Simponi Succeeds in Kids' Colitis
Mucosal healing seen in up to 60%
by Nancy Walsh
Senior Staff Writer, MedPage Today
Action Points
ORLANDO -- Children with moderate-to-severe ulcerative colitis refractory to standard therapy responded successfully to treatment with golimumab (Simponi), a multicenter open-label study found.
Among patients ages 2 to 11 years, 60% were in clinical remission by week 6 of treatment, as were 36% of those ages 12 to 17, according to Jeffrey Hyams, MD, of Connecticut Children's Medical Center in Hartford.
And also at week 6, 60% of the younger group had experienced mucosal healing, with Mayo endoscopy subscores of 1 or lower, as had 52% of the older group, Hyams reported in a poster session here at the 2015 Advances in Inflammatory Bowel Diseases meeting.
Conventional treatments for children with moderate to severe active ulcerative colitis include 5-aminosalicylates (ASAs), corticosteroids, and immunomodulators. Thus far, the only biologic agent approved for this indication in pediatric patients is infliximab (Remicade), which is administered intravenously every 8 weeks.
Like infliximab, golimumab is a tumor necrosis factor (TNF) inhibitor, but it is given subcutaneously every 4 weeks and is approved for adults with moderate to severe ulcerative colitis.
"Golimumab has the potential to offer pediatric ulcerative colitis patients a safe, effective, and convenient treatment option," the investigators stated.
Therefore, to evaluate this agent among young patients, Hyams and colleagues enrolled 35 patients whose mean age was 13, whose mean disease duration was 2.35 years, and whose mean Mayo score was 8.1. The disease was limited to the left side of the colon in 10 patients, but was extensive in 25.
All patients had previously been treated with corticosteroids or immunomodulating agents. Almost all (94.3%) had used corticosteroids, 71.4% had used 6-MPA/azathioprine/methotrexate, and 91.4% had used 5-ASAs. None had received any TNF inhibiting therapies.
The adult induction dose regimen for golimumab is 200 mg at baseline and 100 mg at week 2. That dose was given to children in this study who weighed 45 kg or more, while those weighing less than 45 kg received 90 mg/m2 at baseline and 45 mg/m2 at week 2.
Clinical response was defined as a Mayo score decrease of 30% or more and at least a 3 point decline and a rectal bleeding subscore decrease of 1 or greater or an absolute subscore of 1 or less. This was achieved by 70% of children ages 2 to 11 and 56% of those ages 12 to 17 by week 6.
For comparison, among adults with ulcerative colitis receiving golimumab, clinical response was seen by week 6 in 52% versus 30% of those receiving placebo.
Moreover, while a total of 43% of pediatric patients were in clinical remission at week 6, that response was seen only in 19% of adults at that time point.
Similarly, 54% of the pediatric population showed mucosal healing by week 6, compared with 43% of adults.
"Overall, efficacy outcomes in the golimumab pediatric ulcerative colitis population were consistent with, or numerically greater compared with those observed in the golimumab adult ulcerative colitis population at week 6," the investigators stated.
There also were rapid and "substantial reductions" in objective markers of inflammation by week 6. C-reactive protein levels normalized in 56.3%, fecal calprotectin was within normal limits in 10.7%, and fecal lactoferrin had normalized in 6.3%.
At week 14, remission on the Pediatric Ulcerative Colitis Activity Index (PUCAI) was reached by 40% of patients ages 2 to 11 and by 32% of those ages 12 to 17. remission on this scale was defined as a PUCAI score below 10, and patients' mean score at baseline had been 48.
By week 14, three patients had discontinued because of adverse events. The most common serious adverse events related to ulcerative colitis flare in 10 patients, and abdominal pain, iron deficiency anemia, and acute pancreatitis in one each.
Infections were reported in 13 patients, but none were serious. These included Clostridium difficile infection, pharyngitis, and upper respiratory tract infection. Injection site reactions were reported in six patients, all of which were mild.
There were no opportunistic infections, malignancies, or deaths.
"Golimumab was generally well tolerated in this small, open-label study of pediatric subjects with moderately to severely active ulcerative colitis that is refractory to conventional treatments," the investigators concluded.
