Few data are available to assist clinicians with decisions regarding long-term use of asthma therapies, including omalizumab.
We sought to evaluate the benefit and persistence of response in subjects ...continuing or withdrawing from long-term omalizumab treatment.
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.
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.
Continuation of omalizumab after long-term treatment results in continued benefit, as evidenced by improved symptom control and reduced exacerbation risk.
Objective: To assess real-world costs for patients with hemophilia A treated with bypassing agents versus factor VIII (FVIII) replacement.
Methods: Claims data from a large US health insurer during 1 ...January 2006-30 September 2014 were used for analysis. Treated patients with hemophilia A were identified based on ≥1 medical claim with a diagnosis code for hemophilia A (ICD-9-CM 286.0) and ≥1 medical or pharmacy claim for bypassing therapy and/or FVIII replacement during 1 January 2007-31 August 2014. The bypassing therapy cohort comprised patients with ≥1 claim for bypassing therapy; all others were assigned to the factor replacement therapy cohort. Post-index hemophilia-related costs were computed as combined health plan plus patient paid amounts for medical claims with hemophilia A diagnosis code or hemophilia therapy procedure code (bypassing therapy, FVIII replacement therapy, desmopressin, antifibrinolytic therapy), as well as pharmacy claims for hemophilia therapy.
Results: The study sample represented 580 patients: 50 (8.6%) in the bypassing therapy cohort (mean age: 38.5 years; mean post-index period: 2.1 years) and 530 (91.4%) in the factor replacement therapy cohort (mean age: 29.3 years; mean post-index period: 2.7 years). Compared with the factor replacement therapy cohort, mean per-patient-per-month hemophilia-related total costs were 4.8-fold higher in the bypassing therapy cohort ($57,232 vs. $11,899), comprising 4.4-fold higher medical costs ($45,911 vs. $10,352) and 7.3-fold higher outpatient pharmacy costs ($11,321 vs. $1547).
Conclusions: Patients with hemophilia A treated with bypassing agents between 2007 and 2014 incurred substantially higher monthly hemophilia-related medical and pharmacy costs than patients treated only with FVIII replacement.
Hemophilia A (HA) is marked by substantial economic burden, including costs of ongoing treatment, increased monitoring, bleed events, and other health care utilization associated with managing the ...disease and comorbidities related to the disease. Gene therapies and other anticipated breakthrough treatments hold potential to substantially offset long-term traditional factor VIII (FVIII) prophylaxis in specific populations. Fragmentation of the US insurance system, however, may impact payers' approaches to coverage of new treatments, given concerns about patients "switching" insurance and the payer's ability to offset costs over time.
To assess insurance coverage and switching across payers among people with severe HA (SHA) using real-world data.
Adult men with SHA (FVIII measuring < 1%) in the American Thrombosis and Hemostasis Network dataset between January 2013 and September 2019 were identified. Patients' primary insurance category (ie, commercial, Medicaid, Medicare) and insurance switching over time were described. Outcomes included distribution of current primary insurance coverage by category and mean years of coverage per payer for commercially insured patients, including those with 2 or more commercial payers, and for those who switched insurance categories (eg, coverage by a commercial payer and government payer).
Among the cohort of patients with SHA (N = 3,677), 51.9% had commercial primary insurance and 29.0% had coverage by Medicaid (including state-funded programs). The mean duration of follow-up in the database was 6.3 years for patients with at least 1 year of follow-up. Among patients who had ever been commercially insured, 74.9% had the same commercial payer for the entire follow-up period. The mean time covered by the same commercial insurance was 4.8 years. Only 7.5% of patients switched insurance categories (eg, from commercial to Medicaid). Among those who switched categories, patients averaged 3.9 years of commercial coverage, 4.0 years of Medicaid coverage, and 4.8 years of Medicare coverage during the follow-up period.
Both commercially and government-insured patients with SHA typically maintain continuous coverage for extended periods, with limited switching between payers and insurance categories over time. These findings suggest that should breakthrough treatments be approved, payers would likely be able to realize substantial cost savings associated with avoiding long-term prophylactic therapies during the several years after treatment.
This study was funded by BioMarin Pharmaceutical Inc. Hinds, Chen, and Sammon are employees of BioMarin Pharmaceutical Inc. and own stock/stock options. Solari was an employee of BioMarin Pharmaceutical Inc. at the time of the study. Pezalla is CEO of Enlightenment Bioconsult, LLC. He, Cheng, and Recht are, or were at the time of this study, employees of American Thrombosis and Hemostasis Network (ATHN), which has received ATHNdataset licensing and other fees from BioMarin Pharmaceutical Inc. Research funding to Recht's employers has come from Bayer, BioMarin Pharmaceutical Inc., CSL Behring, Genentech, Grifols, Hema Biologics, LFB, Novo Nordisk, Octapharma, Pfizer, Sanofi, Spark, Takeda, and uniQure. Recht has also worked as a consultant for Catalyst Biosciences, CSL Behring, Genentech, Hema Biologics, Kedrion, Novo Nordisk, Pfizer, Sanofi, Takeda, and uniQure; sits on the board of directors of the Foundation for Women and Girls with Blood Disorders and of Partners in Bleeding Disorders; and is an employee of the Oregon Health & Science University. Data from this study were presented as a poster at AMCP Nexus 2021; October 18-21, 2021; Denver, CO.
Angioedema, present in some patients with chronic idiopathic/spontaneous urticaria (CIU/CSU), may have a negative effect on patient quality of life.
To describe patient-reported angioedema and its ...management in the pivotal omalizumab studies (ASTERIA I, ASTERIA II, GLACIAL).
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.
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).
Treatment with 300 mg of omalizumab was efficacious in reducing patient-reported angioedema. Low-intensity interventions were generally used to manage angioedema episodes.
clinicaltrials.gov Identifiers: NCT01287117 (ASTERIA I), NCT01292473 (ASTERIA II), and NCT01264939 (GLACIAL).
Adherence to omalizumab is not well characterized and its association with asthma control has not been well established.
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.
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.
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.
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.
Patients included in clinical trials do not necessarily reflect the real-world population.
To understand the characteristics, including disease and comorbidity burden, of patients with asthma ...receiving omalizumab in a real-world setting.
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.
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.
The population initiating omalizumab in PROSPERO reported poorly controlled asthma and a substantial disease burden.
ClinicalTrials.gov Identifier: NCT01922037.
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.
To validate an ICD-9-CM-based algorithm for identification of patients with CIU/CSU and thus facilitate claims-based research.
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.
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%.
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.
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.
To characterize health care use and costs associated with high versus low AMR in patients participating in commercial health plans.
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.
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 ($5,733 vs. $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 ($9,811 vs. $8,398; P < 0.001). These increased costs primarily resulted from increased medication costs for patients with high versus low AMR ($4,077 vs. $2,103; P < 0.001).
Although patients with high AMR had more office visits and higher medication (which resulted in higher overall health care) costs, their care was marked by fewer OCS bursts (indicating fewer instances of poor asthma control), fewer ED visits, and fewer hospitalizations and lower non-medication costs than those patients with low AMR. These findings support the use of AMR as a care quality measure for patients with persistent asthma.
This study was funded by Genentech. Luskin has received consulting and lecture fees, research and travel support, and payment for developing educational presentations from Genentech and has received lecture fees from Merck. Raimundo and Solari are employees of Genentech. Antonova was employed by Genentech at the time of this study. Broder and Chang are employees of Partnership for Health Analytic Research, which received funding from Genentech to conduct this research. Study concept and design were contributed by all authors. Broder and Chang conducted analyses. All authors interpreted the data. Antonova wrote the manuscript with assistance from the other authors. All authors participated in manuscript review and revisions.
Hemophilia A is characterized by unpredictable spontaneous bleeds and chronic comorbidities. However, limited data exists at the national level into detailed management patterns related to patient ...clinical characteristics, representative real‐world dosing and treatment frequency, and costs. To assess and characterize the US severe hemophilia A (SHA) population, including subgroups of patients, in terms of clinical and demographic characteristics, healthcare resource utilization received at hemophilia treatment centers (HTCs), and projected annual costs of treatment utilizing data from the ATHNdataset of the American Thrombosis and Hemostasis Network (ATHN). Adult male people with SHA (PwSHA) (FVIII < 1%) were identified in the ATHNdataset between January 2013 and September 2019. This retrospective cohort study described patients’ demographic and clinical characteristics, clinical history, as well as the HTC‐related health resource utilization (HRU), treatment utilization, and projected annual treatment costs of US PwSHA received over the most recent year. Results are reported for the overall population and for three mutually exclusive subpopulations of patients: PwSHA with a history of and/or current inhibitors, PwSHA without a history of inhibitors but with (or a history of) one or more transfusion‐transmitted infections (hepatitis B virus HBV, hepatitis C virus HCV, or human immunodeficiency virus HIV), and PwSHA without a history of inhibitors or of transfusion‐transmitted infections (HBV, HCV, or HIV). Of the overall PwSHA cohort (N = 3677), there was a high prevalence of HCV (24.1%) and HIV (13.7%), while the prevalence of HBV (4.9%) was lower. Note that 20.5% of PwSHA overall currently or ever had FVIII inhibitors. On average, PwSHA had 2.8 total HTC visits per year, including 0.9 comprehensive care visits, 1.1 telephone contact visits, 0.5 office visits, and 0.1 surgeries or other procedures. However, 23.3% of PwSHA were not seen at an HTC, and 33.8% of PwSHA did not have a comprehensive care visit during their most recent year of data. HTC‐related HRU was similar between the overall cohort and across the patient subpopulations, although PwSHA and inhibitors had more frequent HTC visits (a mean of 3.6 visits annually vs. 2.5–2.8 in the other groups). Using reported treatment frequency and dosing, estimated mean annual hemophilia treatment costs varied by treatment and across the three subpopulations: extended half‐life factor product ($893,609–934,301 by subpopulation), standard half‐life factor product ($798,700–930,812), plasma‐derived factor product ($613,220–801,061), and non‐factor product treatment ($765,289—833,240). This study summarized recent sociodemographic and clinical characteristics, HTC‐related HRU, and HA treatments and projected costs among adult PwSHA, including among key subpopulations of PwSHA. PwSHA experience substantial clinical and resource burden on a chronic basis, despite the care coordination efforts of ATHN‐affiliated HTCs. These findings motivate further exploration of the drivers of resource utilization, observed differences across subpopulations and other disparities, and ongoing monitoring of clinical and treatment burden in the face of an evolving care landscape.
Excessive use of short-acting β2-agonists (SABA) indicates impaired asthma control.
To determine whether real-time outreach to excessive SABA users reduces SABA canister dispensings.
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.
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.
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.
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