Background While the treatment with intravenous (IV) CT-P13, an infliximab biosimilar, is effective and well tolerated, a new subcutaneous (SC) CT-P13 formulation (CT-P13 SC) is developed to provide additional, more convenient treatment options and opportunity for self-injection.
Objectives To find the optimal dose of CT-P13 SC and to evaluate efficacy, PK and safety over the first 30 weeks in patients with rheumatoid arthritis.
Methods This study consists of 1 cohort with CT-P13 IV, and 3 cohorts with 3 different doses of CT-P13 SC injected biweekly. All enrolled patients initially received CT-P13 IV at Weeks 0 and 2 and patients who received 2 full doses and displayed no safety concerns were randomly assigned to receive either CT-P13 SC or IV at Week 6. Using part 1 result, PK-PD modelling was conducted for the 3 regimens.
Results A total of 50 patients were enrolled, of whom 48 patients were randomly assigned into 4 cohorts.
Overall, the efficacy results of CT-P13 SC up to Week 30 were comparable to those of CT-P13 IV. Disease improvement by DAS28 and ACR20 were comparable across all 4 cohorts, regardless of the route of administration or dosage of CT-P13 (table 1).
The safety profiles in CT-P13 SC cohorts were generally comparable to CT-P13 IV. One of the 2 patients who experienced a hypersensitivity reaction became anti-drug antibody (ADA) positive at Week 6 and experienced hypersensitivity from Week 2 to 8. All injection site reactions were grade 1 or 2. The proportion of ADA (positive) was lower in the SC cohorts.
In PK-PD modelling, bioavailability was 59% (95% CI, 52%–67%). The dose linearity in SC regimens was confirmed based on Weeks 22 to 30 Ctrough, AUCτ and Cmax, ss (figure 1). Ctrough were greater (above 4 µg/mL) than the target exposure (1 µg/mL) in all SC regimens. There was a trend towards slightly lower DAS28 score in all SC regimens, which was consistent with the higher Ctrough comparing with CT-P13 IV. Based on the exposure-response safety analyses, there was no correlation between PK (AUCτ or Cmax) and safety (IRRs or infections).
Treatment continuation in patients enrolled with SB4 or oETN who were bionaive until enrollment.
Conclusions CT-P13 SC showed comparable efficacy and safety with CT-P13 IV. The preliminary results suggest CT-P13 SC as a future alternative treatment of infliximab.
References  Takeuchi, et al. 2009.
 Mori, et al. 2007.
Disclosure of Interest R. Westhovens Grant/research support from: Celltrion, Inc., BMS and Roche, Consultant for: Celltrion, Inc., Galapagos/Gilead and Janssen, D. H. Yoo Grant/research support from: Celltrion, Inc., J. Jaworski Grant/research support from: Celltrion, Inc., E. Matyska-Piekarska Grant/research support from: Celltrion, Inc., S. Smiyan Grant/research support from: Celltrion, Inc., D. Ivanova Grant/research support from: Celltrion, Inc., PPD, Quintiles, Egis Pharmaceuticals, and Pfizer., A. Zielinska Grant/research support from: Celltrion, Inc., E.-K. Raussi Grant/research support from: Celltrion, Inc. and Board of Estonian Society for Rheumatology, A. Batalov Grant/research support from: Celltrion, Inc., S. J. Lee Employee of: Celltrion, Inc., S. Y. Lee Employee of: Celltrion, Inc., J. H. Suh Employee of: Celltrion, Inc.
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