December 2014

Metotreksata yetersiz yanıt veren romatoid artritli hastalarda baricitinibin 24 haftadaki güvenlik ve etkinliği

Ann Rheum Dis. 2015;74(2):333–340

Recent innovations in the treatment of RA have focused on the use of small molecules to inhibit intracellular kinases such as the JAK family. Baricitinib (LY3009104, formerly INCB028050) is an orally administered, potent, selective and reversible inhibitor of JAK1 and JAK2, which has shown anti-inflammatory effects, as well as preservation of cartilage and bone, in preclinical rodent studies.

This phase IIb study was designed to investigate multiple doses and dosing regimens of baricitin...

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October 2014

Aktif romatoid artritli hastaların üçüncü-sıra tedavisinde metotreksat ile birlikte tofacitinib: Bir Faz 3 çalışmadan hastaların-bildirdiği sonuçlar

Arthritis Care Res (Hoboken). 2014 Sep 3. doi: 10.1002/acr.22453. [Epub ahead of print]

For many patients with rheumatoid arthritis, improvements in pain, physical function, fatigue, and health-related quality of life (HRQoL) are more important and meaningful than improvements in joint swelling, tenderness, or inhibition of structural damage. These patient-perceived benefits of RA therapy contribute importantly to overall clinical efficacy.

This paper presents patient-reported outcomes (PROs) form the ORAL Step trail, which assessed tofacitinib 5 mg or 10 mg twice daily, or ...

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July 2014

Romatoid Artritte Metotreksata Karşı Tofacitinib

N Engl J Med. 2014;370(25):2377–2386.

ORAL Start is the latest trial to be reported in the tofacitinib clinical development programme. It compares the use of tofacitinib monotherapy to MTX monotherapy, in RA patients who have had either no or a sub-therapeutic dose of MTX in the past. Nine hundred and fifty eight patients received either tofacitinib (5 mg or 10 mg) twice daily, or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks. The co primary efficacy endpoints were ACR 70 response, and mean c...

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April 2014

Romatoid Artrit Tedavisinde Kullanılan Janus Kinaz inhibitörü Tofasitinibin Serum Amiloid A ve IL-6 üzerine etkisi

Clinical and Experimental Immunology doi.10.1111/cei.12234

Tofacitinib is a JAK inhibitor currently approved for the treatment of RA in some parts of the world. In this paper, Migita et al tested the effects of tofacitinib on circulating serum amyloid A (SAA). SAA is a major acute-phase reactant in RA and studies have shown it may be a better marker for the assessment of inflammatory joint disease compared with C-reactive protein. SAA is induced by the binding of IL-6 and the activation of the JAK/STAT pathway, which is inhibited by tofacitinib. Results...

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February 2014

Konvansiyonel DMARD, Glukokortikoidler ve Tofasitiniblerin etkinliği: RA tedavisinde EULAR 2013 önerileri hakkında bilgilendiren sistematik literatür derlemesi

Ann Rheum Dis doi:10.1136/annrheumdis-2013-204588

Systematic literature reviews were undertaken to assess the efficacy of csDMARDs, glucocorticoids and tofacitinib in the treatment of RA. The first two were updates to reviews conducted for the 2010 recommendations while the tofacitinib SLR was a complete review.Two studies identified by the csDMARD SLR, tREACH and TEAR, compared efficacy between MTX mono- and combination therapy (MTX+SSZ+HQ). Both of these studies found there was no benefit to immediate triple therapy.Further studies analysing ...

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September 2013

Inhibition of spleen tyrosine kinase in the treatment of rheumatoid arthritis

Rheumatology 2013;52:1556–1562 doi:10.1093/rheumatology/ket225

Both the innate and adaptive immune responses are targeted by current RA treatments, but these treatments do not achieve consistent sustained disease remission. Protein kinase inhibitors represent a promising new therapeutic target, owing to their influence on downstream signalling and oral bioavailability. Fostamatinib (R788) has shown ACR20 responses of 67–72% in MTX inadequate responder patients at doses of 100mg bd and 150mg bd. However, the results in biologic non-responder patients were no...

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August 2013

Oral administration of GLPG0259, an inhibitor of MAPKAPK5, a new target for the treatment of rheumatoid arthritis: a phase II, randomised, double-blind, placebo-controlled, multicentre trial

Ann Rheum Dis. 2013 May; 72(5):741–4

This phase2 trial assessed the efficacy of GLPG0259, a first-in-class ATP-competitive inhibitor of MAPKAPK5. The trail involved 31 patients with active RA and an inadequate response MTX. Patients received either 50 mg/day GLPG0259 with MTX or a placebo with MTX (patients randomised 2:1) for 12 weeks with the primary efficacy variable being ACR 20 response at week 12. Analysis showed that 5 patients (26.3%) in the GLPG0259 group and 3 patients (27.3%) in the placebo group achieved ACR 20 at 12 we...

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The JAK inhibitor tofacitinib for active rheumatoid arthritis: results from phase III trials

International Journal of Clinical Rheumatology June 2013; 8(3):311–13

The tofacitinib ORAL research program involves six phase 3 trials (Standard, Solo, Step, Scan, Sync and Start) to assess the safety and efficacy of tofacitinib 5 and 10 mg twice daily as monotherapy, or with either background MTX or traditional DMARD therapy. This report by Salgado et al. provides an overall analysis of the each of the study designs and the clinical results to date. The results show that tofacitinib effectively controlled the signs and symptoms of RA across a range of patient po...

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June 2013

Small molecules targeting JAKs—a new approach in the treatment of rheumatoid arthritis

Rheumatology 2013: doi: 10.1093/rheumatology/kes417

This article focuses on the development of new small molecular inhibitors of Janus kinases (Jaks) in clinical trials for rheumatoid arthritis (RA). Of these, tofacitinib is at the most advanced stage of its clinical development and this article includes an overview of the results from the main tofacitinib clinical trials to date. These include the ORAL-Start study in methotrexate (MTX)-naïve patients; ORAL-Scan in inadequate responders to MTX; ORAL-Solo and ORAL-Sync in inadequate responders to ...

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A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone

Arthritis & Rheumatism 2012; 64(4):970-81

This study was one of two 24-week, phase 2b studies undertaken to characterise the efficacy and safety dose-response profile of the oral Janus kinase (JAK) inhibitor tofacitinib. Six doses of tofacitinib (20 mg daily and 1, 3, 5, 10 and 15 mg twice daily) and placebo were compared as add-on therapy in adults with active RA despite methotrexate (MTX) therapy. At week 12, ACR 20 response rates were significantly higher with all tofacitinib doses than with placebo (tofacitinib 45.7–58.1%; 33% place...

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