Asthma Exacerbations and Triggers in Children in TENOR: Impact on Quality of Life.

BACKGROUND: Data examining associations between asthma exacerbations, triggers, and asthma-related quality of life (QOL) in children with severe/difficult-to-treat asthma are unavailable. OBJECTIVE: To evaluate real-world data on relationships between asthma exacerbations, triggers, and QOL in children using data from TENOR (The Epidemiology and Natural History of Asthma Outcomes and Treatment Regimens), a 3-year observational study of patients with severe/difficult-to-treat asthma, including those aged 6 to 12 years. METHODS: QOL was examined using the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and defined exacerbations hierarchically (descending order of severity): hospitalization, emergency department visit, steroid burst, no exacerbation, using the highest value from months 6 and 12. One-way ANOVA was used to test for differences in PAQLQ domain scores at month 12 across exacerbation severity, total number of asthma exacerbations, and number of baseline asthma triggers. Mantel-Haenszel chi-square test was used to test the association between the number of triggers and exacerbation hierarchy. RESULTS: Greater severity of asthma exacerbations was associated with significantly (P < .001) lower mean PAQLQ domain scores, indicating poorer QOL. A higher number of asthma exacerbations was associated with significantly (P < .001) lower mean PAQLQ domain scores. PAQLQ scores were significantly lower with higher numbers of baseline triggers. Higher baseline number of asthma triggers was associated with greater severity (P = .05) and number of asthma exacerbations (P < .001). CONCLUSIONS: A higher number of asthma triggers at baseline was associated with greater asthma severity and number of asthma exacerbations and lower QOL in children with severe/difficult-to-treat asthma.

Omalizumab in children with uncontrolled allergic asthma: Review of clinical trial and real-world experience.

Asthma is one of the most common chronic diseases of childhood. Allergen sensitization and high frequencies of comorbid allergic diseases are characteristic of severe asthma in children. Omalizumab, an anti-IgE mAb, is the first targeted biologic therapeutic approved for the treatment of moderate-to-severe persistent allergic asthma (AA) that remains uncontrolled despite high-dose inhaled corticosteroids plus other controller medications. Since its initial licensing for use in adults and adolescents 12 years of age and older, the clinical efficacy, safety, and tolerability of omalizumab have been demonstrated in several published clinical trials in children aged 6 to less than 12 years with moderate-to-severe AA. These studies supported the approval of the pediatric indication (use in children aged ≥6 years) by the European Medicines Agency in 2009 and the US Food and Drug Administration in 2016. After this most recent change in licensing, we review the outcomes from clinical trials in children with persistent AA receiving omalizumab therapy and observational studies from the past 7 years of clinical experience in Europe. Data sources were identified by using PubMed in 2016. Guidelines and management recommendations and materials from the recent US Food and Drug Administration's Pediatric Advisory Committee meeting are also reviewed.

A randomized multicenter study evaluating Xolair persistence of response after long-term therapy.

BACKGROUND: Few data are available to assist clinicians with decisions regarding long-term use of asthma therapies, including omalizumab. OBJECTIVE: We sought to evaluate the benefit and persistence of response in subjects continuing or withdrawing from long-term omalizumab treatment. METHODS: Evaluating the Xolair Persistency Of Response After Long-Term Therapy (XPORT) was a randomized, double-blind, placebo-controlled withdrawal study that included subjects with moderate-to-severe persistent asthma receiving long-term omalizumab. Subjects were randomized by using a hierarchical dynamic randomization scheme to continue their same dose of omalizumab or withdraw to placebo and were then followed every 4 weeks for 1 year. The primary outcome was any protocol-defined severe asthma exacerbation. The secondary outcome was time to first protocol-defined severe asthma exacerbation. Exploratory outcomes included changes in Asthma Control Questionnaire and Asthma Control Test scores. RESULTS: Significantly more subjects in the omalizumab group (67%) had no protocol-defined exacerbation than in the placebo group (47.7%); an absolute difference of 19.3% (95% CI, 5.0%, 33.6%) represents a 40.1% relative difference. Time to first protocol-defined exacerbation analysis revealed a significantly different between-group exacerbation pattern that was consistent with the primary analysis. Subjects continuing omalizumab had significantly better asthma control (mean [SD] change from baseline to week 52: Asthma Control Test score, -1.16 [4.14] vs placebo, -2.88 [5.38], P = .0188; Asthma Control Questionnaire score, 0.22 [0.66] vs placebo, 0.63 [1.13], P = .0039). Discontinuation of omalizumab was associated with an increase in free IgE levels and an increase in basophil expression of the high-affinity IgE receptor. No safety concerns were noted. CONCLUSION: Continuation of omalizumab after long-term treatment results in continued benefit, as evidenced by improved symptom control and reduced exacerbation risk.