P0897Serum concentrations of infliximab are comparable with and without immunosuppression during subcutaneous infliximab induction treatment for Crohn’s disease

Abstract Background Subcutaneous (SC) infliximab (IFX) is available for maintenance treatment of Crohn’s disease (CD) following intravenous induction. In DIRECT-CD, a prospective randomised controlled international trial, CD patients with active disease initially received SC IFX induction at 240 mg at week (W) 0 and 2, followed by 120 mg every other week (eow). As early pharmacokinetic data indicated suboptimal IFX exposure, the protocol was amended to a higher first dose (480 mg at W0) for all patients and a doubled maintenance dose (240 mg eow from W4) for patients ≥80 kg. We compared IFX pharmacokinetics between SC IFX with and without immunomodulator (IMM) use across different induction schemes, and in relation to pharmacogenomic profiles. Methods Patients with moderate-to-severe CD (CD activity index 220 and endoscopic ulceration) received SC IFX induction according to either the original regimen (240 mg at W0 and W2, then 120 mg eow) or the amended regimen (480 mg at W0 and 240 mg at W2), followed by weight-based maintenance dosing (120 mg eow for patients 80 kg and 240 mg eow for patients ≥80 kg). Patients were randomized to SC IFX mono- or combination therapy with an IMM (thiopurine or methotrexate). Serum IFX and anti-drug antibodies (ADA) against IFX were measured at W2, 4, 8 and 14. HLA-DQA1*01-06 genotyping was performed at W0. Results Sixty patients were randomized (53% female, median age 30 years, median body weight 70. 9kg, 62% ileocolonic disease, 70% non-stricturing/non-penetrating disease, 8% active perianal disease, 72% biologic-naïve). 31/60 patients received the original induction, 50/60 received standard maintenance (120 mg eow), 31/60 patients received a concomitant IMM. Patients receiving 480 mg at W0 had higher serum IFX concentrations at W2, W4, and W8, but not W14, compared to original induction (Figure 1A). No differences in serum IFX concentrations were observed between SC IFX mono- and combination therapy (Figure 1B). Across all time points, ADA against IFX (12 AU/mL) were detected 15 times in 9 patients; none occurred at W2. At W14, 8 monotherapy patients and 1 combination therapy patient were ADA-positive (P = 0. 048). The HLA-DQA1*05 allele (31/60, 52%) was associated with lower serum IFX concentrations and higher ADA levels (P = 0. 035). Conclusion In CD patients receiving SC IFX, intensified induction (480-240 mg) resulted in higher early serum concentrations. Combination therapy with IMM did not increase IFX concentrations, yet was associated with a lower proportion of ADA-positive patients at W14. Carriers of HLA-DQ5 showed lower IFX exposure and higher immunogenicity. These data suggest limited added benefit of concomitant IMM for IFX pharmacokinetics during intensified SC IFX induction. Conflict of interest: Anjie, Suzanne: No conflict of interest Jansen, Jeroen Michiel: consultant forJanssen, Galapagos, Takeda en Lilly. Jharap, Bindia: No conflict of interest Mares, Wout: No conflict of interest Duijvestein, Marjolijn: Grant: Speaking fees from Bristol Meyers Squibb, Takeda, Galapagos, Janssen, Dr. Falk, Advisory board fees from Abbvie, Bristol Meyers Squibb, Celltrion, Galapagos Alfasigma, Janssen, Takeda Grant/Research support: Pfizer, Bristol Meyers Squibb, Galapagos, Alfasigma, Janssen, Lilly Ye, Byong Duk: Byong Duk Ye reports consulting fees from AbbVie Korea, BMS Pharmaceutical Korea Ltd. , Celltrion, Chong Kun Dang Pharm, CJ Red BIO, Curacle, Daewoong Pharm, Dong-A ST, Ferring Korea, Hanmi Pharmaceutical, Imscout, IQVIA, Johnson & Johnson, Johnson & Johnson Korea, Jeil Pharmaceutical Co. , Kangstem Biotech, Korea Otsuka Pharm, Korea United Pharm, Lilly Korea, Medtronic Korea, NanoEntek, ORGANOIDSCIENCES Ltd. , Pfizer Korea, Samsung Bioepis, Takeda, Takeda Korea and Yuhan speaker fees from AbbVie Korea, BMS Pharmaceutical Korea Ltd. , Celltrion, Cornerstones Health, Curacle, Daewoong Pharm, Eisai Korea, Ferring Korea, IQVIA, Johnson & Johnson Korea, Pfizer Korea, Samsung Bioepis, and Takeda Korea and research support from Celltrion and Pfizer Korea. Kim, Tae Oh: No conflict of interest Kang, Sang-Bum: Sang-Bum Kang has received research grants from Celltrion, Chong Kun Dang Pharm, Il-Yang Pharm, Pharmbio Korea, and Taejoon Pharm consulting fees from AbbVie Korea, Ferring Korea, Janssen Korea, and Takeda Korea and speaking fees from AbbVie Korea, Celltrion, Ferring Korea, Janssen Korea, Pfizer Korea, Taejoon Pharm, and Takeda Korea. Kim, Eun Soo: Eun Soo Kim has acted as a speaker or advisory board member of AbbVie, Celltrion, J&J, Ferring, Pfizer, Samsung Bioepis, and Takeda. Park, Dong Il: Dong Il Park has served as an advisory board member for AbbVie, Celltrion, Ferring, and Shire (a member of the Takeda group of companies). Maljaars, Jeroen: Grants, consulting fees, payment for lectures: Galapagos, abbvie, takeda Römkens, Tessa: No conflict of interest Oldenburg, Bas: Unrestricted grants: Abbvie, Takeda, Pfizer, Galapagos boards: Abbvie, Takeda, Pfizer, Lilly, Galapagos, Janssen Boukema, Inge: No conflict of interest Janssen, Reimer: No conflict of interest Oldenburg, Lotte: No conflict of interest Van Oostrom, Joep: Other: Speaker fees from Tillott’s and Takeda Van Welsen, Inge: No conflict of interest Clasquin, Esme: No conflict of interest D’Haens, Geert: Grant: Pfizer, BMS, Johnson and Johnson, Abbvie, Alimentiv BV, Eli Lilly, Takeda, Prometheus Laboratories Persona