Entyvio shows promise in pediatric patients with IBD
WASHINGTON – Two studies presented during DDW 2015 showed safety and efficacy of Entyvio used in pediatric patients with a range of inflammatory bowel diseases.
“In summary, vedolizumab was associated with week 6 and week 14 remission in both pediatric ulcerative colitis and pediatric Crohn’s disease patients, with UC patients having higher rates of remission than Crohn’s,” Namita Singh, MD, of Cedars Sinai in Los Angeles, said during her presentation.
Singh presented results of a prospective observational study in which they initiated Entyvio (vedolizumab, Takeda; 6 mg/kg, maximum 300 mg) — off label — via intravenous infusion in pediatric patients. During the study, they monitored routine blood work and inflammatory markers such as CRP and calculated disease activity score using the pediatric Crohn’s disease activity index (PCDAI) and pediatric ulcerative colitis activity index (PUCAI). The primary clinical outcomes was clinical remission at week 6 (PUCAI ≤ 10; PCDAI ≤ 10).
The study looked at 23 patients (15 with Crohn’s; eight with ulcerative colitis) enrolled between June 2014 and October 2014; median age of vedolizumab initiation was 14 years.
At 88%, the patients with ulcerative colitis had a higher rate of remission than those with Crohn’s who were at 40%. This trend sustained at week 14 and Singh said all patients with ulcerative colitis who had received vedolizumab at week 14 were in remission.
Week 6 and week 14 remission rates overall were 56.5% and 57.1%, respectively, and week 6 remission predicted week 14 remission (P < .05).
“Week 6 remission is associated with week 14 remission,” Singh said. “This suggests that we can determine early in therapy whether a patient will be a primary responder to therapy. If not, then perhaps we should move on to another therapy.”
Additionally, Singh showed that there was an association between duration from anti-TNF therapy to vedolizumab treatment and remission.
“Longer duration from last anti-TNF exposure is associated with higher remission rates,” Singh said. “This leads to the question of where to position vedolizumab in your clinical practices. Perhaps we should have a longer wash-out period for patients who are undergoing therapies with anti-TNF treatments or consider its use in anti-TNF-naive patients.”
Overall safety was shown through secondary endpoints.
Continued success with Crohn’s, IBD
Ronen Stein, MD, from the Perelman School of Medicine at the University of Pennsylvania, also presented data on vedolizumab therapy in patients with severe pediatric IBD, who were defined as those that had previously failed therapy.
In this single center, prospective observational cohort study, the primary endpoint was a decrease in PCDAI/PUCAI from baseline to weeks 6, 14 and 22 and secondary endpoints were changes in albumin, hematocrit and CRP as well as remission at the same time points.
Patients received vedolizumab infusions (300 mg) at weeks 0, 2 and 6 for induction and maintenance through week 22.
The researchers included children aged 13 years to 21 years (n = 17) with IBD who weighed 40 kg or more and had a past failure on TNF-alpha inhibitor therapy. Of these patients, 15 had Crohn’s disease and two had unclassified IBD (IBD-U).
More than three-quarters started on systemic corticosteroids at baseline; more than one quarter were on immunomodulators. Seven patients had previous abdominal surgery and 59% of patients had failed more than one biologic therapy.
“This was a pretty sick population,” Stein said.
At each time point in question, this study saw improvement of PCDAI (P < .001 at week 6; P < .05 at week 14; P < .0001 at week 22).
“Starting at week 6, there was a significant decrease in PCDAI that was sustained for weeks 14 and 22.”
Five patients reached remission at week 6.
“There really is no pattern to tell us which patients will be in remission at week 6. They have pretty different characteristics,” Stein said.
Secondarily, he showed that while the percentage of patients on steroids did decline and CRP improved, they were not significant changes. Hematocrit, though, increased from 35.5 at baseline to 38 at week 22 (P < .01).
“By week 22, less than half of patients were still on steroids,” he said.
There were three adverse events in terms of infections, but Stein said they seem to be unrelated.
“At week 6, Crohn’s disease and IBD-U patients on vedolizumab demonstrate significant clinical improvement from baseline in terms of PCDAI and serum albumin. We had sustained improvement through week 22,” he concluded. – by Katrina Altersitz
For more information:
Singh N, et al. Abstract 321. Presented at: Digestive Disease Week, May 16-19, 2015; Washington, D.C.
Stein R, et al. Abstract 322. Presented at: Digestive Disease Week, May 16-19, 2015; Washington, D.C.
Disclosure: Singh reports a financial relationship with Janssen. Stein reports no relevant financial disclosures. Please see the DDW faculty disclosure index for all other researchers’ relevant financial disclosures.Editor's Note: This article was updated on May 29 to accurately reflect the name and location of Singh's institution.