Publications

Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis

N Engl J Med 2017; 377:1537-50. DOI: 10.1056/NEJMoa1615975

Mease P,

Hall S,

FitzGerald O,

van der Heijde D,

Merola J F,

Avila-Zapata F,

Cieslak D,

Graham D,

Wang C,

Menon S,

Hendrikx T,

Kanik K S

In the Phase 3 OPAL Broaden trial of patients with active psoriatic arthritis (PsA) with inadequate response to ≥1 csDMARD, superior efficacy was observed in patients treated with tofacitinib (TOF) compared with those given placebo. Patients were randomised to: 5 mg TOF BID, 10 mg TOF BID, 40 mg adalimumab administered subcutaneously q2W, or placebo with a switch to 5 mg TOF at Month 3. Adalimumab was used as an active control in the study. A variety of primary and secondary endpoints were used ...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3

Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors

N Engl J Med 2017;377:1525–36.

Gladman D,

Rigby W,

Azevedo VF,

Behrens F,

Blanco R,

Kaszuba A,

Kudlacz E,

Wang C,

Menon S,

Hendrikx T,

Kanik KS

The study data presented that tofacitinib (TOF) improves efficacy response rates in patients with severe psoriatic arthritis (PsA) who have an inadequate response to TNF inhibitors.The Phase 3 Oral Psoriatic Arthritis Trial (OPAL) Beyond study evaluated patients with active PsA who had inadequate responses to more than one TNFi. Patients were randomised 2:2:1:1 to 5 mg TOF BID or 10 mg TOF BID for 6 months; or PBO, with a switch to 5 mg TOF BID or to 10 mg BID at 3 months.Primary endpoints were ...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3

The Efficacy and Safety of Clazakizumab, an Anti-Interleukin-6 Monoclonal Antibody, in a Phase 2b Study of Adults with Active Psoriatic Arthritis

Arthritis Rheumatol. 2016 Mar 24. DOI 10.1002/art.39700 [Epub ahead of print]

Mease et al.

Encouraging results have been seen with clazakizumab in RA, but the results of anti-IL6 therapy in patients with psoriatic arthritis (PsA) have so far been unclear. This Phase 2b dose-ranging study examined the efficacy and safety of clazakizumab given subcutaneously q4w, with or without MTX, in 165 patients with PsA who had inadequate response to NSAIDs.ACR20 response at Week 16, the primary endpoint, was significantly higher in patients receiving clazakizumab 100 mg compared with placebo (52.4...

Keywords:

• IL-6,
• Clazakizumab,
• Phase 2

A Retrospective Cohort Study Comparing Utilization and Costs of Biologic Therapies and JAK Inhibitor Therapy Across Four Common Inflammatory Indications in Adult US Managed Care Patients

Adv Ther. 2016 Mar 12. DOI 10.1007/s12325-016-0312-y

Chastek et al.

Biologics are used to treat several inflammatory diseases, including RA, PsO, PsA, and AS; however, the cost of biologic therapies is high compared to non-biologic DMARDs. By using evidence-based assessment of comparative costs between biologics, healthcare resources can be properly allocated. This study used medical and pharmacy claims data to assess the utilitisation and cost of biologic treatment for RA, PsO, PsA, and AS. ETN (45%), ADA (32%), and INF (9%) were the most common medications and...

Keywords:

• JAK,
• Cost / Cost Effectiveness,
• Review

Impact of obesity on the clinical outcome of rheumatologic patients in biotherapy

Autoimmunity Reviews Doi: 10.1016/j.autrev.2016.01.010

Iannone et al

Obesity is increasingly becoming a public health concern as its prevalence continues to grow in the United States and Western nations. Obesity has been shown to be an inflammatory condition that impacts multiple tissues and systems, including the immune system possibly linking to rheumatic diseases. In this review, Iannone et al overview the epidemiology and clinical outcomes of PsA and/or RA patients with comorbid obesity.Large cohort and prospective studies in Italy, the US, and the UK have s...

Keywords:

• ACR

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

W Gao,

T McGarry,

C Orr,

J McCormick,

D J Veale,

U Fearon

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...

Keywords:

• JAK,
• Tofacitinib,
• Basic Science,
• Review

Btk inhibition suppresses agonist-induced human macrophage activation and inflammatory gene expression in RA synovial tissue explants

Ann Rheum Dis Published Online First 24 April 2014 doi:10.1136/annrheumdis-2013-204143

Hartkamp LM,

Fine JS,

van Es IE et al

Bruton’s tyrosine kinase, a downstream target of PI3K signalling, has been shown to be crucial in the B lymphocyte and myeloid cell contribution to murine models of arthritis. Synovial tissue samples were taken from biologically naïve RA (n=16) and PsA (n=12) patients in order to assess the expression of BTK. Separate RA synovial explants (n=8) were used to assess the effects of the specific BTK inhibitor RN486. BTK was expressed at equivalent levels in both RA and PsA synovial tissue, however e...

Keywords:

• BTK,
• Preclinical,
• MOA