Publications

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.

Charles-Schoeman C,

Burmester G,

Nash P,

Zerbini CA,

Soma K,

Kwok K,

Hendrikx T,

Bananis E,

Fleischmann R.

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 ...

Keywords:

• JAK,
• Tofacitinib,
• Review

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.

Tanaka Y,

Takeuchi T,

Yamanaka H,

Nakamura H,

Toyoizumi S,

Zwillich S.

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...

Keywords:

• JAK,
• Tofacitinib,
• Phase 2

The Efficacy and Safety of Subcutaneous Clazakizumab in Patients with Moderate-to-Severe Rheumatoid Arthritis and Inadequate Response to Methotrexate: Results from a Phase IIb, Randomized, Double-Blind, Placebo/Active-Controlled, Dose-Ranging, Multinational Study

Arthritis & Rheumatology. 2015 Jul 2. doi: 10.1002/art.39249. [Epub ahead of print]

Weinblatt ME,

Mease P,

Mysler E,

Takeuchi T,

Drescher E,

Berman A,

Xing J,

Zilberstein M,

Banerjee S,

Emery P

The humanised monoclonal antibody, Clazakizumab (CLZ), binds to circulating interleukin-6 (IL-6) cytokine rather than the IL-6 receptor, blocking both classical and trans-signalling. The purpose of this phase 2B study was to evaluate the efficacy and safety of clazakizumab in patients with inadequate response to methotrexate (MTX). Data on selected response rates – ACR20/50/70, DAS28-CRP, SDAI ≤3.3, CDAI ≤2.8 and the ACR/EULAR Boolean definition – and adverse events were collected from 418 patie...

Efficacy and safety of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional DMARDs in patients with RA at week 97 (SUMMACTA)

Ann Rheum Dis. 10 May 2015 doi:10.1136/annrheumdis-2015-207281 [Epub ahead of print]

Gerd R Burmester,

Andrea Rubbert-Roth,

Alain Cantagrel,

Stephen Hall,

Piotr Leszczynski,

Daniel Feldman,

Madura J Rangaraj,

Georgia Roane,

Charles Ludivico,

Min Bao,

Lucy Rowell,

Claire Davies,

Eduardo F Mysler

Tocilizumab (TCZ) has demonstrated efficacy and a well-established safety profile for intravenous (IV) administration. The Phase III SUMMACTA study evaluated the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) in combination with DMARDS in patients with moderate-to-severe RA and inadequate response to ≥1 DMARD. Patients were randomised to receive TCZ-SC 162 mg weekly or TCZ-IV 8 mg/kg q4w in combination with DMARDs. After a 24-week double-blind period, patients receiving TCZ-SC were re-...

Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme

Ann Rheum Dis. 2015 Apr 22. pii: annrheumdis-2014-205847. doi: 10.1136/annrheumdis-2014-205847. [Epub ahead of print]

Curtis JR,

Lee EB,

Kaplan IV,

Kwok K,

Geier J,

Benda B,

Soma K,

Wang L,

Riese R

The developments of certain malignancies associated with chronic inflammatory diseases such as RA is known to occur to a greater extent than that of the general population. It is also know that certain RA treatments can affect malignancy rates. As such, newer immunomodulatory agents, such as the JAK inhibitor tofacitinib, are closely monitored for safety events of special interest, including malignancies.

This paper analyses pooled malignancy data from the tofacitinib RA clinical develop...

Keywords:

• JAK,
• Safety,
• Malignancy,
• Review

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.

Fleischmann RM,

Damjanov NS,

Kivitz AJ,

et al.

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...

Keywords:

• JAK,
• Decernotinib,
• Phase 2

Efficacy and Safety of Tofacitinib as Monotherapy in Japanese Patients With Active Rheumatoid Arthritis: A 12-Week, Randomized, Phase 2 Study

Mod Rheumatol. 2014 Dec 11:1–25. [Epub ahead of print]

Tanaka Y,

Takeuchi T,

Yamanaka H,

Nakamura H,

Toyoizumi S,

Zwillich S.

In Japan, the biologic DMARDs infliximab, etanercept, adalimumab, golimumab and certolizumab pegol, as well as tocilizumab and abatacept are approved for use in patients with active RA and an inadequate response to existing therapies. However, not all patients respond to these therapies adequately, creating an unmet need for therapeutic options with alternative mechanisms of action.

The oral JAK inhibitor tofacitinib has demonstrated efficacy as monotherapy or in combination with DMARDs ...

Keywords:

• JAK,
• Tofacitinib,
• Phase 2

Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate

Ann Rheum Dis. 2015;74(2):333–340

Keystone EC,

Taylor PC,

Drescher E,

Schlichting DE,

Beattie SD,

Berclaz PY,

Lee CH,

Fidelus-Gort RK,

Luchi ME,

Rooney TP,

Macias WL,

Genovese MC.

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...

Keywords:

• JAK,
• Baricitinib,
• Phase 2

The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis

Ann Rheum Dis. 2014 Nov 14. pii: annrheumdis-2014-206028. doi: 10.1136/annrheumdis-2014-206028. [Epub ahead of print]

Boyle DL,

Soma K,

Hodge J,

Kavanaugh A,

Mandel D,

Mease P,

Shurmur R,

Singhal AK,

Wei N,

Rosengren S,

Kaplan I,

Krishnaswami S,

Luo Z,

Bradley J,

Firestein GS

Targeting intracellular pathways such as JAK/STAT represents a novel approach to the treatment of RA. Tofacitinib is an oral JAK inhibitor, proven to be effective in the treatment of RA, yet the pathways affected by tofacitinib and the effects on gene expression in situ are unknown. In this study, Boyle et al. tested the hypothesis that tofacitinib targets cytokine signalling critical to the pathogenesis of rheumatoid synovitis by investigating tofacitinib effects on synovial pathobiology.

Keywords:

• JAK,
• Tofacitinib,
• Phase 1,
• MOA

Lipid profile changes in patients with chronic inflammatory arthritis treated with biologics and tofacitinib in randomized clinical trials: A systematic review and meta-analysis

Arthritis Rheumatol. 2015;67(1):117–127

Souto A,

Salgado E,

Maneiro JR,

Mera A,

Carmona L,

Gómez-Reino JJ

Systemic inflammation, reflected by high levels of C-reactive protein and the erythrocyte sedimentation rate, has been identified as an independent risk factor for cardiovascular disease, the most important cause of death in RA and SpA. Studies with TNF antagonists have given contradictory results on cardiovascular risk. As such, this systemic literature search aimed to analyse lipid changes in RA and SpA subjects treated with biologics or tofacitinib in randomized clinical trials.

The s...

Keywords:

• JAK,
• Tofacitinib,
• Safety,
• Cardiovascular