COPENHAGEN — Children with juvenile idiopathic arthritis who received etanercept had a surprisingly high rate of inflammatory bowel disease in a review of 1,515 patients.
The incidence of inflammatory bowel disease (IBD) in these patients, drawn from five European registries, was roughly 500 IBD cases per 100,000 patient-years of follow-up, 100-fold higher than in the general pediatric population, Dr. Nico M. Wulffraat said at the annual European Congress of Rheumatology.
“The incidence seems very high. We need more data to confirm this early finding,” said Dr. Wulffraat of the University Medical Center Utrecht (the Netherlands).
It's possible that IBD is an adverse effect of etanercept (Enbrel) treatment, or perhaps IBD is an intestinal complication of juvenile idiopathic arthritis (JIA), Dr. Wulffraat said.
A third possibility is that JIA is an extraintestinal manifestation of IBD. He said this explanation was unlikely because JIA preceded the appearance of IBD by several years; in one case, the interval between diagnosis of JIA and onset of IBD was 12 years.
The study used data on JIA patients that were collected by registries in Denmark, Finland, Germany, Italy, and the Netherlands from 1999 through 2007.
The 1,515 JIA patients listed with the registries as being treated with etanercept were followed for 2,900 patient-years, during which time 18 patients developed IBD.
Of these 18 patients, 16 had their diagnosis confirmed by colonoscopy and pathology studies. Clinical information was available for 12 of these patients.
The review excluded JIA patients who were diagnosed with IBD before they began receiving etanercept.
“The pathology leaves little doubt that this was IBD, and not a transient effect on the colonic mucosa,” Dr. Wulffraat said.
When IBD was diagnosed, patients switched from etanercept to a different tumor necrosis factor inhibitor, such as adalimumab (Humira) or infliximab (Remicade), or to a different type of drug such as sulfasalazine. Adalimumab and etanercept both have Food and Drug Administration–approved indications for treating JIA; infliximab does not.
The high incidence rate contrasts with results from a study published in 2001 that found a population-based IBD incidence of 5.2 per 100,000 person-years in children younger than 16 years from the United Kingdom and the Republic of Ireland who were studied prospectively in 1998-1999 (Lancet 2001;357:1093-4).
Analysis of the 12 patients who had clinical data showed no single, unique presentation of IBD, although all patients had abdominal pain and diarrhea. They were also all negative for HLA-B27, and none had a family history of IBD.
All three IBD types appeared: In all, 75% had Crohn's disease, with the rest developing either ulcerative colitis or indeterminate colitis.
The average time between JIA onset and the diagnosis of IBD was nearly 8 years. The time between the start of etanercept treatment and IBD appearance ranged from 9 days to 5 years.
Dr. Wulffraat said that he and his associates had no financial disclosures.