March 2016

Comparison of adding tocilizumab to methotrexate with switching to tocilizumab in patients with rheumatoid arthritis with inadequate response to methotrexate: 52-week results from a prospective, randomised, controlled study (SURPRISE study)

Ann Rheum Dis 2016 Jan 5 DOI: 10.1136/annrheumdis-2015-208426 [Epub ahead of print

MTX is the primary drug in RA management because of its long-term effectiveness and safety profile; however, in patients who have insufficient response (IR) to MTX, treatment adjustments are needed – either to combine a bDMARD with MTX or to switch to a bDMARD from MTX. In the SURPRISE study, the efficacy and safety of adding TCZ to MTX (ADD-ON) or switching MTX to TCZ (SWITCH) was evaluated in 233 patients with moderate to highly active RA who were randomised 1:1. Both treatment groups were adm...

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January 2016

VX-509 (Decernotinib), an Oral Selective JAK-3 Inhibitor, in Combination With Methotrexate in Patients With Rheumatoid Arthritis

Arthritis Rheumatol. 2016 Jan;68(1):46-55.

VX-509 (decernotinib) is a novel oral, selective inhibitor of JAK-3. JAK-3 is a member of the JAK signalling family that is primarily expressed in hematopoietic cells and associates with only the common γ-chain making it a promising therapeutic drug target. A phase IIb 24-week study of VX-509 in 358 patients with RA, who had prior inadequate response to MTX, uses ACR20 response rate and DAS28-CRP change at Week 12 to assess the efficacy of VX-509. Patients were administered either placebo+MTX or...

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October 2015

Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: results from a European collaborative study

Ann Rheum Dis. 2015 Sep 15. doi:10.1136/ annrheumdis-2015-207760

Biological DMARDs have markedly changed the management and outcome of rheumatoid arthritis. Most international guidelines recommend the use of biological DMARDs in combination with MTX or other synthetic DMARDs (sDMARDs) (where MTX is not tolerated or contraindicated), based primarily on the observation that MTX enhances the efficacy of TNF antagonists in both clinical trials and observational studies.This study examined the effectiveness of tocilizumab (TCZ), an anti-IL-6 monoclonal antibody, ...

Phase 3 studies comparing brodalumab with ustekinumab in psoriasis

N Engl J Med 2015;373:1318–28. doi: 10.1056/NEJMoa1503824

Brodalumab treatment resulted in a rapid reduction in the signs and symptoms of PsO. The median time to a PASI 75 response with 210 mg of brodalumab Q2W was 4 weeks, approximately twice as fast as the median time to a response with ustekinumab.

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Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy: Results from a randomized phase II trial

Modern Rheumatology. 2015 Sep 10:1-9. [Epub ahead of print]

This Phase II study assessed the safety and efficacy of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy. After 12 weeks of treatment, olokizumab was found to rapidly improve disease activity in patients who had previously failed anti-TNF therapy. There was also a significant decrease in ACR20 and ACR50 responder rates at week 12. The safety findings were consistent with the safety profile expected for this drug class. These findin...

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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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]

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...

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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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-...