PSORT-D
Research type
Research Study
Full title
Psoriasis Stratification to Optimise Relevant Therapy Discovery Study (PSORT-D) - Molecular and Immune Biomarkers in Skin and Blood.
IRAS ID
151219
Contact name
Catherine Smith
Contact email
Sponsor organisation
Kings College London
Duration of Study in the UK
4 years, 0 months, 0 days
Research summary
Psoriasis is a chronic inflammatory skin disease that affects 2% of the population. It is characterized by the presence of raised, scaly, red skin plaques. Psoriasis patients suffer from a high degree of morbidity and a decreased quality of life, due to the unpleasant skin lesions and the side effects associated with the therapy. In addition to the skin symptoms, there are important systemic manifestations associated with psoriasis including metabolic syndrome, depression, cancer and the risk of cardiovascular disease (Nestle et al. 2009). There is no definitive cure for the disease, but the introduction of new biologic drugs for disease treatment has improved patients’ quality of life. However biologic therapy is expensive and up to 30% of patients do not respond adequately.
In the USA it is estimated that by 2020 the psoriasis market for biologics will grow to $5.5 billion from $2.6 billion in 2010. In the UK, the introduction into standard clinical practice of NICE approved biologic therapies, targeting TNFα and IL-12/23 pathways, has had a dramatic beneficial effect on clinical outcomes for patients with severe psoriasis. However patient p.a. costs for biologic therapy at ~£10k is not offset by an 80% reduction in inpatient episodes. This may be explained by the fact that it is unknown which biologic is best suited to an individual patient. For example, 90% efficacy rates at 12-16 weeks are 11%, 37% and 45% for etanercept, adalimumab and ustekinumab respectively and each of these drugs may lose effect over time (approximately 15% attrition p.a.). Furthermore, new small molecules, such as apremilast, and biologics including biosimilars and IL-17-inhibitors, are currently in development with a potential wide range in efficacy and cost. There is therefore an urgent need to understand the most cost-effective way of using established biologics and of introducing new agents into clinical practice. Stratifying patients based on predicted response to therapy and understanding the underlying mechanisms would have profound impact on treatment pathways for severe psoriasis.
This interventional study is part of the MRC funded Programme grant, “Psoriasis Stratification to Optimise Relevant Therapy (PSORT)”, which is designed to directly address these critical issues. The hypothesis to be tested is that clinical, immune and genetic biomarkers in skin and blood predict and stratify response of psoriasis to biologic therapies targeting TNFα and IL-12/23 pathways and these are both scalable and cost-effective. The hypothesis will be addressed by collecting quantitative clinical and biological data from 240 psoriasis patients receiving adalimumab (TNF-inhibitor) and ustekinumab (IL-12/23 inhibitor) biologic therapy recruited in Dermatology clinics. In particular blood and skin samples will be collected from psoriasis patients and analysed using a number of relevant methods for which expertise throughout the PSORT consortium is recognised internationally including clinical profiling, pharmacology (PK and immunogenicity), tissue expression studies, genetics, immune monitoring and bioinformatics. There is prior supportive evidence that psoriasis is stratifiable by the methodologies above. Thus, endotypes of psoriasis and of drug response associate with variation in clinical phenotype and genetic architecture. Preliminary data indicate that serum levels of drug associate with response to inhibitors of TNFα and transcriptomic signatures have been identified that reveal distinct molecular subtypes (Ainali et al. 2012). This study will focus on discovery and refinement of markers of possible clinical utility using an adaptive experimental approach. Psoriasis has many benefits as a model disease for stratification by treatment response. These include: i) biologics are used as monotherapy; ii) response to therapy is simple to quantify; and iii) target organ (i.e. skin) sampling is minimally invasive and acceptable to patients. Further, given that there is significant overlap of usage of these agents with other immune-mediated inflammatory diseases e.g. inflammatory bowel disease and inflammatory arthritis, the results could be potentially of much wider interest.
The biomarkers identified in this study will be then validated in ongoing UK wide studies such as the British Association of Dermatologists Biologic Interventions Register (BADBIR – ethics ref: 07/MRE08/9) and Biomarkers of Systemic Treatment Outcomes in Psoriasis study (BSTOP – ethics ref: 11/H0802/7)
In summary the outputs of this study will allow more accurate matching of the treatment to the disease, facilitating more rapid and individualised transitioning onto the most effective and safest drug.
REC name
London - London Bridge Research Ethics Committee
REC reference
14/LO/1685
Date of REC Opinion
18 Feb 2015
REC opinion
Further Information Favourable Opinion