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DENVER — To switch or not to switch? To stack or not to stack? Those are some of the questions dermatologists face when a patient on systemic therapy for psoriasis does not respond fully, when the patient reacts favorably at first but then treatment effectiveness wanes, or when disease or risk factors change over time.

The medical board of the National Psoriasis Foundation defines treatment response as achieving 1% or less of affected body surface area at 3 months and at each 6-month maintenance assessment.

That is the goal, but sometimes patients do not respond to the treatment. A primary treatment failure, when a patient has no initial response, “does happen occasionally,” and a secondary failure involves loss of effectiveness after an initial response, Boni E. Elewski, MD, professor and chair of dermatology at The University of Alabama at Birmingham, said at the American Academy of Dermatology (AAD) 2026 Annual Meeting.

Consider switching systemic therapies when a patient does not meet their treatment target, when therapy worsens their quality of life, or when an escalation of dose fails or is not possible, Elewski said.

Secondary failures can be common. Researchers tracked Psoriasis Area and Severity Index (PASI) 90 response among 687 patients with psoriasis who started a biologic between 2015 and 2021 in the CorEvitas Psoriasis Registry. “Unfortunately, in the real-world CorEvitas study, one quarter lost response at 6 months and even more [half] by 18 months. This isn’t good,” she said.

Reasons for a secondary treatment failure include immunogenicity, poor adherence, and new disease triggers.

Same Class or New Class?

If the initial response was strong and durable, or loss of response was gradual, consider switching within a treatment class, Elewski said. For example, go from one interleukin (IL)-17 inhibitor to another, such as secukinumab to ixekizumab, or go from one IL-23 inhibitor to another, such as risankizumab to guselkumab, she explained.

However, if loss of response is rapid, the patient already did not respond to multiple agents in the class, or they develop new comorbidities like psoriatic arthritis, inflammatory bowel disease, or uveitis, switching to a different class may be warranted.

“We all have patients who fail and we have to move on to something else,” Elewski said.

There are many ways you can switch to a different class, she added. Examples include switching from a TNF inhibitor to an IL-17 or IL-23 inhibitor; from an IL-17 to an IL-23 inhibitor if durability wanes; or from an IL-23 to an IL-17 inhibitor if rapid skin clearance is needed.

Multiple factors can contribute to treatment failure, including smoking, a high BMI, metabolic or cardiovascular comorbidities, and genetic factors. Adverse events such as injection site reactions, severe gastrointestinal complications, recurrent infections, laboratory toxicity (which she said was “not common but possible”), or neuropsychiatric effects are among the additional reasons to switch systemic psoriasis therapies.

“Here’s the big one: disease evolution,” Elewski said. Some patients experience psoriasis phenotype changes, a paradoxical switch to an atopic dermatitis phenotype, or worsening or new-onset psoriatic arthritis. She recommended examining the nails, which are a window to the joints. Patients also can develop generalized pustular psoriasis or erythrodermic flares.

In a 2020 meta-analysis, researchers found up to 12% of 92 patients with plaque psoriasis across multiple studies experienced a phenotypic change to eczema while taking TNF-alpha, IL-17, or IL-23 biologics. In a 2024 follow-up study from the same research group, increasing age, female sex, and history of atopic dermatitis or hay fever were the factors linked to a higher risk for paradoxical eczema.

When to Stack, When Not to Stack

Another treatment strategy when systemic therapy response is not ideal is stacking. “The main reason to stack is when one drug is helping, but not enough,” and switching would risk losing partial control, Elewski said.

Other reasons to stack therapies are a Dermatology Life Quality Index that has not significantly improved despite skin improvement, partial body surface area or PASI responses, or residual disease affecting a “high impact area” like the scalp, nails, or genitals, Elewski said.

There are four main ways to stack systemic psoriasis therapies, Elewski said:

• Biologic agent plus methotrexate: This combination can improve efficacy in the skin and joints and reduces antidrug antibodies.
• Biologic plus apremilast: This combination can help patients with residual disease and psoriatic arthritis.
• Biologic plus acitretin: This combination can be useful to treat hyperkeratotic or palmoplantar psoriasis.
• Biologic plus deucravacitinib: This combination can help patients with residual skin and joint disease.

Consider stacking when skin clears but joints are active, or the other way around, Elewski added.

It is also important to know when not to stack treatments. Elewski did not recommend stacking a JAK inhibitor with a biologic because the safety of that combination is unknown.

In addition, she advised not to stack a primary biologic nonresponder with another biologic from the same class. “You generally don’t stack biologics together,” she said. “Switch class instead.”

“Another interesting way to stack is with obesity,” Elewski said. “We’ve known for a long time that obesity lowers the efficacy of biologic treatments.” A 2025 expert consensus statement based on a literature search confirmed the strong association between psoriasis and obesity, both chronic inflammatory conditions.

This raises the specter of stacking a psoriasis treatment and an obesity treatment, Elewski said. “Adding a GLP-1 may be helpful in obesity or overweight patients.”

Additional Perspective

“We have many drugs in our tool belt to treat moderate-to-severe psoriasis and give patients clear skin. Within the class of biologic medications are various drugs that target distinct pathways that lead to the development of psoriasis,” said Joshua Zeichner, MD, associate professor of dermatology and director of cosmetic and clinical research in dermatology at The Mount Sinai Hospital in New York City, when asked to comment.

If patients are not responding or are losing response to a specific drug, there is the option of switching medications within the same class or changing to a completely different class for an alternative approach, Zeichner agreed. “We also have the option of stacking treatments and treating patients with more than one agent, which in some cases may be necessary.”

For patients with psoriasis, Zeichner added, “the good news is that we have effective treatments that can be prescribed to you by a board-certified dermatologist.”

Elewski disclosed being a consultant for Amgen, Boehringer Ingelheim, Janssen Pharmaceuticals Inc., Novartis Pharmaceuticals Corp., Pfizer Inc., and UCB; an investigator for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Incyte Corporation, Janssen-Ortho Inc., Novartis Pharmaceuticals, Pfizer, and UCB; and a member of the advisory board for the Foundation for Research & Education of Dermatology. Zeichner had no relevant financial disclosures.

Damian McNamara is a freelance contributor to Medscape Medical News. He worked full-time for Medscape and WebMD from 2018 to 2024. Damian has a BA in chemistry and an MA in science, health and environmental reporting/journalism.