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Daily patient-reported health status assessment improvements with benralizumab for patients with severe, uncontrolled eosinophilic asthma.

ABSTRACT: Background:Patients with severe, uncontrolled asthma experience debilitating symptoms that result in meaningful reductions to health-related quality of life. Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody that reduces exacerbations and improves asthma symptoms for patients with severe, uncontrolled eosinophilic asthma. Objective:The objective of this study was to evaluate improvements in daily asthma-related health status outcomes following treatment with benralizumab. Methods:Pooled results from the SIROCCO (NCT01928771) and CALIMA (NCT01914757) Phase III studies were analyzed. Patients aged 12-75 years with severe, uncontrolled asthma, and blood eosinophil counts (BEC) ?300 and ?150 cells/µL were evaluated. Patients received subcutaneous benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W, first three doses Q4W) or placebo and completed a daily diary reporting rescue medication use, night-time awakening requiring rescue medication use, perceived tiredness, and asthma-related activity impairment. Outcome measures were compared across treatment arms from baseline to end of treatment (EOT) using a mixed-effect model for repeated measures analyses. Results:Patients with BEC ?300 cells/µL receiving benralizumab Q8W had greater improvements in all patient-reported outcomes at EOT relative to baseline than patients receiving placebo (all nominal P?0.013). Effects were reported as early as 3 days following the initial dose and sustained throughout treatment for daily and night-time rescue medication use and night-time awakenings requiring rescue medication. For patients with BEC ?300 and ?150 cells/ µL, sustained improvements in activity impairment items (all nominal P<0.05) were achieved with benralizumab Q8W at week 2. Conclusion:Benralizumab produces sustained reductions by as early as 3 days in rescue medication use and activity impairment for patients with severe, uncontrolled eosinophilic asthma.

SUBMITTER: O'Quinn S

PROVIDER: S-EPMC6350639 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Daily patient-reported health status assessment improvements with benralizumab for patients with severe, uncontrolled eosinophilic asthma.

O'Quinn Sean S Xu Xiao X Hirsch Ian I

Journal of asthma and allergy 20190123

<h4>Background</h4>Patients with severe, uncontrolled asthma experience debilitating symptoms that result in meaningful reductions to health-related quality of life. Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody that reduces exacerbations and improves asthma symptoms for patients with severe, uncontrolled eosinophilic asthma.<h4>Objective</h4>The objective of this study was to evaluate improvements in daily asthma-related health status outcomes following ...[more]

PMID: 30774388

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Project description:PurposeIn the Phase III SIROCCO trial (NCT01928771), benralizumab significantly reduced asthma exacerbations and improved lung function and symptoms for patients with severe, uncontrolled eosinophilic asthma. The aim of this subgroup analysis was to evaluate efficacy and safety of benralizumab for Korean patients in SIROCCO.MethodsSIROCCO was a randomized, double-blind, parallel-group, placebo-controlled trial of 1,204 patients aged 12-75 years with severe asthma uncontrolled by high-dosage inhaled corticosteroids/long-acting β₂-agonists (ICS/LABA). Patients received benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W; first 3 doses Q4W) or placebo Q4W for 48 weeks. The primary analysis population comprised patients with blood eosinophil counts ≥ 300 cells/μL. This subgroup analysis evaluated Korean patients from this group.ResultsOf 122 Korean patients randomized, 86 had blood eosinophil counts ≥ 300 cells/μL. Benralizumab reduced the annual asthma exacerbation rate by 70% (Q4W: rate estimate 0.79, rate ratio 0.30 [95% confidence interval {CI}, 0.13-0.65], nominal P = 0.003; n = 28) and 85% (Q8W: rate estimate 0.40, rate ratio 0.15 [95% CI, 0.06-0.36], nominal P < 0.001; n = 30) vs. placebo (rate estimate 2.67, n = 28). Prebronchodilator forced expiratory volume in 1 second was increased with benralizumab treatment by 0.270 L (Q4W: 95% CI, 0.039-0.500, nominal P = 0.023; n = 28) and 0.362 L (Q8W: 95% CI, 0.143-0.582, nominal P = 0.002; n = 30) vs. placebo (n = 27). Total asthma symptom score was similar for patients receiving either benralizumab Q4W (-0.27 [95% CI, -0.83 to 0.30], nominal P = 0.356; n = 27) or benralizumab Q8W (0.10 [95% CI, -0.44 to 0.65], nominal P = 0.708; n = 30) vs. placebo (n = 28). Drug-related adverse events were experienced by 2%, 8%, and 5% of patients in the placebo, benralizumab Q4W, and benralizumab Q8W arms.ConclusionsBenralizumab reduced annual asthma exacerbation rates, increased lung function, and was well-tolerated by Korean patients with severe, uncontrolled eosinophilic asthma.

Project description:The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06-30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24-14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04-1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94-6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71-76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10-19-NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19-269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05-16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22-20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58-91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7-75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9-112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16-73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response.

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Daily patient-reported health status assessment improvements with benralizumab for patients with severe, uncontrolled eosinophilic asthma.

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Daily patient-reported health status assessment improvements with benralizumab for patients with severe, uncontrolled eosinophilic asthma.

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