IBD surgery risk higher in kids with antibodies to infliximab

Last Updated: 2015-02-02

By Reuters Staff

NEW YORK (Reuters Health) - Higher levels of antibodies to infliximab (ATI) are associated with lower concentrations of the drug in children with inflammatory bowel disease (IBD) and may explain their higher risk of surgery, Boston Children's Hospital researchers have found.

"We determined that 20% of pediatric and young adult patients currently receiving infliximab have detectable ATI (5 U/mL). We also demonstrate that ATI correlate with a reduction in infliximab level and a higher risk of surgery in patients with IBD," Dr. Naamah L. Zitomersky and colleagues report in an article published online January 13 in Inflammatory Bowel Disease.

As background, the researchers write that infliximab treatment "has revolutionized therapy of inflammatory bowel disease (IBD) by inducing and maintaining clinical remission, reducing corticosteroid use, and lowering rates of both hospitalization and surgery in patients with Crohn's disease (CD) and ulcerative colitis (UC)."

However, up to 40% of patients may develop adverse reactions or loss of response, they write, and the data on this come from adult studies.

The researchers recruited 134 patients at Boston Children's Hospital between June 14, 2012, and November 2, 2013, for a cross-sectional study of ATI and infliximab in childen and young adults. The patients were currently receiving infliximab (Remicade, Janssen), a chimeric monoclonal antibody.

The team obtained a single serum sample from each patient immediately before the patient underwent infusion with infliximab.

Of the 134 patients in the infliximab group, 85 were male, the mean age was 17.3 years, 114 had CD, and 20 had UC. They had been receiving infliximab treatment for less than six months to up to more than five years.

At serum drawing, 50 patients were also receiving treatment with an immunomodulator, and 84 were receiving infliximab alone.

The researchers found that 77 (57%) of the patients had loss of response to infliximab, of whom 72 had at least one intervention afterward, including an increased dose, increase in infusion frequency or addition of an immumodulator. Ten of the 77 had gastrointestinal surgery since beginning infliximab treatment.

Twenty-seven (20%) patients had ATI levels of 5 U/mL or more, 18 (13%) had ATI levels of 10 U/mL or more, 14 had ATI levels of 12 U/mL, and 13 (10%) had ATI levels of 15 U/mL or more.

The 107 patients with ATI levels less than 5 U/mL had longer duration of therapy than those with 5 U/mL or more (27.6 months vs. 19.2 months, p=0.01). Also, 59% of patients with ATI of 5 U/mL or more had infliximab levels of less than 5 mcg/mL, compared with 14% of patients with ATI less than 5 U/mL (p<0.001).

Of those who underwent surgery 60% had ATI levels of 12 U/mL or more vs. 8% of patients who did not have surgery (p=0.01).

They conclude, "Our pediatric study had similar findings to adult studies regarding the relationship between ATI and IFXL (infliximab level). However, assuming that IFXL correlates with outcome, there may be a lag between antibody development, a decline in infliximab level, and clinical symptoms."

The authors report no external funding or disclosures.

SOURCE: http://bit.ly/1EUsM8z

Inflamm Bowel Dis 2015.