Early Dose Optimisation of Golimumab in Nonresponders to Induction Treatment for Ulcerative Colitis Is Effective and Supported by Pharmacokinetic Data

Abstract

BACKGROUND AND AIMS: In nonresponders to golimumab induction for ulcerative colitis, we assessed clinical response rates and golimumab serum concentrations when the 100-mg dose was used early in the course of maintenance. METHODS: This post-hoc analysis of golimumab maintenance dosing [in the PURSUIT-M study] examined clinical outcomes and golimumab concentrations in early [Week 6] responders and nonresponders to induction, including subgroups based on body weight. RESULTS: In nonresponders to golimumab induction [assessed at Week 6], the 100-mg maintenance dose [starting at Week 6] resulted in a meaningful proportion [28.1%] of patients achieving a partial Mayo response at Week 14. After 1 year of maintenance, clinical outcome [response, remission, mucosal healing, corticosteroid-free state] rates in these "late" [Week 14] responders were similar to those in early [Week 6] responders. Golimumab concentrations in early nonresponders were approximately half those of early responders, suggesting that early nonresponders had more rapid golimumab clearance. Examined by body weight, the early nonresponders weighing <80 kg and receiving 100 mg had golimumab concentrations similar to the early responders [weighing <80 kg or ≥80 kg and receiving 50 mg or 100 mg, respectively]. CONCLUSIONS: Early use of the 100-mg maintenance dose leads to positive clinical outcomes in a meaningful proportion of patients who did not respond to golimumab at Week 6. Early nonresponders <80 kg who received the 100-mg maintenance dose achieved adequate golimumab concentrations and a clinically meaningful proportion of these patients had a late clinical response.PURSUIT-M protocol number C0524T18; ClinicalTrials.gov, NCT00488631; EudraCT, 2006-003399-37.