The growing availability of biologic therapies such as anti-TNF, anti-interleukin-17 (anti-IL-17), and anti-IL-23, along with newer oral agents, is reshaping treatment goals in psoriasis. Achieving Psoriasis Area and Severity Index 90 (PASI-90) or PASI-100 responses and little-to-no impact on quality of life is increasingly becoming the norm rather than the exception. As treatment options have expanded, so has the complexity of evaluating patients who fail to improve or who lose a previously achieved response. When that happens, clinicians are left to ask: Has the mechanism of action failed, was the dose insufficient, was access to treatment inconsistent, is the diagnosis wrong, or does the current complaint no longer reflect active inflammation?

This discussion guided the forum Psoriasis — Treatment: Confronting Challenges With Innovations, held on September 10, 2026, at the 79th Brazilian Congress of Dermatology in Fortaleza, Brazil. Guilherme de Medeiros Holanda, secretary general of the Brazilian Society of Dermatology’s Ceará Regional Chapter, Xinaida Taligare Vasconcelos Lima, associate professor in the Department of Clinical Medicine at the Faculty of Medicine of the Federal University of Ceará, both in Fortaleza, and Artur Antonio Duarte, professor of dermatology at the Faculty of Medicine of the University of Santo Amaro, São Paulo, Brazil, emphasized that the first step is to distinguish between primary and secondary treatment failure. In the former, the patient never achieves a clinically relevant response; in the latter, the patient initially improves but later loses the response. The two situations call for different investigations and decisions.

False Refractoriness

When two classes of treatment fail in succession, it is tempting to conclude that the disease is intractable. Holanda warned, however, that many “false failures” result from poor adherence, underdosing, incorrect dosing frequency, interruptions in dispensing, or an erroneous differential diagnosis. Dermatophytosis, nummular eczema, and mycosis fungoides can mimic resistant plaques; in psoriatic arthritis, irreversible structural damage may be misinterpreted as persistent activity. Before changing treatment, it is necessary to reconstruct the actual use of the medication, verify the dates of application and dispensing, review factors contributing to worsening symptoms, and reexamine the morphology of the lesions.

A recently published Brazilian study shows why adherence cannot be reduced to a matter of individual will. Among 166 patients using biologics, 82 discontinued treatment. Distribution problems increased the risk for discontinuation by 45%, and delays in delivery, shortages, storage, and postapplication management emerged as components of the therapeutic journey. This finding changes the clinical interpretation: A relapse following missed doses due to drug unavailability does not constitute clear evidence of pharmacologic failure. In a country with vast distances and unequal access, the logistics chain is also integral to treatment effectiveness. The study’s authors include professionals affiliated with Bristol Myers Squibb, a US-based global biopharmaceutical company.

The Role of Biomarkers in Research

Objective assessment may include adherence scales, treatment withdrawal records, and, in selected cases, serum drug levels or antidrug antibody testing. Still, there is no routine biomarker recommended before treatment initiation that can predict which biologic will ultimately fail. Antidrug antibody testing is most helpful in patients with secondary loss of response, where it can help distinguish immunogenicity from inadequate drug exposure. Even then, results need to be interpreted in context, including the timing of the blood draw, the specific medication being used, and the patient’s clinical picture. Without a clear clinical indication, ordering the test may add complexity without improving care.

Where Do the New Oral Treatments Come in?

Deucravacitinib offers a selective oral alternative targeting tyrosine kinase 2, which is particularly appealing for patients with a fear of injections or who face barriers to access and storage. Lima noted that the drug showed superiority over apremilast in the POETYK studies, but a direct comparison with the major biologics is not yet available. Indirect comparisons continue to favor IL-17 inhibitors and IL-23 inhibitors for deeper skin responses. Therefore, the convenience of the oral route should not be confused with universal superiority.

Real-world evidence, however, is maturing. In a Japanese cohort study involving 131 patients published in 2026, deucravacitinib reduced PASI and DLQI scores over 104 weeks, regardless of prior use of apremilast or biologics. Among patients who had not previously been treated with apremilast, 53.8% achieved an absolute PASI score of ≤ 1 at week 104, compared with 25% among those who had been previously treated. The study findings suggested that deucravacitinib may provide lasting responses in some patients but also showed that treatment history influences outcomes. Larger registries, prospective comparisons, and sufficient follow-up are still needed to evaluate rare events and populations typically excluded from trials.

Switch Treatment Classes or Optimize?

Optimization may be appropriate when there has been a partial response or secondary failure, adherence is well established, and the mechanism still appears suitable for the disease’s primary manifestations. Switching takes priority in the event of primary failure, significant adverse events, or when the disease profile points toward another target. According to Holanda, refractory axial or joint symptoms deserve particular attention. A patient whose arthritis remains uncontrolled on a regimen aimed primarily at skin disease may need a treatment mechanism with stronger and more consistent evidence of benefit in the musculoskeletal domain.

Data from the BIOREP registry — a Czech-Slovak cohort with data from January 2015 to June 2025, published in 2026 — show that failure with one therapeutic class does not preclude other options. Among 102 patients who switched from an IL-23 inhibitor to an IL-17 inhibitor, 92 made the switch due to insufficient efficacy. In this group, 82.6% achieved PASI-75 after 3 months and 73.5% after 12 months; an absolute PASI score of ≤ 1 was achieved by 66.3% and 52.9%, respectively. Switching drug classes can therefore restore significant control of the disease, but the decline in response over the first year underscores the need for ongoing monitoring rather than a one-time decision followed by passive observation.

Controlled Skin and Persistent Pain

Duarte, on the other hand, draws attention to patients whose skin is in very good condition but whose joint pain persists. For him, “the first step, without a doubt, is to confirm the diagnosis.” This may require a shared evaluation with a rheumatologist and an MRI, especially in the early stages, when x-rays and ultrasound may be less accurate. Fibromyalgia, other forms of arthritis, and structural damage can coexist with psoriasis and cause pain without inflammatory activity that would justify simply switching the biologic agent.

The dermatologist, however, should not wait for deformity to develop. Duarte described this professional as “a sentinel,” because skin lesions generally precede joint involvement. Asking about morning stiffness, joint pain or swelling, enthesial pain, dactylitis, and axial symptoms should be part of the follow-up. “Once deformities and disabilities have set in, they cannot be reversed,” he warned. Performing early screening and sharing in the patient’s follow-up does not diminish the dermatologist’s role but increases the possibility of altering the functional course of the disease.

The questions raised at the beginning of this discussion are rarely mutually exclusive. They may coexist in the same patient. Therefore, three decisions must remain distinct. The first is to confirm whether active disease is present. The second is to verify whether the patient has, in fact, received adequate treatment. The third is to choose between maintaining, optimizing, or changing the mechanism of action depending on which aspect of the disease remains uncontrolled. Mixing up these steps can lead to intensified treatment without a proper diagnosis, attributing treatment failures to the drug itself, and mistaking tissue damage for inflammation. In short, the most useful innovation will not simply be adding another option to the arsenal, but selecting the correct option after precisely defining which problem still needs to be addressed.

This story was translated from Medscape’s Portuguese edition.