March 2016

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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January 2016

Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials

Arthritis Res Ther. 2015 Dec 15;17(1):362

Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. By modulating the signalling of cytokines that are integral to lymphocyte activation, proliferation, and function, tofacitinib may suppress multiple elements of immune response. A systematic literature search including all biologics and tofacitinib procured 66 RCTs and 22 LTEs that were included in a meta-analysis to provide estimated incidence rates, risk ratios, and risk differences of serious infection for each therapy. Es...

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Cytokines in rheumatoid arthritis – shaping the immunological landscape

Nat Rev Rheumatol. 2016 Jan;12(1):63-8

Cytokine-mediated pathways are central to the pathogenesis of rheumatoid arthritis and there has been great advances in understanding and clinical application in the last 20 years. McInnes and colleagues provide a timely and succinct overview the roles of cytokine families in the various phases and tissue compartments of this disease. They particularly review the combinatorial role played by cytokines in mediating the overlapping innate and adaptive immune responses associated with disease onset...

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VX-509 (Decernotinib), an Oral Selective JAK-3 Inhibitor, in Combination With Methotrexate in Patients With Rheumatoid Arthritis

Arthritis Rheumatol. 2016 Jan;68(1):46-55.

VX-509 (decernotinib) is a novel oral, selective inhibitor of JAK-3. JAK-3 is a member of the JAK signalling family that is primarily expressed in hematopoietic cells and associates with only the common γ-chain making it a promising therapeutic drug target. A phase IIb 24-week study of VX-509 in 358 patients with RA, who had prior inadequate response to MTX, uses ACR20 response rate and DAS28-CRP change at Week 12 to assess the efficacy of VX-509. Patients were administered either placebo+MTX or...

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December 2015

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

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.Greater...

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Incidence and complications of interstitial lung disease in users of tocilizumab, rituximab, abatacept and anti-tumor necrosis factor α agents, a retrospective cohort study

Arthritis Research & Therapy (2015) 17:319 DOI: 10.1186/s13075-015-0835-7

Interstitial lung disease (ILD) is a common extra-articular condition for RA patients. This retrospective cohort study of health insurance databases investigates the ILD incidence and exacerbation between ABA, TCZ, RTX, and anti-TNFα agents in adult RA patients with prior biologic therapy. Two definitions of ILD were used: one specific, one sensitive; descriptive results were produced for both. In patients with no history of ILD, the overall incidence rate of ILD ranged from 1.8% to 6.4% (depend...

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Effects of tofacitinib monotherapy on patient-reported outcomes in a randomized phase 3 study of patients with active rheumatoid arthritis and inadequate responses to DMARDs

Arthritis Research & Therapy (2015) 17:307 DOI: 10.1186/s13075-015-0825-9 [Epub ahead of print]

RA presents a significant health and socioeconomic burden particularly in physical functioning, fatigue, and emotional roles. A phase III 6-month study of tofacitinib in patients with active RA, who had prior inadequate responses to cDMARDs or bDMARDs, uses patient-reported outcomes (PROs) to assess the impact on quality of life. Patients were randomized 4:4:1:1 to receive tofacitinib 5 or 10 mg BID, or placebo for 3 months followed by tofacitinib 5 or 10 mg BID. At month 3, tofacitinib 5 and 10...

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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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Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: results from a European collaborative study

Ann Rheum Dis. 2015 Sep 15. doi:10.1136/ annrheumdis-2015-207760

Biological DMARDs have markedly changed the management and outcome of rheumatoid arthritis. Most international guidelines recommend the use of biological DMARDs in combination with MTX or other synthetic DMARDs (sDMARDs) (where MTX is not tolerated or contraindicated), based primarily on the observation that MTX enhances the efficacy of TNF antagonists in both clinical trials and observational studies.This study examined the effectiveness of tocilizumab (TCZ), an anti-IL-6 monoclonal antibody, ...

Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy: Results from a randomized phase II trial

Modern Rheumatology. 2015 Sep 10:1-9. [Epub ahead of print]

This Phase II study assessed the safety and efficacy of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy. After 12 weeks of treatment, olokizumab was found to rapidly improve disease activity in patients who had previously failed anti-TNF therapy. There was also a significant decrease in ACR20 and ACR50 responder rates at week 12. The safety findings were consistent with the safety profile expected for this drug class. These findin...