ABSTRACT
Background
We aimed to determine corticosteroid (CS) use in paediatric inflammatory bowel disease (PIBD, < 18 years), which remains common despite recommendations for limited use and the emergence of steroid‐sparing therapies.
Methods
We conducted a study of all children in Sweden diagnosed with CD (n = 2460) or UC (n = 2470) in 2006–2022. Nationwide health registers provided annual individual‐level data on CS use, classified as any use and excess use (i.e., ≥ 2 courses or ≥ 3 months of use per year).
Results
The mean age at diagnosis was 13.7 (SD = 3.4) for CD and 13.9 (SD = 3.8) years for UC. In CD, the proportion of patients with any annual CS use decreased from 42.9% (2006) to 27.6% (2022; p < 0.001), particularly for excess CS use (decreasing from 33.7% to 19.1%; p < 0.001). Rates in UC remained largely unchanged, with any CS use at 41.0% in 2006 and 43.6% in 2022 (p = 0.43), while excess use was 32.4% in 2006 and 36.2% in 2022 (p = 0.21). Although any CS use was most common during the first year after diagnosis (CD: 63.8%, UC: 70.6%), annual rates stabilised only during the fourth (CD) and fifth (UC) years of diagnosis. Older age at diagnosis and prior IBD‐related hospitalisation were risk factors for excess CS use in both CD and UC.
Conclusions
The use of CS in PIBD remains high, with annual rates showing no reduction in UC over the past more than 15 years, while a marked decline is observed in CD. Our data should inform strategies to reduce excess CS use in children.
Keywords: colitis ulcerosa, IBD, morbus crohn, population based, steroid
key Summary
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Summarise the established knowledge on this subject.
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Corticosteroids (CS) remain commonly used for inflammatory bowel disease (IBD) but their use in children raises concerns about growth, bone health, and metabolic complications.
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Advanced therapies for IBD have expanded over the past 2 decades, offering steroid‐sparing alternatives.
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There is limited data on CS use by IBD subtype, patient characteristics, and longitudinal prescribing patterns in children with IBD, hampering efforts to reduce CS exposure.
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What are the significant and/or new findings of this study?
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This cohort study provided data on CS use in all Swedish children diagnosed with Crohn's disease or ulcerative colitis in 2006–2022.
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During the study period, we observed a marked decline in CS use for Crohn's disease, while the use for ulcerative colitis remained largely unchanged over time.
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In both IBD subtypes, children with older age at diagnosis and prior IBD‐related hospitalisation were at higher risk of excess CS use.
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Abbreviations
- 5‐ASA
5‐aminosalicylic acid
- CD
Crohn's disease
- CI
Confidence interval
- CS
Corticosteroid
- IBD
Inflammatory bowel disease
- IBD‐U
IBD‐unclassified
- ICD
International Classification of Diseases
- IQR
Interquartile range
- NPR
National Patient Register
- OR
Odds ratio
- PIBD
Paediatric‐onset inflammatory bowel disease
- SD
Standard deviation
- SWIBREG
Swedish Quality Register for IBD
- UC
Ulcerative colitis
1. Introduction
Inflammatory bowel disease (IBD) includes chronic, immune‐mediated conditions primarily classified into Crohn's disease (CD) and ulcerative colitis (UC). Over the past decades, there has been a global rise in the incidence of paediatric‐onset IBD (PIBD, < 18 years) [1, 2], the management of which presents marked challenges, with a need to balance timely and effective disease control with the avoidance of adverse effects. Corticosteroids (CS) have long been integral to IBD treatment due to their rapid anti‐inflammatory properties [3]. However, CS use in children requires particular attention to impaired growth, bone health, and metabolic disturbances, raising concerns about their long‐term safety [4, 5, 6, 7].
Over the past 2 decades, the emergence and steady increase in the availability of advanced therapies has reshaped the IBD treatment landscape, providing steroid‐sparing alternatives to immunomodulators. Despite these advancements, and recommendations to limit their use [8, 9, 10], CS remains widely utilised in children, particularly during flares and as a bridge to other therapies. However, today's use of CS in PIBD has been inadequately examined, leaving gaps in understanding its use by IBD subtypes and patient characteristics. Longitudinal data on CS prescription patterns are also lacking. Addressing these knowledge gaps may inform strategies for minimising CS exposure in PIBD.
This nationwide study aimed to determine the overall CS use in PIBD across calendar years and time since IBD diagnosis, and relate to disease, patient and treatment characteristics.
2. Materials and Methods
This register‐based study was based on prospectively collected routine healthcare data from Sweden. The Swedish healthcare system is universal and tax‐funded [11]; therefore, the register captures data on the entire national population. Children (< 18 years) are exempt from co‐payments for prescription drugs and outpatient and inpatient care.
2.1. Study Sample
The source population of this study was all Swedish children with an IBD diagnosis (either incident or prevalent) occurring between 2006 and 2022. We defined IBD as having either ≥ 2 International Classification of Diseases (ICD) codes in the Swedish National Patient Register (NPR) [12, 13] or ≥ 1 ICD code and ≥ 1 relevant ileo‐colorectal histopathology (Systematized Nomenclature of Medicine, SNOMED) code (Supporting Information S1: Tables S1–S2). This IBD definition has demonstrated a positive predictive value of 93%–95% for a clinical diagnosis of IBD in children [14]. Subtype‐specific ICD codes were used to classify UC and CD [15, 16]. Children with a mix of these codes were classified as IBD‐unclassified (IBD‐U) and were excluded due to their particularly high likelihood of later being reclassified as UC or CD [17], which could hamper disease‐specific analyses of longitudinal CS trends. Additionally, treatment approaches for IBD‐U are more heterogeneous compared with those for UC and CD. The NPR captures all inpatient care diagnoses since 1987, with hospital‐based outpatient diagnoses recorded since 2001 [12, 13].
This study included patients with an incident and prevalent diagnosis of CD or UC (Supporting Information S1: Figure S1). Incident diagnoses defined as a first‐ever record of CD or UC in 2006–2022. Patients who fulfilled our PIBD definition and who had a diagnostic IBD record within the past five years and who were still children, alive, and living in Sweden by the end of the year (2006–2022) were considered to have prevalent IBD for that year [17].
The time of diagnosis was determined according to the earliest registered ICD code or SNOMED code representing IBD. The study formation restricted participation to children without any history of solid organ transplantation or immune‐mediated disease (Supporting Information S1: Table S3), the management of which increases the risk of CS use. Patients were characterised according to IBD‐related surgery [15, 18, 19], presence of extra‐intestinal manifestation of IBD, and the extent and location of the disease at diagnosis (Supporting Information S1: Tables S4–S6) [16].
2.2. Outcome: Use of Corticosteroids (CS)
This study considered CS used on or after the time of PIBD diagnosis between 2006 and 2022. We included any oral and intravenously administered CS (Supporting Information S1: Table S7). The start date of CS use was defined as the time of the first redeemed prescription or the first infusion. We defined ‘any CS use’ as a minimum of 1 CS prescription/infusion, while ‘excess CS use’ [20, 21] was defined as ≥ 2 courses or ≥ 3 months of annual CS use (Supporting Information S1: Table S8). A CS course was assumed to be ongoing for 12 weeks minus 1 day. If a new CS prescription was dispensed within 12 weeks (minus 1 day) from a previous one, the last course was assumed to be prolonged by 12 weeks from the date of the previous dispensation. We also estimated the cumulative CS dose, converted into prednisolone equivalents [5], used in the first 3 years since diagnosis.
Drug data were retrieved from three Swedish registers: The Swedish NPR [12, 13], the Swedish Prescribed Drug Register [22], and the Swedish Quality Register for IBD (SWIBREG) [23, 24]. The Prescribed Drug Register, established in July 2005, contains prospectively recorded data on all dispensed prescriptions in Sweden [22].
2.3. Other Data
To examine CS use in relation to other therapies, we identified the use of conventional IBD therapy (i.e., 5‐aminosalicylic acid [5‐ASA] or immunomodulators), and advanced therapies in the three registers mentioned above (Supporting Information S1: Table S7). We classified incident drug use as the first dispensing/administered medical therapy; a hiatus of ≥ 3 months between CS prescription dispensations/administrations or ≥ 6 months between prescription dispensations/administrations of 5‐ASA, immunomodulators and advanced therapies were considered new treatment.
2.4. Statistical Analyses
In the incident CD and UC patients, we plotted the yearly proportion of CS use at 1–11 years since first diagnosis. Follow‐up extended beyond the age of 18 years, with censoring at the time of emigration, death, or end of data capture on December 31, 2022. We plotted the annual proportion of prevalent CD and UC patients with CS use by calendar year (2006–2022). Prevalent patients contributed to analyses of annual CS use for all study years in which they had prevalent PIBD. The annual CS use was classified into any use and excess use. Sensitivity analyses examined patterns of CS use in incident and prevalent patients at major paediatric hospitals located in Stockholm, Göteborg, Uppsala, Linköping/Norrköping and Malmö/Lund. Finally, we, in nationwide analyses, examined trends in CS use without considering budesonide (ATC code A07EA06), which may have lower systemic effects [25].
We plotted the cumulative CS dose (0, > 0–1500, > 1500–4500 and > 4500 mg prednisolone equivalents) in the first year (i.e., 0‐< 365 days) and the first 3 years (0–< 3 years) since incident UC and CD diagnosis. These analyses were restricted to incident PIBD patients with at least 3 years of follow‐up and further categorised by the calendar year of first diagnosis.
We described the course line of CS use (1st, 2nd, 3rd, 4th) in incident CD and UC patients overall and by subsequent treatment decisions: use of conventional IBD therapy (i.e., continuation, addition or switch to oral 5‐ASA or immunomodulator), use of advanced therapy, IBD‐related surgery, the start of new CS or with none of these treatment decisions.
We used Logistic regression to estimate odds ratios (ORs) for the risk of excess CS use during the first year and 2nd–4th year since PIBD diagnosis by patient and treatment characteristics (dependent variables). These characteristics included age at diagnosis (< 6 [reference], 6–< 10, and 10–< 18 years), sex (male [reference] and female) and calendar year of diagnosis (2006–2009 [reference], 2010–2012, 2013–2015, 2016–2018, and 2019–2022); time‐varying data as defined at the 2nd–4th year since diagnosis included history of advanced therapy (yes, no [reference]), IBD‐related surgery (yes, no [reference]) and (non‐surgical) IBD‐related hospitalisation (yes, no [reference]). In addition to unadjusted ORs for excess CS use, estimates were adjusted for age, sex, calendar year of diagnosis, IBD‐related hospitalisation, IBD‐related surgery, and advanced therapy use. The annual proportion difference in CS use and CS excess use in prevalent patients was tested using a chi‐squared test. Data were analysed using SAS software version 9.4 (SAS Institute Inc.).
2.5. Ethics
The Stockholm Ethics Review Board approved this study.
3. Results
We identified 2460 children with an incident CD diagnosis and 2470 children with an incident UC diagnosis in 2006–2022 (Supporting Information S1: Table S9). Among these, 2443 and 2284 individuals contributed to the analyses of prevalent CD and prevalent UC diagnosis, respectively (Supporting Information S1: Table S10). The mean age at first diagnosis was 13.7 (SD 3.4) years in CD and 13.9 (3.8) years in UC. Patients had a median follow‐up of approximately 8 years (Table 1). Children with CD underwent more surgeries and were more often exposed to immunomodulators and advanced therapies compared to those with UC (Table 1).
TABLE 1.
Characteristics of children with incident and prevalent Crohn's disease (CD) and ulcerative colitis (UC) in 2006–2022.
| Incident CD | Incident UC | Prevalent CD | Prevalent UC | |
|---|---|---|---|---|
| N (%) | N (%) | N (%) | N (%) | |
| Total | 2460 | 2470 | 8298 | 7362 |
| N unique patients | 2460 | 2470 | 2443 | 2284 |
| Sex | ||||
| Female | 1066 (43.3%) | 1157 (46.8%) | 3432 (41.4%) | 3558 (48.3%) |
| Male | 1394 (56.7%) | 1313 (53.2%) | 4866 (58.6%) | 3804 (51.7%) |
| Age (years) at first IBD diagnosis (years) a | ||||
| Mean (SD) | 13.7 (3.4) | 13.9 (3.8) | 12.9 (3.4) | 12.8 (3.9) |
| Median (IQR) | 14.5 (11.9–16.5) | 15.2 (12.2–16.7) | 13.5 (11.0–15.6) | 13.8 (10.6–15.9) |
| Categories | ||||
| < 6 | 88 (3.6%) | 138 (5.6%) | 121 (5.0%) | 175 (7.7%) |
| 6–< 10 | 240 (9.8%) | 227 (9.2%) | 311 (12.7%) | 322 (14.1%) |
| 10–< 18 | 2132 (86.7%) | 2105 (85.2%) | 2011 (82.3%) | 1786 (78.2%) |
| Year of first IBD diagnosis a | ||||
| ≤ 1994 | NA | NA | 5 (0.2%) | 9 (0.4%) |
| 1995–2000 | NA | NA | 36 (1.5%) | 70 (3.1%) |
| 2001–2006 | 144 (5.9%) | 183 (7.4%) | 497 (20.3%) | 483 (21.1%) |
| 2007–2012 | 835 (33.9%) | 877 (35.5%) | 682 (27.9%) | 669 (29.3%) |
| 2013–2018 | 846 (34.4%) | 785 (31.8%) | 693 (28.4%) | 594 (26.0%) |
| 2019–2022 | 635 (25.8%) | 625 (25.3%) | 530 (21.7%) | 459 (20.1%) |
| Age (years) at the time of prevalent analysis a | ||||
| Mean (SD) | NA | NA | 14.1 (3.2) | 14.1 (3.6) |
| Categories | ||||
| < 6 | NA | NA | 121 (5.0%) | 176 (7.7%) |
| 6–< 10 | NA | NA | 311 (12.7%) | 322 (14.1%) |
| 10–< 18 | NA | NA | 2011 (82.3%) | 1786 (78.2%) |
| Disease duration (years) at the time of prevalent analysis a | ||||
| Mean (SD) | NA | NA | 1.2 (1.7) | 1.3 (2.0) |
| Categories | ||||
| 0–< 1 | NA | NA | 1815 (74.3%) | 1622 (71.0%) |
| 1–< 5 | NA | NA | 496 (20.3%) | 504 (22.1%) |
| 5–< 10 | NA | NA | 121 (5.0%) | 140 (6.1%) |
| ≥ 10 | NA | NA | 11 (0.5%) | 18 (0.8%) |
| Paris Classification CD b | NA | NA | ||
| N classified | 2460 (100%) | NA | 8278 (99.8%) | NA |
| L2 (colon) | 248 (10.1%) | NA | 973 (11.8%) | NA |
| L1 or L3 or LX (ileocaecal/not defined) | 2212 (89.9%) | NA | 7305 (88.2%) | NA |
| Perianal | 180 (7.3%) | NA | 1161 (14.0%) | NA |
| Paris Classification UC b | ||||
| N classified | NA | 40,389 (99.8%) | NA | 7340 (99.7%) |
| E1 or E2 (proctitis/left‐sided) | NA | 18,722 (46.4%) | NA | 876 (11.9%) |
| E3 or E4 (extensive/pancolitis) | NA | 5472 (13.5%) | NA | 1789 (24.4%) |
| EX (extent not defined) | NA | 16,195 (40.1%) | NA | 4675 (63.7%) |
| Extraintestinal manifestations c | ||||
| Primary sclerosing cholangitis | 14 (0.6%) | 17 (0.7%) | 157 (1.9%) | 308 (4.2%) |
| Other extraintestinal manifestations | 129 (5.2%) | 76 (3.1%) | 886 (10.7%) | 669 (9.1%) |
| Surgery d before the end of the study period | ||||
| Total colectomy | 84 (3.4%) | 191 (7.7%) | 298 (3.6%) | 547 (7.4%) |
| Other bowel surgery | 341 (13.9%) | 147 (6.0%) | 1340 (16.1%) | 463 (6.3%) |
| Perianal surgery | 333 (13.5%) | 73 (3.0%) | 1368 (16.5%) | 246 (3.3%) |
| Out‐ or inpatient IBD care during the prevalent year | ||||
| Number of outpatient care visits | ||||
| Mean (SD) | NA | NA | 4.1 (3.6) | 3.4 (3.4) |
| Inpatient care hospitalisations | ||||
| Mean (SD) | NA | NA | 0.2 (0.6) | 0.2 (0.6) |
| Drug exposure ever before the end of the study period e | ||||
| 5ASA, oral | 1643 (66.8%) | 2325 (94.1%) | 6069 (73.1%) | 6696 (91.0%) |
| 5ASA, any | 1665 (67.7%) | 2391 (96.8%) | 6136 (73.9%) | 6797 (92.3%) |
| Immunomodulators | 1891 (76.9%) | 1566 (63.4%) | 6343 (76.4%) | 4495 (61.1%) |
| Advanced therapies | 1413 (57.4%) | 1010 (40.9%) | 4721 (56.9%) | 2665 (36.2%) |
| Follow‐up time, years | ||||
| Mean (SD) | 8.2 (5.1) | 8.5 (5.1) | NA | NA |
| Median (IQR) | 7.9 (3.8–12.8) | 8.2 (3.9–13.2) | NA | NA |
| Range, min‐max | 0.0–17.0 | 0.0–17.0 | NA | NA |
Abbreviations: 5‐ASA, 5‐aminosalicylic acid; IQR, interquartile range; SD, Standard deviation.
Only the first prevalent analysis counted.
Extent and location of disease at the time of diagnosis as detailed in Supporting Information S1: Table S4.
For definition, please see Supporting Information S1: Table S6.
IBD‐related surgery was defined by relevant surgical codes listed in Supporting Information S1: Table S5.
Medical IBD therapy is defined in Supporting Information S1: Table S7.
Figure 1 shows the CS use in prevalent patients with CD during the study period. In 2006, 42.9% (95% CI, 40.7–45.2) had any annual CS use, compared to 27.6% (95% CI, 25.8–29.4) in 2022 (p < 0.001). There was also a notable decrease in annual excess CS use in CD (33.7% (95% CI, 31.5–35.8) in 2006 and 19.1% (95% CI, 17.5–20.7) in 2022 (p < 0.001)). However, similar downward trends in annual CS use were not seen in UC (Figure 1); rates of any annual CS use were 41.0% (95% CI, 38.9–43.2) in 2006 and 43.6% (95% CI, 41.2–45.9) in 2022 (p = 0.43), while excess CS was seen in 32.4% (95% CI, 30.3–34.4) of UC patients in 2006 compared to 36.2% (95% CI, 34.0–38.5) in 2022 (p = 0.21).
FIGURE 1.
Proportion of corticosteroid use and excess use in prevalent paediatric Crohn's disease (CD) and ulcerative colitis (UC) patients in 2006–2022. Any corticosteroid (CS) use equalled a minimum of one CS prescription/infusion, while excess CS use [20, 21], was defined as ≥ 2 courses or ≥ 3 months of CS use (Supporting Information S1: Table S8).
In incident patients, the use of CS was most common in the first year following CD and UC diagnosis (Figure 2). However, the proportion of initial use of any CS was slightly higher in children diagnosed with UC (70.6%) than in those diagnosed with CD (63.8%). While both CD and UC showed decreasing trends in any CS use since diagnosis, rates seemed to stabilise only at the fourth (CD) and fifth (UC) year of diagnosis. Similar trajectories since diagnosis were observed for excess use (Figure 2). While children with more recently diagnosed CD also had a decreased cumulative CS dose use, particularly for annual doses of ≥ 4500 mg prednisolone equivalents, a similar reduction was not evident for UC (Supporting Information S1: Figure S2).
FIGURE 2.
Proportion of corticosteroid use and excess use by year of disease duration in patients with incident Crohn's disease (CD) and ulcerative colitis (UC) in 2006–2022. Any corticosteroid (CS) use equalled a minimum of one CS prescription/infusion, while excess CS use [20, 21], was defined as ≥ 2 courses or ≥ 3 months of CS use (Supporting Information S1: Table S8). The 95% confidence intervals (CIs) for these estimates were approximately ± 1% per year. Given that the y‐axis ranged from 0% to 100%, the error bars representing the 95% CIs were too narrow to be meaningfully displayed.
Children aged 10–< 18 years had an adjusted OR of 1.91 (95% CI, 1.22–2.98) for excess CS use in the first year of CD diagnosis compared to those < 6 years of age (Supporting Information S1: Table S11). There were no significant age‐related differences in excess CS use at 2–4 years after CD diagnosis (Supporting Information S1: Table S12). Compared with CD diagnosed in 2006–2009, children with the most recent diagnoses (2019–2022) had a 39% reduced risk of excess CS use in the first year (adjusted OR 0.61 [95% CI, 0.49–0.76]; Supporting Information S1: Table S11 and Figure S3) and 56% reduced risk of excess CS use at 2–4 years since diagnosis (adjusted OR 0.44 [95% CI, 0.35–0.56]; Supporting Information S1: Table S12). Similar to above, older rather than younger UC children had an increased risk of first‐year excess CS use, but not for excess use at 2–4 years since UC diagnosis (Supporting Information S1: Tables S13–S14). We observed IBD‐related hospitalisation and advanced therapies to be associated with an increased risk for excess CS use at 2–4 years after CD diagnosis (adjusted OR 1.85 [95% CI, 1.57–2.18] and 1.20 [1.03–1.41], respectively) and UC diagnosis (adjusted OR 2.08 [95% CI, 1.79–2.42] and 1.77 [95% CI, 1.50–2.10], respectively). Conversely, children with prior IBD‐related surgery had half the risk of excess CS use 2–4 years after CD and UC diagnosis (adjusted OR 0.58 [95% CI, 0.37–0.90] and 0.44 [95% CI, 0.27–0.70], respectively).
Table 2 depicts the proportion of children with the use of conventional therapy (5‐ASA or immunomodulator), advanced therapy or surgery by course line of CS. Overall, treatment decisions following CS exposure seemed relatively consistent across IBD subtypes, but with two exceptions: First, changes in conventional therapy, for example, the use of an immunomodulator or 5‐ASA therapy by higher CS course line, were more frequent in UC patients compared with CD patients. Second, while children with UC (compared to CD) less often used advanced therapies, such use was more related to a higher course line of CS.
TABLE 2.
Treatment decisions by the course line of corticosteroid (CS) use in incident Crohn's disease (CD) and ulcerative colitis (UC) patients.
| Treatment decision | Course line of CS use in incident CD | Course line of CS use in incident UC | ||||||
|---|---|---|---|---|---|---|---|---|
| 1st | 2nd | 3rd | 4th | 1st | 2nd | 3rd | 4th | |
| N | 1790 | 1087 | 659 | 414 | 1934 | 1260 | 814 | 503 |
| Use of conventional IBD treatment (oral 5‐ASA or immunomodulator) a , n (%) | 1616 (90.3) | 885 (81.4) | 504 (76.5) | 303 (73.2) | 1872 (96.8) | 1164 (92.4) | 711 (87.3) | 433 (86.1) |
| Oral 5‐aminosalicylic acid, n (%) | 1129 (63.1) | 575 (52.9) | 300 (45.5) | 165 (39.9) | 1816 (93.9) | 1072 (85.1) | 639 (78.5) | 376 (74.8) |
| Immunomodulator, n (%) | 1299 (72.6) | 727 (66.9) | 413 (62.7) | 244 (58.9) | 1065 (55.1) | 779 (61.8) | 467 (57.4) | 298 (59.2) |
| Use of an advanced therapy a , n (%) | 637 (35.6) | 353 (32.5) | 230 (34.9) | 139 (33.6) | 435 (22.5) | 330 (26.2) | 228 (28.0) | 150 (29.8) |
| IBD surgery b , n (%) | 196 (10.9) | 122 (11.2) | 90 (13.7) | 56 (13.5) | 86 (4.4) | 56 (4.4) | 45 (5.5) | 32 (6.4) |
| Colectomy, n (%) | 15 (0.8) | 12 (1.1) | 15 (2.3) | 13 (3.1) | 65 (3.4) | 42 (3.3) | 29 (3.6) | 16 (3.2) |
| Other bowel surgery, n (%) | 103 (5.8) | 70 (6.4) | 55 (8.3) | 35 (8.5) | 44 (2.3) | 37 (2.9) | 27 (3.3) | 20 (4.0) |
| Perianal surgery, n (%) | 111 (6.2) | 52 (4.8) | 39 (5.9) | 26 (6.3) | 19 (1.0) | 13 (1.0) | 10 (1.2) | 11 (2.2) |
| Start of a new steroid treatment, n (%) | 46 (2.6) | 73 (6.7) | 54 (8.2) | 40 (9.7) | 25 (1.3) | 38 (3.0) | 33 (4.1) | 28 (5.6) |
| None of the above/end of follow‐up, n (%) | 61 (3.4) | 57 (5.2) | 49 (7.4) | 28 (6.8) | 23 (1.2) | 34 (2.7) | 34 (4.2) | 13 (2.6) |
Note: A patient could experience one, two or all of the defined treatment decisions.
Abbreviation: 5‐ASA, 5‐aminosalicylic acid.
Dispensed prescription/administration of 5‐aminosalicylic acid, immunomodulator and advanced therapy, respectively, within start and stop date of CS course line 1–4; this reflects the proportion of any use by drug (i.e., continued or first‐time use [addition of switch to that drug]), but not the cumulative proportion of use over time. Data capture of medical IBD therapy is defined in Supporting Information S1: Table S7.
IBD‐related surgery was defined by relevant surgical codes listed in Supporting Information S1: Table S5.
3.1. Sensitivity Analyses
Sensitivity analyses examined CS prescription practices at major paediatric hospitals. Here, the overall trend, showing reduced CS use over time in patients with CD, but not in those with UC (Supporting Information S1: Figure S4), was consistent with our main nationwide analysis. Additionally, the use of CS in incident patients at major hospitals aligned with the findings of our primary analyses (Supporting Information S1: Figure S5). Finally, nationwide analyses of patterns of CS use other than budesonide revealed largely unchanged results (Supporting Information S1: Figures S6–S7).
4. Discussion
Based on Swedish children with CD or UC diagnosis in 2006–2022, this study provides a detailed account of CS use by calendar year, time since diagnosis and other patient and treatment characteristics. Despite the emergence of steroid‐sparing treatments, children with UC have had no appreciable reduction in any or excess CS use since 2006. In contrast, more recent than earlier diagnosed CD patients had reduced their excess CS use by half. With a higher CS exposure overall, treatment changes in UC, including the use of advanced therapies, were more related to the course line of CS used than in CD patients.
The adverse side effect of CS use in growing children implies that its use should, if possible, be avoided. The introduction of advanced IBD therapies, all with steroid‐sparing properties, during the last 2 decades has fuelled hopes that children with IBD in this era would be exposed to less CS. However, recent population‐based studies indicate that CS use in children with IBD remains common. In a Danish study of > 3000 children with incident IBD diagnosis in 2000–2018 [26], more than half had been exposed to CS in the first year, a markedly higher CS rate than for adult‐ or elderly‐onset IBD patients. Still, this CS rate was considerably lower than observed in another population‐based study from Denmark, showing that 75% of patients diagnosed between 1998 and 2008 received CS during the first year after diagnosis [27]. In contrast, a study from the ImproveCareNow network reported that only 12% of children with IBD diagnosed in 2018 were treated with CS during the first year since diagnosis, indicating that a low rate of CS use can be achieved among practices with tools and guidelines promoting steroid‐sparing therapies [28].
In our study, we found that both any use of CS and excess use declined over the study period in CD but not in UC. These findings illustrate the persistent need for CS in PIBD, particularly UC and underscore challenges in achieving and maintaining steroid‐free remission over time. There is a paucity of previous data on long‐term trajectories of CS use in patients with PIBD. However, in the adult population, a population‐based cohort study from the Netherlands of almost 3000 IBD patients [29] showed that patients diagnosed during the advanced therapy era had lower exposure to CS. Also, a recent Canadian study of almost 30,000 IBD patients, of whom some 5% were diagnosed during childhood, reported an overall decline in CS use and a parallel increase in anti‐tumour necrosis factor therapy from 2010 to 2015 [30]. Similar results have been observed in a Swedish regional study on adults with IBD [31], and a separate nationwide analysis (oral communication, Ola Olén), each study demonstrating a reduced proportion of CS use over time, with comparable trends in CD and UC. The current study followed PIBD patients for approximately 8 years from diagnosis and found that after the expectedly high use of CS in the first year, CS remained frequently used during the fourth (CD) and fifth (UC) year after diagnosis. This finding may relate to the challenges of tailoring IBD treatments to individual patients.
Possibly, the more excessive CS use in children with UC compared with CD reflects differences in management strategies across subtypes, including the frequent use of exclusive enteral nutrition as induction therapy for paediatric CD [8]. Furthermore, paediatric UC treatment typically follows a ‘step‐up’ approach in which advanced therapies are initiated only after a suboptimal response to conventional IBD therapy of 5‐ASA and immunomodulators [9].
In contrast, a ‘top‐down’ approach to therapy, based on advanced therapies (foremost infliximab) as first‐line therapy alone or in combination with immunomodulators, is common in children with CD [8]. Supporting this notion, we observed that advanced therapies were more common in CD overall, whereas in UC, advanced therapy use, or other therapy adjustments, was more frequently observed with a higher course line of CS. Because of a lack of granular drug dose data, we were unable to examine post‐CS exposure dose optimisation of current therapies. Future studies, preferably using a clinical trial or target trial emulation design, are needed to clarify how advanced therapy use influences CS requirements. The differing trajectories in excess CS use in CD and UC might also reflect various disease courses per se rather than differing treatment strategies [32, 33, 34]. We observed markedly lower excess CS use following IBD‐related surgery in children with CD or UC, which is consistent with a recently reported substantial reduction in CS use after primary ileocaecal resection in adult CD [35].
4.1. Strengths and Limitations
A significant strength of this study is our nationwide design, which included all Swedish children with an IBD diagnosis between 2006 and 2022. This approach allowed us to identify a more representative population of children with IBD than can be identified by studies using inpatient registers or at referral centres, where patients often suffer from a more severe disease or where CS use trajectories may be related to local rather than national management guidelines. Therefore, our population‐based data ensure the external validity of our results in similar healthcare settings. Prospectively collected data reduced the risk of information bias. In addition, our study sample (> 4000 paediatric patients with IBD) exceeds that of most earlier studies in this field [27, 28]. Its large scale enables precise estimation of contemporary CS use overall and within subgroups of patients.
We defined IBD using a validated diagnostic algorithm based on repeated diagnostic or histopathology codes for the disease. This IBD definition has shown a positive predictive value of 95% for a clinical diagnosis of IBD in children [14]. Multiple register linkages allowed us to account for medical, surgical [18], and inpatient care of IBD.
This study also has some limitations. We had no information from endoscopic examinations, laboratory analyses, or symptoms to define clinical activity; hence, we could not relate differences in CS use over time and across patient subgroups to measures of disease activity. Therefore, our observations of a higher CS use in children with a history of advanced therapies and IBD‐related hospitalisations likely reflect complicated or refractory disease courses rather than causal associations. A related limitation of this study is our lack of data on the indications for CS use. However, the CS use presented in this study is unlikely to reflect treatment for conditions other than IBD since we excluded children with other conditions where CS treatment is common. We could not account for the CS use relative to patient weight, although that should have had limited influence on the results as the vast majority of those exposed were adolescents.
Analyses of post‐CS exposure therapy were limited by our lack of data on exclusive enteral nutrition and exact drug dosing. This study did not capture rectally administered CS, which can still exert systemic effects [36]. Therefore, our estimates may represent a conservative measure of IBD children's corticosteroid exposure. Also, while our definition of excess corticosteroid use (≥ 2 courses or ≥ 3 months annually) was informed by previous studies [20, 21], even lower annual levels repeated over time can accumulate to a substantial exposure. Finally, our register‐based IBD definition did not fully allow for the categorisation of the extent (UC) or location, behaviour and growth trajectory (CD) as described by the Paris classification [16].
Within these limitations, our data reinforce recommendations for managing PIBD activity and treating to target [37], while avoiding excess CS use. Given the long‐term safety concerns of CS, our data should inform strategies to reduce excess CS use in children. This may include revised guidelines and educational initiatives [38] for the judicious prescription of CS in children. On that note, the observed reduction in CS use in children with CD is encouraging given the CD‐associated risks of growth impairment, perianal disease, and surgery [32, 33, 34, 39].
In conclusion, this nationwide cohort study demonstrated a continued frequent use of CS in PIBD, particularly in UC, where there was no reduction in CS use over the past more than 15 years. Our findings motivate strategies to carefully manage disease activity while avoiding excess CS use in children with IBD. Further research is needed to investigate the relationship between excess CS use and concomitant therapies over time.
Author Contributions
ICMJE criteria for authorship read and met: K.M., M.M., P.M., J.S., M.D.W., V.W., T.R., J.B., O.O. Agree with the manuscript's results and conclusions: K.M., M.M., P.M., J.S., M.D.W., V.W., T.R., J.B., O.O. Designed the study: O.O., J.B., J.S., T.R. Collected data: O.O. Analysed the data: J.S. Wrote the first draft of the paper: K.M., O.O. Contributed to the writing of the paper: M.M., P.M., J.S., M.D.W., V.W., T.R., J.B. Interpretation of data approved the final version of the manuscript: K.M., M.M., P.M., J.S., M.D.W., V.W., T.R., J.B., O.O. Responsible for data integrity: O.O. Supervised the project: O.O. Obtained funding: O.O. Guarantor of the article: O.O.
Funding
This work was supported by the Swedish Research Council (Dnr: 2020‐02002 to OO) and Region Stockholm (Dnr: FoUI‐1002495 to OO). The funding sources did not influence any aspect of the study (its design, collection, analysis, and interpretation of data), approval of the manuscript, or the decision to submit it for publication.
Ethics Statement
2021‐06209‐01, 2022‐04384‐02, 2023‐04868‐02, 2024‐03525‐02.
Conflicts of Interest
Dr Mårild is a sub‐investigator at a clinical trial financed by Pfizer. Dr Olén has been PI for projects (unrelated to the current paper) at Karolinska Institutet, financed by Janssen, Takeda, AbbVie, Ferring, Galapagos/Alfasigma, Bristol Myers Squibb and Pfizer grants. Karolinska Institutet has received fees for lectures (OO) and participation on advisory boards (OO) from Janssen, Ferring, Bristol Myers Squibb, Galapagos and Takeda. Dr M Wewer has received grants from Bristol Myers Squibb, Novo Nordisk Foundation, Aage og Johanne Louis‐Hansens Fond and Boehringer Ingelheim and travel support from Pfizer. Dr V Wewer has received grants from Ferring and Aage og Johanne Louis‐Hansens Fond. Dr. Burisch reports grants from AbbVie, Janssen‐Cilag, MSD, Takeda, Tillots Pharma, Bristol Myers Squibb and Novo Nordisk Foundation; personal fees from AbbVie, Janssen‐Cilag, Celgene, MSD, Pfizer, Takeda, Tillots Pharma, Bristol Myers Squibb, Samsung Bioepis, Pharmacosmos, Ferring, Galapagos, Eli Lilly, Dr Falk Pharma, Celltrion and Orion Pharma. Dr Raine has received research/educational grants and/or speaker/consultation fees from AbbVie, Alfasigma, Arena, Aslan, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Domain Therapeutics, Eli Lilly, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, MonteRosa, Mylan, MSD, Novartis, Numab, Pfizer, Roche, Sandoz, Scientia, Takeda, UCB and Xap Therapeutics. Dr Malmborg is an in‐house PI at clinical drug trials financed by Pfizer and AbbVie, contracted to organise an annual national course in IBD financed by Alfasigma, and has received fees for lectures from Ferring, Galapagos and Eli Lilly. The other authors report no conflicts of interest.
Supporting information
Supporting Information S1
SWIBREG study group members: Malin Olsson, Department of Biomedical and Clinical Sciences, Linköping University and Department of Surgery, Linköping, Sweden. Pär Myrelid, Department of Biomedical and Clinical Sciences, Linköping University and Department of Surgery, Linköping, Sweden. Hans Strid, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Centre for Digestive Health, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden. Charlotte Hedin, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Centre for Digestive Health, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden. Susanna Jäghult, Department of Clinical Science and Education, Södersjukhuset, Stockholm, Sweden. Jonas Halfvarson, Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. Caroline Nordenvall, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Pelvic Cancer, Unit of IBD Surgery, Karolinska University Hospital, Stockholm, Sweden. Martin Rejler, Department of Medicine, Höglandssjukhuset Eksjö, Region Jönköping County, Jönköping, Sweden; Jönköping Academy for Improvement of Health and Welfare, Jönköping University, Jönköping, Sweden. Olof Grip, Department of Gastroenterology, Skåne University Hospital, Malmö, Sweden. Ulrika L. Fagerberg, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Centre for Innovation, Research and Education, Region Västmanland, Västerås, Sweden. Pontus Karling, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Mårild, Karl , Malham Mikkel, Malmborg Petter, et al. 2026. “Corticosteroid Use in Childhood‐Onset Inflammatory Bowel Disease: A Nationwide Cohort Study (2006–2022),” United European Gastroenterology Journal: e70160. 10.1002/ueg2.70160.
SWIBREG study group members and affiliations are listed in the Appendix.
Contributor Information
Karl Mårild, Email: karlmarild@gmail.com.
SWIBREG Study Group:
Malin Olsson, Pär Myrelid, Hans Strid, Charlotte Hedin, Susanna Jäghult, Jonas Halfvarson, Caroline Nordenvall, Martin Rejler, Olof Grip, Ulrika L. Fagerberg, and Pontus Karling
Data Availability Statement
No additional data are available because of Swedish regulations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supporting Information S1
Data Availability Statement
No additional data are available because of Swedish regulations.