Despite Expanding Array of Psoriasis Treatments, Opportunities for Improvement Remain

There are a number of new biologic options for treating psoriasis, but undertreatment is still a concern, and more long-term data are needed, according to Junko Takeshita, MD, PhD, MSCE, of Perelman School of Medicine at the University of Pennsylvania.

Takeshita, who is an assistant professor of dermatology and epidemiology, began her presentation at the National Association of Managed Care Physicians Virtual Spring Managed Care Forum with an overview of this chronic inflammatory skin disease. Plaque psoriasis is the most common type, affecting 80% of the 7.5 million patients with psoriasis in the United States.

Although psoriasis appears to be more prevalent in White individuals, Black patients are more likely to have moderate to severe disease, and non-White patients are more likely to have undiagnosed psoriasis.

Treatment approaches are generally decided by disease severity, with mild psoriasis treated with topical therapies and moderate or severe disease treated with phototherapy and systemic therapies, which can be orals or biologics. An approach proposed by the International Psoriasis Council classifies patients as candidates for either topical or systemic therapy based on their level of body surface area involvement, psoriasis presence involving special body areas, and past failure of topical therapy.

Biologics have become the mainstay of therapy for moderate and severe disease, explained Takeshita, with therapeutic targets including tumor necrosis factor (TNF), interleukin (IL)-23, IL-12, IL-17A, and IL-17 receptors. The Psoriasis Area and Severity Index (PASI) end points are used to show levels of improvement, and these have been adapted as treatment options improve.

“PASI 75, which corresponds to at least 75% improvement in PASI score, has traditionally been the gold standard measure of drug efficacy, but with our increasingly efficacious treatments, PASI 90, or at least 90% improvement, rates are increasingly being reported and used as a primary measure of efficacy,” Takeshita explained.

She emphasized this point by showing slides with head-to-head trial results comparing the efficacy of various treatment options. For instance, the IL-17A inhibitor secukinumab was shown to have a statistically significantly higher proportion of patients achieving PASI 90 and even PASI 100 over 52 weeks compared with the IL-12 and IL-23 inhibitor ustekinumab. IL-23 inhibitors risankizumab and guselkumab have also shown superior efficacy to ustekinumab, and guselkumab appears to have superior long-term efficacy to secukinumab, which spurred a quicker response early in the trial before guselkumab caught up at around the 20-week mark.

The general takeaway from all these trials is that biologics are more efficacious than oral systemic drugs, and that newer treatments are generally more efficacious, although the incremental differences between them are relatively small, Takeshita said.

Real-world effectiveness for each of these options is generally lower than is reported in clinical trials, which may be due to differences in adherence or because patients seen in clinics may be sicker than the trial populations.

Recommendations for treatment selection can vary based on a patient’s comorbidities; for example, those with multiple sclerosis should not take TNF inhibitors, whereas those with Crohn disease should not take IL-17 inhibitors. Prescribers can also select a therapy based on its ease of administration, rapid onset of response, or flexible dosing options for patients who are obese.

Takeshita dedicated a part of her presentation to updating the audience on recommendations around psoriasis in the context of the COVID-19 pandemic. While psoriasis itself does not seem to be a risk factor for worse COVID-19 outcomes, those with severe psoriasis are more likely to have comorbidities that do increase that risk, such as obesity and hypertension. Fortunately, investigators have not seen strong signals of increased risk from immunomodulatory treatments of psoriasis, but the data have limitations and it’s still unknown whether certain mechanisms of action are more risky.

In the meantime, the National Psoriasis Foundation recommends that patients without COVID-19 should continue their psoriasis therapy as scheduled in most cases, and they should take the first vaccine made available to them.

Finally, Takeshita discussed the promise of a patient-centered treatment approach for psoriasis. “With all of the advancements in psoriasis treatment over the last decade or so, we really have a great opportunity to make a major impact in helping to improve the lives of our patients living with this chronic disease. In order to do this, we need to make sure to align our treatment goals with what matters to our patients,” she said.

Psoriasis is a highly stigmatizing disease with serious impacts on mental and physical functioning, and increasing PASI clearance scores are associated with increasing proportions of patients saying their psoriasis has no impact on their quality of life.

However, most patients with moderate and severe psoriasis are undertreated, with 55% and 52%, respectively, reporting that they use only topical therapy and 32% and 27% not taking any prescription treatment at all. Takeshita also cited her research showing that Black patients and individuals with higher out-of-pocket drug costs are less likely to receive biologic therapy.

Treat-to-target approaches can help focus clinical care on periodic assessment and adjustment until a goal is reached, and these targets can also be used in value-based care efforts. The Merit-based Incentive Payment system (MIPS) includes a measure with several psoriasis outcome targets, making it the first dermatology outcome measure in MIPS.

“It will be important for us to assess if a treat-to-target approach truly improves patient outcomes, and hopefully the collection of this data through MIPS and through other means will help us to identify this,” Takeshita concluded. “Specifically, we need to understand if this approach improves patient outcomes without significantly increasing potential side effects or other adverse outcomes that may be associated with treatment escalation.”