Publications

View and download slide summaries of the latest original articles focusing on therapies in immune-mediated inflammatory diseases including rheumatology, dermatology, and gastroenterology. All materials produced by the team are subsequently reviewed and approved by individual Steering Committee members.

October 2015

Phase 3 studies comparing brodalumab with ustekinumab in psoriasis

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

Puig L,

Papp K,

Toth D,

Wu JJ,

Paul C,

Bagel J,

Koo J,

Aras G,

Li J,

Song W,

Shi Y,

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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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]

Papp KA,

Abe M,

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...

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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,

Hu C,

Day RM,

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.

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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

Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation

Nature. 2014;510(7503):157–161.

Riol-Blanco L,

Ordovas-Montanes J,

Perro M,

et al.

The abnormal activation of skin immune cells, such as dermal dendritic cells (DDCs) and interleukin (IL)-17-producing γδ T (γδT17) cells, by IL-23 is known to provoke psoriasis-type inflammation. What is less well known is how peripheral nerves regulate cutaneous immune responses. In this study, IL-23-dependent psoriasis-like inflammation was induced in mice to help determine the precise molecular mechanism of neuroimmune communication in the skin. Findings indicate nocic...

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April 2014

Molecular pathways: Molecular basis for sensitivity and resistance to JAK inhibitors

Clin Cancer Research doi:10.1158/1078-0432.CCR-13-0279

Meyer SC and Levine RL

Janus kinases (JAKs) mediate the regulation of a variety of cytokine signals with alterations in JAK1, JAK2, JAK3 and Tyk2 signalling contributing to many disease states including autoimmune diseases and haematological malignancies. Recently tofacitinib and ruxolitinib have been approved for treatment for rheumatoid arthritis and myelofibrosis respectively. Several JAK2 inhibitors, such as momelotinib and pacritinib, currently in development for myelofibrosis and the JAK1/2 inhibitor baricitinib...

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June 2013

Cytokine receptor signaling through the Jak–Stat–Socs pathway in disease

Molecular Immunology 2007; 44:2497-506

This review from 2007 provides an overview of the largest cytokine receptor family, the haematopoietin receptors, as well as other key components involved in one of the major cytokine signalling pathways implicated in autoimmune and inflammatory diseases. This includes the Janus kinases (Jaks), signal transducers and activators of transcription (Stats) and suppressors of cytokine signalling genes (Socs). Essentially, when a cytokine binds to a receptor from this group a functional cytokine recep...

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Janus kinases in immune cell signaling

Immunological Reviews 2009; 228:273-87

Ghoreschi K,

Laurence A,

O'Shea JJ

This review from 2009 describes the Janus Kinases (JAK) that includes JAK1, JAK2, and JAK3, a subgroup of non-receptor protein tyrosine kinases. This protein family has a diverse range of functions including roles in cell growth, survival, development, and differentiation of a variety of cells, and especially immune and haematopoietic cells. Current knowledge of protein structure, regulatory mechanisms, signalling pathways and intracellular interactions for the JAK family is reviewed. The paper ...