Psoriasis: treatment and what icotrokinra shows

What is psoriasis and how many people have it?

Psoriasis is a chronic noncommunicable disease that can affect the skin, nails and joints. The World Health Organization (WHO) describes it in its 2016 global report as painful, disfiguring and disabling, with no cure, linked to higher cardiovascular risk and other noncommunicable diseases, and with frequent stigma and depression¹. ICD-10 code: L40.

A systematic analysis and modelling study in the BMJ (168 studies) estimated adult prevalence from 0.14% in East Asia to 1.99% in Australasia, with high figures in western Europe (1.92%), central Europe (1.83%) and North America (1.50%); in high-income southern Latin America it was 1.10%. Adult incidence ranged from 30.3 per 100,000 person-years in Taiwan to 321.0 in Italy. The authors stress that 81% of the world's countries lack epidemiological information and that the disease is more frequent in high-income regions and in regions with older populations².

Symptoms and how psoriasis is diagnosed

The most common form is plaque psoriasis: well-demarcated red lesions with silvery scale that can itch or hurt and involve elbows, knees, scalp, nails, genitals, hands and feet. The 2020 JAMA review describes it as an immune-mediated disease involving the IL-23 and IL-17 pathway, and describes its clinical presentation, which includes psoriatic arthritis in a share of patients³. Diagnosis is clinical, based on the look and distribution of the lesions; severity is measured with scales such as the PASI index (range 0 to 72) and the Investigator's Global Assessment (IGA), which are also the endpoints of the trials described below¹¹.

Standard treatment for psoriasis today

The joint American Academy of Dermatology and National Psoriasis Foundation (AAD-NPF) guidelines split treatment by extent and severity. For mild to moderate disease, the guideline on topical therapy and alternative modalities reviews topical treatments and the scales used to measure severity⁴. For moderate to severe disease, the biologics guideline reviews the efficacy and safety of each agent and how to use them in practice⁵. The choice depends on extent, high-impact sites (scalp, genitals, hands and feet), the presence of psoriatic arthritis, comorbidities and patient preference³⁵.

Biologics that block IL-23 are now an efficacy benchmark. For example, in two identical phase 3 trials (UltIMMa-1 and UltIMMa-2; 506 and 491 patients), injectable risankizumab achieved PASI 90 at week 16 in 75.3% and 74.8%, versus 4.9% and 2.0% on placebo and 42.0% and 47.5% on ustekinumab; adverse event frequency was similar across groups⁶. That is the comparison point for any new drug, including an oral one.

What peptide research has shown

In psoriasis there is one approved peptide and one peptide that is part of the disease. They are summarized by agent.

Icotrokinra (FDA-approved). It is a targeted oral peptide that binds the IL-23 receptor with high affinity and blocks its signal¹⁴¹⁵. In the phase 2 FRONTIER 1 trial (255 patients, 16 weeks), PASI 75 was 37%, 51%, 58%, 65% and 79% across the five dose groups, versus 9% on placebo, with a significant dose-response relationship¹⁰. Participants had a mean baseline PASI of 19.1 and a mean disease duration of 18.2 years, and 78% had previously received systemic treatment; the share with at least one adverse event was similar on the drug (52%) and on placebo (51%), with no dose-related increase in events¹⁰. In March 2026 the FDA approved it for moderate-to-severe plaque psoriasis in adults and adolescents aged 12 years or older; for adolescents, a weight of at least 40 kg and being a candidate for systemic therapy or phototherapy are required; at that time it was under review in the European Union and Canada¹⁵¹⁶.

The phase 3 ICONIC-LEAD trial randomized 684 adults and adolescents (456 to icotrokinra, 228 to placebo). At week 16, 65% on icotrokinra and 8% on placebo had IGA 0/1; 50% and 4% had PASI 90; and completely clear skin (IGA 0) was 33% versus 1%. Forty-nine percent in each group had at least one adverse event through week 16¹¹. For psoriasis at high-impact sites, the phase 3 placebo-controlled ICONIC-TOTAL trial enrolled people aged 12 years or older with involvement of the scalp, genitals, or hands and feet¹². In ICONIC-ADVANCE 1 and 2 (1505 participants) the response was superior to placebo and to deucravacitinib, and clear or almost clear skin rates held at about 70-75% between weeks 24 and 52, with about half of participants completely clear (PASI 100)¹³. The trials were funded by the manufacturer, Johnson & Johnson¹¹¹³. A pharmacodynamic study from FRONTIER observed that the drug reduced IL-23/IL-17 axis biomarkers and the expression of psoriasis-associated genes in lesional skin at 16 weeks¹⁴.

LL-37 (cathelicidin) in pathophysiology. LL-37 is the human antimicrobial peptide produced by keratinocytes and immune cells. In a 2007 Nature study, LL-37 coupled with self-DNA and activated plasmacytoid dendritic cells in psoriasis, a mechanism linking skin damage to inflammation⁷. A 2026 study of 38 patients found circulating T cells autoreactive to LL-37 or ADAMTSL5 in 20 (52.6%), versus 5 of 33 healthy donors (15.2%); with tildrakizumab, an anti-IL-23 antibody, autoreactivity decreased, and LL-37-reactive patients had a poorer clinical response at weeks 40 and 52⁸. In cell cultures, LL-37 changed chemokine secretion by mononuclear cells from patients with psoriasis⁹. So here LL-37 is a target of the immune system, not a treatment: we found no trials in people that give it for psoriasis, and the evidence is laboratory and observational. For the general picture of the molecule, see LL-37 and antimicrobial peptides.

Safety and precautions

A pooled analysis of four phase 3 trials followed 2400 icotrokinra-treated participants (1840 participant-years) for one year. Through week 16, rates per 100 participant-years versus placebo were comparable: adverse events 232 versus 269, serious events 5.2 versus 6.6, infections 91 versus 104 and discontinuations for adverse events 6.6 versus 10.0. Through week 24, versus deucravacitinib, adverse events were 204 versus 265 and infections 81 versus 119. Through week 52 no new safety signals were observed¹³¹⁷; the most common events in ICONIC-LEAD were nasopharyngitis and upper respiratory tract infection¹¹.

Safety follow-up is still short compared with biologics, which have years of use: the pooled analysis reaches one year¹⁷. Specific contraindications and warnings are in the approved prescribing information and are not reproduced here. For biologics, the AAD-NPF guideline reviews the risks of each agent, including infections⁵.

Frequently asked questions

Is there an approved peptide for psoriasis? Yes: icotrokinra, an oral peptide that blocks the IL-23 receptor, was approved by the FDA in March 2026 for moderate-to-severe plaque psoriasis in adults and adolescents aged 12 years or older (for adolescents, at least 40 kg and candidates for systemic therapy or phototherapy)¹⁵¹⁶.

Is icotrokinra better than injectable biologics? There is no head-to-head trial against an injectable IL-23 drug. A matching-adjusted indirect comparison, with AbbVie (the maker of risankizumab) authors, found greater efficacy for risankizumab; indirect comparisons have limits¹⁸. In direct trials, icotrokinra was superior to oral deucravacitinib and to placebo¹³.

Is LL-37 useful for treating psoriasis? There is no evidence that it is. LL-37 is elevated in the disease and described as an autoantigen; the studies present it as part of the problem⁷⁸.

How fast does icotrokinra work? In the FRONTIER pharmacodynamic study, IL-23 axis biomarkers fell from week 4 and the reduction was sustained through week 52¹⁴. The main clinical efficacy in the trials was measured at week 16¹¹.

Does psoriasis only affect the skin? No. The WHO notes possible involvement of nails and joints, higher cardiovascular risk and psychological and social burden¹.