Epidemiology and health economics in gastrointestinal diseases : real-world evidence from Swedish health registers

Introduction: Eosinophilic esophagitis (EoE) and microscopic colitis (MC) are chronic inflammatory diseases of the gastrointestinal tract. EoE is characterized by dysphagia, and predominantly affects children and young adults of male sex. On the contrary, MC is characterized by watery chronic diarrhea and predominantly affects elderly women. Similarly, the diagnosis of both EoE and MC rely on specific histopathological findings.

EoE and MC have both associated with both been associated with a reduced wellbeing and impaired quality of life. Furthermore, previous epidemiological studies have confirmed association to other comorbidities that contribute to the disease burden of EoE and MC. However, despite rising incidence rates, health economic studies remain scarce. To date, only one prior study has investigated health economics in patients with EoE. Those data have, however, been limited to direct costs related to healthcare resource utilization among commercially insured patients, while no prior data on indirect costs related to productivity losses have been reported. For MC, neither direct nor indirect costs have previously been investigated.

Aim: To investigate the economic burden of EoE and MC from a societal perspective.

Methods: Two cost-of-illness studies with a matched case-control design were performed. To estimate the economic burden of EoE and MC from a societal perspective. The study populations consisted of patients with EoE and MC for Study I and II, respectively. Patients were identified from the ESPRESSO cohort which contains histopathology data on all Swedish individuals between 1963-2017. Each case was matched with up to five general- population comparators matched on year of birth, sex, and county of residence.

Economic costs were derived from healthcare resource utilization, prescribed medications, and work loss due to sick leave or disability leave, based on real-world data from Swedish health registers. Stratified analyses were performed based on sociodemographic subgroups. In Study II, separate analyses were also performed by MC subtype, and by disease activity as defined by the number of required treatments during the first year of diagnosis. Linear regression models were used to calculate mean differences adjusted for age, sex, and education level, and cost ratios were used to construct relative cost measurements. All costs were adjusted for inflation according to the Swedish consumer price index (CPI) in 2023, and converted from Swedish currency, SEK, to USD according to the annual average exchange rate in 2023 (1 USD = 10.61 SEK).

Results: In Study I, patients with EoE had a mean annual societal cost of $6,614 as compared with $4,573 in the general population. The mean annual excess cost of patients with EoE was $2,041 (adjusted mean difference: $1.947 [95%CI: $1,109-$2,785]), corresponding to a cost ratio of 1.45 (+45%). The increased costs were mainly driven by an increased healthcare utilization, while no excess work loss was observed. The cost difference was highest among pediatric patients with EoE who had more than 6 times higher costs than their matched general-population comparators.

The societal economic burden of all patients with EoE in Sweden was estimated to $10.4 million in 2016, corresponding to $1 million per million inhabitants. Out of the total, $3.2 million was attributed to EoE or EoE-related comorbidity, corresponding to $0.3 million per million inhabitants.

In Study II, patients with MC had a mean annual societal cost of $10,492 as compared with $5,687 in the general population. The mean annual excess cost of patients with MC was $4,805 (adjusted mean difference [95% CI], $4,974 [$4,650-$5,298]), corresponding to a cost ratio of 1.84 (+84%). The increased costs were mainly driven by work loss. Furthermore, an additional analysis demonstrated that patients with a high disease activity, as defined by the requirement of budesonide treatment during the first year of diagnosis, was associated with higher societal costs in general, and work loss in particular, compared with patients with a more quiescent disease course during the first year of diagnosis.

The societal economic burden of all patients with MC in Sweden was estimated to $121 million in 2016, corresponding to $12 million per million inhabitants. Out of the total, $55 million was attributed to MC and MC-related comorbidity, which corresponded to $5.6 million per million inhabitants.

Conclusion: By exploring real-world data from Swedish health register, the research presented in this thesis demonstrate that EoE and MC are associated with an extensive economic burden with substantial impacts for both patients and society.

In Study I, patients with EoE were found to have around 45% higher societal costs than the general-population and were mainly driven by an increased healthcare resource utilization while no excess work loss was observed. The societal economic burden of EoE was estimated to $1.0 million per million inhabitants. With the incidence of EoE still rising, the economic burden is expected to continue to grow.

In Study II, patients with MC were found to have around 84% higher societal costs than the general population and were mainly driven by excess work loss. Furthermore, disease activity as defined by the number of treatments required during the first year of diagnosis was associated with increased societal costs in general, and increased work loss in particular. The societal economic burden of MC was estimated to $12 million per million inhabitants. Improved treatment and disease control could potentially mitigate the societal cost of MC, primarily by reducing excess work loss.

List of scientific papers

The Doctoral Degree is based on the following four papers, out of which the first two papers (i-ii) have already been defended as part of a Licentiate Degree at Örebro University. This doctoral thesis will thus be based on the latter two papers listed below (I-II), henceforth referred to by their Roman numerals.

i. Bozorg SR, Song M, Emilsson L, Ludvigsson JF. Validation of serrated polyps (SPs) in Swedish pathology registers. BMC Gastroenterol. 2019 Dec 31;20(1):3. https://doi.org/10.1186/s12876-019-1134-6

ii. Bozorg SR, Söderling J, Everhov ÅH, Lebwohl B, Green PHR, Neovius M, Ludvigsson JF, Mårild K. Work Loss in Patients With Celiac Disease: A Population-based Longitudinal Study. Clin Gastroenterol Hepatol. 2022 May;20(5):1068-1076.e6. https://doi.org/10.1016/j.cgh.2021.09.002

I. Bozorg SR, Söderling J, Mårild K, Garber JJ, Uchida A, Neovius M, Ludvigsson JF, Everhov ÅH. Economic Burden of Eosinophilic Esophagitis: A Nationwide Cost-of-Illness Study. Am J Gastroenterol. 2024 Oct 1;119(10):2122-2125. https://doi.org/10.14309/ajg.0000000000002868

II. Bozorg SR, Bergman D, Peery AF, Mårild K, Neovius M, Everhov ÅH, Khalili H, Ludvigsson JF. Economic Burden of Microscopic Colitis in Relation to Disease Activity: A Nationwide Cost-of-Illness Study. [Manuscript]