October 2015

Tofacitinib regulates synovial inflammation in psoriatic arthritis, inhibiting STAT activation and induction of negative feedback inhibition

Annals of the Rheumatic Diseases. 2015 Sep 9. doi:10.1136/annrheumdis-2014-207201

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis (Ps) and characterised by synovitis and progressive destruction of articular cartilage and bone. Recently developed agents for PsA target IL12p40, IL-6 and IL-17, several of which signal through the JAK family of receptor-associated tyrosine kinases. Tofacitinib is a drug of the JAK inhibitor class and is currently approved for the treatment of RA in 27 countries. This study evaluated the effect of tofacitini...

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June 2015

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]

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...

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May 2015

Differential Effects of IL-17A and TNF-α on Osteoblastic Differentiation of Isolated Synoviocytes and on Bone Explants from Arthritis Patients

Frontiers in Immunology. 2015;6:151. doi:10.3389/fimmu.2015.00151

Inflammatory joint diseases such as RA and OA are characterised by bone and consequent joint destruction. The role of fibroblast-like synoviocytes (FLS) in the pathogenesis of such diseases is already established. This study compared the effects of TNF-α and IL-17A on osteogenic differentiation of isolated FLS and on whole bone explants from 3 RA and 10 OA patients.Results showed that isolated RA-FLS appeared more sensitive to the effects of TNF-α and IL-17A compared to OA-FLS. These findings su...

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January 2015

Potential Mechanisms Leading to the Abnormal Lipid Profile in Patients With Rheumatoid Arthritis Versus Healthy Volunteers and Reversal by Tofacitinib

Arthritis Rheumatol. 2015;67(3):616-25.

Active RA is associated with changes in both high- and low-density lipoprotein cholesterol as well as changes in the level and function of several HDL-associated proteins, yet the pathways and mechanisms involved with systemic inflammation altered lipid metabolism have not been determined. In addition, treatments for active RA are known to modify lipid metabolism, such as increasing circulating cholesterol levels. In the clinical development programme, a proportion of tofacitinib-treated patien...

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