Abstract
Background
Nurses play a key role in inflammatory bowel disease (IBD) management. This randomized controlled trial evaluated intensive nurse-led program in patients with IBD starting advanced therapy.
Methods
Patients were randomized (1:1) to intensive nurse follow‑up (Arm A) or standard care (Arm B). Both arms received baseline nurse education; Arm A additionally had scheduled nurse calls and visits. Primary outcome was reduction in IBD‑Disk score in W12. Secondary outcomes were W52 reduction, robust response (> 20-point improvement), and IBD-Disk remission (score < 40).
Results
Overall, 98 patients were randomized (Arm A: n = 50; Arm B: n = 48) with similar baseline characteristics. Mean baseline IBD‑Disk scores were 49.2 ± 20.7 in Arm A and 42.0 ± 19.8 in Arm B (p = 0.07). At W12, both groups improved, with greater IBD-Disk reductions in Arm A (16.1 ± 22.9 vs. 10.1 ± 20.1, p = 0.09). At W52, improvement was greater in Arm A (18.4 ± 20.7 vs 9.4 ± 17.8; p = 0.08). More patients achieved robust response in Arm A (49% vs 21%, p = 0.013) at W12. By W52, IBD-Disk remission was achieved by 22/25 (88%) patients in Arm A vs 18/28 (64%) in Arm B (p = 0.045).
Conclusions
In this pilot randomized trial, intensive nurse-led follow-up did not significantly improve IBD-Disk at week 12, yet favorable trends of functional outcomes were observed. Intensive nurse‑led follow‑up program may improve quality of life in patients with IBD. These findings support the integration of specialist IBD nurses to improve patient‑centered outcomes.
Keywords: Inflammatory bowel disease, Randomized controlled trial, Nursing care, Quality of life, Multidisciplinary team
Introduction
Inflammatory bowel diseases (IBD) are chronic, relapsing–remitting disorders affecting millions worldwide, with rising prevalence in newly industrialized countries [1]. Long‑term complications include hospitalization, surgery, and disability. The treat‑to‑target paradigm advocates early intervention, tight control, and therapy adjustment based on objective markers. The STRIDE‑II consensus [2] specifies short‑, intermediate‑, and long‑term treatment goals, recommending scheduled assessment of disease activity using patient‑reported outcomes and biomarker normalization together with endoscopic healing. Non‑invasive biomarkers such as CRP and fecal calprotectin are widely used to assess inflammation and monitor response to therapy. Numerous scores have been developed for assessing quality of life in patients with IBD. The IBD‑Disk is a validated visual instrument [3, 4]. It covers ten domains (sleep, energy, pain, mobility, emotional well‑being, education/work, interpersonal interactions, body image, sexual function, and intimacy). Scores decrease when disease activity improves.
Specialist nurses have become integral to multidisciplinary IBD care [5]. They provide education, promote medication adherence, and triage symptoms. Despite this, the role remains undervalued, and there is limited high‑quality evidence for nurse‑led interventions.
This randomized controlled study tested the hypothesis that an intensive nurse‑led follow‑up program improves disability as measured by the IBD-disk [1, 2] compared with standard care among patients initiating advanced therapy.
Methods
Trial Design and Setting
This single‑center, open‑label, parallel‑group randomized controlled trial was conducted at Rabin Medical Center IBD (Israel), a tertiary referral center, from January 2018 to December 2021. The protocol was approved by the institutional review board (IRB #RMC‑17‑0693); all participants gave written informed consent.
Participants
Eligible participants were adults with a confirmed diagnosis of CD or UC based on endoscopic, histologic, and radiologic criteria who were starting biologic or small‑molecule therapy. Key exclusion criteria were prior ileal pouch‑anal anastomosis, severe psychiatric illness impairing consent, or participation in other interventional trials.
Randomization and Masking
Participants were randomly assigned 1:1 to Arm A (Intensive Nurse-Led Follow‑Up) or Arm B (Standard Care).
Interventions
All participants received a baseline nurse consultation, education on the disease, medication administration, and use of an IBD follow‑up card. In both arms, treatment initiation and therapeutic decisions were made by the treating gastroenterologist, including scheduled physician visits at baseline, week 12, and week 52. Arm A participants received a structured intensive nurse-led follow-up, including additional nurse telephone contacts at weeks 0 and 4 to address adherence, side‑effect management, and symptom triage, alongside in‑person nurse visits at week 12 (± 2 weeks) and week 52 (± 4 weeks) focusing on disability and functional assessment (IBD‑Disk), biomarker review, and reinforcement of self‑management. Arm B participants received solely routine physician visits as detailed, with laboratory monitoring per local practice, without scheduled nurse contact beyond standard clinical support.
Outcomes
Assessments were conducted at baseline, week 12 (± 2 weeks), and week 52 (± 4 weeks). The primary outcome was the change in IBD‑Disk score (0–100; higher values indicate greater disability) from baseline to week 12 to assess early change during induction and adjustment to advanced therapy. Secondary outcomes included changes in IBD‑Disk from baseline to week 52 and changes in CRP, fecal calprotectin, hemoglobin, and albumin at weeks 12 and 52. To capture more substantial improvement, we also prespecified a ≥ 20-point as ‘robust response’, an exploratory endpoint; additionally, we report a categorical target: IBD-Disk < 40 for reflecting functional remission [6]. Laboratory tests were performed by the hospital laboratory using standard assays. Demographic and clinical variables were recorded at baseline.
Statistical Analysis
Analyses were conducted with R 4.4.3. Participants with any post‑baseline measurement were analyzed in the arm to which they were randomized (intention‑to‑treat). The IBD‑Disk score difference (baseline minus follow‑up) was calculated for each patient. Between‑group differences were assessed using two‑sample t‑tests for continuous variables and chi‑square tests for categorical variables. Missing data was not imputed. A two‑sided p < 0.05 was considered statistically significant. As this was a pilot study, no formal sample size calculation was performed.
Results
Participant Flow and Baseline Characteristics
Of 105 participants assessed for eligibility, 98 met the inclusion criteria and were randomized (Arm A = 50, Arm B = 48; see Fig. 1). Mean age was 34.8 ± 14.2 years in Arm A and 39.5 ± 16.2 years in Arm B. Sex distribution, diagnosis (CD vs UC), and baseline biomarker values were similar between arms. Baseline IBD‑Disk scores averaged 49.2 in Arm A and 42.0 in Arm B (p = 0.07). Advanced therapies included adalimumab (n = 37), vedolizumab (n = 33), infliximab (n = 24), and ustekinumab (n = 2). Two patients did not receive a specific advanced-therapy recommendation after enrollment. Treatment distribution was similar between study arms (p = 0.77). Table 1 summarizes baseline characteristics.
Fig. 1.
Consort diagram of the study cohort
Table 1.
Baseline characteristics of study participants
| Characteristic | Arm A (n = 50) | Arm B (n = 48) | p value |
|---|---|---|---|
| Age, years (mean ± SD) | 34.8 ± 14.2 | 39.5 ± 16.2 | 0.14 |
| Male sex, n (%) | 24 (48%) | 23 (48%) | 0.99 |
| Diagnosis CD/UC, n | 28/22 | 27/21 | 0.91 |
| IBD‑Disk score | 49.2 ± 20.7 | 42.0 ± 19.8 | 0.07 |
| C‑reactive protein, mg/dL | 2.02 ± 3.28 | 1.25 ± 1.38 | 0.19 |
| Fecal calprotectin, µg/g | 2025 ± 3061 | 1168 ± 1833 | 0.10 |
| Hemoglobin, g/dL | 13.0 ± 1.74 | 13.3 ± 1.63 | 0.37 |
| Albumin, g/dL | 4.36 ± 0.59 | 4.42 ± 0.47 | 0.53 |
| Advanced therapy | 0.77 | ||
| Adalimumab | 18 | 19 | |
| Vedolizumab | 18 | 15 | |
| Infliximab | 13 | 11 | |
| Other | 1 | 3 |
CD Crohn’s disease, IBD inflammatory bowel disease, UC ulcerative colitis
Follow-up data were unavailable for 13/50 patients in Arm A and 14/48 in Arm B at week 12, most commonly because treatment was not initiated (9 and 8 patients, respectively). Between weeks 12 and 52, an additional 13 patients in Arm A and 7 in Arm B lacked week-52 data, most commonly due to loss to follow-up (6 and 7 patients, respectively).
Primary Outcome: Mean Change in IBD-Disk at Week 12
Mean IBD-Disk scores declined in both groups at week 12 (Fig. 2). Arm A improved by 16.1 ± 22.9 points (baseline minus week 12), whereas Arm B improved by 10.1 ± 20.1 points, with a between-group difference of 6.0 points (95% CI -4.3 to 16.3; p = 0.09).
Fig. 2.
Mean IBD‑Disk scores over time by study arm. Both treatment arms improved over time. Error bars indicate the standard error of the mean
Secondary Outcomes
We further assessed additional changes in IBD-DISK through week 12. A ≥ 20-point improvement in IBD-Disk (robust functional response) was achieved by 18/37 (49%) of Arm A versus 7/34 (21%) of Arm B participants [28.8 pp (7.6 to 49.9); p = 0.013].
An IBD-Disk score < 40 (low-disability / functional-remission threshold) was reached by 26/37 (70%) of Arm A and 26/34 (76%) of Arm B at week 12, p = 0.70 (see Table 2).
Table 2.
Change in IBD-Disk score and responder outcomes at weeks 12 and 52
| Outcome | Timepoint (week) | Arm A | Arm B | Between-group difference (A-B), 95% CI | p-value |
|---|---|---|---|---|---|
| Mean change in IBD-Disk (points) | 12 | n = 37, 16.1 ± 22.8 | n = 34, 10.1 ± 20.0 | + 6.2 (− 3.9 to 16.4) | 0.09 |
| 52 | n = 25, 18.4 ± 20.7 | n = 27, 9.4 ± 17.8 | + 6.8 (− 4.5 to 18.2) | 0.08 | |
| ≥ 20-point improvement, n/N (%) | 12 | 18/37 (49%) | 7/34 (21%) | + 28.8 pp (7.6 to 49.9) | 0.013 |
| 52 | 11/25 (44%) | 6/27 (22%) | + 14.1 pp (− 12.3 to 40.5) | 0.09 | |
| IBD-Disk < 40 ("low disability"), n/N (%) | 12 | 26/37 (70%) | 26/34 (76%) | − 5.1 pp (− 26.0 to 15.8) | 0.70 |
| 52 | 22/25 (88%) | 18/27 (66%) | + 23.0 pp (− 0.4 to 46.3) | 0.045 |
Change in IBD-Disk at Week 52
Mean improvement from baseline at week 52 was 18.4 ± 20.7 points in Arm A compared with 9.4 ± 17.8 in Arm B [between-group difference: 6.8 (−4.5 to 18.2); p = 0.08].
A ≥ 20-point improvement was observed in 11/25 (44%) of Arm A versus 6/27 (22%) of Arm B [between-group difference of 14.1 pp (-12.3 to 40.5); p = 0.09].
An IBD-Disk < 40 was achieved by 22/25 (88%) of Arm A participants compared with 18/27 (66%) of Arm B [between-group difference 23 pp (−0.4 to 46.3); p = 0.045].
Changes in Laboratory Markers
Table 3 summarizes changes in biomarkers from baseline to weeks 12 and 52. At week 12, CRP decreased more in Arm A (mean reduction 1.33 ± 3.04 mg/dL) than in Arm B (0.35 ± 2.71 mg/dL), but the difference was not significant (p = 0.19). Reductions in fecal calprotectin were larger in Arm A, but with wide variability and no significant differences. Hemoglobin increased modestly in both groups. By week 52, no biomarker difference was statistically significant, but trended toward better results in group A.
Table 3.
Changes in biomarkers from baseline
| Marker (baseline minus follow‑up) | Week 12 Arm A (mean ± SD) | Week 12 Arm B | p value | Week 52 Arm A | Week 52 Arm B | p value |
|---|---|---|---|---|---|---|
| CRP (mg/dL) | 1.33 ± 3.04 | 0.35 ± 2.71 | 0.19 | 2.06 ± 3.97 | 0.40 ± 6.74 | 0.12 |
| Fecal calprotectin (µg/g) | 1373 ± 3457 | 268 ± 3063 | 0.19 | 1478 ± 3381 | 742 ± 2664 | 0.40 |
| Hemoglobin (g/dL) | − 0.35 ± 1.20 | − 0.48 ± 1.26 | 0.67 | − 0.66 ± 1.27 | − 0.49 ± 1.41 | 0.65 |
| Albumin (g/dL) | − 0.14 ± 0.56 | 0.20 ± 0.46 | 0.008 | − 0.23 ± 0.64 | − 0.20 ± 0.60 | 0.81 |
CRP C-reactive protein
Discussion
This randomized trial evaluated whether a structured, nurse‑led follow‑up program improves disability outcomes compared with standard physician‑led care in patients starting advanced therapy for IBD. Intensive nurse follow‑up produced greater numerical improvements in IBD‑Disk scores at 12 and 52 weeks, although the primary endpoint at week 12 was not statistically different. Significant results were seen for robust responses defined a-priori as an improvement > 20 points in the IBD-disk and in achieving functional “remission” as defined by an IBD-disk score < 40. These findings suggest that nurse‑led interventions may enhance functional outcomes beyond medical treatment.
The IBD‑Disk is a validated visual instrument [3, 4]. It covers ten domains (sleep, energy, pain, mobility, emotional well‑being, education/work, interpersonal interactions, body image, sexual function, and intimacy). Scores decrease when disease activity improves.
A noteworthy aspect of this trial is that all participants were intended to initiate biologic or small‑molecule therapy at baseline. Such advanced therapies are themselves highly effective at inducing disease control and improving disability, and both study arms showed substantial reductions in IBD‑Disk scores over time. It was therefore expected that disability would improve irrespective of follow‑up regimen [7, 8]. The fact that a structured nurse‑led intervention may have conferred additional benefit beyond the pharmacologic effect of biologic induction suggests a synergistic effect of educational support and close monitoring on patient‑reported outcomes. This highlights the potential for allied health professionals to augment the gains achieved by potent therapies.
Our findings align with a growing body of evidence supporting the role of IBD nurse specialists in improving patient outcomes. Several studies have demonstrated that nurse-led interventions can reduce healthcare utilization and enhance disease monitoring. For example, a UK-based evaluation reported improved efficiency and continuity of care following the implementation of a nurse-led biologics service [9], while a Dutch population study observed reduced outpatient visits and increased patient satisfaction after introducing an IBD nurse position [10]. In our study, the proportion of patients achieving meaningful improvement in disability was comparable to or greater than those reported in structured nurse-led follow-up models across Australia and Europe [11, 12]. Notably, a recent randomized trial in Germany found that IBD nurse support significantly enhanced quality of life in patients on biologics [13], reinforcing the benefit of longitudinal nurse-patient relationships, especially in complex care pathways. Moreover, a Cochrane review [14] emphasized that telephone and virtual advice services, when embedded within nurse-led models, can contribute to improved outcomes and care accessibility. Collectively, these findings support our conclusion that structured, nurse-supported follow-up can improve disability and quality of life over time, particularly when sustained beyond the induction phase of treatment.
Strengths of this study include its randomized design, and the use of a validated disability instrument and biomarker assessments. The nurse intervention followed a structured protocol, ensuring consistency across participants. We also examined categorical thresholds of improvement to enhance interpretability. We selected a ≥ 20-point reduction as a marker of robust functional improvement, reflecting a change that might be more clinically meaningful at the individual level. Similarly, an IBD-Disk score < 40 has been proposed to represent low disability or 'functional remission,' consistent with prior validation data [3, 4, 6, 15, 16]. These thresholds provide complementary patient-centered perspectives alongside continuous score changes.
The trial is not without limitations: it was single‑center and open‑label, and performance and detection biases cannot be excluded. Follow-up completion was limited at both week 12 and week 52, as several patients never initiated therapy and others were subsequently lost to follow-up; although attrition was similar between groups, this reduced the effective sample size and may have affected the robustness of the findings. The study may have been underpowered, and baseline IBD‑Disk scores were numerically higher in Arm A, potentially leaving greater room for improvement. As this pilot study was designed to explore feasibility and estimate effect size, rather than provide a definitive efficacy estimate, it is limited by lacking formal sample size calculation that can be further based on these preliminary findings. Biomarker results exhibited wide variability, particularly for fecal calprotectin, limiting statistical power. Our primary outcome assessed early change at week 12, selected a priori to assess early changes during initiation of therapy, did not reach statistical significance; however, an extended follow-up at week 52 may better reflect the cumulative effect of structured nurse-led follow-up. Assessing qualitative patient satisfaction and perceptions of the intensive nurse-led intervention is of added value, and future studies should incorporate such measures alongside clinical and functional outcomes. We also did not prospectively quantify all non-protocol healthcare contacts, including unscheduled phone calls, urgent visits, administrative/email contacts, contacts related to treatment administration, or additional physician/nurse interactions outside the structured study schedule. Future trials should prospectively capture all healthcare contacts as a secondary endpoint.
In conclusion, our findings support the incorporation of IBD‑specialist nurses into multidisciplinary teams and the scheduling of structured follow‑up visits and telephone contacts as part of the patients follow up. Nurses can provide education, reinforce adherence, triage symptoms, and coordinate care with physicians. Nurse‑led programs may improve disability and quality‑of‑life outcomes without increasing physician workload.
Author Contributions
RB, IG, and HY conceived and designed the study. RB, IG, IAB, HB, YS, YB, ID, HY, and JEO recruited patients and collected the data. MF and JEO performed the statistical analysis. RB, MF, and JEO wrote the first draft of the manuscript. All authors critically revised the manuscript and approved the final version.
Funding
Open access funding provided by Tel Aviv University. The study was partially supported by a generous grant from The Leona M. and Harry B. Helmsley Charitable Trust.
Data availability
Data is unavailable due to privacy and ethical restrictions; it may be provided upon reasonable request.
Declarations
Conflict of interest
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Revital Barkan, and Idan Goren were co-first authors.
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Associated Data
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Data Availability Statement
Data is unavailable due to privacy and ethical restrictions; it may be provided upon reasonable request.