A patient's report from the 2019 Cure Symposium

| Richard Seiden J.D.
I had the privilege of attending the 2019 Cure Symposium in Seattle, organized by the National Psoriasis Foundation and co-chaired by Wilson Liao, M.D., and Johann Gudjonsson, M.D., Ph.D.
 
 
First, a few general observations about the symposium:
  • Patients with psoriatic disease are incredibly fortunate to have such extremely passionate (intelligent and articulate) researchers, dermatologists and rheumatologists working on our behalf.
  • There is a remarkable level of coordination, collaboration, mutual awareness and information sharing among the scientists who spoke at and attended the event.
  • A notable number of the speakers acknowledged how NPF had supported their research, by funding, collaboration, resources or from the National Psoriasis Victor Henschel Biobank samples.
Here are my notes as a patient of various speakers at the symposium:
 
1. Alexis Ogdie, M.D. (University of Pennsylvania) – prevention of psoriatic arthritis. Ogden noted the significant advances in therapy for psoriasis and psoriatic arthritis (PsA), commenting on achievable metrics from the 1990s to the present. She noted the heterogeneity (differing symptoms and severity) of the diseases among patients. 
 
2. Nehal Mehta, M.D. (U.S. National Institutes of Health) – prevention of psoriasis comorbidities. Mehta has focused on the cardiovascular complications for psoriasis patients, principally inflammation of the arteries around the heart. Fortunately for patients, he has confirmed that treatment of psoriasis with anti-inflammatory biologic drugs such as tumor necrosis factor inhibitors (Enbrel, Humira, etc.) and even interleukin 17 drugs (Cosentyx and Taltz) tends to modulate the impacts in and around the heart. He commented that it is important for patients to monitor blood pressure and body mass index to attempt to control comorbidities (concurrent conditions) for psoriasis.
 
3. Christopher Ritchlin, M.D. (University of Rochester) – heterogeneity and outcome prediction in psoriatic arthritis. Ritchlin noted the expanded toolbox that rheumatologists now have to treat PsA. Early indications of the disease can appear in skin, nails and bone marrow. He mentioned a comprehensive article that he wrote for the New England Journal of Medicine. Unfortunately, PsA includes multiple disease domains and variable and diverse impacts. 
 
4. Matthew Patrick, Ph.D. (University of Michigan) – psoriasis and type 2 diabetes. There is a small but significant causal effect between these two disease states. Maintaining a healthy body mass index is recommended.
 
5. The keynote speaker, Rachael Clark, M.D., Ph.D. (Brigham and Women’s Hospital) – immunological insights into psoriasis. Clark noted that T-cell mediation was achieved by cyclosporine (a short-term, systemic therapy). She commented that psoriatic disease involves a “uniquely stubborn T-cell” in a uniquely human disease. She discussed the phenomenon of “tissue resident memory T-cells” (TRMs), noting that current therapies only suppress activation of these T-cells; this is best evidenced by the fact that when a therapy is discontinued, there is a recurrence of the disease, typically with lesions at the prior sites of presentation. Of the current available drug therapies, IL-23 is the most effective. Researchers are trying to develop methods of depleting TRMs; one proposed solution is blocking fatty acids. Another treatment has been explored – “photo-bombing” affected areas, where there has been 80 percent depletion of TRMs in mice studies.
 
6. Christopher Griffiths, M.D., OBE (University of Manchester, United Kingdom) – heterogeneity and outcome prediction in psoriasis. Griffiths noted that medical practice was currently reactive, but it needed to be proactive; his key words were “predict, prevent, personalize and participate”. While he praised the drugs that treated the “inflammatory loop” (IL-17 and IL-23), he looked forward to the further development of oral small molecule treatments. He pointed to the BADBIR long-term safety registry in the UK and Ireland. He also mentioned that HLA Cw6+ (a viable DNA segment on a chromosome or allele), which is long known to be evidence of psoriasis, is a predictor of success with biologics. As did other speakers, Griffiths called for early diagnosis and early intervention as the best way to treat psoriatic disease.
 
7. Jose Scher, M.D. (NYU Langone Medical Center) – microbial contributors to psoriatic disease. One focus of Scher’s research has been microbes (a bacteria causing disease) in the gut. Microbes are there to promote the body’s immunity, and there is a core psoriasis gut microbiome (microorganisms). Scher is working on building a predictive model for PsA in high-risk psoriatic populations. He mentioned “Psorcast” – a digital, open-source, smartphone-based platform, an app to track elements of the symptoms and treatment of PsA.
 
8. Christopher Ritchlin, M.D., MPH – heterogeneity and outcome prediction in psoriatic arthritis. Ritchlin thinks that PsA may be seven diseases in one. The heterogeneity among patients challenges efforts to consistently treat to target. Combination therapies have helped to target divergent molecular pathologies. The synovial (lining of the joints) inflammation is different in PsA than rheumatoid arthritis, which may explain why the treatments and their effectiveness are different for the two forms of arthritis.
 
9. Vinod Chandran, M.D., Ph.D. (University of Toronto) – biomarker discovery in psoriatic arthritis. Biomarkers need to be objectively measured and evaluated. This is challenging due to the heterogeneity of PsA as a disease. Medical prediction leads to inferences about the present or future state of the disease, and predictions need to be time denominated. So far, the anatomical indicators are skin psoriasis, scalp psoriasis, uveitis (eye), joint counts and damage. One biomarker may be via a synovial biopsy.
 
10. Junko Takeshita, M.D., Ph.D. (University of Pennsylvania) – cancer screening. Since there is a theoretical concern about the risk of T-cell lymphoma in severe psoriasis patients, guidelines recommend cancer screening for patients with psoriasis. Such patients need to take flu vaccinations every year.
 
11. Jeremy Sokolove (representing AbbVie at the time of the symposium) – insights from industry. Only a limited number of providers are prescribing systemic therapies (less than 20 percent), and most do not follow the NPF Treat to Target recommendations. 
 
12. Philip Mease, M.D. (University of Washington) – clinical trials and cure. We need to review outcomes measures in PsA clinical trials. He defined “remission” as a dilution of seriousness of pain, a “temporary recovery.” This can be determined by clinical, imaging and immunologic testing. “Clinical remission” is minimal disease activity or low disease activity. “DAPSA” (or disease activity in PsA) is a joint-centric measure of PsA. Metrics of psoriasis severity can include ultrasound synovitis measurement, enthesitis (inflammation of the area where the tendon or ligament insert into the bone), and we need more molecular imaging. Central sensitization (e.g., fibromyalgia) occurs in 18 percent of the PsA population. There may well be an expansion of combination therapies to mitigate the disease.
 
13. Breakout session on cure/prevention definitions. One of the most interesting sessions was a small group discussion of cure versus remission. It appeared to me that the participating dermatologists were more optimistic about the potential for a cure for psoriasis than the rheumatologists were as to a cure for PsA. Partly, this reflects the fact that skin subject to psoriatic lesions typically bounces back to normal appearance if treated effectively (e.g., no scarring), while a joint may suffer irreparable damage unless it is treated at a very early stage of disease development within months of diagnosis. Nonetheless, drugs that could trigger a long-term remission of psoriasis or PsA would be a major positive development.
 
14. Several attendees cited comments made by Rachael Clarke, M.D. (see above) regarding TRMs to note that perhaps a cure is elusive but long-term remission should be possible. 
 
Fifty percent of patients are unsatisfied with their treatments. Moderate-to-severe psoriasis patients should be on systemic therapies (topical treatments and phototherapy may not be sufficient to mitigate the disease). Current and future treatments have the potential to change the life trajectory of psoriasis and PsA patients. Identifying patient subgroups is the only reliable way to target patient response. Define the gut as a central target in spondylitis arthritis (spine). Researchers must convince the pharmaceutical industry that their proposal warrants their attention and is capable of being commercialized. Everyone is working to advance drug efficacy and safety.
 
Defining the cure – it is too ambitious without improvements in infrastructure. However, bone marrow transplant patients have been cured of psoriasis. Is remission on therapy or off therapy? A biological definition of cure is difficult if there is a genetic predisposition (and TRMs).
 
There was general agreement that a diagnostic tool for PsA is absolutely necessary to ensure that an early PsA diagnosis followed by early effective intervention (e.g., use of a biologic drug ideally within six months of diagnosis, as per the recently adopted American College of Rheumatology treatment guidelines developed in collaboration with NPF).
 
Rheumatologists have shifted the discussion to prevention of psoriasis. (This is also a focus of upcoming NPF research grants.)
 
15. Breakout session on clinical and scientific gaps in knowledge and how to address. It is not yet clear as to whether psoriasis is one disease or a spectrum of multiple diseases There are clinical subsets of psoriasis. This reflects the clinical heterogeneity of psoriatic disease, and the heterogeneity of treatment responses. 
 
This presents an opportunity to prevent the onset of psoriasis, but what should be studied? Are there biomarkers in the skin, bones or joints? Are the skin biomarkers in the lesions or under the skin? When focusing on immunology, what is the impact of TRMs? What about overlapping diseases such as ankylosing spondylitis (spine), Crohn's, or diabetes? Are there common pathways? What are the models for treatment? What is the burden of disease? There is no U.S. study of the prevalence of psoriasis. That may be important for drug development.
 
How to address the gaps? Each of the following will be relevant - NIH, NPF, patients and clinicians, partnerships with pharmaceutical industry. There needs to be development of study cohorts, real-life stories over time. We need to collaborate on data gathering, and to harmonize and standardize data collection.
 
16. Breakout session on cure working groups and cure organizational road map. Dermatologists are leading the way on immunology and clinical trials. There is a demonstrated need for longitudinal (long-term) studies of psoriasis and PsA patients. Blood samples and microbiome samples should be collected and analyzed. We must study the idea of disease prevention for psoriasis and inhibiting the development of PsA. We need a better understanding of the heterogeneity of psoriasis and PsA.
 
In terms of a cure, we need to continue to explore combination therapies, the elimination of TRMs (since their suppression is not a cure). This may require a transformative way of looking at the disease state.
 
This will require significant funding. NPF can provide the spark, and it can galvanize resources. NPF will use multi-institutional grants to foster greater cooperation and collaboration and data sharing. NPF and the research community will seek further grants from NIH and other funding sources.
 
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Photo: Rick Seiden (right) at the Cure Symposium.

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