Prevalence and mortality rates of IBD
Based on our analysis of three time points within 5 years, we found an overall extrapolated prevalence rate of IBD of 0.37%, whereby the rate increased from 0.32% in 2010, to 0.38% in 2012, and to 0.41% in 2014. This is comparable to estimates in Sweden (0.35%), Finland (0.44%), the US (0.44%) and Canada (0.5%) [
4‐
6,
34]. According to a recently published review by Burisch and colleagues, [
15] 0.3% of the population had IBD in Europe. Our extrapolated prevalence rate was slightly lower than that of a large German insurance-based cohort with 493/100,000 actively treated IBD patients in 2010 (age- and sex-standardized to the German population) [
35]. According to a previous Swiss study, [
26] the estimated prevalence rate for Switzerland was 206/100,000. The incidence of both, CD and UC, were shown to have increased in Switzerland since then, [
25] which was also observed in other countries [
9]. In a large US cohort study, the prevalence rates in 2009 were 241/100,000 for CD and 263/100,000 for UC adult patients (20 years and older), respectively. These rates correspond to an increase compared with the years 2003/2004, where 201/100,000 were estimated to have CD and 238/100,000 were estimated to have UC [
5,
7]. In their claims data based study, patients with at least one IBD-specific medication, combined with at least one claim for CD or UC, were also included in their case definition [
7].
According to our analysis, IBD was more prevalent in women compared to men (403/100,000 vs. 331/100,000), and was lower in persons aged 17 years and younger (24/100,000) as compared with all other age groups. Similarly, a higher rate of female compared to male IBD patients was reported for the Swiss IBD Cohort, [
36,
37] as well as for other countries in Europe [
17,
35]. In US children, prevalence rates were estimated to be 43/100,000 for CD and 28/100,000 for UC, respectively, which is slightly higher than in our findings [
38]. However, our results need to be interpreted with caution, as the sensitivity of our defined IBD identification algorithm is relatively small, whereas the estimated specificity was found to be high. In other words, we possibly underestimate the number of patients with IBD. Reasons for the comparably low sensitivity might, firstly, be due to the fact that we were unable to detect patients with mild disease who weren’t treated with one of the defined medications [
37]. Secondly, there might be incident cases without a history of IBD-related medications. Thirdly, when medications are administered during hospitalization, coding for this treatment is missing by means of our data. Lastly, as the disease is characterized by relapsing intestinal inflammation, the medical treatment varies. However, in absence of clinical data like ICD codes, the use of highly reliable medical claims to estimate the burden of a chronic disease is common. A previous validation study on IBD based on an administrative database has found a sensitivity of 88.9% and 89.2% and a specificity of 91.2% and 89.8% for CD when comparing self-reports with chart-reviews, and a sensitivity of 87.7% and 74.4% and a specificity of 91.3% and 93.7% for UC, respectively [
39].
Looking solely at medical claims, the percentage of IBD patients with a drug prescription amounted to 19% for immunosuppressants and 5% for biologics in our study in 2010. The corresponding figures were 19% and 3% in a Swedish study [
34]. In contrast, their prescription rates for aminosalicylates were considerably lower [
34]. In a Dutch study, 30.1% of the IBD patients received immunosuppressants, 15.1% received biologics, and 39.7% were on 5-ASA in 2011 (as compared with 84.8% of patients with 5-ASA in 2012 in our study) [
17].
We found no increased mortality ratio in patients with IBD compared to the non-IBD cohort. This is in line with previous studies in the Netherlands, Finland or North America [
40‐
42]. Further previous studies assessing mortality rates in IBD patients found a higher mortality ratio in CD, but not UC patients, for example in the US, Denmark, or in overall Europe [
15,
43,
44]. In contrast, slightly higher rates were found for overall IBD patients, [
45‐
47] that were commonly more pronounced in younger patients [
43,
46]. Mortality rates were shown to decrease over the last decades, especially in hospitalized patients [
48].
Health care costs and health care utilization
Based on our findings, the extrapolated median (mean) total health care costs per IBD patient in Switzerland were CHF 5390 (9590) in 2010, CHF 6090 (11,680) in 2012, and costs increased to CHF 6810 (12,790) in 2014. According to a review by Yu et al. [
49] published in 2008, estimated annual direct medical costs per CD patient were approximately 18,000 to 19,000 US$ in the US, and approximately 4000 to 10,000 US$ (converted) in other Western countries. Similarly, lower costs for the treatment of CD and UC in Europe compared to the US have been shown in the review by Odes [
50]. From 1999 to 2005, annual medical costs per patient were estimated to be 18,963 in CD patients versus 5300 US$ in controls, and 15,020 in UC patients versus 4982 US$ in controls in the US [
51]. The calculated increase in total costs in our study is in line with international findings. Based on health claims data, the average annual medical costs per patient with CD and UC amounted to 6561 US$ and 1488 US$, respectively, in the US in 1990 [
52]. Thirteen to fourteen years later, the direct medical costs of CD and UC per patient per year were estimated to be 10,952 US$ (with CD associated treatment costs of US$ 8265) and 7948 US$ (with UC associated treatment costs of US$ 5066) from a social insurance payer perspective, respectively [
18].
Based on our study findings, women incurred higher total health care costs than men. And in the multivariate regression model on total costs in IBD patients, costs were highest in the youngest age group. However, the confidence interval in the youngest patients are wide, suggesting great variance and heterogeneity in the management of the youngest patients.
In contrast to our findings, no significant sex-related differences were found concerning total health care costs in a large US study [
18]. In that same study, younger patients (aged <20 years) were shown to incur higher mean annual health care costs compared to their older counterparts, especially in CD patients [
18,
53]. The higher costs in the youngest age group were explained 1) by a higher number of incident cases in this age group, 2) by a more severe course of disease when IBD is diagnosed at young age, and moreover 3) by a possibly more progressive treatment pattern of pediatric gastroenterologists [
18].
There has been a shift from inpatient to outpatient costs in recent years, due to the introduction of new medical therapies like biologics, mainly in patients with CD [
16,
18,
50]. This is comparable to our results, where outpatient costs made up 79% in 2010 and 84% in 2014. However, the increase in outpatient costs might also be a consequence of the introduction of the Swiss DRG in 2012, which might have led to a shift of treatments and dispensing of medications from the inpatient to the outpatient setting. In earlier studies conducted in the US, [
49,
52] and in European countries, [
19,
49] more than half of the total costs were attributable to inpatient costs. Medical and surgical hospitalization made up a little more than 30% in a US study conducted between 2003 and 2004 [
18]. In a recent Dutch study [
17] that looked at the societal perspective of the costs of IBD, medication costs accounted for 71% of the total costs in CD and for 59% in UC patients. Inpatient costs made up as little as approximately 20% of the total costs in 2011 [
17].
In 2014, 98.3% of IBD patients in our sample had at least one physician visit. The extrapolated median (IQR) number of visits per IBD patient was 15 (15-16) in 2014, compared to 4 (4-4) in the non-IBD sample, whereby the greatest differences referred to specialist visits. The proportion of IBD patients with at least one hospital admission in 2014 was nearly 24%. The median (mean) length of hospital stay amounted to 7 (16) days in those patients.
In a previous Swiss study, [
37] the mean (± SD) number of outpatient visits was 2.1 (± 3.6) and 2.3 (± 3.2) in UC and CD patients during the 3-months follow-up, respectively, whereby patients more frequently consulted a specialist rather than a primary care physician in their analyses as well. However, they only investigated IBD-related resource consumption, whereas we didn’t consider the reason for hospitalization or consultation. Almost 14% of the IBD patients were hospitalized for at least 1 day in their 12-months follow-up [
37]. Their calculated mean (± SD) number of days in hospital was 1.5 (± 6.1) and 2.0 (± 8.8) in UC and CD patients, respectively. Yet, they didn’t exclude patients without any consultation or hospitalization in their study. Similarly, about 14% of the IBD patients were hospitalized in the UK [
54]. In a Swedish study, 24% of the IBD patients had undergone at least one major IBD-related surgery during the study period [
34]. According to a recent review, the hospitalization rates varied considerably between European countries [
15]. The proportion of IBD patients with surgery ranged between 0.5% in an Hungarian and 35% in a Danish cohort during 1 year of observation. To conclude, the diversity in the definition or classification of visits does not allow always for direct comparison of the results found in our study with previous study findings.
Comparison of IBD patients with and without the use of biologics
In 2014, 13% of all IBD patients in the Helsana cohort received biologics. They incurred four times higher total costs compared with patients without such a prescription. About 70% of the costs were attributable to medication costs. But the higher medication costs were not compensated by lower inpatient costs. However, these results need to be interpreted with caution as we could not take the year of diagnosis or the disease severity into account. It is known that patients treated with biologics are mostly affected by a more severe disease course. Furthermore, inpatient costs were not limited to an IBD-related hospitalization.
Thus, similar results were found by Kappelman et al. [
18] in 2003 and 2004. According to their study, biologics (namely infliximab) were the most expensive medications in CD patients, whereas aminosalicylates were the most costly drugs in UC patients. A higher consumption of health care resources in patients treated with biologics has also been found in further studies [
37,
55]. The higher resource consumption mainly occurred in the first 1-3 years after initiation of the treatment in those analyses, which might be another reason for the higher costs in young patients reported in our study.
In contrast, a Danish cohort study has demonstrated that the increased use of thiopurines and biologics in IBD over time was associated with a persistent significant decrease in surgery rates, along with a significant decrease in the use of 5-ASA and corticosteroids [
56]. The study, however, did not have the power to demonstrate a surgery-sparing effect of these newer medications [
56]. The Swiss study by Safroneeva et al. [
57] demonstrated that early treatment of CD patients with immunosuppressants and biologics was associated with reduced risk of developing bowel strictures, and early immunosuppressants reduced the risk of intestinal and perianal surgery. Therefore, further research with longer follow-up periods is needed.
Strengths and limitations
The strength of the present study is the large number of patients included that enabled us to give a representative overview of the IBD situation in Switzerland. To the best of our knowledge, this is the first study to explore prevalence, mortality as well as health care costs and utilization for IBD patients treated in all settings in Switzerland. Moreover, the data weren’t collected by means of self-report and therefore results were not distorted due to recall bias.
One major limitation of this study is the fact, that we were lacking diagnosis information in the ambulatory setting. Since medication therapy is the main pillar in the treatment of IBD patients [
20,
22,
58] the identification of patients via ATC codes seems natural. The combination of at least one claim for UC and CD and at least one pharmacy claim for 5-ASA, Immunosuppressants or biologics has been used in previous studies on the prevalence and health care costs of patients with CD and UC [
5,
18]. Due to the selected ATC codes for the definition of IBD, patients with mild disease severity are likely to be underrepresented. This in turn may lead to an overestimation of the health care costs of IBD patients when compared with a non-IBD population as we more likely missed those cases incurring lower costs. Because of the known diagnostic delay distinctive of IBD, as well as the relapsing and remitting nature of IBD, the number of IBD patients may be even higher [
59,
60]. Furthermore, this study is based on outpatient prescription drug dispending and does not consider medications applied during hospitalizations. Moreover, patients who consulted a pediatric gastroenterologist who is registered as a pediatrician rather than a gastroenterologist might be misclassified as not having IBD. This may lead to an underestimation of the prevalence of IBD, especially in younger patients.
A second major limitation is the fact that time trends are based on the analysis of three time points over a 5-year-period. One should therefore be careful drawing conclusions on time trends.
It is conceivable that further factors might influence the study findings, like the time of diagnosis or the treatment delay, which cannot be identified by means of the Helsana data [
61]. In addition, we were not able to discriminate between health care costs and utilization that were solely attributable to IBD.