July 2015

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]

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-...

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

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]

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 ...

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December 2014

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

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...

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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]

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.

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October 2014

Tofacitinib with methotrexate in third-line treatment of patients with active rheumatoid arthritis: Patient-reported outcomes from a Phase 3 trial

Arthritis Care Res (Hoboken). 2014 Sep 3. doi: 10.1002/acr.22453. [Epub ahead of print]

For many patients with rheumatoid arthritis, improvements in pain, physical function, fatigue, and health-related quality of life (HRQoL) are more important and meaningful than improvements in joint swelling, tenderness, or inhibition of structural damage. These patient-perceived benefits of RA therapy contribute importantly to overall clinical efficacy.

This paper presents patient-reported outcomes (PROs) form the ORAL Step trail, which assessed tofacitinib 5 mg or 10 mg twice daily, or ...

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September 2014

Secukinumab in Plaque Psoriasis — Results of Two Phase 3 Trials

N Engl J Med. 2014;371(4):326–338.

Secukinumab is a fully human monoclonal antibody that selectively binds to and neutralises interleukin-17A, a cytokine shown to play a crucial role in plaque psoriasis, as well as other immune-mediated diseases.

These two pivotal phase 3 studies in plaque psoriasis, FIXTURE and ERAUSRE, were sponsored by Novartis Pharmaceuticals. Secukinumab met all primary endpoints, PASI 75 response and the response of 0 or 1 on the modified investigator’s global assessment, as well as key secondary end...

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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 2014

Differential regulation of anti-inflammatory genes by p38 MAP kinase kinase 6

Journal of Inflammation 2014, 11:14

Several p38α inhibitors have been developed and evaluated in RA. However, despite pre-clinical data showing promise, the compounds have been shown to have little therapeutic efficacy. Previous studies have suggested this may be a result of inhibitors blocking the role of p38 in limiting inflammation. Previous studies by the same authors have shown that the targeting of MKK3 or MKK 6, which are the upstream activators of p38, may be superior to p38 blockade as the anti-inflammatory effects ...

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May 2014

Safety and Efficacy of Tofacitinib, an Oral Janus Kinse Inhibitor, for the Treatment of Rheumatoid Arthritis, in Open-Label Longterm Extension Studies

J Rheumatol 2014;41;837-852

This study pooled data from two LTE studies involving patients who had previously participated in qualifying phase I, II and III studies. Data up to 60 months was included for safety aspects and efficacy data up to 48 months. However data for 10 mg BID and tofacitinib monotherapy was limited after 24 and 36 months respectively. Over the two studies, 4102 patients were treated for a total of 5963 patient years.Herpes zoster, both serious and non-serious, had a higher incidence rate in tofacitinib...

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