Diagnoses and prescription patterns among users of medications for obstructive airway diseases in Finland

Obstructive airway diseases are among the most common chronic diseases worldwide. An estimated 300 million people worldwide have chronic obstructive pulmonary disease (COPD), and 262 million people have asthma [1]. In Finland, the prevalence of physician-diagnosed asthma and COPD was 11.2% and 2.6%, respectively, among adults in 2016 in a questionnaire study [2].

Much work has been done in Finland to improve asthma and COPD awareness, recognition and diagnostics through the National Asthma Programme (1994–2004), the National COPD Programme (1998–2007) and national guidelines [3, 4]. Among adults, both asthma and COPD are diagnosed and treated mainly in primary care and occupational health care. Physicians are always instructed to confirm asthma and COPD diagnoses with lung function tests [5, 6], and both spirometry and peak expiratory flow (PEF) monitoring are widely available in primary care [3]. Special reimbursement for asthma or COPD medications is dependent on diagnosis based on lung function measures. Thus, there is an economical incentive to always confirm the diagnosis with objective tests.

Group R03 drugs in the Anatomical Therapeutic Chemical (ATC) Classification System consist of drugs for obstructive airway diseases, including inhaled corticosteroids (ICS), long- and short-acting beta-agonists (LABA and SABA), long- and short-acting muscarinic antagonists (LAMA and SAMA), leukotriene receptor antagonists (LTRA), theophylline and roflumilast [7]. Most of these are indicated for both asthma and COPD, but their roles are different in these diseases. Treatment of asthma is based on maintenance treatment with ICS, and other classes are used as add-on maintenance drugs or as relievers [8]. Treatment of COPD is based on maintenance use of long-acting bronchodilators (e.g., LABA and LAMA), and ICS are used only if there is evidence of eosinophilic airway inflammation and recurrent acute exacerbations [9]. According to clinical experience, off-label use of R03 medications is quite common. There is little published data on how the use of these drugs is divided between diagnosed and undiagnosed adult patients, and off-label use is often related to the treatment of symptoms associated with airway infections [10‐12]. Published data from paediatric populations also suggest that off-label use as short courses for airway infections is remarkable (19.2–38.1%) [13, 14].

The aims of this study were to describe (1) for which diagnoses each R03 drug class is used, (2) the usage pattern of different R03 drug classes for asthma and COPD, and (3) how often R03 medications are used without a diagnosis of asthma or COPD in Finland.

In this study, we found that approximately 60% of the subjects dispensed R03 medications in Finland reported having doctor-diagnosed asthma, 5% reported both asthma and COPD, and 5% reported COPD only. Approximately a quarter reported not having a doctor-diagnosed obstructive airway disease. In line with this, for all other R03 drug classes except LAMA, asthma was the most frequent indication. Among subjects with asthma or asthma and COPD, ICS were by far the most frequently dispensed class of drugs. Even among subjects with COPD, ICS were equally frequently dispensed as a long-acting bronchodilator. LTRA were dispensed mainly for asthmatic individuals only but far less frequently than ICS. The use of SAMA, theophylline and roflumilast was very infrequent.

Among the subjects who were dispensed R03 medications in this study, the proportion of patients with asthma (67.3%) was approximately six times higher than the proportion of patients with COPD (10.8%). This roughly six-to-one ratio was even higher than epidemiological data showing the prevalence of doctor-diagnosed asthma (11.2%) as approximately 4 times higher than that of COPD (2.6%) in surveys among Finnish adults [2]. One reason for the higher proportion of asthma patients in the current study in comparison to epidemiological data may be that a higher proportion of patients with mild COPD in comparison to mild asthma may not use any R03 medications and hence were not included in this study based on dispensed R03 medications.

One previous study from Portugal examined dispensed medications for respiratory diseases at the national level and estimated diagnoses based on treatment patterns [17]. In the study, the proportions of patients with likely any asthma (asthma only or asthma and COPD) and likely any COPD (COPD only or asthma and COPD) were approximately the same (51% vs. 54%, respectively). This one-to-one ratio between patients with asthma and COPD is much closer to the global estimate of asthma and COPD prevalence being approximately the same [1]. The difference between Finnish and global relative proportions of COPD and asthma is likely related to lower levels of smoking, better occupational hygiene, and higher rates of allergic diseases and asthma in Finland. In addition, local diagnostic practice favours the diagnosis of asthma in any subject with a significant bronchodilator response, although internationally, a fair proportion of subjects labelled as having COPD show significant reversibility [18]. In Finland, during the time of the study, it was easier to obtain special reimbursement for R03 medications if one had asthma in comparison to having COPD. Any asthma that had met the diagnostic criteria, patient had used anti-inflammatory maintenance medication for at least 6 months and needed regular maintenance medication, was granted the special reimbursement. On the contrary, in cases of COPD, the patient needed to have a fairly severe disease (FEV₁ < 40% predicted, or FEV₁ < 50% predicted and recurrent exacerbations despite of treatment) to get the special reimbursement. This discrepancy in the criteria may have directed physicians to make a diagnosis of asthma instead of COPD in cases with challenges in differential diagnostics or features of both diseases. The possible COPD related stigma may also have favoured the self-reporting of asthma over COPD.

Among patients with asthma or both asthma and COPD, ICS were the most frequently dispensed class of drugs. This is in line with national and international guidelines promoting the importance or maintenance of anti-inflammatory treatment [6, 8]. However, patients with COPD without asthma were dispensed ICS almost as frequently as LABA, which probably reflects previous guidelines in which ICS/LABA combinations were often recommended, and the use of dual bronchodilators was not as well established [19]. Thus, there is probably some degree of overuse of ICS in the treatment of COPD in Finland compared to what the current guidelines recommend [9].

Approximately 60% of patients with COPD or asthma and COPD were dispensed LAMA in line with current guidelines [9]. Although some LAMA-containing inhalers are also indicated for asthma, only 4% of patients with asthma were dispensed LAMA. This is a fairly low number, although tiotropium has been recommended for the treatment of asthma in the Finnish national guidelines since 2012 [20]. However, as the total number of subjects with asthma was much higher than the number of patients with COPD only, the number of LAMA users with only asthma was almost as high as the number of patients with only COPD.

Among the patients with asthma, SABA were dispensed to fewer patients than ICS, and none of the subjects used LABA without concurrent ICS. This is important since both overreliance on SABA and maintenance use of LABA without concurrent ICS are related to poor asthma outcomes [8, 21]. The use of SAMA was very infrequent for asthma, but approximately 5% of patients with COPD used SAMA. Overall, the role of anticholinergics has been advocated more in the treatment of COPD due to discussions on the role of increased cholinergic tone in COPD [22], but, actually, many asthmatic individuals also respond favourably to both short-acting and long-acting anticholinergics [23, 24]. The use of theophylline was also very infrequent and in line with current guidelines not recommending its use [8, 9]. Additionally, the use of roflumilast was very infrequent, although it is included in both national and international guidelines for the treatment of COPD [5, 9]. Its use is probably restricted by side effects and by the fact that a separate application for reimbursement of roflumilast is needed in Finland.

More than a quarter of the subjects who were dispensed R03 medications reported not having a diagnosis of asthma or COPD. Such use may include short courses of relievers or ICS for prolonged cough or airway infections, although there is no evidence to support this kind of prescription practice. Two previous studies, one from Australia [10] and one from the Netherlands [11], evaluated the prescribing of ICS to treat respiratory infections among subjects without chronic airway diseases. Both studies suggested that off-label use of ICS is common. In previous studies among children, acute airway infections have been a frequent off-label indication for R03 medications [13, 14]. In a Spanish study by Villamañán et al., the off-label prescription of inhaled bronchodilators was common among hospitalised patients, and the most common indications were dyspnoea that was not related to asthma or COPD, respiratory infections, and heart failure [12]. In Finland, diagnostic assessment of suspected asthma in adults includes a two-week PEF monitoring with twice-daily measurements before and after SABA use [6]. Part of the reason for dispensed SABA to subjects without asthma or COPD may be related to investigations for possible asthma in which SABA are used to conduct the two-week PEF monitoring. A treatment trial with anti-inflammatory medication is used in asthma diagnostics [6, 8], so it is possible that part of the use of ICS among subjects not having reported asthma is explained by this.

A strength of this study is that it was based on a random sample of all subjects who were dispensed R03 medications in Finland. As there are no over-the-counter R03 medications available in Finland, all users of R03 medications were represented in the sample. The limitations of the study are that the overall response rate was approximately 40% (which is in line with that in other surveys these days), the diagnoses were self-reported and could not be verified from patient records and that the patients with milder COPD or asthma might be excluded from the study because of less frequent medicine purchases. Nonresponders were on average slightly younger and more often men. Nonresponders used anti-inflammatory medication and long-acting beta-2-agonists slightly less often, but there were no significant differences in the use of short-acting relievers or long-acting anticholinergics. We concluded that the responders represented the population of Finnish subjects using R03 medications, but there may have been a slight bias towards a more severe chronic airway disease among the responders and possibly a higher proportion of asthmatic individuals in comparison to COPD among responders when compared to nonresponders. Since special reimbursement for R03 medications in Finland is dependent on a firm diagnosis of asthma or COPD based on lung function measures, these diagnoses are generally reliable.

Most of the subjects who were dispensed R03 medications reported being treated for asthma and far less frequently for COPD. Nevertheless, a quarter of subjects who were dispensed R03 medications reported not having a diagnosis of asthma or COPD. Among subjects reporting asthma, ICS were used most frequently, and guideline-based anti-inflammatory treatment was well adopted. Among subjects reporting COPD, the use of ICS was equally frequent as the use of long-acting bronchodilators, suggesting possible overuse of ICS.