Publications

Efficacy and Safety of Filgotinib, a Selective Janus Kinase 1 Inhibitor, in Patients with Active Psoriatic Arthritis (EQUATOR): Results from a Randomised, Placebo-controlled, Phase 2 Trial

Lancet. 2018 Dec 1;392(10162):2367-2377. DOI 10.1016/ S0140-6736(18)32483-8

Mease P,

Coates LC,

Helliwell PS,

Stanislavchuk M,

Rychlewska-Hanczewska A,

Dudek A,

Abi-Saab W,

Tasset C,

Meuleners L,

Harrison P,

Besuyen R,

Van der Aa A,

Mozafarian N,

Greer JM,

Kunder R,

Van den Bosch F,

Gladman DD

In this first clinical trial of filgotinib in patients with PsA, filgotinib was effective in treating the signs and symptoms of active PsA across various disease manifestations.The EQUATOR trial was a randomized, double-blind, placebo-controlled, Phase 2 trial, that enrolled 191 adult patients from 25 sites in seven countries. Patients with active moderate-to-severe PsA and an insufficient response or intolerance to at least one csDMARD were assigned 1:1 to receive filgotinib 200 mg or placebo o...

Keywords:

• JAK,
• Filgotinib,
• Phase 2

Efecto de Filgotinib, un inhibidor selectivo de JAK1, con o sin Metotrexate en pacientes con Artritis Reumatoide: Resultados Informados por los Pacientes

Arthritis Res Ther 2018; 20(1):57 doi: 10.1186/s13075-018-1541-z

Genovese MC,

Westhovens R,

Meuleners L,

van der Aa A,

Harrison P,

Tasset C,

Kavanaugh A

Patient-reported outcomes (PROs) from two, Phase 2b, filgotinib (FIL) studies, DARWIN 1 and 2, revealed that patients receiving FIL had improved and sustained PRO responses compared with placebo. With suboptimal RA treatment, patients lose joint functional ability, which heavily influences patient quality of life. The previously reported data from the DARWIN studies, concluded that patients given FIL achieved clinically relevant dose-dependent improvements compared with patients given placebo¹,²...

Keywords:

• JAK,
• Filgotinib,
• PRO / QoL

Professor Iain McInnes Reviews the Most Important Papers from 2017

Please click the links below to go to the CSF review of each paper.

McInnes I

2017 was a successful year for rheumatoid arthritis research, with some key advances in JAK inhibitors and IL-6 inhibitors, as outlined below. - Tofacitinib was suggested as a potential treatment for psoriatic arthritis, and NICE recommended tofacitinib as a treatment for moderate to severe rheumatoid arthritis - Baricitinib studies supported the potential use of baricitinib as a treatment for rheumatoid arthritis - Filgotinib Phase 2 studies suggested that filgotinib could be effective a...

Keywords:

• Review

Inhibición de JAK como una estrategia terapéutica para Enfermedades Inmunes e Inflamatorias

Nat Rev Drug Discov 2017;16:843–62 DOI: 10.1038/nrd.2017.201

Schwartz DM,

Kanno Y,

Villarino A,

Ward M,

Gadina M,

O’Shea JJ

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. T...

Keywords:

• JAK,
• Review

Eficacia, Seguridad, Farmacocinética y Farmacodinamia de Filgotinib, un inhibidor selectivo de la quinasa Janus 1, después de tratamiento a curto-plazo de Artritis Reumatoide: Resultados de dos Ensayos Aleatorizados, fase IIA

Arthritis Rheumatol. 2017 Oct;69(10):1949-1959. doi: 10.1002/art.40186

Vanhoutte F,

Mazur M,

Voloshyn O,

Stanislavchuk M,

Van der Aa A,

Namour F,

Galien R,

Meuleners L,

van ‘t Klooster G

In two 4-week exploratory Phase 2a trials in MTX-inadequate responder (IR) patients with RA, the highly selective JAK1 inhibitor filgotinib met the primary endpoint of ACR20 at Week 4, showing greater response than placebo.Study 1, a proof-of-concept study, included 127 patients randomised to placebo, filgotinib 100 mg BID or filgotinib 200 mg QD. Study 2, was a dose-ranging study and included 91 patients randomised to placebo, filgotinib 30 mg QD, filgotinib 75 mg QD, filgotinib 150 mg QD or fi...

Keywords:

• JAK,
• Filgotinib,
• Phase 2,
• PK/PD

Filgotinib (GLPG0634/GS-6034), in inhibidor selectivo oral de JAK1, es efectivo como monoterapia en pacientes con artritis reumatoide activa: resultados de un estudio aleatorizado para definición de dosis (DARWIN 2)

Ann Rheum Dis 2017;76:1009–19

A. Kavanaugh,

J. Kremer,

L. Ponce,

R. Cseuz,

O. V. Reshetko,

M. Stanislavchuk,

M. Greenwald,

A. Van der Aa,

F. Vanhoutte,

C. Tasset and P. Harrison

In these two Phase 2b studies, filgotinib (a selective JAK-1 inhibitor) was shown to improve the signs and symptoms of RA (compared with placebo), either as monotherapy or when added to MTX.DARWIN 1 included 594 patients with moderate to severe RA on a stable dose of MTX, while DARWIN 2 included 283 patients who stopped taking MTX before the start of the study. After 12 weeks’ treatment, significantly more patients who were receiving filgotinib 100 mg or 200 mg daily in DARWIN 1 or any filgotini...

Keywords:

• JAK,
• Filgotinib,
• Phase 2

Filgotinib (GLPG0634/GS-6034), un inhibidor selectivo oral de JAK1, es efectivo en combinación con metotrexate (MTX) en pacientes con artritis reumatoide activa y respuesta insuficiente: resultados de un estudio aleatorizado para definición de dosis (DARWIN 1)

Ann Rheum Dis 2017;76:998–100

R. Westhovens,

P. C. Taylor,

R. Alten,

D. Pavlova,

F. Enríquez-Sosa,

M. Mazur,

M. Greenwald,

A. Van der Aa,

F. Vanhoutte,

C. Tasset and P. Harrison

In these two Phase 2b studies, filgotinib (a selective JAK-1 inhibitor) was shown to improve the signs and symptoms of RA (compared with placebo), either as monotherapy or when added to MTX.DARWIN 1 included 594 patients with moderate to severe RA on a stable dose of MTX, while DARWIN 2 included 283 patients who stopped taking MTX before the start of the study. After 12 weeks’ treatment, significantly more patients who were receiving filgotinib 100 mg or 200 mg daily in DARWIN 1 or any filgotini...

Keywords:

• JAK,
• Filgotinib,
• Phase 2

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]

Namour F,

Diderichsen PM,

Cox E,

Vayssière B,

Van der Aa A,

Tasset C,

Van't Klooster G.

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.

Keywords:

• JAK,
• Filgotinib,
• PK/PD,
• Phase 1

Caracterización preclínica de GLPG0634, un inhibidor selectivo de la JAK1, para el tratamiento de las enfermedades inflamatorias

Journal of Immunology 2013;191:3568–77

Van Rompaey L,

Galien R,

van der Aar EM,

et al

JAK inhibitors have been identified as having a critical role as therapeutic targets for autoimmune, inflammatory and oncological diseases. GLPG0634 was shown to inhibit JAK1/JAK2 but with a much greater effect on JAK1, a critical pathway in the signal transduction of many inflammatory cytokines. In rodent testing, GLPG0634 showed significant dose-dependent reduction in disease progression in collagen-induced arthritis models, with comparable efficacy to etanercept. An orally bioavailable treatm...

Keywords:

• JAK,
• Filgotinib,
• Preclinical