P698 Early dose optimisation in non-responders to golimumab induction treatment for ulcerative colitis is supported by pharmacokinetic data

Abstract

Introduction: In the PURSUIT-M study, ulcerative colitis (UC) patients who were nonresponders to golimumab (GLM) induction treatment at Wk6 (by full Mayo score) were given GLM 100mg q4wk from Wk6 through Wk60. We previously showed that, compared with Wk6-Responders, Wk6-Nonresponders have lower GLM trough levels (TLs) at Wk6, and that Wk6-Nonresponders on the 100mg maintenance dose (at Wk6 and Wk10) achieved TLs at Wk14 that were similar to the TLs at Wk14 in Wk6-Responders on the 50mg dose (1). At Wk14, 28% of the Wk6-Nonresponders became responders (by partial Mayo score) after receiving 100mg at Wk6 and Wk10 (2). Here, we report on GLM TLs in the PURSUIT-M trial, in responders and nonresponders to induction treatment, through Wk50. Aims and Methods: GLM TLs were measured at Wk 6, 10, 14, 18, 26, 34, 42 and 50. To eliminate artefactual changes in median values due to dropouts/missing data, only patients with TLs available at all the timepoints were included in this post-hoc analysis. Also, subgroups based on body weight (BW) <80kg and >=80kg were examined: Wk6-Responders with BW < 80kg on 50mg (n=42), Wk6-Responders with BW < 80kg on 100mg (n=42), Wk6-Responders with BW>=80kg on 100mg (n=18), and Wk6-Nonresponders with BW < 80kg on 100mg (n=62). The 80kg cutpoint was selected based on the maintenance doses currently approved in the EU: either 50mg for BW < 80kg, or 100mg for BW>=80kg. Result(s): At Wk14 (steady-state), Wk6-Nonresponders with BW < 80kg on 100mg and Wk6-Responders with BW < 80kg on 50mg had the same median TL (0.98 mg/mL). At Wk26, 42, and 50, the IQ ranges of GLM TL were largely overlapping in these same two subgroups (Table). At each time point, the highest median TLs were observed in Wk6-Responders with BW < 80kg on 100mg, a posology that is not approved in the EU label of GLM for UC. Conclusion(s): Based on TLs observed at steady state then followed over 1 year, these data suggest that patients with initial nonresponse to GLM induction who weigh < 80kg may require the GLM 100mg maintenance dose to achieve TLs similar to the TLs in induction responders receiving the maintenance doses currently approved in EU (either 50mg forBW < 80kg, or 100mg for BW>=80kg).