ORLANDO – Ulcerative colitis sufferers with higher vedolizumab trough scores at 6 weeks in the GEMINI-1 study were found to have higher rates of mucosal healing, a post hoc, population pharmacokinetics analysis has shown.
The findings’ significance, however, is still a matter of debate, according to Maria Rosario, Ph.D., a director at Takeda Pharmaceuticals, and the data’s presenter at this year’s annual Advances in Inflammatory Bowel Disease meeting sponsored by the Crohn’s and Colitis Foundation of America.
“We have established a relationship between higher endoscopic scores and faster clearance, but we need to be careful how we interpret the data,” she concluded in her presentation, citing a lack of an established causal relationship between the two.
Results from the GEMINI-1 study lead to the Food and Drug Administration’s 2013 indication of vedolizumab, a disease-modifying monoclonal antibody, for the treatment of refractory ulcerative colitis (UC) and Crohn’s disease.
In the phase III study, two cohorts of UC patients were either double-blinded to vedolizumab 300 mg or placebo; or, to open-label vedolizumab 300 mg at weeks 0 and 2 during induction.
At week 6, responders to the medication in each cohort were re-randomized to either placebo or the study drug every 4 or 8 weeks during maintenance, up to week 52. Induction placebo patients and week 6 nonresponders continued their respective regimens.
For the post hoc analysis, serum levels of the drug in both cohorts were determined at weeks 6 and 46 according to each person’s Mayo Clinic endoscopic subscore at weeks 6 and 52. Trough concentration levels were divided into quartiles at weeks 6 and 46, as were the associated rates of mucosal healing at weeks 6 and 52. Dr. Rosario and her colleagues then used population pharmacokinetic modeling to estimate individual clearance values.
Patients who had higher levels of drug serum concentrations at week 6 were also found to have more mucosal healing. In the 55 patients who had an endoscopic subscore of 0, median trough concentrations were 34.5 mcg/mL; 30.4 mcg/mL in the 223 patients with subscores of 1; 24.0 mcg/mL in the 224 patients with a subscore of 2; and 19.6 mcg/mL in the 188 patients who had a subscore of 3.
Dr. Rosario also noted that in median week 6, trough concentrations in patients with the highest subscores lagged behind the overall week 6 median GEMINI-1 results, which were 25.6 mcg/mL.
Because this study did not measure fecal levels of the drug, these preliminary findings should encourage further investigation, said Dr. Rosario, who said the role of disease severity would be key to more precise interpretation of the data. Dr. Rosario is a director at Takeda Pharmaceuticals, manufacturer of Entyvio, the brand name for vedolizumab.
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