December 2015

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

Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs

Annals of the Rheumatic Diseases. 2015 Aug 14. doi:pii: annrheumdis-2014-207178.

This study evaluated the efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in patients with inadequate response to sDMARDs or bDMARDs. Findings from this study show both doses of tofacitinib were associated with improvements in efficacy parameters at month 3 versus placebo, and clinical response was numerically greater with bDMARD-naïve versus bDMARD-IR patients (95% CI overlapping). Safety parameters were generally similar; however, patients receiving glucocorticoids had more ...

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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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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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July 2014

Tofacitinib Versus Methotrexate In Rheumatoid Arthritis

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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June 2013

Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis

The New England Journal of Medicine 2012; 367(6):495-507

This is the first phase 3 study to be published for the oral Janus kinase (JAK) inhibitor tofacitinib. This study investigated tofacitinib as a monotherapy in adults with active rheumatoid arthritis who previously failed to respond to disease modifying anti-rheumatic drugs (DMARDs). The study demonstrated that tofacitinib, compared to placebo, was more likely to be associated with reductions in the signs and symptoms of rheumatoid arthritis and improvement in physical function. 59.8% of patients...

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Tofacitinib or adalimumab versus placebo in rheumatoid arthritis

The New England Journal of Medicine 2012; 367(6):508-19

The ORAL Standard trial is one of six studies conducted as part of the phase 3 research programme for the oral Janus kinase (JAK) inhibitor tofacitinib. This 12-month, phase 3 study compared the efficacy of tofacitinib with the TNF inhibitor adalimumab or placebo. Patients with active RA despite background methotrexate (MTX) were randomised to 5 or 10 mg tofacitinib twice daily, 40 mg adalimumab fortnightly, or placebo, which was switched to tofacitinib at month 3 in non-responders and month 6 f...

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Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate: Twelve-month data from a twenty-four–month phase III randomized radiographic study

Arthritis & Rheumatism 2013; 65(3):559-70

The ORAL Scan trial is one of six studies conducted as part of the phase 3 research programme for the oral Janus kinase (JAK) inhibitor tofacitinib. This is the 12-month interim results published for the ORAL Scan study, a 24-month, phase 3 study that compared the effects of tofacitinib and placebo on structural preservation in patients with active RA despite methotrexate therapy. Patients were randomised to 5 or 10 mg tofacitinib twice daily or placebo, which was switched to 5 or 10 mg tofaciti...

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