Effects of Immunomodulators on the Pharmacokinetics and Efficacy of Golimumab in Patients with Moderately to Severely Active Ulcerative Colitis: Results from Phase 2/3 PURSUIT-SC Induction and Maintenance Studies (2013)

Purpose: To assess the effects of concomitant immunomodulators (IMs) on PK and efficacy of golimumab (GLM) in patients from the PURSUIT-SC studies. Methods: PURSUIT-SC induction randomized ulcerative colitis (UC) patients with Mayo scores of 6-12 inclusive, including an endoscopic subscore ≥2 to PBO/PBO (n=331), GLM100 mg/50 mg (before Ph3 dose selection only, n=72), GLM200 mg/100 mg (n=331), or GLM400 mg/200 mg (n=331) at weeks 0 and 2. PURSUIT maintenance enrolled 1,228 pts from PURSUIT-IV and PURSUIT-SC induction studies. Primary analysis population for maintenance were patients (n=464), who responded to GLM induction and were randomized to PBO, GLM50 mg, or GLM100 mg at baseline (week 0) and q4wks through wk52. Serum GLM concentration (SGC) was measured in samples collected through wk6 of induction and wk54 of maintenance using a validated electrochemiluminescent immunoassay. Antibodies to GLM (ATG) were assessed at wk6 of induction, and at wk30 and wk54 of maintenance using an enzyme immunoassay. Efficacy outcomes by IM use were assessed at wk6 (clinical response and remission) for induction; and through wk54 (sustained clinical response) and at wk30 and wk54 (sustained clinical remission) for maintenance. Results: 1227 pts had ≥1 measurable SGC during study. Among these pts, 32.2% were receiving IMs at wk 0 of induction (AZA/6-MP [n=379] and MTX [n=16]). Among GLM induction responders randomized to GLM or PBO, 349 remained on their randomized dose of GLM100 mg, GLM50mg or PBO through wk54. Of these, 29.5% were receiving IMs. During induction within each SC group, median SGC levels were similar between pts receiving vs those not receiving IMs. During maintenance, IM use had no substantial impact on median SGC in those receiving GLM100mg, while median SGC was slightly but consistently higher in the GLM50mg in combination with IM vs without IM. During induction and maintenance, there was a positive E-R relationship between SGC and efficacy outcomes regardless of IM use. Concomitant IM use did not appear to affect efficacy outcomes. Among pts who received ≥1 dose of GLM across these UC studies, ATG incidence was higher (p=0.02) in pts who remained on PBO during maintenance vs those who remained on GLM 50 mg or GLM 100 mg (8.8% vs 2.6%). ATG incidence was lower in pts receiving IMs vs those who were not (1.5% vs 3.5%, overall 2.8%). Median SGC was lower and there was an apparent trend towards lower rates of clinical response through wk54 in pts positive for ATG. Among GLM induction responders who remained on PBO during maintenance, those positive for ATG were not receiving IMs. Conclusion: Concomitant IM use is associated with a decreased incidence of ATG, but does not substantially affect GLM serum levels, efficacy, or E-R in UC. Disclosure - Omoniyi J Adedokun, Zhenhua Xu, Colleen Marano, Richard Strauss, Hongyan Zhang, Jewel Johanns, Joyce Ford, Honghui Zhou, and Hugh M Davis-all employees: Janssen Research and Development, LLC; JF Colombel, Walter Reinisch, Brian G. Feagan, Paul Rutgeerts, William Sandborn-all Grant/Research Support: Janssen Research and Development, LLC. This research was supported by an industry grant from Janssen Research and Development, LLC.