Cytokine Signalling Forum

Publications





December 17

JAK Inhibition as a Therapeutic Strategy for Immune and Inflammatory Diseases

Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O’Shea JJ.
Nat Rev Drug Discov 2017;16:843–62 DOI: 10.1038/nrd.2017.201

Janus kinases (JAKs) are essential mediators of downstream signaling pathways in many inflammatory and autoimmune diseases. This review summarizes current clinical data on first- and second-generation JAK inhibitors (jakinibs) and discusses their use for the treatment of immune and inflammatory conditions. First generation jakinibs such as tofacitinib, baricitinib, and ruxolitinib, non-selectively inhibit JAK-dependent pro-inflammatory cytokines, which are major contributors to immunopathology. ...

Keywords: JAK, Tofacitinib, Clinical, Efficacy

December 16

Efficacy of VX-509 (decernotinib) in Combination with a Disease-modifying Antirheumatic Drug in Patients with Rheumatoid Arthritis: Clinical and MRI Findings

Genovese M, Yang F, Østergaard M and Kinnman N.
Ann Rheum Dis 2016;75:1979–83

This Phase 2b study of VX-509 (decernotinib), a selective JAK3 inhibitor, showed that VX-509 in combination with stable DMARD therapy was effective for improving synovitis and osteitis as assessed by MRI in patients who had an inadequate response to DMARD therapy. Patients were randomised to treatment groups receiving either placebo, VX-509 100 mg, 200 mg or 300 mg for 12 weeks. Minimum inclusion criteria included Grade ≥2 clinical synovitis in either the wrist or two metacarpophalangeal joi...

Keywords: JAK, Decernotinib, Clinical, Phase 2

January 16

VX-509 (Decernotinib), an Oral Selective JAK-3 Inhibitor, in Combination With Methotrexate in Patients With Rheumatoid Arthritis

Genovese MC, van Vollenhoven RF, Pacheco-Tena C, Zhang Y, Kinnman N.
Arthritis Rheumatol. 2016 Jan;68(1):46-55.

VX-509 (decernotinib) is a novel oral, selective inhibitor of JAK-3. JAK-3 is a member of the JAK signalling family that is primarily expressed in hematopoietic cells and associates with only the common γ-chain making it a promising therapeutic drug target. A phase IIb 24-week study of VX-509 in 358 patients with RA, who had prior inadequate response to MTX, uses ACR20 response rate and DAS28-CRP change at Week 12 to assess the efficacy of VX-509. Patients were administered either placebo+...

Keywords: JAK, Decernotinib, Clinical, Phase 2

March 15

A Randomized, Double-Blind, Placebo-Controlled, Twelve-Week, Dose-Ranging Study of Decernotinib, an Oral Selective JAK-3 Inhibitor, as Monotherapy in Patients With Active Rheumatoid Arthritis

Fleischmann RM, Damjanov NS, Kivitz AJ, et al.
Arthritis Rheumatol. 2015;67(2):334–343.

Decernotinib (VX-509; Vertex Pharmaceuticals Incorporated) is a JAK 3 inhibitor currently under investigation for its potential use in the treatment of RA. The potency and selectivity profiles of this oral compound have already been established in previous trials, so this study aimed to establish the efficacy and safety profiles of the drug, in RA patients who have had an inadequate response to at least one DMARD. Four doses; 25 mg, 50 mg, 100 mg and 150 mg, were evaluated in this placebo-contr...

Keywords: JAK, Decernotinib, Clinical, Phase 2