Infantile-Onset IBD Associated With Worse Disease Course

Children with infantile-onset IBD have a more complicated disease course, including higher rates of steroid dependency, hospitalizations, surgeries, and growth delay.

Outcomes in children with very early-onset inflammatory bowel disease (VEOIBD) have not improved during the past 15 years, and infantile-onset IBD is associated with worse outcomes compared with IBD in older children, according to study results published in Clinical Gastroenterology and Hepatology.

Researchers used data from the Israeli IBD Research Nucleus cohort to assess the incidence, management, disease course, and outcomes of VEOIBD compared with IBD in older children. The study participants (N=5243) were diagnosed with IBD before age 18 years between January 1, 2005 and January 7, 2020. Pediatric IBD (PIBD) was categorized according to the Paris classification as either adolescent-onset disease (ages 10-18 years), early-onset disease (ages 6-10 years), and VEOIBD (age <6 years). The VEOIBD group was further categorized into infantile-onset IBD (age <2 years) and toddler-onset IBD (ages 2-6 years).

Among the study participants, 3490 (67%) had Crohn disease (CD) and 1753 (33%) had ulcerative colitis (UC). A total of 4444 (85%) had adolescent-onset disease, 548 (10%) had early-onset disease, and 251 (4.8%) had VEOIBD, with 81 in the latter group (1.5%) having infantile-onset disease, and 170 (3.3%) having toddler-onset disease, respectively. The median follow-up was 6.3 years (IQR, 3.1-10.4) for 36,056 person-years.

The national incidence rate of PIBD increased significantly from 10.8 per 100,000 children in 2005 to 15.3 per 100,000 in 2019 (average annual percentage change [AAPC], 2.8%; 95% CI, 2.2%-3.4%), with a significant inflection point occurring in 2010. The incidence of VEOIBD was stable during this period (1.4-1.6 per 100,000; AAPC, 0%; 95% CI, -2.5% to 2.6%).

Being a specific risk group, our results support specific treatment considerations in infants, in parallel to genetic testing, which is mandatory in this age group.

The trend in incidence was insignificant in the infantile-onset group (2.1-0.5 per 100,000; AAPC, 0.4%; 95% CI, -6.1% to 7.4%) and toddler-onset group separately (1.7 to 1.6 per 100,000; AAPC, -0.4%; 95% CI, -4.2% to 3.6%).

Use of biologics was less common in the VEOIBD group compared with the early-onset and adolescent-onset groups (36% ever used vs 57% and 53%, respectively; P <.001). There was no difference in biologic use between the infantile-onset and toddler-onset groups (36% vs 35%, respectively; P =.5).

Participants in the VEOIBD group had a shorter time to steroid dependency compared with older children. The times to hospitalizations and first gastrointestinal-related surgery were shorter in the infantile-onset group, with no difference between the toddler-onset group and older children. Growth delay was more common in the VEOIBD group vs the early-onset group.

Use of therapies changed from 2005 to 2017. Overall, mesalamine use decreased (AAPC, -3.2; 95% CI, -4.0 to -2.4) and immunomodulator (AAPC, 1.9; 95% CI, 1.2-2.7) and biologic use (AAPC, 12.2; 95% CI, 10.8-13.8) increased. Disease outcomes improved in the overall cohort as the rate of steroid dependency (AAPC, -2.5%; 95% CI, -4 to -0.9), hospitalizations (AAPC, -1.1%; 95% CI, -1.8 to -0.3), and surgeries (AAPC, -4.3%; 95% CI, -6.3 to -2.3) was significantly reduced, and the rate of biologic failure was stable (AAPC, -0.4; 95% CI, -1.8 to 1.0). In the adolescent-onset group, the rate of steroid dependency, hospitalization, and surgeries decreased over time, and steroid dependency decreased in the early-onset group. For VEOIBD, the rate of the 3 outcomes did not improve over time.

Multivariate analysis showed that the time to steroid dependency was shorter in the VEOIBD group vs the early-onset group (hazard ratio [HR], 0.8; 95% CI, 0.6-0.99), but not vs the adolescence-onset group (HR, 0.9; 95% CI, 0.7-1.1). Infantile-onset IBD was associated with increased risks for surgery (HR, 1.4; 95% CI, 1.1-1.9) and hospitalization (HR, 1.7; 95% CI, 1.2-2.5) compared with the toddler-onset group.

The study was limited by the unavailability of clinical variables such as disease location, endoscopic severity, and genotype. All cases were classified as either CD or UC, and diagnostic delay could have changed patients from one age group to another.

“Our data support revisiting the Paris classification by differentiating infantile-onset IBD from toddler onset,” according to the researchers. “Being a specific risk group, our results support specific treatment considerations in infants, in parallel to genetic testing, which is mandatory in this age group.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References:

Atia O, Benchimol EI, Ledderman N, et al. Incidence, management, and outcomes of very early onset inflammatory bowel diseases and infantile-onset disease: an Epi-IIRN study. Clin Gastroenterol Hepatol. Published online November 3, 2022. doi: 10.1016/j.cgh.2022.10.026