Inadequate therapeutic strategies increase the disease burden
Because chronic inflammatory skin diseases are caused by a disbalanced immune system, treatment is aimed at counteracting the disbalance with immunosuppressive drugs. The specific disbalance of the individual patient, i.e. the individual signature, is unknown. This declassifies expensive, targeted drugs into generalized treatment. It causes therapeutic efforts for many patients to be characterized by complicated and inefficient protocols, often through a ‘one-size-fits-all' approach based on general guidelines. Drugs recommended in the guidelines may show efficacy on a group level and in randomized clinical trials, but they are often far less effective for individual patients in daily clinical practice. Similarly, individual treatment might have to be discontinued due to problematic side effects, leading to discontinuation of therapy and long-term insufficient disease control. Many patients suffer from long-term inadequate treatment before reaching the desired clinical response/outcome.
High health care costs in dermatology
‘One size-fits all’ treatment protocols with costly targeted drugs lead to very high and ever-increasing healthcare costs in dermatology. To illustrate, average medication costs for treatment with very targeted medications costs approx. € 15.000 annually per patient, and has to be used life-long to maintain disease control. Furthermore, many drugs are increasingly used off label, i.e. without direct market authorisation and without evidence, as an experiment for patients with insufficient response to other ‘on-label’ drugs. Hence, our society is challenged with an economic burden estimated to be as high as 5 billion US$ annually. Just in the Netherlands, between 2018-2020 more than 1,1 billion EUR were spent on drugs for chronic inflammatory diseases. Moreover, these costs are expected to increase due to rising incidence rates and increasing life expectancy, as no disease modifying cure is available nor foreseen in the near future.
Unexploited potential of biomarker profiles
for personalized care
The development of therapies in dermatology has been neglected for decades, resulting in the current ‘one size fits all’ nature of care. Only recently this concept is changing and the unmet needs of patients are slowly starting to be addressed by pharmaceutical and biotech companies. The focus is shifting to identifying disease biomarkers: characteristics that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. The latest developments in dermatological technologies and methodologies bring individualized, highly-effective treatment of chronic inflammatory skin diseases within reach. NGID envisions to capitalize on current advances to construct individual signatures (biomarker profiles) allowing for individual characterization of a patient’s immune disbalance and to develop targeted and truly personalised care. Our mission is to provide “the right care for the right patient, at the right time”. This whole concept is however still in its infancy and will require an array of scientific and societal breakthroughs via inter- and multidisciplinary approaches across the entire knowledge chain.
This project creates an initial knowledge base on personalised dermatological healthcare, as well as the first uptake in education. The aim is to further spread and develop this knowledge via research and education, and further integrate it into the clinical work force. The strong knowledge base and skilled work force will lead to a structural frontrunner position of The Netherlands in personalised dermatological care, particularly in advanced clinical trials for (immuno)dermatology. There will be a special focus on universities of applied sciences, their contribution to scientific challenges and subsequent integration in education. NGID strengthens the competitive advantage of Dutch and/or European-based technology and pharmaceutical companies, by providing a knowledge chain that leads to the development of new drugs, and new/adjusted medical devices for more precise dermatological diagnoses.
Six exemplary immuno-dermatological disorders:
Atopic Dermatitis | Plaque Psoriasis | Cutaneous Lupus Erythematosus | Hidradenitis Suppurativa | Chronic Spontaneous Urticaria | Mycosis fungoides
This unique set of inflammatory skin pathologies combines common and rare diseases, intrinsic and extrinsic diseases, and those with better or poorer understanding. Capturing biomarkers from these diseases will reveal several shared but also some distinct markers, identifying common or specific disease mechanisms, unlocking the potential for specific drug targeting. This key knowledge on disease mechanisms and patient profiles also allows for potential drug repositioning (use of already developed drugs for another disease). This is of particular benefit for diseases like hidradenitis suppurativa, cutaneous lupus, and mycosis fungoides, where only a limited number of drugs are available.
We have also selected these six diseases because of their high degree of feasibility for a prospective, centralized trial conduct. Since a robust fundament and existing knowledge are available in our consortium, the chosen diseases are perfectly suited for the development of the NGID-approach and highly feasible in execution. The latter cannot be emphasized enough because dermatological clinical trials are often hampered in their slow and fragmented executability or failure of patient recruitment.
Team up for better care
NGID will have a lasting impact on Dutch dermatological research in, through the new collaborations forged and the creation of the NGID-infrastructure for continued data input, analysis and expansion to other indications. Our unique consortium contains high-specialized expertise on all aspects of skin science: from beta to gamma, all across our nation. The consortium unites all relevant stakeholders, and forges novel interdisciplinary and multidisciplinary collaborations between (academic) dermatologists, technology developers, (basic) scientists, clinical trial specialists, patient and societal organizations, pharmaceutical and (bio)tech companies, to make personalised care a reality for patients with chronic inflammatory skin diseases:
- Patient associations and societal organizations
- All University Medical Centres in The Netherlands
- University laboratories (UL, UT, RU, UvA, MU, TUD) and universities of applied sciences (HSL, HAN)
- Pharmaceutical partners (Janssen, Almirall, Maruho)
- (Bio)technology companies (Scibase, CELLnTEC, Perimed, Clinical Microbiomics, Damae Medical)
- Dermatology departments of community hospitals as part of the clinical trial network (CONNECTED)
- Hospitals collaborating with registries for real-world evidence data (BioDay, TREAT, BioCAPTURE)
- Implementation specialists (guideline committees, patient associations, NVDV, NVED)
- International partners and consortia (BIOMAP, Hippocrates, ImmUniverse, A*STAR)
- General Practitioners research network (LEON)
Project structure
The aim of our project is to revolutionize dermatological care by providing an infrastructure for personalised patient care. Personalised care requires comprehensive and ultra-deep disease understanding for every individual patient. To make this possible, we will build an infrastructure containing a wealth of unique, multimodal data for six different diseases from clinical trials, and combine it with existing data (CHDR, Janssen). By linking the data to the individual patients using individual signatures, it is possible to identify disease endotypes and to predict the most suitable treatment option to achieve “the right treatment for the right patient at the right time”. To achieve our objectives we use four stepping stones: Technology, Trials, Biomarkers and Implementation. Each stepping stone consists of two work packages, that are inter-related within and between the stepping stones. After the project, the Stepping Stones-approach is used to add additional disease to the NGID-infrastructure and towards personalised care.
Technology is the backbone for our project. In WP1.1 the secure Data infrastructure is built that contains all the patient-derived data generated in this project. The data is stored in machine-readable, interoperable formats for easy and FAIR use in other stepping stones. WP1.2 Modular (omics)platforms focusses on the technologies used to obtain high-resolution skin data. We will use an unprecedented number of state-of-the art techniques at a very large scale, many of which will need to be further developed and fine-tuned for use within dermatological trials and daily practice. The WP also develops harmonized workflows (analysis pipeline) per technology and skin disease, that guarantee high data quality and usability. During the project the infrastructure and the platforms are continuously improved using feedback loops from the other stepping stones, resulting in build-test-learn cycles.