Periodic Reporting for period 1 - HIPPOCRATES (Health Initiatives in Psoriasis and PsOriatic arthritis ConsoRTium European States)
Período documentado: 2021-07-01 hasta 2022-06-30
The HIPPOCRATES project seeks to address key areas of concern for people with Psoriatic Arthritis (PsA) and their healthcare providers. These are being tackled through a series of interconnected Work Packages (WPs):
WP 1. There is no diagnostic test for the early diagnosis of PsA and as a result failure to achieve early diagnosis often results in worse outcomes. WP1 is focused on the development of a test or algorithm for early accurate diagnosis of PsA.
WP 2. Most people with PsA develop their arthritis on a background of longstanding skin psoriasis. PsA develops in about 30% of those with psoriasis but it is not possible to predict which persons with psoriasis will develop PsA. In WP2 we are aiming to identify clinical or molecular markers of progression from skin psoriasis to PsA, this will open the possibility of PsA-prevention studies.
WP 3. Joint damage in PsA can be severe and is always irreversible. If we could predict which patients might develop joint damage, then it may be possible to introduce treatments aimed at prevention.
WP 4. Several new treatments for PsA have recently been introduced but the choice of which drug should be used is challenging. WP4 is directed towards developing approaches to match an individual’s personal or disease characteristics with the best treatment choice. Such a “precision medicine” approach would greatly improve patient outcomes.
WP 1. There is no diagnostic test for the early diagnosis of PsA and as a result failure to achieve early diagnosis often results in worse outcomes. WP1 is focused on the development of a test or algorithm for early accurate diagnosis of PsA.
WP 2. Most people with PsA develop their arthritis on a background of longstanding skin psoriasis. PsA develops in about 30% of those with psoriasis but it is not possible to predict which persons with psoriasis will develop PsA. In WP2 we are aiming to identify clinical or molecular markers of progression from skin psoriasis to PsA, this will open the possibility of PsA-prevention studies.
WP 3. Joint damage in PsA can be severe and is always irreversible. If we could predict which patients might develop joint damage, then it may be possible to introduce treatments aimed at prevention.
WP 4. Several new treatments for PsA have recently been introduced but the choice of which drug should be used is challenging. WP4 is directed towards developing approaches to match an individual’s personal or disease characteristics with the best treatment choice. Such a “precision medicine” approach would greatly improve patient outcomes.
Much of the work in year 1 of HIPPOCRATES has occurred across the WPs with 3 working groups, being established and focused on Clinical Data Harmonisation (CDH), Imaging and Biomarkers. In a key first step, the extensive cohorts of psoriatic disease patients identified as being beneficial to the objectives of the project were reviewed by the CDH working group and a list of prioritised cohorts agreed by WPs 1-4. At the same time, discussions began on the development of a HIPPOCRATES Data Sharing Agreement. These discussions have involved representatives of WP1-5 with significant (including legal) contributions from Novartis, the Swiss Institute of Bioinformatic and the Fraunhofer. The agreement is in final draft and, when approved, will facilitate the flow of data. An associated Material Transfer Agreement is also in final draft.
While the cohorts to be included within HIPPOCRATES are predominantly retrospective, there are advanced plans to include 2 prospective studies. The first study, the HIPPOCRATES Prospective Observational Study (HPOS) is part of WP2, will on-line recruit 25,000 people with skin/nail psoriasis and follow them for the development of PsA. In collaboration with patients, the on-line platform has been developed and the study will be launched in January 2023. It is also planned to use patient-centric sampling to remotely collect a blood sample from a subset of HPOS participants identified as being at high risk of developing PsA. The second study, the COMprehensive characterization of PsoriAtiC arthriTis (COMPACT) is part of WP3. In this smaller study it is planned to recruit PsA patients and undertake imaging and molecular assessment of blood or tissue samples. The study protocol for COMPACT is in the final stages of development.
Within WP2, a pilot study to identify molecular factors which may predict the development of PsA in people with psoriasis has started. Serum samples from people with psoriasis and no features of PsA, samples from people with psoriasis and perhaps some early PsA features as well as samples from people with established PsA (30 subjects each group) have been shared with the UGLA, UMAN, KTH and Atturos. Each centre has analysed the samples and is undertaking data analysis. A statistical analysis plan for an integration of the data is under development with WP5. This will leverage the artificial intelligence expertise provided at the Fraunhofer. If molecular candidates are identified, their performance will be verified in separate larger cohorts.
If we can identify reliable markers of disease progression, we may be able to design studies aimed at preventing progression to PsA. Before undertaking such a ‘prevention’ strategy, it will be important to find out what level of risk people with psoriasis or PsA would consider as important to intervene and what treatment interventions might be acceptable. A discrete choice experiment to explore patient preferences is being designed by AMS and UOXF.
As noted, 3 working groups have been established to facilitate cross-WP efforts related to CDH, Imaging, and Biomarkers. The working groups have each made substantial progress. Within the CDH working group, data managers from all HIPPOCRATES partners providing cohort data to the consortium (WP1-4), have met bi-weekly and a HIPPOCRATES Glossary Expert group has been set up to develop a PsA glossary. To harmonize the glossary, these meetings have included input from the IMI BIOMAP team. A secure data platform which will conform with the final Data Sharing Agreement has been designed and is being set up by the Swiss Institute for Bioinformatics (WP5). The implementation of a data repository server (sFTP) is completed.
The focus of the Imaging Working group (involving representatives from WP1, WP3) has been on the identification of cohorts with imaging data and the collection of imaging metadata. The Biomarker Working group (with WP1-4 representatives) have mapped sample volumes required and have defined requirements for sample collection, processing and storage.
Finally, within WP7 the HIPPOCRATES Website has been launched and both Twitter and LinkedIn accounts set-up. A communication Toolkit with resources has been developed. In total, there has been 1 peer reviewed paper and 29 presentations (https://www.hippocratesimi.eu/publications). Presentations include a HIPPOCRATES Patient Advisory Council abstract on meaningful patient involvement which was presented at EULAR 2022 by PRP Lars Werner.
While the cohorts to be included within HIPPOCRATES are predominantly retrospective, there are advanced plans to include 2 prospective studies. The first study, the HIPPOCRATES Prospective Observational Study (HPOS) is part of WP2, will on-line recruit 25,000 people with skin/nail psoriasis and follow them for the development of PsA. In collaboration with patients, the on-line platform has been developed and the study will be launched in January 2023. It is also planned to use patient-centric sampling to remotely collect a blood sample from a subset of HPOS participants identified as being at high risk of developing PsA. The second study, the COMprehensive characterization of PsoriAtiC arthriTis (COMPACT) is part of WP3. In this smaller study it is planned to recruit PsA patients and undertake imaging and molecular assessment of blood or tissue samples. The study protocol for COMPACT is in the final stages of development.
Within WP2, a pilot study to identify molecular factors which may predict the development of PsA in people with psoriasis has started. Serum samples from people with psoriasis and no features of PsA, samples from people with psoriasis and perhaps some early PsA features as well as samples from people with established PsA (30 subjects each group) have been shared with the UGLA, UMAN, KTH and Atturos. Each centre has analysed the samples and is undertaking data analysis. A statistical analysis plan for an integration of the data is under development with WP5. This will leverage the artificial intelligence expertise provided at the Fraunhofer. If molecular candidates are identified, their performance will be verified in separate larger cohorts.
If we can identify reliable markers of disease progression, we may be able to design studies aimed at preventing progression to PsA. Before undertaking such a ‘prevention’ strategy, it will be important to find out what level of risk people with psoriasis or PsA would consider as important to intervene and what treatment interventions might be acceptable. A discrete choice experiment to explore patient preferences is being designed by AMS and UOXF.
As noted, 3 working groups have been established to facilitate cross-WP efforts related to CDH, Imaging, and Biomarkers. The working groups have each made substantial progress. Within the CDH working group, data managers from all HIPPOCRATES partners providing cohort data to the consortium (WP1-4), have met bi-weekly and a HIPPOCRATES Glossary Expert group has been set up to develop a PsA glossary. To harmonize the glossary, these meetings have included input from the IMI BIOMAP team. A secure data platform which will conform with the final Data Sharing Agreement has been designed and is being set up by the Swiss Institute for Bioinformatics (WP5). The implementation of a data repository server (sFTP) is completed.
The focus of the Imaging Working group (involving representatives from WP1, WP3) has been on the identification of cohorts with imaging data and the collection of imaging metadata. The Biomarker Working group (with WP1-4 representatives) have mapped sample volumes required and have defined requirements for sample collection, processing and storage.
Finally, within WP7 the HIPPOCRATES Website has been launched and both Twitter and LinkedIn accounts set-up. A communication Toolkit with resources has been developed. In total, there has been 1 peer reviewed paper and 29 presentations (https://www.hippocratesimi.eu/publications). Presentations include a HIPPOCRATES Patient Advisory Council abstract on meaningful patient involvement which was presented at EULAR 2022 by PRP Lars Werner.
By addressing the key areas of unmet needs in PsA and doing so in a coordinated and integrated manner we expect that HIPPOCRATES will lead to the development of diagnostic algorithm(s) for use in primary care settings, as well as in dermatology and rheumatology clinics. We will identify combined clinical and molecular markers for disease progression from skin psoriasis to PsA for further validation in HPOS and other large datasets. The molecular mechanisms underlying joint damage in PsA will be better understood opening the possibility of targeting those at risk of damage with accelerated treatment strategies. Finally, we expect to have further defined the molecular profiles underlying treatment response or non-response in PsA. Together these will support an era of precision medicine in PsA which will have considerable patient, societal and economic benefits.