July 2016

Switching from Adalimumab to Tofacitinib in the Treatment of Patients with Rheumatoid Arthritis

Arthritis Research & Therapy. 2016. DOI 10.1186/s13075-016-1049-3 [Epub ahead of print]

Results are reported from an analysis exploring the safety and efficacy of open-label tofacitinib (TOF) following blinded treatment with TOF or adalimumab (ADA) in patients with moderate to severe RA. The analysis included patients from ORAL Sequel, an open-label long-term extension study, which all patients entered following ORAL Standard (one of the studies in the TOF phase 3 program). Only those patients who had been randomized to ADA 40 mg Q2W + MTX or 10 mg TOF + MTX in ORAL Standard were i...

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Biologics or Tofacitinib for Rheumatoid Arthritis in Incomplete Responders to Methotrexate or Other Traditional Disease-Modifying Anti-Rheumatic Drugs: A Systematic Review and Network Meta-Analysis

Cochrane Database of Systematic Reviews 2016 Issue 5. Art. No.: CD012183 [DOI: 10.1002/14651858.CD012183].

Treatment options for RA patients who are MTX/DMARD incomplete responders (IR) include other DMARDs, biologics or tofacitinib (TOF). However, there is a lack of head-to-head studies to show any important differences between these options in terms of benefits and harms. This review provides an update of the 2009 Cochrane overview and network meta-analysis (NMA) of biologics for RA.1Nine biologics (abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, a...

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Risk for Gastrointestinal Perforation Among Rheumatoid Arthritis Patients Receiving Tofacitinib, Tocilizumab, or Other Biologics

Arthritis Rheumatol. 2016 May 17. DOI 10.1002/art.39761 [Epub ahead of print]

Historically, patients with RA have suffered with upper tract gastrointestinal perforation (GIPs), associated with NSAID use. More recently, the IL-6 receptor antagonist tocilizumab (TCZ) has been associated with lower tract GIPs. Janus kinase (JAK) inhibitors, including tofacitinib (TOF), with some downstream effects on IL-6 signalling, also have potential for an increased risk of GIPs.There is limited real-world evidence and almost no comparative evidence on the risk for GIP associated with TC...

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May 2016

Initial Experience with Tofacitinib in Clinical Practice: Treatment Patterns and Costs of Tofacitinib Administered as Monotherapy or in Combination with Conventional Synthetic DMARDs in 2 US Health Care Claims Databases

Clin Ther. 2016 Mar 28. doi: 10.1116/j.clinthera. 2016.03.038 [Epub ahead of print]

This study analyzes data from two US claims databases between November 2012 and June 2014. It was designed to build upon knowledge from tofacitinib Phase 3 clinical trials providing clinical insights from independent sources on treatment patterns and costs for tofacitinib. Data were collected from 337 patients in the Truven Marketscan (TM) and 118 patients in the Optum Clinformatics (OC) databases. In this early experience cohort for tofacitinib, approximately 75% of patients had previously rece...

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Real-world Comparative Risks of Herpes Virus Infections in Tofacitinib and Biologic-treated Patients with Rheumatoid Arthritis

Ann Rheum Dis. 2016 Apr 25;0:1–5 doi: 10.1136/annrheumdis-2016-209131

Herpes Zoster (HZ) complications can cause considerable morbidity including debilitating pain syndromes. Clinical trials of tofacitinib have suggested it may increase the risk of HZ. Although unclear, the mechanism may involve reduced CD4 T-cell function and interference of interferon signalling. Following approval of tofacitinib in the US in 2012, real-world data from Medicare (2006–2013) and from the US longitudinal database, Marketscan, (2010–2014) were analysed. A total of 2526 patients who...

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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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