Epidemiology and comorbidity of juvenile idiopathic arthritis in Poland – a nationwide study

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Methods Public healthcare utilization records from the National Health Fund (NHF) were screened between 2010–2022. For individuals aged < 16 years, we utilized a narrow JIA case definition combining repeat ICD-10 encoding with DMARDs prescription based on ATC codes. Results Of 37 mln patients in the NHF database, 29 758 individuals fulfilled our case definition. Over time, the number of newly detected cases ranged between 1381–2394. In 2022, the incidence and prevalence rate per 100,000 persons was calculated at 4.14 and 73.9, respectively. Stable incidence trends were observed with mean incidence rate estimated at 5.65 (95%CI 4.80–6.50). Gender-related differences confirm JIA susceptibility among females. Among JIA-related comorbidities, allergic rhinitis (N = 5 200, 17.5%), bronchial asthma (N = 3 661, 12.3%) and growth restriction (N = 2 311, 7.8%) were common. Over 214 285 visits, we calculated the total and median cost of JIA treatment at over 3.54 mln€ and 232 000€, respectively. Conclusions This is a comprehesive, nationwide study that provides a contemporary estimate for JIA burden and cost in Poland. epidemiology incidence inflammatory arthritis juvenile idiopathic arthritis prevalence morbidity disease occurrence Figures Figure 1 Figure 2 Figure 3 Figure 4 Key Message This nationwide, healthcare system analysis examines temporal changes in JIA burden of the Polish population, including co-morbidities and direct costs of ambulatory care Cyclic and age-dependent trends in incidence rates were observed, with significant comorbidity recorded for every fourth patient with JIA In comparison to higher welfare nations, comprehesive data on JIA epidemiology from lower income countries in Europe are scarce Introduction In pediatric care, juvenile idiopathic arthritis (JIA) represent the most common type of inflammatory arthritis 1 . On a nosological level, JIA represents a clinical concept that encompasses several complex and heterogeneous conditions that are marked by arthritis persisting for six weeks or more, which present in patients under the age of 16. The most widespread criteria of the International League of Associations for Rheumatology (ILAR) allow for categorization into seven distinct subtypes based on joint count, serology, and associations with features like uveitis, psoriasis or enthesitis. However, over time, patients can transition to different phenotypes, manifesting new symptomatology, while others remain undifferentiated 2 . The global incidence can be estimated between 1 to 23 cases per 100,000 pediatric subjects 3 , 4 . While no specific geographic predominance is observed, the majority of studied populations originate from Europe and North America 2 , with a comprehensive review reporting a pooled incidence of 8 per 100,000 Caucasian children 5 . There are no population-based studies in Poland that quantify the epidemiologic burden of JIA. Prior retrospective estimates reported for 2008–2010 relied solely upon singular ICD-10 encoding sourced from the National Health Fund (NHF) claims 6 . The transition to stringent control and goal-directed therapy has changed management of rheumatic disorders under the treat-to-target (T2T) approach. In contrast to adult forms of arthritis, the evidence in JIA accumulates with certain lag 7 , 8 , with international recommendations by Ravelli et al. 9 for T2T utilization published only in 2018. Despite advances in treatment, longitudinal cohort studies still report suboptimal outcomes in JIA, with a high burden of disease in adulthood 10 . Management of JIA in Poland is provided by pediatric rheumatologists, but the division to pediatric and adult specialists complicates care for transition age patients. Transitional age JIA management is a difficult problem that is recognized globally 11 , 12 . Rheumatologists often exhibit variable practice patterns, not always compliant with recommendations, which stems (in part) from both medical and non-medical barriers 13 . Details on rheumatology in Poland, including treatment available and healthcare organization is available elsewhere 14 . This nation-wide study aims to contribute an array of epidemiologic evidence contributing to the current understanding of population burden, temporal trends and co-morbidity prevalence in JIA subjects. Understanding these factors will facilitate data-driven decision for the policy maker, and enable reliable informing of future research directions and healthcare strategies. Methods This is a nation-wide, retrospective study based on electronic reimbursement claims recorded in public healthcare. The recruitment pool considered all records of healthcare professional contact in either ambulatory or inpatient services. Definitions To limit bias associated with the diagnostic process, we developed an expert-based, operating case definition for JIA. The surrogate measure for JIA presence was based on repeat diagnostic records of ICD-10 encoding as primary cause for services rendered within: at least 2 visits in outpatient rheumatology care, with a minimum interval of 90 days between visits, at least 1 visit with a general practitioner (GP) or specialist rheumatologist and realization of at least 1 prescription for any of the following arthritis-specific medications: cyclosporine, methotrexate, leflunomide, sulfasalazine, chloroquine or hydroxychloroquine, at least 1 visit in inpatient care, The specifics of ICD10 encoding are detailed in Supplementary Material. Fulfillment of the case definition determined an estimated date of arthritis onset. If a patient satisfied multiple definitions, the earliest occurring event determined the disease onset date. All patients were required to fulfill the case definition prior to 16 years of age, to limit the overlap with rheumatoid arthritis or psoriatic arthritis. We also tested an alternative definition with maximum age of 17 years at diagnosis. However, due to very similar trends and possibility of greater bias (16 to 18 years represents transitional age), we retained the more conservative definition (< 16 years of age). Data Collection and Preparation Utilizing the adopted case definition, we extracted the absolute number of annual incident and prevalent JIA cases between January 1, 2010 – December 30, 2022, as well as any events of death recorded among JIA patients. All information was sourced from the repositories of the National Health Fund. To better understand changes within the population burden, we calculated several known epidemiological measures: Prevalence rates: one year period prevalence was calculated per annum, using the total number of prevalent cases collected up to December 31 of each year. For each year, the population at risk was adjusted; this represents a conservative estimate, given the decremental population trend. The prevalence rate was then computed as the proportion of prevalent cases divided by the adjusted population at risk, multiplied by 100,000. Incidence rates were calculated similarly by dividing the number of new cases observed each year by the population at risk. Analysis and visualization were performed using R version 4.3.3 (R Core Team, 2024) with the use of publically available tidyverse packages. Ethical approval This analysis relies solely on data obtained from the National Health Fund electronic databases. Obtaining institutional ethical approval was not required. Results 3.1 Temporal Trends in JIA Prevalence, Incidence, and Mortality Between 2010-2022, we identified a total 29 758 individuals with JIA up to the age of 16, with incidence ranging between 1381-2394 new JIA cases, per year (details in Table 1). The most common diagnoses were M08.9 (22.3%), M08.8 (20.6%), M08.0 (15.5%), M08.4 (13.6%), M08 (11.7%), M08.3 (4.7%), M08.2 (2.4%), M06 (1.7%), M06.9 (1.2%) and M06.4 (1.2%). By 2022, the incidence and prevalence rate per 100,000 persons of the GP was calculated as 4.14 and 73.9, respectively. Earlier, between 2010-2015, incidence and prevalance ranged between 6.22-10.3 and 10.4-38.4, respectively. From 2016-2022, both prevalence, but not incidence rates, showed incremental trends with a range of 44.3-69.5 and 3.61-5.94, respectively. For a detailed overview see Figure 1 (raw data in Table 1). Due to stable temporal trends, the mean (95% CI) incidence rate was calculated as 5.65 (4.80-6.50). Overall, death was a very rare event with only 74 cases recorded in total throughout this time. Annual estimates of the mortality rate ranged from 0 (2010-2012), 0.01 (2013-2014, 2017-2020) to 0.04 (2021-2022) per 100 000 individuals. With the enhanced population burden of JIA, we investigated potential gender-related differences and identified a stable trend with female predominance (see Figure 2), which corresponds to an average temporal female-to-male incidence ratio of 1.24 (95%CI 1.29-1.18). 3.2 Age Specific JIA Prevalence and Incidence Rates In order to understand age-specific dynamics in JIA epidemiology, we examined incidence and prevalence rates across age groups (see Figure 3). For prevalence trends, between 2010-2022, incremental rates were observed for patients with ages between 13-18 years. We observed a plateau phase for children aged 2-6 years and and a late plateau for older children 7-12 years of age. By contrast, incidence rates were similar across age groups, with a modest, generally decremental trend. From an exploratory perspective, we also tracked individuals who previously fulfilled our case definition for JIA (from 2010 and thereafter). Increasing prevalence with very stable incidence rate indicates these individuals of transitional age shift towards other diagnoses. While in absolute counts, or respective to age-specific population size (Figure 3), high prevalence was observed for adults with JIA history, but after considering the adult general population size (ie, true denominator), the annual point prevalence ranged from approximately ~0.3-0.5% in 2022. Of note, we observed that following transition to adult care, in 2022, most patients were not recorded with inflammatory arthritis (N=10 289, 66.9%), while rheumatoid arthritis (N=3 813, 24.8%), psoriatic arthritis (N=775, 5.0%), ankylosing spondylitis (N=812, 5.3%), Still’s disease (N=78, 0.5%) and inflammatory axial disease (N=430, 2.8%) were the most common transitional patterns. 3.3 Co-morbidity in JIA For the pediatric JIA population, we examined trends in comorbidity based on healthcare utilization data. In general, pulmonary (N=13 619, 36.4%), ocular (N=12 437, 39.84%), genitourinary (N=6827, 20.0%), neurologic (N=5664, 16.6%), infectious (M=5329, 15.6%), genetic/growth abnormalities (N=5129, 15.0%), ear disorders (N=5013, 14.7%), gastroenterologic (N=4859, 14.2%), neoplasms (N=4730, 13.8%), psychiatric (N=3032, 8.9%), cardiovascular (N=2751, 8.1%) and hematologic (N=1995, 5.8%) disorders, respectively. We also calculated composite comorbidity scores: the Elixhauser (0 – 9384, 27.5%; 1 – 18 638, 54.5%; 2 – 4 803, 14.1%; 3 – 1 067, 3.1%; 4 – 224, 0.7%) and Charlson score (0 – 25 704, 75.2%; 1- 7 695, 22.5%; 2 – 729, 2.1%; 3- 47, 0.1%) for the whole pediatric JIA population. For comparative purposes and consistency with the JIA definition, we also examined a restricted population of JIA subjects (pediatric population ≤16 years of age). The most frequent comorbidities were: allergic rhinitis (N=5 200, 17.5%), scoliosis (N=3 844, 12.9%), bronchial asthma (N=3661, 12.3%), chronic tonsillitis/pharyngitis (N=3 641, 12.2%), acne (N=2 879, 9.7%), growth restriction (N=2 311, 7.8%), congenital hip disorder (N=2 304, 7.7%), viral warts (N=2 268, 7.6%), non-purulent middle ear infection (N=2 120, 7.1%), atopic dermatitis (N=2 014, 6.8%), speech disorder (N=1 833, 6.2%), headache syndromes (N=1 703, 5.7%), heart murmur (N=1 651, 5.6%), reactive arthropathy (N=1646, 5.5%), chorioretinal disorders (N=992, 3.3%) and chronic sinusitis (N=990, 3.3%). 3.4 Direct cost of JIA Over 214 285 visits, we calculated healthcare costs of JIA treatment based on claims from public care visits with corresponding primary reimbursement claims, which amount to an annual median (IQR, range) cost of 37.8€ (47.4-11.6€, 30.3-86.1€, respectively) per patient. Between 2010-2022, the total cost of JIA treatment amounts to over 3 540 000€, with a median (IQR, range) JIA cost of 232 000€ (178 000-309 000€, 103 000-573 000€, respectively) per year (Figure 4). The median (IQR, range) cost per visit was 14.1€ (12.1-18.3€, 9.70-33.8€), respectively. Discussion This is the first robust study that quantifies the epidemiological burden of JIA in Poland between 2010-2022. We utilized a complex case definition, which combines repeat ICD-10 encoding, prescription data and accounts for hierarchical structure in healthcare. We calculated prevalence and incidence rates for the JIA population at 73.9 and 4.14 per 100 000 persons in 2022. To date, there have been no population-based studies for JIA in Poland. Previously, estimates were derived from an observational, cohort study conducted on a regional level 15 . Another prior domestic report for 2008-2012 aimed to evaluate JIA burden, though the authors focused on regional and rural-urban differences, while also utilizing singular ICD-10 claims to identify JIA 6 . In this study, we observed that incidence of JIA is stable and potentially decremental over time. Whether this corresponds to a true decrease incidence or reflects healthcare restriction in the pandemic years (among other potential confounding factors) is currently unknown. However, with the often chronic nature of JIA, the prevalent population of patients is growing (on par with the aging general population). In broad terms, our findings are comparable with those of other studies. Recent studies from the UK reported an overall age-standardized incidence rate at 5.61 and prevalence rate of 43.5 per 100 000 persons in 2018 16 . Using a database of 3-4 mln patients, Horneff et al. reported incidence rates between 34-60 and 133-168 per 100 000 patients was reported 17 . In Nordic countries, incidence and prevalence rates tend to be higher (18.5 and 159, respectively). A prior systematic review synthesized the pooled incidence and prevalence rates with an estimate of 7.8 (95% CI 7.6, 8.1) and 20.5 (95% CI 19.8, 21.3), respectively. In historical cohorts (1990’s and earlier), the prevalence was estimates ranged between 60 – 400 per 100 000 for JIA 18 . Gathering additional epidemiological data is of high importance due to considerable variability on a geographical and ethnic level, both in disease burden and course 19–21 . While JIA may attenuate throughout young adulthood, the majority of patients exhibit ongoing signs of disease 22 , and likely transition into undifferentiated or adult form of arthritis. A study by Glerup et al. based on a cohort study from Scandinavian countries shows the high burden of disease that persists into adulthood, with only one third of patients achieving remission, despite being diagnosed in the early biologic era 10 . Delayed introduction of biologic DMARDS leads to enhanced disability and quality of life, including lower chances for drug-free remission after transitioning into adulthood 23 . In contrast to earlier epidemiologic studies, we did not restrict the scope of the investigation to individuals 16 years or younger, as we know little about transitional age JIA. We observed that a substantial proportion of JIA patients are young adolescents or adults, which is important from a management perspective. Transition into adulthood is tied to a change in the healthcare provider, but also carries psychosocial considerations. Adherence and illness coping is worse in adolescence 24 . Despite initially high effectiveness of biologics, long term retention is suboptimal 25 . A single monocentric study from Poland showed that adult JIA is highly heterogenous and difficult to treat, with less than 50% of patients meeting criteria for adult types arthritis 26 . Our findings emphasize the population burden, and further showcase the importance of future studies of the transitional JIA population. We also examined the most common chronic causes for healthcare contact among JIA patients. Our results are similar to a recent report by Horneff et al. from Germany, who observed the common concurrent presence of atopic dermatitis, allergic diseases and others 17 . However, we did not observe such a high rate of uveitis (Horneff et al. - 11%), with the most common ocular condition (after additional analysis) reported as refractive disorders (21.9%), strabismus (3.5%) and anterior uveitis (3.3%), as would be expected. Haslak et al. reported allergic rhinitis, attention disorders and atopic dermatitis as the most common concurrent conditions 27 . Other reports from smaller cohorts indicate the common prevalence of uveitis (18%), allergic rhinitis (14.5%), migraine (8.7%) and atopic dermatitis (8.7%) 28 , which may markedly differ from population estimates due to sampling heterogeneity. The limitations of this study include retrospective character and utilization of secondary sources to establish a proxy diagnosis. Incidence calculations are based on the use of a denominator of population size at-risk of developing disease at a given time (per year), which does not always equate to person-years at-risk, which is the ideal case scenario for epidemiologic estimates 29 . While we utilized fixed population size at a given time, the chronicity of JIA and young age distribution limits the bias associated with incomplete follow-up (i.e., an imprecise denominator). We are unable to account for additional sources of bias such as miscoding, incompleteness or errors within the diagnostic and therapeutic process, which would results in false fulfillment of the JIA definition. While the use of a complex case definition and near complete population coverage with public healthcare are the strengths of this report, the validity of these estimates requires further replication in population cohorts. Geographical differences are likely to be present throughout Europe, but due to the demographic and ethnic structure of Poland, this cohort is likely representative of Central-Eastern Europe. Conclusion Providing reliable epidemiological results regarding population burden of JIA is important for the policy maker in healthcare resource allocation and identifying areas of priority for intervention. This comprehensive nation-wide study from Poland examines population prevalence and incidence of JIA across 2010-2022. Utilizing a complex definition integrating ICD-10 encoding and prescription data, relatively high population burden can be ascertained, as compared with the rest of Europe. Despite a potential declining trend in JIA incidence over time, the prevalent population is growing, highlighting the importance of tailored care as patients transition into adulthood. Declarations Ethics approval: Not necessary due to the retrospective nature of the data; data were anonymized prior to analysis with subgroup size > 5 cases Consent for publication: Not applicable Availability of data and materials: Raw data is publically available in abridged form on the online platform for Strategic Analyses published by the Ministry of Health, but also available in greater detail upon reasonable request from the authors. Competing interests: none to declare Funding: This paper was prepared as a part of the "Maps of Health Needs – Database of Systematic and Implementation Analysis" (grant number POWR.05.02.00-00-0149/15) and ‘Integrated Analytical Platform’ projects (grant number POPC.02.02.00-00-0015/18-00), both co-financed by the European Union from the European Social Fund and European Regional Development Fund respectively. Author contributions: Conceptualization: ZZ, BB, MK-W, MSz, BK; Methodology: MK-W, MSz, BB, ZZ, KP, BK; Literature review, preparation and writing the original article: MK-W, MSz, MSt, BB, ZZ; Visualisation: MK-W, MSz, KB, KP; Reviewing and editing the manuscript: MK-W, MSz, KB, BB, ZZ, MO, KP, JS, JJ, MŚ, MB, AŚ, BK; Supervision: MK-W, MSz, BB, ZZ, BK. All authors fulfill all authorship criteria by ICMJE and take full responsibility for the accuracy and integrity of all aspects of the work. References Petty, R. E. et al. 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Year Prevalent JIA, N Incident JIA, N Mortality, N 2010 6 117.00 2 163.00 1 2011 8 088.00 1 972.00 1 2012 10 275.00 2 190.00 3 2013 12 380.00 2 107.00 2 2014 14 766.00 2 394.00 8 2015 17 044.00 2 283.00 5 2016 19 263.00 2 228.00 9 2017 21 341.00 2 087.00 9 2018 23 294.00 1 959.00 6 2019 25 216.00 1 930.00 8 2020 26 583.00 1 381.00 14 2021 28 147.00 1 578.00 14 2022 29 758.00 1 625.00 14 Supplementary Files supplement.docx Cite Share Download PDF Status: Published Journal Publication published 28 Mar, 2025 Read the published version in Pediatric Rheumatology → Version 1 posted Reviewers agreed at journal 03 Jul, 2024 Reviewers invited by journal 03 Jul, 2024 Editor assigned by journal 01 Jul, 2024 First submitted to journal 27 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Żuber","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABB0lEQVRIiWNgGAWjYDACCTCZAGF8MABxGBuAhAVxWhhnGICpBrg4QS3MPAiluLXIz+4x/vijIs3e4Hbzsc82BXfq+KUPN35g3IFbC+OcM2YSEmdymA3uHEuenWPwTEKyL7FZgvEMbi3MEjlmDIZtFWwGN3KMmXMMDksYnGFskGBsw62FTSLH+EPivwoegxv5n5ktgFrszzA2/8CnhUcix0DiYEOOBNAWZmYGkC08QPX4tEjIHCuTbDiWZiB555gxY4/BYckZZxjbLBLx+EV+dvPmjz9qku35bjc/Zvjx5zA/fw/74xsfd9jg1MLAwGGARTCxAY8OBvYHWAQZ8WoZBaNgFIyCEQYA+AdPplNKcJsAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-9581-0601","institution":"Krakowska Akademia im Andrzeja Frycza Modrzewskiego","correspondingAuthor":true,"prefix":"","firstName":"Zbigniew","middleName":"","lastName":"Żuber","suffix":""},{"id":322151585,"identity":"e061f60b-c0e1-400a-972b-a6184a16423d","order_by":1,"name":"Krzysztof Podwójcic","email":"","orcid":"","institution":"Institute of Labor and Social Sciences, Warsaw, 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Krakowie","correspondingAuthor":false,"prefix":"","firstName":"Krzysztof","middleName":"","lastName":"Batko","suffix":""},{"id":322151589,"identity":"6b5281bb-26c5-44a3-8829-05c5e5a30e45","order_by":5,"name":"Michał Orleański","email":"","orcid":"","institution":"Ministry of Health of the Republic of Poland","correspondingAuthor":false,"prefix":"","firstName":"Michał","middleName":"","lastName":"Orleański","suffix":""},{"id":322151590,"identity":"459ec8cd-bac8-48e8-ba8e-2b045644170a","order_by":6,"name":"Jakub Sowiński","email":"","orcid":"","institution":"Ministry of Health of the Republic of Poland","correspondingAuthor":false,"prefix":"","firstName":"Jakub","middleName":"","lastName":"Sowiński","suffix":""},{"id":322151591,"identity":"7799fd98-ed51-4110-88e2-81530540692a","order_by":7,"name":"Maria Świderek","email":"","orcid":"","institution":"Ministry of Health of the Republic of Poland","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"","lastName":"Świderek","suffix":""},{"id":322151592,"identity":"b1a56016-84ae-4795-b5d4-827d7f1ccec3","order_by":8,"name":"Agata Śmiglewska","email":"","orcid":"","institution":"Ministry of Health of the Republic of Poland","correspondingAuthor":false,"prefix":"","firstName":"Agata","middleName":"","lastName":"Śmiglewska","suffix":""},{"id":322151593,"identity":"d395320e-b973-4406-b3cd-3ef89cdfc664","order_by":9,"name":"Michał Maluchnik","email":"","orcid":"","institution":"Medical University of Gdansk: Gdanski Uniwersytet Medyczny","correspondingAuthor":false,"prefix":"","firstName":"Michał","middleName":"","lastName":"Maluchnik","suffix":""},{"id":322151594,"identity":"e938219e-1788-4e07-b68e-3a1741a28dae","order_by":10,"name":"Marek Brzosko","email":"","orcid":"","institution":"Pomeranian Medical University: Pomorski Uniwersytet Medyczny w Szczecinie","correspondingAuthor":false,"prefix":"","firstName":"Marek","middleName":"","lastName":"Brzosko","suffix":""},{"id":322151595,"identity":"951d1af6-37d1-40a8-baaa-80dafca3ae1e","order_by":11,"name":"Brygida Kwiatkowska","email":"","orcid":"","institution":"Narodowy Instytut Geriatrii Reumatologii i Rehabilitacji","correspondingAuthor":false,"prefix":"","firstName":"Brygida","middleName":"","lastName":"Kwiatkowska","suffix":""},{"id":322151596,"identity":"8f960ad3-762a-4ec8-9c16-2358c10250cb","order_by":12,"name":"Marcin Stajszczyk","email":"","orcid":"","institution":"silesian center for rheumatology","correspondingAuthor":false,"prefix":"","firstName":"Marcin","middleName":"","lastName":"Stajszczyk","suffix":""},{"id":322151597,"identity":"8aacc32e-553e-4402-9376-df63fa0e7f28","order_by":13,"name":"Bogdan Batko","email":"","orcid":"","institution":"Krakowska Akademia im Andrzeja Frycza Modrzewskiego","correspondingAuthor":false,"prefix":"","firstName":"Bogdan","middleName":"","lastName":"Batko","suffix":""}],"badges":[],"createdAt":"2024-06-27 19:08:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4650683/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4650683/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12969-025-01065-8","type":"published","date":"2025-03-28T15:57:56+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":61197578,"identity":"52ed5c86-1b5a-47f4-8782-0c2bf3ad6fdc","added_by":"auto","created_at":"2024-07-27 00:32:59","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":178768,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this 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version\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4650683/v1/4d1f1a62804764761487ebe4.png"},{"id":61197580,"identity":"2228322a-0206-4688-83d2-38b3644667a2","added_by":"auto","created_at":"2024-07-27 00:32:59","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":188263,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4650683/v1/f90fadad94f003d29d2c0dca.png"},{"id":79604925,"identity":"e008285d-dd3e-4395-ab0e-026c2675ede8","added_by":"auto","created_at":"2025-03-31 16:09:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2079909,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4650683/v1/2b3a6593-2c36-4a4b-82ff-aefe9c2c311d.pdf"},{"id":61198427,"identity":"51d04a25-b7ee-4522-a208-8e8fc93c155d","added_by":"auto","created_at":"2024-07-27 00:40:59","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15613,"visible":true,"origin":"","legend":"","description":"","filename":"supplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-4650683/v1/18d2b21feacb993e3db64b31.docx"}],"financialInterests":"","formattedTitle":"Epidemiology and comorbidity of juvenile idiopathic arthritis in Poland – a nationwide study","fulltext":[{"header":"Key Message","content":"\u003cul\u003e\n \u003cli\u003eThis nationwide, healthcare system analysis examines temporal changes in JIA burden of the Polish population, including co-morbidities and direct costs of ambulatory care\u003c/li\u003e\n \u003cli\u003eCyclic and age-dependent trends in incidence rates were observed, with significant comorbidity recorded for every fourth patient with JIA\u003c/li\u003e\n \u003cli\u003eIn comparison to higher welfare nations, comprehesive data on JIA epidemiology from lower income countries in Europe are scarce\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003eIn pediatric care, juvenile idiopathic arthritis (JIA) represent the most common type of inflammatory arthritis\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. On a nosological level, JIA represents a clinical concept that encompasses several complex and heterogeneous conditions that are marked by arthritis persisting for six weeks or more, which present in patients under the age of 16. The most widespread criteria of the International League of Associations for Rheumatology (ILAR) allow for categorization into seven distinct subtypes based on joint count, serology, and associations with features like uveitis, psoriasis or enthesitis. However, over time, patients can transition to different phenotypes, manifesting new symptomatology, while others remain undifferentiated\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe global incidence can be estimated between 1 to 23 cases per 100,000 pediatric subjects\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. While no specific geographic predominance is observed, the majority of studied populations originate from Europe and North America\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, with a comprehensive review reporting a pooled incidence of 8 per 100,000 Caucasian children\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. There are no population-based studies in Poland that quantify the epidemiologic burden of JIA. Prior retrospective estimates reported for 2008\u0026ndash;2010 relied solely upon singular ICD-10 encoding sourced from the National Health Fund (NHF) claims\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe transition to stringent control and goal-directed therapy has changed management of rheumatic disorders under the treat-to-target (T2T) approach. In contrast to adult forms of arthritis, the evidence in JIA accumulates with certain lag\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e, with international recommendations by Ravelli et al.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e for T2T utilization published only in 2018. Despite advances in treatment, longitudinal cohort studies still report suboptimal outcomes in JIA, with a high burden of disease in adulthood\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eManagement of JIA in Poland is provided by pediatric rheumatologists, but the division to pediatric and adult specialists complicates care for transition age patients. Transitional age JIA management is a difficult problem that is recognized globally\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Rheumatologists often exhibit variable practice patterns, not always compliant with recommendations, which stems (in part) from both medical and non-medical barriers\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Details on rheumatology in Poland, including treatment available and healthcare organization is available elsewhere\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis nation-wide study aims to contribute an array of epidemiologic evidence contributing to the current understanding of population burden, temporal trends and co-morbidity prevalence in JIA subjects. Understanding these factors will facilitate data-driven decision for the policy maker, and enable reliable informing of future research directions and healthcare strategies.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis is a nation-wide, retrospective study based on electronic reimbursement claims recorded in public healthcare. The recruitment pool considered all records of healthcare professional contact in either ambulatory or inpatient services.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eDefinitions\u003c/strong\u003e \u003cp\u003eTo limit bias associated with the diagnostic process, we developed an expert-based, operating case definition for JIA. The surrogate measure for JIA presence was based on repeat diagnostic records of ICD-10 encoding as primary cause for services rendered within:\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eat least 2 visits in outpatient rheumatology care, with a minimum interval of 90 days between visits,\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eat least 1 visit with a general practitioner (GP) or specialist rheumatologist and realization of at least 1 prescription for any of the following arthritis-specific medications: cyclosporine, methotrexate, leflunomide, sulfasalazine, chloroquine or hydroxychloroquine,\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eat least 1 visit in inpatient care,\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eThe specifics of ICD10 encoding are detailed in Supplementary Material.\u003c/p\u003e \u003cp\u003eFulfillment of the case definition determined an estimated date of arthritis onset. If a patient satisfied multiple definitions, the earliest occurring event determined the disease onset date. All patients were required to fulfill the case definition prior to 16 years of age, to limit the overlap with rheumatoid arthritis or psoriatic arthritis.\u003c/p\u003e \u003cp\u003eWe also tested an alternative definition with maximum age of 17 years at diagnosis. However, due to very similar trends and possibility of greater bias (16 to 18 years represents transitional age), we retained the more conservative definition (\u0026lt;\u0026thinsp;16 years of age).\u003c/p\u003e \u003cp\u003eData Collection and Preparation\u003c/p\u003e \u003cp\u003eUtilizing the adopted case definition, we extracted the absolute number of annual incident and prevalent JIA cases between January 1, 2010 \u0026ndash; December 30, 2022, as well as any events of death recorded among JIA patients. All information was sourced from the repositories of the National Health Fund.\u003c/p\u003e \u003cp\u003eTo better understand changes within the population burden, we calculated several known epidemiological measures:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003ePrevalence rates: one year period prevalence was calculated per annum, using the total number of prevalent cases collected up to December 31 of each year. For each year, the population at risk was adjusted; this represents a conservative estimate, given the decremental population trend. The prevalence rate was then computed as the proportion of prevalent cases divided by the adjusted population at risk, multiplied by 100,000.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eIncidence rates were calculated similarly by dividing the number of new cases observed each year by the population at risk.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eAnalysis and visualization were performed using R version 4.3.3 (R Core Team, 2024) with the use of publically available tidyverse packages.\u003c/p\u003e\u003cp\u003eEthical approval\u003c/p\u003e\n\u003cp\u003eThis analysis relies solely on data obtained from the National Health Fund electronic databases. Obtaining institutional ethical approval was not required.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e3.1 Temporal Trends in JIA Prevalence, Incidence, and Mortality\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBetween 2010-2022, we identified a total 29 758 individuals with JIA up to the age of 16, with incidence ranging between 1381-2394 new JIA cases, per year (details in Table 1). The most common diagnoses were M08.9 (22.3%), M08.8 (20.6%), M08.0 (15.5%), M08.4 (13.6%), M08 (11.7%), M08.3 (4.7%), M08.2 (2.4%), M06 (1.7%), M06.9 (1.2%) and M06.4 (1.2%).\u003c/p\u003e\n\u003cp\u003eBy 2022, the incidence and prevalence rate per 100,000 persons of the GP was calculated as 4.14 and 73.9, respectively. Earlier, between 2010-2015, incidence and prevalance ranged between 6.22-10.3 and 10.4-38.4, respectively. From 2016-2022, both prevalence, but not incidence rates, showed incremental trends with a range of 44.3-69.5 and 3.61-5.94, respectively. For a detailed overview see Figure 1 (raw data in Table 1). Due to stable temporal trends, the mean (95% CI) incidence rate was calculated as 5.65 (4.80-6.50).\u003c/p\u003e\n\u003cp\u003eOverall, death was a very rare event with only 74 cases recorded in total throughout this time. Annual estimates of the mortality rate ranged from 0 (2010-2012), 0.01 (2013-2014, 2017-2020) to 0.04 (2021-2022) per 100 000 individuals.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWith the enhanced population burden of JIA, we investigated potential gender-related differences and identified a stable trend with female predominance (see Figure 2), which corresponds to an average temporal female-to-male incidence ratio of 1.24 (95%CI 1.29-1.18).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3.2 Age Specific JIA Prevalence and Incidence Rates\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn order to understand age-specific dynamics in JIA epidemiology, we examined incidence and prevalence rates across age groups (see Figure 3). For prevalence trends, between 2010-2022, incremental rates were observed for patients with ages between 13-18 years. We observed a plateau phase for children aged 2-6 years and and a late plateau for older children 7-12 years of age.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBy contrast, incidence rates were similar across age groups, with a modest, generally decremental trend. From an exploratory perspective, we also tracked individuals who previously fulfilled our case definition for JIA (from 2010 and thereafter). Increasing prevalence with very stable incidence rate indicates these individuals of transitional age shift towards other diagnoses. While in absolute counts, or respective to age-specific population size (Figure 3), high prevalence was observed for adults with JIA history, but after considering the adult general population size (ie, true denominator), the annual point prevalence ranged from approximately ~0.3-0.5% in 2022.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOf note, we observed that following transition to adult care, in 2022, most patients were not recorded with inflammatory arthritis (N=10\u0026nbsp;289, 66.9%), while rheumatoid arthritis (N=3\u0026nbsp;813, 24.8%), psoriatic arthritis (N=775, 5.0%), ankylosing spondylitis (N=812, 5.3%), Still\u0026rsquo;s disease (N=78, 0.5%) and inflammatory axial disease (N=430, 2.8%) were the most common transitional patterns.\u003c/p\u003e\n\u003cp\u003e3.3 Co-morbidity in JIA\u003c/p\u003e\n\u003cp\u003eFor the pediatric JIA population, we examined trends in comorbidity based on healthcare utilization data. In general, pulmonary (N=13 619, 36.4%), ocular (N=12 437, 39.84%), genitourinary (N=6827, 20.0%), neurologic (N=5664, 16.6%), infectious (M=5329, 15.6%), genetic/growth abnormalities (N=5129, 15.0%), ear disorders (N=5013, 14.7%), gastroenterologic (N=4859, 14.2%), neoplasms (N=4730, 13.8%), psychiatric (N=3032, 8.9%), cardiovascular (N=2751, 8.1%) and hematologic (N=1995, 5.8%) disorders, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe also calculated composite comorbidity scores: the Elixhauser (0 \u0026ndash; 9384, 27.5%; 1 \u0026ndash; 18 638, 54.5%; 2 \u0026ndash; 4 803, 14.1%; 3 \u0026ndash; 1 067, 3.1%; 4 \u0026ndash; 224, 0.7%) and Charlson score (0 \u0026ndash; 25 704, 75.2%; 1- 7 695, 22.5%; 2 \u0026ndash; 729, 2.1%; 3- 47, 0.1%) for the whole pediatric JIA population.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor comparative purposes and consistency with the JIA definition, we also examined a restricted population of JIA subjects (pediatric population \u0026le;16 years of age). The most frequent comorbidities were: allergic rhinitis (N=5 200, 17.5%), scoliosis (N=3 844, 12.9%), bronchial asthma (N=3661, 12.3%), chronic tonsillitis/pharyngitis (N=3 641, 12.2%), acne (N=2 879, 9.7%), growth restriction (N=2 311, 7.8%), congenital hip disorder (N=2 304, 7.7%), viral warts (N=2 268, 7.6%), non-purulent middle ear infection (N=2 120, 7.1%), atopic dermatitis (N=2 014, 6.8%), speech disorder (N=1 833, 6.2%), headache syndromes (N=1 703, 5.7%), heart murmur (N=1 651, 5.6%), reactive arthropathy (N=1646, 5.5%), chorioretinal disorders (N=992, 3.3%) and chronic sinusitis (N=990, 3.3%).\u003c/p\u003e\n\u003cp\u003e3.4 Direct cost of JIA\u003c/p\u003e\n\u003cp\u003eOver 214 285 visits, we calculated healthcare costs of JIA treatment based on claims from public care visits with corresponding primary reimbursement claims, which amount to an annual median (IQR, range) cost of 37.8\u0026euro; (47.4-11.6\u0026euro;, 30.3-86.1\u0026euro;, respectively) per patient. Between 2010-2022, the total cost of JIA treatment amounts to over 3 540 000\u0026euro;, with a median (IQR, range) JIA cost of 232 000\u0026euro; \u0026nbsp; (178 000-309 000\u0026euro;, 103 000-573 000\u0026euro;, respectively) per year (Figure 4). The median (IQR, range) cost per visit was 14.1\u0026euro; (12.1-18.3\u0026euro;, 9.70-33.8\u0026euro;), respectively.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is the first robust study that quantifies the epidemiological burden of JIA in Poland between 2010-2022. We utilized a complex case definition, which combines repeat ICD-10 encoding, prescription data and accounts for hierarchical structure in healthcare. We calculated prevalence and incidence rates for the JIA population at 73.9 and 4.14 per 100 000 persons in 2022.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo date, there have been no population-based studies for JIA in Poland. Previously, estimates were derived from an observational, cohort study conducted on a regional level\u003csup\u003e15\u003c/sup\u003e. Another prior domestic report for 2008-2012 aimed to evaluate JIA burden, though the authors focused on regional and rural-urban differences, while also utilizing singular ICD-10 claims to identify JIA\u003csup\u003e6\u003c/sup\u003e. In this study, we observed that incidence of JIA is stable and potentially decremental over time. Whether this corresponds to a true decrease incidence or reflects healthcare restriction in the pandemic years (among other potential confounding factors) is currently unknown. However, with the often chronic nature of JIA, the prevalent population of patients is growing (on par with the aging general population). In broad terms, our findings are comparable with those of other studies. Recent studies from the UK reported an overall age-standardized incidence rate at 5.61 and prevalence rate of 43.5 per 100\u0026nbsp;000 persons in 2018\u003csup\u003e16\u003c/sup\u003e. Using a database of 3-4 mln patients, Horneff et al. reported incidence rates between 34-60 and 133-168 per 100\u0026nbsp;000 patients was reported\u003csup\u003e17\u003c/sup\u003e. In Nordic countries, incidence and prevalence rates tend to be higher (18.5 and 159, respectively). A prior systematic review synthesized the pooled incidence and prevalence rates with an estimate of 7.8 (95% CI 7.6, 8.1) and 20.5 (95% CI 19.8, 21.3), respectively. In historical cohorts (1990\u0026rsquo;s and earlier), the prevalence was estimates ranged between 60 \u0026ndash; 400 per 100\u0026nbsp;000 for JIA\u003csup\u003e18\u003c/sup\u003e. Gathering additional epidemiological data is of high importance due to considerable variability \u0026nbsp;on a geographical and ethnic level, both in disease burden and course\u003csup\u003e19\u0026ndash;21\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eWhile JIA may attenuate throughout young adulthood, the majority of patients exhibit ongoing signs of disease\u003csup\u003e22\u003c/sup\u003e, and likely transition into undifferentiated or adult form of arthritis. A study by Glerup et al. based on a cohort study from Scandinavian countries shows the high burden of disease that persists into adulthood, with only one third of patients achieving remission, despite being diagnosed in the early biologic era\u003csup\u003e10\u003c/sup\u003e. Delayed introduction of biologic DMARDS leads to enhanced disability and quality of life, including lower chances for drug-free remission after transitioning into adulthood\u003csup\u003e23\u003c/sup\u003e. In contrast to earlier epidemiologic studies, we did not restrict the scope of the investigation to individuals 16 years or younger, as we know little about transitional age JIA. We observed that a substantial proportion of JIA patients are young adolescents or adults, which is important from a management perspective. Transition into adulthood is tied to a change in the healthcare provider, but also carries psychosocial considerations. Adherence and illness coping is worse in adolescence\u003csup\u003e24\u003c/sup\u003e. Despite initially high effectiveness of biologics, long term retention is suboptimal\u003csup\u003e25\u003c/sup\u003e. A single monocentric study from Poland showed that adult JIA is highly heterogenous and difficult to treat, with less than 50% of patients meeting criteria for adult types arthritis\u003csup\u003e26\u003c/sup\u003e. Our findings emphasize the population burden, and further showcase the importance of future studies of the transitional JIA population.\u003c/p\u003e\n\u003cp\u003eWe also examined the most common chronic causes for healthcare contact among JIA patients. Our results are similar to a recent report by Horneff et al. from Germany, who observed the common concurrent presence of atopic dermatitis, allergic diseases and others\u003csup\u003e17\u003c/sup\u003e. However, we did not observe such a high rate of uveitis (Horneff et al. - 11%), with the most common ocular condition (after additional analysis) reported as refractive disorders (21.9%), strabismus (3.5%) and anterior uveitis (3.3%), as would be expected. Haslak et al. reported allergic rhinitis, attention disorders and atopic dermatitis as the most common concurrent conditions\u003csup\u003e27\u003c/sup\u003e. Other reports from smaller cohorts indicate the common prevalence of uveitis (18%), allergic rhinitis (14.5%), migraine (8.7%) and atopic dermatitis (8.7%)\u003csup\u003e28\u003c/sup\u003e, which may markedly differ from population estimates due to sampling heterogeneity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe limitations of this study include retrospective character and utilization of secondary sources to establish a proxy diagnosis. Incidence calculations are based on the use of a denominator of population size at-risk of developing disease at a given time (per year), which does not always equate to person-years at-risk, which is the ideal case scenario for epidemiologic estimates\u003csup\u003e29\u003c/sup\u003e. While we utilized fixed population size at a given time, the chronicity of JIA and young age distribution limits the bias associated with incomplete follow-up (i.e., an imprecise denominator). We are unable to account for additional sources of bias such as miscoding, incompleteness or errors within the diagnostic and therapeutic process, which would results in false fulfillment of the JIA definition. While the use of a complex case definition and near complete population coverage with public healthcare are the strengths of this report, the validity of these estimates requires further replication in population cohorts. Geographical differences are likely to be present throughout Europe, but due to the demographic and ethnic structure of Poland, this cohort is likely representative of Central-Eastern Europe.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eProviding reliable epidemiological results regarding population burden of JIA is important for the policy maker in healthcare resource allocation and identifying areas of priority for intervention. This comprehensive nation-wide study from Poland examines population prevalence and incidence of JIA across 2010-2022. Utilizing a complex definition integrating ICD-10 encoding and prescription data, relatively high population burden can be ascertained, as compared with the rest of Europe. Despite a potential declining trend in JIA incidence over time, the prevalent population is growing, highlighting the importance of tailored care as patients transition into adulthood.\u0026nbsp;\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003eEthics approval: Not necessary due to the retrospective nature of the data; data were anonymized prior to analysis with subgroup size \u0026gt; 5 cases\u003c/p\u003e\n\u003cp\u003eConsent for publication: Not applicable\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials: Raw data is publically available in abridged form on the online platform for Strategic Analyses published by the Ministry of Health, but also available in greater detail upon reasonable request from the authors.\u003c/p\u003e\n\u003cp\u003eCompeting interests: none to declare\u003c/p\u003e\n\u003cp\u003eFunding: This paper was prepared as a part of the \u0026quot;Maps\u0026nbsp;of\u0026nbsp;Health\u0026nbsp;Needs\u0026nbsp;\u0026ndash;\u0026nbsp;Database\u0026nbsp;of\u0026nbsp;Systematic\u0026nbsp;and\u0026nbsp;Implementation\u0026nbsp;Analysis\u0026quot; (grant number POWR.05.02.00-00-0149/15) and \u0026lsquo;Integrated Analytical Platform\u0026rsquo; projects (grant number POPC.02.02.00-00-0015/18-00), both co-financed by the European Union from the European Social Fund and European Regional Development Fund respectively.\u003c/p\u003e\n\u003cp\u003eAuthor contributions: Conceptualization: ZZ, BB, MK-W, MSz, BK; Methodology: MK-W, MSz, BB, ZZ, KP, BK; Literature review, preparation and writing the original article: MK-W, MSz, MSt, BB, ZZ; Visualisation: MK-W, MSz, KB, KP; Reviewing and editing the manuscript: MK-W, MSz, KB, BB, ZZ, MO, KP, JS, JJ, MŚ, MB, AŚ, BK; Supervision: MK-W, MSz, BB, ZZ, BK. All authors fulfill all authorship criteria by ICMJE and take full responsibility for the accuracy and integrity of all aspects of the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePetty, R. E. \u003cem\u003eet al.\u003c/em\u003e International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. \u003cem\u003eJ Rheumatol\u003c/em\u003e \u003cstrong\u003e31\u003c/strong\u003e, 390\u0026ndash;392 (2004).\u003c/li\u003e\n\u003cli\u003ePalman, J., Shoop-Worrall, S., Hyrich, K. \u0026amp; McDonagh, J. E. Update on the epidemiology, risk factors and disease outcomes of Juvenile idiopathic arthritis. \u003cem\u003eBest Pract Res Clin Rheumatol\u003c/em\u003e \u003cstrong\u003e32\u003c/strong\u003e, 206\u0026ndash;222 (2018).\u003c/li\u003e\n\u003cli\u003eSavolainen, E., Kaipiainen-Sepp\u0026auml;nen, O., Kr\u0026ouml;ger, L. \u0026amp; Luosuj\u0026auml;rvi, R. 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K. \u003cem\u003eet al.\u003c/em\u003e Epidemiology of juvenile idiopathic arthritis in a multiethnic cohort: ethnicity as a risk factor. \u003cem\u003eArthritis Rheum\u003c/em\u003e \u003cstrong\u003e56\u003c/strong\u003e, 1974\u0026ndash;1984 (2007).\u003c/li\u003e\n\u003cli\u003eNordal, E. \u003cem\u003eet al.\u003c/em\u003e Ongoing disease activity and changing categories in a long-term nordic cohort study of juvenile idiopathic arthritis. \u003cem\u003eArthritis Rheum\u003c/em\u003e \u003cstrong\u003e63\u003c/strong\u003e, 2809\u0026ndash;2818 (2011).\u003c/li\u003e\n\u003cli\u003eOliveira Ramos, F. \u003cem\u003eet al.\u003c/em\u003e Influence of the timing of biological treatment initiation on Juvenile Idiopathic Arthritis long-term outcomes. \u003cem\u003eArthritis Res Ther\u003c/em\u003e \u003cstrong\u003e25\u003c/strong\u003e, 177 (2023).\u003c/li\u003e\n\u003cli\u003eKirchner, S. \u003cem\u003eet al.\u003c/em\u003e Adherence, helpfulness and barriers to treatment in juvenile idiopathic arthritis - data from a German Inception cohort. \u003cem\u003ePediatr Rheumatol Online J\u003c/em\u003e \u003cstrong\u003e21\u003c/strong\u003e, 31 (2023).\u003c/li\u003e\n\u003cli\u003eMour\u0026atilde;o, A. F. \u003cem\u003eet al.\u003c/em\u003e Effectiveness and long-term retention of anti-tumour necrosis factor treatment in juvenile and adult patients with juvenile idiopathic arthritis: data from Reuma.pt. \u003cem\u003eRheumatology (Oxford)\u003c/em\u003e \u003cstrong\u003e55\u003c/strong\u003e, 697\u0026ndash;703 (2016).\u003c/li\u003e\n\u003cli\u003eFelis-Giemza, A., Chmurzyńska, K., Kołodziejczyk, B. \u0026amp; Gazda, A. Revising diagnosis of juvenile idiopathic arthritis in adults: a single-center retrospective study. \u003cem\u003eRheumatol Int\u003c/em\u003e \u003cstrong\u003e43\u003c/strong\u003e, 1307\u0026ndash;1311 (2023).\u003c/li\u003e\n\u003cli\u003eHaşlak, F. \u003cem\u003eet al.\u003c/em\u003e Non-Rheumatic Chronic Comorbidities in Children with Juvenile Idiopathic Arthritis. \u003cem\u003eTurkish archives of pediatrics\u003c/em\u003e \u003cstrong\u003e58\u003c/strong\u003e, 212\u0026ndash;219 (2023).\u003c/li\u003e\n\u003cli\u003eRaab, A. \u003cem\u003eet al.\u003c/em\u003e Comorbidity profiles among adult patients with juvenile idiopathic arthritis: results of a biologic register. \u003cem\u003eClin Exp Rheumatol\u003c/em\u003e \u003cstrong\u003e31\u003c/strong\u003e, 796\u0026ndash;802 (2013).\u003c/li\u003e\n\u003cli\u003eSpronk, I. \u003cem\u003eet al.\u003c/em\u003e Calculating incidence rates and prevalence proportions: not as simple as it seems. \u003cem\u003eBMC Public Health\u003c/em\u003e \u003cstrong\u003e19\u003c/strong\u003e, 512 (2019).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Annual number of prevalent and incident JIA cases, as well as death.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"top\"\u003e\n \u003cp\u003eYear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\"\u003e\n \u003cp\u003ePrevalent JIA, N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\"\u003e\n \u003cp\u003eIncident JIA, N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\"\u003e\n \u003cp\u003eMortality, N\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e6 117.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 163.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e8 088.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 972.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e10 275.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 190.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e12 380.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 107.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e14 766.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 394.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e17 044.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 283.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e19 263.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 228.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e21 341.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2 087.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e23 294.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 959.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e25 216.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 930.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e26 583.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 381.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e28 147.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 578.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e29 758.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.252525252525253%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 625.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.242424242424242%\" valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"proj","sideBox":"Learn more about [Pediatric Rheumatology](http://ped-rheum.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/proj/default.aspx","title":"Pediatric Rheumatology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"epidemiology, incidence, inflammatory arthritis, juvenile idiopathic arthritis, prevalence, morbidity, disease occurrence","lastPublishedDoi":"10.21203/rs.3.rs-4650683/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4650683/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOver time, the revised juvenile idiopathic arthritis (JIA) classification and a shift towards goal-oriented treatment with disease-modifying drugs (DMARDs) may have changed the epidemiologic landscape of JIA.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePublic healthcare utilization records from the National Health Fund (NHF) were screened between 2010\u0026ndash;2022. For individuals aged\u0026thinsp;\u0026lt;\u0026thinsp;16 years, we utilized a narrow JIA case definition combining repeat ICD-10 encoding with DMARDs prescription based on ATC codes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf 37 mln patients in the NHF database, 29 758 individuals fulfilled our case definition. Over time, the number of newly detected cases ranged between 1381\u0026ndash;2394. In 2022, the incidence and prevalence rate per 100,000 persons was calculated at 4.14 and 73.9, respectively. Stable incidence trends were observed with mean incidence rate estimated at 5.65 (95%CI 4.80\u0026ndash;6.50). Gender-related differences confirm JIA susceptibility among females. Among JIA-related comorbidities, allergic rhinitis (N\u0026thinsp;=\u0026thinsp;5 200, 17.5%), bronchial asthma (N\u0026thinsp;=\u0026thinsp;3 661, 12.3%) and growth restriction (N\u0026thinsp;=\u0026thinsp;2 311, 7.8%) were common. Over 214 285 visits, we calculated the total and median cost of JIA treatment at over 3.54 mln\u0026euro; and 232 000\u0026euro;, respectively.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis is a comprehesive, nationwide study that provides a contemporary estimate for JIA burden and cost in Poland.\u003c/p\u003e","manuscriptTitle":"Epidemiology and comorbidity of juvenile idiopathic arthritis in Poland – a nationwide study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-27 00:32:54","doi":"10.21203/rs.3.rs-4650683/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2024-07-03T18:52:42+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-03T09:55:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-02T00:53:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Rheumatology","date":"2024-06-27T15:07:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"proj","sideBox":"Learn more about [Pediatric Rheumatology](http://ped-rheum.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/proj/default.aspx","title":"Pediatric Rheumatology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fced0ceb-b5d5-48bb-ae44-108f754a706a","owner":[],"postedDate":"July 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-03-31T16:03:37+00:00","versionOfRecord":{"articleIdentity":"rs-4650683","link":"https://doi.org/10.1186/s12969-025-01065-8","journal":{"identity":"pediatric-rheumatology","isVorOnly":false,"title":"Pediatric Rheumatology"},"publishedOn":"2025-03-28 15:57:56","publishedOnDateReadable":"March 28th, 2025"},"versionCreatedAt":"2024-07-27 00:32:54","video":"","vorDoi":"10.1186/s12969-025-01065-8","vorDoiUrl":"https://doi.org/10.1186/s12969-025-01065-8","workflowStages":[]},"version":"v1","identity":"rs-4650683","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4650683","identity":"rs-4650683","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}