BackgroundEfficacy and safety of a new subcutaneous (SC) formulation (CT-P13 SC) up to Week 30 were comparable with intravenous (IV) formulation (CT-P13 IV) in both patients with rheumatoid arthritis (RA) [1] and Crohn's disease [2].ObjectivesThis report is to further investigate pharmacokinetics, efficacy and overall safety of CT-P13 SC in patients with RA throughout the 1-year treatment period.MethodsPatients with active RA (presence of 6 or more swollen and tender joints [of 28 assessed], and serum C-reactive protein [CRP] concentration >0.6 mg/dL) were treated with CT-P13 IV at Weeks 0 and 2, and were randomized for continuation with CT-P13 IV or SC administration at Week 6. The IV cohort received CT-P13 IV 3 mg/kg every 8 weeks and the SC cohorts received CT-P13 SC 90 mg, 120 mg or 180 mg, respectively, every 2 weeks up to Week 54. Pharmacokinetics blood samples were collected before study drug administration at each visit and drug levels were determined by electrochemiluminescent assay. Efficacy parameters including DAS28 and ACR criteria and overall safety were evaluated.ResultsA total of 50 patients were enrolled, of whom 48 patients were randomly assigned at Week 6 into 4 cohorts (1:1:1:1 ratio). The mean Ctrough (pre-dose serum concentration of CT-P13 before next dose injection) of SC cohorts throughout the study visits were higher than those of IV cohort after randomization at Week 6. Ctrough levels increased with SC dose and were sufficiently higher than the target therapeutic concentration (1 μg/mL) throughout the study period (Figure 1). Overall, the efficacy results of CT-P13 SC up to Week 54 were comparable to those of CT-P13 IV. Disease improvement by DAS28 (CRP) and ACR20 were comparable across all 4 cohorts, regardless of the route of administration or dosage of CT-P13 (Table 1). The safety profiles which occurred after study drug administration at Week 6 in SC cohorts were generally comparable to those of IV cohort and appeared similar to those previously reported for IV infliximab [3]. All injection site reactions were grade 1 or 2. No malignancy or death was reported (Table 1).ConclusionThe results from 1-year treatment suggest similar efficacy and safety of CT-P13 SC to CT-P13 IV in RA. The mean serum concentration in all SC cohorts consistently exceeded the threshold of target therapeutic concentration. These results show that the novel SC formulation of CT-P13 may enhance treatment options for use of infliximab biosimilar by providing high consistency in drug exposure.Reference1Westhovens et al., Annals of the Rheumatic Disease 2018;77:315.2Schreiber et al., Gastroenterology 2018;154(6):S-1371.3Yoo et al., Arthritis Research & Therapy 2016;18:82. Disclosure of InterestsDaeHyun Yoo Grant/research support from: Celltrion, Inc., Consultant for: Celltrion, Inc., Janusz Jaworski Grant/research support from: Celltrion, Inc., Ewa Matyska-Piekarska Grant/research support from: Celltrion, Inc., Svitlana Smiyan Grant/research support from: Celltrion, Inc., Delina Ivanova Grant/research support from:...

BackgroundWhile 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.ObjectivesTo 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.MethodsThis 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.ResultsA 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)[1][2] 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).Abstract THU0191 – Table 1Efficacy and safety up to Week 30Cohort 1IV 3 mg/kg(n=13)Cohort 2SC 90 mg(n=11)Cohort 3SC 120 mg(n=12)Cohort 4SC 180 mg(n=12) DAS28 (CRP), mean±SDWeek 05.4±0.86.3±0.85.7±0.95.5±0.8 Week 63.9±1.54.6±1.13.9±1.23.4±1.2Week 223.9±1.63.7±1.03.3±1.42.8±1.3Week 303.3±1.33.0±1.13.1±1.02.7±1.0ACR20,n (%)Week 68 (61.5)8 (72.7)7 (58.3)7 (58.3)Week 228 (61.5)8 (72.7)9 (75.0)11 (91.7)Week 3011 (84.6)10 (90.9)10 (83.3)12 (100)Safety, n (%)Hypersensitivity/IRR01 (9.1)1 (8.3)0Injection site reactions02 (18.2)02 (16.7)Infections4 (30.8)2 (18.2)04 (33.3)ADA9 (69.2)3 (27.3)4 (33.3)1 (8.3)Abstract THU0191 – Figure 1Mean (± SD) Simulated CT-P13 Serum Concentration vs Time Profiles for the Simulated Fixed Dose SC Maintenance Dosing Regimens with Overlaid IV Maintenance Reference Treatment (Semi-Logarithmic Scale). Solid line=Period 1 (IV reference regimen: IV loading+IV maintenance dose). Dashed line=Period 2 (SC test regimen: IV loading+SC maintenance dose)Abstract ...