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Selection inhibition of JAK-1 may present a scope for
RA treatment as the highly selective JAK-1 inhibitor, filgotinib was found
effective and well-tolerated in RA patients.
Treatment of rheumatoid arthritis (RA) has crossed miles and progressed considerably over the past decade with the evolution of biological targeting inflammatory cytokines. This progression has been obtained with Janus kinase (JAK) inhibitors, an orally available disease-modifying anti-rheumatic cytokines. These show a great efficacy in RA management. These inhibitors are of several types with different clinical benefits. Here, scientists selected a Janus kinase 1 inhibitor, filgotinib and compared its efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) with less selective JAK inhibitors. The two 4-week exploratory, placebo-controlled, double-blind phase IIa trials were conducted for evaluation. The trials involved RA patients who had an insufficient response to methotrexate (MTX). The patients either received filgotinib oral capsules 100 mg twice daily or 30, 75, 150, 200, or 300 mg once daily or placebo. These patients added to a stable regimen of MTX. The total number and percentage of patients in both treatment group, who achieved American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 4 was taken as the primary efficacy endpoint.
The patients at 75-300 mg filgotinib met
the primary endpoint and exhibited early onset of efficacy. The ACR20 response rates increased steadily in 4
weeks, whereas the levels of C-reactive protein got decreased. The levels
of C-reactive protein reflected the
Disease Activity Score in 28 joints. Serum CRP level and other PD markers
showed marked and sustained improvements as well. The pharmacokinetics of
filgotinib and its major metabolite was dose proportional over the 30-300 mg.
No side effects were noticed with other less selective JAK inhibitors. However,
a little consistent decrease was seen in neutrophils without neutropenia with
immunomodulatory effects through JAK-1 inhibition. No infections were noticed
during the treatment. Overall, the tolerability of filgotinib was well
accepted. The events noticed during filgotinib treatment were mild to moderate
and short-term during therapy. The most prevalent event noticed was nausea. On
the whole, filgotinib is effective and safe for RA patients.
Arthritis Rheumatol. 2017 Jun 16
Efficacy, safety, pharmacokinetics, and pharmacodynamics of filgotinib, a selective Janus kinase 1 inhibitor, after short-term treatment of rheumatoid arthritis: Results of two randomized Phase IIA trials
Vanhoutte F et al.
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