Tofacitinib Scores Again for RA Resistant to TNF Inhibitors


New positive results for JAK inhibitor tofacitinib in RA, a commentary on TNF and JAK inhibitors, a review on polymalgia rheumatica, and a case report describes Jaccoud's arthropathy.

Last week's articles on rheumatology in the major nonspecialty journals:

Rheumatoid Arthritis

Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. The Lancet, Jan 5, 2013  (Full text $31.50)

In a phase 3 trial, twice as many treatment-refractory RA patients reached ACR20 with tofacitinib plus methotrexate as did patients with methotrexate alone. This follows similar results in two phase 3 trials reported in the New England Journal of Medicine last year. Safety was consistent with earlier studies. In this latest study, all patients were resistant to tumor necrosis factor inhibitors (TNFi). Tofacitinib is a Janus kinase (JAK) inhibitor.

Kinase inhibition in rheumatoid arthritis: a big advance? The Lancet, Jan 5, 2013  (Full text $31.50)

This commentary in the same issue of The Lancet reviews TNF and JAK inhibitors, including monoclonal antibodies, fusion proteins of soluble receptors, and small-molecule inhibitors. These inhibitors target B and T cells, but also receptors of inflammatory cytokines such as IL-6, IFN-1, IL-12, and IL-23, which act on two other classes of cells, monocyte-derived cells (macrophages, dendritic cells, and osteoclasts) and mesenchymal-derived cells (osteoblasts, chondrocytes, and synoviocytes). The trials included in the review all had inflammation as their major endpoint. The next trials must have an endpoint of bone and cartilage destruction, and even joint repair, says the commentary.

Jaccoud's arthropathyJaccoud's arthropathyThe Lancet,  Jan 4, 2013 (Free full text

A case report, available in full text online for free, describes Jaccoud's arthropathy. This benign chronic arthropathy without functional impairment must be differentiated from the fixed and non-correctable deformities of rheumatoid arthritis or systemic lupus erythematosus.

Polymyalgia rheumatica
Seminar: Polymyalgia rheumaticaThe Lancet,  5 Jan 2013 | (Full text $31.50)

Even with new imaging techniques, diagnosis of polymyalgia rheumatica is still difficult, says this review. Although provisional classification criteria were published in April 2012 by EULAR and the American College of Rheumatology, genetic studies have been small and as yet there are no diagnostic biomarkers or targeted immunotherapies.

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