IL Inhibitors and TYK2 Blocker Near Approval

A new generation of therapeutics nearing approval and groundbreaking research exploring factors ranging from genetics to comorbidity associations could move the focus of plaque psoriasis treatment from control to cure within 5 to 10 years, according to a panel of experts speaking on the Dermatology Times® Viewpoints video program.

The anticipated launches of new biologics and an oral therapy in the next several years point to ongoing opportunities to treat this skin disease more effectively while maintaining safety standards, they say.

Panelists April W. Armstrong, associate dean of clinical research, Keck School of Medicine at the University of Southern California, Los Angeles, Calif., Andrew Blauvelt, MD, MBA, president of the Oregon Medical Research Center, Portland, Ore., and Erin E. Boh, MD, PhD, FAAD, professor and chairman, Joseph Chastain Endowed Chair of Clinical Dermatology, Tulane University School of Medicine, New Orleans, La. joined moderator Andrew F. Alexis, MD, MPH, chair of the Department of Dermatology, Mount Sinai Morningside and Mount Sinai West, New York City, N.Y., in presenting a strategic look at the opportunities and challenges ahead in a series of videos developed for dermatologytimes.com on “The Changing Treatment Landscape of Plaque Psoriasis.”

CURRENT STANDARDS OF CARE

“The old paradigm for treating patients with psoriasis involving more extensive body surface area (BSA) was going from phototherapy to oral systemic therapy to biologics. In the last 3 to 5 years, that shifted to thinking about biologics, oral therapies, and phototherapies concurrently,” says Armstrong. “Now, a key recommendation is to consider biologics as one of the first-line treatments for most patients with moderate-to-severe plaque psoriasis.”

Systemic therapies have an added role in treatment regimens for patients with psoriasis and psoriatic arthritis (PsA). “If a patient has psoriasis but also PsA, then we really want to think about systemic treatments that can target both,” says Armstrong.

• Tumor necrosis factor (TNF)inhibitors etanercept, adalimumab, certolizumab, and infliximab, all of which are U.S. Food and Drug Administration (FDA)-approved for both psoriasis and PsA.
• Interleukin (IL)-17 inhibitors secukinumab and ixekizumab, both FDA-approved for psoriasis and PsA, and brodalumab, approved for psoriasis in the United States but also for PsA in other parts of the world.
• IL-23 inhibitors guselkumab, tildrakizumab, and risankizumab. Guselkumab, recently gained approval for PsA.

BSA AND BEYOND

“I'm not stuck on BSA,” says Blauvelt. “I’m looking at a little bit broader use of biologics compared to just the BSA criteria. I find that I can get a drug for most of my patients that meets one of these criteria: failure of a topical, BSA greater than 10%, or special area involved. That fits with some new recommendations that the International Psoriasis Council has put forth on treating patients.”

Comorbidities “absolutely influence my choice,” he adds. PsA tops that list. Blauvelt estimates 40% to 50% of patients in his practice have PsA, significantly higher than the 25% to 33% typically reported. “My class of choice is actually IL-17 blockers," he says. “I consider TNF blockers as the second line for my patients with PsA because the data are comparable in joint data with TNFs and IL-17s. We also see the skin data and safety profile being better for IL-17s.” The other major comorbidity is heart disease. "It’s common with more severe psoriasis and less common with more mild disease. Any patient with psoriasis with over 10% BSA is at risk for heart disease, according to Blauvelt.

“I don’t necessarily go with class. I try to think about clearing psoriasis to zero,” says Blauvelt. “It’s pretty rare for me to use a TNF blocker. I favor IL-17 blockers if the patients have PsA and IL-23 inhibitors if they don’t,” he adds.

SAFETY PROFILES AND STRATEGIES

Biologics as a group have a good safety profile, which has proven consistent as patients use these medications over the long term. But practitioners need to weigh various risk factors.

TNF inhibitor medications. “They aren’t for everyone,” says Erin E. Boh, MD. Special consideration may be needed for patients with severe congestive heart failure; those with morbid obesity; those with first-degree relatives who have multiple sclerosis (MS) since this medication can induce or unmask MS and, as a group, can deregulate, and those at risk for reactivation of tuberculosis and hepatitis B. Less common adverse events (AEs) include increasing or inducing elevations in liver tests and “a very slight increased risk” of malignancy, particularly squamous cell carcinoma. Boh recommends additional blood work and more vigilant monitoring than that required for third-generation biologics for patients at risk.

Ustekinumab or the interleukin (IL)-12/23 inhibitors. Both have a very good safety profile, Boh says. Key concerns could include the patient’s ability to commit to the entire 12-week program for ustekinumab and also whether the patient has psoriatic arthritis. “Ustekinumab is not as good for joints as TNFs, which are first line for prominent PsA,” Boh points out.

The IL-17 inhibitors. “They’re even safer and have fewer AEs compared with the TNFs,” Boh says. However, brodalumab has a black box warning regarding increased risk of depression. Patients with psoriasis “generally are more depressed” than the general population, notes Boh, but in her experience, brodalumab does not significantly worsen the condition. However, she recommends that all patients with psoriasis be screened for depression.

Though the risk is low, IL-17 blockers could unmask or induce inflammatory bowel disease. Taking a careful history and screening would help mitigate that, she adds. These biologics may slightly increase the risk of yeast infections and candida infections, including oral candidiasis.

All classes: Hypersensitivity is a consideration across all biologics, says April W Armstrong, MD. Other potential AEs include injection site reactions, nasal pharyngitis, and upper respiratory tract infections, seen with the biologics in some patients with an increased risk compared to the placebo.

WHAT’S NEXT?

Looking to the future, Armstrong predicts further development of agents with a higher efficacy not only in the skin but also in the joint. “We have a long way to go in treating psoriatic arthritis,” she says. “We still use ACR20 as our bar. That aspect of psoriatic disease will need to be addressed better with newer therapies," she adds. “We will also see newer agents in different classes of topical and oral therapies that work very differently from traditional therapies. These medications would address the needs of patients who prefer oral therapies and those who have limited psoriasis and want safe, effective topical therapies.”

Additional IL-17 and IL-23 inhibitors will likely be approved in 2021 or shortly thereafter, forecasts Blauvelt. A new oral therapy that blocks the molecule TYK2 also may launch soon. “It’s not going to be close to the best biologic therapy, but for those looking for oral therapies, it’s going to go to the head of the class, ahead of apremilast, methotrexate, cyclosporin, and acitretin,” he says.

However, as effective as these new therapies are, they all require continued use, he adds. That’s starting to change. “We’re going to be using the C[cure]-word more in the next 5 to 10 years,” says Blauvelt, who serves on the National Psoriasis Foundation’s Scientific Advisory Committee and is involved with its Milestones to a Cure initiative.

CHALLENGES REMAIN

Despite advances in psoriasis treatment, there are still a number of issues for multiple patient populations relating to medication access and affordability, as well as patient and dermatologist education. For Boh, Medicare patients are a major population with unmet needs. “The only drugs we can get are infliximab or the tilrakizumab if you go through the Medicare major medical,” she says. Boh and Armstrong stress the importance of not backing down from fighting insurance companies to obtain superior treatment methods for Medicare patients.

Boh adds that pediatric patients are benefitting from a number of new treatments entering this population. But, says Armstrong, more research is needed, not on safety alone, but on long term effects. “Are we doing any disease modification in this patient population by treating them earlier?” she asks.

Doctor and patient education is another area for improvement in treating psoriasis. “Just put the patient first, just think about that human being in front of you. If it was your brother or your mother, would you want them to go on methotrexate?” says Blauvelt. “It’s a woefully low percentage of patients who need biologics are on them in this country.”