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:...
In milk and milk products, a number of organic acids naturally occur. We investigated the contents of some naturally occurred food preservatives (sorbic acid, benzoic acid, propionic acid, nitrite, and nitrate) contained in domestic and imported cheeses to establish the standard for the allowable range of food preservatives content in cheese. 8 kinds of domestic precheeses (n=104), 16 kinds of domestic cured cheeses (n=204) and 40 kinds of imported cheeses (n=74) were collected. Each domestic cheese was aged for a suitable number of months and stored for 2 mon at 5℃ and 10℃. No preservatives were detected in domestic soft and fresh cheeses, except cream cheese. In case of semi-hard cheeses, 2-5 mg/kg of benzoic acid was detected after 1-2 mon of aging. In imported cheeses, only benzoic acid and propionic acid were detected. The average benzoic acid and propionic acid contents in semi-hard cheese were 8.73 mg/kg and 18.78 mg/kg, respectively. Specifically, 1.16 mg/kg and 6.80 mg/kg of benzoic acid and propionic acid, respectively, were contained in soft cheese, 3.27 mg/kg and 2.84 mg/kg, respectively, in fresh cheese, 1.87 mg/kg and not detected, respectively, in hard cheese, and 2.07 mg/kg and 182.26 mg/kg, respectively, in blended processed cheese.
This study sought to investigate the change of naturally occurring benzoic acid (BA) during skim milk fermentation by 4 kinds of commercial cheese starters used in domestic cheese. The culture was incubated at 3-h intervals for 24h at 30, 35, and 40°C. The BA content during fermentation by Streptococcus thermophilus STB-01 was detected after 12h at all temperatures, sharply increasing at 30°C. In Lactobacillus paracasei LC431, BA was detected after 9h at all temperatures, sharply increasing until 18h and decreasing after 18h at 30 and 35°C. In the case of R707 (consisting of Lactococcus lactis ssp. lactis and Lactococcus lactis ssp. cremoris), BA increased from 6h to 15h and decreased after 15h at 40°C. The BA during STB-01 and CHN-11 (1:1; mixture of S. thermophilus, Lc. lactis ssp. lactis, Lc. lactis ssp. cremoris, Lc. lactis ssp. diacetylactis, Leuconostoc mesenteroides ssp. cremoris) fermentation was detected after 3h at 35 and 40°C, sharply increasing up to 12h and decreasing after 15h at 35°C, and after 6h, increasing up to 9h at 30°C. After 3h, it steadily decreased at 40°C. The highest amount of BA was found during the fermentation by R707 at 30°C; 15h with 12.46mg/kg.
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