Publications

Efectos de Un Año de Terapia con Tofacitinib en el Metabolismo Óseo en Artritis Reumatoide

Osteoporos Int 2021 Feb 9 DOI 10.1007/s00198-021-05871-0

Hamar A,

Szekanecz Z,

Pusztai A,

Czókolyová M,

Végh E,

Pethő Z,

Bodnár N,

Gulyás K,

Horváth Á,

Soós B,

Bodoki L,

Bhattoa H. P,

Nagy G,

Tajti G,

Panyi G,

Szekanecz É,

Domján A,

Hodosi K,

Szántó S,

Szűcs G,

Szamosi S

Thought to be the first study of its kind, Hamar, et al. have demonstrated the effect of one-year tofacitinib treatment on bone mineral density (BMD) in RA patients. While the association between RA and osteoporosis is well known, and evidence indicates that up to 70% of these patients have reduced BMD, little information is available on how the JAK inhibitor tofacitinib affects bone status, areal and volumetric BMD, and bone turnover markers. In this prospective study, 30 patients were assessed...

Keywords:

• JAK,
• Tofacitinib,
• Bone

Señalización JAK/STAT Inducida por Citoquinas está Asociada con Artritis Reumatoide y Actividad de la Enfermedad

PLoS ONE 2021;16(1):e0244187

Ptacek J,

Hawtin RE,

Sun D,

Louie B,

Evensen E,

Mittleman BB,

Cesano A,

Cavet G,

Bingham CO III,

Cofield SS,

Curtis JR,

Danila MI,

Raman C,

Furie RA,

Genovese MC,

et al

This analysis provides evidence that immune cell signalling pathways are important in RA. There were consistent differences between RA patients and healthy controls in IFNα, IL-6, IL-10 and GM-CSF+ IL-2 induced JAK/STAT signalling in multiple immune cell subsets.We know that RA is characterised by dysregulation of immune responses, but the exact cause is unknown. Recently, single-cell transcriptomics and mass cytometry confirmed the critical role of activated immune cells and fibroblasts, increa...

Keywords:

• JAK,
• Basic Science

Baricinitb Inhibe la Progresión del Daño Estructural en Pacientes con Artritis Reumatoide – Una Revisión Global

Arthritis Res Ther 2021;23(1):3.

Emery P,

Durez P,

Hueber AJ,

Ide la Torre I,

Larsson E,

Holzkämper T,

Tanaka Y

MRI studies have shown that BARI reduces joint inflammation and damage in patients with moderate-to-severe active RA. This review summarises the effects of BARI on structural joint damage progression and the mechanisms underlying these effects, using MRI data from across the clinical trial program. Early preclinical animal models showed a significant reduction in joint inflammation, ankle width, and bone resorption. Efficacy and safety of BARI have been confirmed in an extensive programme, inclu...

Keywords:

• JAK,
• Baricitinib,
• Radiographic,
• Review

Highlights of 2020

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

McInnes. I

2020 unfolded apace, dominated by COVID-19 - we have all had to adapt in our practice and in our knowledge base. Amid this there have continued to be a constant flow of publications and science in cytokine signaling, and as in previous years as we come the end of 2020, I will highlight some of the notable papers of the year. You can find the most notable papers, as selected by CSF Steering Committee Chair Professor Iain McInnes, with links to their respective detailed summaries below:

Keywords:

• Review

Eficacia de Baricitinib en el Tratamiento de la Artritis Reumatoide: Efecto Modulatorio en Biomarcadores Inflamatorios y de Fibrose en un Escenario de Vida Real

Int Immunopharmacol. 2020 Sep;86:106748.

Alessandro M,

Perillo F,

Refini R,

Bergantini L,

Bellisai F,

Selvi E,

Cameli P,

Manganelli S,

Conticini E,

Cantarini L,

Sestini P,

Frediani B,

Bargagli E

BARI demonstrated to be a safe immune modulator that reduces the concentrations biomarkers of lung fibrosis and inflammation in RA patients, including a subgroup with interstitial lung involvement. Professor Alessandro and colleagues analysed the effects of baricitinib in a population of RA and RA-ILD patients in a real-life setting, describing any changes in lung function parameters, serum inflammatory biomarkers and fibrotic biomarkers after 6 months of treatment. Fifteen patients were recruit...

Keywords:

• JAK,
• Baricitinib,
• Basic Science,
• Biomarkers

Evaluación de la Asociación de los Anticuerpos anti-CarbV y anti- MCV en el baseline con la respuesta al tratamiento y con la progresión radiográfica en una población con AR tratada con Metotrexato o Baricitinib: un análisis post-hoc de RA-BEGIN

Arthritis Res Ther. 2020;22(1):193

López-Romero P,

Martinez-Gamboa L,

Bang H,

de la Torre I,

Holzkämper T,

Feist E

Autoantibodies associated with the onset of RA have gained attention in recent years as prognostic biomarkers. Though not used diagnostically, anti-CarbV (carbamylated vimentin) and anti-MCV (vimentin modified by citrullination) baseline titers are being investigated as predictors of treatment response. In this post-hoc analysis of data from the RA-BEGIN cohort of active RA patients, López-Romero and colleagues consider the potential predictive values of baseline anti-CarbV and anti-MCV titers r...

Keywords:

• JAK,
• Baricitinib,
• Efficacy,
• Bone,
• Radiographic

Fenebrutinib versus Placebo o Adalimumab en Artritis Reumatoide: Un estudio doble ciego aleatorizado de fase II (Estudio ANDES)

Arthritis Rheumatol. 2020 Sep; 72(9): 1435–1446.

Cohen S,

Tuckwell K,

Katsumoto TR,

Zhao R,

Galanter J,

Lee C,

Rae J,

Toth B,

Ramamoorthi N,

Hackney JA,

Berman A,

Damjanov N,

Fedkov D,

Jeka S,

Chinn LW,

Townsend MJ,

Morimoto AM,

Genovese MC

In this randomised phase II trial with MTX treatment-refractory RA patients, greater efficacy was observed with fenebrutinib 150 mg once daily or 200 mg twice daily compared to placebo, while response rates were numerically similar to those observed with adalimumab. BTK inhibitors have demonstrated clinical efficacy in B cell malignancies and multiple sclerosis, although there is limited clinical evidence of its efficacy in RA. Fenebrutinib (FEN) an orally active and selective non-covalent inhib...

Keywords:

• BTK,
• Fenebrutinib,
• Phase 2

Filgotinib, un Inhibidor JAK1, Modula Biomarcadores Relacionados con la Enfermedad en la Artritis Reumatoide: Resultados de 2 Estudios Aleatorizados, Controlados de Fase 2

Rheumatol Ther. 2020 DOI: 10.1007/s40744-019-00192-5

Tarrant JM,

Galien R,

Wanying L,

Goyal L,

Pan Y,

Hawtin R,

Zhang W,

Van der Aa A and Taylor PC

In this study examining the effect of FIL on a panel of biomarkers, FIL down-modulated several key inflammatory mediators of signalling pathways in RA - independent of MTX background therapy. This confirmed the strong network effects of the JAK1 node in autoimmunity, matrix and cartilage degradation, angiogenesis, and leukocyte adhesion and recruitment. Biomarkers key to RA pathophysiology were measured at baseline, Wk4 and Wk12 in FIL 100 mg, FIL 200 mg or PBO treatment groups from two phase 2b...

Keywords:

• JAK,
• Filgotinib,
• Phase 2,
• MOA,
• Biomarkers

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

Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study

Arthritis Research & Therapy (2016) 18:13 DOI: 10.1186/s13075-015-0913-x

Bay-Jensen A,

Platt A,

Siebuhr A,

Christiansen C,

Byrjalsen I,

Karsdal M

One of the major challenges of RA treatment is choosing the correct treatment and dose for the individual patient, as treatment response can be heterogeneous. To help select the appropriate treatment, there is a need for effective and non-invasive ways to monitor disease activity and progression. In the LITHE study, Bay-Jensen et al. investigate whether early biomarker measurements could predict early joint protection response to TCZ. The biomarkers (CRPM, VICM, C1M, C2M, C3M, and CTX-I/OC [bone...

Keywords:

• IL-6,
• Tocilizumab,
• Biomarkers