Omalizumab improves sleep and health status for patients with chronic rhinosinusitis with nasal polyps: An analysis of randomized clinical trials.

BACKGROUND: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have high incidence of sleep impairment. We evaluated the impact of omalizumab treatment on sleep characteristics and associated health status in patients with CRSwNP. METHODS: Prespecified exploratory analysis assessed outcomes from patients included in the POLYP 1 and POLYP 2 phase 3 clinical trials and the open-label extension. Sleep was assessed by the sleep domain of the Sino-Nasal Outcome Test-22 (SNOT-22; MCID > 4 in patients with CRS) and the Medical Outcomes Study Sleep Scale (MOS-Sleep). Health status was assessed by Healthy Days Core Module (HDCM) and sinonasal-specific Patient Global Impression of Change (PGIC). RESULTS: Omalizumab improved sleep as assessed by the SNOT-22 sleep domain. At week 24, adjusted mean (95%CI) SNOT-22 sleep scores had reduced from baseline by -8.5 (-9.9 to -7.1) with omalizumab versus -2.7 (-4.1 to -1.3) with placebo. At week 52 (all patents on OMA), adjusted mean (95%CI) SNOT-22 sleep scores had reduced from baseline by -10.1 (-11.4 to -8.7) with omalizumab. Improvements were observed in all eight items of the SNOT-22 sleep domain: difficulty falling asleep, fatigue, frustration/restlessness/irritability, lack good night's sleep, reduced concentration, reduced productivity, wake up tired, and wake up at night. In addition, omalizumab improved six of eight sleep outcomes on the MOS-Sleep scale. There were concurrent improvements in HDCM and PGIC. CONCLUSION: Omalizumab improved sleep and self-reported health status in patients with CRSwNP. This contributes to evidence that omalizumab provides value for patients beyond the reduction of sinonasal symptoms.

Omalizumab improves sinonasal outcomes in patients with chronic rhinosinusitis with nasal polyps regardless of allergic status.

BACKGROUND: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) often have atopic comorbidities, including elevated IgE levels and comorbid asthma. Omalizumab, an IgE monoclonal antibody, is an effective treatment for CRSwNP, but the impact of allergy or asthma status on response to omalizumab in patients with CRSwNP has not been well studied. OBJECTIVE: To evaluate the impact of allergy and asthma status on omalizumab treatment in patients with CRSwNP, this posthoc exploratory analysis assessed sinonasal outcomes from subgroups of patients included in POLYP 1 and POLYP 2 and the open-label extension (OLE) trials. METHODS: Patients (N = 249) were grouped by the presence/absence of comorbid allergy (≥ 1 physician-reported allergic rhinitis, allergic sinusitis, food allergy, or atopic dermatitis), presence/absence of comorbid asthma, baseline serum total IgE (≥ 150 or <150 IU/mL), and baseline blood eosinophil levels (>300 or ≤ 300 cells/µL). Sinonasal outcomes were the nasal polyps score, nasal congestion score, and sino-nasal outcome test-22. RESULTS: During POLYP 1 and POLYP 2 and the OLE, omalizumab treatment improved the nasal polyps score, nasal congestion score, and sino-nasal outcome test-22 score in patients with/without physician-reported allergic comorbidities, with/without asthma, with higher/lower total IgE levels, and with higher/lower blood eosinophil counts. In the OLE, the pattern of improvement was similar in patients who continued or switched to omalizumab. CONCLUSION: In patients with CRSwNP, omalizumab improved sinonasal outcomes independent of allergic status, which suggests that a wide range of patients with different endotypes and phenotypes of CRSwNP may benefit from omalizumab treatment. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03280550, NCT03280537, NCT03478930.

The Role of IgE in Upper and Lower Airway Disease: More Than Just Allergy!

Immunoglobulin E (IgE) is a well-known key factor in allergic airway disease; however, its central role in non-allergic airway inflammation is often underestimated. In some airway diseases, IgE is produced as a result of allergic sensitization. However, in others, IgE production occurs despite the lack of a specific allergen. Although multiple pathways contribute to the production of IgE in airway disease, it is its activity in mediating the inflammatory response that is associated with disease. Therefore, an understanding of IgE as the unifying component of upper and lower airway diseases has important implications for both diagnosis and treatment. Understanding the role of IgE in each upper and lower airway disease highlights its potential utility as a diagnostic marker and therapeutic target. Further classification of these diseases by whether they are IgE mediated or non-IgE mediated, rather than by the existence of an underlying allergic component, accounts for both systemic and localized IgE activity. Improvements in diagnostic methodologies and standardization of clinical practices with this classification in mind can help identify patients with IgE-mediated diseases. In doing so, this group of patients can receive optimal care through targeted anti-IgE therapeutics, which have already demonstrated efficacy across numerous IgE-mediated upper and lower airway diseases.

Defining the Efficacy of Omalizumab in Nasal Polyposis: A POLYP 1 and POLYP 2 Subgroup Analysis.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with variable underlying pathophysiologies. Numerous patient factors have been linked to differences in disease severity, control, and response to treatment, including asthma status, aspirin sensitivity, previous sinonasal surgery, and blood eosinophil levels. OBJECTIVE: The present study examines the efficacy of the anti-immunoglobulin E therapy, omalizumab, versus placebo in patients with CRSwNP from the replicate POLYP 1 (NCT03280550) and POLYP 2 (NCT03280537) trials, grouped by inherent patient characteristics to determine the response to therapy. METHODS: Patients in prespecified subgroups from POLYP 1 and POLYP 2 (studies pooled for analysis) were examined. Subgroups included blood eosinophil count at baseline (>300 or ≤300 cells/µL), previous sinonasal surgery (yes or no), asthma status (yes or no), and aspirin sensitivity status (yes or no). Subgroups were examined for subgroup-specific adjusted mean difference (95% confidence interval [CI]) (omalizumab-placebo) in change from baseline at week 24 in Nasal Congestion Score (NCS), Nasal Polyp Score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22), Total Nasal Symptom Score (TNSS), and University of Pennsylvania Smell Identification Test (UPSIT). RESULTS: Adjusted mean difference (95% CI) (omalizumab-placebo) in NCS, NPS, SNOT-22, TNSS, and UPSIT change from baseline at week 24 consistently favored omalizumab treatment over placebo in patients with blood eosinophil count >300 and ≤300 cells/µL, with or without previous sinonasal surgery, asthma, and aspirin sensitivity. CONCLUSION: Together, these data suggest broad efficacy of omalizumab across clinical and patient-reported outcomes in patients with CRSwNP, independent of the underlying patient factors examined, including those with high eosinophil levels and those who have undergone previous surgery, which are associated with high recurrence. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: POLYP 1: ClinicalTrials.gov identifier NCT03280550 (https://clinicaltrials.gov/ct2/show/NCT03280550); POLYP 2: ClinicalTrials.gov identifier NCT03280537 (https://clinicaltrials.gov/ct2/show/NCT03280537).

Patient-reported outcomes of dual bronchodilator fixed-dose combination versus bronchodilator monotherapy in individuals with COPD.

Background: This study compared real-world patient-reported outcomes (PROs) measured by the Clinical COPD Questionnaire (CCQ), the London Chest Activities of Daily Living (LCADL) scale, and the Work Productivity and Activity Impairment (WPAI) questionnaire between individuals with COPD initiating LAMA/LABA fixed-dose combination (FDC) dual therapy versus either long-acting muscarinic antagonist (LAMA) or long-acting beta2-agonist (LABA) monotherapy. Methods: Individuals with COPD aged ≥40 years initiating a LAMA/LABA FDC dual therapy or a LAMA or LABA monotherapy (index date = first prescription date) between January 1, 2016 and December 31, 2016 were identified from a large US administrative claims database. Individuals were excluded if they were prescribed an inhaled corticosteroid (ICS) or ICS/LABA two months prior to the index date or were diagnosed with cystic fibrosis, idiopathic pulmonary fibrosis, or asthma. The cohorts were propensity score matched (PSM) 1:1 for COPD severity using baseline measures. Each participant completed a survey. Results: Surveys were completed by 399 participants in the dual therapy cohort, and 718 participants in the monotherapy cohort. Following PSM, 379 participants remained in each cohort for analysis (monotherapy: 369 LAMA and 10 LABA). The dual therapy cohort reported fewer COPD-related symptoms (CCQ symptom score 2.75 vs 2.97, respectively, P=0.023), and, fewer limitations in leisure activities (LCADL leisure score 4.78 vs 5.17, respectively, P=0.021) versus the monotherapy cohort. No significant differences were found in the WPAI. A greater percentage of participants in the dual therapy cohort stayed on index therapy (63.1%) when compared with the monotherapy cohort (30.3%, P<0.0001). Conclusions: Only 30% of the participants prescribed monotherapy, usually with a LAMA, remained on index therapy alone at the time of survey administration. In the dual therapy cohort, 63% of the participants remained on the index medication and had fewer COPD-related symptoms and fewer limitations in leisure activities compared with participants in the monotherapy cohort.

A Retrospective Claims Analysis of Dual Bronchodilator Fixed-Dose Combination Versus Bronchodilator Monotherapy in Patients with Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) increasingly receive combination bronchodilator therapies. Real world evidence for the benefits of combination therapy compared to monotherapy is lacking. METHODS: COPD patients aged ≥ 40 years initiating monotherapy (MT) with either a long-acting muscarinic antagonist (LAMA) or long-acting beta2-agonist (LABA) or dual therapy (DT) with a LAMA/LABA fixed dose combination (FDC) between January 1, 2016 and December 31, 2016 were identified from a large U.S. administrative claims database. Patients diagnosed with cystic fibrosis, idiopathic pulmonary fibrosis, or asthma were excluded. Cohorts were propensity score matched 1:1 using baseline measures (e.g., exacerbations, hospitalizations) as proxies for COPD severity to create balanced cohorts. RESULTS: Following propensity score matching (PSM), 1286 patients remained in each cohort for analysis. Patients were followed for approximately 1 year. Patients in the DT versus MT cohort had lower rates of exacerbations leading to hospitalization (incidence rate ratio 0.7886; p=0.019), lower mean COPD-related pharmacy costs per patient per month (PPPM) ($300 versus $379, respectively; p<0.001) and total costs PPPM ($990 versus $1203, respectively; p=0.003). This occurred despite lower mean COPD-related pharmacy fills PPPM in the DT versus MT cohorts (1.41 versus 1.51, respectively; p=0.038). Patients in the DT cohort had lower rates of switching (p<0.001) and augmentation (p<0.001), and higher rates of non-persistence (p<0.001) versus the MT cohort. Rates of discontinuation were similar. CONCLUSIONS: Patients in the DT cohort had lower rates of exacerbations leading to hospitalization, lower COPD-related pharmacy and total costs PPPM, and lower rates of switching and augmentation compared to patients in the MT cohort.