Publications

Structural Damage Progression in Patients with Early Rheumatoid Arthritis Treated with Methotrexate, Baricitinib, or Baricitinib plus Methotrexate Based on Clinical Response in the Phase 3 RA-BEGIN Study

Clinical Rheumatology 2018;37:2381–90 DOI 10.1007/s10067-018-4221-0

van der Heijde D,

Durez P,

Schett G,

Naredo E,

Østergaard M,

Meszros G,

De Leonardis F,

De La Torre I,

López-Romero P,

Schlichting D,

Nantz E,

Fleichmann R

Patients with active RA and little or no prior DMARD treatment, who achieved sustained clinical responses, were less likely to show structural damage progression, irrespective of treatment.RA-BEGIN was a 52-week double-blind, multicentre Phase 3 trial, which assessed the safety and efficacy of BARI as monotherapy or in combination with MTX versus MTX monotherapy, in RA patients with no or limited prior DMARDs use.1-4 This post-hoc analysis evaluated the structural damage progression in patients ...

Keywords:

• JAK,
• Baricitinib,
• Phase 3,
• Radiographic

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

Pathogenetic Insights from the Treatment of Rheumatoid Arthritis

Lancet 2017;389:2328–37 DOI 10.1016/S0140-6736(17)31472-1

McInnes I,

Schett G

This review paper examines the understanding gained from looking at the effects of specific immune interventions in the treatment of RA.The introduction of novel IL-6 agents has provided the ideal opportunity to explore the distinct effect of cytokine inhibition, as opposed to receptor inhibition, at the molecular level. Mechanistic insights into TNF could also be obtained in the future with advanced molecular and informatics approaches, and future biopsy studies will be important to explore the...

Keywords:

• Basic Science,
• Review

TNF-α and IL-6 differentially regulate Dkk-1 in the inflamed arthritic joint

Arthritis Rheumatol. 2015 May 4. doi: 10.1002/art.39183. [Epub ahead of print]

Yeremenko N,

Zwerina K,

Rigter G,

Pots D,

Fonseca J,

Zwerina J,

Schett G,

Baeten D.

Different inflammatory joint diseases have distinct patterns of bone damage, but the molecular pathways determining each one remains poorly defined. This study investigates the wingless (Wnt)-signalling pathway, by analysing the expression of Dkk-1 (an inhibitor of the Wnt pathway) and its regulation by the pro-inflammatory cytokines TNF-α and IL-6 in SpA versus RA inflamed peripheral joints.Findings from the study show an inverse correlation of Dkk-1 with IL-6 in vivo and a differential regulat...

Keywords:

• IL-6,
• Basic Science,
• MOA,
• Review

Combined inhibition of TNFα and IL-17 as therapeutic opportunity for treatment in rheumatoid arthritis: Development and characterization of a novel bispecific antibody

Arthritis Rheumatol. 2015;67(1):51–62

Fischer JA,

Hueber AJ,

Wilson S,

Galm M,

Baum W,

Kitson C,

Auer J,

Lorenz S,

Moelleken J,

Bader M,

Tissot AC,

Tan SL,

Seeber S,

Schett G

Single cytokine inhibition, e.g. TNFα or IL-6, has fundamentally improved the therapeutic armamentarium for the treatment of RA; yet clinically meaningful responses are achieved in only about half of RA patients treated. In addition, it is now well established that the pathogenesis of RA involves multiple mechanisms of cell activation and cell recruitment. These two factors have led to the emergence of the concept of dual specificity, sparking interest in the biologic arena, with a focus o...

Keywords:

• IL-17,
• TNF

Cytokines in the pathogenesis of rheumatoid arthritis

Nature Reviews Immunology 2007; 7:429-42

McInnes IB,

Schett G

The imbalance between the activity of pro- and anti-inflammatory cytokines favouring induction of autoimmunity, chronic inflammation and joint damage is well known, but how cytokines are organised within a hierarchical regulatory network and which cytokines are the best targets for clinical intervention is uncertain. This review therefore examines the effector function of cytokines in the immunological processes central to the pathogenesis of rheumatoid arthritis (RA). The paper aims to try and ...

Keywords:

• JAK,
• Basic Science,
• MOA,
• Review

The pathogenesis of rheumatoid arthritis

The New England Journal of Medicine 2011; 365:2205-19

McInnes IB,

Schett G

This review article describes the pathogenic processes involved in rheumatoid arthritis (RA) and discusses the genetic factors and environmental triggers implicated in the disease. Data from twin studies are discussed along with candidate genes with single nucleotide polymorphisms (SNPs) that have been linked to RA. It is now thought a multistep progression to the development of RA occurs via environmental factors, epigenetic modification of susceptible genes that leads to altered post-transcrip...

Keywords:

• Basic Science,
• MOA,
• Review