Identification of Inflammatory Bowel Disease (IBD)-Specific Diagnostic Biomarkers Using Transcriptional Profiling of Peripheral Blood Mononuclear Cells (PBMC) From Treatment NaïVE Children With Either IBD or Non-IBD Gastrointestinal Inflammatory Disorders

Abstract

2010, we identified pediatric patients who had pelvic MRI for perianal fistula prior to starting anti-TNF alpha therapy. RESULTS: We identified 15 patients (11 male; mean age 14 years; range 8-19 years) who had an MRI identifying a perianal fistula and subsequently received infliximab (5-10mg/kg). Subjects who failed treatment with infliximab or developed an adverse reaction changed to adalimumab or certolizumab. Nine patients had perianal fistulas, 3 had combined perianal/peritoneal fistulas, 1 had a recto-vaginal and 2 had recto-scrotal fistulas. 10 of the 15 patients had multiple fistulas on presentation and 11 had associated fluid collections seen on MRI. Based on the Parks criteria, there were 9 intersphincteric fistulas, 12 transphincteric, and 3 suprasphincteric. Six of 15 patients (40 percent) with perianal fistulas had a complete clinical response (mean duration to resolution 29.3 months); 1 of these 6 patients relapsed after infliximab was discontinued and did not respond to retreatment (6 months). Two patients (13 percent) had a partial clinical response to antiTNF therapy and 7 patients (47 percent) had minimal response with continued drainage. Seton drainage and/or fistulectomy were used prior to medical treatment in a total of 6 patients, 2 of whom had a complete response. Of the 6 patients with complete clinical response, 1 had a recto-vaginal fistula, and 1 had a recto-scrotal fistula. Repeat MRI evaluation was performed on 4 of the 6 patients with complete clinical response, showing complete radiologic healing in 3 patients and persistence of fistula with active inflammation in 1 patient. Both of the patients with partial response had MRI:one showed worsening of the fistula tract and the other was improved. Three of the 7 patients with minimal response to anti-TNF therapy had repeat imaging and all demonstrated persistence of active fistulous tracts. Two of these patients eventually required diversion procedures. CONCLUSIONS: TNF alpha antagonist therapy resulted in complete healing in 40 percent of pediatric and adolescent Crohn's patients with perianal fistulas and partial healing in 13 percent. Mean time to complete clinical response was longer than expected almost 30 months. Clinical response to treatment correlated with radiologic evaluation in 7 of 9 patients who underwent repeat imaging. Based on Parks criteria, the complexity of the fistula did not appear to influence the response to treatment. Supported in part by a grant from The Pediatric IBD Foundation