Pharmacokinetics, pharmacodynamics, short term efficacy and safety of RCT-18, a novel BLyS/APRIL fusion protein, in patients with rheumatoid arthritis.

Abstract

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. 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. 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 180mg RCT-18, whereas weekly administration of 360mg 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 4-6weeks 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. The study results support further development of RCT-18 in RA patients and provide important information for future dose selection.