A Care Pathway for the Treatment of IBD Reduces Healthcare Costs and Is Cost‐Effective: Results of the Multicentre IBD Value Study

ABSTRACT

Background

An advanced therapy care pathway (ACP) for the treatment of patients with IBD can reduce practice variation and improve outcomes.

Aims

This study aimed to estimate the effect of the ACP on costs and quality of life, and to assess the cost‐effectiveness of the ACP.

Methods

A cost‐utility and cost‐effectiveness analysis was conducted from a societal perspective. The ACP was implemented in six hospitals, and two hospitals in the same region served as controls. Costs and quality of life were assessed during a baseline period (December 2020–December 2021) and an intervention period after implementing the ACP (March 2022–March 2023). Quality‐adjusted life years (QALYs) were derived from the EQ‐5D‐5L; disease control from the IBD‐Control questionnaire. A difference‐in‐differences (DiD) analysis was conducted, and the net monetary benefit and incremental cost‐effectiveness ratio (ICER) were calculated.

Results

In total, 1,173 patients were included (intervention n = 841, control n = 332). Baseline costs per patient were €23,259.96 in the intervention hospitals and €22,837.93 in the control hospitals. During the intervention period, costs decreased to €20,959.76 in intervention hospitals. This reduction was not observed in control hospitals (€22,191.21). The DiD‐analysis showed cost savings of −€1933.69; QALYs (0.001) and disease control (0.15) did not change. The ICER indicated cost savings without compromising quality of life or disease control.

Conclusions

The implementation of an ACP for the treatment of patients with IBD reduces costs, maintains quality of life and disease control, and is cost‐effective. These results emphasise that the implementation of care pathways in current practices should be considered. Trial registration number: NL‐OMON21751. Website: Value‐based healthcare for Inflammatory Bowel Disease: Improving (cost‐) effectiveness.

This study provides real‐world evidence that implementing an advanced therapy care pathway for patients with IBD leads to significant healthcare cost savings without compromising quality of life. These findings support broader implementation of care pathways in the management of patients with chronic conditions to optimise care delivery and resource utilisation.

Abbreviations

ACP

advanced therapy care pathway

CD

Crohn's disease

DiD

Difference‐in‐Differences

IBD

inflammatory bowel disease

ICER

incremental cost‐effectiveness ratio

NMB

net monetary benefit

QALYs

quality‐adjusted life years

UC

ulcerative colitis

WTP

willingness‐to‐pay

1. Introduction

Due to the chronic and relapsing nature of inflammatory bowel disease (IBD, Crohn's disease and ulcerative colitis), most patients require lifelong medication. Many advanced therapies, such as biologics and small molecules, are available for the management of patients with IBD [1]. However, these treatments are costly and lead to increasing IBD‐attributable healthcare expenses globally [2, 3, 4, 5]. A Dutch study on healthcare use of patients with IBD in an outpatient clinic showed that the frequency of healthcare usage exceeded the recommended IBD care guidelines by two‐fold [6]. In response to escalating costs and increased healthcare utilisation, while ensuring the quality of care, healthcare providers need to implement structured approaches in patient management.

A proposed method to optimise resource utilisation is the implementation of care pathways. Care pathways delineate the sequence of assessments, interventions, and treatments that should occur at specific time points during a patient's follow‐up, ensuring that care is evidence‐based and of high‐quality [7, 8, 9]. Through standardising care processes and optimising resource use, care pathways have the potential to reduce healthcare costs [10].

Care pathways for patients with IBD have been developed and appear to have promising effects on outcomes, such as a reduction in disease flares, emergency department visits, and costs [11, 12, 13]. However, these studies only focused on specific points of IBD care, had a retrospective design, and cost‐effectiveness was not assessed. Therefore, in the southwest region of the Netherlands, an advanced therapy care pathway (ACP) was developed. This ACP provides recommendations for several aspects of IBD care, such as treatment initiation and follow‐up per biologic or small molecule, conducting annual outpatient visits, and management of potential exacerbations [14].

This study aimed to estimate the causal effect of implementing the ACP on costs and quality of life, and to assess whether the ACP is cost‐effective based on a cost‐utility analysis. In addition, a secondary cost‐effectiveness analysis was conducted to evaluate the effect of the ACP on patient‐reported disease control.

2. Methods

2.1. The IBD Value Study

This study is part of a larger initiative known as IBD Value [14]. Eight hospitals located in the southwest region of the Netherlands participated in this project: Albert Schweitzer Hospital, Amphia Hospital, Erasmus Medical Centre, Franciscus Hospital, Ikazia Hospital, IJsselland Hospital, Maasstad Hospital, and Reinier de Graaf Gasthuis. The participating hospitals are the hospitals located in the southwest region of the Netherlands and are members of the IBD BeterKeten, a collaborative network to improve IBD‐care within the region. This distribution provides a representative cross‐section of the Dutch IBD‐care.

In each hospital, IBD care is delivered by a group of IBD‐specialised gastroenterologists and nurses. Multidisciplinary team meetings are conducted within the hospitals, involving gastroenterologists, nurses, dieticians, surgeons, and other healthcare providers engaged in IBD care. Additionally, regional IBD BeterKeten meetings are conducted to discuss complex cases. While the affiliation with a quality network implies a high baseline standard of care, the inclusion of different hospital types and a patient population encompassing a wide range of socioeconomic, ethnic, and educational backgrounds ensures the findings are reflective of broader clinical practice [15, 16].

2.2. Study Design

IBD Value was a multicentre longitudinal non‐randomised parallel cluster trial carried out from December 2020 until March 2023 [14]. Initially, a baseline period was conducted to assess the standard of care (December 2020 to December 2021). Subsequently, over a three‐month period, an ACP for the treatment of patients with IBD was implemented in six intervention hospitals (December 2021 to March 2022). The other two hospitals in the same region served as controls. After the implementation period, there was a one‐year follow‐up period (March 2022 to March 2023). A comprehensive outline of the study design is available in the protocol [14].

The selection of intervention and control hospitals was based on pragmatic considerations. Initially, only the intervention hospitals were part of the BeterKeten collaboration. Before the study commenced, the control hospitals joined the collaboration but were not involved in the design or implementation of the ACP. Consequently, they served as natural controls, and this study can be considered a natural experiment. Natural experiments provide an opportunity to estimate causal effects with assumptions that can be more plausible than controlling for confounding. This design is recommended when evaluating the impact of an intervention at the population level [17, 18].

2.3. Advanced Therapy Care Pathway

The ACP is a clinical framework and was developed by a multidisciplinary and multicentre working group, guided by international and national guidelines, available scientific evidence, current best practices, and expert opinions in the absence of scientific evidence [19, 20]. The working group consisted of four gastroenterologists, an IBD nurse, all affiliated with the intervention hospitals, and a patient representative. The control hospitals were not involved in the design phase and delivered care according to their own local protocols.

The ACP was designed to provide a minimum of care that should be given to patients with IBD and can be adapted by healthcare providers based on individual patient needs. It includes systematic flare assessment, structured treatment algorithms, annual review of disease activity, and colorectal cancer surveillance. For each approved medical treatment (e.g., infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, tofacitinib, filgotinib, and ozanimod), the ACP outlines standardised induction and maintenance protocols with predefined clinical and laboratory evaluations (e.g., blood samples at week 0, 6, and 14 during the start of medication), safety monitoring, and timing of follow‐up visits (two per year after more than one year on therapy). While the exact format of consultations (in‐person, telephone, or digital) may vary between centres, the sequence and content of care were uniform across all intervention hospitals. An overview of the differences and similarities between the ECCO guidelines and the ACP can be found in Table S1.

2.4. Study Population

For this study, all patients from the IBD Value study were included. The inclusion and exclusion criteria can be found in the published protocol [14].

2.5. Data Collection

In line with the guidelines of the Dutch Healthcare Institute, the analysis was conducted from a societal perspective, encompassing healthcare costs, patient costs, and economic loss [21]. Healthcare costs were further subdivided into primary care and hospital costs. Primary care utilisation was assessed using the abbreviated version of the Medical Consumption Questionnaire with three‐monthly questionnaires [22]. Healthcare utilisation in secondary care was automatically obtained from electronic medical records in collaboration with the business intelligence departments and included, among others, the number of outpatient clinic visits, admissions, use of medication, and procedures such as colonoscopies. Patient costs were assessed using a questionnaire that encompassed travel expenses related to healthcare, the duration of informal care provided, over‐the‐counter medication, and other expenses directly related to IBD. Informal care refers to providing care and support for individuals with disabilities or elderly persons, typically by family members or friends. Economic losses were evaluated using the Institute of Medical Technology Assessment Productivity Cost Questionnaire every three months [23]. For the cost‐utility analysis, utility values, as measured with the EQ‐5D‐5L, were assessed every six months [24]. To objectively assess inflammatory activity and supplemented patient‐reported outcomes, biochemical remission was evaluated as a clinical endpoint. Biochemical remission was defined as a faecal calprotectin level < 100 μg/g for patients with CD and < 250 μg/g for patients with UC. All questionnaires were sent digitally to participants. A detailed overview of the included costs, sources, and definitions can be found in Table S2.

2.6. Data Analysis

Baseline characteristics were analysed utilising descriptive statistics and compared using t‐tests, chi‐square tests, Fisher's exact test, or Wilcoxon tests, depending on the distribution of the variables. To estimate the causal effect on costs, quality of life, and cost‐effectiveness of the ACP, the guidelines of the National Healthcare Institute, along with the methodology detailed in the IBD Value protocol, were used [14, 21].

Costs were determined by multiplying the measured healthcare use and productivity loss by reference prices from the guideline for conducting economic evaluations in healthcare in the Netherlands [21]. All costs were standardised to a common baseline year (2022) and adjusted for inflation using the Consumer Price Index, without discounting costs and effects. To facilitate international comparison, costs were converted to United Kingdom (UK) Pounds (£) using the 2022 Purchasing Power Parity conversion factor [25]. Utility was calculated with the EQUATION 5D‐5 L questionnaire (Dutch and UK tariffs) [26, 27]. Missing data were handled using single imputation nested within a bootstrap procedure based on predictive mean matching with the mice package in R [28, 29].

2.7. Cost‐Utility Analysis

The analysis used a difference‐in‐Differences (DiD) approach to estimate causal effects of implementation of the ACP, assuming that differences between the control and intervention hospitals do not change over time and that factors that change over time affect both groups equally. This approach deviated from the previously published protocol and was implemented to more rigorously correct for the observed time trends. Previously conducted analyses showed a reduction in costs and an increase in quality of life within both the intervention and control groups, suggesting that a before‐and‐after analysis could potentially yield biased results. The DiD approach is commonly used to analyse the effects of an intervention using longitudinal data [30]. It compares the change in outcomes over time in the intervention hospitals, relative to the change in the control hospitals. The analysis corrects for both time‐invariant and general, time‐varying confounding. This contrasts with standard regression analysis, where only measured confounders are corrected. For the comparison to be valid, the parallel trends assumption needs to be satisfied, meaning that the intervention and control hospitals would have followed the same trend over time, in the absence of the ACP [30, 31, 32].

The incremental costs and incremental quality‐adjusted life years (QALYs) were derived from the post‐intervention DiD effects (≥ 21 months). These were used to calculate the incremental cost‐effectiveness ratio (ICER) and the net monetary benefit (NMB). To address the uncertainty surrounding the ICER and NMB, a bootstrap procedure was performed. The NMB expresses both the costs and quality of life of an intervention in financial terms and helps determine whether the monetary benefits outweigh the loss in quality of life across different willingness‐to‐pay (WTP) thresholds. The proportion of bootstrap replications in which the ACP was cost‐effective at different WTP thresholds is visualised in the cost‐effectiveness acceptability curve. The maximum WTP threshold in the Netherlands is set at €80,000, representing the maximum investment for conditions with a severe disease burden and poor prognoses, and is therefore included as the maximum WTP threshold in the cost‐utility analysis. In addition, cost‐utility analyses were performed separately for CD and UC.

2.8. Cost‐Effectiveness Analysis

In addition to the primary cost‐utility analysis based on QALYs, a secondary cost‐effectiveness analysis was conducted using disease control as the clinical outcome. Disease control was assessed using the IBD‐Control questionnaire, a validated patient‐reported outcome measure capturing self‐reported control over IBD [33]. This cost‐effectiveness analysis was performed using the same methodological approach as the cost‐utility analysis.

2.9. Sensitivity Analysis

A sensitivity analysis was conducted to evaluate whether the results of the DiD analysis were influenced by significant differences in baseline characteristics between patients in the intervention and control hospitals.

All statistical analyses were conducted using R version 2024.04.2 + 764. Imputed datasets were generated using the mice package [29]. Custom scripts were developed to summarise and integrate results from each imputed dataset into the final analysis; artificial intelligence‐generated content tools were not used. All authors had access to the study data and reviewed and approved the final manuscript.

2.10. Patient and Public Involvement

Crohn & Colitis NL (Dutch Crohn's and Colitis Patient Organisation) actively participated in the design of the IBD Value study. They provided critical revisions to the study design and assisted in piloting the questionnaires. Furthermore, they were engaged in the working group responsible for the development of the ACP.

3. Results

3.1. Baseline Characteristics

A total of 1173 patients were included in the study, of which 841 were in the intervention group and 332 in the controlgroup. Patients were comparable on most characteristics, but there were a few significant differences between patients in intervention and control hospitals, as can be seen in Table 1. Patients in the intervention hospitals had more rheumatological extra‐intestinal manifestations (p < 0.01), and more patients had previously been treated with infliximab (p = 0.01) and adalimumab (p = 0.02). Baseline characteristics per hospital can be found in Table S3.

TABLE 1.

Baseline characteristics.

Characteristic	Missing data	Intervention hospitals n = 841	Control hospitals N = 332	p‐value
Demographics a
Age	0%	45 (33, 58)	47 (33, 60)	0.26
Female	0%	473 (56%)	172 (52%)	0.18
Education level	12%			0.24
Lower		200 (27%)	75 (25%)
Middle		277 (38%)	103 (34%)
Higher		260 (35%)	123 (41%)
Smoking status	18%			0.16
Never		315 (46%)	111 (40%)
Ex		251 (37%)	120 (43%)
Current		118 (17%)	48 (17%)
Comorbidities a
SCQ	38%	1.00 (0.00, 3.00)	1.00 (0.00, 2.50)	0.21
History of TBC	18%	9 (1.3%)	3 (1.1%)	1.00
History of Hepatitis B	18%	12 (1.8%)	2 (0.7%)	0.37
HIV/AIDS	18%	2 (0.3%)	0 (0.0%)	1.00
PSC	18%	14 (2.1%)	3 (1.1%)	0.42
Diagnosis a
Crohn's disease	0.3%	543 (65%)	209 (63%)	0.61
Ulcerative colitis	0.3%	279 (33%)	117 (35%)	0.55
IBD‐Unknown	0.3%	16 (1.9%)	6 (1.8%)	1.00
Montreal Classification a
Disease extent	0.3%			0.36
E1		14 (1.7%)	4 (1.2%)
E2		93 (11%)	30 (9.0%)
E3		188 (22%)	89 (27%)
Age at diagnosis	0.3%			0.05
A1		51 (6.1%)	12 (3.6%)
A2		384 (46%)	138 (42%)
A3		108 (13%)	59 (18%)
Disease location	0.3%			0.61
L1		131 (16%)	54 (16%)
L2		114 (14%)	51 (15%)
L3		296 (35%)	102 (31%)
L4 (isolated)		2 (0.2%)	1 (0.3%)
Concomitant proximal small bowel disease	0.3%	71 (8.5%)	20 (6.0%)	0.35
Disease behaviour	0.3%			0.08
B1		336 (40%)	147 (44%)
B2		119 (14%)	29 (8.7%)
B3		87 (10%)	33 (9.9%)
Perianal disease	0.3%	148 (18%)	49 (15%)	0.50
Extra‐intestinal manifestations a
History of dermatological EIMs	0%	60 (7.1%)	15 (4.5%)	0.12
History of rheumatological EIMs	0%	133 (16%)	18 (5.4%)	< 0.01
History of hepatobiliary EIMs	0%	17 (2.0%)	2 (0.6%)	0.12
History of opthalmogical EIMs	0%	32 (3.8%)	8 (2.4%)	0.29
Treatment history a
Previous therapy with infliximab	< 0.1%	294 (35%)	91 (27%)	0.01
Previous therapy with adalimumab	< 0.1%	203 (24%)	58 (18%)	0.02
Previous therapy with golimumab	< 0.1%	10 (1.2%)	7 (2.1%)	0.27
Previous therapy with vedolizumab	< 0.1%	54 (6.4%)	24 (7.3%)	0.68
Previous therapy with ustekinumab	< 0.1%	31 (3.7%)	9 (2.7%)	0.49
Previous therapy with tofacitinib	< 0.1%	10 (1.2%)	9 (2.7%)	0.07
History of IBD‐related surgery	0%	279 (33%)	98 (30%)	0.24
Treatment at baseline a				0.47
Infliximab		272 (32%)	108 (33%)
Adalimumab		226 (27%)	77 (23%)
Golimumab		6 (0.7%)	1 (0.3%)
Vedolizumab		124 (15%)	49 (15%)
Ustekinumab		79 (9.4%)	45 (14%)
Tofacitinib		14 (1.7%)	5 (1.5%)
No Biologic		120 (14%)	47 (14%)

Abbreviations: EIM, extra‐intestinal manifestations; HIV/AIDS, human immunodeficiency virus/acquired immunodeficiency syndrome; IBD, inflammatory bowel disease; IQR, interquartile range; PSC, primary sclerosing cholangitis; SCQ, self‐administered comorbidity questionnaire; TBC, tuberculosis.

^a Median (IQR); n (%).

3.2. Costs

During the baseline period, total costs per patient per year were comparable in the intervention hospitals (€23,286.26, 95% CI: €22,222.54 to €24,493.69) and the control hospitals (€22,803.40, 95% CI: €21,334.47 to €24,363.70), with a cost difference of €580.86 (Figure 1A,B and Table S14). In the year following the implementation of the ACP, total costs decreased to €20,957.47 (95% CI: €19,800.33 to €22,159.73) in intervention hospitals. A smaller reduction in costs was observed for patients treated in the control hospitals; total costs per patient were €22,197.86 (95% CI: €20,553.20 to €23,935.09). In both groups, the primary cost drivers were hospital costs and productivity losses. The DiD‐analysis showed cost savings primarily driven by reduced hospital costs −€1933.69 (95% CI: € −3812.67 to €104.06) (Table 2 and Figure 1C). There was no significant difference in costs in the first six months of the intervention period; however, a significant difference was observed in the subsequent six months. The results of the sensitivity analysis, in which we corrected for significant differences in baseline characteristics between hospitals, were consistent with the primary analysis (Table 2). The pre‐intervention trend of total costs can be found in Figure S1. Absolute differences in cost components between hospitals in the baseline and intervention period can be found in Table S5 to Table S8. The overall cost reduction was primarily driven by a decrease in biologic costs (€−1395.99 in intervention hospitals vs. €220.07 in control hospitals), admission costs (€−284.99 in intervention hospitals vs. €−74.34 in control hospitals), and laboratory costs (€−112.69 in intervention hospitals vs. €−44.01 in control hospitals).

FIGURE 1.

Costs per category and per group over time and Difference‐in‐Differences analysis for total costs. Note: Figure B shows the difference‐in‐differences estimates of cost differences between the intervention and control groups at three time points (12, 21, and 27 months), with a 95% confidence interval. Positive values indicate higher costs in the intervention group relative to the controls, while negative values indicate cost savings associated with the intervention. The horizontal dashed line represents zero cost difference. All costs are in euros (€).

TABLE 2.

Difference‐in‐Differences effects.

Outcome	Mean (95% CI)
Primary analysis
Total costs	−€1933.69 (95% CI: €−3812.67 to €104.06)
Hospital costs	−€2153.9 (95% CI: −€3407.46 to −€923.15)
Primary care costs	€15.42 (95% CI: −€75.53 to €127.95)
Patient costs	€11.26 (95% CI: −€261.95 to €308.62)
Productivity loss	€83.43 (95% CI: −€494.51 to €675.53)
QALY	0.008 (95% CI: −0.013 to 0.03)
IBD‐Control	0.15 (95% CI: −0.48 to 0.8)
Sensitivity analysis
Total costs	−€1933.69 (95% CI: €−3812.67 to €104.06)
Hospital costs	−€2090.30 (95% CI: −€3174.49 to −€1021.07)
Primary care costs	−€0.13 (95% CI: −€171.13 to €181.13)
Patient costs	€180.50 (95% CI: −€307.55 to €656.37)
Productivity loss	€186.68 (95% CI: −€857.91 to €1335.95)
QALY	0.001 (95% CI: −0.022 to 0.028)

Note: All costs are in €.

Abbreviations: CI, confidence interval; QALY, quality‐adjusted life years.

3.3. Quality Of Life

During the baseline period, quality of life was comparable between the control hospitals (0.835, 95% CI: 0.814 to 0.855) and the intervention hospitals (0.839, 95% CI: 0.825 to 0.852). Both increased during the intervention period, in the control hospitals to 0.844 (95% CI: 0.823 to 0.863) and to 0.849 (95% CI: 0.835 to 0.862) in the intervention hospitals (Figure 2A,B and Table S4). The visualisation of the pre‐intervention trends confirmed the validity of the parallel trend assumption, thereby justifying the use of the DiD‐analysis (Figure S2). Although the point estimate suggested a small positive effect, the 95% confidence interval included zero, indicating statistical uncertainty around the true impact of the ACP on QALYs QALY difference: 0.001 (95% CI: −0.019 to 0.023) (Figure 2C).

FIGURE 2.

Quality‐adjusted life years per group over time and Difference‐in‐Difference analysis. Note: Figure C shows the difference‐in‐differences estimates of quality‐of‐life differences between the intervention and control groups at three time points (12, 21, and 27 months), with a 95% confidence interval. Positive values indicate a higher quality of life in the intervention group relative to the controls, while negative values indicate lower quality‐of‐life values associated with the intervention. The horizontal dashed line represents zero difference. Abbreviations: QALY, quality‐adjusted life years.

3.4. IBD‐Control

Disease control, as measured with the IBD‐Control questionnaire, was comparable between the intervention (12.11, 95% CI: 11.77 to 12.41) and control hospitals (12.26, 95% CI: 11.75 to 12.74) during the baseline period (Figure 3A,B and Table S4). The estimated DiD effect was 0.15 (95% CI: −0.48 to 0.8), indicating a small non‐significant increase in IBD‐Control scores in the intervention hospitals relative to the control hospitals over time (Figure 3C).

FIGURE 3.

IBD‐Control scores per group over time and Difference‐in‐Difference analysis. Abbreviations: IBD, inflammatory bowel disease. Note: Figure C shows the difference‐in‐differences estimates of disease control measured with the IBD‐Control questionnaire quality‐of‐life differences between the intervention and control groups at three time points (12, 21, and 27 months), with a 95% confidence interval. Positive values indicate higher score values in the intervention group relative to the controls, while negative values indicate lower scores associated with the intervention. The horizontal dashed line represents zero difference.

3.5. Cost‐Utility Analysis

Figure 4 shows the cost‐utility (CU) plane; the plot represents 1000 bootstrap replications and illustrates the incremental difference in costs and QALYs associated with the ACP. The mean difference of the replications is −€1933.69 and is located in the lower right quadrant of the CU‐plane. This indicates that the ACP is associated with a reduction in costs while maintaining quality of life. The distribution of incremental cost and QALY pairs is skewed, with 73% falling on one side of the y‐axis and 23.5% on the other. This indicates that while the average estimated effect of the ACP on QALYs is small, there is considerable uncertainty. In contrast, there is less uncertainty concerning the effect on costs, as the majority of the pairs are positioned below the x‐axis. The probability that the ACP had a positive NMB was high, independent of the WTP threshold (Figure 4). This means that across a range of different values representing what a decision‐maker is willing to pay for an increase in QALYs, the ACP consistently showed a high likelihood of producing more monetary benefit than it costs in quality of life.

FIGURE 4.

Cost‐utility plane and cost‐utility acceptability curve. Abbreviations: QALY, Quality‐adjusted life years.

Interestingly, cost‐utility analysis showed contrasting results per IBD subtype. For patients with CD, the ACP had a high probability of a positive NMB regardless of WTP thresholds. In contrast, for patients with UC, a positive NMB was reached at a WTP threshold of €70,000 (see Figures S4, S5).

The cost‐utility analysis using UK values confirmed that the ACP remained cost‐effective see Figure S6 to Figure S8. This suggests that the clinical improvement observed is valued similarly across geographical regions.

3.6. Cost‐Effectiveness Analysis

The cost‐effectiveness plane (Figure 5) illustrates that the ACP is associated with reduced costs and a small increase in IBD‐Control scores, with the majority of estimates located in the southeast quadrant. The corresponding cost‐effectiveness acceptability curve (Figure 5) indicates that the ACP has a higher probability of being cost‐effective compared to usual care across all WTP thresholds. This suggests that, although the ACP has a small effect on IBD‐Control scores, the associated cost savings are sufficient to render it likely cost‐effective. These results are in line with the cost‐utility analysis.

FIGURE 5.

Cost‐effectiveness plane and cost‐effectiveness acceptability curve. Abbreviations: IBD, inflammatory bowel disease.

3.7. Biochemical Remission

During the baseline period, the proportion of patients in biochemical remission was comparable between the intervention and control hospitals (approximately 55% and 53%, respectively). During the intervention period, both groups demonstrated an increase in the proportion of patients in remission. As shown in Figure S9, there was no significant difference between the control and intervention hospitals, as the 95% confidence intervals crossed the zero line. These findings indicate that the implementation of the ACP did not adversely affect objective clinical outcomes compared to standard care.

4. Discussion

This study estimated the causal effect of an ACP for the treatment of IBD in patients using advanced therapies. We assessed the effect of the ACP on costs, quality of life, and disease control and conducted a cost‐utility and cost‐effectiveness analysis. Our findings indicate that the ACP was associated with a reduction in costs, primarily due to reduced hospital costs, while maintaining quality of life and disease control, independent of geographical area. Compared to standard care, the ACP emerged as a dominant strategy and demonstrated cost‐effectiveness across different WTP thresholds. Even at the maximum Dutch WTP threshold of €80,00, the ACP remained cost‐effective, suggesting it represents a sound investment from a health‐economic perspective. These findings could be of importance for healthcare policymakers and providers in IBD care because of the continuously increasing costs of treating this complex disease [5].

Given the economic burden of IBD, care pathways have been proposed to standardise care, reduce treatment variation and costs [10, 34]. However, research on care pathways and their effect on costs in IBD care remains limited [13, 35, 36]. Our study addresses this gap by implementing an ACP that integrates evidence‐based protocols across all aspects of IBD care and by conducting cost‐effectiveness and cost‐utility analyses [14]. The implementation of the ACP resulted in a reduction of costs and demonstrated cost‐effectiveness compared to standard care. The reduction in costs can be attributed to decreased healthcare utilisation, with substantial cost reductions observed in admissions, laboratory tests, outpatient clinic visits, and medication. The decrease in medication costs could be explained by the inclusion of de‐escalation recommendations. Importantly, these financial gains did not compromise clinical outcomes; a slight improvement in patient‐reported disease control scores was observed, indicating that disease control was maintained or marginally improved from a patient perspective. The use of cost‐utility and cost‐effectiveness analyses enabled assessment of both disease‐specific and patient‐centred outcomes, aligning with the value‐based healthcare principles [37]. Relying solely on generic quality‐of‐life metrics may obscure important clinical differences that are highly relevant in chronic disease management. Our results suggest that standardising clinical practice not only improves consistency in care but may also enhance early identification of disease activity, potentially prevent hospital admissions, and delay transitions to more costly treatment strategies. As such, the ACP offers a pragmatic and scalable strategy to optimise both clinical outcomes and resource use in IBD care [10, 38, 39].

Consistent with prior research, our study found that total annual costs for patients with IBD were primarily driven by healthcare costs [5, 6, 40, 41, 42]. Nevertheless, our annual direct costs (€18,738.77 in control hospitals and €19,456.57 in intervention hospitals) exceeded the estimated costs reported by The Lancet Gastroenterology & Hepatology Commission, which were $12,000 for Crohn's disease (CD) and $9000 for ulcerative colitis (UC) [43]. When adjusted to 2022 values and converted to euros, the costs were approximately €11,412 for CD and €8559 for UC per patient per year. Several factors may explain this discrepancy in costs, even after implementation of the ACP. One of the reasons for the higher costs in our study might be the inclusion of patients who were treated with advanced therapies only, which is associated with higher costs [40, 42, 44]. Second, the Commission's estimates are derived from data spanning different time periods, in which new guidelines and advanced therapies became available. Third, differences in healthcare systems, including pricing, reimbursement structures, and access to high‐cost therapies, likely contribute to variation in reported costs. Finally, our study used non‐contracted rates for cost calculations. In the Dutch healthcare system, these rates represent the maximum reimbursement levels and are generally higher than the actual negotiated prices paid by insurers for IBD care.

The ACP is closely aligned with ECCO guidelines, can reduce healthcare costs and might serve as a standard model for IBD care internationally. However, despite designing the ACP as a minimal care model, two outpatient consultations per year might increase workload and costs in less‐resourced care units. To mitigate this, a risk‐stratified ACP could be considered, using our ACP as a framework. High‐risk patients can be monitored twice yearly, whilst patients in stable remission might be monitored less frequently or based on patient‐initiated follow‐up. However, current guidelines recommend twice‐annual outpatient clinic visits when treated with advanced therapies [45]. Further studies should investigate whether monitoring frequency can be reduced for patients in stable remission.

As our research group has shown before, there was little to no treatment variation in IBD attributed to the hospitals [16]. In healthcare systems with greater regional variation, the impact of the ACP might differ and even be greater. Systems that have a higher baseline variation have more opportunities to eliminate low‐value care and optimise resource use [46, 47, 48]. Our ACP, focusing on standardising IBD‐care, such as outpatient clinic visits and laboratory testing, could be an effective strategy to reduce treatment variation and costs. As shown in the subgroup analysis, the ACP is cost‐effective for patients with CD independent of the WTP threshold. This might be explained by the difference in disease presentation and course, and could be a reason to apply the ACP only to patients with CD in countries where WTP‐thresholds are used.

Before this ACP can be disseminated to other hospitals in the Netherlands or other countries, future research should investigate adherence to the ACP, barriers and facilitators of its implementation and use, and its effect on other patient‐reported outcomes measures, which will be conducted by this research group [14]. The implementation of care pathways can be perceived as complex, and healthcare providers may not always support their use [49].

One of the strengths of this study is the use of observational real‐world data obtained from a natural experiment with a quasi‐experimental design, instead of data obtained from a randomised clinical trial. The study did not maintain strict inclusion criteria. This design enabled us to include a heterogeneous patient population that reflects routine clinical practice, and the results are therefore more representative of expected outcomes in comparable hospitals [50, 51, 52]. This enhances the external validity of our findings. Considering real‐world heterogeneity is particularly important in IBD, where disease phenotype and severity influence treatment patterns, costs, and outcomes. Despite relying on observational data, we estimated the causal effect of the ACP on outcomes. This was achieved through the design of the IBD Value study together with the DiD approach. Our approach mitigates potential biases arising from both between‐group and temporal differences [53, 54].

While interpreting these results, some limitations must be considered. First, the generalisability of our findings to other countries may be limited, as Dutch standard pricing was used to calculate costs. The healthcare organisation and reimbursement system in the Netherlands may differ from those in other countries. We mitigated this limitation by adding a cost‐utility analysis based on UK Pounds. Another limitation of this study is the absence of a standardised baseline, as patients were enrolled at varying points in their care trajectory. This may introduce heterogeneity in patient characteristics and treatment exposure at the time of inclusion, complicating comparability and potentially biasing estimates of the intervention's effect. However, we wanted to evaluate the effect of the ACP on overall IBD care, without specifying the effect per patient status. Thirdly, there may be residual confounding due to unmeasured hospital effects. Nevertheless, these results provide an indication of costs in a real‐world high‐income setting and the potential for cost reduction through the implementation of healthcare interventions. We tried to mitigate biases by implementing a DiD approach and conducting a sensitivity analysis, in which no effect of differences in baseline characteristics was observed.

5. Conclusion

The implementation of an ACP for the treatment of patients with IBD is cost‐effective and a dominant strategy compared to standard care. It reduces healthcare costs while maintaining quality of life and disease control. These results emphasise that clinical care pathways can reduce healthcare costs for complex diseases, and implementation in current practices should be considered.

Author Contributions

Hestia Vermeulen: writing – review and editing, resources, data curation. Sanne van der Wiel: writing – review and editing, resources, data curation. K. Evelyne Verweij: writing – review and editing, resources, data curation. Elyke H. Visser: funding acquisition, writing – original draft, methodology, visualization, writing – review and editing, formal analysis, data curation. Vincent de Jonge: writing – original draft, writing – review and editing, resources, data curation, conceptualization. Claire Fitzpatrick: writing – review and editing, resources, data curation. Martijn. A. Oude Voshaar: supervision, resources, formal analysis, writing – review and editing, methodology. Reinier C. A. van Linschoten: conceptualization, writing – review and editing, methodology, project administration, data curation. Alexander G. L. Bodelier: writing – review and editing, resources, data curation. R. L. West: writing – review and editing, conceptualization, investigation, funding acquisition, methodology, data curation, supervision, resources, project administration. D. van Noord: project administration, resources, supervision, data curation, writing – review and editing, methodology, conceptualization, investigation, funding acquisition. Daniëlle van der Horst: conceptualization, writing – review and editing. C. Janneke van der Woude: conceptualization, funding acquisition, writing – review and editing, methodology, resources, supervision, data curation.

Funding

This study was supported by this study was partly funded by AbbVie, Celltrion, Falk, Ferring, Janssen, Lilly, MSD, Pfizer, Takeda and Galapagos. The funders of the study had no role in the design of the study, collection, analysis, or interpretation of the data, or writing the report.

Ethics Statement

The medical ethical review committee of the Erasmus Medical Centre deemed the study not to be subject to the Medical Research Involving Human Subjects Act and provided a waiver (registration number MEC‐2020‐075).

Conflicts of Interest

E.H.V. received a speaker fee from Lilly. CJvdW has received research grants from ZonMW, Falk, and Pfizer; received consulting fees from Janssen, Galapagos, and Pfizer; received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Ferring and AbbVie; and held leadership roles in the European Crohn's & ColitisOrganisation, United European Gastroenterology Council and the Dutch Association for Gastroenterology. DvN has received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Janssen, Takeda, AbbVie, Galapagos, and B.M.S. R.L.W. has received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Ferring, Pfizer, Galapagos, AbbVie, and Janssen.

Supporting information

Table S1: Comparison of ECCO guidelines with ACP.

Table S2: Outcomes and their respective sources and definitions. Adapted from van Linschoten et al. [2].

Table S3: Baseline characteristics per hospital.

Table S4: Descriptive statistics by group and per year.

Table S5: Healthcare Costs.

Table S6: Primary care costs.

Table S7: Patient costs.

Table S8: Economic loss.

Figure S1: Pre‐intervention trend visualisation for total costs.

Figure S2: Pre‐intervention trends visualisation for quality of life.

Figure S3: Pre‐intervention trends visualisation for the IBD‐Control questionnaire.

Figure S4: Cost‐utility plane and cost‐utility acceptability curve for patients with CD.

Figure S5: Cost‐utility plane and cost‐utility acceptability curve for patients with UC.

Figure S6: Costs per category and per group over time, and Difference‐in‐Differences analysis for total costs.

Figure S7: Quality‐adjusted life years per group over time and Difference‐in‐Difference analysis.

Figure S8: Cost‐utility plane and cost‐utility acceptability curve.

Figure S9: Proportion biochemical remission per group over time (A) and DiD‐analysis (B).

Visser E. H., Voshaar M. A. O., van Linschoten R. C. A., et al., “A Care Pathway for the Treatment of IBD Reduces Healthcare Costs and Is Cost‐Effective: Results of the Multicentre IBD Value Study,” Alimentary Pharmacology & Therapeutics 64, no. 3 (2026): 313–325, 10.1111/apt.70690.

Data Availability Statement

Data are available upon reasonable request.