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Role of biologics: ustekinumab


The role of biologics in moderate-to-severe psoriasis: ustekinumab


In a continuation of an analysis of biologics in moderate-to-severe psoriasis, this article looks at the mAb that binds to interleukins 12 and 23


Eva Vilarrasa MD Lluís Puig MD Dermatology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain


Ustekinumab (CNTO-1275, Stelara®


Janssen Biotech, Inc, Horsham, PA, US) is a fully human IgG1 kappa monoclonal antibody developed by Centocor, which binds specifically to p40 subunit of interleukin (IL)-12 and IL-23.


Mode of action


Ustekinumab targets the p40 subunit shared by two cytokines, IL-12 and IL-23. It interacts with the same epitope within the D1 domain of the p40 subunit of each cytokine.1


Consequently, ustekinumab prevents the interaction of IL-12 and IL-23 with the cell surface IL-12Rß1 receptor, thereby blocking subsequent signalling, T-cell differentiation and cytokine production, central to inflammatory diseases.2,3


IL-12 is produced by dendritic cells and macrophages and plays a central role in the cellular immune-mediated response to parasitic and intracellular bacterial infections.4


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IL-23 is a pro-inflammatory cytokine essential for the differentiation and activation of T helper 17 (Th17) lymphocytes, a subset of Th lymphocytes that produce IL-17, which are implicated in autoimmune activation and chronic


www.hospitalpharmacyeurope.com Licensed indications


Ustekinumab was approved for use in psoriasis by the European Medicines Agency and US Food and Drug Administration in 2009.11,12


In the EU, it is indicated for those ,


inflammation in psoriasis, but also in other chronic inflammatory or immune mediated diseases such as rheumatoid arthritis, psoriatic arthritis, Crohn’s disease and multiple sclerosis.3,5–9 Furthermore, in an animal model of spondyloarthropathy, IL-23 has been shown to activate a subpopulation of entheseal resident T cells that produce IL-6, IL-17, IL-22 and different chemokines, resulting in the development of enthesitis and entheseal new bone formation, as well as inflammation at the aortic root and valve, as in the human condition.10


inadequate response to previous non- biological disease-modifying anti- rheumatic drugs.12


Besides psoriasis and psoriatic arthritis, ustekinumab has also been studied as a treatment in a number of other indications, including: Crohn’s disease, ankylosing spondylitis, rheumatoid arthritis and multiple sclerosis, though its clinical development has been discontinued for the latter indication because of lack of efficacy.13–20


Psoriasis


Well-designed phase II and III randomised-controlled clinical trials have demonstrated that subcutaneous (SC) ustekinumab (45 or 90mg) is effective in the treatment of moderate-to-severe plaque psoriasis.8,21–23


“Phase II and III randomised-controlled clinical trials have demonstrated that subcutaneous ustekinumab is effective in the treatment of moderate-to-severe plaque psoriasis”


who failed to respond to, have a contraindication to, or are intolerant to other systemic therapies and phototherapy.12 In 2013, ustekinumab, alone or in combination with methotrexate, was also approved for the treatment of active psoriatic arthritis in adult patients in both the EU and the US.11,12


In the EU, ustekinumab is indicated when there is


In a phase II, double-blind, placebo controlled trial of ustekinumab conducted in 320 adult patients with moderate-to- severe psoriasis, 52% and 81% of the patients in the 45mg and 90mg ustekinumab groups, respectively, reached a PASI75, compared with 2% in the placebo group (p<0.001).21 Two phase III studies, PHOENIX 1


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