Dataset Information

Clinical Phenotypes and Outcomes in Monogenic Versus Non-monogenic Very Early Onset Inflammatory Bowel Disease.

ABSTRACT:

Background and aims

Over 80 monogenic causes of very early onset inflammatory bowel disease [VEOIBD] have been identified. Prior reports of the natural history of VEOIBD have not considered monogenic disease status. The objective of this study is to describe clinical phenotypes and outcomes in a large single-centre cohort of patients with VEOIBD and universal access to whole exome sequencing [WES].

Methods

Patients receiving IBD care at a single centre were prospectively enrolled in a longitudinal data repository starting in 2012. WES was offered with enrollment. Enrolled patients were filtered by age of diagnosis <6 years to comprise a VEOIBD cohort. Monogenic disease was identified by filtering proband variants for rare, loss-of-function, or missense variants in known VEOIBD genes inherited according to standard Mendelian inheritance patterns.

Results

This analysis included 216 VEOIBD patients, followed for a median of 5.8 years. Seventeen patients [7.9%] had monogenic disease. Patients with monogenic IBD were younger at diagnosis and were more likely to have Crohn's disease phenotype with higher rates of stricturing and penetrating disease and extraintestinal manifestations. Patients with monogenic disease were also more likely to experience outcomes of intensive care unit [ICU] hospitalisation, gastrostomy tube, total parenteral nutrition use, stunting at 3-year follow-up, haematopoietic stem cell transplant, and death. A total of 41 patients [19.0%] had infantile-onset disease. After controlling for monogenic disease, patients with infantile-onset IBD did not have increased risk for most severity outcomes.

Conclusions

Monogenic disease is an important driver of disease severity in VEOIBD. WES is a valuable tool in prognostication and management of VEOIBD.

SUBMITTER: Collen LV

PROVIDER: S-EPMC9455789 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Clinical Phenotypes and Outcomes in Monogenic Versus Non-monogenic Very Early Onset Inflammatory Bowel Disease.

Collen Lauren V LV Kim David Y DY Field Michael M Okoroafor Ibeawuchi I Saccocia Gwen G Whitcomb Sydney Driscoll SD Green Julia J Dong Michelle Dao MD Barends Jared J Carey Bridget B Weatherly Madison E ME Rockowitz Shira S Sliz Piotr P Liu Enju E Eran Alal A Grushkin-Lerner Leslie L Bousvaros Athos A Muise Aleixo M AM Klein Christoph C Mitsialis Vanessa V Ouahed Jodie J Snapper Scott B SB

Journal of Crohn's & colitis 20220901 9

<h4>Background and aims</h4>Over 80 monogenic causes of very early onset inflammatory bowel disease [VEOIBD] have been identified. Prior reports of the natural history of VEOIBD have not considered monogenic disease status. The objective of this study is to describe clinical phenotypes and outcomes in a large single-centre cohort of patients with VEOIBD and universal access to whole exome sequencing [WES].<h4>Methods</h4>Patients receiving IBD care at a single centre were prospectively enrolled ...[more]

PMID: 35366317

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Project description:IntroductionTherapeutic options are critically needed for children with refractory very early onset inflammatory bowel disease (VEO-IBD). Our aim was to evaluate clinical response to canakinumab, an anti-IL-1β monoclonal antibody, in patients with VEO-IBD whose phenotype resembles those with monogenic autoinflammatory disease.MethodsThis is a single center retrospective study of patients with VEO-IBD with autoinflammatory phenotype (AIP) in the absence of identified monogenic disease treated with canakinumab for >6 months. AIP was defined as confirmed IBD with associated signs of systemic inflammation in the absence of infection, including leukocytosis, markedly elevated inflammatory markers, and extraintestinal manifestations (recurrent fevers, oral ulcers, arthritis). Primary outcomes included clinical response in disease activity indices after 6 months of therapy. Secondary outcomes included rate of AIP signs and symptoms, growth, surgery, steroid use, hospitalizations, and adverse events.ResultsNineteen patients were included: 47% with infantile onset, 58% classified as IBD-U, and 42% classified as CD. At baseline, 37% were biologic naïve, and canakinumab was used as dual therapy in 74% of patients. Clinical response was achieved in 89% with statistically significant improvement in PCDAI and PUCAI. Clinical remission was achieved in 32% of patients. There was significant improvement in the clinical manifestations of AIP and the biochemical markers of disease. Number of hospitalizations (p<0.01) and length of stay (p<0.05) decreased. Growth improved with median weight-for-length Z-score increasing from -1.01 to 1.1 in children less than 2 years old. There were minimal adverse events identified during the study period.ConclusionCanakinumab may be an effective and safe treatment for a subset of children with VEO-IBD with AIP, as well as older patients with IBD. This study highlights the importance of a precision medicine approach in children with VEO-IBD.

Dataset Information

Clinical Phenotypes and Outcomes in Monogenic Versus Non-monogenic Very Early Onset Inflammatory Bowel Disease.

Background and aims

Methods

Results

Conclusions

Publications

Clinical Phenotypes and Outcomes in Monogenic Versus Non-monogenic Very Early Onset Inflammatory Bowel Disease.

Similar Datasets

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