Study design
This was a retrospective, database cohort study using the Taiwan National Health Insurance Research Database (NHIRD) from 2007 to 2011.
Data sources
The NHIRD contains comprehensive claims records of outpatient and inpatient care of enrollees in the National Health Insurance (NHI) program in Taiwan, which covers over 99 % of the population in Taiwan (more than 23 million people). This health claims database includes health care data and medical utilization details as well as basic information from all hospitals contracted with the NHI program, and is updated annually. Each individual is assigned a unique identity number (hence longitudinal data are available), and the available information includes basic demographics, details of medical services, detailed information on prescribed medications, diagnoses from specialists’ referrals and hospital admissions.
The NHI Bureau has established a uniform system to control the quality of medical services and coding. The identification data of the beneficiaries in the NHIRD is scrambled to protect their privacy before they are released for research purposes. NHIRD was not freely available and Chang Gung Memorial Hospital (CGMH) and Novartis, Taiwan granted access to it. This study was supported by CGMH and Novartis, Taiwan [Grant XMRPG 3C1071] and was exempted from full review by the Institutional Review Board of CGMH (102-3778B).
Sample size justification
Since this is a retrospective, descriptive study in which no formal statistical testing was performed, the use of point estimates and 95 % confidence intervals (CIs) served to quantify the level of precision. There were 46, 130, 156, 196 patients prescribed with omalizumab, respectively, based on which year they received it in the NHIRD claims database, allowing to quantify the patterns of omalizumab usage and other anti-asthmatic regimen in routine practice with sufficient precision (frequency, proportions and 95 % CIs were calculated).
Patient population
Patients with allergic asthma (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] codes 493.0, 493.9, 493.1 and 493.8) were identified from the dataset. The source population consisted of all subjects who had at least one prescription for omalizumab as part of an anti-asthma regimen between January 1, 2008 and December 31, 2011. The index date was defined as the time of first prescription of omalizumab. Data were collected from 1 year before the initiation of omalizumab treatment to 4 years after treatment initiation or until the end of 2011, whichever came first. The patients who discontinued omalizumab remained in the database and were followed up until the end of the observation period. We were only evaluating patients who receive omalizumab > 4 months. We aimed to investigate the efficacy, discontinuation and medical resource utilization of omalizumab in the real-life setting in Taiwan. In addition, we evaluated the reduction in asthma medication post omalizumab therapy and severe exacerbations and hospitalizations from baseline to the end of follow-up longitudinally. Thus, we did not enroll a matched cohort not receiving omalizumab who are equally severe.
Variables (outcomes of interests)
Demographics and patient characteristics recorded from the database included age at cohort entry, gender, asthma disease history, and diagnosis. Past medical history, previous asthma medication, co-morbidities, diagnosing/prescribing doctor’s specialty and level of institution were also recorded.
Omalizumab use and treatment observation
Data on the treatment regimen including dose, duration, prescription refill schedule/interval, change in dose and discontinuation were recorded. Information on the co-use of other asthma medication, previous medication, co-medications, and their doses, and whether or not they were used with omalizumab (ICS, LABA + ICS, oral corticosteroids [OCS], short-acting muscarinic antagonist [SAMA] and long-acting muscarinic antagonist [LAMA]) was also recorded. Data were collected at initiation, and then 4, 6, 8, and 12 months before discontinuing omalizumab, and 2, 6, and 12 months after discontinuing omalizumab. Discontinuation of therapy was defined as a gap in therapy of 56 days.
Treatment effectiveness
The number of asthma events, and asthma-related medical resource utilization including hospitalization, ER visits and medication use to manage acute exacerbations were recorded. The time to recurrence (exacerbation event) or worsening of asthma symptoms after discontinuing omalizumab treatment was also recorded. Other data including the number of clinically significant asthma exacerbations and severity of these exacerbations, and the use of OCS and other asthma maintenance medications and the reasons for discontinuing or changing omalizumab treatment defined as asthma exacerbations were also recorded. Severe exacerbation was defined as: ER visit or hospitalization >1 day with OCS >20 mg/day; Non-severe exacerbation was defined as: OCS >20 mg/day without ER visit or hospitalization.
Data analysis
All the analysis was conducted using SAS statistical software, version 9.3 (SAS Institute Inc, Cary, NC). Exacerbations in baseline and follow-up period were expressed as percentage and compared by using Fisher’s exact test. Patient number and dosages, ER visit and hospitalization of using other asthma medication post omalizumab therapy were defined as continuous variables and were compared by using Fisher’s exact test. Mean changes from baseline for ER visits and hospitalizations post omalizumab therapy was expressed by frequency and using paired-T test for comparison. Data were summarized with respect to demographic and baseline characteristics, effectiveness, and reasons for discontinuing omalizumab treatment. Descriptive statistics were presented as number, mean, and standard deviation (SD) for continuous variables, and frequency, percentage, and 95 % CI for categorical variables.
In addition to the overall analysis, the evaluations were stratified according to treatment persistence (duration). The prescriptions, usage, co-medications, asthma-related events, number of acute exacerbations, medical resource utilization, and cost were analyzed and compared between different treatment persistence groups.