Abstract
Purpose
This study aimed to compare the long-term clinical characteristics, treatment patterns, and prognosis of inflammatory bowel disease (IBD) in patients diagnosed before and after 18 years of age.
Methods
A retrospective study was conducted using data from 384 patients with IBD with a disease duration exceeding 10 years across five hospitals. Baseline characteristics, disease status, and treatment patterns were analyzed at diagnosis, 5 years, 10 years, and present.
Results
Of the 384 patients, 84 (21.9%) and 300 (78.1%) were diagnosed before and at or older than the age of 18 years, respectively. Patients diagnosed before 18 years of age more frequently presented with Crohn’s disease (CD) (83.3% vs. 40.0%), whereas ulcerative colitis (UC) was predominant in those diagnosed later (16.7% vs. 60.0%). Younger patients had a significantly higher prevalence of abdominal pain (64.3% vs. 48.7%), malnutrition/weight loss (21.4% vs. 10.7%), and anal fistulas/abscesses (26.2% vs. 5.7%) at the time of diagnosis. Younger patients had more pancolitis-type UC (50% vs. 32.2%) and more perianal diseases in the CD group (51.4% vs. 20.8%). Younger patients initially exhibited higher rates of steroid usage, with a gradual shift towards biologics, such as infliximab. Multivariable Cox regression identified discontinuation of biologic therapy during follow-up as a significant risk factor for disease recurrence.
Conclusion
Our findings suggest that the age at IBD onset significantly is associated with disease progression and treatment outcomes, underscoring the need for age-tailored management strategies in long-term IBD care.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12876-026-04630-x.
Keywords: Inflammatory bowel disease, Pediatrics, Long-term, Risk factors
Introduction
Inflammatory bowel disease (IBD) is a global, growing group of chronic disease that causes intestinal inflammation, and includes Crohn’s disease (CD) and ulcerative colitis (UC) [1, 2]. Approximately 20–30% of patients are diagnosed during childhood or adolescence [3], whereas 25–35% present after the age of 60 [4]. Pediatric-onset IBD often shows a more extensive and aggressive disease course than adult-onset IBD, and children may face a longer disease duration and additional developmental or psychosocial impacts [5–7]. Although a small subset of patients diagnosed before the age of six may have underlying monogenic etiologies, these cases are rare [8]. Previous studies have identified several predictors of disease course in pediatric IBD, including age at diagnosis, disease location and behavior, serologic markers, and genetic variants such as NOD2/CARD15 [9]. Despite these findings, there remains limited evidence directly comparing long-term clinical outcomes between pediatric- and adult-onset IBD, particularly as an increasing proportion of children transition into adulthood with chronic disease.
The introduction of biologic agents has improved long-term outcomes in young patients, with early biologic therapy shown to reduce surgery and steroid dependency in CD [10–12]. However, reports on the follow-up of patients with IBD aged over 10 years using biological agents are still lacking. Therefore, this study aimed to compare the clinical features, treatment patterns, and long-term outcomes of patients with IBD with a disease duration of ≥ 10 years, stratified by diagnosis before or after 18 years of age.
Methods
Patients and study design
This multi-institutional retrospective study included patients with IBD followed for more than 10 years at five university hospitals between January 2010 and June 2023 and was conducted by the IBD research group of the Korean Association for the Study of Intestinal Diseases (KASID) in Korea. Diagnoses of UC and CD were based on clinical, endoscopic, histopathological, and radiologic findings [13, 14]. The baseline characteristics of the patients were obtained from the electronic medical data of each hospital, including patient demographics, type and disease status of IBD, symptoms at the time of IBD diagnosis, extraintestinal manifestations, comorbid diseases, family history of IBD, smoking/alcohol consumption, operations, and medication records at the time of diagnosis.
The subjects were patients who had been diagnosed with IBD for more than 10 years. The exclusion criteria were as follows: (i) in cases where the current disease status could not be confirmed or data were insufficient; (ii) in other cases where the researcher determined it was not appropriate. Therefore, 384 patients were enrolled in this study (Fig. 1). The analysis was divided into cases diagnosed before the age of 18 and cases diagnosed after the age of 18. We investigated IBD disease behavior and extent of invasion, severity, disease activity, treatment medication, and surgical status and followed up on the current status 5 and 10 years after diagnosis. All participating centers followed national KASID and ECCO guideline-based treatment strategies during the study period. This study was performed in accordance with the ethical guidelines of the 1975 Declaration of Helsinki and approved by the Institutional Review Board of each hospital.
Fig. 1.
Patient enrollment
Data collection
IBD disease behavior and activity were investigated at the time of diagnosis, 5 years later, 10 years later, and at present. Patients with insufficient data or difficulty in judging were excluded from the study. In patients with CD, disease localization and behavior were characterized based on the Montreal classification [15]. Disease activity was assessed using the Pediatric Crohn’s Disease Activity Index (PCDAI) in children under 18 years of age [16], but the Crohn’s Disease Activity Index (CDAI) [17] was also used in some cases; therefore, both were investigated. The CDAI was administered to adults aged 18 years or older.
In patients under 18 years of age, the Pediatric Ulcerative Colitis Activity Index (PUCAI) [18] was used, and cases in which the Mayo score or partial Mayo score had been applied were also reviewed. In adults 18 years of age or older, the mayo score or partial mayo score was used. The Mayo score was calculated based on the following four factors: (i) bowel frequency, (ii) rectal bleeding, (iii) endoscopic findings, and (iv) physician assessment [19]. In cases where endoscopic results were not available at the time of investigation, the partial Mayo score, including the three factors was used [19]. Among pediatric patients with Crohn’s disease, CDAI was applied in 4 of 70 cases (5.71%) in which PCDAI data were unavailable. Similarly, among pediatric patients with ulcerative colitis, the Mayo score was used in 1 of 14 cases (7.14%), whereas PUCAI was available in the remaining patients.
Outcomes and follow-up
We investigated the current medications used at the time of diagnosis, 5 years later, and 10 years later, and whether biologics were used or discontinued. Outcomes included recurrence, hospitalization, and death, as well as intestinal and extraintestinal complications (EIC) and systemic infections.
It is defined as follows: Recurrence is a clinical recurrence requiring corticosteroid administration, hospitalization, or intensification of treatment; Extraintestinal complications are identified inflammatory or drug-related systemic symptoms; Hospitalization is an unplanned admission related to disease activity or complications.
Statistical analysis
Continuous variables were summarized as medians with interquartile ranges and compared using the Mann–Whitney U test due to non-normal distributions confirmed by the Shapiro–Wilk test. Categorical variables were analyzed using the χ² test or Fisher’s exact test as appropriate.
Additionally, for cross-analyses of categorical data with large differences in size between the patient groups being compared, an effect size analysis was performed, using Cohen’s w. For continuous data, Cohen’s d was used to calculate the effect size.
Long-term outcomes, including recurrence was evaluated using Kaplan–Meier analyses with log-rank tests. Cox proportional hazards models were constructed to assess the association between age at diagnosis and clinical outcomes. The proportional hazards assumption was examined using Schoenfeld residuals, and no violations were detected. Multivariate analysis adjusted for gender and age, and variables that were significant with a P value of less than 0.05 in univariate analysis were analyzed. A small proportion of variables contained missing values, with no apparent patterns suggesting differential or informative missingness. Because the overall extent of missing data was minimal, all multivariable analyses were performed using a complete-case approach. The number of observations included in each analysis is reported accordingly. Data were analyzed using the SPSS software (version 25.0; IBM Corp., Armonk, NY, USA). A P-value of < 0.05 was considered statistically significant. The effect size was calculated using R software (version 4.4.1; https://www.r-project.org/).
Results
Comparison of baseline characteristics of diagnosed < 18 years and ≥ 18 years groups
Table 1 summarizes the baseline demographic and clinical characteristics of the two groups. A total of 384 patients with IBD were followed-up for more than 10 years at five university hospitals between January 2010 and June 2023. The early-onset IBD group consisted of 84 people (21.9%), and the adult-onset group consisted of 300 people (78.1%). At the time of IBD diagnosis, symptoms were abdominal pain (64.3% vs. 48.7%, P = 0.011) and malnutrition/weight loss (21.4% vs. 10.7%, P = 0.010), anal fistula/abscess (26.2% vs. 5.7%, P = 0.001) in those under 18 years of age compared to those over 18 years of age. In adults, bloody stools (39.3% vs. 70.7%, P = 0.001) and diarrhea (60.7% vs. 67.0%, P = 0.284) were common.
Table 1.
Baseline characteristics of IBD patients diagnosed before and after the age of 18
| Variables | Total (n = 384) |
< 18yrs (n = 84, 21.9%) |
≥ 18 yrs (n = 300, 78.1%) |
P-value |
|---|---|---|---|---|
| Male sex | 250 (65.1) | 54 (64.3) | 196 (65.3) | 0.859 |
| Symptoms at the time of IBD diagnosis | ||||
| Bloody stool | 245 (63.8) | 33 (39.3) | 212 (70.7) | 0.001 |
| Diarrhea | 252 (65.6) | 51 (60.7) | 201 (67.0) | 0.284 |
| Abdominal pain | 200 (52.1) | 54 (64.3) | 146 (48.7) | 0.011 |
| Fever | 27 (7.0) | 7 (8.3) | 20 (6.7) | 0.597 |
| Malnutrition/weight loss | 50 (13.0) | 18 (21.4) | 32 (10.7) | 0.010 |
| Anal fistula/abscess | 39 (10.2) | 22 (26.2) | 17 (5.7) | 0.001 |
| No symptom or diagnosis at colonoscopy | 10 (2.6) | 0 (0) | 10 (3.3) | 0.090 |
| Extra-intestinal manifestations | 108 (28.1) | 24 (28.6) | 84 (28.0) | 0.918 |
| Comorbidity | 165 (43.0) | 20 (23.8) | 145 (48.3) | 0.001 |
| Family history of IBD | 15 (3.9) | 2 (2.4) | 13 (4.3) | 0.414 |
| Alcohol | 0.001 | |||
| No | 295 (76.8) | 77 (91.7) | 218 (73.9) | |
| Social drinking | 86 (22.4) | 7 (8.3) | 79 (26.3) | |
| Heavy drinking | 3 (0.8) | 0 (0) | 3 (1.0) | |
| Smoking | 0.001 | |||
| No | 303 (79.3) | 81 (96.4) | 222 (74.5) | |
| Yes | 44 (11.5) | 3 (3.6) | 41 (13.8) | |
| Ex-smoker | 35 (9.2) | 0 (0) | 35 (11.7) | |
| Operation-related IBD | 123 (32.0) | 33 (39.3) | 90 (30.0) | 0.107 |
| Operation-others | 90 (23.5) | 15 (17.9) | 75 (25.1) | 0.168 |
| IBD type | 0.001 | |||
| Crohn’s disease | 190 (49.5) | 70 (83.3) | 120 (40.0) | |
| Ulcerative colitis | 194 (50.5) | 14 (16.7) | 180 (60.0) | |
Data are expressed as median (interquartile range, IQR) or n (%)
IBD Inflammatory bowel disease
*P-value for comparing IBD patients diagnosed before and after the age of 18
In addition, concomitant diseases, alcohol consumption, and smoking history were higher in patients aged ≥ 18 years. CD was significantly diagnosed in those under 18 years of age (83.3%), and UC was diagnosed in those over 18 years of age (60%) (Table 1).
Changes in medication use over time
Table 2; Fig. 2 present changes in medication use during follow-up. Steroid use at diagnosis was significantly higher in patients < 18 years than in those ≥ 18 years (65.1% vs. 45.0%, P = 0.001). At 5 years, the use of immunomodulators (56.0% vs. 42.0%, P = 0.023) and anti-TNF (44.0% vs. 28.0%, P = 0.005) remained higher in the younger group.
Table 2.
Distribution of medication use at the time of IBD diagnosis, 5 years later, and 10 years later
| Variables | Total (n = 384) |
< 18yrs (n = 84, 21.9%) |
≥ 18 yrs (n = 300, 78.1%) |
P-value | Effect Size 95%CI |
|---|---|---|---|---|---|
| Medication at diagnosis | |||||
| 5-ASA | 346 (90.1) | 75 (89.3) | 271 (90.3) | 0.776 | −0.03(−0.28 to 0.21) |
| Steroid | 189 (49.3) | 54 (65.1) | 135 (45.0) | 0.001 | 0.41(0.16 to 0.65) |
| IMM | 119 (31.0) | 31 (36.9) | 88 (29.3) | 0.185 | 0.16(−0.08 to 0.40) |
| Anti-TNF | 23 (6.0) | 6 (7.1) | 17 (5.7) | 0.614 | 0.06(−0.18 to 0.29) |
| Non-TNF Biologics | 2 (0.5) | 1 (1.2) | 1 (0.3) | 0.335 | 0.10(−0.14 to 0.35) |
| Others | 11 (2.9) | 4 (4.9) | 7 (2.3) | 0.224 | 0.14(−0.11 to 0.38) |
| Unknown | 18 (4.7) | 2 (2.4) | 16 (5.3) | 0.258 | −0.16(−0.40 to 0.09) |
| Medication at 5 years | |||||
| 5-ASA | 301 (78.4) | 61 (72.6) | 240 (80.0) | 0.146 | −0.17(−0.42 to 0.07) |
| Steroid | 87 (22.7) | 17 (20.2) | 70 (23.3) | 0.549 | −0.08(−032 to 0.17) |
| IMM | 173 (45.1) | 47 (56.0) | 126 (42.0) | 0.023 | 0.28(0.04 to 0.52) |
| Anti-TNF | 121 (31.5) | 37 (44.0) | 84 (28.0) | 0.005 | 0.33(0.09 to 0.58) |
| Non-TNF Biologics | 5 (1.3) | 2 (2.4) | 3 (1.0) | 0.324 | 0.11(−0.13 to 0.35) |
| Others | 8 (2.1) | 2 (2.4) | 6 (2.0) | 0.829 | 0.03(−0.22 to 0.27) |
| Unknown | 12 (3.1) | 2 (2.4) | 10 (3.3) | 0.657 | −0.06(−0.30 to 0.18) |
| Medication at 10 years | |||||
| 5-ASA | 271 (70.6) | 45 (53.6) | 226 (75.3) | 0.001 | −0.46(−0.70 to −0.22) |
| Steroid | 45 (11.7) | 3 (3.6) | 42 (14.0) | 0.009 | −0.39(−0.63 to −0.14) |
| IMM | 153 (39.8) | 45 (53.6) | 108 (36.0) | 0.004 | 0.36(0.11 to 0.60) |
| Anti-TNF | 144 (37.5) | 44 (52.4) | 100 (33.3) | 0.001 | 0.39(0.14 to 0.63) |
| Non-TNF Biologics | 52 (13.5) | 9 (10.7) | 43 (14.3) | 0.392 | −0.11(−0.35 to 0.13) |
| Others | 8 (2.1) | 1 (1.2) | 7 (2.3) | 0.515 | −0.09(−0.33 to 0.15) |
| Unknown | 8 (2.1) | 2 (2.4) | 6 (2.0) | 0.829 | 0.03(−0.22 to 0.27) |
| Medication currently used | |||||
| 5-ASA | 252 (65.6) | 39 (46.4) | 213 (71.0) | 0.001 | −0.50(−0.75 to −0.26) |
| Steroid | 14 (3.6) | 0 (0) | 14 (4.7) | 0.044 | −0.44(−0.68 to −0.19) |
| IMM | 125 (32.6) | 36 (42.9) | 89 (29.7) | 0.023 | 0.28(0.03 to 0.52) |
| Anti-TNF | 116 (30.3) | 38 (45.2) | 78 (26.1) | 0.001 | 0.40(016 to 0.64) |
| Non-TNF Biologics | 72 (18.8) | 15 (17.9) | 57 (19.0) | 0.813 | −0.03(−0.27 to 0.21) |
| Others | 5 (1.3) | 0 (0) | 5 (1.7) | 0.234 | −0.26(−0.50 to −0.02) |
| Unknown | 8 (2.1) | 1 (1.2) | 7 (2.3) | 0.517 | −0.09(−0.33 to 0.15) |
| Biologics combo therapy | 131 (62.1) | 40 (70.2) | 91 (59.1) | 0.141 | 0.22(−0.09 to 0.52) |
| Period until 1 st biologics use | 0.037 | 0.18(0.00 to 0.31) | |||
| <1 year | 30 (15.2) | 8 (15.1) | 22 (15.2) | ||
| 2–5 years | 63 (31.8) | 24 (45.3) | 39 (26.9) | ||
| ≥5 years | 105 (53.0) | 21 (39.6) | 84 (57.9) | ||
| Whether to maintain biologics | 0.091 | 0.13(0.00 to 0.22) | |||
| Never use | 164 (43.3) | 29 (34.5) | 135 (45.8) | ||
| Keep biologics | 180 (47.5) | 50 (59.5) | 130 (44.1) | ||
| Stop | 20 (5.3) | 3 (3.6) | 17 (5.8) | ||
| Unknown | 15 (4.0) | 2 (2.4) | 13 (4.4) | ||
| Reasons for discontinuation of biologics | 0.023 | 0.43(0.04 to 0.80) | |||
| Loss of response | 10 (35.7) | 4 (80.0) | 6 (26.1) | ||
| Anti-drug antibody | 0 (0) | 0 (0) | 0 (0) | ||
| Compliance | 0 (0) | 0 (0) | 0 (0) | ||
| Others | 18 (64.3) | 1 (20.0) | 17 (73.9) | ||
Data are expressed as median (interquartile range, IQR) or n (%)
5-ASA 5-aminosalicylic acid, IMM immunomodulatory, TNF tumor necrosis factor
*P-value for comparing IBD patients diagnosed before and after the age of 18
Fig. 2.
Changes in medication use: (A) < 18 years group and (B) ≥ 18 years group
Although early biologic use within 1 year did not differ between the groups (15.1% vs. 15.2%), biologic initiation after 5 years was more common in adults (39.6% vs. 57.9%). The median duration of biologic maintenance was 8.0 years (IQR, 3.74–11.22), with no significant difference between the groups (9.0 vs. 8.0 years, P = 0.536) (Table 3).
Table 3.
Clinical course of subjects
| Variables | Total (n = 384) |
< 18yrs (n = 84, 21.9%) |
≥ 18 yrs (n = 300, 78.1%) |
P-value |
|---|---|---|---|---|
| Age at diagnosis (yrs) | 30.12 (19.00–44.44.00.44) | 14.92 (12.91–16.57) | 34.52 (25.0–48.43.0.43) | 0.001 |
| Recur | 286 (74.5) | 62 (73.8) | 224 (74.7) | 0.873 |
|
Time to recur (from diagnosis, yrs) |
3.28 (1.10–6.11) | 2.78 (0.96–5.83) | 3.44 (1.15–6.21) | 0.611 |
| Admission | 224 (58.3) | 63 (75.0) | 161 (53.7) | 0.001 |
| Time to admission (yrs) | 1.05 (0–5.21.21) | 0.038 (0–1.39.39) | 2.24 (0.09–5.59) | 0.007 |
| Time to maintain biologics | 8.0 (3.74–11.22) | 9.0 (6.0–11.92.0.92) | 8.0 (3.20–11.00) | 0.536 |
| Final status | 0.645 | |||
| Follow-up | 346 (90.3) | 77 (92.8) | 269 (89.7) | |
| Follow-up loss | 36 (9.4) | 6 (7.2) | 30 (10.0) | |
| Death | 0 (0) | 0 (0) | 0 (0) | |
| Follow up period (yrs) | 13.12 (11.54–16.26) | 13.30 (11.42–16.80) | 13.04 (11.57–16.15) | 0.467 |
| GI Complication† | 85 (22.1) | 13 (15.5) | 72 (24.0) | 0.096 |
| Extra-intestinal complication†† | 130 (33.9) | 23 (27.4) | 107 (35.7) | 0.156 |
| Systemic infection | 10 (2.6) | 1 (1.2) | 9 (3.0) | 0.357 |
Data are expressed as median (interquartile range, IQR) or n (%)
GI gastrointestinal
*P-value for comparing patients
†stricture, fistula, viral colitis (CMV, C.difficile), ileus, hemorrhoid, abscess, polyp
††Erythema nodosum, IMM or biologics induced CNS symptom/leukopenia/hepatitis, tuberculosis
While biologic and IMM use was numerically higher in patients < 18 years, the difference was not significant (70.2% vs. 59.1%, P = 0.141). Biologic discontinuation occurred in 3.6% of younger patients and 5.8% of adults. Notably, loss of response accounted for 80% of discontinuations in the < 18 years group, whereas 73.9% of adults discontinued for reasons unrelated to treatment efficacy.
Clinical course of IBD patients over time
Table 3 summarizes long-term clinical outcomes. The median age at diagnosis was 14.92 years (IQR, 12.91–16.57) in those under 18 years of age and 34.52 years (IQR, 25.0–48.43.0.43) in those over 18 years of age (P = 0.001). There was no significant difference in recurrence rates between the two groups, with 73.8% of patients diagnosed before 18 years and 74.7% of those diagnosed at or after 18 years. However, the younger patient group was hospitalized significantly earlier (0.038 years [0–1.39.39] vs. 2.24 years [0.09–5.59]; P = 0.001). Approximately 90% of patients were followed up continuously, and the follow-up period was 13.12 years (IQR, 11.54–16.26). In addition, GI complications, extraintestinal complications, and systemic infections were all reported more frequently in patients aged ≥ 18 years, but there was no significant difference (Table 3).
Changes in disease extent, behavior, and disease activity
Crohn’s disease
Table 4; Figs. 3 and 4 summarize changes in CD phenotype and disease activity. Among 190 CD patients, 70 (36.8%) were < 18 years and 120 (63.2%) were ≥ 18 years.
Table 4.
Changes in disease extent, behavior and disease activity in patients with crohn’s disease (n = 190)
| Variables | Total (n=190) |
< 18yrs (n=70, 36.8%) |
≥ 18 yrs (n=120, 63.2%) |
P-value |
|---|---|---|---|---|
| Age at diagnosis | 0.001 | |||
| A1 (≤16yr) | 56 (29.5) | 56 (80.0) | 0 (0) | |
| A2 (17-40yr) | 124 (65.3) | 14 (20.0) | 110 (91.7) | |
| A3 (>40yr) | 10 (5.3) | 0 (0) | 10 (8.3) | |
| Location at diagnosis | 0.006 | |||
| L1 (Ileal) | 57 (30.5) | 11 (15.7) | 46 (39.3) | |
| L2 (Colonic) | 18 (9.6) | 11 (15.7) | 7 (6.0) | |
| L3 (Ileo-colonic) | 108 (57.8) | 47 (67.1) | 61 (52.1) | |
| L4 (Isolated upper disease) | 3 (1.6) | 1 (1.4) | 2 (1.7) | |
| L3+L4 | 1 (0.5) | 0 (0) | 1 (0.9) | |
| Behavior at diagnosis | 0.001 | |||
| B1 (non-stricturing non-penetrating) | 89 (47.6) | 27 (38.6) | 62 (53.0) | |
| B2 (Stricturing) | 25 (13.4) | 7 (10.0) | 18 (15.4) | |
| B3 (Penetrating) | 12 (6.4) | 0 (0) | 12 (10.3) | |
| p (Perianal) | 3 (1.6) | 2 (2.9) | 1 (0.9) | |
| B1+p | 46 (24.6) | 28 (40.0) | 18 (15.4) | |
| B2+p | 8 (4.3) | 4 (5.7) | 4 (3.4) | |
| B3+p | 4 (2.1) | 2 (2.9) | 2 (1.7) | |
| Disease activity | ||||
| PCDAI | 45.60 (31.25–122.28.25.28) | 45.60 (31.25–122.28.25.28) | - | |
| CDAI | 216.00 (158.30–285.75.30.75) | 136.20 (91.25–188.30.25.30) | 220.64 (166.25–293.80.25.80) | 0.067 |
| Location at 5years | 0.003 | |||
| L1 (Ileal) | 55 (29.3) | 11 (15.7) | 44 (37.3) | |
| L2 (Colonic) | 13 (6.9) | 9 (12.9) | 4 (3.4) | |
| L3 (Ileo-colonic) | 113 (60.1) | 49 (70.0) | 64 (54.2) | |
| L4 (Isolated upper disease) | 2 (1.1) | 0 (0) | 2 (1.7) | |
| L1+L4 | 1 (0.5) | 1 (1.4) | 0 (0) | |
| L2+L4 | 1 (0.5) | 0 (0) | 1 (0.8) | |
| L3+L4 | 3 (1.6) | 0 (0) | 3 (2.5) | |
| Behavior at 5years | 0.001 | |||
| B1 (non-stricturing non-penetrating) | 71 (37.8) | 24 (34.3) | 47 (39.8) | |
| B2 (Stricturing) | 29 (15.4) | 7 (10.0) | 22 (18.6) | |
| B3 (Penetrating) | 19 (10.1) | 0 (0) | 19 (16.1) | |
| B1+p (Perianal) | 50 (26.6) | 30 (42.9) | 20 (16.9) | |
| B2+p | 11 (5.9) | 5 (7.1) | 6 (5.1) | |
| B3+p | 8 (4.3) | 4 (5.7) | 4 (3.4) | |
| Disease activity | ||||
| PCDAI | 5.0 (0.0–20.00.0.00) | 5.0 (0.0–20.00.0.00) | - | |
| CDAI | 64.20 (19.11–129.15.11.15) | 100.0 (49.0–180.0.0.0) | 58.00 (13.95–120.79.95.79) | 0.230 |
| Location at 10years | 0.003 | |||
| L1 (Ileal) | 55 (28.9) | 11 (15.7) | 44 (36.7) | |
| L2 (Colonic) | 9 (4.7) | 7 (10.0) | 2 (1.7) | |
| L3 (Ileo-colonic) | 118 (62.1) | 50 (71.4) | 68 (56.7) | |
| L4 (Isolated upper disease) | 2 (1.1) | 0 (0) | 2 (1.7) | |
| L1+L4 | 1 (0.5) | 1 (1.4) | 0 (0) | |
| L3+L4 | 5 (2.6) | 1 (1.4) | 4 (3.3) | |
| Behavior at 10years | 0.001 | |||
| B1 (non-stricturing non-penetrating) | 60 (31.6) | 22 (31.4) | 38 (31.7) | |
| B2 (Stricturing) | 28 (14.7) | 6 (8.6) | 22 (18.3) | |
| B3 (Penetrating) | 24 (12.6) | 2 (2.9) | 22 (18.3) | |
| B1+p | 47 (24.7) | 31 (44.3) | 16 (13.3) | |
| B2+p | 18 (9.5) | 6 (8.6) | 12 (10.0) | |
| B3+p | 13 (6.8) | 3 (4.3) | 10 (8.3) | |
| Disease activity | ||||
| PCDAI | 12.00 (0.0–51.10.0.10) | 12.00 (0.0–51.10.0.10) | - | |
| CDAI | 48.30 (16.45–94.33.45.33) | 48.50 (24.50–77.00.50.00) | 48.20 (13.53–96.03.53.03) | 0.188 |
Data are expressed as median (interquartile range, IQR) or n (%). *P-value for comparing patients
PCDAI Pediatric Crohn’s Disease Activity Index, CDAI Crohn disease activity index
Fig. 3.
CD location: (A) < 18 years group and (B) ≥ 18 years group
Fig. 4.
CD behavior: (A) < 18 years group and (B) ≥ 18 years group
At diagnosis, L3 (ileocolonic) was the most common location in patients < 18 years, and the distribution showed no significant change at 5 and 10 years (67.1%→70.0%→71.4%). Some patients shifted from L2 (colonic) to L3 over time. In contrast, adult-onset CD more frequently involved L1 (ileal) and L3 (ileocolonic), with stable distribution during follow-up.
Regarding disease behavior, B1 (nonstricturing, nonpenetrating) was most common at diagnosis in the < 18 years group, with 40% presenting with perianal disease. These patterns persisted at 5 and 10 years, with a slight increase in perianal involvement and a small proportion progressing to B3 (penetrating). Adults more frequently had B1 disease at diagnosis (53.0%), but B2, B3, and perianal disease gradually increased over time.
Disease activity was high at diagnosis but improved markedly in both age groups at 5 and 10 years, with no significant between-group differences.
Ulcerative colitis
Table 5; Figs. 5 and 6 summarize phenotypic and activity changes in UC. Among 194 UC patients, 14 (7.2%) were < 18 years and 180 (92.8%) were ≥ 18 years. In the < 18 years group, E3 (pancolitis) accounted for 50% at diagnosis and remained most common during follow-up, although E1 (proctitis) increased over time (21.4%→42.9%).
Table 5.
Changes in disease extent/severity and disease activity in patients with ulcerative colitis (n = 194)
| Variables | Total (n = 194) |
< 18yrs (n = 14, 7.2%) |
≥ 18yrs (n = 180, 92.8%) |
P-value |
|---|---|---|---|---|
| At diagnosis | ||||
| UC Extension | 0.429 | |||
| E1 (proctitis) | 74 (38.1) | 3 (21.4) | 71 (39.4) | |
| E2 (left-side) | 50 (25.8) | 4 (28.6) | 46 (25.6) | |
| E3 (pan-colitis) | 65 (33.5) | 7 (50.0) | 58 (32.2) | |
| Unknown | 5 (2.6) | 0 (0) | 5 (2.8) | |
| UC severity | 0.396 | |||
| S0 (asymptomatic) | 1 (0.5) | 0 (0) | 1 (0.6) | |
| S1 (mild) | 71 (36.6) | 4 (28.6) | 67 (37.2) | |
| S2 (moderate) | 79 (40.7) | 9 (64.3) | 70 (38.9) | |
| S3 (severe) | 31 (16.0) | 1 (7.1) | 30 (16.7) | |
| Unknown | 12 (6.2) | 0 (0) | 12 (6.7) | |
| Disease activity | ||||
| PUCAI | 25.0 (13.25–51.25) | 25.0 (13.25–51.25) | - | |
| Mayo score | 6.0 (5.0–8.0) | 4.0 (4.0–4.0) | 6.0 (5.0–8.0) | 0.322 |
| Partial mayo score | 3.5 (2.0–6.25.0.25) | - | 3.5 (2.0–6.25.0.25) | |
| At 5 years | ||||
| UC Extension | 0.494 | |||
| E1 (proctitis) | 64 (33.0) | 5 (35.7) | 59 (32.8) | |
| E2 (left-side) | 57 (29.4) | 2 (14.3) | 55 (30.6) | |
| E3 (pan-colitis) | 69 (35.6) | 7 (50.0) | 62 (34.4) | |
| Unknown | 4 (2.1) | 0 (0) | 4 (2.2) | |
| UC severity | 0.954 | |||
| S0 (asymptomatic) | 42 (21.6) | 3 (21.4) | 39 (21.7) | |
| S1 (mild) | 87 (44.8) | 7 (50.0) | 80 (44.4) | |
| S2 (moderate) | 48 (24.7) | 3 (21.4) | 45 (25.0) | |
| S3 (severe) | 11 (5.7) | 1 (7.1) | 10 (5.6) | |
| Unknown | 6 (3.1) | 0 (0) | 6 (3.3) | |
| Disease activity | ||||
| PUCAI | 10.0 (5.0–17.5.0.5) | 10.0 (5.0–17.5.0.5) | - | |
| Mayo score | 3.0 (0.0–5.0) | 3.0 (1.25–9.25) | 3.0 (0.0–5.0) | 0.428 |
| Partial mayo score | 2.0 (0.0–2.0) | - | 2.0 (0.0–2.0) | |
| At 10 years | ||||
| UC Extension | 0.571 | |||
| E1 (proctitis) | 65 (33.5) | 6 (42.9) | 59 (32.8) | |
| E2 (left-side) | 58 (29.9) | 2 (14.3) | 56 (31.1) | |
| E3 (pan-colitis) | 69 (35.6) | 6 (42.9) | 63 (35.0) | |
| Unknown | 2 (1.0) | 0 (0) | 2 (1.1) | |
| UC severity | 0.377 | |||
| S0 (asymptomatic) | 77 (39.7) | 7 (50.0) | 70 (38.9) | |
| S1 (mild) | 66 (34.0) | 6 (42.9) | 60 (33.3) | |
| S2 (moderate) | 37 (19.1) | 0 (0) | 37 (20.6) | |
| S3 (severe) | 9 (4.6) | 1(7.1) | 8 (4.4) | |
| Unknown | 5 (2.6) | 0 (0) | 5 (2.8) | |
| Disease activity | ||||
| PUCAI (< 18 year) | 0.0 (0.0–10.0) | 0.0 (0.0–10.0) | - | |
| Mayo score (≥ 18 year) | 2.0 (0.0–4.0) | 1.0 (0–4.5.5) | 2.0 (0.0–4.0) | 0.977 |
| Partial mayo score (≥ 18 year) | 0.0 (0.0–2.0) | - | 0.0 (0.0–2.0) | |
Data are expressed as median (interquartile range, IQR) or n (%)
UC ulcerative colitis, PUCAI Pediatric Ulcerative Colitis Activity Index
*P-value for comparing patients
Fig. 5.
UC extension: (A) < 18 years group and (B) ≥ 18 years group
Fig. 6.
UC severity: (A) < 18 years group and (B) ≥ 18 years group
Among adults, E1, E2, and E3 were observed at similar frequencies throughout the disease course. Regarding disease severity, 64.3% of younger patients initially had S2 (moderate) disease, which improved to predominantly S0–S1 by 10 years. Adults had a higher proportion of S3 (severe) disease at diagnosis (16.7%), though severity improved in both groups over time.
Risk factors of recurrence
Table 6 presents the Cox regression analysis of relapse risk. In univariate analysis, asymptomatic presentation, extraintestinal manifestations, comorbidities, biologic discontinuation, and both GI and extraintestinal complications were significantly associated with relapse.
Table 6.
Relative risk of recur (Cox-regression)
| Variable | Uni-variate analysis | Multi-variate analysis | ||
|---|---|---|---|---|
| HR (95% CI) | P-value | Adjusted HR (95% CI) | P-value | |
| Male sex | 1.110 (0.864–1.424) | 0.414 | 0.934 (0.720–1.213) | 0.610 |
| Diagnosis under 18yrs | 1.096 (0.825–1.456) | 0.526 | 1.101 (0.820–1.478) | 0.523 |
| Symptom at diagnosis | ||||
| Bloody stool | 1.078 (0.848–1.368) | 0.540 | ||
| Diarrhea | 0.949 (0.744–1.209) | 0.671 | ||
| Abdominal pain | 1.142 (0.904–1.443) | 0.265 | ||
| Fever | 1.267 (0.812–1.978) | 0.297 | ||
| Malnutrition/weight loss | 0.949 (0.683–1.320) | 0.757 | ||
| Fistula/abscess | 1.287 (0.902–1.835) | 0.164 | ||
| Extra-intestinal manifestation | 1.311 (1.016–1.692) | 0.037 | 0.873 (0.623–1.223) | 0.429 |
| Comorbidity | 1.390 (1.098–1.759) | 0.006 | 1.168 (0.880–1.551) | 0.283 |
| Family history of IBD | 1.717 (0.937–3.147) | 0.080 | ||
| Alcohol | ||||
| No | 1.0 (ref.) | |||
| Social drinking | 0.990 (0.753–1.301) | 0.941 | ||
| Heavy drinking | 1.046 (0.260–4.215) | 0.950 | ||
| Smoking | ||||
| No | 1.0 (ref.) | |||
| Yes | 1.085 (0.765–1.540) | 0.647 | ||
| Ex-smoker | 1.027 (0.688–1.533) | 0.896 | ||
| IBD type | ||||
| Crohn’s disease | 1.0 (ref.) | |||
| Ulcerative colitis | 0.938 (0.743–1.185) | 0.591 | ||
| Biologics combo therapy | 1.126 (0.830–1.528) | 0.444 | ||
| Whether to maintain biologics | ||||
| Never use | 1.0 (ref.) | 1.0 (ref.) | ||
| Keep biologics | 1.213 (0.936–1.571) | 0.144 | 1.163 (0.889–1.522) | 0.271 |
| Stop | 1.737 (1.045–2.887) | 0.033 | 1.704 (1.002–2.900.002.900) | 0.049 |
| Unknown | 0.472 (0.239–0.929) | 0.030 | 0.512 (0.259–1.010) | 0.053 |
| GI Complication† | 1.452 (1.107–1.905) | 0.007 | 1.346 (0.980–1.849) | 0.066 |
| Extra-intestinal complication†† | 1.552 (1.222–1.972) | 0.001 | 1.359 (1.010–1.828) | 0.042 |
| Systemic infection | 1.115 (0.526–2.365) | 0.777 | ||
HR hazard ratio, CI confidence interval, IBD Inflammatory bowel disease, GI gastrointestinal
†Stricture, fistula, viral colitis (CMV, C.difficile), ileus, hemorrhoid, abscess, polyp
††Erythema nodosum, IMM or biologics induced CNS symptom/leukopenia/hepatitis, tuberculosis
After adjusting for age and sex, discontinuation of biologic therapy (HR 1.704; 95% CI 1.002–2.900; P = 0.049) and extraintestinal complications (HR 1.359; 95% CI 1.010–1.828; P = 0.042) remained significant predictors. The risk of recurrence in patients with CD and UC, respectively, is summarized in Supplementary Tables 1 and 2.
Kaplan–Meier curves demonstrated no difference in time to recurrence between pediatric- and adult-onset groups (log-rank P = 0.525), whereas time to hospitalization was significantly shorter in the younger group (log-rank P = 0.004). These findings are depicted in Supplementary Fig. 1.
Discussion
Inflammatory bowel disease (IBD) is a chronic, relapsing condition that can significantly impair quality of life due to recurrent inflammation, complications, and the need for long-term therapy. Pediatric-onset IBD accounts for approximately 10–15% of all cases [20–22], and its incidence continues to rise globally, including in regions where pediatric IBD was previously rare [23]. Early-onset IBD is generally characterized by more extensive and aggressive inflammation, rapid progression, and distinct genetic and immunologic features compared with adult-onset disease. Previous studies have reported that children with CD typically present with inflammatory behavior but often progress to stenotic or penetrating phenotypes during follow-up [24–27].
In our study, pediatric CD patients most commonly presented with ileocolonic involvement (L3, 67.1%), B1 behavior (38.6%), and perianal lesions (51.4%), with gradual progression toward B2 and B3 at 5 and 10 years. Similarly, earlier literature has reported that up to 74.7% of early-onset pediatric UC cases present with pancolitis [28]. In our cohort, 50% of pediatric UC patients exhibited E3 disease at diagnosis, and 64.3% showed moderate activity (S2). Furthermore, abdominal pain, malnutrition/weight loss, and perianal fistula or abscess were significantly more common in pediatric patients than in adults, consistent with earlier reports linking pediatric-onset IBD with an increased risk of growth delay [29, 30] and higher likelihood of surgical intervention [7, 25]. These findings underscore the importance of timely diagnosis and early therapeutic intervention in this population.
Long-term disease management is essential for patients diagnosed during the transition from childhood to adulthood. The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the European Crohn’s and Colitis Organization (ECCO) recommend structured transition programs to ensure continuity of care [31, 32]. In our cohort, most pediatric-onset patients remained in continuous follow-up (92.8%), and biologic therapy was maintained for a median of nine years. Although steroid use was higher at diagnosis among pediatric patients, it decreased markedly over 5 and 10 years as patients transitioned to immunomodulators and biologics.
Multiple studies have confirmed the long-term efficacy and safety of anti-TNF therapy in pediatric IBD [33–35]. Vahabnezhad et al. [34] reported that 82% of pediatric CD patients maintained infliximab treatment for five years, with discontinuation mainly due to anti-drug antibodies and infusion reactions. Our findings similarly demonstrate durable biologic maintenance exceeding nine years, with loss of response (LOR) being the most frequent reason for discontinuation (80.0% in < 18 years). Pediatric patients more frequently initiated biologics within five years of diagnosis compared with adults, supporting the increasing emphasis on early biologic treatment in young patients with high-risk features.
IBD is a lifelong disease associated with complications, cancer risk, and comorbid illnesses over time [36, 37]. Although IBD is increasingly recognized among older adults [38, 39], our cohort did not include elderly patients; the adult-onset group in our study had a relatively young mean age of 34.5 years. Nevertheless, adults exhibited higher rates of comorbidities and gastrointestinal and extraintestinal complications. UC was more prevalent among adults, with many patients presenting with bloody stools and severe disease (S3) at diagnosis. During follow-up, neoplastic complications were rare but notable, including five cases requiring polypectomy or ESD (1.6%) and two colorectal cancers (0.7%). These findings stress the importance of continuous surveillance and a multidisciplinary approach.
Although recurrence rates were similar between pediatric- and adult-onset IBD (73.8% vs. 74.7%), pediatric patients experienced earlier and more frequent hospitalizations (75.0% vs. 53.7%). Cox regression analysis identified discontinuation of biologic therapy as a significant predictor of relapse. Stoker et al. demonstrated substantially higher relapse rates after biologic withdrawal, with cumulative relapse rates of 47–58% in discontinuation groups compared with 18% in maintenance groups at 36 months [40]. In our study as well, the primary reason for biologic discontinuation was LOR (35.7%), whereas remission, patient preference, pregnancy, and side effects accounted for a smaller proportion. Maintaining biologic therapy therefore appears critical for long-term remission control.
Extraintestinal complications (EICs) may arise from both disease activity and pharmacologic therapy. Drug-related arthropathy, neuropathy, hepatotoxicity, and nephrotoxicity have been described in previous studies [41]. In our cohort, EICs such as erythema nodosum, treatment-related CNS symptoms, leukopenia, hepatitis, and tuberculosis occasionally necessitated treatment modification, potentially increasing relapse risk.
This study has several limitations. First, as a multicenter retrospective analysis, heterogeneity in disease activity assessment and missing data was unavoidable. In pediatric patients, CDAI or Mayo/partial Mayo scores were sometimes used instead of PCDAI or PUCAI, introducing the potential for measurement bias and requiring separate analyses for each index. Treatment practices may also have varied across institutions and clinicians, although management was generally guided by KASID and ECCO recommendations. Second, the number of pediatric-onset UC cases was small (n = 14), resulting in limited statistical power and restricted generalizability; thus, conclusions regarding changes in disease extent should be interpreted with caution. Third, differences in approval criteria for non–anti-TNF biologics (e.g., vedolizumab, ustekinumab, tofacitinib) between children and adults raise the possibility of temporal or selection bias. Nevertheless, trends observed in Table 2 indicate that the 10-year follow-up period was sufficient to evaluate overall treatment patterns. Fourth, biologic use and discontinuation were analyzed as baseline covariates rather than time-dependent exposures, even though these treatments change during follow-up. This approach may introduce bias in the estimated effects, and future prospective studies with detailed longitudinal treatment data are needed to apply fully time-dependent Cox models. In addition, this study did not adjust for potential confounders such as socioeconomic status or detailed genetic information, which may influence disease phenotype and long-term outcomes in IBD. These unmeasured factors could have contributed to residual confounding and should be considered when interpreting the results. However, although these limitations exist, a major strength of our study is the long-term follow-up of more than 10 years, allowing comprehensive evaluation of disease behavior, treatment patterns, and outcomes in Korean patients with both pediatric- and adult-onset IBD.
Conclusion
In conclusion, this multicenter study with over 10 years of follow-up demonstrates clear age-related differences in the presentation and course of IBD. Pediatric-onset patients showed more extensive disease, frequent perianal involvement, and earlier need for immunomodulators and biologics. Although recurrence rates were similar, younger patients were hospitalized earlier, and sustained biologic therapy was a key factor in preventing relapse. These findings highlight the importance of early recognition, age-appropriate treatment strategies, and consistent long-term management.
Clinically, the results support early biologic intervention in high-risk pediatric IBD and emphasize the need for structured transition programs to maintain continuity of care. Future studies should further evaluate the optimal timing and duration of biologic therapy and assess long-term outcomes of emerging therapeutic agents across age groups.
Supplementary Information
Supplementary Material 2: Supplementary Figure 1. Kaplan Meier plots for (a) time to recurrence and (b) time to hospitalization by age at diagnosis groups
Acknowledgements
Guarantor of the article: P.S.B.
Specific author contributions: P.Y.E.: data acquisition, data analysis and interpretation, and manuscript drafting. K.S.B.: Data acquisition, study concepts, and design. P.Y.: Data acquisition, study concept, and design. K.D.S: study concept and design, and critical revision of the manuscript for important intellectual content. N.S-Y.: Study concept and design, and critical revision of the manuscript for important intellectual content. M.W.: study concept and design, critical revision of the manuscript for important intellectual content. P.S.B.: data acquisition; study concept and design; critical revision of the manuscript for important intellectual content. All authors approved the final version of the manuscript, including the authorship list.
Ethical considerations
This study was performed in accordance with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the institutional review board of each hospital. HPIRB 2023-07-025-003; PNUY IRB 55-2023-044; Daejeon St. Mary’s Hospital IRB; EWS IRB 2024-01-028; KYUH IRB 2023-09-018-002.
Authors’ contributions
Specific author contributions: P.Y.E.: data acquisition, data analysis and interpretation, and manuscript drafting. K.S.B.: Data acquisition, study concepts, and design. P.Y.: Data acquisition, study concept, and design. K.D.S: study concept and design, and critical revision of the manuscript for important intellectual content. N.S-Y.: Study concept and design, and critical revision of the manuscript for important intellectual content. M.W.: study concept and design, critical revision of the manuscript for important intellectual content. P.S.B.: data acquisition; study concept and design; critical revision of the manuscript for important intellectual content. All authors approved the final version of the manuscript, including the authorship list.
Funding
This study was supported by the Research Supporting Program of the Korean Association for the Study of Intestinal Diseases for 2023.
Data availability
The data that support the findings of this study are not publicly available due to privacy or ethical restrictions. Data are available from the corresponding author upon reasonable request and with approval from the relevant institutional review board.
Declarations
Ethics approval and consent to participate
This study is a retrospective medical record analysis study, and consent was waived by the IRB.
Consent for publication
Not Applicable.
Competing interests
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.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary Material 2: Supplementary Figure 1. Kaplan Meier plots for (a) time to recurrence and (b) time to hospitalization by age at diagnosis groups
Data Availability Statement
The data that support the findings of this study are not publicly available due to privacy or ethical restrictions. Data are available from the corresponding author upon reasonable request and with approval from the relevant institutional review board.