Biomarker Predicts Crohn's Disease Relapse in Children

Crohn's disease is a type of inflammatory bowel disease (IBD). It causes inflammation of the digestive tract, which can lead to abdominal pain, severe diarrhea, fatigue, weight loss and malnutrition. Other complications outside the gastrointestinal tract may include anemia, skin rashes, arthritis, inflammation of the eye, and lethargy.

A complete blood count may reveal anemia, which commonly is caused by blood loss leading to iron deficiency or by vitamin B₁₂ deficiency, usually caused by ileal disease impairing vitamin B₁₂ absorption. Rarely autoimmune hemolysis may occur. Ferritin levels help assess if iron deficiency is contributing to the anemia. Erythrocyte sedimentation rate (ESR) and C-reactive protein help assess the degree of inflammation, which is important as ferritin can also be raised in inflammation.

Pediatricians at the Samsung Medical Center (Seoul, Korea) evaluated predictors related to Crohn's disease relapse from anti-tumor necrosis factor (TNF)-α therapy in children, except for calprotectin. From January 2010 to February 2019, 121 children with active Crohn's disease in this study were given TNF-α therapy. Patients were eligible if they were under 18 and received anti-TNF-α therapy for a year. The mean age of patients was approximately 15, and close to 80% were boys. The average observation time was 3.7 years. There were 5% of patients with a previous history of bowel resection surgery. The average Pediatric Crohn’s Disease Activity Index (PCDAI) score was 35 at diagnosis. About 80% of patients received infliximab, with the remainder receiving adalimumab.

Clinical data at the time of one year after anti-TNF-α started were collected retrospectively from electronic charts including the PCDAI score, white blood cell count, hematocrit, platelet count, serum albumin level, serum globulin level, albumin-to-globulin ratio (AGR), erythrocyte sedimentation rate, C-reactive protein, trough levels (TLs) of anti-TNF-α, presence of ADA. Anti-drug antibodies (ADA) were quantified using enzyme-linked immunosorbent assay kits (Matriks Biotek, Ankara, Turkey) at an optical density of 450 nm.

The scientists reported that relapse was observed in 59/121 (48.8%) of patients. The level of calprotectin (odds ratio [OR] = 2.13) and the AGR at one year after anti-TNF-α therapy (OR = 0.0002) were associated with relapse. The AGR at one year after anti-TNF-α therapy was the only factor associated with the time-to-relapse (hazard ratio [HR] = 0.02). The optimal AGR cutoff value for the prediction of relapse was 1.47 (area under the curve, 0.916). The median infliximab trough level (TL) was lower in patients with AGRs <1.47 than in those with AGRs ≥1.47. Anti-drug antibody (ADA) concentrations were negatively correlated with the AGR at one year of anti-TNF-α therapy.

The authors concluded that AGR can be used to predict relapse. Patients with AGRs <1.47 at one year after anti-TNF-α therapy are more likely to have low drug TLs and develop ADAs, which increase the possibility of relapse than those with AGRs ≥1.47. Therefore, if the AGR at one year after anti-TNF-α therapy is less than 1.47, clinicians should monitor disease activity, assess the TLs of the anti-TNF-α agents. The study was published on June 9, 2021 in the journal Gut and Liver.

Related Links:
Samsung Medical Center
Matriks Biotek