Initiating Systemic Therapy for Psoriasis

Until about 20 years ago, systemic treatment options for moderate/severe psoriasis were limited and nonspecific. To get an idea of how much the field has changed, clinical guidelines on psoriasis management from the American Academy of Dermatology (AAD) published in 1993 filled a modest six journal pages. Systemic therapies consisted of methotrexate, hydroxyurea, retinoids, antibiotics, and “other.” Targeted and biologic therapies remained in various stages of development.

The most recent AAD/National Psoriasis Foundation (NPF) clinical guidelines, published from 2019 to 2021, consist of six sections and more than 200 journal pages. Still, the section on systemic non-biologic therapies lists only a handful of FDA-approved therapies, one of which — apremilast (Otezla) — was approved within the past decade. None of the Janus kinase (JAK) inhibitors were included. Discussion of the non-biologic systemic therapies began with methotrexate, approved more than 50 years ago.

The section on biologics did include almost a dozen FDA-approved therapies, though several recent approvals were not on the list. An updated list of therapeutics from the NPF included 16 FDA-approved biologic agents. The still-growing list reflects recent advances in precision medicine that target specific components of the inflammatory cascade that drives psoriasis, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, IL-17, IL-23, IL-36, and activated T cells.

Choices and More Choices

The expanded — and still growing — number of treatment options for moderate/severe psoriasis raises the obvious question of how to select initial treatment. Multiple factors come into play, including clinical judgment, disease characteristics, patient preference, and the overarching impact of insurance coverage. An additional issue is approval status: some therapies have approval for psoriasis only and others have approval for psoriasis and psoriatic arthritis, which occur together in up to a third of patients.

“My go-to treatment for skin-only psoriasis is the IL-23 inhibitors,” said Kyle Cheng, MD, of UCLA Health in Los Angeles. “I think they have the fewest side effects and they can be dosed as little as once every 3 months.”

“I tell all of my patients that, ultimately [the treatment] is up to their insurance, whether they’ll pay for it, and that tends to be a roadblock for just about every patient,” he added. “Working with a dermatologist the patient trusts and who is comfortable prescribing biologics and helping [the treatment] get authorized is important.”

Insurance might also have implications for primary care providers’ involvement in a patient’s treatment. Some insurers require dermatologists to prescribe the more expensive medications, said Cheng.

Psoriasis With a Side of Arthritis

Biologics also represent the first choice of systemic therapy for Oyetewa Asempa, MD, of Baylor College of Medicine in Houston. When she considers oral therapy, methotrexate is often her first choice, often due to insurance considerations. The older medication also represents an acceptable option for patients with skin psoriasis and psoriatic arthritis.

“Some of my patients will say right up front that they don’t want anything that requires a needle,” said Asempa. “In those cases I definitely consider oral medications.”

TNF inhibitors, the original biologic agents, still have a prominent role in Asempa’s clinical practice.

“Even though we have drugs that offer a little better efficacy, TNF inhibitors are still the go-to drug for a lot of insurance companies,” she said. “I still put a lot of patients on adalimumab [Humira] because I think the TNF inhibitors are better for arthritis. That’s not necessarily what the data say, but in the clinic, I feel like adalimumab is still a really great initial option.”

For patients with skin-only psoriasis and no insurance issues, Asempa also prefers IL-23 inhibitors, for their impact on quality of life as much as their efficacy.

“Adalimumab is dosing every 2 weeks during maintenance, as compared with every 12 weeks with a drug like risankizumab [Skyrizi],” she said. “Patients really love that because they can kind of live their lives as though they don’t have psoriasis.”

IL-17 inhibitors offer rapid onset of action and effective treatment for patients with skin and joint disease but cannot be used in patients with inflammatory bowel disease or other gastrointestinal problems, said Asempa.

Paolo Romanelli, MD, of the University of Miami, also prescribes adalimumab for many of his patients with skin psoriasis and psoriatic arthritis.

“I still think it works better for arthritis than the IL-17 and IL-23 drugs,” he said.

Every patient is different and treatment selection should take that into account.

“Believe it or not, I still have some patients who are on etanercept [Enbrel],” said Romanelli. “They come to me and say they like it. I still tell them about these newer drugs that might be safer and a little more effective, but I let them decide.”

As a dermatology resident 20 years ago, Romanelli studied histopathology and became interested in the concept of “tailor-made treatment,” better known today as precision medicine.

“I would offer to do a biopsy of a psoriasis plaque and then stain the tissue for immunohistochemistry markers, such as TNF-alpha, IL-17, -23, -36, and see which one was expressed, then decide on the best biologic treatment for the patient,” said Romanelli. “This is something that is not easy to do in clinical practice, but patients like the idea of having something objective to base the treatment decisions on.”

“I still like the idea for the future, but I was talking about this in 2005, so who knows whether I will ever see it happen,” he added.

Other Considerations

Patients with difficult-to-treat areas — scalp, inframammary folds, groin, other intertriginous areas — may require more than a systemic agent. Topical agents often are used in combination with systemic therapy. Availability of foam-based formulations has helped to improve convenience, tolerability, and adherence of some topical therapies.

Newer biologic agents have a favorable safety profile. In contrast, TNF inhibitors, though generally safe, can increase a patient’s risk of infections, and the agents confer a small risk of lymphoma, Cheng noted. However, TNF inhibitors, particularly certolizumab (Cimzia), have proven safe for use in pregnancy. A registry documenting use of IL-17 and IL-23 inhibitors has been launched, and data collected so far have shown no significant problems with birth defects or other pregnancy issues, he added.

Working with primary care physicians is another consideration for starting systemic therapy. After dermatologists, primary care physicians treat more skin conditions than any other specialty. As Cheng pointed out, some insurers require dermatologist authorization for certain systemic medications. However, some healthcare plans require referral from a primary care physician, and Asempa noted that busy dermatology practices can have lengthy waits for appointments.

“If a [primary care physician] is comfortable with prescribing a medication, after they’re sure it is psoriasis, that’s excellent, because it really improves access to care, and that’s a huge problem in dermatology right now,” said Asempa. “Access to care is definitely not where it needs to be, and patients really suffer in the mean time. They often end up in the emergency department for something the ED really can’t help them with. Patients are more likely to be put on prednisone, which just makes things worse.”

As a final thought on working with primary care providers, Asempa said, “If you’re really not sure that it’s psoriasis, then referring the patient to a dermatologist can be really helpful.”

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