This year saw 4 new FDA approvals for the chronic condition. But dermatologists are still not satisfied.
Whether it’s recognized as such or not, psoriasis is one of the most dominating subjects in modern medicine.
The condition and its common comorbidities are among the most profitable for the pharmaceutical industry, given that 3 of the top 10 most profitable prescription drugs address either psoriasis or psoriatic arthritis. Part of that profitability, of course, is due to its commonality: about 2% of the population suffers from this chronic skin disease. Research suggests that the rate is rising.
Despite this, the causes of psoriasis remain largely opaque. Nevertheless, there are a number of different ways that clinicians choose to treat the skin condition. In fact, this year opened new doors for dermatologists treating psoriasis, the often-misunderstood autoimmune disease known to cause immense physical and emotional discomfort for so many.
Peter Lio, MD, a clinical assistant professor of dermatology and pediatrics at the Northwestern University Feinberg School of Medicine, described psoriasis treatment as a staircase, with an advancement in options depending on how well each patient performs under a type of therapy. The staircase can go from wet wraps and topical steroids to the next step—options like phototherapy, biologics, immunosuppressants—then up to JAK inhibitors if all else fails. His colleagues agree the progression of innovation has been substantial.
“Interestingly—despite everyone thinking that maybe we've accomplished everything we need to over the past couple of decades—it’s still amazing progress, even in this past year for new therapies that are hitting the market for our patients,” Raj Chovatiya, MD, PhD, an assistant professor of the Department of Dermatology at Northwestern University Feinberg School of Medicine, told HCPLive.
This year, a number of advancements were added to this staircase of treatment options for psoriasis, including 4 major US Food and Drug Administration (FDA) approvals. Each of these treatments has gone through extensive study and they have proven themselves useful for dermatologists seeking to treat psoriasis. Understanding the condition remains an elusive target, but researchers are drawing closer and quickly expanding their abilities to address the disease.
In July of 2022, the FDA approved roflumilast cream (ZORYVE) 0.3%, a topical phosphodiesterase-4 (PDE4) inhibitor, as a treatment for plaque psoriasis in patients aged ≥12 years.
The FDA approval was based on data from the phase 3 DERMIS-1 and DERMIS-2 trials, in which topical therapy roflumilast cream was shown to give patients statistically significant improvements for plaque psoriasis symptoms and disease severity outcomes compared to vehicle.
The trial investigators had noted the fact that while topical therapy is usually used as a first-line treatment option for psoriasis, there had not been a single novel, nonsteroidal option approved for the patient population in 2 decades.
The DERMIS trial data for roflumilast showed substantial improvements in Psoriasis Area Severity Index 75% improvement (PASI-75; P <.0001), intertriginous IGA (I-IGA; P <.01), and Worst Itching Intensity Numerical Rating Scale (WI-NRS) improvement (P <.0001) for the treatment group versus placebo through 8 weeks.
“For decades, the treatments we’ve been using are primarily topical corticosteroids,” said Mark Lebwohl, MD, professor and chair of the Department of Dermatology at Icahn School of Medicine at Mount Sinai, in an HCPLive interview. “There are many of them on the market…but they’re associated with a number of adverse side effects.”
Roflumilast cream 0.3% was shown in the DERMIS trials to have statistically significant improvements across all assessed endpoints, in addition to showing favorable local tolerability.
“The reason why this is pretty exciting is because we know that phosphodiesterase-4 activity is highly elevated in psoriatic skin compared to healthy skin,” Chovatiya said. “And when you inhibit (PDE4) activity, you get down-regulation of all those inflammatory cytokines and signals we think about with psoriasis.”
In May 2022, the FDA approved tapinarof (VTAMA) cream 1% for plaque psoriasis in adults regardless of disease severity, which made it the first and only FDA-approved steroid-free topical medication of its class.
Tapinarof has made its mark in the world of dermatology as a versatile, once-daily, steroid-free topical treatment. The new option is well-timed. According to a survey analysis presented at Fall Clinical Dermatology 2022, despite psoriasis patients using 2.5 topical treatments on average, they ideally would prefer a single topical therapy to be used anywhere on the body.
“Most respondents were open to using a new topical treatment for psoriasis and want a product that offers improvement of both plaques and itch,” the survey investigators wrote. Tapinarof is the closest thing to what the survey found patients believed to be ideal, as far as simplicity.
Tapinarof influences gene expression and reduction in TH17 cytokines and TH2 cells. TH17 cytokines are proteins that are crucial to cell signaling, and reducing them leads to reduced inflammation.
The approval followed the positive results of the PSOARING 1 and PSOARING 2, during which tapinarof cream treatment was followed by statistically significant improvements in Physician Global Assessment (PGA) score of “clear” or “almost clear.”
The cream showed a minimum 2-grade improvement in the treatment versus the vehicle group from baseline to 12 weeks.
"Topicals are a cornerstone of this disease," said Mona Shahriari, MD, FAAD, assistant clinical professor of dermatology at Yale University School of Medicine, "And innovation has been lacking in the topical arena.”
In both trials, the investigators did note that a majority of adverse events, which included folliculitis, contact dermatitis, and nasopharyngitis, were found to be localized to the application site and were mild-to-moderate.
"In the past, there was often a convoluted, complex regimen for patients to follow, having to use different medications on different parts of their body," Shahriari said. "This medication can simplify treatment: one topical, that you can use anywhere on your body. This could really make a difference in the lives of our patients."
The FDA approved deucravacitinib (Sotyktu) treatment for moderate-to-severe plaque psoriasis in adult patients eligible for systemic or phototherapy. Deucravacitinib is known as an oral, allosteric TYK2 inhibitor and is also the first in its class approved to treat psoriasis.
The approval followed the release of data from the phase 3 POETYK PSO-1 and PSO-2 trials, where 6 mg dose once-daily was compared to twice-daily 30 mg apremilast and placebo in 1684 adult patients reporting moderate-to-severe plaque psoriasis.
“The approval of deucravacitinib represents an exciting day for patients suffering from moderate-to-severe plaque psoriasis who are not satisfied with topical and conventional treatments,” said Bristol Myers Squibb chief medical officer Samit Hirawat, MD. “This is another extraordinary achievement…the first oral treatment approved in nearly 10 years, and the first orally dosed once-daily treatment for moderate-to-severe plaque psoriasis.”
In the trials, 58% and 69% of participants treated with deucravacitinib achieved PASI 75 by 16 weeks and 24 weeks, respectively, compared to 13% of the placebo arm by 16 weeks (P <.0001), and 35% and 38% of patients treated with apremilast by weeks 16 and 24, respectively (P <.0001).
They also found that another 36% and 42% of those treated with deucravacitinib achieved PASI 90 by 16 and 24 weeks, compared to 20% and 22% of those in the apremilast group, respectively.
The fourth major FDA approval to occur in the dermatology space for psoriasis was Boehringer Ingelheim’s spesolimab (SPEVIG). The new treatment option is most notable for its being the first major treatment of generalized pustular psoriasis (GPP) flares in adult patients.
An uncommon, heterogenous skin disease, GPP is the result of neutrophils accumulating in the skin leading to painful, sterile pustules. GPP flares have the potential to even lead to hospitalization due to major complications like heart failure, renal failure, or sepsis, which is why spesolimab’s approval was seen as a positive step forward.
Spesolimab is a selective monoclonal antibody known to block the activation of the interleukin 36 (IL-36) receptor in patients’ immune systems. This receptor is involved in the pathogenesis of GPP flares for patients.
“This important approval reflects our successful efforts to accelerate our research with the aim to bring innovative treatments faster to the people most in need,” said Carinne Brouillon, from the Board of Managing Directors for Human Pharma at Boehringer Ingelheim.
“We recognize how devastating this rare skin disease can be for patients, their families and caregivers,” she said. “GPP can be life-threatening and until today there have been no specific approved therapies for treating the devastating GPP flares.”
Looking into the future of psoriasis treatment, there have been a wide variety of predictions and prospects aimed at advancing in the field further. Genetic testing is one major future advancement that may end up getting a lot more attention.
Karan Lal, DO, the director of pediatric dermatology and cosmetic surgery for Affiliated Dermatology Scottsdale and social media chair for the Society for Pediatric Dermatology, reflected on this year and on the future of psoriasis treatment.
“So, I think four treatments in a year for a very systemic disease is a pretty big deal,” Lal explained in an HCPLive interview. “And I think in general medicine, we're becoming more interested in genotype-phenotype correlation. So that means genetically testing people to find out what their disease is and what mutations it harbors, to treat them more targetedly.”
Lal also described the company Mindera, which he believes has a device that may become more widely-known in the dermatology space. While serving as a sub-investigator in a trial, he became familiar with the “Mindera patch.”
“And essentially, you can put this little non-invasive patch on psoriasis plaques and find out if the patient is a responder or non-responder to certain biologics,” Lal explained. Picking the right biologic for patients through methods like these may end up being the future of psoriasis treatment.
Another expert shared her own list of anticipated breakthroughs in psoriasis—the variety of which speaks to the heterogeneous approach to managing the chronic disease and its various effects on patients, as well as the emerging preference of patients to have as many options as possible.
At the SDPA 2022 Fall Dermatology Conference, Cynthia Trickett, MPAS, PA-C, described in-study advancements for the following agent types to treat psoriasis:
It is likely that the future of psoriasis treatment, given the wide array of oral, injectable, and topical options available and in-study today, may focus more on targeting the specific phenotypes of patients.
Expanding the predictive capability of clinicians, potentially through genetic testing, may prove to be the future of treatment. In the meantime, more and more data is being gathered so that addressing patients’ phenotypes can become a reality in the years to come.