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Pharmacokinetics, pharmacodynamics, short term efficacy and safety of RCT‐18, a novel BLyS/APRIL fusion protein, in patients with rheumatoid arthritis
Author(s) -
Chen Xia,
Zhao Qian,
Hou Yong,
Jiang Ji,
Zhong Wen,
Wang Wenxiang,
Yao Xuejing,
Li Lin,
Fang Jianmin,
Zhang Fengchun,
Hu Pei
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12908
Subject(s) - medicine , randomized controlled trial , rheumatoid arthritis , pharmacodynamics , placebo , pharmacokinetics , dosing , biomarker , adverse effect , clinical trial , gastroenterology , pharmacology , pathology , biochemistry , chemistry , alternative medicine
Aim RCT‐18 is a recombinant fusion protein that interferes with the selection and survival of mature B‐lymphocytes by inhibiting B‐lymphocyte stimulator and a proliferation‐inducing ligand. Methods This single blind, randomized, placebo controlled, clinical pharmacological study explored the short term efficacy and safety of RCT‐18 in 21 rheumatoid arthritis (RA) patients with three different dosing regimens. The pharmacological behaviour of RCT‐18 was also characterized through a six level biomarker cascade approach to identify potential predictors for clinical responses. Results Nine out of 10 patients (>80%) experienced moderate to good EULAR response at the end of 3 months with once or twice weekly doses of 180 mg RCT‐18, whereas weekly administration of 360 mg RCT‐18 or placebo, however, only resulted in moderate improvement in one patient in each group. Absence of IgM‐type rheumatoid factor reduction, recovery of IgM 2 weeks after drug cessation, lack of decrease in the count of CD27(+) B‐lymphocytes and a DAS28 change from baseline <6 in 4–6 weeks after the treatment initiation may indicate poor clinical response. No anti‐drug antibody of RCT‐18 was detected. The active treatments were well tolerated, although more mild to moderate infections were reported in patients receiving RCT‐18. Conclusion The study results support further development of RCT‐18 in RA patients and provide important information for future dose selection.