Treatment patterns in US patients hospitalized with COVID-19 and pulmonary involvement.

This study describes the baseline characteristics and treatment patterns of US patients hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) and pulmonary involvement. Patients hospitalized with pulmonary involvement due to COVID-19 (first hospitalization) were identified in the IBM Explorys® electronic health records database. Demographics, baseline clinical characteristics, and in-hospital medications were assessed. For evaluation of in-hospital medications, results were stratified by race, geographic region, age, and month of admission. Of 6564 hospitalized patients with COVID-19-related pulmonary involvement, 50.4% were male, and mean (SD) age was 62.6 (16.4) years; 75.2% and 23.6% of patients were from the South and Midwest, respectively, and 50.2% of patients were African American. Compared with African American patients, a numerically higher proportion of White patients received dexamethasone (19.7% vs. 31.8%, respectively), nonsteroidal anti-inflammatory drugs (NSAIDs; 27.1% vs. 34.9%), bronchodilators (19.8% vs. 29.5%), and remdesivir (9.3% vs. 21.0%). Numerically higher proportions of White patients than African American patients received select medications in the South but not in the Midwest. Compared with patients in the South, a numerically higher proportion of patients in the Midwest received dexamethasone (20.1% vs. 34.5%, respectively), NSAIDs (19.6% vs. 55.7%), bronchodilators (15.9% vs. 41.3%), and remdesivir (10.6% vs. 23.1%). Inpatient use of hydroxychloroquine decreased over time, whereas the use of dexamethasone and remdesivir increased over time. Among US patients predominantly from the South and Midwest hospitalized with COVID-19 and pulmonary involvement, differences were seen in medication use between different races, geographic regions, and months of hospitalization.

The Added Burden of Allergen Sensitization Among Children with Severe or Poorly Controlled Asthma.

BACKGROUND: Allergen sensitization (AS) may negatively affect asthma outcomes in children with severe or poorly controlled (SPC) asthma. OBJECTIVES: To examine the impact of AS on asthma exacerbations, health care use, and costs among children with SPC asthma in private and public insurance settings. METHODS: This retrospective study analyzed children with SPC asthma aged 6 to 11 years from the MarketScan Commercial (private insurance) and Medicaid databases. Selection of children with SPC asthma was based on medical claims and asthma medication prescription claims. AS status was based on diagnoses of extrinsic asthma and allergic conditions. Children were followed for at least 12 months. Outcomes included asthma exacerbations, days with oral corticosteroids (OCS), and asthma-related health care use and costs. Adjusted generalized linear models were fit to compare outcomes in children with versus those without AS. RESULTS: Among children with SPC asthma, 34% had AS (private insurance: N = 11,448; Medicaid: N = 10,800), 20% did not have AS (private insurance: N = 7744; Medicaid: N = 6535), and, in the remainder, AS status could not be determined. Claims data were available for ≥3 years on average. Children with AS had significantly higher adjusted rates of asthma exacerbations during follow-up than children without AS, and significantly more days with OCS use. Rates of asthma-related hospitalizations, emergency department visits, and health care costs were significantly higher among children with AS than among children without AS. CONCLUSIONS: Children with SPC asthma and AS have relatively greater asthma-related health care use and costs compared with children with SPC asthma without AS.

Baseline Demographics and Clinical Characteristics Among 3471 US Patients Hospitalized with COVID-19 and Pulmonary Involvement: A Retrospective Study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can present as a range of symptoms, from mild to critical; lower pulmonary involvement, including pneumonia, is often associated with severe and critical cases. Understanding the baseline characteristics of patients hospitalized with COVID-19 illness is essential for effectively targeting clinical care and allocating resources. This study aimed to describe baseline demographics and clinical characteristics of US patients hospitalized with COVID-19 and pulmonary involvement. METHODS: US patients with COVID-19 and pulmonary involvement during an inpatient admission from December 1, 2019, to May 20, 2020, were identified using the IBM Explorys® electronic health records database. Baseline (up to 12 months prior to first COVID-19 hospitalization) demographics and clinical characteristics and preadmission (14 days to 1 day prior to admission) pulmonary diagnoses were assessed. Patients were stratified by sex, age, race, and geographic region. RESULTS: Overall, 3471 US patients hospitalized with COVID-19 and pulmonary involvement were included. The mean (SD) age was 63.5 (16.3) years; 51.2% of patients were female, 55.0% African American, 81.6% from the South, and 16.8% from the Midwest. The most common comorbidities included hypertension (27.7%), diabetes (17.3%), hyperlipidemia (16.3%), and obesity (9.7%). Cough (27.3%) and dyspnea (15.2%) were the most common preadmission pulmonary symptoms. African American patients were younger (mean [SD], 62.5 [15.4] vs. 67.8 [6.2]) with higher mean (SD) body mass index (33.66 [9.46] vs. 30.42 [7.86]) and prevalence of diabetes (19.8% vs. 16.7%) and lower prevalence of chronic obstructive pulmonary disease (5.6% vs. 8.2%) and smoking/tobacco use (28.1% vs. 37.2%) than White patients. CONCLUSIONS: Among US patients primarily from the South and Midwest hospitalized with COVID-19 and pulmonary involvement, the most common comorbidities were hypertension, diabetes, hyperlipidemia, and obesity. Differences observed between African American and White patients should be considered in the context of the complex factors underlying racial disparities in COVID-19.

Validity and responsiveness of the Urticaria Activity and Impact Measure: A new patient-reported tool.

BACKGROUND: Chronic spontaneous urticaria (CSU), also known as chronic idiopathic urticaria, may produce hives, itch, and angioedema. The Urticaria Activity and Impact Measure (U-AIM) is a newly developed 9-item patient-reported measure designed for use in routine clinical practice to assess CSU activity and impact during the previous 7 days. OBJECTIVE: To evaluate validity, responsiveness, and clinically meaningful change of the U-AIM. METHODS: Data from a 24-week, open-label, single-arm period of a randomized, placebo-controlled study of omalizumab were used to assess the psychometric properties of U-AIM items for itch, hives, and angioedema. RESULTS: A total of 206 patients (75% female; mean age, 44.6 years) were enrolled. At baseline, U-AIM results included prevalent severe itch (55%) and more than 12 hives (67%), angioedema (15%), and bother by itch (84%), hives (84%), and angioedema (49%). The Urticaria Patient Daily Diary (UPDD) mean weekly scores were 15.4 (itch severity), 16.8 (number of hives), and 32.2 (Urticaria Activity Score [UAS7]). At baseline, week 12, and week 24, U-AIM itch and hives items and UAS7 proxy scores (the sum of itch severity and number of hives during 7 days) demonstrated strong correlation coefficients with their corresponding measures from the UPDD (itch severity: 0.634-0.806; hives number: 0.735-0.843; UAS7 proxy: 0.724-0.852). Changes in U-AIM scores differentiated patients by their perspective of symptom improvement. Meaningful change thresholds were established for itch severity and number of hives scores (range, 0.8-1.0 for both) and the UAS7 proxy score (range, 10.5-12.5). CONCLUSION: The U-AIM is valid and responsive to change and may help clinicians monitor CSU activity and track treatment effectiveness.

Angioedema in the omalizumab chronic idiopathic/spontaneous urticaria pivotal studies.

BACKGROUND: Angioedema, present in some patients with chronic idiopathic/spontaneous urticaria (CIU/CSU), may have a negative effect on patient quality of life. OBJECTIVE: To describe patient-reported angioedema and its management in the pivotal omalizumab studies (ASTERIA I, ASTERIA II, GLACIAL). METHODS: Enrolled patients with CIU/CSU remained symptomatic despite treatment with histamine1 (H1)-antihistamines at licensed doses (ASTERIA I, ASTERIA II) or H1-antihistamines at up to 4 times the approved dose plus H2-antihistamines and/or a leukotriene receptor antagonist (GLACIAL). All studies administered omalizumab (75, 150, or 300 mg in ASTERIA I and ASTERIA II; 300 mg in GLACIAL) or placebo subcutaneously every 4 weeks for at least 12 weeks. Urticaria Patient Daily Diary entries were completed by patients and summarized. RESULTS: At baseline, angioedema prevalence was higher in GLACIAL (53.1%) than in ASTERIA I (47.5%) or ASTERIA II (40.7%). The mean proportion of angioedema-free days during weeks 4 to 12 was greater for patients treated with 300 mg of omalizumab than placebo in ASTERIA I (96.1% vs 88.2%, P < .001), ASTERIA II (95.5% vs 89.2%, P < .001), and GLACIAL (91.0% vs 88.7%, P = .006). Most patient-reported angioedema was managed by low-intensity interventions (doing nothing or taking medication). CONCLUSION: Treatment with 300 mg of omalizumab was efficacious in reducing patient-reported angioedema. Low-intensity interventions were generally used to manage angioedema episodes. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT01287117 (ASTERIA I), NCT01292473 (ASTERIA II), and NCT01264939 (GLACIAL).

Timing and duration of omalizumab response in patients with chronic idiopathic/spontaneous urticaria.

BACKGROUND: Few data are available that describe response patterns in patients with chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) treated with omalizumab. OBJECTIVE: We sought to describe response patterns by using data from the 3 pivotal omalizumab CIU/CSU trials. METHODS: Every 4 weeks, randomized patients received dosing with placebo or 75, 150, or 300 mg of omalizumab (ASTERIA I: n = 318, 24 weeks; ASTERIA II: n = 322, 12 weeks) or placebo or 300 mg of omalizumab (GLACIAL: n = 335, 24 weeks). Response was defined as well-controlled urticaria (weekly Urticaria Activity Score [UAS7] ≤ 6) or complete response (UAS7 = 0). RESULTS: Response rates were dose dependent and highest with 300 mg of omalizumab. Some patients responded early (before week 4). At week 12, a higher proportion of patients treated with 300 mg of omalizumab reported a UAS7 ≤ 6 (26.0% [75 mg of omalizumab], 40.0% [150 mg of omalizumab], 51.9% [300 mg of omalizumab], and 11.3% [placebo] for ASTERIA I; 26.8% [75 mg of omalizumab], 42.7% [150 mg of omalizumab], 65.8% [300 mg of omalizumab], and 19.0% [placebo] for ASTERIA II; and 52.4% [300 mg of omalizumab] and 12.0% [placebo] for GLACIAL) or a UAS7 = 0 (11.7% [75 mg of omalizumab], 15.0% [150 mg of omalizumab], 35.8% [300 mg of omalizumab], and 8.8% [placebo] for ASTERIA I; 15.9% [75 mg of omalizumab], 22.0% [150 mg of omalizumab], 44.3% [300 mg of omalizumab], and 5.1% [placebo] for ASTERIA II; and 33.7% [300 mg of omalizumab] and 4.8% [placebo] for GLACIAL). In patients receiving 300 mg of omalizumab with 24 weeks of treatment, median time to achieve a UAS7 ≤ 6 was 6 weeks (ASTERIA I and GLACIAL) and median time to achieve a UAS7 = 0 was 12 or 13 weeks (ASTERIA I and GLACIAL, respectively). Some patients who achieved well-controlled urticaria or complete response sustained response throughout the treatment period. CONCLUSION: Benefits of omalizumab treatment were evident early (before week 4) in some patients and persisted to week 24. Use of 300 mg of omalizumab demonstrated best results in controlling CIU/CSU symptoms.

The minimal important difference for measures of urticaria disease activity: Updated findings.

BACKGROUND: The Urticaria Patient Daily Diary (UPDD) is a validated patient-reported outcome that captures key measures of urticaria disease activity. OBJECTIVE: To update estimates of the minimal important difference (MID) for urticaria disease activity measures in the UPDD, including the weekly itch severity score, weekly number of hives score, weekly average size of largest hive score, and the composite measure of itch severity and number of hives over 7 days, or urticaria activity score 7 (UAS7). METHODS: A total of 975 subjects with chronic idiopathic urticaria from three randomized, double-blind, placebo-controlled studies completed the UPDD and other patient-reported outcome assessments (the Dermatology Life Quality Index, Medical Outcomes Study Sleep Scale, the Chronic Urticaria Quality-of-Life Questionnaire, the EuroQoL-5 Dimension Questionnaire) multiple times. MIDs were estimated through a combination of distribution- and anchor-based methods. RESULTS: MID estimates ranged from 4.5 to 5.0 for the weekly itch severity score, 5.0 to 5.5 for weekly hives count score, 9.5 to 10.5 for the UAS7, and 4.0 to 4.5 for the weekly size of the largest hive score. CONCLUSION: This analysis provided confirmation of the previous MID estimates for the urticaria disease activity measures in the UPDD.

Risk of corticosteroid-related adverse events in asthma patients with high oral corticosteroid use.

BACKGROUND: Oral corticosteroids (OCS) are a mainstay of asthma treatment. Their use increases the risk of various corticosteroid-related adverse events, but the extent of risk is poorly characterized. OBJECTIVE: To determine the incremental risk of possible corticosteroid-related adverse events (AE) in asthma among patients with high OCS use compared with patients who do not use OCS. METHODS: Patients with asthma in a commercial health care claims data base who were high-OCS users (≥30 days of OCS use annually) were matched to no-OCS users by age, sex, and geographic region, and the presence or absence of chronic obstructive pulmonary disease (COPD) as a comorbidity. We examined bone-related conditions, pneumonia, opportunistic infections, diabetes mellitus, and other disorders as potential AEs by using χ(2) tests to compare potential AE prevalence between the cohorts, with and without stratification by a COPD diagnosis. We controlled for the number of inhaled steroids (ICS) canisters filled. RESULTS: A total of 3604 patients with asthma and high OCS use were matched to 3604 patients who did not use OCS (mean age, 54.4; 68.1% female; 44.9% with COPD). Patients with high OCS use had statistically significantly higher rates of any potential AE compared with patients who did not use OCS (83.5% versus 78.1%), (p < 0.001). Rates of individual potential AEs were also higher in patients who used higher doses of OCS. Patterns of AEs were similar in patients with and those without COPD, with statistically significantly higher overall AE risk and individual risks in high-OCS users. The number of ICS canisters filled was not a significant predictor of AE. CONCLUSION: Patients with asthma who were treated with OCS for ≥30 days per year have a greater overall risk of possible corticosteroid-related AEs compared with those patients with no OCS use, whether or not they had COPD.

Changes in asthma control, work productivity, and impairment with omalizumab: 5-year EXCELS study results.

BACKGROUND: Asthma poses a significant disease burden worldwide. Current guidelines emphasize achieving and maintaining asthma control. OBJECTIVE: To describe longitudinal changes of asthma control and asthma-related work, school, and activity impairment for patients with moderate-to-severe asthma treated with omalizumab and those who did not receive omalizumab in a real-world setting. METHODS: This study used 5 years of data from patients ages ≥12 years old with moderate-to-severe persistent allergic asthma who were enrolled in the Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma observational study. Asthma control was assessed with the Asthma Control Test for 5 years, and asthma-related work, school, and activity impairment was measured with the Work Productivity/Activity Impairment-Asthma questionnaire for the first 2 years. RESULTS: The percentage of patients treated with omalizumab (n = 4930) and with well-controlled asthma (Asthma Control Test score, >20) increased from 45% at baseline to 61% at month 60, and it was 49% (baseline) and 67% (month 60) for the non-omalizumab-treated cohort (n = 2779). For new starters to omalizumab (n = 576), the percentage with well-controlled asthma increased from 25% at baseline to 51% at month 6, and to 60% at month 60. Patients in the omalizumab-treated cohort and those in the non-omalizumab-treated cohort experienced a reduction in asthma-related work, school, and activity impairment. The amount of improvement in asthma control achieved and the reduction in asthma-related work, school, and activity impairment were similar, regardless of asthma severity. CONCLUSION: On average, patients in the Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma observational study who initiated omalizumab experienced clinically significant improvement in asthma control, which was observed within 6 months and persisted for 5 years.

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.

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

BACKGROUND: There is no specific International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for chronic idiopathic urticaria or spontaneous urticaria (CIU/CSU), a skin condition characterized by hives and angioedema lasting at least 6 weeks with no known cause. OBJECTIVE: To validate an ICD-9-CM-based algorithm for identification of patients with CIU/CSU and thus facilitate claims-based research. METHODS: Patient records were reviewed at 4 US practices. Patients included in the study were from a random sample of those identified by their physician as having CIU/CSU or because they met the following diagnosis-based algorithm: (1) at least 2 outpatient ICD-9-CM diagnosis codes 708.1, 708.8, or 708.9 at least 6 weeks apart or (2) 1 outpatient diagnosis of 708.1, 708.8, or 708.9 and 1 diagnosis of 995.1 at least 6 weeks apart. Data collected included ICD-9-CM codes, diagnoses of urticaria and allergy-related conditions, and medication use. Sensitivity and positive predictive value were calculated. The study was approved by the Western Institutional Review Board. RESULTS: One hundred forty-nine patient records were reviewed (mean age 41.1 years; 73.8% were women; 69.1% were white): 115 were identified with the diagnosis-based algorithm, 90 were patients with "known CIU/CSU", and 56 were in the 2 groups. The mean duration of CIU/CSU was 2.9 to 3.1 years. The 2 cohorts most frequently had diagnoses of idiopathic urticaria, unspecified urticaria, and other specified urticaria. The diagnosis-based algorithm had a positive predictive value of 90.4% and a sensitivity of 71.1%. CONCLUSION: The high positive predictive value suggests that patients identified using the algorithm are highly likely to have CIU/CSU. The 71.1% sensitivity suggests that most patients with CIU/CSU will be identified. The validation statistics support the use of the diagnosis-based algorithm in claims-based research, although future studies could refine the algorithm further.

Real-time asthma outreach reduces excessive short-acting ß2-agonist use: a randomized study.

BACKGROUND: Excessive use of short-acting ß2-agonists (SABA) indicates impaired asthma control. OBJECTIVE: To determine whether real-time outreach to excessive SABA users reduces SABA canister dispensings. METHODS: After real-time determination of a seventh SABA canister dispensing in the prior 12 months by using informational pharmacy technology, 12 to 56 year old patients with physician-coded asthma and inhaled corticosteroid dispensing were block randomized by prior asthma specialist care and medication step-care level into intervention (n = 1001) and control groups (n = 998). Intervention included real-time letter notification to patients and an electronic message to their physician with management suggestions, including facilitated allergy referral for patients without prior asthma specialist care. The control group received this organization's standard asthma care management without research contact. Frequency of the seventh SABA canister dispensing in the follow-up year was the primary outcome. RESULTS: Compared with controls, intervention patients reached 7 SABA canister dispensings less frequently (50.7% vs 57.1%; risk ratio 0.89 [95% CI, 0.82-0.97]; P = .007) and later (hazard ratio 0.80 [95% CI, 0.71-0.91; P < .001). SABA canister dispensings (mean ± SD) were less in intervention (7.5 ± 4.9 canisters) than controls (8.6 ± 5.3 canisters) (rate ratio 0.87 [95% CI, 0.82-0.93]; P < .001). The intervention reduced the risk of ≥7 SABA canister dispensings in patients without specialist care compared with patients with specialist care in the prior 3 years (P < .001) (P = .04 for interaction by prior specialist care). Visits to allergists were more frequent for intervention patients (30.9%) than for control patients (16.8%) (risk ratio 1.83 [95% CI, 1.54-2.16]; P < .001). Asthma exacerbations were unaffected. CONCLUSIONS: A novel administrative-based asthma outreach program improves markers of asthma impairment in patients without prior asthma specialist care and is adaptable to managed care organizations with electronic medical records.

Demonstrating measurement equivalence of the electronic and paper formats of the Urticaria Patient Daily Diary in patients with chronic idiopathic urticaria.

BACKGROUND: The Urticaria Patient Daily Diary (UPDD), originally developed on paper, is a measure of key symptoms of chronic idiopathic urticaria (CIU). The development of the electronic version (eUPDD) involved moderate modifications to the appearance of the paper version. OBJECTIVE: This study assessed the measurement equivalence of the electronic and paper versions of the UPDD in a sample of patients with CIU. METHODS: This was a cross-over study of patients with moderate-severe CIU refractory to H1 antihistamines. Patients were randomized to either the eUPDD followed by the paper UPDD or vice versa. The UPDD includes morning and evening questions; both sets were administered together in this study. An hour-long filler task was given between paper and electronic administrations. Patients with stable symptoms between the two assessments were included in the analyses. Cohen's kappa coefficients and intraclass correlation coefficients (ICC) were computed as applicable to assess equivalence. RESULTS: A total of 91 patients participated (mean age 43 years, 79.1 % female). Symptoms were stable between assessments for 67-74 (74-81 %) patients (varied by symptom). Kappa coefficients ranged from 0.82 to 1.00 for the individual UPDD items. For the Urticaria Activity Score (the sum of the 'itch severity' and 'number of hives' item scores) the ICC was 0.90 for the morning (Wilcoxon p = 0.331) and 0.95 for the evening (Wilcoxon p = 0.836). CONCLUSIONS: All test-retest statistics in this study were well above the accepted threshold, indicating excellent agreement between the two administration methods. Findings support the measurement equivalence of the electronic and paper versions of the UPDD to measure CIU symptoms.

Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy.

BACKGROUND: Patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) often continue to experience symptoms despite receiving standard-of-care therapy with H1-antihistamines along with 1 or more add-on therapies. OBJECTIVES: We sought to evaluate the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent CIU/CSU despite treatment with H1-antihistamines at up to 4 times the approved dose plus H2-antihistamines, leukotriene receptor antagonists, or both. METHODS: In this phase III study patients were randomized to receive 6 subcutaneous injections at 4-week intervals of either 300 mg of omalizumab or placebo, followed by a 16-week observation period. The primary objective of the study was to evaluate the overall safety of omalizumab compared with placebo. Efficacy (itch severity, hive, and urticaria activity scores) was evaluated at weeks 12 and 24. RESULTS: The overall incidence and severity of adverse events and serious adverse events were similar between omalizumab and placebo recipients; the safety profile was consistent with omalizumab in patients with allergic asthma. At week 12, the mean change from baseline in weekly itch severity score was -8.6 (95% CI, -9.3 to -7.8) in the omalizumab group compared with -4.0 (95% CI, -5.3 to -2.7) in the placebo group (P < .001). Significant improvements were seen for additional efficacy end points at week 12; these benefits were sustained to week 24. CONCLUSION: Omalizumab was well tolerated and reduced the signs and symptoms of CIU/CSU in patients who remained symptomatic despite the use of H1-antihistamines (up to 4 times the approved dose) plus H2-antihistamines, leukotriene receptor antagonists, or both.

Longitudinal changes in asthma control with omalizumab: 2-year interim data from the EXCELS Study.

BACKGROUND: Asthma guidelines emphasize the importance of achieving and maintaining asthma control; however, many patients with moderate to severe asthma fail to achieve adequate control. OBJECTIVE: This 2-year interim analysis evaluated the longitudinal effects of omalizumab on asthma control in patients treated in real-world clinical practice settings. METHODS: EXCELS is an ongoing observational cohort study of approximately 5000 omalizumab-treated and 2500 non-omalizumab-treated patients aged ≥12 years with moderate to severe asthma. Asthma control was measured using the Asthma Control Test (ACT) every 6 months. RESULTS: Subgroups of the omalizumab cohort included those who initiated omalizumab at baseline (new starts, n = 549) and those treated with omalizumab >7 days before baseline (established users, n = 4421). For reference, data are also presented for patients who were not receiving omalizumab prior to or at the time of enrolment (non-omalizumab, n = 2867). Over half of the new starts (54%) achieved improvement in ACT consistent with the minimally important difference (MID, defined as ≥3-point improvement) by Month 6 and this proportion increased throughout the follow-up period, reaching 62% at Month 24. Similar results were observed in patients stratified by moderate and severe asthma. Established users of omalizumab maintained asthma control throughout the observation period. CONCLUSION: Over a 2-year period, patients initiating omalizumab therapy experienced clinically relevant improvements in asthma control, which were maintained during 2 years of longitudinal follow-up. Established users of omalizumab maintained asthma control over the 2-year period with a small improvement similar to that seen in non-omalizumab users.

Adaptation and validation of the Urticaria Patient Daily Diary for adolescents.

The Urticaria Patient Daily Diary, including the Urticaria Activity Score, has recently been validated in adults with chronic idiopathic urticaria (CIU), but its validity in adolescents is unknown. This study was designed to (1) assess the content validity of the Adolescent Urticaria Patient Daily Diary and, (2) collect exploratory data on symptom experiences, sleep interference, and health-related quality of life (HRQOL) of adolescents with CIU. The Urticaria Patient Daily Diary was modified to increase its relevance with an adolescent population. A qualitative, cross-sectional, multicenter study was then conducted in the United States so that adolescent subjects could provide information on the impact of urticaria on their lives and comment on the diary. Data were collected via in-person semistructured interviews with subjects 12-17 years of age with moderate-to-severe CIU. The most bothersome symptom was itching (44%). The impact of CIU on HRQOL varied. The majority of subjects (78%) reported waking up at least once a night. Overall, subjects found the diary to be clear, easy to comprehend, and easy to complete. Revisions were made to the diary based on feedback from subjects. After nine interviews, no new information was received. The symptoms of CIU are bothersome to adolescents, particularly itch, and urticaria has a negative impact on the sleep of adolescent patients. The final Adolescent Urticaria Patient Daily Diary has evidence of content validity in patients with CIU ranging from 12 to 17 years of age.

Cost, utilization, and patterns of medication use associated with chronic idiopathic urticaria.

BACKGROUND: The literature on chronic idiopathic urticaria (CIU) lacks large-scale population-based studies. OBJECTIVE: To characterize an insured population with CIU, including their demographic characteristics and comorbidities. METHODS: We conducted a cross-sectional analysis using insurance claims. We included patients with 1 outpatient claim with an International Classification of Diseases, 9(th)Edition, Clinical Modification (ICD-9-CM) code for idiopathic, other specified, or unspecified urticaria (ICD-9-CM 708.1, 708.8, or 708.9) and either (1) another of these claims 6 or more weeks later; (2) a claim for angioedema (ICD-9-CM 995.1) 6 or more weeks from the urticaria diagnosis; or (3) overlapping claims for 2 prescription medications commonly used for CIU. RESULTS: We identified 6,019 patients who had claims consistent with CIU. The mean age was 36 years. Fifty-six percent of patients had primary care physicians as their usual source of care, 14% had allergists, and 5% had dermatologists. Allergic rhinitis was diagnosed in 48%, asthma in 21%, other allergy in 19%, and atopic dermatitis in 8%. Sixty-seven percent of patients used prescription antihistamines, 54% used oral corticosteroids (OCSs), 24% used montelukast, and 9% used oral doxepin. Antihistamine users received a mean of 152 days of prescription antihistamines, OCS users 30 days of OCSs, montelukast users 190 days of montelukast, and oral doxepin users 94 days of doxepin. CONCLUSIONS: Primary care physicians managed most patients with CIU. Antihistamines were the most common treatment for CIU, although OCSs were frequently prescribed. Thirty days of OCS supply among users may represent multiple steroid bursts each year. Given the known risks of OCSs, identifying other CIU treatments with more favorable safety profiles may be beneficial.

Evaluating the minimally important difference of the urticaria activity score and other measures of disease activity in patients with chronic idiopathic urticaria.

BACKGROUND: The Urticaria Activity Score (UAS) is a widely used patient-reported outcome measure for patients with chronic idiopathic urticaria (CIU) that includes 2 items: intensity of pruritus and number of hives. Items are scored individually, and the UAS7 is calculated as the sum of pruritus and number of hives over 1 week. Recently, its instructions were enhanced. OBJECTIVE: To assess the measurement properties of the enhanced UAS. METHODS: Seventy-three subjects with CIU completed the UAS with enhanced instructions, other measures of disease activity including the size of the largest hive, and collateral measures during a multicenter, randomized, double-blind, placebo-controlled study of omalizumab for the treatment of CIU. The minimal important difference (MID) was estimated through distribution- and anchor-based approaches. Test-retest reliability was assessed with the intraclass correlation coefficient (ICC); internal consistency reliability was evaluated with Cronbach's alpha; 3 responsiveness coefficients were calculated; known groups validity was assessed based on physician in-clinic UAS scores; and construct validity was assessed through Spearman correlation coefficients with collateral measures. RESULTS: The MID ranged from 9.5 to 10.5 for the UAS7, 5.0 to 5.5 for number of hives (weekly average), and 4.5 to 5.0 for pruritus and size of largest hive (weekly average). Internal consistency was supported by alpha coefficients greater than 0.80. The ICC values for test-retest reliability ranged from 0.602 to 0.884. For subjects on active treatment, responsiveness coefficients were greater than 0.80. Known-groups validity was supported for most UAS scores; and construct validity was demonstrated by relationships with collateral measures. CONCLUSIONS: The enhanced UAS has adequate measurement properties to support its use in clinical research.

Concomitant asthma medication use by patients receiving omalizumab 2003-2008.

OBJECTIVE: To examine patterns of omalizumab use in the first 5 years of its availability. METHODS: Our study comprised a series of descriptive retrospective cohort analyses using healthcare claims data. The study population comprised patients of any age who had omalizumab claims in the 5 years after 1 July 2003, and we created five 1-year cohorts from this population. Each cohort included patients continuously enrolled for at least 12 months with ≥2 omalizumab claims during the year. Cohorts contained between 302 and 1382 unique omalizumab users, and over 99% of patients with an omalizumab claim had at least one asthma diagnosis. RESULTS: In all years, the specialty most commonly seen in conjunction with the initial omalizumab prescription was allergy/immunology. In all years, omalizumab was used in conjunction with three or more additional classes of asthma medications at least 70% of the time and with five or more classes at least 33% of the time; the proportion of patients filling omalizumab prescriptions who had no other concomitant classes of asthma medications varied from 4% to 8%. The most common pattern of asthma medication treatment in all years was omalizumab with combination steroids/long-acting beta-agonist inhaler, a leukotriene receptor antagonist, a short-acting beta-agonist inhaler, and at least one course of oral corticosteroids. CONCLUSIONS: In this study of a large sample of commercial health insurance claims covering the first 5 years after approval of omalizumab, we found that omalizumab was infrequently used as a single agent or without concomitant inhaled corticosteroids, and most omalizumab prescriptions came from specialist physicians.