BMJ open · 2025
Клиническая характеристика пациентов с коморбидным IBD и MS и соответствующее влияние услуг в условиях вторичной медицинской помощи в Англии: ретроспективное когортное исследование.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Машинный перевод · не проверен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Coxam Baptiste, Sheikh Faisal, Kew Hanna, Fraser Maeve, Levick Bethany, Rolfe Chris, Ellison Tracey, Pollock Kevin G
Аннотация
ЦЕЛИ: Воспаленные кишечные заболевания (ИБД) и множественный склероз (МС) являются подстрекательскими заболеваниями, возникающими в результате взаимодействия генетических и экологических факторов. Цель этого исследования состоит в том, чтобы описать распространенность пациентов, которым диагностированы оба заболевания среди лиц, получающих больничное обслуживание в Англии, а также характерные особенности и использование медицинских ресурсов (НСРУ) таких пациентов. DESIGN: Это исследование является ретроспективным когортным исследованием наблюдений. СИТТИНГ: Исследование проводилось на основе вторичного использования базы данных статистики эпизоды английских больниц. В рамках программы < < ХЕС > > регистрируются услуги, оказываемые больницами Англии, и соответствующие диагнозы.УЧАСТНИКИ: Пациенты, у которых был диагностический код для IBD или MS, зарегистрированный в HES в период с января 2014 и май 2020 были включены. Пациенты были классифицированы как имеющие каждый диагноз индивидуально или оба диагноза, и в этом случае они были дополнительно классифицированы в зависимости от времени. Меры, принимаемые в ходе первого и второго цикла: Главным результатом этого было распространение среди пациентов зарегистрированного диагноза в виде IBD, MS или обоих в течение учебного периода. Вторичные итоговые показатели включали демографические и клинические характеристики пациентов, а также HCRU 6 Месяцами до и после диагностирования интереса.РЕЗУЛЬТАТЫ: Из общей группы 352 698 пациенты, 1016 (В тыс.0.3%) имел оба диагноза. Среди тех, у кого есть оба, 29.8% (В тыс.303) имел запись IBD сначала, 40.5% (В тыс.411) впервые диагностировали MS и 29.7% (В тыс.302) имел первую запись обоих диагнозов в одном и том же эпизоде. Из общей группы, 80.9% (В тыс.285 439) пациентов с одним диагнозом IBD, и 18.8% (В тыс.66 243) пациентов с одним диагнозом MS. ВЫВОДЫ: Население с двойным диагнозом МБД и МБ больше, чем сообщалось ранее, и свидетельствует о частых контактах со вторичной медицинской помощью.
Оригинал публикации
Clinical profile of patients with comorbid IBD and MS, and associated service impact in England's secondary care setting: a retrospective cohort study.
OBJECTIVES: Inflammatory bowel diseases (IBDs) and multiple sclerosis (MS) are inflammatory diseases resulting from an interplay of genetic and environmental factors. This study aims to describe the prevalence of patients diagnosed with both conditions among those receiving hospital care in England, as well as the characteristics and healthcare resource use (HCRU) of such patients.
DESIGN: This study is a retrospective observational cohort study.
SETTING: The study was conducted through secondary use of the English Hospital Episode Statistics (HES) Database. HES records care delivered by hospitals in England and associated diagnoses.
PARTICIPANTS: Patients who had a diagnosis code for either IBD or MS recorded in HES between January 2014 and May 2020 were included. Patients were classified as having each diagnosis individually or as having both diagnoses, in which case they were further categorised based on temporal occurrence.
PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the prevalence of patients with a recorded diagnosis of either IBD, MS or both during the study period. Secondary outcome measures included patient demographic and clinical characteristics, as well as HCRU in the 6 months before and after the diagnosis of interest.
RESULTS: From an overall cohort of 352 698 patients, 1016 (0.3%) had both diagnoses. Among those with both, 29.8% (303) had a record of IBD first, 40.5% (411) had MS diagnosed first and 29.7% (302) had the first record of both diagnoses in the same episode. From the overall cohort, 80.9% (285 439) of patients had a single diagnosis of IBD, and 18.8% (66 243) of patients had a single diagnosis of MS.
CONCLUSIONS: The population with a dual diagnosis of IBD and MS is larger than previously reported and shows evidence of frequent interactions with secondary care.
Перевод полного текста: Перевод в очереди
Читать найденный полный текст
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .
STRENGTHS AND LIMITATIONS OF THIS STUDY
A large population of patients with dual multiple sclerosis (MS) and inflammatory bowel disease (IBD) diagnoses is described. The study includes all relevant patients from across English National Health Service (NHS) hospital care during the study period.
The Hospital Episode Statistics (HES) Database allows for linkage across hospital-admitted patient care, outpatient care and accident and emergency attendance, including the clinical specialists delivering care, providing a comprehensive and complete view of the cohorts’ wider hospital care use and pathways.
HES data only include confirmed diagnoses reported as part of hospital attendance, and International Classification of Diseases V.10 codes could not be used to identify MS subgroups. It was not possible to confirm the date of the cohort’s first diagnosis for either MS or IBD and, therefore, to describe the modality of their diagnosis or the time between each diagnosis first being made.
Only grouped data reporting high-cost drug use are available in HES, and as such, no pharmaceutical interventions for either diagnosis are reported in this study.
As the data analysis was descriptive, we are unable to make inferences about the significance of the differences between the cohorts or the presence or direction of any causal relationships.
Introduction
Inflammatory bowel disease (IBD) is the chronic inflammation of the bowel. Crohn’s disease and ulcerative colitis are the archetypal forms of IBD. In the UK, estimates of IBD incidence are 21–37.5 per 100 000 person-years. 1
Multiple sclerosis (MS) is a chronic inflammatory degenerative condition affecting the central nervous system. 2 MS has a higher prevalence in women 3 4 and typically affects young adults. In England, MS has an estimated incidence of 8–11 per 100 000 person-years. 5
IBD and MS each result from genetic and environmental factors leading to aberrant and dysregulated immune responses, heterogeneous phenotypes and clinical features. 6 Studies describe a potential relationship between the incidence of MS and IBD 7 8 ; however, most are based on small populations. A systematic review of 17 studies reported that patients with MS had a higher risk of developing Crohn’s disease than controls, 9 and patients with IBD had a higher prevalence of MS than controls. One study in the UK using the General Practice Research Database established that the incidence of MS was higher in patients with IBD compared with matched controls, and another showed a higher incidence of IBD in patients with MS. 10 11 Epidemiological and clinical data on the prevalence of dual diagnosis of MS and IBD and any potential functional relationship is sparse.
A recent genetic association study identified shared genetic traits between MS and IBD, and a Mendelian randomisation study reported evidence that the direction of the causal pathway is from MS to IBD rather than the reverse. 12
Co-occurrence of the diagnoses can impact patients’ burden on healthcare needs and resource utilisation, including the likelihood of greater use of treatment to manage two conditions. Treatment options for one disorder may be contraindicated in patients with the other disorder. 13 Additionally, there is a lack of evidence about clinical outcomes for patients with co-occurring diagnoses and their healthcare resource use (HCRU). This study aims to describe the scale of comorbid IBD and MS diagnosis among patients treated in hospitals in England and to describe this population, including relevant clinical characteristics and outcomes. This data will provide insight into the scale of comorbid diagnosis in patients in England associated with the burden. If trends observed in other settings are reflected here, it could indicate a population that could benefit from specific care planning and approaches for patients with comorbid IBD and MS in the NHS in England. The primary objective of this study was to determine the prevalence of patients treated in hospitals in England with recorded diagnoses for MS and IBD. We additionally describe patient characteristics and disease burden; assess how these diseases present and their progression; quantify HCRU and pathways of care in this population of patients and describe the prevalence of other comorbidities in patients with MS and IBD.
Methods
Participants, study design and setting
This retrospective, observational, real-world study describes adults in England with a hospital-recorded diagnosis of either IBD, MS or both. This study used the Hospital Episode Statistics (HES) Database, an administrative database which contains details for all admissions, Accident and Emergency (A and E) attendances and outpatient appointments at all NHS hospitals in England. 14 In 2020–2021, over 16 million consultant care episodes were recorded. 15 HES and Secondary Use Service data are subject to an extensive quality control and checking process 16 and, as a result, have high accuracy and validity for research use. 17 Data were available from 1 January 2012 to 31 July 2022. A washout period of 2 years from IBD and MS diagnoses was implemented to increase the certainty of multiple diagnosis status and the order of diagnoses. The study period for diagnosis status was, therefore, from 1 January 2014 to 30 June 2020.
Eligible participants had a recording of a WHO International Classification of Diseases V.10 18 (ICD-10) code indicating IBD (K50-51) or MS (G35) at any time during the study period and were adults or young adults (16 years or older) at the date of their first relevant diagnosis recording during the study period (see figure 1 ). This may not represent patients’ first-ever or definitive diagnosis for either the first or second condition observed.
Study design visualisation. HCRU, healthcare resource use; IBD, inflammatory bowel disease; ICD-10, International Classification of Diseases V.10; MS, multiple sclerosis.
Diagnosis pattern groups
Patients were grouped as those with a single diagnosis who presented with either an IBD or MS diagnosis code during a hospital spell or as patients with both diagnoses. Patients with a second diagnosis were grouped according to which diagnosis was recorded on the earliest date in their records. Patients with both diagnosis codes recorded for the first time during the same spell were grouped as having both diagnoses together.
Data variables
Primary objectives
The study’s primary objective included recording the order and date of diagnosis of IBD and MS, if there was a dual diagnosis, and the diagnosis patterns when this was the case.
Secondary objectives
Frequencies of each diagnosis/diagnosis group were summarised, alongside key patient characteristics, including age at first relevant diagnosis, gender, ethnicity, deprivation index and NHS region of patient registration. The frequency of MS-related comorbidities, including optic neuritis (indicated by an ICD-10 code of G36.0) and 19 demyelination disorders (indicated by an ICD-10 code of G36.8, G37.8 or G37.9), was reported for all included patients. The specific IBD diagnosis recorded (Crohn’s disease or ulcerative colitis) was reported for patients with an IBD diagnosis.
We summarised key comorbidities reported in the literature as commonly observed or associated with a diagnosis of either IBD or MS. 19 20 Patients were classified as having a diagnosis of one of these comorbidities or not, based on their recorded diagnoses in HES APC (Admitted Patient Care) and OP (Outpatient (appointments)). A full code list for these diagnoses is provided in online supplemental material S1 .
In cases of dual diagnosis, we report clinical outcome variables and HCRU outcomes for the 6 months prior to the first diagnosis of interest (diagnosis date 1 (DD1)), up until 6 months after the second diagnosis (DD2). HCRU outcome variables included total hospital attendance after the first diagnosis and before the second diagnosis, as well as admission method (elective/non-elective). The use of high-cost drugs (HCDs) was reported: HCD is a designation applied to drugs with a disproportionately high cost that typically requires specialist involvement to administer or monitor. 21 Additionally, data were collected on specialty care delivered (clinical specialties of the units that patients were admitted to) and reasons for admission (diagnosis attributed as the reason for admission) in the 6 months following DD2.
No medicines are reported for patients in this study, as only a restricted proportion of prescriptions are available in HES.
Analysis
Data were analysed using the SQL Management Studio V.18, R statistical software V.4.0.4 and Microsoft Excel. Analyses were descriptive in nature, so no inferential statistics were conducted. Distributions and descriptive statistics of both central tendency (medians and arithmetic or geometric means) and dispersion (SD and IQR) were presented for quantitative variables. Nominal variables were described with frequencies and percentages, while continuous variables also have medians and IQR described. All percentages were reported to the nearest whole number. Analyses of study variables were conducted, excluding missing data, in which case the number and percentage of patients with missing data were reported for each variable.
Patient and public involvement statement
Patients or the public were not involved in the design or conduct of this study. This work uses data provided by patients and collected by the NHS as part of their care and support.
Results
Frequency of MS and IBD in hospital-treated patients in England, and demographic information of MS and IBD in each diagnosis pattern group
The overall cohort size of patients with either an IBD or MS diagnosis recorded during the study period was 352 698. From this overall cohort, 81.2% (286 455) of patients had an IBD diagnosis, and 19.1% (66 243) had an MS diagnosis. From the overall cohort, 80.9% (285 439) of patients had a single diagnosis of IBD, and 18.8% (66 243) had a single diagnosis of MS. The prevalence of IBD in patients with MS was 1.51% (1016/67 259), and MS in patients with IBD was 0.35% (1016/286 455).
Online supplemental materials S2, table 1 summarises the number of patients with each diagnosis, the specific IBD diagnosis in patients with IBD and the MS-related diagnoses in each group. From the overall cohort, 0.3% (1016) of patients had both diagnoses recorded. From the cohort with a dual diagnosis (n=1016), 40.5% (411) of patients had MS diagnosed first, 29.8% (303) had IBD diagnosed first and 29.7% (302) had both diagnoses first recorded during the same spell.
Among patients with IBD in the overall cohort, 68.5% (187 617) were specifically diagnosed with ulcerative colitis and 42.0% (120 245) with Crohn’s disease. Patients with a single diagnosis of MS had a 0.4% (243) prevalence of optic neuritis, patients with a single diagnosis of IBD had <0.01% (10) prevalence of optic neuritis and patients with a dual diagnosis had a 0.3% prevalence of optic neuritis. The prevalence of other demyelination disorders was 0.3% (1054) in the overall cohort. In patients with a single diagnosis of MS, the prevalence of other demyelination disorders was 1.5% (964). In patients with a dual diagnosis, there was a prevalence of 2.9% (29) of other myelination disorders. No patients with a single IBD diagnosis had a recorded diagnosis for other demyelination disorders.
Population demographic and clinical characteristics
Online supplemental materials S2, table 2 summarises the demographic information for the overall cohort and the individual diagnosis pattern groups. The mean (SD) age at the index for the overall cohort was 52 (18.7) years. In the single diagnosis cohort, patients with MS had a higher mean (SD) age of 53.3 (16) years compared with patients with IBD, who had a mean age (SD) of 51.7 (19.2) years. Patients with a dual diagnosis, who were diagnosed with IBD first and then MS, had a mean (SD) age of 49.9 (16.8) years; patients diagnosed with MS first and then IBD had a mean (SD) age of 53.6 (14.9) years and patients diagnosed with MS and IBD during the same spell had a mean (SD) age of 58.2 (13.9) years.
In the overall cohort, there were more females than males (55.2%; 194 736). When looking at the single diagnosis groups, this difference was more apparent in the MS group compared with the IBD group, with 70% (46 350) female in the MS group versus 51.8% (147 703) female in the IBD group. In the dual diagnosis cohort, there were more females than males (67.2%; 683). There was a higher proportion of females in patients with MS with an IBD diagnosis compared with patients with IBD with an MS diagnosis (71.3% (293) vs 65.3% (198)).
In terms of ethnicity, the majority of the overall cohort (90.4%, 273 011) was white. This is reflected across the diagnosis group cohorts, which range from 89.9% (219 854) white (IBD only) to 97% (262) white in the cohort where both diagnoses are seen for the first time in the first episode. There was little difference in the proportion of cohorts in each decile of the Multiple Deprivation Index.
Comorbidities of interest
Online supplemental materials S2, table 3 , summarises other comorbidities of interest in the cohort. In patients with Parkinson’s, the prevalence in the dual diagnosis groups was 2.3% (23) compared with 0.9% (3340) of the overall cohort. The prevalence of Parkinson’s as a comorbidity in patients with IBD with an MS diagnosis was 3.0% (9).
HCRU and outcomes
Prior HCRU
In the overall cohort, when categorising the total number of hospital attendances, the largest proportion of patients (63.9%; 225 390) had between 1 and 5 total attendances. The large majority of the overall cohort (88.0%; 310 278) had no inpatient admissions in the 6 months prior to their first diagnosis. Online supplemental materials S2, table S4 summarises the HCRU in all diagnosis groups in the 6 months prior to their first diagnosis.
HCRU during follow-up
A large proportion of patients with IBD with a subsequent MS diagnosis were given HCDs (11.3%; 32). In the overall cohort, 5.7% of patients received HCDs (20 145), and in the dual diagnosis cohort, 6.2% of patients did (60). A greater proportion of patients with a dual diagnosis had more total hospital attendances compared with patients with a single diagnosis: 29.0% (281) of patients with a dual diagnosis had 6–12 hospital attendances compared with 20.4% (71 772) of the overall cohort, and 10.0% (97) of the dual diagnosis cohort had 13–24 total hospital attendances compared with 5.1% (18 125) of the overall cohort. Online supplemental materials S2, table 4 summarises the HCRU in the 6 months after the second diagnosis.
Discussion
This study reports the frequency of a dual diagnosis of IBD and MS among patients treated in English hospitals. This study is one of the few in Europe (or internationally) to describe the prevalence of such dual diagnoses at the national level and as observed in hospital care. This up-to-date investigation of the data also describes key demographic and HCRU measures for the population, with diagnoses recorded for both conditions. These data indicate there is a patient population who could benefit from specialist care planning and design across gastroenterology and neurology care and an opportunity to coordinate existing good practices for patients with comorbid diagnoses into a cross-provider approach.
The study identified over 1000 patients with a dual diagnosis of MS and IBD. Among patients with a dual diagnosis, an initial diagnosis of MS with a secondary diagnosis of IBD (411 patients) was most common, followed by an initial diagnosis of IBD with a secondary diagnosis of MS (303 patients) and both diagnoses first recorded during the same spell (302 patients).
Evidence on epidemiological and functional associations between IBD and MS is developing: this study is one of the largest such studies conducted in Europe using secondary care data. However, our results are consistent with other studies in England and in other geographies. The prevalence of MS in patients with IBD of 0.3% is in line with a systematic review and meta-analysis study, although the estimated prevalence of 1.51% of IBD in patients with MS is higher than the 0.6% reported in the same study. 9 A study conducted using the Disease Analyser Database in Germany reported a prevalence of MS diagnosis of 0.9% in patients with Crohn’s disease (CD) and 0.7% in patients with Ulcerative Colitis (UC) after 10 years of follow-up. 22 Our findings further align with those of a study using the General Practice Research Database in England that showed that the incidence of MS was higher in patients with IBD compared with matched controls, and they also align with the findings of a US questionnaire study showing a higher incidence of IBD in patients with MS. 7 8
A larger proportion of females had a dual diagnosis compared with males (67.2% vs 32.8%). The large predominance of females in the dual diagnosis group is likely driven by the general gender imbalance associated with MS. 23 White patients were over-represented in the cohort based on the general population of England (the 2021 census estimated that 81.7% of the population was white). 24 This corresponds with studies showing that both IBD and MS disproportionately affect people of European descent 25 26 and may be an important factor when comparing the prevalence of an IBD and MS dual diagnosis across geographies.
The frequency of certain comorbidities, such as depression, anxiety and Parkinson’s disease, was high in the dual-diagnosis cohort. Studies have shown shared causal pathways between inflammatory diseases such as MS and IBD and psychiatric diseases. 27 28 Definitive identification of a relationship between these conditions (and the direction of this) would require further investigation. Aside from potential shared functional pathways, these results indicate that the population with comorbid IBD and MS may also need more broadly clinically complex care, reiterating the advantages of cross-specialist cooperation.
HCRU prior to the initial diagnosis in each diagnosis pattern group was similar. There was a particularly high frequency of HCD use in patients with IBD with an MS diagnosis in the 6 months following the second diagnosis (11.3% of patients), which may indicate complex specialist care needs in this group. HCRU in the 6 months following the second diagnosis reveals that hospital attendance is more frequent in patients with a dual diagnosis after the second diagnosis. This aligns with observations in other studies of this population 13 and corresponds with a second separate diagnosis likely requiring more hospital care and resource use in general. There could be potential patient benefits and service level efficiencies in designing a targeted care approach for patients with comorbidities.
Limitations
HES data include only confirmed diagnoses reported as part of hospital attendance, and as such, this study may underestimate the true number of cases nationally. While ICD-10 coding in the HES dataset allows for the identification of the specific IBD diagnosis, the MS subgroup is not coded. For that reason, we are unable to consider the relationship between subtypes of MS (and associated morbidity) and the presence of a dual diagnosis.
This study does not include diagnoses only recorded in the data outside of the study period or not noted in the HES Database. However, the inclusion of a 2-year washout period prior to the initiation of data collection was implemented to mitigate the impact of this uncertainty, particularly from very recent diagnoses prior to the study period. Both IBD and MS diagnoses are expected to receive some level of specialist treatment in the UK NHS, making this most likely to create uncertainty around the timing of the relevant diagnoses in relation to the observed codes rather than general diagnosis status.
As this study was descriptive, we cannot make inferences about the significance of the differences between the cohorts, the presence or direction of any causal relationships or any underlying functional pathways for the co-occurrence of the two conditions. This initial exploratory descriptive study indicates that the population with co-diagnosis is present in the UK NHS and such relationships could be explored formally.
Conclusions
We describe the population of patients with a diagnosis of both IBD and MS who received hospital care across England. This cohort shows evidence of frequent interactions with secondary care, and patients with additional comorbidities, including Parkinson’s disease and depression. Future research should investigate whether the observed variations in HCRU are related to shared disease pathways, age-related effects or artefacts of shared clinical care such as medications.
Clinical pathways and management of patients with both diagnoses should reflect their clinical needs in relation to clinical and demographic characteristics, comorbidities, HCRU and treatment management. This study offers a large data perspective that provides an accurate account of the prevalence of dual diagnoses in the cohort and its high burden of disease.
Supplementary material
Acknowledgements
Editorial support (in the form of writing assistance, including preparation of the draft manuscript under the direction and guidance of the authors, collating and incorporating authors’ comments for each draft, assembling tables and figures, grammatical editing and referencing) was provided by Yusuf Daniju, a former employee of OPEN Health, and was funded by Bristol Myers Squibb. Sue Beecroft (Harvey Walsh, at the time of the study initiation) assisted with data access and study design. Expert advice on the direction of the manuscript was provided by the clinical steering committee of Dr. Chris McGuigan, Professor Daniel R. Gaya, Dr. Martin Duddy and Professor Subrata Ghosh.
Footnotes
Funding: This study was funded by Bristol Myers Squibb. Harvey Walsh (operating as OPEN Health) received funding from Bristol Myers Squibb to support this study. The study was supported by Bristol Myers Squibb (Uxbridge, UK). Bristol Myers Squibb had a role in the design of the study, analysis and interpretation of the data, review and approval of the manuscript and decision to submit the manuscript for publication.
Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online ( https://doi.org/10.1136/bmjopen-2024-088808 ).
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Not applicable.
Ethics approval: Harvey Walsh, part of the OPEN Health group, is licensed by NHS Digital to receive Hospital Episode Statistics data under the data sharing agreement DARS-NIC-05934-M7V9K, which contains approval to use the data for epidemiological research studies. This agreement has been approved by the Independent Group Advising on the Release of Data (IGARD).
Data availability free text: Harvey Walsh, part of the OPEN Health group, is licensed by NHS Digital to receive Hospital Episode Statistics data under the data sharing agreement DARS-NIC-05934-M7V9K, which contains approval to use the data for epidemiological research studies. This agreement has been approved by the Independent Group Advising on the Release of Data (IGARD).
Patient and public involvement: Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Data availability statement
Data may be obtained from a third party and are not publicly available.
References
A large population of patients with dual multiple sclerosis (MS) and inflammatory bowel disease (IBD) diagnoses is described. The study includes all relevant patients from across English National Health Service (NHS) hospital care during the study period.
The Hospital Episode Statistics (HES) Database allows for linkage across hospital-admitted patient care, outpatient care and accident and emergency attendance, including the clinical specialists delivering care, providing a comprehensive and complete view of the cohorts’ wider hospital care use and pathways.
HES data only include confirmed diagnoses reported as part of hospital attendance, and International Classification of Diseases V.10 codes could not be used to identify MS subgroups. It was not possible to confirm the date of the cohort’s first diagnosis for either MS or IBD and, therefore, to describe the modality of their diagnosis or the time between each diagnosis first being made.
Only grouped data reporting high-cost drug use are available in HES, and as such, no pharmaceutical interventions for either diagnosis are reported in this study.
As the data analysis was descriptive, we are unable to make inferences about the significance of the differences between the cohorts or the presence or direction of any causal relationships.
Introduction
Inflammatory bowel disease (IBD) is the chronic inflammation of the bowel. Crohn’s disease and ulcerative colitis are the archetypal forms of IBD. In the UK, estimates of IBD incidence are 21–37.5 per 100 000 person-years. 1
Multiple sclerosis (MS) is a chronic inflammatory degenerative condition affecting the central nervous system. 2 MS has a higher prevalence in women 3 4 and typically affects young adults. In England, MS has an estimated incidence of 8–11 per 100 000 person-years. 5
IBD and MS each result from genetic and environmental factors leading to aberrant and dysregulated immune responses, heterogeneous phenotypes and clinical features. 6 Studies describe a potential relationship between the incidence of MS and IBD 7 8 ; however, most are based on small populations. A systematic review of 17 studies reported that patients with MS had a higher risk of developing Crohn’s disease than controls, 9 and patients with IBD had a higher prevalence of MS than controls. One study in the UK using the General Practice Research Database established that the incidence of MS was higher in patients with IBD compared with matched controls, and another showed a higher incidence of IBD in patients with MS. 10 11 Epidemiological and clinical data on the prevalence of dual diagnosis of MS and IBD and any potential functional relationship is sparse.
A recent genetic association study identified shared genetic traits between MS and IBD, and a Mendelian randomisation study reported evidence that the direction of the causal pathway is from MS to IBD rather than the reverse. 12
Co-occurrence of the diagnoses can impact patients’ burden on healthcare needs and resource utilisation, including the likelihood of greater use of treatment to manage two conditions. Treatment options for one disorder may be contraindicated in patients with the other disorder. 13 Additionally, there is a lack of evidence about clinical outcomes for patients with co-occurring diagnoses and their healthcare resource use (HCRU). This study aims to describe the scale of comorbid IBD and MS diagnosis among patients treated in hospitals in England and to describe this population, including relevant clinical characteristics and outcomes. This data will provide insight into the scale of comorbid diagnosis in patients in England associated with the burden. If trends observed in other settings are reflected here, it could indicate a population that could benefit from specific care planning and approaches for patients with comorbid IBD and MS in the NHS in England. The primary objective of this study was to determine the prevalence of patients treated in hospitals in England with recorded diagnoses for MS and IBD. We additionally describe patient characteristics and disease burden; assess how these diseases present and their progression; quantify HCRU and pathways of care in this population of patients and describe the prevalence of other comorbidities in patients with MS and IBD.
Methods
Participants, study design and setting
This retrospective, observational, real-world study describes adults in England with a hospital-recorded diagnosis of either IBD, MS or both. This study used the Hospital Episode Statistics (HES) Database, an administrative database which contains details for all admissions, Accident and Emergency (A and E) attendances and outpatient appointments at all NHS hospitals in England. 14 In 2020–2021, over 16 million consultant care episodes were recorded. 15 HES and Secondary Use Service data are subject to an extensive quality control and checking process 16 and, as a result, have high accuracy and validity for research use. 17 Data were available from 1 January 2012 to 31 July 2022. A washout period of 2 years from IBD and MS diagnoses was implemented to increase the certainty of multiple diagnosis status and the order of diagnoses. The study period for diagnosis status was, therefore, from 1 January 2014 to 30 June 2020.
Eligible participants had a recording of a WHO International Classification of Diseases V.10 18 (ICD-10) code indicating IBD (K50-51) or MS (G35) at any time during the study period and were adults or young adults (16 years or older) at the date of their first relevant diagnosis recording during the study period (see figure 1 ). This may not represent patients’ first-ever or definitive diagnosis for either the first or second condition observed.
Study design visualisation. HCRU, healthcare resource use; IBD, inflammatory bowel disease; ICD-10, International Classification of Diseases V.10; MS, multiple sclerosis.
Diagnosis pattern groups
Patients were grouped as those with a single diagnosis who presented with either an IBD or MS diagnosis code during a hospital spell or as patients with both diagnoses. Patients with a second diagnosis were grouped according to which diagnosis was recorded on the earliest date in their records. Patients with both diagnosis codes recorded for the first time during the same spell were grouped as having both diagnoses together.
Data variables
Primary objectives
The study’s primary objective included recording the order and date of diagnosis of IBD and MS, if there was a dual diagnosis, and the diagnosis patterns when this was the case.
Secondary objectives
Frequencies of each diagnosis/diagnosis group were summarised, alongside key patient characteristics, including age at first relevant diagnosis, gender, ethnicity, deprivation index and NHS region of patient registration. The frequency of MS-related comorbidities, including optic neuritis (indicated by an ICD-10 code of G36.0) and 19 demyelination disorders (indicated by an ICD-10 code of G36.8, G37.8 or G37.9), was reported for all included patients. The specific IBD diagnosis recorded (Crohn’s disease or ulcerative colitis) was reported for patients with an IBD diagnosis.
We summarised key comorbidities reported in the literature as commonly observed or associated with a diagnosis of either IBD or MS. 19 20 Patients were classified as having a diagnosis of one of these comorbidities or not, based on their recorded diagnoses in HES APC (Admitted Patient Care) and OP (Outpatient (appointments)). A full code list for these diagnoses is provided in online supplemental material S1 .
In cases of dual diagnosis, we report clinical outcome variables and HCRU outcomes for the 6 months prior to the first diagnosis of interest (diagnosis date 1 (DD1)), up until 6 months after the second diagnosis (DD2). HCRU outcome variables included total hospital attendance after the first diagnosis and before the second diagnosis, as well as admission method (elective/non-elective). The use of high-cost drugs (HCDs) was reported: HCD is a designation applied to drugs with a disproportionately high cost that typically requires specialist involvement to administer or monitor. 21 Additionally, data were collected on specialty care delivered (clinical specialties of the units that patients were admitted to) and reasons for admission (diagnosis attributed as the reason for admission) in the 6 months following DD2.
No medicines are reported for patients in this study, as only a restricted proportion of prescriptions are available in HES.
Analysis
Data were analysed using the SQL Management Studio V.18, R statistical software V.4.0.4 and Microsoft Excel. Analyses were descriptive in nature, so no inferential statistics were conducted. Distributions and descriptive statistics of both central tendency (medians and arithmetic or geometric means) and dispersion (SD and IQR) were presented for quantitative variables. Nominal variables were described with frequencies and percentages, while continuous variables also have medians and IQR described. All percentages were reported to the nearest whole number. Analyses of study variables were conducted, excluding missing data, in which case the number and percentage of patients with missing data were reported for each variable.
Patient and public involvement statement
Patients or the public were not involved in the design or conduct of this study. This work uses data provided by patients and collected by the NHS as part of their care and support.
Results
Frequency of MS and IBD in hospital-treated patients in England, and demographic information of MS and IBD in each diagnosis pattern group
The overall cohort size of patients with either an IBD or MS diagnosis recorded during the study period was 352 698. From this overall cohort, 81.2% (286 455) of patients had an IBD diagnosis, and 19.1% (66 243) had an MS diagnosis. From the overall cohort, 80.9% (285 439) of patients had a single diagnosis of IBD, and 18.8% (66 243) had a single diagnosis of MS. The prevalence of IBD in patients with MS was 1.51% (1016/67 259), and MS in patients with IBD was 0.35% (1016/286 455).
Online supplemental materials S2, table 1 summarises the number of patients with each diagnosis, the specific IBD diagnosis in patients with IBD and the MS-related diagnoses in each group. From the overall cohort, 0.3% (1016) of patients had both diagnoses recorded. From the cohort with a dual diagnosis (n=1016), 40.5% (411) of patients had MS diagnosed first, 29.8% (303) had IBD diagnosed first and 29.7% (302) had both diagnoses first recorded during the same spell.
Among patients with IBD in the overall cohort, 68.5% (187 617) were specifically diagnosed with ulcerative colitis and 42.0% (120 245) with Crohn’s disease. Patients with a single diagnosis of MS had a 0.4% (243) prevalence of optic neuritis, patients with a single diagnosis of IBD had <0.01% (10) prevalence of optic neuritis and patients with a dual diagnosis had a 0.3% prevalence of optic neuritis. The prevalence of other demyelination disorders was 0.3% (1054) in the overall cohort. In patients with a single diagnosis of MS, the prevalence of other demyelination disorders was 1.5% (964). In patients with a dual diagnosis, there was a prevalence of 2.9% (29) of other myelination disorders. No patients with a single IBD diagnosis had a recorded diagnosis for other demyelination disorders.
Population demographic and clinical characteristics
Online supplemental materials S2, table 2 summarises the demographic information for the overall cohort and the individual diagnosis pattern groups. The mean (SD) age at the index for the overall cohort was 52 (18.7) years. In the single diagnosis cohort, patients with MS had a higher mean (SD) age of 53.3 (16) years compared with patients with IBD, who had a mean age (SD) of 51.7 (19.2) years. Patients with a dual diagnosis, who were diagnosed with IBD first and then MS, had a mean (SD) age of 49.9 (16.8) years; patients diagnosed with MS first and then IBD had a mean (SD) age of 53.6 (14.9) years and patients diagnosed with MS and IBD during the same spell had a mean (SD) age of 58.2 (13.9) years.
In the overall cohort, there were more females than males (55.2%; 194 736). When looking at the single diagnosis groups, this difference was more apparent in the MS group compared with the IBD group, with 70% (46 350) female in the MS group versus 51.8% (147 703) female in the IBD group. In the dual diagnosis cohort, there were more females than males (67.2%; 683). There was a higher proportion of females in patients with MS with an IBD diagnosis compared with patients with IBD with an MS diagnosis (71.3% (293) vs 65.3% (198)).
In terms of ethnicity, the majority of the overall cohort (90.4%, 273 011) was white. This is reflected across the diagnosis group cohorts, which range from 89.9% (219 854) white (IBD only) to 97% (262) white in the cohort where both diagnoses are seen for the first time in the first episode. There was little difference in the proportion of cohorts in each decile of the Multiple Deprivation Index.
Comorbidities of interest
Online supplemental materials S2, table 3 , summarises other comorbidities of interest in the cohort. In patients with Parkinson’s, the prevalence in the dual diagnosis groups was 2.3% (23) compared with 0.9% (3340) of the overall cohort. The prevalence of Parkinson’s as a comorbidity in patients with IBD with an MS diagnosis was 3.0% (9).
HCRU and outcomes
Prior HCRU
In the overall cohort, when categorising the total number of hospital attendances, the largest proportion of patients (63.9%; 225 390) had between 1 and 5 total attendances. The large majority of the overall cohort (88.0%; 310 278) had no inpatient admissions in the 6 months prior to their first diagnosis. Online supplemental materials S2, table S4 summarises the HCRU in all diagnosis groups in the 6 months prior to their first diagnosis.
HCRU during follow-up
A large proportion of patients with IBD with a subsequent MS diagnosis were given HCDs (11.3%; 32). In the overall cohort, 5.7% of patients received HCDs (20 145), and in the dual diagnosis cohort, 6.2% of patients did (60). A greater proportion of patients with a dual diagnosis had more total hospital attendances compared with patients with a single diagnosis: 29.0% (281) of patients with a dual diagnosis had 6–12 hospital attendances compared with 20.4% (71 772) of the overall cohort, and 10.0% (97) of the dual diagnosis cohort had 13–24 total hospital attendances compared with 5.1% (18 125) of the overall cohort. Online supplemental materials S2, table 4 summarises the HCRU in the 6 months after the second diagnosis.
Discussion
This study reports the frequency of a dual diagnosis of IBD and MS among patients treated in English hospitals. This study is one of the few in Europe (or internationally) to describe the prevalence of such dual diagnoses at the national level and as observed in hospital care. This up-to-date investigation of the data also describes key demographic and HCRU measures for the population, with diagnoses recorded for both conditions. These data indicate there is a patient population who could benefit from specialist care planning and design across gastroenterology and neurology care and an opportunity to coordinate existing good practices for patients with comorbid diagnoses into a cross-provider approach.
The study identified over 1000 patients with a dual diagnosis of MS and IBD. Among patients with a dual diagnosis, an initial diagnosis of MS with a secondary diagnosis of IBD (411 patients) was most common, followed by an initial diagnosis of IBD with a secondary diagnosis of MS (303 patients) and both diagnoses first recorded during the same spell (302 patients).
Evidence on epidemiological and functional associations between IBD and MS is developing: this study is one of the largest such studies conducted in Europe using secondary care data. However, our results are consistent with other studies in England and in other geographies. The prevalence of MS in patients with IBD of 0.3% is in line with a systematic review and meta-analysis study, although the estimated prevalence of 1.51% of IBD in patients with MS is higher than the 0.6% reported in the same study. 9 A study conducted using the Disease Analyser Database in Germany reported a prevalence of MS diagnosis of 0.9% in patients with Crohn’s disease (CD) and 0.7% in patients with Ulcerative Colitis (UC) after 10 years of follow-up. 22 Our findings further align with those of a study using the General Practice Research Database in England that showed that the incidence of MS was higher in patients with IBD compared with matched controls, and they also align with the findings of a US questionnaire study showing a higher incidence of IBD in patients with MS. 7 8
A larger proportion of females had a dual diagnosis compared with males (67.2% vs 32.8%). The large predominance of females in the dual diagnosis group is likely driven by the general gender imbalance associated with MS. 23 White patients were over-represented in the cohort based on the general population of England (the 2021 census estimated that 81.7% of the population was white). 24 This corresponds with studies showing that both IBD and MS disproportionately affect people of European descent 25 26 and may be an important factor when comparing the prevalence of an IBD and MS dual diagnosis across geographies.
The frequency of certain comorbidities, such as depression, anxiety and Parkinson’s disease, was high in the dual-diagnosis cohort. Studies have shown shared causal pathways between inflammatory diseases such as MS and IBD and psychiatric diseases. 27 28 Definitive identification of a relationship between these conditions (and the direction of this) would require further investigation. Aside from potential shared functional pathways, these results indicate that the population with comorbid IBD and MS may also need more broadly clinically complex care, reiterating the advantages of cross-specialist cooperation.
HCRU prior to the initial diagnosis in each diagnosis pattern group was similar. There was a particularly high frequency of HCD use in patients with IBD with an MS diagnosis in the 6 months following the second diagnosis (11.3% of patients), which may indicate complex specialist care needs in this group. HCRU in the 6 months following the second diagnosis reveals that hospital attendance is more frequent in patients with a dual diagnosis after the second diagnosis. This aligns with observations in other studies of this population 13 and corresponds with a second separate diagnosis likely requiring more hospital care and resource use in general. There could be potential patient benefits and service level efficiencies in designing a targeted care approach for patients with comorbidities.
Limitations
HES data include only confirmed diagnoses reported as part of hospital attendance, and as such, this study may underestimate the true number of cases nationally. While ICD-10 coding in the HES dataset allows for the identification of the specific IBD diagnosis, the MS subgroup is not coded. For that reason, we are unable to consider the relationship between subtypes of MS (and associated morbidity) and the presence of a dual diagnosis.
This study does not include diagnoses only recorded in the data outside of the study period or not noted in the HES Database. However, the inclusion of a 2-year washout period prior to the initiation of data collection was implemented to mitigate the impact of this uncertainty, particularly from very recent diagnoses prior to the study period. Both IBD and MS diagnoses are expected to receive some level of specialist treatment in the UK NHS, making this most likely to create uncertainty around the timing of the relevant diagnoses in relation to the observed codes rather than general diagnosis status.
As this study was descriptive, we cannot make inferences about the significance of the differences between the cohorts, the presence or direction of any causal relationships or any underlying functional pathways for the co-occurrence of the two conditions. This initial exploratory descriptive study indicates that the population with co-diagnosis is present in the UK NHS and such relationships could be explored formally.
Conclusions
We describe the population of patients with a diagnosis of both IBD and MS who received hospital care across England. This cohort shows evidence of frequent interactions with secondary care, and patients with additional comorbidities, including Parkinson’s disease and depression. Future research should investigate whether the observed variations in HCRU are related to shared disease pathways, age-related effects or artefacts of shared clinical care such as medications.
Clinical pathways and management of patients with both diagnoses should reflect their clinical needs in relation to clinical and demographic characteristics, comorbidities, HCRU and treatment management. This study offers a large data perspective that provides an accurate account of the prevalence of dual diagnoses in the cohort and its high burden of disease.
Supplementary material
Acknowledgements
Editorial support (in the form of writing assistance, including preparation of the draft manuscript under the direction and guidance of the authors, collating and incorporating authors’ comments for each draft, assembling tables and figures, grammatical editing and referencing) was provided by Yusuf Daniju, a former employee of OPEN Health, and was funded by Bristol Myers Squibb. Sue Beecroft (Harvey Walsh, at the time of the study initiation) assisted with data access and study design. Expert advice on the direction of the manuscript was provided by the clinical steering committee of Dr. Chris McGuigan, Professor Daniel R. Gaya, Dr. Martin Duddy and Professor Subrata Ghosh.
Footnotes
Funding: This study was funded by Bristol Myers Squibb. Harvey Walsh (operating as OPEN Health) received funding from Bristol Myers Squibb to support this study. The study was supported by Bristol Myers Squibb (Uxbridge, UK). Bristol Myers Squibb had a role in the design of the study, analysis and interpretation of the data, review and approval of the manuscript and decision to submit the manuscript for publication.
Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online ( https://doi.org/10.1136/bmjopen-2024-088808 ).
Provenance and peer review: Not commissioned; externally peer reviewed.
Patient consent for publication: Not applicable.
Ethics approval: Harvey Walsh, part of the OPEN Health group, is licensed by NHS Digital to receive Hospital Episode Statistics data under the data sharing agreement DARS-NIC-05934-M7V9K, which contains approval to use the data for epidemiological research studies. This agreement has been approved by the Independent Group Advising on the Release of Data (IGARD).
Data availability free text: Harvey Walsh, part of the OPEN Health group, is licensed by NHS Digital to receive Hospital Episode Statistics data under the data sharing agreement DARS-NIC-05934-M7V9K, which contains approval to use the data for epidemiological research studies. This agreement has been approved by the Independent Group Advising on the Release of Data (IGARD).
Patient and public involvement: Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this research.
Data availability statement
Data may be obtained from a third party and are not publicly available.
References