaCharacteristicOverall<18 y≥18 yN303911861853Sex: female (%)58.8 (56.4-61.2)46.5 (42.7-50.3)63.1 (60.1-66.0)Race/ethinicity Non-Hispanic white67.8 (63.4-71.9)56.5 (51.1-61.8)71.8 (67.5-75.8) Non-Hispanic black15.8 (13.0-18.9)20.5 (16.6-25.0)14.1 (11.6-17.1) Hispanic10.6 (8.6-13.0)16.2 (13.2-19.7)8.6 (6.7-10.9) Asian and other Non-Hispanic races5.9 (4.7-7.3)6.8 (5.1-9.1)5.5 (4.2-7.2)BMI (kg/m2), mean (SE)28.5 (0.23)22.4 (0.27)30.6 (0.25)Poverty to income ratio,∗Family income to poverty level as per the Department of Health and Human Services annual poverty guidelines. mean (SE)2.6 (0.08)2.4 (0.09)2.7 (0.09)Health insurance, % (CI) No coverage13.2 (11.1-15.6)6.9 (4.7-10.1)15.4 (12.9-18.3) Of those insured:Private insurance65.9 (62.7-68.9)58.7 (65.3-71.9)68.7 (65.3-71.9)Public insurance34.0 (31.0-37.1)41.2 (35.1-47.6)31.2 (28.0-34.6)Other insurance0.1 (0.0-0.4)0.03 (0.0-0.2)0.1 (0.03-0.5)Asthma-related questions (CI) Severe asthma†Severe asthma defined as current asthma and on ICS combined with LABA or anticholinergic agent and with ≥1 exacerbation requiring emergency room or urgent care visit in previous 12 months.3.1 (2.3-4.2)2.8 (1.8-4.5)3.2 (2.3-4.5) Emergency room or urgent care visit for asthma, past 12 mo21.6 (18.8-24.8)22.4 (18.6-26.6)21.4 (18.1-25.0) On ICS8.3 (6.9-9.8)11.1 (9.2-13.3)7.3 (5.7-9.3) On ICS/LABA15.3 (13.4-17.5)9.9 (7.9-12.5)17.2 (14.7-20.1)‡Patients had to have reported oral corticosteroids for ≥3 months.On oral corticosteroids2.5 (1.9-3.3)2.9 (1.8-4.7)2.3 (1.7-3.2)Smoking status (CI) Current smoker25.3 (22.1-28.6)NA25.3 (22.1-28.6) Former smoker25.5 (23.3-28.0)NA25.5 (23.3-28.0) Nonsmoker49.2 (45.7-52.7)NA49.2 (45.7-52.7)Hematological indices Eosinophil count, mean (SE)272 (6.4)336 (16.2)251 (5.9) Eosinophil count <150 cells/mm3, %30.4 (28.4-32.5)24.0 (20.6-27.7)32.7 (30.3-35.3) Eosinophil count ≥150-300 cells/mm3, %25.0 (23.1-27.0)18.2 (15.2-21.7)27.4 (25.1-30.0) Eosinophil count ≥300-400 cells/mm3, %14.9 (13.4-16.5)15.5 (12.4-19.2)14.7 (12.9-16.8) Eosinophil count ≥400 cells/mm3, %29.6 (27.7-31.6)42.3 (38.4-46.3)25.1 (23.1-27.3)Total serum IgE (mg/dL) IgE <3029.3 (24.1-34.6)17.0 (10.6-23.3)31.4 (25.2-37.5) IgE 30-70063.6 (59.2-68.1)68.6 (62.3-75.8)62.8 (57.2-68.4) IgE >700-13003.8 (2.0-5.7)8.3 (5.5-11.1)3.1 (1.1-5.2) IgE >13003.2 (1.8-4.6)6.1 (1.9-10.4)2.7 (1.3-4.2)Sensitivity to perennial aeroallergens,%59.4 (49.7-69.1)67.2 (56.2-79.2)56.3 (45.1-62.1)NA, not applicable/available.∗ Family income to poverty level as per the Department of Health and Human Services annual poverty guidelines.† Severe asthma defined as current asthma and on ICS combined with LABA or anticholinergic agent and with ≥1 exacerbation requiring emergency room or urgent care visit in previous 12 months.‡ Patients had to have reported oral corticosteroids for ≥3 months. Open table in a new tab Table E2Imputation results: IgE and sensitivity to perennial allergensVariables imputedOriginal dataImputed dataTotal serum IgE (mg/dL)∗Total serum IgE using the Pharmacia Diagnostics ImmunoCAP 1000 System (Kalamazoo, Mich). IgE <3027.2 (21.8-33.4)30.1 (22.9-37.3) IgE 30-70065.2 (58.2-71.6)63.1 (57.3-68.8) IgE >700-13004.4 (2.6-7.3)3.6 (1.1-6.2) IgE >13003.2 (1.5-6.5)3.2 (1.4-5.1)Sensitivity to perennial aeroallergens, %60.3 (55.6-64.9)58.2 (47.2-69.3)∗ Total serum IgE using the Pharmacia Diagnostics ImmunoCAP 1000 System (Kalamazoo, Mich). Open table in a new tab Table E3Eligibility for mAbs based on current drug labelingEosinophil count (cells/mm3)Patients 6 to <12 y,∗Patients <6 years of age are not eligible for any of the currently approved biologics. Serum IgE (IU/mL)<3030-1300>1300<150NoneOmalizumab†To be eligible for omalizumab, patients also need to demonstrate sensitivity to a perennial allergen, and weigh 44-330 lb if <12 years or 66-330 lb if ≥12 years.None≥150Omalizumab†To be eligible for omalizumab, patients also need to demonstrate sensitivity to a perennial allergen, and weigh 44-330 lb if <12 years or 66-330 lb if ≥12 years.MepolizumabMepolizumabMepolizumabEosinophil count (cells/mm3)Patients 12 to <18 y, Serum IgE (IU/mL)<3030-700>700<150NoneOmalizumab†To be eligible for omalizumab, patients also need to demonstrate sensitivity to a perennial allergen, and weigh 44-330 lb if <12 years or 66-330 lb if ≥12 years.None150-<300OmalizumabDupilumabDupilumabDupilumabMepolizumabMepolizumabMepolizumab≥300OmalizumabDupilumabDupilumabDupilumabMepolizumabMepolizumabMepolizumabBenralizumabBenralizumabBenralizumabEosinophil count (cells/mm3)Patients ≥18 y, Serum IgE (IU/mL)<3030-700>700<150NoneOmalizumab†To be eligible for omalizumab, patients also need to demonstrate sensitivity to a perennial allergen, and weigh 44-330 lb if <12 years or 66-330 lb if ≥12 years.None150-<300OmalizumabDupilumabDupilumabDupilumabMepolizumabMepolizumabMepolizumab300-<400OmalizumabDupilumabDupilumabDupilumabMepolizumabMepolizumabMepolizumabBenralizumabBenralizumabBenralizumab≥400OmalizumabDupilumabDupilumabDupilumabMepolizumabMepolizumabMepolizumabBenralizumabBenralizumabBenralizumabReslizumabReslizumabReslizumab∗ Patients <6 years of age are not eligible for any of the currently approved biologics.† To be eligible for omalizumab, patients also need to demonstrate sensitivity to a perennial allergen, and weigh 44-330 lb if <12 years or 66-330 lb if ≥12 years. Open table in a new tab NA, not applicable/available.