Biologics Redefine Clear in Psoriasis

December 11, 2019
psoriasis

The idea of treating a cancer patient really spoke to Melodie Young, MSN, ANP-c.
She wanted to go into oncology when she entered medicine decades ago, and it was behind very vitreous thinking. Even when she couldn’t cure a cancer, she could be there to at least care for someone managing the worst diagnosis of their life.

Whether the prognosis is good or bad, a cancer patient always needs help.

Then Young met patients with psoriasis. She saw—very literally—the burden of disease on patients. She saw the effect a chronic skin disease can have on a patient’s wellbeing, and their outlook on care. And she saw a specialty which had fewer experts, fewer tools, and just as many new patients as ones like oncology.

“I thought, well, this disease isn’t killing them, but it's robbing them of their lives,” Young told MD Magazine®. She and her fellow care providers were prescribers without a cure, motivators without a high ceiling.

The greatest advancement in dermatology since 2010 is not a cure, though since 2003 the US Food and Drug Administration (FDA) has approved nearly a dozen interleukin- (IL) or tumor necrosis factor- (TNF) inhibiting agents for psoriasis and are commonly used in atopic dermatitis, as well.

Rather, it is the effect delivered by these therapies: skin clearance, to a degree previously unattained by Young and her colleagues—a proverbial cure for the most burdensome symptom of the most common dermatologic conditions.

The Psoriasis Area Severity Index (PASI) score is a seven-grade metric from the 1970s, designed to indicate the skin-clearing benefit of therapies in clinical trials. Its use in investigative endpoints usually includes a percentage response rate: PASI 50, PASI 75, PASI 90, or PASI 100.

Though it—and other similar condition tools such as the Eczema Area and Severity Index—is considered a relatively basic metric for modern medicine, its use for primary endpoint assessment in promising dermatological therapies has remained consistent.

Brad Glick, DO, a dermatologist and principal investigator with GSI Clinical Research, recalled the guarantee he could give patients when biologics were beginning to reach the market in the mid-2000s: “we can get your skin clearer.” By 2008, investigators were seeing patients on new agents consistently reach PASI 75.

Etanercept (Enbrel), the first FDA-approved therapy for cutaneous psoriasis as a twice-weekly injection, could help one-third of patients reach PASI 75 in 12 weeks. Then, 50% of patients in twice that time.

Infliximab (Remicade), an FDA-approved TNF inhibitor indicated for severe psoriasis, showed 80% of patients were reaching PASI 75 in 24 weeks—albeit with increased risk for opportunistic infections or cardiovascular events—by 2005.

Those marks are now decimated by newer biologics. The FDA approved risankizumab (Skyrizi) last April based on a pair of phase 3 findings which showed three-fourths of psoriasis patients achieved PASI 90 in 16 weeks. A head-to-head comparison of guselkumab (Tremfya) and secukinumab (Cosentyx) showed 84.5% of those on the former reached PASI 90 in 48 weeks, compared to 70% on the latter.

And new reSURFACE 2 findings from October showed tildrakizumab (Ilumya) was able to retain 60% of patients at PASI 90 at 3 years. One-third of patients achieved PASI 100—total clearance.

Glick has had to refine his guarantee to patients: “we can get your skin clear.” Period.

“We have agents right now that more than 50% of the time in the clinical trials have individuals with completely clear skin at the end of 1 year—and some of the even newer agents, the numbers are even more specific, where we're close to 70% of the patients being 100% percent clear at the end of 1 year,” Glick told MD Mag this year.



These advances have led to the adoption of PASI 90 as the new gold standard in clinical outcomes. But there’s also been greater emphasis on patient quality of life. Melissa Davis, PA-C, of the Associates in Dermatology practice in Louisville, has noticed the embrace of patient-centric outcomes and surveys in newer trials.

With clearer skin benefits becoming obvious, clinicians want to ensure the auxiliary effects of the disease are also lessening.

“They're no longer itchy and no longer suffering the psychosocial impacts that go on along with that, too,” Davis told MD Mag. “So it's sort of like the holistic improvement of the patient, in my opinion.”

The newer therapies have also eased the process of care with a significantly reduced regimen. Young, now with Modern Dermatology in Dallas, noted the amount of therapy needed to help patients with moderate psoriasis achieve skin clearance in a year could fit in a shot glass. It’s a huge leap from where she saw patients just more than a decade ago: either willing to try questionable, unproven therapies for relief, or jaded from failure experienced with such sham drugs.

Even the earliest biologics, which could offer up to a 50% chance of significant skin clearance, required patients visit the office once-weekly over 3 months to even have a chance of improvement 6 months later.

“They thought it was too much work,” Young said. “It's very hard to get a patient to come in and to commit to something like that, especially if you live very far away.”

From Young’s perspective, chronic skin conditions like psoriasis and atopic dermatitis have a crippling effect on patients, particularly those diagnosed in their teens or 20s. Their confidence shrinks, their social lives are more a stressor than they are an escape, and their mental wellbeing is worse from all of it. Many patients will even confide to Young they don’t want to start a family—they don’t want to risk passing their chronic condition to children.

What these newer, stronger, more reliable biologic agents have brought is a greater confidence in patients. They can’t be cured, but there is a new sense of control.

Young recalled one patient she had for 10 years—a young man whose skin constantly appeared scaly and sometimes even bloody. His eyes were constantly bloodshot, and his personality seemed jilted. He was among her first patients to receive dupilumab (Dupixent) for his eczema.

One month later, a handsome, relaxed man came into Young’s office. She had to double-check her chart to ensure this was the same patient. His skin had improved gradually over weeks, but his symptoms bettered overnight. In fact, he told her, he recently had his first full night of sleep since his diagnosis—no waking up from pain in the middle of the night, no ice packs, no late-night snack while struggling to find a comfortable position.

“The disease had that sort of a life-changing impact on him, and he literally looks like a younger, healthy version of himself now,” Young said. “That’s the way that the disease can just totally be gone—it just melts away. And we hear those stories all the time.”

What originally drove Young to dermatology was a need to help those with little hope. But she believes the newest wave of specialists will come for the opposite cause: these therapies are actually healing more and more people. She wondered aloud what the protocol is for treating a patient who’s had cleared skin for 20 years. She’s never heard of one before, but she knows that’s the job of the next dermatologists.

But there’s still plenty of education needed for the personnel currently treating these patients, especially with regard to these new therapies. Davis originally worked in primary care, and though skin conditions are among the most common issues patients first present to their frontline care provider, she doesn’t believe their education equips them all to navigate therapy benefits, risks, and symptom management.

“And I think it's not their fault,” Davis explained. “It wasn't an education that was available for them. And if they're interested in skin, they may be continuing education in that. But if not, where are they going to get that information?”

Particularly for patients whose conditions are being driven by an inflammatory issue, there are significant risks for cardiovascular events and other potential comorbid conditions that need to be considered. Davis said it’s critical the primary care field understand who is at most need of a specialist referral. Especially for a field with fewer experts and millions of new patients, there’s a significant need for guidance that considers the new therapies’ outcomes and risks.

Whatever will be eventually available to prescribers, they will at least have a patient population that is finally motivated by successful results to adhere to treatment, and less burdened by comorbid conditions and depression.

There’s even more options coming. Glick spoke about arrow hydrocarbon receptor agonists, a cytokine-decreasing drug class which may decrease inflammation in patients with psoriatic disease. He called the preliminary data from IL-17 inhibitor bimekizumab “quite exceptional.” These all may be available in the coming year-plus.

But the work is never done, and 100% guarantees are not anywhere close to coming in dermatology.

“We certainly need to provide more education, not only to our patients, but also to our colleagues,” Glick said. “I think that we need cost-effective agents. I think we need oral systemic agents that are almost, if not equally, as effective as biologics, with really nice safety profiles. Hopefully we can get those.”

To a specialist like Young, who can remember the days when patients had little hope, these seem like good problems to have.

“I mean, any immunology or psoriasis book that I have, if it's more than 10 years old, I can throw it away,” she said.
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