Clinical Response and Remission in Patients With Severe Asthma Treated With Biologic Therapies

BackgroundThe development of novel targeted biologic therapies for severe asthma has provided an opportunity to consider remission as a new treatment goal.Research QuestionHow many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment?Study Design and MethodsThe Danish Severe Asthma Register is a nationwide cohort including all adult patients receiving biologic therapy for severe asthma in Denmark. This observational cohort study defined “clinical response” to treatment following 12 months as a ≥ 50% reduction in exacerbations and/or a ≥ 50% reduction in maintenance oral corticosteroid dose, if required. “Clinical remission” was defined by cessation of exacerbations and maintenance oral corticosteroids, as well as a normalization of lung function (FEV1 > 80%) and an Asthma Control Questionnaire-6 score ≤ 1.5 following 12 months of treatment.ResultsFollowing 12 months of treatment, 104 (21%) of 501 biologic-naive patients had no response to treatment, and 397 (79%) had a clinical response. Among the latter, 97 (24%) fulfilled the study criteria of clinical remission, corresponding to 19% of the entire population. Remission was predicted by shorter duration of disease and lower BMI in the entire population of patients treated with biologic therapy.InterpretationClinical response was achieved in most adult patients initiating biologic therapy, and clinical remission was observed in 19% of the patients following 12 months of treatment. Further studies are required to assess the long-term outcome of achieving clinical remission with biologic therapy. The development of novel targeted biologic therapies for severe asthma has provided an opportunity to consider remission as a new treatment goal. How many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment? The Danish Severe Asthma Register is a nationwide cohort including all adult patients receiving biologic therapy for severe asthma in Denmark. This observational cohort study defined “clinical response” to treatment following 12 months as a ≥ 50% reduction in exacerbations and/or a ≥ 50% reduction in maintenance oral corticosteroid dose, if required. “Clinical remission” was defined by cessation of exacerbations and maintenance oral corticosteroids, as well as a normalization of lung function (FEV1 > 80%) and an Asthma Control Questionnaire-6 score ≤ 1.5 following 12 months of treatment. Following 12 months of treatment, 104 (21%) of 501 biologic-naive patients had no response to treatment, and 397 (79%) had a clinical response. Among the latter, 97 (24%) fulfilled the study criteria of clinical remission, corresponding to 19% of the entire population. Remission was predicted by shorter duration of disease and lower BMI in the entire population of patients treated with biologic therapy. Clinical response was achieved in most adult patients initiating biologic therapy, and clinical remission was observed in 19% of the patients following 12 months of treatment. Further studies are required to assess the long-term outcome of achieving clinical remission with biologic therapy. Take-home PointsStudy Question: How many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment?Results: This study highlights that almost one in five patients with severe asthma achieve remission following treatment with biologic therapy. Remission was predicted by shorter disease duration at time of treatment initiation and lower BMI.Interpretation: Clinical remission is an achievable treatment goal in adult patients with severe asthma. Larger prospective studies are needed to describe the impact of remission on treatment on longer-term clinical outcomes. Study Question: How many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment? Results: This study highlights that almost one in five patients with severe asthma achieve remission following treatment with biologic therapy. Remission was predicted by shorter disease duration at time of treatment initiation and lower BMI. Interpretation: Clinical remission is an achievable treatment goal in adult patients with severe asthma. Larger prospective studies are needed to describe the impact of remission on treatment on longer-term clinical outcomes. Severe asthma is a highly burdensome condition, affecting approximately 5% to 10% of patients with asthma whose disease remains uncontrolled despite high-dose controller therapy and in whom other causes, including lack of adherence, inadequate inhaler technique, and influence of untreated comorbidities, have been ruled out.1Porsbjerg C. Ulrik C. Skjold T. et al.Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults.Eur Clin Respir J. 2018; 51440868Crossref Scopus (36) Google Scholar, 2Global Initiative for Asthma (GINA)Global Strategy for Asthma Management and Prevention, 2021 report.2021Google Scholar, 3Chung K.F. Wenzel S.E. Brozek J.L. et al.International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma.Eur Respir J. 2014; 43: 343-373Crossref PubMed Scopus (2722) Google Scholar, 4Bel E.H. Sousa A. Fleming L. et al.Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI).Thorax. 2011; 66: 910-917Crossref PubMed Scopus (307) Google Scholar Severe asthma is associated with high morbidity, loss of quality of life, and iatrogenic side effects to treatment, most notably from oral corticosteroids (OCS) prescribed either intermittently to treat exacerbations or as maintenance therapy (maintenance OCS [mOCS]).5Volmer T. Effenberger T. Trautner C. Buhl R. Consequences of long-term oral corticosteroid therapy and its side-effects in severe asthma in adults: a focused review of the impact data in the literature.Eur Respir J. 2018; 521800703Crossref PubMed Scopus (179) Google Scholar,6Sullivan P.W. Ghushchyan V.H. Globe G. Schatz M. Oral corticosteroid exposure and adverse effects in asthmatic patients.J Allergy Clin Immunol. 2018; 141: 110-116.e7Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar Previously, asthma treatment has been focused on achieving disease control.7Thomas D. McDonald V.M. Pavord I.D. Gibson P.G. Asthma remission—what is it and how can it be achieved?.Eur Respir J. 2022; 602102583Crossref Scopus (40) Google Scholar,8Menzies-Gow A. Bafadhel M. Busse W.W. et al.An expert consensus framework for asthma remission as a treatment goal.J Allergy Clin Immunol. 2020; 145: 757-765Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar However, with the development of novel biologic therapies targeting the underlying inflammatory mechanisms, it is natural to consider remission as an achievable treatment target in severe asthma. A similar shift in disease management has been observed in rheumatology. Disease-modifying antirheumatic drugs and targeted biologic therapies have transformed the view on the course of rheumatoid arthritis from a chronic disease to a potentially curable condition, and remission on treatment has been associated with minimal or no clinically detectable disease activity persisting in some patients even after tapering or discontinuing the biologic therapy.9Brahe C.H. Krabbe S. Østergaard M. et al.Dose tapering and discontinuation of biological therapy in rheumatoid arthritis patients in routine care—2-year outcomes and predictors.Rheumatology. 2019; 58: 110-119Crossref Scopus (28) Google Scholar Remission as a treatment outcome is clinically important at two levels. First, patients who achieve complete control of their asthma may have a better long-term prognosis in terms of a reduced risk of excessive lung function decline and future exacerbations. Second, patients achieving clinical remission may also have a better chance of tapering biologic therapy.10Hamada K. Oishi K. Murata Y. Hirano T. Matsunaga K. Feasibility of discontinuing biologics in severe asthma: an algorithmic approach.J Asthma Allergy. 2021; 14: 1463-1471Crossref PubMed Scopus (17) Google Scholar Hence, understanding the likelihood and predictors of remission is clinically important and a key step toward describing the longer term beneficial implications of achieving short-term remission on a biologic treatment. There is currently no clear consensus as to what constitutes clinical response or remission in severe asthma, but a definition has been proposed by Menzies-Gow et al.8Menzies-Gow A. Bafadhel M. Busse W.W. et al.An expert consensus framework for asthma remission as a treatment goal.J Allergy Clin Immunol. 2020; 145: 757-765Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar They include definitions of remission on and off treatment, using varying combinations and cutoffs of absence of symptoms, no OCS use for asthma, stabilization of lung function, and agreement by health care professional and patient about remission assessed over a period of 12 months. This definition of remission may be regarded as a more clinically relevant outcome than previous definitions of super-response,11Upham J.W. Le Lievre C. Jackson D.J. et al.Defining a severe asthma super-responder: findings from a Delphi process.J Allergy Clin Immunol Pract. 2021; 9: 3997-4004Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar as it describes whether the patient achieves complete control following treatment rather than the magnitude of response, which is dependent on the baseline level of control. The aim of the current study was to describe the real-life effectiveness of biologic therapy in severe asthma, to evaluate the proportion of patients who achieve a clinical response and clinical remission, and to identify predictors of nonresponse and remission. Patients were included from the Danish Severe Asthma Register (DSAR), a nationwide cohort of all patients treated with a biologic for severe asthma in Denmark.12Hansen S. Hilberg O. Ulrik C.S. et al.The Danish Severe Asthma Register: an electronic platform for severe asthma management and research.Eur Clin Respir J. 2021; 81842117Crossref Scopus (5) Google Scholar Patient information in DSAR is collected prospectively and follows a clinical protocol with a baseline visit when biologic treatment is commenced, following 4 and 12 months of treatment, and then annually. DSAR is approved by Videnscenter for Dataanmeldelser in the Capital Region (VD-2018-31), and all patients provide written consent for their data to be used for research. For the current analysis, biologic-naive patients commencing biologic therapy between January 1, 2016, and December 31, 2021, were included. All but two patients were aged ≥ 18 years at time of treatment start (the remaining two patients were 16 and 17 years of age, respectively). Indication criteria for all biologic therapies in Denmark are described in e-Table 1. As illustrated, in addition to fulfilling the criteria for biologic therapy (high-dose inhaled corticosteroids plus a second controller), adherence to treatment, and a complete systematic assessment, all patients must have had ≥ 2 exacerbations in the previous 12 months or use mOCS at least 50% of the time in the previous 12 months to qualify for biologic therapy. Patients were included who fulfilled these criteria and for whom complete data were available. A flowchart of the study population is presented in e-Figure 1. The current study assessed two levels of response to treatment after 12 months: clinical response and clinical remission. To define clinical response, we applied a definition reflecting the clinical response that would be perceived as clinically relevant. Hence, in the clinical setting, a clinically relevant response should include an effect on the criteria that set the indication: either exacerbations and/or mOCS use. Clinical response was defined as: (1) a reduction of at least 50% in the annualized exacerbation rate if the indication was based on ≥ 2 exacerbations in the 12 months prior to treatment, and (2) a reduction of at least 50% in the OCS dose from baseline if the indication was based on the need for mOCS. If a patient fulfilled both criteria, a reduction in exacerbations of at least 50%, while maintaining OCS use, was also considered a clinically relevant response, whereas a reduction in OCS dose without a reduction in exacerbations was not, as this would likely indicate undertreatment with OCS to some extent. Nonresponse was defined as patients not fulfilling the criteria for clinical response, as well as discontinuation or switching treatment prior to 12 months. For clinical remission, the definition proposed by Menzies-Gow et al8Menzies-Gow A. Bafadhel M. Busse W.W. et al.An expert consensus framework for asthma remission as a treatment goal.J Allergy Clin Immunol. 2020; 145: 757-765Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar was applied: clinical remission on treatment following 12 months of treatment was defined as a complete absence of exacerbations and need for mOCS and well-controlled symptoms defined as a score on the six-question Asthma Control Questionnaire (ACQ-6) of ≤ 1.5 after 12 months of treatment. Optimization and stabilization of lung function were interpreted as a normalization of lung function (FEV1 > 80% of predicted value). Continuous variables are described by mean ± SD and median (25th percentile-75th percentile); categorical variables are described as number (%). The effectiveness of biologic therapy was assessed in all biologic therapies combined by describing the change in ACQ-6, FEV1 percent predicted value, exacerbations, and mOCS use in the overall study population using paired t tests or signed-rank test for continuous variables, where appropriate, and by McNemar’s test for categorical variables. Furthermore, we calculated the proportion of patients with no response vs a clinical response to biologic therapy following 12 months of treatment and the proportion of patients going into clinical remission in the full study population and in the three drug classes (anti-IgE, anti-IL-5/IL-5R, and anti-IL-4Rα). Baseline characteristics of patients were compared according to response to treatment using χ2 tests for categorial variables and t tests and U tests for parametric and nonparametric variables, respectively. This was done in the entire population and in the individual drug classes. The association between baseline characteristics that in univariate analyses were associated with remission with P < .10 were furthermore included in a multivariate logistic regression model to examine their independent impact on the odds of achieving remission. Variables that were part of the remission definition (exacerbations, mOCS, ACQ-6, and FEV1 percent predicted) were not included in this model, neither were the comorbidities associated with remission to avoid including too many categorical variables that would lead to a regression model that would not converge. Finally, due to collinearity, duration of disease and asthma onset could not both be included in the same model; we chose to keep duration of disease in the final model. All P values were two-sided and considered significant at α < 0.05. If there were less than five observations in a cell, P values were based on the Fisher exact test. No P values were presented if the Fisher exact test did not converge. Analyses were conducted by using SAS Enterprise guide (SAS Institute, Inc.). Of the 775 biologic-naive patients identified in the DSAR, 501 fulfilled the criteria for the current study (e-Fig 1). Baseline characteristics of the population are summarized in Table 1, and the indications for commencing biologic therapy in the entire study population are illustrated in e-Figure 2.Table 1Baseline Characteristics of Biologic-Naive Patients Commencing Biologic Therapy in the Danish Severe Asthma RegisterBaseline VariableStudy Population (N = 501)Demographic variables Age, y56 ± 14 Female254 (51) BMI, kg/m228 ± 6 Duration of disease, y22 ± 18 Duration of disease ≥ 10 y244 (62) Age at asthma onset, y34 ± 21 Onset during childhood (age ≤ 18 y)125 (31) Late onset (age ≥ 40 y)179 (45) Smoking statusNever smoked262 (53)Previously smoked227 (46)Currently smokes6 (1)Pack-y in previously smoked and currently smokes13 (4-23)Symptom control ACQ-6 score2.52 ± 1.22 ACQ-6 score ≤ 1.591 (25) Exacerbations past 12 mo3.00 (2.00-5.00)Medication use Budesonide equivalent dose, μg1,600 (800-1,600) mOCS211 (42) mOCS dose, mg10.00 (5.00-12.50) ICS221 (44) ICS/LABA357 (71) ICS/LABA/LAMA27 (5) LAMA178 (36) LABA/LAMA30 (6) SABA262 (52) LTRA217 (43) Theophylline23 (5)Lung function FEV1, L2.24 ± 0.85 FEV1, percent predicted69 ± 21 FEV1/FVC0.66 ± 0.15Allergy Positive SPT and/or positive specific IgE183 (50) Positive SPT57 (49) Positive specific IgE159 (51)Inflammatory markers Blood eosinophils, cells × 109/L0.34 (0.14-0.62) Blood eosinophils ≥ 0.3 109/L (%)264 (56) IgE, IU/mL144 (54-381) IgE ≥ 150 IU/mL173 (49) Feno, ppb32 (16-64) Feno ≥ 25 ppb258 (61)Comorbidities ABPA18 (4) Allergic rhinitis252 (51) Atopic dermatitis87 (18) Aspirin sensitivity35 (7) Bronchiectasis125 (25) Cardiovascular disease142 (29) Chronic rhinosinusitis294 (60) COPD104 (21) Diabetes41 (8) Dysfunctional breathing40 (8) EGPA14 (3) Eosinophilic pneumonia18 (4) GERD149 (31) Nasal polyposis203 (42) Obesity (BMI ≥ 30 kg/m2)141 (29) OSA syndrome57 (12) Psychiatric disease66 (13) Vocal cord dysfunction9 (2)Data are presented as mean ± SD, No. (%), or median (25th percentile-75th percentile). ABPA = allergic bronchopulmonary aspergillosis; ACQ-6 = six-question Asthma Control Questionnaire; EGPA = eosinophilic granulomatosis with polyangiitis; Feno = fractional exhaled nitric oxide; GERD = gastroesophageal reflux disease; ICS = inhaled corticosteroid; LABA = long-acting beta-agonist; LAMA = long-acting muscarinic antagonist; LTRA = leukotriene receptor antagonist; mOCS = maintenance oral corticosteroid; SABA = short-acting beta-agonist; SPT = skin prick test. Open table in a new tab Data are presented as mean ± SD, No. (%), or median (25th percentile-75th percentile). ABPA = allergic bronchopulmonary aspergillosis; ACQ-6 = six-question Asthma Control Questionnaire; EGPA = eosinophilic granulomatosis with polyangiitis; Feno = fractional exhaled nitric oxide; GERD = gastroesophageal reflux disease; ICS = inhaled corticosteroid; LABA = long-acting beta-agonist; LAMA = long-acting muscarinic antagonist; LTRA = leukotriene receptor antagonist; mOCS = maintenance oral corticosteroid; SABA = short-acting beta-agonist; SPT = skin prick test. The overall effectiveness of biologic therapy is shown in Figure 1. Following 4 months of treatment, the mean ACQ-6 score had decreased from 2.52 ± 1.22 to 1.54 ± 1.15; following 12 months, it had decreased to 1.47 ± 1.19, compared with baseline, thus meeting the minimal clinically important difference of a change of at least 0.5. An improvement was observed in FEV1 from 2.24 ± 0.90 L to 2.49 ± 0.92 L after 4 months and to 2.42 ± 0.90 L after 12 months, which was statistically significant; the findings reached a minimal clinically important difference of 0.2 L after 4 months but not after 12 months. At the 12-month follow-up, 325 patients (68%) had not experienced any OCS-related exacerbations since commencing biologic treatment. At baseline, 211 (42%) patients were taking mOCS; after 12 months of follow-up, 114 (25%) patients were users of mOCS. After 12 months of treatment, 397 (79%) patients fulfilled the study criteria for a clinical response in the indication that set the treatment, whereas 104 (21%) had no response to treatment (Fig 2). Among the 397 clinical responders, 97 patients (24% of those with a clinical response, 19% of the total study population) had achieved clinical remission. For the three individual drug classes, the proportion of clinical response varied from 72% in anti-IgE, 78% in anti-IL-5/IL-5R, and 92% in anti-IL-4Rα, whereas the proportions of patients achieving remission in these three groups were 6%, 19%, and 30%, respectively (Fig 3).Figure 3Response pattern following 12 months of treatment with biologic therapy and baseline biomarkers predicting remission in each drug class compared with patients with a clinical response. aProportion in the entire population. Feno = fractional exhaled nitric oxide.View Large Image Figure ViewerDownload Hi-res image Download (PPT) In the overall population, we found few baseline predictors of having a clinical response to biologic therapy compared with no response (Fig 2, Table 2). Nonresponders were more likely to use mOCS at baseline compared with clinical responders and to have fewer exacerbations. They were also less likely to have blood eosinophils ≥ 0.3 cells × 109/L and to have eosinophilic pneumonia. Patients achieving remission were more likely to be male, to have a lower BMI, to be older at asthma onset, to be nonusers of mOCS, to have a lower ACQ-6 score, to have higher FEV1 and FEV1 percent predicted, and to have higher median blood eosinophil count (Fig 2, Table 3). There were also less likely to have COPD, dysfunctional breathing, and nasal polyposis. In a multivariate model, the strongest predictors of remission were BMI (OR for 1-unit increase, 0.91; 95% CI, 0.86-0.97) and duration of disease (OR for 1-year increase, 0.98; 95% CI, 0.97-0.99) (Table 4). Doubling concentrations of blood eosinophil count and fractional exhaled nitric oxide yielded ORs of 1.18 (95% CI, 0.98-1.42) and 1.02 (95% CI, 0.81-1.27), respectively, and male sex was associated with an OR of 1.57 (95% CI, 0.88-2.83), compared with female sex.Table 2Baseline Characteristics Comparing No Response to Clinical Response Following 12 Months of Treatment in All Patients Treated With Biologic TherapiesBaseline VariableNo Response (n = 104)Clinical Response (Including Patients With Clinical Remission)(n = 397)P ValueDemographic variables Age, y55 ± 1556 ± 13.58 Female55 (53)199 (50).62 BMI, kg/m229 ± 728 ± 5.05 Duration of disease, y21 ± 1922 ± 18.88 Duration of disease ≥ 10 y45 (62)199 (63).83 Age at asthma onset, y35 ± 2034 ± 21.71 Onset during childhood (age ≤ 18 y)26 (33)100 (30).58 Late onset (age ≥ 40 y)31 (41)146 (45).79 Smoking status.20Never smoked55 (53)207 (53)Previously smoked45 (44)182 (46)Currently smokes3 (3)3 (1)Pack-y10 (2-20)15 (5-25).04Medication use Budesonide equivalent dose, μg1,600 (600-1,600)1,600 (800-1,600).59 mOCS65 (63)146 (37)< .001 mOCS dose, mg10.00 (5.00-10.00)10.00 (5.00-12.50).26 Biologic class.02Anti-IgE13 (13)34 (9)Anti-IL-5/IL-5R85 (82)298 (75)Anti-IL-4Rα6 (6)65 (16)Symptom control ACQ-6 score2.59 ± 1.212.50 ± 1.22.59 ACQ-6 score ≤ 1.516 (24)75 (25).86 Exacerbations in the past 12 mo2.90 ± 2.854.01 ± 2.82< .001 Exacerbations in the past 12 mo3.00 (1.00-4.00)3.00 (2.00-5.00)< .001Lung function FEV1, L2.15 ± 0.772.27 ± 0.87.21 FEV1, percent predicted67 ± 1970 ± 22.18 FEV1/FVC0.67 ± 0.140.66 ± 0.15.58Inflammatory markers Blood eosinophils, cells × 109/L0.25 (0.13-0.56)0.39 (0.15-0.64).14 Blood eosinophils ≥ 0.3 109/L42 (44)222 (59).01 IgE, IU/mL116 (54-343)147 (55-384).36 IgE ≥ 150 IU/mL30 (46)143 (50).61 Feno, ppb28 (13-59)32 (17-65).41 Feno ≥ 25 ppb46 (55)212 (62).27Comorbidities ABPA6 (6)12 (3).16 Allergic rhinitis46 (46)206 (52).25 Atopic dermatitis18 (18)69 (18).94 Aspirin sensitivity4 (4)31 (8).18 Bronchiectasis24 (24)101 (26).68 Cardiovascular disease30 (30)112 (29).73 Chronic rhinosinusitis54 (55)240 (62).22 COPD25 (25)79 (20).33 Diabetes8 (8)33 (8).61 Dysfunctional breathing8 (8)32 (8).93 EGPA2 (2)12 (3).58 Eosinophilic pneumonia8 (9)10 (3).01 GERD30 (31)119 (31).95 Nasal polyposis37 (39)166 (42).61 Obesity (BMI ≥ 30 kg/m2)34 (33)107 (28).25 OSA syndrome15 (15)42 (11).23 Psychiatric disease17 (17)49 (13).24 Vocal cord dysfunction2 (2)7 (2).90Data are presented as mean ± SD, No. (%), or median (25th percentile-75th percentile). ABPA = allergic bronchopulmonary aspergillosis; ACQ-6 = six-question Asthma Control Questionnaire; EGPA = eosinophilic granulomatosis with polyangiitis; Feno = fractional exhaled nitric oxide; GERD = gastroesophageal reflux disease; ICS = inhaled corticosteroid; mOCS = maintenance oral corticosteroid. Open table in a new tab Table 3Baseline Characteristics Comparing Clinical Responders vs Patients Achieving Remission Following 12 Months of TreatmentBaseline VariableClinical Response (Excluding Patients With Clinical Remission)(n = 300)Clinical Remission (n = 97)P ValueDemographic variables Age, y56 ± 1456 ± 13.85 Female162 (54)37 (38).01 BMI, kg/m228 ± 626 ± 4.001 Duration of disease, y23 ± 1918 ± 17.02 Duration of disease ≥ 10 y158 (67)41 (51).01 Age at asthma onset, y33 ± 2138 ± 21.04 Onset during childhood (age ≤ 18 y)78 (31)22 (25).25 Late onset (age ≥ 40 y)101 (42)45 (54).18 Smoking status.40Never smoked152 (51)55 (57)Previously smoked141 (48)41 (43)Currently smokes3 (1)0 (0)Pack-y15 (5-25)15 (6-22).91Medication use Budesonide equivalent dose, μg1,600 (800-1,600)1,600 (800-2,000).53 mOCSaPart of the definition for remission and therefore not considered a predictor of remission.122 (41)24 (25).01 mOCS, median dose10.00 (5.00-15.00)7.50 (5.00-10.00).08 Biologic class.04Anti-IgE31 (10)3 (3)Anti-IL-5/IL-5R225 (75)73 (75)Anti-IL-4Rα44 (15)21 (22)Symptom control ACQ-6 score2.67 ± 1.172.01 ± 1.26< .001 ACQ-6 score ≤ 1.5aPart of the definition for remission and therefore not considered a predictor of remission.39 (17)36 (48)< .001 Exacerbations in the past 12 monthsaPart of the definition for remission and therefore not considered a predictor of remission.4.11 ± 2.913.73 ± 2.51.26 Exacerbations in the past 12 monthsaPart of the definition for remission and therefore not considered a predictor of remission.3.00 (2.00-5.00)3.00 (2.00-5.00).32Lung function FEV1, L2.10 (0.81)2.78 (0.85)< .001 FEV1, percent predictedaPart of the definition for remission and therefore not considered a predictor of remission.66 ± 2183 ± 19< .001 FEV1/FVC0.65 ± 0.160.68 ± 0.12.03Inflammatory markers Blood eosinophils, cells × 109/L0.32 (0.13-0.58)0.50 (0.25-0.75).01 Blood eosinophils ≥ 0.3 109/L154 (55)68 (72).001 IgE, IU/mL132 (47-350)182 (92-406).12 IgE ≥ 150 IU/mL100 (47%)43 (57%).16 Feno, ppb31 (15-60)36 (21-75).08 Feno ≥ 25 ppb150 (60)62 (68).16Comorbidities ABPA11 (4)1 (1).19 Allergic rhinitis160 (54)46 (48).31 Atopic dermatitis58 (20)11 (12).07 Aspirin sensitivity21 (7)10 (11).29 Bronchiectasis80 (27)21 (22).32 Cardiovascular disease92 (31)20 (21).06 Chronic rhinosinusitis176 (60)64 (67).20 COPD70 (24)9 (9).003 Diabetes27 (9)6 (6).38 Dysfunctional breathing30 (10)2 (2).01 EGPA12 (4)0 (0).05 Eosinophilic pneumonia6 (2)4 (4).24 GERD97 (33)22 (23).06 Nasal polyposis114 (38)52 (54).01 Obesity (BMI ≥ 30 kg/m2)94 (32)13 (13).001 OSA syndrome36 (12)6 (6).11 Psychiatric disease42 (14)7 (7).08 Vocal cord dysfunction7 (2)0 (0).13Data are presented as mean ± SD, median (25th percentile-75th percentile), or n (%). ABPA = allergic bronchopulmonary aspergillosis; ACQ-6 = six-question Asthma Control Questionnaire; EGPA = eosinophilic granulomatosis with polyangiitis; Feno = fractional exhaled nitric oxide; GERD = gastroesophageal reflux disease; ICS = inhaled corticosteroid; mOCS = maintenance oral corticosteroid.a Part of the definition for remission and therefore not considered a predictor of remission. Open table in a new tab Table 4Baseline Predictors of Clinical Remission After 12 Months of Biologic Therapy Analyzed in a Multivariate Logistic Regression Model With Remission as the OutcomeOR (95% CI)P ValueSex.13 Male1.57 (0.88-2.83) Female1.00 (Reference)BMI (kg/m2) (1 unit increase)0.92 (0.86-0.99).02Duration of disease (1 year increase)0.98 (0.97-0.99).047Blood eosinophil count (doubling concentration)1.18 (0.98-1.42).09Feno (doubling concentration)1.02 (0.81-1.27).88Feno = fractional exhaled nitric oxide. Open table in a new tab Data are presented as mean ± SD, No. (%), or median (25th percentile-75th percentile). ABPA = allergic bronchopulmonary aspergillosis; ACQ-6 = six-question Asthma Control Questionnaire; EGPA = eosinophilic granulomatosis with polyangiitis; Feno = fractional exhaled nitric oxide; GERD = gastroesophageal reflux disease; ICS = inhaled corticosteroid; mOCS = maintenance oral corticosteroid. Data are presented as mean ± SD, median (25th percentile-75th percentile), or n (%). ABPA = allergic bronchopulmonary aspergillosis; ACQ-6 = six-question Asthma Control Questionnaire; EGPA = eosinophilic granulomatosis with polyangiitis; Feno = fractional exhaled nitric oxide; GERD = gastroesophageal reflux disease; ICS = inhaled corticosteroid; mOCS = maintenance oral corticosteroid. Feno = fractional exhaled nitric oxide. Regarding the individual drug classes, biomarkers that predicted remission are illustrated in Figure 3, and all predictors of response are presented in e-Tables 2 to 4. Remission in patients treated with anti-IL-5/IL-5R was predicted by higher baseline blood eosinophils and higher total IgE, whereas remission in patients treated with anti-IL-4Rα was predicted by higher fractional exhaled nitric oxide levels. The temporal response to biologic therapy in patients with a clinical response and remission is illustrated in Figure 4. In patients obtaining a clinical response to treatment, 17% had a baseline ACQ-6 score ≤ 1.5; this number improved to 50% following 4