March 2016

Comparison of adding tocilizumab to methotrexate with switching to tocilizumab in patients with rheumatoid arthritis with inadequate response to methotrexate: 52-week results from a prospective, randomised, controlled study (SURPRISE study)

Ann Rheum Dis 2016 Jan 5 DOI: 10.1136/annrheumdis-2015-208426 [Epub ahead of print

MTX is the primary drug in RA management because of its long-term effectiveness and safety profile; however, in patients who have insufficient response (IR) to MTX, treatment adjustments are needed – either to combine a bDMARD with MTX or to switch to a bDMARD from MTX. In the SURPRISE study, the efficacy and safety of adding TCZ to MTX (ADD-ON) or switching MTX to TCZ (SWITCH) was evaluated in 233 patients with moderate to highly active RA who were randomised 1:1. Both treatment groups were adm...

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Impact of obesity on the clinical outcome of rheumatologic patients in biotherapy

Autoimmunity Reviews Doi: 10.1016/j.autrev.2016.01.010

Obesity is increasingly becoming a public health concern as its prevalence continues to grow in the United States and Western nations. Obesity has been shown to be an inflammatory condition that impacts multiple tissues and systems, including the immune system possibly linking to rheumatic diseases. In this review, Iannone et al overview the epidemiology and clinical outcomes of PsA and/or RA patients with comorbid obesity.Large cohort and prospective studies in Italy, the US, and the UK have s...

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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

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...

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April 2015

Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: Results of a phase III study

Arthritis Rheumatol. Vol. 67, No. 6, June 2015, pp 1424–1437

Biologic DMARDs targeting TNF-alpha, IL-1, T-cell co-stimulatory blockade, B-cell depletion, and IL-6R, as well as the newer JAK inhibitors have greatly improved clinical outcomes in RA. However, not all patients respond to current biologic or small molecule DMARDs.

Sarilumab is a fully human anti-IL-6Rα mAb that binds membrane-bound and soluble human IL-6R with high affinity, blocking cis and trans IL-6-mediated signalling. This study (MOBILITY) is the first randomised, double-blin...

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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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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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December 2014

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

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.

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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

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...

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September 2014

The active metabolite of spleen tyrosine kinase inhibitor fostamatinib abrogates the CD4+T cell-priming capacity of dendritic cells

Rheumatology (Oxford). 2015;54(1):169–177

SYK is a core signalling protein that drives inflammatory responses and is fundamental to the propagation of signals via numerous immune receptors. While the clinical development of the first SYK inhibitor, fostamatinib, was stopped due to poor results in the phase 3 RA programme, there remain important questions of mechanism which may aid future developments of this target.

In these murine studies, investigators sought to gain an understanding of how the active metabolite of fostamatini...

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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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