Introduction

Patients with inflammatory bowel disease (IBD) require long-term, intensive care. To optimise future healthcare delivery, identifying patients suitable for remote monitoring is crucial. Patient-reported outcome measures integrated within eHealth systems, such as the 4-item Mobile Health Index (mHI)¹, offer potential for predicting disease activity. This study explores the predictive value of the mHI within the e-health system DEARhealth² at a Dutch university medical centre.

Aims & Methods

This multi-centre prospective cohort study tracked IBD patients within the e-health system. Patients were categorised into high-, intermediate-, and low-risk groups based on current and past biochemical disease activity. High-risk patients had current biochemical disease activity (FCP > 150 µg/g and/or CRP > 5 mg/L), intermediate-risk patients were in remission but experienced a biochemical flare within the last three years, while low-risk patients had been in biochemical remission for at least three years. A personalised care pathway, considering both risk group and medication usage, dictated the frequency of outpatient visits and lab tests. Over a 24-month period, patients are monitored according to standard of care (biochemical disease activity; endoscopic disease activity) and with mHI scores at both pre-defined time points and patient-initiated moments. These preliminary results focus on assessing the predictive value of the mHI, above a validated cut-off value¹, at baseline for predicting a flare within six months. Sensitivity, specificity, and predictive values are calculated alongside simple logistic regression and Kaplan-Meier analyses.

Results

Out of 319 patients (56.7% Crohn’s Disease (CD), median age 43 years, median disease duration 15 years), 89 exhibited biochemical disease activity at baseline and were excluded from the current analysis. Among the 230 patients in remission at baseline, 51 (21.3%) scored above the mHI cut-off point at baseline and 79 (34.3%) experienced a biochemical flare-up within six months of follow-up. The relative risk of experiencing a disease flare in Ulcerative Colitis (UC) patients with a baseline mHI score above the cut-off point was 2.44 (p = 0.04) with sensitivity of 42.1%, specificity of 82.4%, positive predictive value of 40.0%, and negative predictive value of 83.6%. In CD patients, this relative risk was 1.62 (p = 0.39) with sensitivity of 38.5%, specificity of 73.4%, positive predictive value of 14.7%, and a negative predictive value of 90.9%. Logistic regression analysis revealed a significant association between a mHI score above the cut-off point and disease flares in UC patients (OR = 3.394, 95% CI: 1.110-10.330, p = 0.03), whereas in CD patients, such an association was not significant (OR = 1.724, 95% CI: 0.487-5.603, p = 0.37). Similarly, Kaplan-Meier analysis demonstrated a longer flare-free survival in UC patients with a baseline mHI score below the cut-off point (p = 0.03), while no significant difference was observed in CD patients (p = 0.14).

Conclusion

This study indicates that the mHI could be a valuable tool for predicting disease activity, and particularly quiescent disease, in UC patients. However, this predictive capability was not observed in patients with CD. These results underscore the potential utility of mHI in enhancing the management of IBD patients, with implications for personalised care and resource allocation within healthcare systems. Further research should explore repeated mHI measurements in combination with biomarkers like calprotectin for a more comprehensive approach.

References

¹ Van Deen, W. K., van der Meulen-de, A. E., Parekh, N. K., Kane, E., Zand, A., DiNicola, C. A., ... & Hommes, D. W. (2016). Development and validation of an inflammatory bowel diseases monitoring index for use with mobile health technologies. Clinical gastroenterology and hepatology, 14(12), 1742-1750.

² DEARhealth: Software as a medical device using Dynamic & Risk-based care pathways and Smart Decision Support Recommendations. DEARhealth. (n.d.). https://dearhealth.com/hospital/

Disclosure

PWJM reports consulting fees from Abbvie and Takeda, and payment for presentations from Galapagos and Takeda. PWV reports consulting fees from Abbvie, Galapagos, BMS, Janssen, Lilly, and Takeda, and payment for presentations from Galapagos and Takeda. AEvdMdJ received research grants from Nestle, Norgine, Cablon, Galapagos, and ZonMw, including speaker’s fees from, Tramedico, Janssen Pharmaceuticals, Takeda, Galapagos, Vedanta, Ferring, and AbbVie. These are not related to this work. All other authors have no conflicts of interest to declare.
This study has received funding from Galapagos/Alfasigma

Introduction

Lifestyle factors are significant contributors to fatigue, which affects approximately 45% of patients with Inflammatory Bowel Disease (IBD) in remission.

Aims & Methods

In this study, we evaluated the effect of a digital multimodal lifestyle intervention on fatigue in patients with IBD. Patients with IBD in biochemical remission (fecal calprotectin <150 mg/kg) were enrolled in a multicenter, non-randomized, controlled interventional study. The intervention group participated in a 12-month lifestyle program—provided by the non-profit organization Voeding Leeft—that included digital group meetings with a nutritionist and a lifestyle coach focusing on gradual and sustainable behavior change regarding nutrition, physical activity, sleep, and stress management. In addition, the program encouraged patients to exercise more self-control over their personal health. Following the initial six months, attendance at online sessions was not mandatory; however, patients could attend online sessions every six to 12 weeks to stay motivated and foster the lifestyle habits they acquired throughout the course. Patients in the control group received standard care that included an informational leaflet about the potential causes of fatigue in IBD, the leaflet also included basic lifestyle information and advice to exercise more, eat a healthier diet, stop smoking, reduce alcohol intake, improve sleeping habits, and manage stress. The allocation to a study group was determined by the availability within the group and participant’s ability to attend the scheduled intervention. Clinical data and patient-reported outcomes were collected. Fatigue was measured with the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F); any increase in FACIT-F after six months was considered a positive response to the intervention. The Minimal Clinically Important Difference (MCID) for fatigue was at least a four-point increase in the FACIT-F score¹. Inverse probability treatment weighting was used to correct confounding by indication.

Results

Thirty-six patients in the intervention group and 32 in the control group were compared. After six months, more patients in the intervention group (82.1% of patients) than in the control group (54.2% of patients) experienced improvement in fatigue, P = 0.029. Likewise, significantly more patients in the intervention group (71.4% of patients) than the control group (33.3% of patients) achieved a MCID regarding fatigue; P = 0.006. The improvements in fatigue were sustained throughout the study period in the intervention group. Acceptance of the health status was a significant factor for improvement in fatigue (β 7.813, SE 1.908, P < 0.001). Compared to the control group, quality of life improved in the intervention group; these patients gained 0.05 more quality-adjusted life years throughout the study. Last but not least, significant improvements in dietary quality were observed as early as three months after the baseline in the intervention but not the control group; these improvements in the intervention group were sustained throughout the study period.

Conclusion

Multimodal lifestyle intervention improves fatigue, quality of life, and dietary quality in patients with IBD who are in remission. Acceptance of the health status appears essential for fatigue improvement; instruments evaluating acceptance could help to personalize treatment and maximize its effectiveness.

References

1. Cella D, Yount S, Sorensen M, et al. Validation of the Functional Assessment of Chronic Illness Therapy Fatigue Scale relative to other instrumentation in patients with rheumatoid arthritis. J Rheumatol 2005;32:811-9.

Disclosure

AEvdMdJ received unrestricted research grants from Galapagos, Norgine, Vedanta, Nestle, including speaker’s fees from Galapagos, Tramedico, Takeda, Ferring, and Janssen Pharmaceuticals. PWV has received speaker fee from Galapagos and Takeda and served on the advisory board of Lilly, Galapagos, Janssen, BMS, Takeda, and Abbvie. RL has received travel expenses from Galapagos and Cablon Medical and served on the advisory board at Cablon Medical. NW and MJHB are employed by the non-profit organization Voeding Leeft and were a part of the team that guided participants in the intervention group. All other authors have no conflicts of interest to declare.

Introduction

Frailty is prevalent among older patients with Inflammatory Bowel Disease (IBD). A geriatric assessment is a method to assess the presence of frailty and its course over time. However, the predictive value of the geriatric assessment and the longitudinal course of frailty have not yet been studied in patients with IBD.

Aims & Methods

The primary aim was to evaluate the course of frailty and to identify factors associated with changes in level of frailty over 18 months follow-up in older patients with Inflammatory Bowel Disease (IBD). The second aim was to study the association of frailty with hospitalizations during follow-up. A prospective multicenter cohort study was conducted in IBD patients (≥ 65 years). At baseline, a geriatric assessment was performed in all 405 patients, assessing impairment in five domains: the somatic domain, (instrumental) activities of daily living, physical capacity, mental and social domain. Follow-up was conducted after 18 months. Part of the patients were seen for a second, follow-up geriatric assessment. The rest of the patients was contacted by phone for a follow-up assessment. Primary outcome was change in the level of frailty, defined as a change in the number of impaired domains at follow-up compared to baseline (an increase in number of impaired domains suggests an increase in level of frailty, a decrease in number of impaired domains suggests a decrease in level of frailty). Secondary outcomes were all-cause, acute and IBD-related hospitalizations during 18 months. Logistic regression was performed to identify factors associated with changes in level of frailty, adjusted for age, sex, type of IBD and educational level. Cox regression analyses were performed to study the association of frailty with adverse outcomes, adjusted for age, sex and biochemical disease activity (C-reactive protein ≥ 10 mg/L and/or fecal calprotectin ≥250 μg/g).

Results

Out of 405 patients (median age: 70 years) with a geriatric assessment at baseline, 160 (39.5%) patients had 2 or 3 impaired domains and 32 patients (7.9%) had 4 or 5 impaired domains. Follow-up was conducted in 356 patients (87.9%), of which 154 (43.3%) patients were seen for a geriatric assessment and 202 patients (56.7%) were contacted by phone. In the geriatric assessment, 32.5% had increased and 26.0% decreased ≥ 1 in number of impaired domains compared to baseline. Use of systemic corticosteroids at or three years prior to baseline associated with an increase in impaired domains (adjusted odds ratio (aOR) 3.00; 95% confidence interval (95% confidence interval (CI)) 1.11-8.08; p-value= 0.030), while initiation of biological therapy associated with a decrease in impaired domains (aOR 4.92, 95%CI 1.41-17.15, p-value=0.013). Over 18 months, all-cause hospitalizations occurred 136 times in 96 patients (23.7%). Of all hospitalizations, 103 (75.7%) were acute occurring in 74 patients and 41 were IBD-related (30.1%) occurring in 28 patients. Frailty was independently associated with both all-cause (adjusted hazard ratio (aHR) 1.28, 95% confidence interval [CI] 1.05-1.56, p-value=0.016) and acute hospitalizations (aHR 1.30, 95% CI 1.04-1.61, p-value=0.020). No association was found for IBD-related hospitalizations.

Conclusion

The level of frailty is dynamic in 58.5% of the older patients with IBD over 18 months. In addition, frailty at baseline is independently associated with all-cause and acute hospitalizations. Future studies should establish how interventions targeting frailty could improve health outcomes.

Introduction

Inflammatory bowel disease (IBD) is strongly associated with joint inflammation, as is highlighted by the high prevalence of spondyloarthritis (SpA) in patients with IBD (up to 13%) compared to the general population (0.2-1.6%) [1, 2]. IBD and SpA have many overlapping features, including genetic risk factors, changes in the gut microbiota, and therapies targeting TNF-α , IL-23, or JAK [3]. However, current therapies for both diseases are unable to break the cycle of chronic inflammation, and still a significant proportion of patients fail to respond. Disease heterogeneity likely plays a role in this [4, 5], underscoring the necessity to improve management and refine classification.

Aims & Methods

In this study, 92 inflammation-related proteins were quantified in serum of patients from one IBD and one SpA cohort using the novel Olink proteomics proximity extension assay. Fold changes (FC) in expression with |log₂FC| > 0.5 were considered meaningful, and false discovery rates (FDR) <0.05 were considered significant. The IBD cohort existed of 255 IBD patients with (n=155) and without (n=100) self-reported joint complaints [8]. From the patients with joint complaints, 58 fulfilled any of the SpA criteria. The SpA cohort, or SPACE cohort, consisted of 169 patients with chronic back pain (≥3 months, ≤2 years) of unknown origin [9]. After 2 years of follow-up, 85 patients had proven axSpA. Serum samples were taken at baseline, and 167/169 samples from the SPACE cohort and 241/255 samples from the IBD cohort passed quality control and were included in the analysis.

Results

Thirty-four proteins were differentially expressed between 95 IBD patients without joint complaints and 85 proven axial SpA (axSpA) patients from the SPACE cohort, of which 14 were higher in IBD patients (including 4E‑BP1, IFN‑γ, TNF, FGF‑21, CD8A, and CCL9), and 20 were higher in axSpA patients (including CASP‑8, SIRT2, STAMBP, FGF‑19, ST1A1, and EN‑RAGE). In addition, the immune profile of IBD patients with joint complaints differed from IBD patients without joint complaints: 4E‑BP1, CASP-8, STAMBP, SIRT2, AXIN1, and TNFSF14, were significantly upregulated in patients with joint complaints. Of note, if IBD patients without joint complaints were compared to the subgroup of 58 patients with joint complaints who met criteria for SpA, the same proteins showed significant upregulation, suggesting minimal difference between IBD patients with joint complaints who meet or who do not meet SpA criteria. Direct comparison of patients who met and who did not meet SpA criteria within the group of IBD patients with joint complaints indeed showed no noteworthy difference in serum immune profile. Within the SPACE cohort, comparison of patients with chronic back pain with and without axSpA diagnosis also showed no significant difference in serum protein expression.

Conclusion

This study shows that patients with axSpA versus patients with IBD without joint complaints have differing serum immune profiles. Within IBD patients with self-reported joint complaints and within patients with self-reported chronic back pain (from the SPACE cohort), no distinct difference in immune profile is observed, regardless of SpA diagnosis. The inflammation signatures of patients with chronic inflammatory diseases should be further investigated to provide insights for enhancing disease management in the future.

References

1. Karreman, M.C., et al., The Prevalence and Incidence of Axial and Peripheral Spondyloarthritis in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis, 2017. 11(5): p. 631-642.
2. Stolwijk, C., et al., Global Prevalence of Spondyloarthritis: A Systematic Review and Meta-Regression Analysis. Arthritis Care Res (Hoboken), 2016. 68(9): p. 1320-31.
3. Gracey, E., et al., Revisiting the gut-joint axis: links between gut inflammation and spondyloarthritis. Nat Rev Rheumatol, 2020. 16(8): p. 415-433.
4. van Unen, V., et al., Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets. Immunity, 2016. 44(5): p. 1227-39.
5. Gulino, G.R., M. Van Mechelen, and R. Lories, Cellular and molecular diversity in spondyloarthritis. Semin Immunol, 2021. 58: p. 101521.
6. van Erp, S.J., et al., Classifying Back Pain and Peripheral Joint Complaints in Inflammatory Bowel Disease Patients: A Prospective Longitudinal Follow-up Study. J Crohns Colitis, 2016. 10(2): p. 166-75.
7. Marques, M.L., et al., Can rheumatologists unequivocally diagnose axial spondyloarthritis in patients with chronic back pain of less than 2 years duration? Primary outcome of the 2-year SPondyloArthritis Caught Early (SPACE) cohort. Ann Rheum Dis, 2024. 83(5): p. 589-598.

Disclosure

FAG: grants from Stichting vrienden van Sole Mio and Stichting ASAS, grants and/or consulting fees from Abbvie, ASAS, BMS, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB.
AEM: grants from Nestle, Norgine, Cablon, Galapagos, and ZonMW, ad boards/speaker fees from Tramedico, Janssen, Takeda, Galapagos, Vedanta, Ferring, AbbVie, and Dear Health.
PV: speaker fees from Takeda and Galapagos, advisory board: Takeda, Galapagos, Lilly, BMS, Janssen, and Abbvie

Introduction

Eight hospitals in the southwest of the Netherlands collaborate to provide high quality, uniform care for inflammatory bowel disease (IBD). To achieve this, a care pathway (CP) was implemented for treating IBD with biologics and small molecules (1). The CP is a decision-support tool that provides guidelines for medication prescribing, procedures, treatment adjustments, and recommendations for follow-up.

Aims & Methods

This study aimed to evaluate the effect of a CP on patient outcomes and healthcare utilization.
A longitudinal multicentre non-randomised cohort study with a baseline observation period (December 2020 – December 2021) and a follow-up period (March 2022 – March 2023) was conducted, in which adult patients with IBD treated with biologics or small molecules were included. Outcomes were collected according to the International Consortium for Health Outcomes Measurement (ICHOM) standard set from electronic health records or through validated questionnaires. Missing data were handled using single imputation nested within a bootstrap procedure. Effect of the CP on these outcomes were analysed with case-mix adjusted (generalized) linear mixed models.

Results

A total of 1,173 patients participated in the study, with the majority being female (55%) and a median age of 45 years (IQR 33-58). Most patients had Crohn's disease (64%). The CP was associated with a 0.22 increase on the ibd-control-8 score (β=0.22, p=0.28), and an increase on the probability of achieving endoscopic/radiologic (β=0.14, p=0.29), biochemical (β=0.18, p=0.22) and patient-reported remission (β=0.19, p=0.21). Probability of clinician-reported remission decreased slightly (β=-0.09, p=0.59). Emergency room visits (β=-0.36, p=0.13), hospital admissions (β=-0.41, p=0.10), and length of stay (β=-0.09, p=0.56) reduced, although these associations were not significant. The CP had no effect on quality of life (β=0.00, p=0.83), anaemia probability (β=-0.01, p=0.95) or on nutritional status (β=-0.01, p=0.34).

Conclusion

A CP for the management of IBD with biologicals and small molecules has clinically significant potential to reduce healthcare utilization, while improving patient-reported disease control, and disease remission. These results emphasize that clinical care pathways can improve care and reduce healthcare utilisation for complex diseases. However, the adherence to the CP and whether these results lead to a reduction in healthcare costs should be further investigated.

References

(1) van Linschoten R, van Leeuwen N, Nieboer D, Birnie E, Scherpenzeel M, Verweij KE, et al. Value-based care pathway for inflammatory bowel disease: a protocol for the multicentre longitudinal non-randomised parallel cluster IBD Value study with baseline period. (2044-6055 (Electronic))

Disclosure

Drs. Visser received a speaker fee from Lilly, Prof. Dr. van der Woude reports grants from Pfizer and Janssen and personal fees from AbbVie and Celltrion, Dr. van Noord reports personal fees from Janssen, Takeda, and Falk, Dr. West reports personal fees from AbbVie, Janssen, and Pfizer outside the submitted work.

Introduction

Inflammatory bowel disease (IBD) exerts a significant socioeconomic burden in Western nations. Drugs are a consistent driver of direct healthcare costs. However, healthcare utilisation, which varies considerably between individuals, contributes substantially. Predicting the patients who are more likely to be higher utilizers of healthcare is challenging, as symptom burden does not always reflect underlying disease activity.^​

Aims & Methods

We aimed to establish whether model-based clustering could be used to identify novel subgroups, or clusters, of patients with IBD, and if baseline cluster membership could predict adverse disease outcomes during longitudinal follow up. We recruited patients with a diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) between 2012 and 2015. In addition to baseline demographic data, we collected data regarding somatoform symptom-reporting using the patient health questionnaire-15, anxiety or depression using the hospital anxiety and depression scale, and stool frequency, extracolonic features, and general wellbeing derived from overlapping components of the Harvey Bradshaw Index for patients with CD, and the simple clinical colitis activity index for patients with UC, all of which were used as variables for modelling. Using LatentGOLD version 6.0, we performed latent class analysis (LCA) to establish the novel clusters and select the optimal model. We measured clinical outcomes during longitudinal follow up, including flare or glucocorticosteroid prescription, treatment escalation, hospitalisation, and intestinal resection. We then performed multivariate Cox regression analysis, controlling for all baseline characteristics, to establish if individual cluster membership was an independent predictor for these outcomes, expressing results as hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

Of the 760 patients recruited, 692 (91.1%) provided complete baseline data (mean age 43.6 (age range 17 to 89 years), 382 (55.2%) female, 647 (93.8%) Caucasian, and 394 (56.9%) with CD). The best LCA solution was obtained using a three-cluster model. Cluster 1 was defined by below average gastrointestinal and psychological symptom burden, cluster 2 by average gastrointestinal and psychological symptom burden, and cluster 3 by above average gastrointestinal and psychological symptom burden. Proportions with faecal calprotectin <250mcg/g at baseline were similar between clusters. Compared with cluster 1, patients in cluster 3 were at significantly increased risk of glucocorticosteroid prescription or flare, escalation, a composite of escalation, hospitalization, or intestinal resection, or any of the endpoints of interest (table 1). Effect sizes increased when only including individuals in biochemical remission at baseline. Healthcare utilization was highest in cluster 3.

Table 1- Disease outcomes according to cluster membership at baseline.

Conclusion

It is feasible to derive novel clusters of patients with IBD, based not only on gastrointestinal symptoms, but also on measures of psychological health. The cluster with the highest psychological symptom burden identifies patients at higher risk of adverse disease outcomes who are high volume users of healthcare.

Disclosure

None.

Introduction

Patients with inflammatory bowel disease (IBD) have an increased risk of developing intestinal and extra-intestinal cancers. Specific therapies used to control inflammation in IBD may have a different impact on cancer risk. However, there are no long-term studies investigating cancer risk in patients with IBD.

Aims & Methods

In the present study we aimed to quantify the overall risk for of developing cancer and to identify specific risk factors for the occurrence of intestinal and extra-intestinal cancers in 560 consecutive patients with Crohn's disease (CD, N=310) or ulcerative colitis (UC, N=250) referred to our outpatient department between January 2021 and February 2022. Demographic data, smoking status, alcohol consumption, age at IBD diagnosis, disease location and course, therapies, and cancer development after IBD diagnosis were recorded. Odds ratios (OR) were estimated by logistic regression analysis. Standardized Incidence Ratios (SIRs) were estimated compared with the general population.

Results

During a median follow-up interval or time of 10 years (range 1-26 years), 6.6% of patients (37/550, female 65 %, mean age 51 years) developed cancer (SIR 1.94, 95%CI 1.4-2.6). The most common cancers were colorectal (12.3%), skin (8.2%), and breast cancer (7.2%). Female patients had an increased risk for all cancers (SIR 3.11, 95%CI 2.06-4.3), melanoma (SIR 5.6, 95%CI 1.14-16.2) and colorectal cancer (SIR 7.59, 95%CI 3-15.4). Male patients had an increased risk of lymphoma (SIR 26.15, 95%CI 3.2-95.7). Younger age at diagnosis of CD (A1 Montreal classification, OR 37.9, 95%CI 10-14), immunosuppressive monotherapy (OR 5.5, 95%CI 2.65- 11) or in combination with anti-TNFα (OR 9.9, 95%CI 3.3-29.09) were associated with an increased risk of cancer in the study population.

Conclusion

We have identified subgroups of IBD patients who would particularly benefit from screening programs. Our findings need to be validated in independent cohorts.