Migraine treatment and healthcare costs: retrospective analysis of the China Health Insurance Research Association (CHIRA) database

Migraine is a primary headache disorder characterized by disabling attacks of moderate-to-severe pain, accompanied by nausea, photophobia, or phonophobia, which impair ability to function and adversely impact quality of life [1‐3]. Migraine has an estimated global prevalence of 14.4% and is the second highest cause of years lived with disability based on the Global Burden of Disease Study [3].

In China, population-based estimates of the 1-year prevalence of migraine range from 7.9% to 14.3% in adults [4‐6]. Health-related quality-of-life studies in China, including Taiwan, have demonstrated substantial negative effects of migraine on physical and emotional functioning, impacting work, household, and leisure activities [5, 7‐9]. In a population of 1.4 billion, migraine presents a significant clinical burden in China.

Migraine treatment guidelines for China are consistent with those for Europe and the United States (US) in supporting a stratified approach to acute (abortive) treatment, whereby medication choice is based on attack severity and symptoms, the efficacy and side effect profile of the drug, and the patient’s previous response to acute treatment [10‐12]. Chinese guidelines recommend non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, compound analgesics containing caffeine (cautioning that caffeine could increase the risk of drug addiction and medication overuse headache), and triptans; opioids, barbiturates, and ergotamine derivatives are not recommended for regular use [10].

Preventive (prophylaxis) treatment can be offered in the case of recurring migraine that is interfering with daily routine despite acute treatment; failure of, contraindication to, or side effects from acute medications; risk of acute medication overuse; circumstances such as hemiplegic migraine; high or increasing attack frequency; and patient preference [13]. Metoprolol, propranolol, flunarizine, valproic acid, and topiramate are the recommended preventives based on Level A evidence in Chinese and European guidelines [10, 11]. An estimated 34% to 39% of patients with migraine in Europe and the US are eligible for preventive migraine treatment [14, 15]. However, in the European Eurolight study, less than 14% of eligible patients actually received preventive medication, and in the American Migraine Prevalence and Prevention (AMPP) study, 32% of never-users of preventive treatment would benefit from their use, suggesting undertreatment and inadequate disease management [14, 15].

Information on the prescribing patterns and treatment costs of migraine in mainland China is limited. Although there is substantial evidence for the economic burden of migraine in the US and Europe, this information cannot be generalized to China because of the differences in diagnosis and treatment practices, availability of prescription medication, and use of traditional Chinese medicine alongside Western medicine. A population-based survey in China in 2009 estimated the total annual direct costs of migraine diagnosis and treatment to be 58.0 billion Chinese yuan renminbi (CNY) (8.4 billion US dollars [USD]) [5]. However, this survey relied on patient-reported information for migraine diagnosis and healthcare resource use. Hence, there is a need for China-specific data reflecting local diagnostic and treatment practices and the use of complementary medicine.

This retrospective analysis of the China Health Insurance Research Association (CHIRA) nationwide medical insurance claims data aimed to understand the treatment patterns, direct medical costs, and healthcare resource utilization among adult patients with migraine in mainland China.

This is the first study to describe the treatment patterns and costs of migraine treatment in urban mainland China using a retrospective analysis of the large CHIRA medical insurance claims database. The treatment patterns for adult migraine patients in this study indicate relatively low levels of headache management in China. Only 26.4% of patients were prescribed acute medication, which contrasts with higher rates (73%) from Japanese insurance claims data [17]; this may reflect cultural differences in prescribing patterns or greater reliance on over-the-counter rather than prescription acute medications in China. In the US, approximately half of patients used prescription acute medication, with or without over-the-counter acute medication [18], and much higher rates were reported among patients consulting specialist neurologists and physicians for their migraine [19].

Non-aspirin NSAIDs, primarily ibuprofen, were by far the most commonly prescribed acute medication in our study, which is in accordance with international treatment guidelines [10‐12] and may also reflect their accessibility and relatively low cost. There is evidence to support ibuprofen as effective for severe migraine attacks; however, NSAIDs are non–migraine-specific, and their acute use can be associated with peptic ulcer or renal disease, which should be considered in treatment decisions [12].

Triptans are a class of recommended migraine-specific acute medication [10‐12] and are also effective in about 60% of non-responders to NSAIDs [20]. Three types of triptan are commercially available in China: sumatriptan, zolmitriptan, and rizatriptan. Although the Level A evidence supporting triptan use is recognized in Chinese as well as international treatment guidelines [10‐12], the rate of triptan prescribing in this study was low; of patients receiving acute medication, only 3.3% were prescribed triptans. Surveys of migraine patients attending hospital neurology departments in mainland China have also found triptan use to be rare [21, 22]. In contrast, triptans are among the most commonly prescribed acute medications for migraine in Europe, the US, and Japan [17, 19, 23, 24]. The lower rate of triptan use in China may be explained by barriers to access owing to limited triptan availability in most hospitals and pharmacies. Limited over-the-counter purchase of triptans has also been reported in China, with their relatively high price making triptans unaffordable to many patients with migraine [22].

In our study, opioids were prescribed for 7.1% of patients receiving acute medication. In contrast, more patients are prescribed opioids for migraine in the US, from 16% in the AMPP study [25] to 36% in the Chronic Migraine Epidemiology and Outcomes study [26]. The consumption of opioids in China is far lower than the global average, with a mean defined daily opioid dose in 2011 to 2013 of 96 units per million people per day in China compared with 3027 units globally [27]. Opioids are subject to government regulation in China [28] and are not recommended for the acute treatment of migraine in Chinese, US, or European guidelines [10‐12] due to the potential for medication overuse and transformation from episodic to chronic migraine [29, 30]. Although we cannot determine whether the 7.1% of patients who were prescribed opioids in our study were non-responders to other medications, this rate of opioid prescription demonstrates an unmet need for additional migraine-specific acute treatments that lack the safety concerns of opioids.

Preventive medication was prescribed for only 15% of patients in our study, consistent with insurance claims data for Japan, which showed that 15% of patients received preventive treatment. However, these rates are well below the estimated 34% to 39% of patients who would benefit from migraine preventive treatment reported for Europe and the US [14, 15]. The limited available evidence from other studies in China also suggests that preventive medications are underutilized, with ≤5% of patients receiving preventive medication [21, 31]. In our study, the calcium-channel blocker flunarizine was the most commonly prescribed preventive, used by 87.6% of patients receiving preventives. The preferential use of flunarizine over other migraine preventives in China may reflect its relatively mild adverse effects, which can include fatigue, weight gain, and mood changes [32].

Approximately one quarter of patients in our study were prescribed Chinese patent medicine and over 11% were prescribed Chinese herbal medicine. Moreover, the mean annual direct costs for traditional Chinese medicine (patent or herbal) were almost twice the estimated direct cost of prescribed Western medicine. Although a meta-analysis has suggested efficacy for Chinese patent medicines in the treatment of migraine, many available studies are of poor methodological quality and the potential mechanisms of action are unclear [33]. This is consistent with the finding by Luo et al. of lower rates of satisfaction with Chinese patent medicine compared with Western medicine in migraine treatment [22]. Given the high direct costs of traditional Chinese medicine shown in our study and potentially low rates of satisfaction, there is a need for greater understanding of their efficacy in migraine treatment and the factors driving the prescription of traditional Chinese medicine in preference to Western medicine.

The mean total annual outpatient costs for medication, diagnostic tests, and non-medication costs for physical therapy or oxygen treatment were estimated to be 46.5 USD per patient. This is lower than the annual direct costs previously reported by Yu et al. for migraine diagnosis and treatment in China, which were estimated to be 105 USD per patient [5]. This difference may reflect study design differences, with Yu et al. including all out-of-pocket expenses for diagnosis and treatment, in contrast with our study, which included medical insurance claims and excluded over-the-counter purchases from pharmacies. A retrospective case-control analysis of the Taiwanese nationwide National Health Insurance Research Database estimated annual total drug costs from outpatient visits to be significantly higher for patients with refractory migraine compared with that for non-migraine control subjects, but the estimated costs were higher than reported in our study owing to the inclusion of costs associated with comorbid conditions [34].

The strengths of the current study include the wide urban population coverage of the CHIRA database. Approximately 95% of China’s population is covered by public health insurance [16], and China’s urban population represents approximately 59% of the total population [35]. CHIRA data also represent a range of localities, including municipalities, provincial capital cities, and prefecture-level cities, and include primary- through to tertiary-level hospitals. However, the findings may not be representative of patients in rural areas or those without urban employee or resident basic medical insurance. Patients who did not seek treatment from a healthcare provider and used only over-the-counter medications would also be excluded from the study. In addition, the database does not include medications purchased outside of hospital pharmacies by the enrolled patients and is therefore likely to underestimate medication use. Only patients with a primary diagnosis of migraine were included in the analysis; however, some medications (eg, calcium antagonists) may have been prescribed for other indications, resulting in an overestimation of certain prescriptions for migraine. Lastly, although it was not possible to determine the incidence of chronic and episodic migraine in this population, the cost analysis was based on actual prescription data and, therefore, would reflect the potentially more frequent use of medication in patients with chronic migraine.

Our findings from the analysis of this large nationwide database are a representative reflection of migraine treatment and costs in urban mainland China. Prescribing rates for acute medication in China were low compared with the US and Japan. NSAIDs were the most commonly prescribed acute medication, while there was low utilization of migraine-specific triptans and preventive medications. Traditional Chinese medicine was commonly prescribed in clinical practice, and with the costs of traditional Chinese medicine comprising the largest proportion of total drug costs. The findings indicate an economic burden associated with the diagnosis and treatment of migraine in China, and possible unmet needs for effective migraine-specific acute treatment as well as preventive medication.