May 2016

Extended-release once-daily formulation of tofacitinib: evaluation of pharmacokinetics compared with immediate-release tofacitinib and impact of food

J Clin Pharmacol. 2016 Mar 11. doi: 10.1002/jcph.734. [Epub ahead of print]

PK profile of TOF is rapid absorption and elimination with time to max concentration 0.5-1 hour and terminal half-life at 3 hours. It is currently approved for immediate release (IR) 5 mg BID, 10 mg total; however, decreasing the dosage to QD dosing may help increase compliance. This study performed in 24 healthy males compared the PK of XR and IR TOF under both single and multiple dose conditions and evaluated the effect of a high-fat meal on the PK of XR TOF. There were no clinically important...

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Effects of Tofacitinib and other DMARDs on Lipid Profiles in Rheumatoid Arthritis: Implications for the Rheumatologist

Semin Arthritis Rheum 2016;46:71–80

Increased inflammation and CV disease have been associated with lower total cholesterol (TC) and low density lipoprotein (LDL-C) levels in RA patients – an apparent paradox to what is observed in the general population. Previously, reduced high-density lipoprotein (HDL-C) levels have been associated with increased risk of CV, and an inverse relationship observed with levels of HDL-C level and C-reactive protein (CRP).This analysis of the literature with regard to studies using DMARDs in RA patie...

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March 2016

Tofacitinib or adalimumab versus placebo: patient-reported outcomes from a phase 3 study of active rheumatoid arthritis

Strand et al. Rheumatology (Oxford). 2016 Feb 29. doi:pii: kev442. [Epub ahead of print]

RA not only affects the physical aspects of a patient’s health but also has an impact on the psychological well-being causing a significant disease burden. This paper reports on the patient-reported outcomes (PROs) from the ORAL Standard study. This study investigated tofacitinib 5mg BID, 10mg BID, adalimumab vs. placebo over 12 months with a primary endpoint at month 3. All treatment groups showed significant improvements over placebo in HAQ-DI, PtGA and Pain with LSM changes in baseline sustai...

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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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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

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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Cost-effectiveness of Tofacitinib in the Treatment of Moderate to Severe Rheumatoid Arthritis in South Korea

Clinical Therapeutics. 2015:37(8). [Epub ahead of print]

This study evaluated the cost-effectiveness of introducing tofacitinib, an oral Janus kinase inhibitor, to the treatment of Korean patients with RA and an inadequate response to conventional DMARDs. The model showed that the inclusion of tofacitinib as a treatment strategy for moderate to severe RA is cost-effective; this conclusion was considered robust based on multiple sensitivity analyses.First-line tofacitinib used before the standard of care (base-case analysis) increased both treatment c...

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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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September 2015

Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study

Modern Rheumatology. 2015 Jul;25(4):514-21. doi: 10.3109/14397595.2014.995875.

The oral Janus kinase (JAK) inhibitor, Tofacitinib, preferentially inhibits signalling by heterodimeric receptors associated with JAK3 and/or JAK1, blocking signalling for several cytokines. The purpose of this study was to evaluate the efficacy of tofacitinib monotherapy versus placebo in Japanese patients with inadequate response to disease-modifying anti-rheumatic drugs (DMARDs). Data on response rates – ACR20/50/70, DAS28-4(ESR), and HAQ-DI – laboratory parameters and adverse events were col...

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July 2015

Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two, randomised, placebo-controlled, Phase 3 trials

British Journal of Dermatology. 7 July 2015 DOI: 10.1111/bjd.14018. [Epub ahead of print]

The management of moderate to severe chronic plaque psoriasis has benefited from the introduction of biological therapies, but unmet needs still remain, especially for oral therapies. Tofacitinib is an orally active agent that blocks signalling of key cytokines implicated in the immune response and inflammatory pathways of psoriasis. The Phase III studies presented in this paper analysed efficacy and safety endpoints.Both studies demonstrated that tofacitinib in both 5 mg and 10 mg twice daily d...

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