Remicade provides clinical response in children with acute severe ulcerative colitis

Michael J. Rosen

SAN DIEGO — Drug clearance was associated with a reduction in disease activity in children who responded to Remicade for the treatment of acute severe ulcerative colitis, according to study results presented at Digestive Disease Week.

“[Remicade (infliximab, Janssen)] is the most common treatment for severe, steroid-refractory UC in children,” Kaitlin G. Whaley, MD, of Cincinnati Children’s Hospital Medical Center, said in her presentation. “However, outcomes after infliximab in this patient population are not reflected by the major pediatric UC trial.

Research, according to Michael J. Rosen, MD, MSCI, medical director of the Schubert-Martin Inflammatory Bowel Disease Center at Cincinnati Children's Hospital Medical Center, has shown that more than half of children who are hospitalized with acute severe UC (ASUC) and treated with conventional dosing of 5 mg/kg will undergo colectomy by 1 year.

“Our best evidence shows that about 25% of children treated with conventional dosing of infliximab for corticosteroid-refractory acute severe ulcerative colitis will require a colectomy prior to discharge,” Rosen told Healio Gastroenterology and Liver Disease. “We wanted to determine if overall exposure to infliximab, modeled on serial drug levels during the first week of treatment, is associated with outcomes in pediatric acute severe UC.”

Researchers analyzed data from the ARCH study — an ongoing study of children hospitalized for ASUC or unspecified inflammatory bowel disease (Pediatric UC Activity Index [PUCAI] 65) who are initiated on infliximab — to determine if baseline clinical, laboratory of infliximab pharmacokinetics are associated with day 7 clinical response in children with ASUC. The primary endpoint of the study was the relationship between infliximab exposure and day 7 clinical response defined as PUCAI less than 35 without colectomy.

The 38 patients in the trial had a median PUCAI at admission of 75 and received a median of 9.9 mg/kg dose of infliximab.

Whaley and colleagues found that 71% of patients achieved clinical response by day 7, and none of the patients in the trial underwent colectomy through day 7. There was no difference in baseline measurements of PUCAI or other activity measure between responders and non-responders. Infliximab exposure through day 3 prior to any rescue infusions was similar between responders and non-responders.

A measurement of PUCAI of 45 or less on day 3 predicted day 7 clinical response with a sensitivity of 66.7% (95% CI, 38.4%–88.2%) and a specificity of 87.5% (95% CI, 47.4%–99.7%).

Among patients who achieved clinical response, researchers found that the magnitude of PUCAI reduction correlated with slower infliximab clearance, and it trended toward a correlation with a longer half-life of infliximab.

Whaley said the lack of a link between infliximab exposure and day 7 clinical response suggests that doses greater than 10 mg/kg likely would not provide additional improvement toward clinical response.

“Amongst responders, there was a correlation between infliximab clearance and a reduction in PUCAI, which may indicate a drug exposure duration-response relationship in those that responded,” Whaley said.

Rosen, who was part of the study, did note, however, that there was a limitation to the study.

“The main limitation of the analysis at this point is that we can only looked at day 7 outcomes,” he said. “This cohort was followed for 26 weeks; ongoing analyses will assess the association between infliximab exposure and outcomes at 8 and 26 weeks.” – by Alex Young and Ryan McDonad

Reference:

Whaley KG, et al. Abstract 235. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Disclosures: Whaley and Rosen report no relevant financial disclosures. Please see the meeting disclosure index for all other authors’ relevant financial disclosures.