October 2015

Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs

Annals of the Rheumatic Diseases. 2015 Aug 14. doi:pii: annrheumdis-2014-207178.

This study evaluated the efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in patients with inadequate response to sDMARDs or bDMARDs. Findings from this study show both doses of tofacitinib were associated with improvements in efficacy parameters at month 3 versus placebo, and clinical response was numerically greater with bDMARD-naïve versus bDMARD-IR patients (95% CI overlapping). Safety parameters were generally similar; however, patients receiving glucocorticoids had more ...

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September 2015

The Efficacy and Safety of Subcutaneous Clazakizumab in Patients with Moderate-to-Severe Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results from a Phase IIb, Randomized, Double-Blind, Placebo/Active-Controlled, Dose-Ranging, Multinational Study

Arthritis & Rheumatology. 2015 Jul 2. doi: 10.1002/art.39249. [Epub ahead of print]

The humanised monoclonal antibody, Clazakizumab (CLZ), binds to circulating interleukin-6 (IL-6) cytokine rather than the IL-6 receptor, blocking both classical and trans-signalling. The purpose of this phase 2B study was to evaluate the efficacy and safety of clazakizumab in patients with inadequate response to methotrexate (MTX). Data on selected response rates – ACR20/50/70, DAS28-CRP, SDAI ≤3.3, CDAI ≤2.8 and the ACR/EULAR Boolean definition – and adverse events were collected from 418 patie...

July 2015

Long-term Safety of Tocilizumab: Results from 3 Years of Followup Postmarketing Surveillance of 5573 Patients with Rheumatoid Arthritis in Japan

The Journal of Rheumatology. 1 June 2015 DOI: 10.3899/jrheum.141210 [Epub ahead of print]

The humanised anti-interleukin 6 receptor monoclonal antibody tocilizumab (TCZ) has been available in clinical practice for several years. The purpose of this study was to evaluate the long-term safety of for the treatment of RA in a real-world clinical setting as a long-term extension of a single-arm, observational post marketing surveillance study. Data on selected adverse events (AEs) - fatal events, serious infection, malignancy, GI perforation, and serious cardiac dysfunction - were collect...

March 2015

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

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...

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Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection

Clin Pharmacokinet. 2015 Feb 14. [Epub ahead of print]

Filgotinib (GLPG0634) is a selective inhibitor of JAK1 currently in development for the treatment of RA and Crohn’s disease. This paper describes the pharmacokinetics of filgotinib and its active metabolite, as well as the PK/PD modelling to support dose selection for phase IIB.

Two phase I, randomised, double-blind, placebo-controlled trials in healthy volunteers and one phase IIa proof-of-concept study in RA patients were used to evaluate single and multiple doses of filgotinib.

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A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases

Nat Med. 2015 Feb 16. doi: 10.1038/nm.3806. [Epub ahead of print]

A team of scientists at Trinity College Dublin and the University of Queensland Australia, led by Professor Luke O'Neill, have identified a key molecule that may result in the development of new anti-inflammatory therapies for diseases such as: cryopyrin-associated periodic syndrome (CAPS), multiple sclerosis, type 2 diabetes, Alzheimer’s disease and atherosclerosis.

Professor O'Neill and his team have identified MCC950 as a potent, selective, small-molecule inhibitor of the NLRP3 infla...

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January 2015

The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1/2 inhibitor, in healthy volunteers

Mod J Clin Pharmacol. 2014 Dec;54(12):1354-61. doi: 10.1002/jcph.354.

Current biologic therapies for RA, such as biologic cytokine inhibitors, which selectively target inflammatory molecules with an exquisite degree of specificity, are not clinically effective in all patients with rheumatoid arthritis. As such, there remains an unmet clinical need for more effective and better tolerated therapies. Baricitinib (LY3009104, also previously known as INCB028050) is a potent and selective small molecule inhibitor of JAK1/2, which play an important role in cytokine signa...

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December 2014

Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate

Ann Rheum Dis. 2015;74(2):333–340

Recent innovations in the treatment of RA have focused on the use of small molecules to inhibit intracellular kinases such as the JAK family. Baricitinib (LY3009104, formerly INCB028050) is an orally administered, potent, selective and reversible inhibitor of JAK1 and JAK2, which has shown anti-inflammatory effects, as well as preservation of cartilage and bone, in preclinical rodent studies.

This phase IIb study was designed to investigate multiple doses and dosing regimens of baricitin...

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Lipid profile changes in patients with chronic inflammatory arthritis treated with biologics and tofacitinib in randomized clinical trials: A systematic review and meta-analysis

Arthritis Rheumatol. 2015;67(1):117–127

Systemic inflammation, reflected by high levels of C-reactive protein and the erythrocyte sedimentation rate, has been identified as an independent risk factor for cardiovascular disease, the most important cause of death in RA and SpA. Studies with TNF antagonists have given contradictory results on cardiovascular risk. As such, this systemic literature search aimed to analyse lipid changes in RA and SpA subjects treated with biologics or tofacitinib in randomized clinical trials.

The s...

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September 2014

Secukinumab in Plaque Psoriasis — Results of Two Phase 3 Trials

N Engl J Med. 2014;371(4):326–338.

Secukinumab is a fully human monoclonal antibody that selectively binds to and neutralises interleukin-17A, a cytokine shown to play a crucial role in plaque psoriasis, as well as other immune-mediated diseases.

These two pivotal phase 3 studies in plaque psoriasis, FIXTURE and ERAUSRE, were sponsored by Novartis Pharmaceuticals. Secukinumab met all primary endpoints, PASI 75 response and the response of 0 or 1 on the modified investigator’s global assessment, as well as key secondary end...

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