Higher golimumab concentrations mean better clinical response in ulcerative colitis

Last Updated: 2016-01-14

By Will Boggs MD

NEW YORK (Reuters Health) - Higher serum concentrations of golimumab are associated with better clinical response rates in patients with refractory ulcerative colitis (UC), a small study hints.

"We were surprised that despite the relatively small sample size of the study a clear difference in exposure between responders and non-responders was observed and this very early in treatment," Dr. Ann Gils, from Catholic University Leuven, Belgium, told Reuters Health by email.

In the PURSUIT trial, higher golimumab concentrations appeared to be associated with greater rates of clinical response and remission, but the optimal therapeutic window for golimumab in UC is unknown.

Dr. Gils and colleagues generated monoclonal antibodies toward golimumab and developed assays to determine golimumab and anti-golimumab concentrations in 21 patients with refractory UC who started golimumab therapy (three of them in combination with thiopurines).

Ten patients showed at least partial clinical response at week 14, and three of these had a complete clinical response. Four of 10 partial responders (two of three complete responders) experienced mucosal healing.

Median serum golimumab concentrations were higher at week 2 and week 6 in complete responders (10.4 mcg/mL and 7.7 mcg/mL, respectively) than in partial responders and nonresponders (8.0 mcg/mL and 3.7 mcg/mL, respectively), according to the January 6 Journal of Crohn's and Colitis online report.

Patients who achieved mucosal healing also had higher serum golimumab concentrations at week 2 and week 6 than patients who did not have mucosal healing.

Because of the sample size, neither of these differences achieved statistical significance.

Four of 21 patients tested for anti-golimumab antibodies at least once during the 14 weeks of treatment, but this had no obvious impact on clinical outcomes - two of these patients were in partial clinical response, one had complete clinical response with mucosal healing, and one had no clinical response.

"Only three out of 10 patients previously exposed to anti-TNF (tumor necrosis factor) responded (partially) to golimumab therapy, which we consider very low," Dr. Gils said. "Monitoring of serum golimumab concentrations is therefore recommended from the beginning in order to allow targeted dose intensification in those patients who don't sufficiently respond to golimumab."

"This study confirms the association of golimumab serum concentrations and response to therapy," she concluded. "Larger cohort studies are needed to define an optimal cut-off at different time points to allow optimization of treatment that results in better care of patients."

Dr. Manuela G. Neuman, from In Vitro Drug Safety and Biotechnology, Toronto, Ontario, Canada, who recently reviewed biologic therapies in inflammatory bowel disease (http://bit.ly/1ZmTorb), told Reuters Health by email, "UC is not a uniform disease. Each individual in this cohort presented different localization of the disease and probably a different degree of the severity of diseased mucosa. Moreover, some patients have been naive to anti-TNF medication and other patients have been exposed to different anti-TNFs."

"However, the study shows the importance of measuring the serum level of the drug," Dr. Neuman said. "The gastroenterologists have to follow up the clinical feature of the patients and correlate the changes in the UC-score with the blood levels of the anti-TNF they use."

The Fund for Scientific Research Flanders and Science and Technology in Flanders supported this research. Three coauthors reported disclosures.

SOURCE: http://bit.ly/1URVCxy

J Crohns Colitis 2016.