Only one biomarker was useful in predicting the relapse of Crohn’s disease in children after anti-tumor necrosis factor (TNF)-α therapy, Korean researchers found in a retrospective observational study.
At 1 year following anti-TNF-α therapy, albumin-to-globulin ratio (AGR) was the only marker associated with time-to-relapse in Crohn’s disease (HR 0.02, 95% CI 0.002-0.181, P<0.001), reported Yon Ho Choe, MD, PhD, and colleagues from the Samsung Medical Center in Seoul.
In predicting relapse, researchers found the optimal cutoff value for AGR was 1.47 (area under the curve 0.916, 95% CI 0.870-0.961, P<0.001), according to the findings in Gut and Liver.
Drug concentrations affect the efficacy of biologics in Crohn’s disease. Lower AGRs put patients with Crohn’s disease at risk for relapse, since they lower drug trough levels, resulting in anti-drug antibody concentrations.
“Drug concentration is influenced by dose according to body weight, drug degradation, anti-drug antibodies (ADA) to anti-TNF-α, or drug leakage into gastrointestinal tract,” the authors wrote. “Anti-TNF-α administered to a patient can induce an immune reaction such as the development of ADA, which is associated with low drug trough levels and can mediate loss of clinical response to the drug.”
This is the first study to evaluate predictors related to Crohn’s disease relapse from anti-TNF-α therapy in children, except for calprotectin, the authors noted.
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. Patients were excluded if they had unspecified-irritable bowel disease, ulcerative colitis, or initially failed anti-TNF-α therapy.
Symptomatic relapse, defined by a Pediatric Crohn’s Disease Activity Index (PCDAI) above 10 with a prior visit difference change, was the primary endpoint. Primary endpoints extended to more intense patient treatments, such as adding a new drug, increasing drug dosage during maintenance, or the need for intestinal surgery (due to narrowing/penetrating Crohn’s disease).
The average age of patients was about 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 PCDAI score was 35 at diagnosis. About 80% of patients received infliximab (Remicade), with the remainder receiving adalimumab (Humira).
Researchers found 51% of patients maintained clinical remission and 49% of patients went into relapse. Both levels of calprotectin and the AGR at 1 year following anti-TNF-α therapy, were found to be associated with Crohn’s disease relapse.
Other studies reported fecal calprotectin as the only factor in association with endoscopic activity after therapy, but the authors added it is not easy to obtain samples and requires several days to collect them. In order to determine the best therapeutic strategies for Crohn’s disease, knowledge is needed on more factors that can predict relapse in children, the authors noted.
Median infliximab trough levels at 1 year were significantly lower in patients with AGRs less than 1.47 compared to patients with AGRs greater than or equal to 1.47.
Limitations of this study included unstructured follow-up, small sample sizes, the quantitative amount of calprotectin measured, and limited statistical analyses.
Researchers urged clinicians to closely monitor disease activity for pediatric Crohn’s disease patients with low AGRs after 1 year of therapy.
“Clinicians should monitor disease activity, assess the trough levels of the anti-TNF-α agents, test for ADAs and determine the appropriate therapeutic strategies,” they wrote.
The authors declared no conflicts of interest. Research was funded by the Korean government (MSIT) and supported by the National Research Foundation of Korea (NRF).