- Tuesday, October 25, 2022
- PETER VAN DE KERKHOF
- Expert Insights, Treatment
Chief Medical Officer, International Psoriasis Council
Amsterdam, Netherlands
TERMS TO KNOW
- Personalized care uses a patient’s genetic profile and individual needs and experiences to inform decisions about prevention, diagnosis, and treatment.
- Personalized medicine and precision medicine are often used interchangeably with “personalized care.”
THE 101
- The biggest advancements in personalized care have been in oncology, but increasingly more specialties — including dermatology — are moving toward personalized care.
- Personalized care is still a work in progress. When it comes to psoriasis, we’re just scratching the surface.
TIMELINE OF KEY ACHIEVEMENTS
1901: Karl Landsteiner at the University of Vienna in Vienna, Austria discovers the ABO blood system to improve outcomes of blood transfusions — one of the earliest examples of personalized care.
1956: Researchers discover an association between antimalarial drugs and G6PD deficiency. This becomes one of the first known instances of applying the principles of personalized care in practice, and it propels the movement toward a future of personalized care.
1969: The CYP2D6 enzyme, which is involved in the metabolism of antidepressants and antipsychotic medications, is discovered. This discovery is among the first examples of how a personalized approach can alter treatment.
1990: The Human Genome Project is launched. Researchers from the US, the UK, France, Germany, Japan, and China collaborate to create a complete map of the human genome, map and sequence genomes of other organisms that are critical to studying biology, and develop DNA analyzing technology.
1999: The term “personalized medicine” is first used in publications.
2003: The Human Genome Project culminates with a complete sequencing of the human genome, furthering our understanding of interactions of the DNA sequence, metabolome, proteome, epigenome, transcriptome, and epigenome.
2021-2022: Researchers across the globe study the relationship between individual biomarkers and COVID-19 outcomes.
RECENT RESEARCH
Dand N, Mahil SK, Capon F, Smith CH, Simpson MA, Barker JN. Psoriasis and Genetics. Acta Derm Venereol. 2020 Jan 30;100(3):adv00030. doi: 10.2340/00015555-3384. PMID: 31971603.
Gunter NV, Yap BJM, Chua CLL, Yap WH. Combining Understanding of Immunological Mechanisms and Genetic Variants Toward Development of Personalized Medicine for Psoriasis Patients. Front Genet. 2019 May 3;10:395. doi: 10.3389/fgene.2019.00395. PMID: 31130981; PMCID: PMC6509197.
van de Kerkhof PC. Psoriasis in the perspective of predictive, preventive participatory and personalized medicine. J Dermatolog Treat. 2018 Mar;29(2):107-108. doi: 10.1080/09546634.2018.1437739. PMID: 29457561.
Yan D, Gudjonsson JE, Le S, Maverakis E, Plazyo O, Ritchlin C, Scher JU, Singh R, Ward NL, Bell S, Liao W. New Frontiers in Psoriatic Disease Research, Part I: Genetics, Environmental Triggers, Immunology, Pathophysiology, and Precision Medicine. J Invest Dermatol. 2021 Sep;141(9):2112-2122.e3. doi: 10.1016/j.jid.2021.02.764. Epub 2021 Jul 22. PMID: 34303522; PMCID: PMC8384663.
Personalized care has become increasingly utilized in the past two few decades, evolving as we have gained a greater understanding of the human genome and recognized the importance of shifting away from a “one size fits all” approach to medicine.
Peter van de Kerkhof, MD, PhD, Chief Medical Officer at the International Psoriasis Council, is an avid proponent of further adopting personalized care for psoriasis treatment. He is here to share his thoughts on the current use of personalized medicine in psoriasis and his hopes for the future.
How is personalized care a move away from traditional evidence-based medicine?
Currently, the medical community tends to think of medicine through the lens of outcomes of randomized, controlled, double-blind trials. We create an average patient with the results, and we consider the average patient to be representative of all individual patients.
But in practice, we know this isn’t true. There is enormous variability in people with psoriasis, such as the phenotype, extent, location, course of the illness, severity, or comorbidities. There are populations that cannot be considered “average”, such as children or the elderly, because they are underrepresented in trials.
Then, there are the psychosocial factors and a person’s quality of life. Those essential factors are often overlooked.
This doesn’t mean we should abandon randomized control trials. It provides a gross estimate of the average response. But we need to prioritize more real-world studies.
What makes personalized care so well-suited for patients with psoriasis?
It is in the heterogeneous nature of the disease. Everyone has their own psoriasis, unique to them.
In the modern stepwise approach, many countries do not prioritize patients for active treatment if they have a Psoriasis Area and Severity Index (PASI) below 10. However, we know from experience that PASI alone may not always be enough. We must consider other aspects of the psoriasis phenotype, the comorbidities, and patients’ quality of life, as well. Personalized care recognizes that.
Think about the director of an IT company who works 80 hours a week, but can’t sleep because her psoriasis is itchy. Or a patient who is the victim of stigma and, while we are starting with small steps that yield minor or no improvement, he is struggling mentally and socially.
Why should we put these patients through a step-by-step approach when they desperately need a fast and substantial improvement in their psoriasis — permitting them to cover all of their responsibilities in life — when we know that they could have better results with the most effective drug?
Additionally, personalized care considers comorbidities and lifestyle, like travel to certain environments, which can impact the drug that a patient should be prescribed. For instance, a patient who is traveling to an area with high rates of tuberculosis, should not be prescribed a tumor necrosis factor (TNF)-alpha inhibitor (anti-TNF-alphas), as these medications may increase the risk of developing active tuberculosis.
Gathering this quality of life data is critical. It allows us to increase shared decision-making with patients, finding them the treatments that best suit their personal needs.
Personalized care utilizes registries of patient data. Some critics argue that registries may not contain enough data about minority populations, which could exacerbate existing health disparities. What is your take on that?
This is a valid concern. We do not want to risk having data repositories that only represent certain sects of the population.
But when we are intentional about focusing on psychosocial factors and a patient’s socioeconomic conditions, we may be able to avoid widening gaps in health outcomes.
Consider a single mother who has psoriasis and is living below the poverty line. As someone who is already part of two populations that are known to experience health disparities (being a single mother and living in poverty), and as the sole provider for her children, she cannot afford to let her psoriasis stand in the way of employment. She is a prime example of someone who should be prioritized for starting with active treatments.
What is the role of computational medicine in personalized care?
We can create a cloud of data containing the genome, transcriptome, proteome, and microbiome, as well as a person’s medical history and lifestyle information. This data can then provide answers to questions concerning a patient’s likelihood of developing severe symptoms or comorbidities, which treatments they may respond well to, if they require active and early intervention, or where are in respect to the course of the disease.
Leroy Hood, the co-founder of the Institute for Systems Biology (ISB), is a pioneer in the world of personalized medicine, and he explains this very well: With the correct data, we can potentially create a therapy that targets disease before it even manifests itself as a detectable phenotype. If you’re interested in learning more about personalized medicine, I would recommend looking at his work and the work being done in the Hood-Price Lab for Systems Biomedicine.
How have the data from the registries provided insight into biomarkers and treatment so far?
The actual insight in biomarkers is increasing, although the value in clinical practice is still limited. But there has been promise.
There is evidence that the HLA-C*06 allele indicates an increased chance for treatment responsiveness to methotrexate and ustekinumab. The impact of HLA-C*06 is slight, but it is there and it is significant.
Biomarkers may also be of great help in the future to identify those patients who benefit most from early active intervention.
In addition, we can also look at how we dose medications, since there is such great variability in pharmacokinetics. For example, it has been shown that we often dose TNF-alpha inhibitors too high or too low. When we give a patient adalimumab, it is imperative to measure drug levels in their blood in the first three months of treatment. In addition to ensuring that the patient is getting the optimal therapeutic dose, monitoring levels may show that we can decrease the amount and make treatment more cost-effective.
“Providers need to diversify. On one hand, he should be in the position to prescribe his patient a highly effective but expensive treatment right from the beginning. And in other patients, where there is much less urgency, he may give a more traditional, less expensive treatment. In this way, the providers reserve the expensive treatments for the patient with high need and do not posteriorize the highly effective as last resort, so late that they may generate little efficacy anymore.”
— Peter van de Kerkhof, MD, PhD, Chief Medical Officer at the International Psoriasis Council
Personalized care sounds like a very effective approach, so what is holding some providers back from using it?
Often, it comes down to cost. Healthcare systems, payors — they want providers to go with the least expensive option first. But that might end up becoming more expensive in the long run, when we consider sustainable disease modification versus life long maintenance with expensive medications.
It’s actually a wiser financial investment to go with what’s most effective for an individual patient right from the beginning. There’s a business case for it, but organizations have to learn to prioritize this approach.
What is your hope for the future of personalized care in psoriasis?
For the patient of today: Let us get personalized. For each individual patient, let’s find the best solution.
For the patient of tomorrow: Targeted treatments. It’s highly likely that we will glean more data from biomarkers and be able to translate that data into practice, like we use glucose level as a biomarker for diabetes. That’s my dream for psoriasis — that we find biomarkers and can use them the way we do for diabetes.
