Summary and comparison of findings with existing literature
In this study, we analyzed patients with headache/migraine in a real-world setting in order to increase knowledge related to current treatment patterns of these patients in Germany. The goal of this research is to outline ongoing challenges related to the diagnosis and treatment of migraine patients in order to pave the way for improvements in medical care for patients with migraine.
Management of migraine and headache is multidimensional. Emphasis should be placed upon educating patients about appropriate use of OTC medication, improving the quality of advice provided to patients by pharmacists, as well as integrating, coordinating and synchronizing services offered by primary healthcare providers as well as specialists. Around 50% of migraine patients with relatively mild and infrequent attacks attempt to independently manage their disease through use of OTC remedies, and thus may not consult a physician. Nevertheless, at least 50% of patients require some degree of medical follow-up or consultation [14]. To a large extent, demand for clinical consultations among migraine patients is driven by the inefficacy of OTC drugs and the resulting need for prescription treatment. It has been previously reported that up to one-third of all migraine patients who suffer from frequent migraine attacks, are probably in need of prophylactic medication [4]. It is particularly important for these patients to receive adequate treatment to improve clinical outcomes, well-being, and productivity in the workplace [15], [16]. Our findings indicate that, even in a relatively well-resourced country like Germany, only a small portion of patients expected to benefit from migraine medication actually receive treatment.
Our study reveals that nearly half of all patients with migraine/headache diagnoses did not receive any prescription of acute or prophylactic medication in 2017 (43.47%). Approximately one-third of the patients received only acute medications (33.81%) and just one fifth (22.72%) were prescribed prophylactic agents. Our exploratory analysis of patients who heavily depend on prescribed triptans (> 8DDDs per months or > 5DDDs per months with additional indicators of high disease severity) revealed a stark unmet need for prophylactic agents, since less than 10% of these patients received subsequent prescriptions for prophylactic medication. These findings align with those of previous studies which have demonstrated generally poor treatment patterns and disease performance in headache/migraine patients throughout Germany and elsewhere in Europe. A recent medical chart review reported that 27.5%-58.4% of migraine patients do not receive any therapy [17], while a study of 8,000 migraine patients from 10 EU countries confirmed that very few patients received adequate migraine-specific treatment including both, acute and prophylactic medications [8]. Further to these findings, one study in Germany demonstrated an overall low frequency of migraine-specific prescriptions, especially among general practitioners (GPs) [17].
However, reasons for the low quality of care afforded to migraine and headache in patients throughout Germany and across the world are manifold. Despite the fact that migraine is highly prevalent and is associated with huge adverse consequences for affected people and the society, it is generally not considered a significant medical problem by patients, healthcare providers and health policymakers [18]. Oftentimes people affected by migraine are not aware of their disease and thus, do not consult a doctor to receive a diagnosis or proper treatment for their symptoms. One study provided evidence that awareness of migraine was low among both affected patients and healthcare providers [19]. These findings were corroborated by a study in France which indicated that 60% of 10,000 patients with migraine were unaware of their diagnosis [20]. With this in mind, we acknowledge potential underestimation of unmet need in our patient population, since not all patients in need of therapy will have visited physicians during the study period and, therefore, were not included in this analysis. A previous study in Germany provided evidence that only 42% of patients with migraine consulted a physician, while a clear majority of patients relied exclusively on OTC medications, despite reporting symptoms [21]. This presents a limitation of the present study, as data on OTC medication use for our patient population were not available in the dataset.
In addition to the potential lack of awareness regarding migraine diagnoses, some GPs and specialists may not perceive headaches to be medically important enough to spend time diagnosing/treating symptoms, providing patients with detailed advice, or following-up with regard to the presentation of new symptoms. A study conducted in 10 headache centers in Italy revealed that only 26.8% of patients with migraine had received a previous diagnosis that was correct [22]. Another multinational study found that only 28 percent of migraine patients (who were subsequently referred to specialized headache centers) had been diagnosed with migraine by their treating GPs [23]. Furthermore, as shown by a study conducted in the UK, some GPs do not follow established treatment guidelines when patients with headache symptoms attend their practice [24]. As a consequence, patients receive either no treatment or improper treatment, as demonstrated in the Europe-wide EUROLIGHT study [8].
However, among patients who received a new prescription for prophylactic therapy in our study (N = 9,005), 60.78% discontinued prophylactic treatment within two years, without re-initiation. Ultimately, low medication compliance constitutes another key driver of poor medical care and high unmet need among patients. Poor adherence to prophylactic medication for migraine has been observed in previous research and was shown to result from insufficient effectiveness and/or treatment-related side effects [25]. One retrospective claims analysis in the US revealed that over two-thirds of chronic migraine patients discontinued their medication within six months of initiation, and that more than 80% of patients discontinued treatment within twelve months [26]. Such challenges related to treatment adherence and potential side effects signal an ongoing need for the improvement of migraine therapies, with regard to effectiveness and safety.
Our HCRU and cost analysis confirmed high levels of unmet need in a substantial proportion of observed patients, particularly in those who receive medications. According to our analysis, patients taking prophylactic medications were hospitalized more frequently and logged more sick days than patients who did not receive prophylactic treatment. Although this may be due in part to the likelihood of more severe cases among those who received prophylactic treatment, and these findings are likely biased by indication (i.e. higher proportion of migraine patients in this cohort), patients with prophylactic migraine medications had higher utilization of acute medications too, indicating a higher headache frequency. Unfortunately, no data on headache frequency among study participants was available in the database to confirm this. Generally, economic consequences of migraine, comprised of direct and indirect costs, are enormous.
Cost estimates are an important measure used to inform health policymaking via the estimation of expenses incurred by different healthcare services. In Europe, financial costs attributed to migraine are estimated to range between 50 € and 111 € billion, with direct and indirect costs accounting for 7% and 93% respectively [27]. Direct costs incurred by healthcare services attributed to migraine, were found to be 1,222 € per person [27]. Another European study reported comparable average costs over three months, ranging from 373.8 € in Germany to 929.6 € in the UK [28]. Indirect costs, as shown within these studies, constitute most of the economic burden, with productivity loss accounting for two-thirds of indirect costs [27]. Our analysis confirmed that indirect costs (related to days absent from work) should not be neglected in analyses of migraine related HCRU and cost. On the contrary, it must be emphasized that average monthly costs associated with diminished productivity at work (presenteeism) are higher than those arising from sick leave (absenteeism) [29]. However, an estimation of costs related to onsite productivity loss was not possible in this study and research in this area is generally limited.
Limitations
Strengths of this study include an absence of study site/patient selection bias, coverage of all inpatient and outpatient healthcare sectors, and utilization of a large cohort of 199,283 patients. Nevertheless, we acknowledge that some limitations may apply. First, generalizability of results could be affected by the fact that the health insurance fund which provided the data only covers patients in two regions of Germany (Saxony and Thuringia). However, since health reimbursement rules are identical across Germany, considerable differences in the management of migraine patients are not expected. Second, information on the number of migraine attacks in observed patient cohorts was not available. Third, analysis of prophylactic treatment with monoclonal antibodies such as erenumab, galcanezumab and fremanezumab was not included as these medications were not available during the period of observation. Fourth, dosage as well as persistence analyses were conducted using data on filled prescriptions only. Information on unfilled prescriptions as well as OTC medications was not analyzed, as those data were not available in the relevant sickness fund dataset. Ultimately, the latter may have caused an underestimation of medication use in our patient population. Moreover, HCRU among headache/migraine patients may have been underestimated if alternate therapies not covered by the participating sickness fund were accessed by patients via alternate means (i.e. supplementary insurance, out-of-pocket payments, etc.). Fifth, this analysis was exclusively descriptive, and no adjusted analyses were performed. Finally, our HCRU and cost analysis was based on reimbursements only, which exclude patient co-payments. However, these costs are generally low in Germany.