IGF-1 levels tied to infliximab response in pediatric Crohn's disease

Last Updated: 2018-02-06

By David Douglas

NEW YORK (Reuters Health) - Increased insulin-like growth factor-1 (IGF-1) levels are associated with improved bone and muscle accrual after initiation of infliximab treatment in young patients with Crohn's disease, according to a prospective cohort study.

As Mark D. DeBoer told Reuters Health by email, "Crohn's disease can result in high levels of systemic inflammation that suppress IGF-1, a key factor for growth in height and bone density."

In a January 10 online article in the Journal of Clinical Endocrinology & Metabolism, Dr. DeBoer of the University of Virginia, in Charlottesville, and colleagues further note that "no longitudinal studies have examined the associations among changes in IGF-1 levels, bone density and structure, and muscle mass in childhood chronic inflammatory disease."

To investigate, the team studied 75 patients (46 boys) ages 5 to 21 with Crohn's disease. None had previously used anti-TNF-alpha therapy. After initiation of infliximab treatment, they were followed for a year. Data were available for 63 patients at 12 months.

IGF-1 Z-scores rose highly significantly from a median of minus 1.0 at baseline to a median of minus 0.36 at 10 weeks. Over time, lesser disease severity and systemic inflammation, and in girls greater estradiol Z-scores, were significantly associated with greater IGF-1 Z-scores.

Compared to reference data - as measured by dual-energy X-ray absorptiometry (DXA) whole-body bone-mineral content, leg lean mass, and total hip and femoral neck bone mineral density (BMD) - Z-scores were low at baseline and improved significantly over the course of 12 months.

In addition, greater increases in IGF-1 Z-scores over 10 weeks predicted improvement in DXA bone and muscle outcomes, as well as tibia peripheral quantitative-CT trabecular BMD and cortical area.

Because changes in bone outcomes may be mediated by changes in muscle mass, the researchers observe "we further tested these associations following inclusion of change in measures of muscle in the model." This, they say, "markedly attenuated the associations between IGF-1 levels and bone outcomes."

"This suppression of IGF-1," concluded Dr. DeBoer, "can result in delays in growth and lower bone mass, underscoring the importance of early diagnosis and effective treatment of Crohn's disease in childhood."

Dr. Jarod Wong of the University of Glasgow, UK, told Reuters Health by email that the study "shows that treatment of young people with Crohn's disease with anti-tumor necrosis alpha therapy led to increase in IGF-1, which is a marker of growth hormone action, extending our understanding of how such treatment can improve bone and growth."

Dr. Wong, a senior clinical lecturer in the Developmental Endocrinology Research Group, added, "Whilst treatment leads to improvement in IGF-1 at 10 weeks, this did not normalize IGF-1 levels by 1 year. Indeed, the investigators have previously reported on improvement, but not normalization, of bone mass in these children. Future studies of exercise, nutritional intervention, and strategies to improve growth, in addition to anti-tumor necrosis factor therapy for Crohn's disease, may need to be explored."

SOURCE: http://bit.ly/2BSeoS4

J Clin Endocrinol Metab 2018.