Publications

Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a Phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1)

J Am Acad Dermatol 2015;73:37-49. doi: 10.1016/j.jaad.2015.03.049

Papp K,

Reich K,

Leonardi CL,

Kircik L,

Chimenti S,

Langley RG,

Hu C,

Stevens RM,

Day RM,

Gordon KB,

Korman NJ,

Griffiths CE

Here, investigators reported that efficacy measures for skin and scalp were significantly greater for apremilast than for placebo in patients with PsO at baseline. Previously, clinical study data has highlighted that the use of apremilast leads to a reduction in the expression within the epidermis of numerous inflammatory cytokines relevant to PsO. As a result, ESTEEM 1 evaluated the efficacy/safety of apremilast at 30 mg BID for moderate to severe PsO.

Keywords:

• Apremilast,
• Efficacy,
• Safety,
• Phase 3

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]

Strand V,

Kremer J,

Wallenstein G,

Kanik KS,

Connell C,

Gruben D,

Zwillich SH,

Fleischmann R

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...

Keywords:

• JAK,
• Tofacitinib,
• PRO / QoL,
• Phase 3

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]

Takeuchi T,

Tanaka Y,

Yamanaka H,

Amano K,

Nagamine R,

Park W,

Shiozawa K,

Tsukano M,

Wei J,

Shao J,

Togo O,

Mashimo H

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...

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...

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]

Papp KA,

Menter MA,

Abe M,

Elewski B,

Feldman SR,

Gottlieb AB,

Langley R,

Luger T,

Thaci D,

Buonanno M,

Gupta P,

Proulx J,

Lan S,

Wolk R; OPT Pivotal 1 and OPT Pivotal 2 Investigators.

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...

Keywords:

• JAK,
• Tofacitinib,
• Phase 3

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-...

Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: Results of a phase III study

Arthritis Rheumatol. Vol. 67, No. 6, June 2015, pp 1424–1437

Genovese MC,

Fleischmann R,

Kivitz A et al.

Biologic DMARDs targeting TNF-alpha, IL-1, T-cell co-stimulatory blockade, B-cell depletion, and IL-6R, as well as the newer JAK inhibitors have greatly improved clinical outcomes in RA. However, not all patients respond to current biologic or small molecule DMARDs.

Sarilumab is a fully human anti-IL-6Rα mAb that binds membrane-bound and soluble human IL-6R with high affinity, blocking cis and trans IL-6-mediated signalling. This study (MOBILITY) is the first randomised, double-blin...

Keywords:

• IL-6,
• Phase 3

Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection

Clin Pharmacokinet. 2015 Feb 14. [Epub ahead of print]

Namour F,

Diderichsen PM,

Cox E,

Vayssière B,

Van der Aa A,

Tasset C,

Van't Klooster G.

Filgotinib (GLPG0634) is a selective inhibitor of JAK1 currently in development for the treatment of RA and Crohn’s disease. This paper describes the pharmacokinetics of filgotinib and its active metabolite, as well as the PK/PD modelling to support dose selection for phase IIB.

Two phase I, randomised, double-blind, placebo-controlled trials in healthy volunteers and one phase IIa proof-of-concept study in RA patients were used to evaluate single and multiple doses of filgotinib.

Keywords:

• JAK,
• Filgotinib,
• PK/PD,
• Phase 1