Cytokine Signalling Forum

Publications





April 21

Filgotinib, a Novel JAK1-Preferential Inhibitor for the Treatment of Rheumatoid Arthritis: An Overview from Clinical Trials

Tanaka Y, Kavanaugh A, Wicklund J, McInnes IB.
Mod Rheumatol. 2021 Mar 19:1-26. Epub ahead of print. DOI 10.1080/14397595.2021.1902617

Filgotinib is the latest JAKinib to enter the international market for the treatment of RA, receiving regulatory approval in Japan and Europe late last year. In this review paper, Tanaka Y et al. examine the clinical evidence supporting its use as a later-line treatment, in accordance with international RA management guidelines, and provide their expert opinions on JAKinibs from a clinical perspective. The core clinical programme evaluating filgotinib in patients with moderately-to-severely acti...

March 21

Seguridad y Eficacia de Filgotinib: Resultados de Hasta 4 Años de un Estudio de Extensión Abierto de los Programas de Fase 2 en Artritis Reumatoide

Kavanaugh A, Westhovens RR, Winthrop KL, Lee SJ, Tan Y, An D, Ye L, Sundy JS, Besuyen R, Meuleners L, Stanislavchuk M, Spindler AJ, Greenwald M, Alten R, Genovese MC.
J Rheumatol. 2021 Feb 1:jrheum.201183. DOI: 10.3899/jrheum.201183.

A long-term extension study of filgotinib showed consistent safety profile and sustained efficacy with the drug for up to four years. The DARWIN 3 study, for patients who previously completed either the 24-week DARWIN 1 study (filgotinib + MTX) or the DARWIN 2 study (filgotinib monotherapy), enrolled 739 patients with RA. At the time of analysis, 440 patients had received four years or more of filgotinib. Exposure-adjusted incidence rate per 100 patient-years-of-exposure for TEAEs was 24.6 i...

Keywords: JAK, Filgotinib, Clinical, Phase 2

Estudio de Seguridad Comparativa Pos-Aprobación de Tofacitinib y Fármacos Biológicos Antirreumáticos Modificadores de la Enfermedad: Resultados de 5 años de un Registro de Artritis Reumatoide basado en los Estados Unidos

Kremer JM, Bingham CO 3rd, Cappelli LC, Greenberg JD, Madsen AM, Geier J, Rivas JL, Onofrei AM, Barr CJ, Pappas DA, Litman HJ, Dandreo KJ, Shapiro AB, Connell CA, Kavanaugh A.
ACR Open Rheumatol. 2021 Feb 11.

Analysis from the US Corrona RA registry has provided the longest-term real-world safety data for a JAK inhibitor to date. The analysis showed that the cohorts had similar adverse events, except for higher herpes zoster rates for tofacitinib initiators vs bDMARDs. Kremer JM, et al. analysed adult patients with RA newly initiating tofacitinib, or a bDMARD, to compare incidence rates of MACE, SIEs, HZ, malignancies and death. VTE data were also collected prospectively and assessed descriptively t...

Keywords: JAK, Tofacitinib, Clinical

June 18

Resultados Radiográficos de Largo Plazo y Resultados Informados por los Pacientes en pacientes con Artritis Reumatoide Tratados con Tofacitinib: Análisis Post-hoc de ORAL Start y ORAL Scan

Strand V, Kavanaugh A, Kivitz AJ, van der Heijde D, Kwok K, Akylbekova E, Soonasra A, Snyder M, Connell C, Bananis E, Smolen JS.
Rheumatol Ther. 2018 Dec;5(2):341-353. doi: 10.1007/s40744-018-0113-7

Tofacitinib (TOF) therapy reduced the progression of structural joint damage at 2 years, in patients of all disease states, compared with patients given methotrexate (MTX). Early intervention with DMARDs aim to prevent the development of future RA symptoms and inhibit the progression of structural damage to the joints. This post-hoc analysis uses data from two Phase 3 TOF studies, to examine the efficacy of early intervention with TOF on long-term radiographic outcomes and disease activity sta...

Keywords: JAK, Tofacitinib, Clinical, Radiographic

Translated by: Igor Kos

April 18

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

Genovese MC, Westhovens R, Meuleners L, van der Aa A, Harrison P, Tasset C, Kavanaugh A.
Arthritis Res Ther 2018; 20(1):57 doi: 10.1186/s13075-018-1541-z

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 placebo&s...

Keywords: JAK, Filgotinib, Clinical, PRO

October 17

Impacto de Tocilizumab Monoterapia en los Resultados Informados por los Pacientes (PROs) con Artritis Reumatoide de dos Ensayos Controlados Aleatorizados

Strand V, Michalska M, Birchwood C, Pei J, Tuckwell K, Finch R, Gabay C, Kavanaugh A, Jones G.
RMD Open;3:e000496. doi: 10.1136/rmdopen-2017-000496

This post hoc analysis of 2 randomised controlled trials (RCTs) AMBITION and ADACTA found that tocilizumab monotherapy results in substantial and clinically meaningful improvements in patient-reported outcomes (PROs) over 24 weeks. PROs assessed included patient global assessment (PtGA), pain, HAQ-DI, Functional Assessment of Chronic Illness Therapy (FACIT-F) and Short-Form-36 (SF-36) physical component summary (PCS) and mental component summary (MCS) and eight domain scores. Tocilizumab (TCZ)...

Keywords: IL-6, Tocilizumab, Clinical, PRO

Translated by: Igor Kos

December 15

Comparison of lipid and lipid-associated cardiovascular risk marker changes after treatment with tocilizumab or adalimumab in patients with rheumatoid arthritis

Gabay C, McInnes IB, Kavanaugh A, Tuckwell K, Klearman M, Pulley J, Sattar N.
Ann Rheum Dis. 2015;0:1-7. doi:10.1136/annrheumdis-2015-207872 [Epub ahead of print]

RA patients have increased risk of CVD compared with the general population that is not fully explained by traditional risk factors. This is a post-hoc analysis of data from a clinical trial that compared IL-6 and TNF-α signaling inhibition to compare changes in lipids and lipid-associated CV risk markers in 324 patients treated with TCZ IV q4w or ADA SC q2w for 24 weeks. HDL-SAA and sPLA2 IIA is also measured in an additional subpopulation of 87 and 97 TCZ and ADA patients, respectively. ...

December 14

The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis

Boyle DL, Soma K, Hodge J, Kavanaugh A, Mandel D, Mease P, Shurmur R, Singhal AK, Wei N, Rosengren S, Kaplan I, Krishnaswami S, Luo Z, Bradley J, Firestein GS.
Ann Rheum Dis. 2014 Nov 14. pii: annrheumdis-2014-206028. doi: 10.1136/annrheumdis-2014-206028. [Epub ahead of print]

Targeting intracellular pathways such as JAK/STAT represents a novel approach to the treatment of RA. Tofacitinib is an oral JAK inhibitor, proven to be effective in the treatment of RA, yet the pathways affected by tofacitinib and the effects on gene expression in situ are unknown. In this study, Boyle et al. tested the hypothesis that tofacitinib targets cytokine signalling critical to the pathogenesis of rheumatoid synovitis by investigating tofacitinib effects on synovial pathobiology. A...

June 13

Un inhibidor oral de la tirosina quinasa esplénica (Syk) para la artritis reumatoide

Weinblatt ME, Kavanaugh A, Genovese MC, et al.
The New England Journal of Medicine 2010; 363(14):1303-12

This is the first phase 2 study to be published for spleen tyrosine kinase (Syk) inhibitor R788 (fostamatinib). This phase 2 study ingestigated the efficacy and safety of fostamatinib in patients with active RA despite long-term treatment with methotrexate. In this 6-month, double-blind, placebo-controlled trial, patients were randomised to receive two doses of R788 (100 mg twice daily or 150 mg once daily) or placebo once or twice daily. Significantly more patients on R788 achieved ACR 20 respo...

Keywords: Cytokine Signalling, Clinical, Phase 2

Un inhibidor oral de la quinasa Syk en el tratamiento de la artritis reumatoide: Un estudio de fase II aleatorizado, controlado con placebo de 3 meses en pacientes con artritis reumatoide activa que no respondieron a agentes biológicos

Genovese MC, Kavanaugh A, Weinblatt ME, et al.
Arthritis & Rheumatism 2011; 63(2):337-45

This was the first phase 2 study to be published investigating the efficacy and safety of the spleen kinase (Syk) inhibitor R788 (fostamatinib) in patients with refractory rheumatoid arthritis (RA). In this multicentre, randomised, double-blind, placebo-controlled, 3-month trial, patients with active RA on stable background treatment (excluding biologics) were randomised to receive 100 mg R788 or placebo twice daily. Differences in ACR20 responses were significant at week 6 (p=0.003), but not th...

Keywords: Cytokine Signalling, Clinical, Phase 2

Efectos de fostamatinib (R788), un inhibidor oral de la tirosina quinasa esplénica, en la calidad de vida relacionada con la salud en pacientes con artritis reumatoide: análisis de resultados reportados por los pacientes de un estudio aleatorizado, doble ciego, controlado con placebo

Weinblatt ME, Kavanaugh A, Genovese MC, et al.
The Journal of Rheumatology 2013; 40(3):369-78

This phase 2 clinical trial assessed the influence of fostamatinib on patient reported outcomes (PROs) in 457 patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). Patients received either placebo or fostamatinib 100 mg twice daily or 150 mg once daily (1:1:1) for 24 weeks in addition to their baseline MTX. Patients taking fostamatinib 100 mg twice daily had statistically significant improvements in health-related quality of life scores for pain, p...

Keywords: Cytokine Signalling, Clinical, Phase 2