Co-Chairs: Valerie M. Harvey, M.D., MPH, Victoria Barbosa M.D., MPH, MBA, Ginette A. Okoye, M.D.
The Dismantling Racism panel was very interesting in that it highlighted the importance of representation in the field of dermatology. Many of the speakers talked about the loneliness they felt as residents and medical students as they were often the only person of color in their program.
AAD President-elect, Dr. Susan Taylor’s talk was incredibly inspirational. To come from West Philadelphia to graduating from UPenn and then Harvard, starting the first Skin of Color clinic, and then becoming not only AAD President but the first person of African American Descent to be AAD President is simply a remarkable achievement.
Journal of the American Academy of Dermatology (JAAD) Game Changers
Presenter: Richard Langley, M.D.
The purpose of this Game Changer session was to vote on the publication in JAAD that had the biggest effect on dermatologic practice. This year’s Game Changer was determined to be a research article by previous NPF Medical Board member, Dr. Richard Langley. Dr. Langley’s study evaluated the impact of systemic treatment on mortality risk in patients enrolled in the Psoriasis Longitudinal Assessment and Registry (PsOLAR). This study found that biologic therapy was associated with a reduced mortality risk in patients with psoriasis.
JAAD Game Changers
Presenter: Clinton Enos, M.D.
This presentation focused on Dr. Enos’s NPF-supported work using data from the CorEvitas registry to assess possible associations of comorbid obesity, type 2 diabetes, hypertension, and high cholesterol with response to biologic treatments at 6 months.
This is a companion study to additional work exploring the effect of comorbidities on treatment outcomes. This study found that individuals on TNF- inhibitors and IL-17 inhibitors with obesity or a history of diabetes were less likely to achieve PASI 75 or PASI 90 compared to individuals on IL-12/23 inhibitors with obesity or a history of diabetes.
JAK Inhibitors: A New Frontier in Dermatology
Presenter: April Armstrong, M.D., MPH, NPF Medical Board Chair
Dr. Armstrong covered the basic pathogenesis of psoriasis, how JAK inhibition alters the systemic inflammatory process of psoriasis, and discussed how TYK2 inhibition represents a novel way of inhibiting the Janus Kinase pathway.
TYK2/JAKs contain both an active and regulatory domain. The active domain is more similar across JAK1, JAK2, JAK3, and TYK2, but the regulatory domains are more unique. Prior JAK inhibitors have focused on the active domain, as a result. Deucravacitinib, however, focuses on the regulatory domain of TYK2 to inhibit IL-23/17 to produce high levels of treatment response (PASI 75) with minimal adverse effects. The high level of treatment response is also likely for those who have already achieved PASI 75 using another treatment. PASI 75 was maintained by 90% of those treated by deucravacitinib for up to 2 years. The different mechanism of action for deucravacitinib opens up a range of possible combination therapies to treat either treatment-resistant psoriasis or individuals with psoriasis and psoriatic arthritis (PsA) whose PsA responds better to a TNFi.
Dr. Armstrong presented an off-label case where a patient with treatment-resistant psoriasis was placed on a regimen of a biologic supplemented with deucravacitinib in order to achieve PASI 75. While deucravacitinib is the first treatment to use the TYK2 pathway, there are others in development – notably TAK-279 (NDI-034858) which is being developed by Takeda after being acquired by Nimbus Therapeutics. TAK-279 recently had positive phase 2b trial results and is moving to phase 3 trials later this year. VTX958 is a TYK2 in development by Ventyx Biosciences. VTX958 has completed phase 1 trials and is currently the focus of a phase 2 clinical trial.
With the discovery that modulating the regulatory domain of the Janus kinase pathway leads to high-efficacy treatments with low adverse effects, JAK inhibition will remain an exciting area for psoriasis and other inflammatory diseases. It is not entirely unexpected for researchers to look at the effect of modulating the regulatory domain of JAK 1, JAK 2, or JAK 3 to see if results similar to TYK2 can be realized.
Rheumatology for the Dermatologist
Presenter: Joseph F. Merola, M.D., MMSc
This session provided an overview of the role dermatologists can play in managing patients with rheumatologic conditions (e.g., PsA, spondylitis). The presentation featured the Psoriasis Epidemiology Screening Tool (PEST) as a means to screen patients with psoriasis for PsA, and the PsAID 12 as a measure of quality of life.
In particular, the presentation mentioned the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) app that provides both tools for free. In addition to screening tools and patient-reported symptoms of PsA, joint and radiographic characteristics of PsA were also presented.
Dr. Langley and Joel M. Gelfand, M.D., MSCE, debated the future of phototherapy.
Richard Warren, M.D., presented treatments for palmoplantar psoriasis and discussed the mechanism of action for spesolimab, which binds to the IL-36 receptor.
In terms of the treatment pipeline, there are several JAK inhibitors in development (especially those targeting the TYK2 pathway mentioned above. There is also a PDE4 (Orismilast) also in development.
The biggest takeaway from the session is that there are several programs to develop oral agents, including an oral IL-17 in development. This could potentially be huge as IL-17s are highly efficacious and oral treatments are preferred by patients.
Boni Elizabeth Elewski, M.D., presented on nail psoriasis. Nail psoriasis usually occurs on both hands but not always on all nails. Nail psoriasis may accompany PsA and special areas such as scalp or genital areas. Among psoriasis patients, only 5% have disease only on the nails. Nail psoriasis is characterized by nail pitting, hyperkeratosis splinter hemorrhages, crumbling nails, and other manifestations.
Mild nail psoriasis can be treated with topical steroids or topical vitamin D analogs, whereas more severe nail psoriasis can be treated with oral medications or biologics. Recent studies show that ixekizumab currently may be among the better treatment options for nail psoriasis. The JAK inhibitor tofacitinib also shows promise in treating severe nail psoriasis but more studies are needed.
Poster Session – Racial and Ethnic Differences in Prescribing Patterns for Psoriasis
Presenter: Elishama Petion, candidate for M.D.
This turned out to be an interesting study design with surprising results. This study used an online survey to assess whether Black or Hispanic patients are prescribed biologics less frequently than white patients.
The survey presented a clinical scenario presenting a patient with moderate to severe psoriasis with the race of the patient randomized. The study found that there was no statistical difference in prescribing patterns between white, Black, or Hispanic patients. However, costs and insurance were more frequently mentioned for Black and Hispanic patients. There are some limitations to the study, but it would be interesting to use its methods to look at the diagnosis of psoriasis among primary care providers or dermatologists (e.g., randomize images of different color skin with psoriasis and other skin diseases).
Poster Session – Systematic Review of Intermittent Fasting in Psoriasis and Psoriatic Arthritis
Presenter: Ashley Gray, M.D.
This poster presented data from an NPF-funded study to examine the role and impact of intermittent fasting on psoriasis. While the main study is still underway, the poster presented results from a systematic literature review (SLR) used to inform the development of the study protocol. The SLR showed that intermittent fasting might have a positive impact on psoriasis and PsA compared to losing weight alone.
GRAPPA Adjacent to AAD
The most noted observation at GRAPPA was the international panel. Panelists from Spain, Taiwan, and the United Kingdom discussed a range of topics from the perspective of treating patients with psoriasis and PsA in their respective countries. All countries have considerable step therapy and utilization management protocols that must be navigated. For Spain and the UK, all treatments have to be reviewed by an economic review panel to prove their cost-effectiveness. These panels are similar to Institute for Clinical and Economic Review (ICER). A big topic for the panel was their experience with biosimilars. In all countries, biosimilars are the preferred first-line treatment for biologic-naive patients. In Spain, none of the originator products remain in the market, indicating the complete dominance of biosimilars. This should be especially noteworthy for the U.S. as biosimilars come on the market.
So many Biologics, So Little Time: How to Pick Your Poison in an Era of Biologic Overload
Presenter: George Han, M.D., Ph.D.
Dr. Han, a member of the NPF Medical Board, gave a presentation on the status of systemic therapies for psoriasis. He began his presentation with an overview of all the available options, including phototherapy with or without topical treatments, and some of the older oral and biologic medications such as cyclosporin and etanercept.
He also presented an overview of the increase in number of new biologics including the expanding list of IL-17 and IL-23 inhibitors. He presented a clinical case where a patient’s psoriasis was not well managed with topicals but showed good response to ustekinumab. There are situations where biologics might be contraindicated or showed poor response in some patients. Studies show that IL-17A inhibitors may worsen inflammatory bowel disease (IBD), where IL-17F inhibitors have been reported to be protective of bowel inflammation.
IL-23 inhibitors, used to treat psoriasis, are also protective of bowel inflammation providing multiple options for patients with comorbidities in addition to their psoriatic disease. Because biologics may not be appropriate for all patients, new oral medications may be more appropriate. Deucravacitinib, a JAK inhibitor that targets TYK2, a component of the IL-12 and IL-23 pathways, is one such treatment.
Data showed that Deucravacitinib achieved a PASI 75 of 58.4% after 16 weeks compared to apremilast at 35.1% as the comparator. Studies were also presented showing that biologics targeting different pathways had different kinetics to PASI improvement. TNF and IL-17 inhibitors reached peak PASI improvement at 12-16 weeks whereas IL-23 inhibitors reached their peak as late as 28 weeks. Studies of head-to-head comparisons of various classes of biologics were also present.
Late Breaking Research: Session 1
Presenter: April Armstrong, M.D., MPH
Dr. Armstrong presented a late-breaking research session on a phase 2b clinical trial on a new TYK2 inhibitor, NDI-034858. The randomized, double-blind, placebo-controlled study was on patients with moderate to severe psoriasis who were randomized to receive doses of 2, 5, 15, or 30mg once daily with a primary endpoint of PASI 75 at week 12. After 12 weeks, patients achieved a PASI 75 at doses greater than 5mg, achieving a PASI 75 of 67% at the highest dose of 30mg. The safety profile was acceptable. These results indicate that additional trials in psoriasis are needed.
AAD/NPF Guidelines for the Treatment of Psoriasis
Presenter: Joel M. Gelfand, M.D., MSCE
Dr. Gelfand presented on the treatment and management of psoriasis with awareness of comorbidities. Individuals with psoriasis are at greater risk of having or developing cardiovascular disease (CVD). The strong link between psoriasis and CVD is supported by the fact that both diseases are associated with obesity and smoking as risk factors.
In addition, both share some common genetic susceptibility loci and both involve similar immunologic pathways including TNF and IL-17. Meta-analysis shows that the greater the severity of psoriasis, the greater the likelihood of developing adverse outcomes for CVD.
An evaluation of several treatments for psoriasis showed they have different effects on CVD risk. For example, apremilast had no effect on vascular inflammation, whereas ustekinumab showed improvement in aortic vascular inflammation. It is recommended that psoriasis patients be screened for CVD risk factors including hypertension, cholesterol, and HbA1c. Furthermore, care should be coordinated between dermatologists and cardiologists where appropriate based on screening results.