Peficitinib, a JAK Inhibitor, in the Treatment of Moderate-to-Severe Rheumatoid Arthritis in Patients With an Inadequate Response to Methotrexate.

OBJECTIVE: To evaluate the efficacy and safety of orally administered once-daily peficitinib in combination with methotrexate (MTX) in patients with moderate-to-severe rheumatoid arthritis (RA) who had an inadequate response to MTX. METHODS: In this multinational, phase IIb, randomized, double-blind, placebo-controlled, dose-ranging trial, patients with RA (n = 378) were treated with peficitinib 25 mg, 50 mg, 100 mg, or 150 mg plus MTX, or matching placebo plus MTX once daily for 12 weeks. The primary end point was the percentage of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 12. RESULTS: ACR20 response rates at week 12 were 43.9%, 61.5% (P < 0.05 versus placebo), 46.4%, 57.7%, and 44.4% in the peficitinib 25 mg, 50 mg, 100 mg, 150 mg, and placebo groups, respectively. Significant decreases from baseline in the Disease Activity Score in 28 joints using the C-reactive protein level were seen in the peficitinib 50 mg (P < 0.05) and 150 mg (P < 0.01) groups compared with placebo at week 12. Overall, the incidence of adverse events (AEs) was similar between peficitinib and placebo. The most common AEs were urinary tract infection (n = 22 [6%]), upper respiratory tract infection (n = 16 [4%]), and diarrhea (n = 16 [4%]). There were 3 cases of herpes zoster infection (2 in the peficitinib 100 mg group and 1 in the 150 mg group) and 2 cases of serious infection (viral infection in the peficitinib 100 mg group and erysipelas in the 150 mg group). CONCLUSION: The ACR20 response rate in the group receiving peficitinib 50 mg plus MTX was significantly different compared with the rate in patients receiving placebo, but there were no apparent dose-dependent responses, and the placebo response rate was high. Peficitinib plus MTX in patients with moderate-to-severe RA was well tolerated, with limited safety signals emerging.

Expression of muscarinic cholinergic receptors on lymphocytes in various subsets of rheumatoid arthritis and their variabilities connected with treatment.

OBJECTIVE: To investigate muscarinic cholinergic receptors on lymphocytes from various subsets of patients with rheumatoid arthritis (RA). METHODS: The level of muscarinic receptors on peripheral blood lymphocytes from 38 patients with various subsets of RA [5 with inactive, 13 with active RA, 13 with rheumatoid vasculitis and 5 with reactive secondary amyloidosis (RSA)] was determined by the binding studies of specific muscarinic ligand [3H] quinuclidinyl benzilate in comparison to healthy individuals. RESULTS: Expression of muscarinic cholinergic receptors on lymphocytes in patients with RA was significantly higher (mean 1022; SD +/- 567) compared to healthy individuals (mean 647; SD +/- 170) (p < 0.01). The phytohemagglutinin (PHA) stimulation index in acetylcholine treated lymphocytes in patients was statistically significantly lower than in healthy individuals (p < 0.05). The highest levels of muscarinic receptors on lymphocytes was observed in patients with RA with vasculitis and RSA and showed a significant correlation with disease activity. The number of muscarinic receptors on lymphocytes as well as PHA stimulation index in acetylcholine treated and untreated lymphocytes showed a tendency to decrease after the treatment. The number of muscarinic receptors on lymphocytes decreased significantly after the treatment only in the group of patients with clinical improvement (p < 0.05). CONCLUSION: Our results suggest that cholinergic stimulation may be connected with activity and/or heterogeneity of the disease in patients with RA.