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Advancing Knowledge. Enhancing Care.

Psoriasis News

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The International Psoriasis Council (IPC) Think Tank brings together member experts in dermatology to deliberate on the issues that contribute to the widespread undertreatment of tens of millions of people with psoriasis worldwide.

Held in Lisbon, Portugal in early December, the 2019 IPC Think Tank convened 60 specialists in psoriasis from all over the world to discuss the most pressing issues affecting psoriasis care and treatment globally. The outcome of these discussions will inform IPC initiatives in 2020 and beyond.

Presentations and discussions for the 2019 Think Thank centered on three broad areas of activity identified by the World Health Organization and captured in the IPC 2020 Strategic Plan as critical to improve the lives of people with psoriasis. These include increasing access to care; educating health care providers to better understand and treat the disease; and conducting additional research into psoriasis and its comorbidities. 

Increasing Access to Care

Despite the number of safe and effective therapies available, a large number of people with psoriasis remain undertreated or not treated at all. IPC is working to understand and address this unnecessary epidemic of uncontrolled psoriasis. The following 2019 Think Tank presentations helped illuminate the depth of the issue and stimulated conversation on the role of the global IPC network in addressing this complicated issue.

Assessing severity and outcomes

Matthias Augustin, MD, Germany

Defining psoriasis severity in a representative and comprehensive manner is a decades-old conundrum. Assessing severity as mild, moderate or severe as determined by BSA, drives many access to care decisions by clinicians, private health insurers, industry and government. However, assessing severity by BSA only has many drawbacks. To begin, the definition of moderate BSA is too broad. There are shortcomings to the current assessment tools. For example, PASI scores do not correlate with DLQI scores and may not reflect true disease burden on an individual.

Though it appears to be small change, redefining severity has the potential to make a huge impact on psoriasis care and treatment. When redefining severity, we must consider the answers to these questions:

  • Is severity, not as an endpoint but as a predictor of treatment impact, all we need to know?
  • Using the value-based health care model, how do we incorporate patient-reported outcomes to assess what is meaningful to patients with regards to disease management?
  • What long-term considerations must we include when redefining severity?

The IPC reclassification of severity project is a good starting point. The next phase of the project must include patients. Additionally, the WHO International Classification of Functioning may provide a good model for further refinement of the IPC severity definition.

Redefining severity is one thing; doing something with the new definition is another. We need better clinical tools to provide individualized care to psoriasis patients in the current health care climate.

Challenges to introducing biologics to the developing world

Mahira Hamidy El Sayed, MSc., MD, Egypt

Egypt lags behind in psoriasis care and treatment due to socio-economic and political factors. As a result, Egyptians with moderate to severe psoriasis are undertreated and have significant disease burden.

Dermatologists are limited in the range care they can provide to their psoriasis patients. Biologic use is not widespread in Egypt due in part to the reticence of dermatologists to prescribe these medications and lack of consensus on use. The most available biologic is adalimumab, but the government restricts its use to 6 months in total. However, positive steps have been taken towards state sponsoring of biologics. Egypt has the highest prevalence of hepatitis C in the world, which also hinders physicians' ability to prescribe anti-TNFs. (This may be changing as the unprecedented Egyptian campaign to detect and treat HCV in a bid to eliminate the disease by 2022 has started and so far, more than 6 million people have received treatment). Due to undertreatment with biologics, many co-morbidities are observed among psoriasis patients in Egypt including severe psoriatic arthritis.

Social and cultural barriers also contribute to the number of undertreated psoriasis patients in Egypt. People with psoriasis face social stigma that prevent some from seeking treatment for fear of judgement. Gender rules also play a part as female psoriasis patients want to be treated by female dermatologists due to religious beliefs and social expectations. Additionally, some patients reject biologics as a treatment because they fear the drug will cause cancer.

There are several actions that will address access to care issues in for Egyptians with psoriasis. These include implementing a national strategy involving both physicians and patients to raise awareness of early diagnosis and treatment of psoriasis; educating dermatologists in Egypt on optimal psoriasis care; conducting needed research in Egypt, with Egyptians, focusing on comorbidities; and publishing regional guidelines and treatment protocols for Middle East/Northern Africa to encourage governments to recognize psoriasis as a disabling disease and worthy of allocation of more resources.

IPC disease severity project

Bruce Strober, United States

Using a Delphi exercise, IPC developed a consensus statement on the classification of psoriasis severity that could be used for both clinical use and in clinical trials and addresses the real-world use of systemic medications.

The process included 70 statements subjected to three rounds of voting. The statement that  received the highest score endorsed a simple and practical approach to assessing psoriasis severity.

In summary, the consensus statement separates patients for topical therapy versus patients for systemic therapy as measured by one of three criteria. Patients are eligible for systemic therapy if the patient has failed a topical therapy; and/or patient has a BSA >10; and/or patient has psoriasis lesions on sensitive areas such as hands/feet, nails, scalp, genitals or face.

Conclusions

People with psoriasis everywhere face common barriers to care. Perhaps most pressing,  inability to access the right treatment to control disease symptoms. This is particularly true in underserved regions such as Northern Africa where the availability of biologics and the clinical knowledge to prescribe them is rather limited.

These presentations underscore the importance of IPC's work to address barriers to psoriasis care in underserved areas by educating health care providers in early diagnosis and appropriate treatment; recategorizing disease severity for clinical practice and beyond; and researching the scope and scale of access barriers by conducting a world-wide inventory of epidemiology of psoriasis and availability of treatments in partnership with the GPA.

Expanding Psoriasis Research

Although there is a considerable body of psoriasis research published over the past 20 years, many questions remain insufficiently answered. Additional research is needed into the etiology, pathogenesis and epidemiology of psoriasis along with study of comorbid conditions and additional external factors that present barriers to care. A deeper understanding of this disease will allow physicians to personalize therapy to the individual patient, leading to better disease control and improved health.

Biologic drug survivability

Lone Skov, MD, PhD, Denmark

The efficacy of biologics in the real world is often shown as drug survivability, which measures length of treatment until the discontinuation of a drug and depends on effectiveness, side effects and safety.

Clinical trial results for recently introduced biologic therapies, in particular the new IL17 and IL23 inhibitors, demonstrate high efficacy short term. However, there is no long-term efficacy or drug survival data for these new biologics. In general, clinical trial findings on efficacy are not representative of patients’ experience in the real world.

To determine the predictors of drug survival in the real world for anti-TNFs, Dr. Skov analyzed patient registry data and journal publications on the subject. Her findings suggested the major predictors of drug survival for these therapies were:

  • Time: Overall, biologics in the real world have good overall survivability but efficacy decreases over time
  • Efficacy: Loss of response is the main reason for discontinuation of anti-TNF biologics
  • Epidemiological: Common predictors for discontinuation include high BMI, previous exposure to biologics and female sex
  • Side effects: Females discontinue treatment more often due to side effects than males

These findings demonstrate that more data on drug survival for the newer biologic drugs is needed to assess long-term efficacy in the real world. However, drug survival data should be interpreted with caution because sometimes it is incomplete.

Therapeutic drug monitoring and personalized dosing of biologics

Catherine Smith, MD, England

Therapeutic drug monitoring (TDM) in psoriasis considers the relationship between dose given, drug exposure (serum profile) and outcome (psoriasis clearance). The right dosage for the desired outcome helps to minimize harm, maximize benefits and potentially save on drug costs.

Though not widely practiced in dermatology, therapeutic drug monitoring is an effective tool for individualizing dosage to a patient’s situation. Individualized dosing addresses some of the current issues with standard treatment with biologics especially dose escalation, which is not always effective. Double the dose does not necessarily mean double the amount of drug circulating and equally important, may be associated with increased risk of infection as has been shown in rheumatoid arthritis.

The principal requirements for TDM are:

  • Association between drug exposure and outcome of interest
  • A target serum concentration
  • An assay
  • Ability to alter the dose
  • Proven clinical utility

Evidence suggests that TDM of patients on adalimumab, especially non-responders, can improve outcomes and may reduce costs.  The current approaches to TDM for adalimumab rely on dosing to a target serum drug levels  and may be ‘reactive’ (i.e.in non-responders or when losing response) or proactive (dosing to target during induction and/or maintenance).

Pharmacometric modeling and incorporation of findings into Bayesian-type ‘dashboard’ systems offers opportunity to bring TDM and individualized dosing into practice for all biologics. However, this will require collaboration with industry  for access to PKPD data to develop the models, and with diagnostic laboratories to develop the appropriate tests. 

Are obesity and psoriasis linked? How to assess causality

Sara Brown, MD, Scotland

Obesity and psoriasis are associated, but epidemiological studies to date have not been able to assess whether one causes the other. Understanding the direction of the effect, if psoriasis risk increases with obesity or vice versa, is important and may provide therapeutic opportunities

Mendelian randomization (MR) is a useful tool to investigate causation between psoriasis and obesity. MR is a method of statistical analysis that uses a genetic definition of disease or phenotype, rather than measuring the phenotype directly. It tests the causal effect of genetic risk, not the disease itself, so findings represent a lifetime effect rather than an intervention. MR can minimize confounding factors and reverse causation, which are limitations in observational epidemiology

MR studies in large European and smaller Japanese population cohorts have shown that there is a causal effect of BMI on psoriasis risk but there is no evidence that psoriasis causes an increase in BMI. In particular, the studies revealed:

  • Genetic risk for higher BMI leads to higher risk of psoriasis
  • Psoriasis risk increases 9% per 1 unit increase in BMI
  • Psoriasis risk increases 53% with 5 units higher BMI
  • There was no evidence that psoriasis leads to a higher BMI so there is no rationale for using biologics to aid weight loss

Using Mendelian randomization to identify causation, future studies could focus on pathways, intermediate psoriasis phenotypes and effects on disease of gene expression, methylation, etc. 

Immune mechanisms in pustular forms of psoriasis

Johan Gudjonsson, MD, PhD, United States

Psoriasis and psoriasis subtypes represent a variable contribution of adaptive and innate immune responses. Adaptive immune responses (IL-17/IFN-g) dominate in plaque psoriasis while innate responses (IL-1/IL-36) dominate in generalized pustular psoriasis (GPP).

Pustular psoriasis represents 1-2% of total psoriasis cases. It is difficult to treat with existing therapeutics. The real-world instance of pustular psoriasis is higher in females, though the biology behind this disease bias is unclear.

Gene mutations associated with pustular psoriasis are IL36RN, CARD14 and AP1S3.

IL-36 appears to be the predominate driver of autoinflammatory response in psoriasis, especially in pustular psoriasis. The IL-36 inflammatory axis, is activated and amplified by neutrophils, which are the predominant cell type in pustular psoriasis, and IL-36 represent a novel therapeutic target in psoriatic disease. 

Hunting the elusive psoriasis antigen

Jorge Prinz, MD, Germany

HLA-class I molecules present peptide antigens from cytoplasmic proteins to CD8+ T cells. Therefore, an HLA-class I-restricted immune response is directed primarily against target cells expressing these proteins.

HLA-C*06:02 is the main risk allele for psoriasis. In HLA-C*06:02 carriers, variants of the endoplasmic reticulum aminopeptidase 1 (ERAP1), control psoriasis risk by gene-gene interaction with the HLA-C*06:02 allele.

Psoriasis lesions develop upon recruitment, activation and clonal expansion of CD8+ T cells in the epidermis. In psoriasis, HLA-C*06:02 mediates CD8+ T-cell mediated autoimmune response against melanocytes in the epidermis through autoantigen presentation. The immune response against melanocytes determines why psoriasis is primarily a skin disease.

As identified by a pathogenic psoriatic T-cell receptor, a peptide from ADAMTS-like protein 5 is a melanocyte autoantigen in psoriasis. Generation of this peptide antigen from the parent protein involves the aminopeptidase activity of ERAP1. This way, ERAP1 variants control the immunogenic potential of melanocytes and determine the risk to develop psoriasis in interaction with HLA-C*06:02.

Global Psoriasis Atlas

Christopher EM Griffiths, OBE, MD, FRCP FMedSci and Darren Ashcroft, BPharm, MSc, PhD, FRPharmS, England

The Global Psoriasis Atlas (GPA) is a long-term, iterative project to inform the worldwide epidemiology of psoriasis. In 2019, GPA researchers completed the largest systematic review on the incidence and prevalence of psoriasis; this underpins all GPA data. A second systematic review of epidemiological studies on the risk of developing or dying from cancer among people with psoriasis was completed and published in JAMA Dermatology. Also in 2019, GPA researchers published new study in the JEADV on longitudinal trends in the incidence and prevalence of psoriasis in Israel and conducted an eDelphi survey to establish consensus on clinical examination-based diagnostic criteria for chronic plaque psoriasis in adults.  Lastly, GPA staff conducted field work in Tanzania to gather information on psoriasis prevalence and on the ability of psoriasis patients to access timely and appropriate healthcare.

In 2020, the GPA project will publish a study on the incidence of psoriasis in Chile and launch a new study examining the epidemiology of psoriasis and psoriatic arthritis in Taiwan.

Conclusions

In a disease as heterogeneous as psoriasis with a plethora of treatment options, it is IPC's major task to develop individualized treatment selection for the patient of today and tomorrow. These presentations provide pieces of the information clinicians need to personalize care and achieve patient/provider treatment goals long-term.

Long-term effective and safe control is reflected in long drug survival. Common predictors for discontinuation include high BMI, previous exposure to biologics and female sex. From Mendelian randomization studies it was concluded that genetic risk for higher BMI leads to higher risk of psoriasis and not the reverse. Such implies that there is no rationale for using biologics to aid weight loss. Further evidence is accumulating that low-calorie diets may improve psoriasis.

Personalizing the dosage of biologics by therapeutic drug monitoring is improving cost effective dosage management of biologics. Insights in genetics and immunology will develop biomarkers  which help is treatment management in individual patients. Such as the IL-36 inflammatory axis representing a novel therapeutic target for pustular psoriasis. GPP is a neutrophil dominant disease, which potentially contributes to the activation and amplification of IL-36. New treatments targeting IL-36 are in development. Research on the pathogenesis  of psoriasis may reveal new treatment targets. The question was addressed whether ERAP1 variants controls the immunogenic potential of melanocytes and determine the risk to develop psoriasis in interaction with HLA-C*06:02.

Educating Health Care Providers

Important to furthering the understanding of psoriasis among physicians is the opportunity to participate in an exchange of ideas among colleagues. The 2019 Think Tank hosted a free communications session featuring research snapshots from IPC experts.   

Registries

Marcus Schmitt-Egenolf, MD, PhD, Sweden

Registries are the best tool to collect real-world data. As an example of the utility of real world evidence, data from physician-managed registries can help document undertreatment,

Biosimilars/Anti-TNF

Arnon Cohen, MD, MPH, PhD, Israel

Potential future price reductions in biologics will mandate a paradigm change in treatment. As biosimilars become first-line treatment in regions such as Europe, we must consider updates to the treatment algorithm that include such outcomes as maximized personal care, cost savings, increased efficacy and decreased side effects.

Gut-skin access

Jo Lambert, MD, Belgium

Gut and skin appear to be linked in psoriasis. Dr. Lambert's research will explore whether modified intermittent fasting can improve psoriasis and the gut biome, setting the stage for a better understanding gut-skin axis in psoriasis.

Biomarkers

Min Zheng, China

In studying novel biomarkers for psoriasis in Chinese patients, Dr. Zheng's research concludes that there is some relationship between these biomarkers and disease severity.

Relationship between the skin and the central nervous system

Fernando Valenzuela, MD, Chile and Cesar Gonzales, MD, Columbia

Some investigations have demonstrated neurotransmitters have a role in the development of numerous skin conditions, including psoriasis. As a proof of concept, Drs. Valenzuela and Gonzales treated 8 patients with stable and recalcitrant plaques with botulinum toxin.

At week 4, all patients showed a 50% or more improvement in plaques treated with botulinum toxin.

Mark your calendars – the 2020 IPC Think Tank is scheduled for December 9, in London, England.

UPCOMING EVENT

Hot topics and challenging cases in psoriasis: A focus on biologics

Thursday, March 19, 2020
2:00 – 5:00 pm
Denver, colorado
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