Paul G. Solari

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.

Omalizumab adherence in an observational study of patients with moderate to severe allergic asthma.

BACKGROUND Adherence to omalizumab is not well characterized and its association with asthma control has not been well established. OBJECTIVE To evaluate adherence in patients initiating omalizumab in the Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate to Severe Asthma (EXCELS) observational study. METHODS Adherence was assessed over 5 years using the proportion of patients who missed any dose, rates of doses missed, and proportions of patients with good (<10% doses missed) or poor (≥30% doses missed) adherence. Multivariable analyses identified independent predictors of good adherence. Associations between adherence and asthma control were assessed using the minimum important difference for the Asthma Control Test at various time points. RESULTS A total of 289 patients newly initiated on omalizumab completed 5 years of EXCELS. Of these, 83.0% on the 2-week dosing regimen (n = 152) and 65.0% on the 4-week dosing regimen (n = 137) missed at least 1 dose. More frequent dosing was associated with a larger number of missed doses. Older age (odds ratio per year 1.02, 95% confidence interval 1.01-1.03) and lower prebronchodilator percentage of predicted forced expiratory volume in 1 second (<76; odds ratio 1.88, 95% confidence interval 1.09-3.24) were independent predictors of good adherence. CONCLUSION Adherence to omalizumab is characterized by distinct factors. Patients receiving the 4-week dosing regimen achieved better adherence than those treated every 2 weeks. Improved adherence could be associated with better asthma control. Age and lung function could interact with dosing frequency to affect patient adherence, thus warranting prospective planning at the time of prescribing to support long-term adherence.

Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO

BACKGROUND Patients included in clinical trials do not necessarily reflect the real-world population. OBJECTIVE To understand the characteristics, including disease and comorbidity burden, of patients with asthma receiving omalizumab in a real-world setting. METHODS The Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab (PROSPERO) was a US-based, multicenter, single-arm, and prospective study. Patients (≥12 years of age) with allergic asthma initiating omalizumab treatment based on physician-assessed need were included and followed for 12 months. Exacerbations, health care use, adverse events, and Asthma Control Test (ACT) scores were assessed monthly. Biomarkers (blood eosinophils, fractional exhaled nitric oxide, and periostin) were evaluated and patient-reported outcomes (Asthma Quality of Life Questionnaire for 12 Years and Older [AQLQ+12] and Work Productivity and Activity Impairment: Asthma questionnaire [WPAI:Asthma]) were completed at baseline and months 6 and 12. The Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) was completed at baseline and 12 months. RESULTS Most of the 806 enrollees (91.4%) were adults (mean age 47.3 years, SD 17.4), white (70.3%), and female (63.5%). Allergic comorbidity was frequently reported (84.2%), as were hypertension (35.5%) and depression (22.1%). In the 12 months before study entry, 22.1% of patients reported at least 1 asthma-related hospitalization, 60.7% reported at least 2 exacerbations, and 83.3% reported ACT scores no higher than 19 (uncontrolled asthma). Most patients had low biomarker levels based on prespecified cut-points. Baseline mean patient-reported outcome scores were 4.0 (SD 1.4) for AQLQ+12, 2.7 (SD 1.4) for MiniRQLQ, and 47.7 (SD 28.9) for WPAI:Asthma percentage of activity impairment and 33.5 (SD 28.7) for percentage of overall work impairment. CONCLUSION The population initiating omalizumab in PROSPERO reported poorly controlled asthma and a substantial disease burden. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01922037.

Development and Validation of an Algorithm for Identifying Patients with Hemophilia A in an Administrative Claims Database

BACKGROUND The accuracy with which hemophilia A can be identified in claims databases is unknown. OBJECTIVE Develop and validate an algorithm using predictive modeling supported by machine learning to identify patients with hemophilia A in an administrative claims database. METHODS We first created a screening algorithm using medical and pharmacy claims to identify potential hemophilia A patients in the US HealthCore Integrated Research Database between January 1, 2006 and April 30, 2015. Medical records for a random sample of patients were reviewed to confirm case status. In this validation sample, we used lasso logistic regression with cross-validation to select covariates in claims data and develop a predictive model to estimate the probability of being a confirmed hemophilia A case. RESULTS The screening algorithm identified 2,252 patients and we reviewed medical records for 400 of these patients. The screening algorithm had a positive predictive value (PPV) of 65%. The predictive model identified 18 predictors of being a hemophilia A case or noncase. The strongest predictors of case status included male sex, factor VIII therapy, office visits for hemophilia A, and hospitalizations for hemophilia A. The strongest predictors of noncase status included hospitalizations for reasons other than hemophilia A and factor VIIa therapy. A probability threshold of ≥0.6 resulted in a PPV of 94.7% (95% CI: 92.0-97.5) and sensitivity of 94.4% (95% CI: 91.5-97.2). CONCLUSIONS We developed and validated an algorithm to identify hemophilia A cases in an administrative claims database with high sensitivity and high PPV.

Patient Outcomes, Health Care Resource Use, and Costs Associated with High Versus Low HEDIS Asthma Medication Ratio

BACKGROUND The Healthcare Effectiveness Data and Information Set (HEDIS) quality measures for asthma include the asthma medication ratio (AMR) as a marker of quality of care for patients with asthma. Few data are available to describe the association between health care use and costs in patients with high versus low AMR. OBJECTIVE To characterize health care use and costs associated with high versus low AMR in patients participating in commercial health plans. METHODS In a commercial claims database, this study retrospectively identified patients aged 5 to 64 years on December 31, 2011, who met the HEDIS definition of asthma in the premeasurement year (January 1, 2010-December 31, 2010) and the measurement year (January 1, 2011-December 31, 2011). Each patient was classified as having either high or low AMR based on the HEDIS definition. AMR was calculated as the ratio of controller to total asthma medications; high AMR was defined as ≥ 0.5. Annual per-patient health care use and costs were compared in patients with high versus low AMR using (a) multivariable linear regression models to estimate mean annual number of office visits, oral corticosteroids (OCS) bursts (≤ 15-day supply), and costs and (b) negative binomial models to estimate mean annual hospitalization and emergency department (ED) visits. All estimates were adjusted for age, sex, region, and Charlson Comorbidity Index score to control for differences between patients with high versus low AMR. RESULTS Patients were identified with high (30,575) and low (6,479) AMR. An average patient with high AMR had more all-cause office visits (14.1 vs. 11.0; P < 0.001), fewer all-cause hospitalizations (0.109 vs. 0.215; P < 0.001), fewer all-cause ED visits (0.321 vs. 0.768; P < 0.001), and fewer OCS bursts (0.83 vs. 1.33; P < 0.001) than an average patient with low AMR. An average patient with high AMR had fewer asthma-related hospitalizations (0.024 vs. 0.088; P < 0.001) and ED visits (0.060 vs. 0.304; P < 0.001) than an average patient with low AMR. Numbers of asthma-related annual office visits were similar between the high and low AMR groups (high 2.2 vs. low 2.2; not significant). The rate of poor asthma control events (≥ 6 short-acting beta-agonist dispensing events or ≥ 2 OCS bursts, asthma-related ED visits, or hospitalizations) was greater in patients with low AMR than in patients with high AMR (74.3% vs. 26.9%). An average patient with high AMR had lower annual nonmedication costs than an average patient with low AMR (

Real-Time Asthma Outreach Reduces Excessive Short-acting β2-Agonist Use: A Randomized Study

5,733 vs.

Validation of an ICD-9-based claims algorithm for identifying patients with chronic idiopathic/spontaneous urticaria.

6,295; P = 0.011). Similar trends emerged for asthma-related costs. A patient with high AMR had higher average total annual health care costs than a patient with low AMR (

Angioedema in the omalizumab chronic idiopathic/spontaneous urticaria pivotal studies

9,811 vs.

Evaluating omalizumab persistency of response after long-term therapy (XPORT)

8,398; P < 0.001). These increased costs primarily resulted from increased medication costs for patients with high versus low AMR (

Surgical Experience in Two Multicenter, Open-Label Phase 3 Studies of Emicizumab in Persons with Hemophilia A with Inhibitors (HAVEN 1 and HAVEN 2)

4,077 vs.