The economic and personal burden of cluster headache: a controlled cross-sectional study

The majority of the cluster headache (CH) population is episodic (eCH) and experience attacks in bouts, thus being in remission for months to years [1, 2]. The remission period relieves the patients of the severe pain and may also ease known comorbidities, such as depression and anxiety [3]. Yet, it has been reported that avoidance behavior and worries about future attacks continue throughout the remission period [4] and for many patients sleep disturbances persist outside the bout[2, 5]. In addition, CH-related symptoms such as shadow attacks (a mild pain attack that resembles a CH attack but is short-lasting and less intense) and solitary attacks are not uncommon during remission [6]. This raises the question whether CH patients in remission can be regarded as “healthy” or as sufferers from a chronic disease with some symptoms manifesting cyclically and others permanently. Therefore, our first hypothesis was that eCH patients in remission were more burdened compared to controls. Anecdotally, CH tends to abate over time [7] but clinically, usually lasts for at least several decades with an early age of onset typically in the third decade [8]. This combination of early onset and long-term disease duration have enormous potential to impact both the individual, with regards to life choices in family and professional matters, but also the society in terms of direct and indirect costs. Per definition, chronic CH (cCH) patients do not go into meaningful remission periods [9] and intuitively this group should be more burdened by the disease. Overall, the literature supports this notion, however, a recent review concludes that the current evidence level is too sparse to draw firm conclusions [10]. Our second hypothesis was therefore that cCH patients were more burdened in personal life and costs compared to eCH patients.

We aimed to explore the impact on both personal and societal parameters to compile a comprehensive assessment of the disease burden in a large cohort of eCH and cCH patients compared to controls.

The data was obtained from the Danish Cluster Headache Survey, which is a cross-sectional questionnaire study. Data collection was performed between 2012 and 2017. The publication on the primary analysis describes the methodology in details [2] and succeeding publications [11‐16] are based on the same methodology.

In total, 600 participants completed both the questionnaire and the semi-structured interview. Response rates were 400 out of 645 (62%) for patients and 200 out of 328 (61%) for controls. 253 participants were diagnosed with eCH and 146 with cCH. At time of interview one patient could not be classified as eCH or cCH (first bout) and was excluded from sub-analyses. Patients in bout, 124 out of 253 eCH patients (49%), were defined as having one or more attacks within the last month. In a previous publication from the same patient group [16] we found that male patients constituted a significantly larger part in the episodic group compared to the chronic group, respectively 182 out of 253 eCH patients (72%) and 86 out of 146 cCH patients (59%). The patients were 46.2 ± 11.5 years and had an average 3.6 ± 2.3 attacks/day. The controls were 44.7 ± 13.1 years and 133 (67%) were male. See Table 1 for further demographics. Pain intensity of usual attacks was rated severe or very severe by 95% of patients. Details regarding sleep, lifestyle, comorbidities, diagnostic factors and treatment have previously been published [12‐14, 16].

CH impacts all investigated aspects of everyday life, especially in the chronic subgroup (Fig. 3). Not unexpectedly, health was rated significantly worse in periods with attacks compared to periods without attacks and to controls, but we could also demonstrate a significant burden for the patients in remission compared to controls. Finally, amongst the 400 CH patients we also identified a mean annual direct cost of 5178 €/patient and substantial loss of productivity resulting in a higher mean annual indirect cost of 6561 €/patient.

Self-rated health was significantly reduced in periods with attacks and cCH patients had ten-fold lower odds of rating their health as good or very good compared to controls. Even eCH patients who had been out of bout for more than a year did not rate their health as good as the controls. Self-rated health is an important predictor and strongly associated with increased mortality [21]. CH have been associated with an increased suicidality [22] and an unhealthy lifestyle increasing the risk of cardiovascular diseases [14]. The combined increased mortality risk should be taken serious by physicians treating CH patients. We unfortunately did not investigate the suicidality in the present study. Self-rated health was in part restored in remission periods but still not equal to the control group. The attack burden, but also comorbidities such as depression, anxiety and suicidality, are eased but still reported during remission [23, 24]. In addition, we found that CH influences many eCH patients when taking important life decisions, such as having (more) children, and their professional life was impacted by job loss and passing up projects at work. The pronounced effect on personal and professional life is in line with previous publications [4, 18, 25, 26]. Therefore, we put forward the argument that eCH, also, is a chronically disabling illness despite the cyclic nature of the bouts, at least for this patient population recruited from a hospital-based headache center. Current preventative is limited by targeting the bout once it occurs whereas the ideal preventative would prevent the occurrence of the bouts. Currently, physicians might reduce the anxiety by making the treatment plan during the remission.

In our cohort, 19% received full/part-time disability pension and this level was expected based on the general distribution for chronic pain patients in Denmark [27]. Full-time disability pension was received by 13% of the CH population and although this is high it is in line with previous findings ranging from 8–15% [18, 28‐30]. Of note, the CH population is better educated compared to the general population receiving disability pension, in our cohort 29% had a bachelor or master degree and in the general disability pension population this only accounted for 13% [31]. This was also confirmed by another Scandinavian study, in which the CH diagnosis reduced the effects of education on odds of receiving disability pension [30]. This points to CH causing social drift, rather than social causation. The subgroup with early onset had a stronger affiliation to the job market compared to a later onset. This could indicate that disease severity worsens with later onset; however, this is heavily biased by the Danish social welfare system where it takes time to go through the bureaucratic motions of testing ability to work and hearings. Further, after a reform in 2013 the general rule is that permanent support, such as disability pension, cannot be granted before the age of 40 years. Education level seems relatively unaffected by CH [4] and we demonstrated that this was also true for the patients who debuted young. In patients who debuted in the last 10 years, 21% had experienced a job loss due to CH. In previous studies from Denmark, Italy and the USA, 10–17% of the patients had reported loss of a job due to CH [18, 29, 32] whereas this only occurred in 3% in a recent Korean study [25]. It is worrying that the number of patients losing their job was unchanged from previous publications, however, in our cohort we may have more cCH patients compared to the previous cohorts [29]. New treatment options are highly needed to change the trend of job loss due to CH.

As hypothesized, the described burden is much more pronounced in cCH compared eCH. For example, 11% of the eCH patients indicate that they are without job compared to almost half the cCH patients. Previously, it was found that CH patients had higher employment rates compared to their unaffected family relatives, but this study only included eCH patients[33]. Sick days for employed patients and healthy controls were similar to previous findings in a registry study [34]. Notably, the eCH patients have almost identical number of sick days as controls when excluding CH related sick days but the chronic patients who are employed have twice the amount of sick days. This could be due to higher degree of comorbidities even in the 33% of the chronic population that are still employed.

The direct and indirect cost of CH were high especially in cCH patients where the total cost was three times that of the eCH patients. The direct costs of eCH patients were slightly higher in a German study (1,819 €/half year vs 2,763 €/year) from 2011 [19]. The Italian study from 2020 found a mean cost of 1755 € per bout but since the cost were calculated per bout the findings are not directly comparable to our study. The direct cost of the cCH patients (approximately 9000 €) was similar to the findings by the Italian group [32]. However, the German study found a direct cost of 9073 € within 6 months, but they included high cost procedures as implantation with occipital nerve stimulation and alternative treatments such as massage which were not included in our cost-calculation. The bulk of the cost was attributed to triptans and this is a common denominator in the three studies [19, 32]. Considering the high cost associated with triptans it is important to consider that this cost might be out-weighed by the resultant increased work productivity consequently lowering the indirect cost of CH. Our dataset unfortunately does not allow us to explore this as we were unable to quantify the presenteeism.

The direct cost was in this study based on patient reported outcome, another strategy to investigate this could be via the pharmacy databases in Denmark. Applying different methods of estimating the costs are a strength as they will reduce the common method bias. The indirect cost can be difficult to compare between the studies as there are both methodological and structural differences in social welfare systems. In our analysis we included part- and fulltime disability pensions as an indirect cost as we have no better way to estimate the productivity loss. The imprecisions in the evaluation of the indirect costs are stated as assumptions in the method section. The total indirect cost also includes presenteeism, rehabilitation, the work absence for the spouse and other costs [35]. This is of course a limitation to the final output as generally the indirect cost is hard to quantify. However, similar rates of part-time disability pension was found in another registry study [30]. The Danish welfare system is characterized by high redistribution of income and therefore we believe the human capital approach is the best fit even if it tends to overestimate the cost [36].

Our data is limited due to its cross-sectional nature, self-reports and recruitment from a tertiary headache center. The high rate of CCH patients reflects inclusion primarily form a specialized clinic and the results might not be representative for the entire CH population in Denmark. Another limitation is that we used validated health surveys, and did not investigate the emotional burden, the reason for this was the questionnaire already being quite comprehensive. Also, our control group was more educated than the patient groups and this might bias the health ratings [37]. The strengths being the largest population of validated CH patients diagnosed according to the ICHD-criteria, unbiased to burden alone due to a very broad questionnaire and where both personal and societal burden are explored. It is important to notice that our results have a high variance indicating for some, even a short cluster period may have devastating effects on career and/or family life whereas others are relatively unaffected in their everyday life by cCH. This may depend on attack frequency, treatment response, social network, and education, and still other factors. The treatment response for this population has been published separately [13].

In conclusion, CH affects the patients significantly on both an economic and personal level. The chronic patients are much more affected in everyday life and costly than in the episodic patients. As expected eCH patients are less affected in remission than in bout, however, eCH patients in remission are still limited in important life and career choices. Therefore, we argue that eCH, also, is a chronically disabling illness despite the cyclic nature of the bouts. Hopefully, new emerging treatments will ease this for patients and society.