Extent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma

BACKGROUND: Characterization of uncontrolled asthma burden in a natural treatment setting can influence treatment recommendations and clinical practice. The objective was to characterize and compare the economic burden of severe or difficult-to-treat asthma in uncontrolled and controlled patients. METHODS: Baseline patient data (age > or = 13 years; n = 3916) were obtained from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study. Disease control was assessed using two approaches: (i) applying criteria for control based on the Gaining Optimal Asthma Control study, and (ii) using the Asthma Therapy Assessment Questionnaire (ATAQ) to identify the number of asthma control problems. Assessments were performed at baseline, and at months 12 and 24. Monetary values were assigned to productivity loss and medical resource use. Direct and indirect costs were aggregated over 24 months and compared using Student's t-test for continuous measures and chi-squared for categorical variables. RESULTS: Throughout the study, most patients had uncontrolled asthma (83% uncontrolled; 16% inconsistent control; 1.3% controlled). Controlled patients experienced fewer work or school absences and less healthcare resource use than uncontrolled patients at all study time points. Using the multilevel ATAQ control score, asthma costs increased directly with the number of asthma control problems. Costs for uncontrolled patients were more than double those of controlled patients throughout the study (14,212 vs 6,452 US Dollars; adjusted to 2002 Dollars; P < 0.0001). Conclusions: This study demonstrated that few severe or difficult-to-treat asthma patients achieved control over a 2-year period and the economic consequence of uncontrolled disease is substantial.     

Asthma score: predictive ability and risk factors

BACKGROUND: Definition of asthma as a continuous score is a promising tool for population studies that has not yet been fully evaluated. OBJECTIVE: We assessed (i) the predictive ability of an asthma score against the occurrence of different asthma-related outcomes and (ii) the risk factors identified when using an asthma score. METHODS: The European Community Respiratory Health Study II included subjects from the general population randomly studied during 1991-1993 who were followed up in the years 1998-2001, from 29 centres in 14 countries. A total of 8956 subjects were included. The asthma score consisted of a simple sum of the positive answers to five respiratory symptoms. RESULTS: Asthma score at baseline showed a linear relationship with incidence of asthma, the occurrence of asthma attacks, use of asthma medication and bronchial reactivity at the end of the follow-up. Asthma score at the end of follow-up was associated with known risk factors at baseline such as IgE to grass, rhinitis or body mass index, in addition to passive smoking in men [average score ratio (RR) = 1.30; 95% confidence interval (CI) 1.09-1.50] or changes in body mass index (RR = 1.27; 95% CI 1.05-1.27, per each kg/m(2)). CONCLUSION: The asthma score had good predictive ability against outcomes related with asthma and also good ability to detect risk factors. This encourages the use of the score as a measure of asthma in epidemiological studies on aetiology of asthma.     

Efficacy and safety of treatment with dupilumab for severe asthma: A systematic review of the EAACI guidelines—Recommendations on the use of biologicals in severe asthma

Dupilumab, a fully human monoclonal antibody against interleukin-4 receptor α, is approved as add-on maintenance treatment for inadequately controlled type 2 severe asthma. This systematic review evaluated the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled severe asthma. PubMed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. Three RCTs including 2735 subjects >12 years old and 24-52 weeks of follow-up were included. Dupilumab reduced with high certainty severe asthma exacerbations (Incidence rate ratio 0.51; 95% CI 0.45-0.59) and the percentage use of oral corticosteroid use (mean difference (MD) −28.2 mg/d; 95% CI −40.7 to −15.7). Asthma control (ACQ-5), quality of life (AQLQ) and rescue medication use [puffs/d] improved, without reaching the minimal important clinical difference: ACQ-5 MD −0.28 (95% CI −0.39 to −0.17); AQLQ MD +0.28 (95% CI 0.20-0.37); and rescue medication MD −0.35 (95% CI −0.73 to +0.02). FEV₁ increased (MD +0.15; 95% CI +0.11 to +0.18) (moderate certainty). There was an increased rate of dupilumab-related adverse events (AEs) (moderate certainty) and of drug-related serious AEs (low certainty). The incremental cost-effectiveness ratio of dupilumab versus standard therapy was 464 000$/QALY (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population.     

Increased risk of asthma attacks and emergency visits among asthma patients with allergic rhinitis: a subgroup analysis of the improving asthma control trial

BACKGROUND: Inadequately controlled allergic rhinitis (AR) in asthmatic patients can contribute towards increased asthma exacerbations and poorer symptom control, which may increase medical resource use. We assessed asthma-related medical resource use and attacks in asthmatic patients who did and did not have concomitant AR and were adding montelukast or salmeterol to baseline treatment with inhaled fluticasone. METHODS: A post hoc resource use analysis of a 52-week, double-blind multicentre clinical trial (Investigation of Montelukast as a Partner Agent for Complementary Therapy) [corrected] including 1490 adults with chronic asthma, aged 15-72 years, with FEV(1) 50-90% of predicted and > or =12% increase in FEV(1) after salbutamol administration, treated with either montelukast 10 mg daily or salmeterol 50 microg twice daily in addition to fluticasone 200 microg, was undertaken. Asthma-related medical resource use included medical visits (defined as either an unscheduled visit [to a general practitioner, a specialist or a non-medical provider] or a specialist visit), emergency room visits and hospitalizations during follow-up. Asthma attacks were defined as the worsening of asthma requiring unscheduled visit, emergency visit, hospitalization or oral/intravenous/intramuscular corticosteroids. RESULTS: A self-reported history of concomitant AR was identified in 60% of the patients (n=893). Univariate analysis suggests that significantly more patients with concomitant AR experienced emergency room visits (3.6% vs. 1.7%, P=0.029) and asthma attacks (21.3% vs. 17.1%, P=0.046). Multivariate analysis adjusting for treatment group, age and baseline asthma severity confirmed these results since the presence of concomitant AR in patients with asthma increases the likelihood of emergency room visit (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.12-4.80) and asthma attack (OR=1.35, 95% CI=1.03-1.77). Patients with asthma alone compared with patients with both conditions did not differ in terms of unscheduled or specialist visits and hospitalizations. CONCLUSIONS: Presence of self-reported concomitant AR in patients with asthma resulted in a higher rate of asthma attacks and more emergency room visits compared with asthma patients without concomitant AR.     

Insurance status and asthma-related health care utilization in patients with severe asthma.

BACKGROUND: Medicaid insurance has been associated with worse asthma outcomes, but the degree to which demographic factors contribute to this relationship has not been well explored. OBJECTIVE: To evaluate whether insurance status is independently associated with health care utilization (HCU) and asthma control when demographic differences are taken into account. METHODS: We used baseline data from adults with severe asthma in the Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study. HCU was defined as hospitalization or emergency department visit for asthma in the past 3 months. Asthma control was evaluated using the Asthma Therapy Assessment Questionnaire. Multiple logistic regression was used to compare HCU and asthma control in patients with Medicaid vs those with private health insurance. RESULTS: Of 1315 patients analyzed, 130 (9.9%) had Medicaid insurance and 1,185 (90.1%) had private insurance. Medicaid insurance was associated with younger age, female sex, race other than white, obesity, active smoking, lower education level, and unemployment. In unadjusted analyses, Medicaid patients had significantly higher HCU (odds ratio [OR], 3.08; 95% confidence interval [CI], 2.11-4.50) and poorer asthma control (OR, 2.56; 95% CI, 1.84-3.57) compared with patients with private insurance. After adjusting for demographic differences, insurance status was no longer associated with HCU (OR, 1.43; 95% CI, 0.92-2.23), and the strength of its association with asthma control was reduced (OR, 1.67; 95% CI, 1.17-2.40). CONCLUSIONS: Medicaid insurance is not associated with increased HCU in patients with severe asthma once demographic factors have been taken into account but remains modestly associated with poorer asthma control.     

Asthma prevalence among Alaska Native and nonnative residents younger than 20 years enrolled in Medicaid.

BACKGROUND: No study of childhood asthma prevalence in Alaska or among Alaska Natives has been conducted. OBJECTIVE: To determine asthma prevalence among Alaska Medicaid enrollees younger than 20 years, with an emphasis on Alaska Natives, the state's largest minority and predominant rural citizens. METHODS: A master database was obtained that included all children enrolled in Medicaid during July 1998 through June 1999. Physician, pharmacy, and hospital claims files for International Classification of Diseases codes 493.0x to 493.9x were linked to this master database. Asthma was defined as any asthma-related care or medication claim. RESULTS: Asthma prevalence among the study population was 6.9%. Alaska Natives had a lower asthma prevalence than nonnatives (risk ratio [RR], 0.70; 95% confidence interval [CI], 0.66-0.75), but among the subgroup of children residing in the state's major urban center, Alaska Natives had a higher prevalence. Overall, 0.22% of the study population experienced an asthma-related hospitalization, with Alaska Natives having a higher risk of hospitalization than nonnatives (RR, 1.6; 95% CI, 1.2-2.3). Among hospitalized children, Alaska Natives were less likely to have received a long-term control medication (RR, 0.54; 95% CI, 0.33-0.88). CONCLUSIONS: Compared with nonnatives, Alaska Natives have a lower risk of asthma but only among nonurban residents. The increased risk of hospitalization among Alaska Natives may be related to underuse of long-term control medications.     

The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma

BACKGROUND: Patients with severe persistent asthma who are inadequately controlled despite treatment according to current asthma management guidelines have a significant unmet medical need. Such patients are at high risk of serious exacerbations and asthma-related mortality. METHODS: Here, we pooled data from seven studies to determine the effect of omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, on asthma exacerbations in patients with severe persistent asthma. Omalizumab was added to current asthma therapy and compared with placebo (in five double-blind studies) or with current asthma therapy alone (in two open-label studies). The studies included 4308 patients (2511 treated with omalizumab), 93% of whom had severe persistent asthma according to the Global Initiative for Asthma (GINA) 2002 classification. Using the Poisson regression model, results were calculated as the ratio of treatment effect (omalizumab : control) on the standardized exacerbation rate per year. RESULTS: Omalizumab significantly reduced the rate of asthma exacerbations by 38% (P < 0.0001 vs control) and the rate of total emergency visits by 47% (P < 0.0001 vs control). Analysis of demographic subgroups showed that the efficacy of omalizumab on asthma exacerbations was unaffected by patient age, gender, baseline serum IgE (split by median) or by 2- or 4-weekly dosing schedule, although benefit in absolute terms appeared to be greatest in patients with more severe asthma, defined by a lower value of percentage predicted forced expiratory volume in 1 s (FEV(1)) at baseline. CONCLUSIONS: These results suggest that omalizumab may fulfil an important need in patients with severe persistent asthma, many of whom are not adequately controlled on current therapy.     

Prognostic factors of asthma severity: a 9-year international prospective cohort study

BACKGROUND: The natural history of asthma severity is poorly known. OBJECTIVE: To investigate prognostic factors of asthma severity. METHODS: All current patients with asthma identified in 1991 to 1993 in the European Community Respiratory Health Survey were followed up, and their severity was assessed in 2002 by using the Global Initiative for Asthma categorization (n = 856). Asthma severity (remittent, intermittent, mild, moderate, severe) was related to potential determinants evaluated at baseline and during the follow-up by a multinomial logistic model, using the intermittent group as the reference category for relative risk ratios (RRRs). RESULTS: Asthma severity measured at baseline was a determinant of a patient's severity at the end of the follow-up. At baseline, severe persistent had a poorer FEV1% predicted, a poorer symptom control, higher IgE levels (RRR, 2.06; 95% CI, 1.38-3.06), and a higher prevalence of chronic cough/mucus hypersecretion (RRR, 4.90; 95% CI, 2.18-11.02) than patients with intermittent asthma. Moderate persistent showed the same prognostic factors as severe persistent, even if the associations were weaker. Mild persistent had a distribution of prognostic factors that was similar to patients with intermittent asthma, although the former showed a poorer symptom control than the latter. Remission mainly occurred in patients with less severe asthma and was negatively associated with a change in body mass index (RRR, 0.86; 95% CI, 0.75-0.97). Allergic rhinitis, smoking, and respiratory infections in childhood were not associated with asthma severity. CONCLUSION: Patients with moderate and severe persistent asthma are characterized by early deterioration of lung function. High IgE levels and persistent cough/mucus hypersecretion are strong markers of moderate/severe asthma, which seems to be a different phenotype from mild persistent or intermittent asthma. CLINICAL IMPLICATIONS: Our results suggest that the evolution of asthma severity is to a large extent predictable.     

Association of β2-adrenergic receptor polymorphisms with severe asthma

BACKGROUND: There is considerable interest in the role of different candidate loci in the development of asthma. This study investigates the association between asthma severity and previously identified polymorphisms at two sites within the beta2-adrenergic receptor (beta2AR) gene: the Arg16-->Gly16 and Gln27-->Glu27 alleles. METHODS: Restriction enzyme analysis of amplified beta2AR gene products (PCR-RFLP) was used to analyse the frequency of the Arg16-->Gly16 and Gln27-->Glu27 polymorphisms within the beta2AR gene in 95 severe asthmatic patients (with a markedly increased risk of death from asthma), 59 mild asthmatic patients, and a control group of 92 nonasthmatic subjects. RESULTS: The Gly16 polymorphism was significantly associated with asthma severity with odds ratios (95% CI) for the Gly16 allele being 1.56 (1.02-2.40, P = 0.04) and 0. 98 (0.61-1.57, P = 0.92) for the severe and mild asthma groups, respectively. The corresponding odds ratios (95% CI) for Gly16 homozygotes were 1.91 (0.82-4.41, P = 0.13) and 0.82 (0.35-1.92, P = 0.65) for the severe and mild asthma groups, respectively. There was no significant association between either polymorphism at amino acid 27 and asthma or asthma severity. CONCLUSIONS: We conclude that the polymorphisms of amino acids 16 and 27 of the beta2AR gene are not associated with the development of asthma per se, but that the Gly16 polymorphism may play a role in the pathogenesis of asthma severity.     

Relationship between adherence to inhaled corticosteroids and poor outcomes among adults with asthma

BACKGROUND: Regular use of inhaled corticosteroids (ICSs) can improve asthma symptoms and prevent exacerbations. However, overall adherence is poor among patients with asthma. Objective To estimate the proportion of poor asthma-related outcomes attributable to ICS nonadherence. METHODS: We retrospectively identified 405 adults age 18 to 50 years who had asthma and were members of a large health maintenance organization in southeast Michigan between January 1, 1999, and December 31, 2001. Adherence indices were calculated by using medical records and pharmacy claims. The main outcomes were the number of asthma-related outpatient visits, emergency department visits, and hospitalizations, as well as the frequency of oral steroid use. RESULTS: Overall adherence to ICS was approximately 50%. Adherence to ICS was significantly and negatively correlated with the number of emergency department visits (correlation coefficient [ R ] = -0.159), the number of fills of an oral steroid ( R = -0.179), and the total days' supply of oral steroid ( R = -0.154). After adjusting for potential confounders, including the prescribed amount of ICS, each 25% increase in the proportion of time without ICS medication resulted in a doubling of the rate of asthma-related hospitalization (relative rate, 2.01; 95% CI, 1.06-3.79). During the study period, there were 80 asthma-related hospitalizations; an estimated 32 hospitalizations would have occurred were there no gaps in medication use (60% reduction). CONCLUSIONS: Adherence to ICS is poor among adult patients with asthma and is correlated with several poor asthma-related outcomes. Less than perfect adherence to ICS appears to account for the majority of asthma-related hospitalizations.     

Allergic rhinitis and asthma comorbidity in a survey of young adults in Italy

BACKGROUND: Several studies have provided evidence of a strong association between asthma and allergic or nonallergic rhinitis, leading to the hypothesis that allergic rhinitis (AR) and asthma represent a continuum of the same disease. AIM: The aims of our study were: (i) to measure the comorbidity of AR and asthma and asthma-like symptoms and (ii) to assess whether asthma, AR, and their coexistence share a common pattern of individual risk factors. METHODS: The subjects are participants from the Italian multicentre, cross-sectional survey on respiratory symptoms in the young adult general population (Italian Study of Asthma in Young Adults, ISAYA). The relationship between individual risk factors and asthma, AR and their coexistence, was studied by means of a multinomial logistic regression. RESULTS: About 60% of asthmatics reported AR. On the other hand, subjects with AR presented an eightfold risk of having asthma compared to subjects without AR. Age was negatively associated with asthma [OR = 0.89, 95% confidence interval (CI): 0.82-0.96], AR (OR = 0.92, 95% CI: 0.86-0.98), and asthma associated with AR (OR = 0.83, 95% CI: 0.79-0.88). The risk of AR without asthma was significantly higher in the upper social classes (OR = 1.23, 95% CI: 1.08-1.39). Active current smoking exposure was positively associated with asthma alone (OR = 1.24, 95% CI: 1.09-1.41) and negatively associated with AR with (OR = 0.69, 95% CI: 0.54-0.88) or without (OR = 0.76, 95% CI: 0.69-0.84) asthma. CONCLUSIONS: Asthma and AR coexist in a substantial percentage of patients; bronchial asthma and AR, when associated, seem to share the same risk factors as AR alone while asthma without AR seems to be a different condition, at least with respect to some relevant risk factors.     

Food allergy is associated with an increased risk of asthma

Background The atopic march is well documented, but the interrelationship of food allergy (FA) and asthma is not well understood.
Objective The aim of this study was to examine the strength of the association and temporal relationships between FA and asthma.
Methods This analysis included 271 children 6 years (older group) and 296 children <6 years (younger group) from a family-based FA cohort in Chicago, IL. Asthma was determined by parental report of physician diagnosis. FA status was determined based on the type and timing of clinical symptoms after ingestion of a specific food, and results of prick skin test (Multi-Test II) and allergen-specific IgE (Phadia ImmunoCAP). Analyses were carried out using logistic regression accounting for important covariates and auto-correlations among siblings. Kaplan–Meier curves were used to compare the time to onset of asthma with the FA status.
Results Symptomatic FA was associated with asthma in both older [odds ratio (OR)=4.9, 95% confidence interval (CI): 2.5–9.5] and younger children (OR=5.3, 95% CI: 1.7–16.2). The association was stronger among children with multiple or severe food allergies, especially in older children. Children with FA developed asthma earlier and at higher prevalence than children without FA (Cox proportional hazard ratio=3.7, 95% CI: 2.2–6.3 for children 6 years, and hazard ratio=3.3, 95% CI: 1.1–10 for children <6 years of age). No associations were seen between asymptomatic food sensitization and asthma.
Conclusions Independent of markers of atopy such as aeroallergen sensitization and family history of asthma, there was a significant association between FA and asthma. This association was even stronger in subjects with multiple food allergies or severe FA.     

Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE

BACKGROUND: Patients with severe persistent asthma who are inadequately controlled despite Global Initiative for Asthma (GINA) 2002 step 4 therapy are a challenging population with significant unmet medical need. We determined the effect of omalizumab on clinically significant asthma exacerbations (requiring systemic corticosteroids) in the first omalizumab study to exclusively enrol patients from this difficult-to-treat patient population. METHODS: Following a run-in phase, patients (12-75 years) inadequately controlled despite therapy with high-dose inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABA) with reduced lung function and a recent history of clinically significant exacerbations were randomized to receive omalizumab or placebo for 28 weeks in a double-blind, parallel-group, multicentre study. RESULTS: A total of 419 patients were included in the efficacy analyses. The clinically significant asthma exacerbation rate (primary efficacy variable), adjusted for an observed relevant imbalance in history of clinically significant asthma exacerbations, was 0.68 with omalizumab and 0.91 with placebo (26% reduction) during the 28-week treatment phase (P = 0.042). Without adjustment, a similar magnitude of effect was seen (19% reduction), but this did not reach statistical significance. Omalizumab significantly reduced severe asthma exacerbation rate (0.24 vs 0.48, P = 0.002) and emergency visit rate (0.24 vs 0.43, P = 0.038). Omalizumab significantly improved asthma-related quality of life, morning peak expiratory flow and asthma symptom scores. The incidence of adverse events was similar between treatment groups. CONCLUSIONS: In patients with inadequately controlled severe persistent asthma, despite high-dose ICS and LABA therapy, and often additional therapy, omalizumab significantly reduced the rate of clinically significant asthma exacerbations, severe exacerbations and emergency visits. Omalizumab is effective and should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy.     

Allergic rhinitis and asthma comorbidity: ARIA classification of rhinitis does not correlate with the prevalence of asthma

BACKGROUND: Allergic rhinitis and asthma comorbidity is supported by both the similar underlying pathogenesis and immunologic mechanisms. The aim of this study was to verify whether the characteristics of rhinitis classified according to the new Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines correlate with the prevalence of asthma. METHODS: From 1 March to 30 June 2002, a multi-centre cross-sectional study was conducted by 154 allergists chosen from throughout Italy. Duration, severity of rhinitis (according to the ARIA classification) and the type of allergic sensitizations were compared with the prevalence of asthma. RESULTS: One thousand three hundred and twenty-one consecutive rhinitis-allergic patients aged 18 years or older were enrolled for the study. The majority of patients, 1060 (80.24%), were on medication at the time of their specialist visit. Mild intermittent rhinitis was diagnosed in 7.7% of patients, moderate/severe intermittent in 17.1%, mild persistent in 11.6%, and moderate/severe persistent in 63.6%. The prevalence of asthma was 48% in patients with mild intermittent rhinitis, 49.6% in moderate-severe intermittent rhinitis, 36.6% in mild persistent rhinitis and 47.5% in moderate severe persistent patients. No correlation between the ARIA categories of rhinitis and the prevalence of asthma was found. A multivariate analysis, after adjustment for age, sex, type of sensitization, level of severity and duration of rhinitis classified according to the ARIA guidelines, demonstrated that age, over 41 years [risk ratio (RR) 1.260, 95% confidence interval (CI) 1.072-1.482] and especially over 51 years (RR 1.460, 95% CI 1.237-1.723), sensitization to indoor allergens (mite and cat), (RR 1.203, 95% CI 1.060-1.366), and polysensitization (RR 1.178, 95% CI 1.004-1.383) are significant risk factors for asthma. CONCLUSION: In allergic rhinitis (AR) patients referred to a specialist, the features of AR as defined by the ARIA classification are not able to predict the presence of asthma, therefore all such patients should be assessed for asthma.     

Omalizumab improves asthma-related quality of life in patients with severe allergic asthma

BACKGROUND: We have previously shown that omalizumab, a recombinant humanized monoclonal anti-IgE antibody, reduces asthma exacerbations and decreases inhaled corticosteroid (ICS) requirement in patients with severe allergic asthma who were symptomatic despite moderate-to-high doses of ICSs. OBJECTIVE: The aim of the present study was to assess the effects of omalizumab on asthma-related quality of life (QOL). METHODS: These analyses were part of a multicenter, 52-week, randomized, double-blind, placebo-controlled study assessing the efficacy, safety, and tolerability of subcutaneous omalizumab (> or =0.016 mg/kg of IgE [in international unit per milliliter] per 4 weeks) in 525 adults with severe allergic asthma. A 16-week steroid-stable phase was followed by a 12-week steroid-reduction phase and a 24-week double-blind extension phase. The effect of treatment on asthma-related QOL was evaluated by using the Asthma Quality of Life Questionnaire (AQLQ) administered at baseline and at weeks 16, 28, and 52. RESULTS: The 2 treatment groups were comparable in terms of baseline AQLQ scores. At weeks 16, 28, and 52, omalizumab-treated patients demonstrated statistically significant improvements across all AQLQ domains, as well as in overall score. Moreover, a greater proportion of patients receiving omalizumab achieved a clinically meaningful improvement in asthma-related QOL during each phase of the study. Greater than 50% of both patients and investigators rated treatment similarly with omalizumab as excellent or good compared with less than 40% of placebo recipients. CONCLUSION: In patients requiring moderate-to-high doses of ICSs for severe allergic asthma, the measurably improved disease control afforded by add-on omalizumab therapy is paralleled by clinically meaningful improvements in asthma-related QOL.     

Efficacy and safety of treatment with biologicals (benralizumab,dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma

Allergic asthma is a frequent asthma phenotype. Both IgE and type 2 cytokines are increased, with some degree of overlap with other phenotypes. Systematic reviews assessed the efficacy and safety of benralizumab, dupilumab and omalizumab (alphabetical order) vs standard of care for patients with uncontrolled severe allergic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. All three biologicals reduced with high certainty the annualized asthma exacerbation rate: benralizumab incidence rate ratios (IRR) 0.63 (95% CI 0.50 − 0.81); dupilumab IRR 0.58 (95%CI 0.47 − 0.73); and omalizumab IRR 0.56 (95%CI 0.42 − 0.73). Benralizumab and dupilumab improved asthma control with high certainty and omalizumab with moderate certainty; however, none reached the minimal important difference (MID). Both benralizumab and omalizumab improved QoL with high certainty, but only omalizumab reached the MID. Omalizumab enabled ICS dose reduction with high certainty. Benralizumab and omalizumab showed an increase in drug-related adverse events (AEs) with low to moderate certainty. All three biologicals had moderate certainty for an ICER/QALY value above the willingness to pay threshold. There was high certainty that in children 6-12 years old omalizumab decreased the annualized exacerbation rate [IRR 0.57 (95%CI 0.45-0.72)], improved QoL [relative risk 1.43 (95%CI 1.12 −1.83)], reduced ICS [mean difference (MD) −0.45 (95% CI −0.58 to −0.32)] and rescue medication use [ MD −0.41 (95%CI −0.66 to −0.15)].     

Long-Term Outcomes of Internet-Based Self-Management Support in Adults With Asthma: Randomized Controlled Trial

Background

Long-term asthma management falls short of the goals set by international guidelines. The Internet is proposed as an attractive medium to support guided self-management in asthma. Recently, in a multicenter, pragmatic randomized controlled parallel trial with a follow-up period of 1 year, patients were allocated Internet-based self-management (IBSM) support (Internet group [IG]) or usual care (UC) alone. IBSM support was automatically terminated after 12 months of follow-up. In this study, IBSM support has been demonstrated to improve asthma-related quality of life, asthma control, lung function, and the number of symptom-free days as compared to UC. IBSM support was based on known key components for effective self-management and included weekly asthma control monitoring and treatment advice, online and group education, and communication (both online and offline) with a respiratory nurse.

Objective

The objective of the study was to assess the long-term effects of providing patients 1 year of IBSM support as compared to UC alone.

Methods

Two hundred adults with physician-diagnosed asthma (3 or more months of inhaled corticosteroids prescribed in the past year) from 37 general practices and 1 academic outpatient department who previously participated were invited by letter for additional follow-up at 1.5 years after finishing the study. The Asthma Control Questionnaire (ACQ) and the Asthma Quality of Life Questionnaire (AQLQ) were completed by 107 participants (60 UC participants and 47 IG participants). A minimal clinical important difference in both questionnaires is 0.5 on a 7-point scale.

Results

At 30 months after baseline, a sustained and significant difference in terms of asthma-related quality of life of 0.29 (95% CI 0.01-0.57) and asthma control of -0.33 (95% CI -0.61 to -0.05) was found in favor of the IBSM group. No such differences were found for inhaled corticosteroid dosage or for lung function, measured as forced expiratory volume in 1 second.

Conclusions

Improvements in asthma-related quality of life and asthma control were sustained in patients who received IBSM support for 1 year, even up to 1.5 years after terminating support. Future research should be focused on implementation of IBSM on a wider scale within routine asthma care.

Trial Registration

International Standard Randomized Controlled Trial Number (ISRCTN): 79864465; http://www.controlled-trials.com/ISRCTN79864465 (Archived by WebCite at http://www.webcitation.org/6J4VHhPk4).     

Efficacy and safety of treatment with biologicals (benralizumab,dupilumab, mepolizumab,omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma

Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV₁, without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV₁. More data on long-term safety are needed together with more efficacy data in the paediatric population.