New treatment approved for excessive sweating!
We are excited to announce that one of the clinical studies that we and our patients participated in met its ultimate goal: approval by the Federal Drug Administration (FDA). Qbrexza cloths will be available as a prescription beginning in October 2018.
Qbrexza cloths are the first new treatment for hyperhidrosis (excessive sweating) since 2011 and are approved for use in adults and children ages 9 and above.
To learn more, visit https://sweathelp.org/sweatsolutions-newsletter/news-blog/413-finally-new-hyperhidrosis-treatment-fda-approved.html
Heart Attacks and Psoriasis
If you have psoriasis, it places you at a higher risk for having a heart attack when compared to someone who doesn't have psoriasis. The old saying from a 1970’s TV commercial, “the heartbreak of psoriasis,” is true! If you have a little bit of psoriasis, then the risk is a little bit. If you have a medium amount of psoriasis, then the risk is medium, and if you have a lot of psoriasis, your risk for a heart attack is high. Why is this the case? The amount of inflamed skin due to psoriasis that we can see with our eyes is directly correlated with the amount of inflamed tissue that occurs on the inside of the body. More specifically, inflammation from the skin spills into the bloodstream and causes the inner linings of arteries to become inflamed. This, in turn, makes the arteries more likely to become blocked, which can then lead to things like heart attacks and strokes. Emerging new evidence suggests that treatments for psoriasis, like the biologics Stelara and Cosentyx, improve the skin and are then likely to decrease the risk of heart attacks. This makes psoriasis much more than a cosmetic skin disease, and more of a general health issue, for those who suffer from it. Get your psoriasis cleared up and improve your overall health.Publications
Dupixent
In a December 2016 issue of New England Journal of Medicine, and a May 2017 issue of Lancet, two of the world’s most prominent medical journals, OMRC’s Dr. Andrew Blauvelt and colleagues reported the results of phase 3 studies using dupilumab (also known as Dupixent) for the treatment of moderate-to-severe atopic dermatitis (also known as eczema). Dupilumab was shown to be safe and highly effective for this disabling disease. Most patients had significant improvement in their itch and chronic skin disease. Eye dryness and redness was the most common side effect. Importantly, dupilumab was not associated with an increased risk of infections or cancers and did not cause any laboratory abnormalities. These studies led to the FDA approval of dupilumab/Dupixent in March of 2017. Dr. Blauvelt, a leading authority on this new drug, was a top enroller in these studies and has served as a key scientific advisor for Regeneron, the makers of dupilumab and the pharmaceutical company that sponsored these clinical studies. New dupilumab studies are now underway in children with moderate-to-severe atopic dermatitis.
Part One (.PDF)
Part Two (.PDF)
Biosimilars
Biosimilars are biologic medications that are near identical, or similar, copies of original FDA-approved biologic medications. Some people view them as "generic biologics," although technically they are not generic drugs, since generics are 100% identical to original medications. In this article published in the magazine Dermatology World, the current state of biosimilars is discussed, especially as it relates to biosimilars of Enbrel, Humira, and Remicade, well-known and popular originator biologics used to treat psoriasis. Dr. Andrew Blauvelt of OMRC has been involved in the testing of biosimilars for psoriasis, has been the leader of the Biosimilars Working Group of the International Psoriasis Council, has advised pharmaceutical companies on the development of biosimilars, and has spoken widely to general dermatology audiences on this area. He is frequently quoted throughout the attached biosimilar update, an article that would serve as a good introduction for those interested in learning more about this hot topic in dermatology.
Why Your Psoriasis Treatment Isn’t Working: Common Mistakes
Oregon Medical Research Center
Understanding Psoriasis and Its Treatments
Psoriasis is a chronic skin condition that is marked by red, itchy, and scaly patches. While there is no cure for psoriasis, a variety of treatments are available to help control symptoms and manage flare-ups. These treatments range from topical ointments and phototherapy to systemic drugs and biologics. Despite these options, many individuals find their treatments ineffective. This often stems from common missteps in how treatments are applied or managed.
Common Mistakes in Psoriasis Management
1. Inconsistent Application of Treatments
One of the most significant barriers to successful treatment is inconsistency. For topical treatments to work effectively, they must be applied regularly as prescribed. Skipping doses or irregular application can significantly diminish their effectiveness, leading to frustration and poor symptom control.
2. Lack of Treatment Tailoring
Psoriasis is a highly individual condition, and what works for one person may not work for another. A treatment plan should be as unique as the individual receiving it. Failing to tailor the treatment to the patient’s specific condition, lifestyle, and symptoms can lead to ineffective treatment.
3. Neglecting to Monitor Progress
Regular check-ups are crucial. Without them, it’s difficult to gauge the effectiveness of a treatment plan. These appointments are not just for assessing progress but also for discussing any side effects and making necessary adjustments to the treatment regimen.
4. Poor Lifestyle Choices
Lifestyle factors such as diet, stress, smoking, and alcohol consumption can exacerbate psoriasis symptoms. Patients often overlook the impact of their lifestyle choices on their condition, but addressing these can sometimes improve treatment outcomes significantly.
5. Overlooking Early Signs of Flare-ups
Recognizing and responding to early signs of a psoriasis flare-up can be crucial in managing the condition effectively. Timely intervention can prevent a full-blown flare, reducing both the severity and the duration of symptoms.
Psychological Impact of Ineffective Treatment
The emotional toll of living with psoriasis can be as challenging as the physical symptoms, especially when treatments fail to provide relief. It is crucial for patients to seek support, whether through therapy, support groups, or connections with others who understand the struggle, to manage the psychological impact effectively.
Adjusting Treatment Strategies
When to Seek a Second Opinion
If your treatment isn’t working, and your concerns seem to be unheard, it might be time to seek a second opinion. A fresh perspective can sometimes make a big difference, offering new treatments or approaches you hadn’t considered.
Exploration of Alternative Therapies
While traditional medications are the cornerstone of psoriasis treatment, alternative therapies such as stress management techniques, diet changes, and herbal remedies might provide additional relief and can be integrated into your treatment plan.
Innovation in Psoriasis Treatment
The field of psoriasis treatment is always advancing. New medications and therapies are continually being researched and developed, offering hope to those who have not had success with existing treatments.
Practical Tips for Managing Psoriasis
Here are a few practical tips to help manage your psoriasis more effectively:
- Set reminders to apply your medications or attend therapy sessions.
- Keep a symptom diary to track what helps and what doesn’t, which can be useful during consultations with your healthcare provider.
- Make lifestyle adjustments such as incorporating a balanced diet, regular exercise, and stress reduction techniques.
Access to New Options
If you’ve tried various psoriasis treatments without success, participating in clinical research could be a promising alternative. Clinical trials offer access to new, investigational treatments that are not yet available to the public. These studies are crucial for advancing psoriasis treatment and provide participants with cutting-edge therapies often at no cost. In addition to receiving potentially effective treatments, participants in clinical trials contribute to valuable research that could lead to significant breakthroughs in psoriasis care. By joining a clinical trial, you not only gain access to new therapeutic options but also play a vital role in the discovery of future treatments that could benefit millions worldwide. Consider discussing clinical research opportunities with your dermatologist to see if this could be the right path for you in your journey toward better management of psoriasis.
Immunodermatology: Part 2: Practical Immunology
Andrew Blauvelt, MD, MBA
Practical immunology is important for dermatologists to understand as it relates to a wide variety of pipeline drugs currently under investigation. In Dr Blauvelt’s view, there are three major cell types involved in psoriasis pathogenesis: 1) dendritic cells (upstream/initiating immune responses); 2) T cells (making pro-inflammatory cytokines); and 3) keratinocytes. Targeting IL-23, which is made by dendritic cells, leads to reductions in Th17 cells, since IL-23 is the major survival and growth factor for this type of T cell. Thus, ustekinumab is an indirect T-cell targeting agent. The main cytokine that is being made by the Th17 cells is IL-17A, which leads to activation and growth of keratinocytes. IL-17A is now considered the main effector cytokine of psoriasis. So, by targeting IL-17, downstream function of keratinocytes can be normalized.
A recent study looked at patients on either etanercept or ixekizumab (an anti IL-17A antibody currently under investigation for the treatment of psoriasis). Within two weeks of initiation of therapy, ixekizumab led to the down-modulation of psoriasis-related gene expression to a much greater extent when compared to etanercept. Of the 959 genes up-regulated with psoriasis, 559 were turned off within two weeks of ixekizumab therapy versus 84 with etanercept therapy. This proof-of-concept translational study supports the idea that IL-17A is a key cytokine involved in the pathogenesis of psoriasis.
Pipeline products that specifically block IL-23
These products are unlike ustekinumab in that they do not block IL-12.
MK-3222, an anti-p19 monoclonal antibody (mAb), from Merck
Phase 3 studies underway
CNTO1959, an anti-p19 mAb, from Janssen
Phase 2 studies completed
AMG139, an anti-p19 mAb, from Amgen
Phase 1 studies completed
Pipeline products that block IL-17A function
Secukinumab, a fully human anti-IL-17A mAb, from Novartis
In Phase 3 studies, phase 2 studies published in 2012 (Br J Dermatol)
Ixekizumab, a humanized anti-IL-17A mAb, from Lilly
In Phase 3 studies, phase 2 studies published in 2012 (N Engl J Med)
Brodalumab, a fully human anti-IL-17RA receptor mAb, from Amgen
In Phase 3, phase 2 studies published in 2012 (N Engl J Med)
According to Dr. Blauvelt, all three of the IL-17 blockers look incredibly good from published results and the safety signals, thus far, also look good. If Phase 3 studies confirm these initial results, clinicians will soon have a variety of new promising agents to treat psoriasis patients.
Acquired T-cell Immunity
Regarding the normal function of Th17 cells, individuals who have impaired Th17 responses develop chronic mucocutaneous infections, especially with Candida albicans and Staphylococcus aureus (e.g., Job’s syndrome); these patients also do not develop psoriasis. Normal Th17 responses lead to healing of acute infections with these organisms and no psoriasis (e.g., healthy individuals). Exaggerated Th17 responses lead to healing of acute infections, but eventual development of psoriasis. Of importance, the IL-23/Th17 pathway seems to be less important to systemic immunity when compared to skin and mucosal immunity.
Interestingly, there is also emerging literature regarding the role of IL-17A in the pathogenesis of atherosclerosis. This may mean that targeting of IL-17A may not only treat psoriasis, but also improve atherosclerosis. This, in turn, may decrease the risk of cardiovascular disease associated with psoriasis.
Looking into the Future
As dermatologists, it is important to consider whether drugs that inhibit IL-23 or IL-17 cause or worsen skin or mucosal infections, such as those caused by S. aureus and Candida. Based upon the normal function of this immune pathway, it is unlikely that these drugs will cause or worsen systemic infections. Lastly, it remains to be determined whether they will impact systemic anti-inflammatory activity, including atherosclerosis. Obviously, this latter point will be very important when choosing the proper therapy for patients with moderate-to-severe psoriasis.
Immunodermatology: Part 1
Andrew Blauvelt, MD, MBA
Immunodermatology is an important content area for dermatologists to consider when managing patients with psoriasis. The genetics of psoriasis has been an exciting and complex area of research over the last few years, especially in terms of how genetics relate to the immunology of psoriasis. A recent paper highlighted how psoriasis genetics and pathogenesis are much more complicated than was formerly believed. Previously, there were 26 identified genetic susceptibility loci associated with psoriasis risk, and now there have been an additional 15 loci identified. Dr. Blauvelt, when discussing psoriasis with his patients, describes it as a complex polygenic disease; yet, according to Dr. Blauvelt, up to 60% of psoriasis patients will have no other family members with the disease. According to the paper, investigators are “just scratching the surface” and these 41 genetic signals account for approximately 22 percent of estimated psoriasis heritability and further genetic studies, including fine-mapping studies and searches for uncommon susceptibility variants, are in order (Tsoi LC, et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet. 2012;44(12):1341-1348).
It is also important to consider the overlap between psoriasis genes and susceptibility genes identified for other autoimmune diseases, such as Crohn’s disease, ulcerative colitis, celiac disease, ankylosing spondylitis, rheumatoid arthritis, systemic lupus, multiple sclerosis, and types 1 and 2 diabetes. All of these diseases are polygenic (numerous genes are contributing to the susceptibility), which is a common theme of many common diseases. Of particular interest is the fact that 11 out of 41 susceptibility genes overlap between psoriasis and Crohn’s disease; in fact, six of the 11 genes are related to the IL-23/Th17 cell signaling pathway, suggesting that Crohn’s disease may respond to IL-23/Th17 blockade.
Psoriasis genes fall into five major functional categories and are either related to the innate or acquired immune system. These categories include genes linked with IL-23/Th17 cell activation (acquired); antigen presentation (acquired); type 1 interferon induction (innate); NF-kB signaling (innate); and skin barrier function (innate). Genes that are psoriasis-specific, i.e., no other disease associations, are mostly associated with innate immunity.
Examples
IL-36
The genetic basis for generalized pustular psoriasis has been identified. Mutations occur in the gene that encodes for the IL-36 receptor antagonist. This is an example of classic Mendelian inheritance, in that patients who have mutations in this gene develop disease; if they do not have defects, then they do not have the disease. Therapeutically, there is no IL-36 antagonist drug yet, however, this may be developed in the future for patients with generalized pustular psoriasis. IL-36 normally stimulates keratinocytes to produce IL- 8, which is a major neutrophil chemotactic factor. IL-36 will drive neutrophils into the skin, and patients who have this defect in their IL-36 antagonist will have uncontrolled levels of IL-36, leading to elevations in other more downstream pro-inflammatory cytokines (TNF, IL-8, IL-6, IL-1).
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CARD14
CARD14 is another example of Mendelian inheritance, being that patients who have critical mutations in this gene develop chronic plaque psoriasis. On chromosome 17, a mutation in Card14 (G to A) at position 349 was seen in certain familial cases of psoriasis. CARD14 mutation is involved in the innate immune system. Dysfunction in this gene leads to increased NF-kB activity; this, in turn, leads to increased pro-inflammatory cytokine production by keratinocytes.
Numerous other CARD14 variations are associated with non-familial cases of psoriasis as well. These variations however, are not Mendelian. The genetic variations translate into increased NF-kB activity in keratinocytes and increased risk to develop psoriasis.
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IL23R
Dr. Blauvelt notes that this gene is very clinically relevant as it relates to the mechanism of action of ustekinumab. The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans. If patients don’t have fully functional IL-23 receptor, then IL-23 does not function well as a stimulator of Th17 cells; thus, this gene defect protects against psoriasis development. This is a genetic “hit” to the system, whereas ustekinumab would be a pharmacologic “hit” to the system.
Other genes associated with the IL-23/Th17 pathway include the p19 subunit and the p40 subunit of IL-23 itself.
Summary
There is a tremendous amount of new information regarding genes and psoriasis. Psoriasis pathogenesis represents a complex interplay between innate (how the skin initially reacts) and acquired immunity (mostly related to the IL-23/Th17 pathway). There is certainly a lot more detailed research to come in this area. Regarding translating this information to the bedside, the hope is that genetic profiling will help clinicians predict severity and course of disease as well as to help determine the response to specific therapeutic agents.