Psoriasis between biology, early action and new oral horizons

From molecular subtypes to an oral IL-23 receptor peptide; timing, intensity and tailored choices may extend remission and improve everyday care.

Understanding endotypes

Opening the session, Prof. Denis Jullien (Lyon, France) argued that psoriasis is best understood as a collection of endotypes - molecularly defined entities with different trajectories and treatment propensities - rather than a single clinicopathologic label. Integrating genomics, transcriptomics, immunology, metabolomics and microbiota allows mechanism-based stratification. Some signals are already clinically tangible: the IL-36 axis in pustular psoriasis supports targeted inhibition; monogenic interferonopathies (e.g., ADAR1) illustrate how genetics can point to interferon-directed approaches. Early GWAS/PRS work and skin transcriptomic deconvolution suggest subgroups with differing probabilities of responding to methotrexate, IL-17 or IL-23 inhibitors. The message was aspirational but cautious: promising tools, pending standardisation and validation before routine use.

Towards a cure: hit early, hit hard

Dr. Andrew Blauvelt (Portland, US) centred his talk on short disease duration (SDD) as a determinant of depth and durability of response. Across trials, patients treated early achieved higher skin clearance and longer drug-free control after withdrawal - shown with secukinumab (including withdrawal/Step-In data) and guselkumab (GUIDE), and echoed by real-world observations with risankizumab and IL-17 agents. A plausible mechanism is better suppression of tissue-resident memory T cells (TRM), often blamed for “relapse in the same spot”. Anti-IL-23 therapies may exert a stronger effect on TRM than anti-IL-17, aligning with longer remissions.

Blauvelt then discussed the “hit hard” component: more intensive induction with IL-23 inhibitors to maximise early clearance and potentially prolong remission without new safety signals. In the Knockout experience with risankizumab at higher-than-standard induction doses, early PASI100 rates were very high and relapses were delayed even after treatment discontinuation, with notable reductions in TRM-17 months later. Looking ahead, a long half-life anti-IL-23 (ORKA-001) is being developed to formally test early + intensive strategies in SDD cohorts. Not a universal “cure,” but a credible path to durable control in selected patients. This concept resonates with the broader treat-to-target paradigm already established in psoriatic arthritis, where early, intensive treatment is linked to sustained remission and prevention of structural damage. Translating a similar mindset into cutaneous psoriasis may shift expectations from controlling flares to maintaining long-term disease quiescence, aligning dermatology and rheumatology goals.

Oral treatments

Despite the dominance of injectables, Prof. Richard Warren (Manchester, UK) highlighted enduring roles for oral options - patient preference, needle-phobia, logistics, and paediatric settings among them. Apremilast remains the reference for safety with modest efficacy. Next-generation PDE4 candidates are in earlier phases. The TYK2 pathway (deucravacitinib) has shown superiority over apremilast with sustained outcomes and a reassuring safety profile distinct from broader JAK inhibition; additional TYK2 molecules are progressing and will clarify whether they can narrow the efficacy gap with biologics.

The most disruptive entrant is the oral IL-23 receptor peptide, icotrokinra (JNJ-2113). In the ICONIC programme, phase-3 studies have shown meaningful PASI and IGA responses with a tolerability profile broadly comparable to placebo in the short term. Importantly, a trial focusing on difficult sites reported clear benefits in scalp and genital psoriasis, while responses on palms/soles were more modest - consistent with the clinical challenge of acral disease. An ustekinumab head-to-head is underway. For many, this could expand oral choices (including ≥12 years where applicable) when injections are less acceptable, while biologics remain first-line for the severest cases.

Diet and psoriasis

Closing the session, Prof. Wendy Hall (London, UK) examined diet with a clinician’s pragmatism. Observational data, including large cohorts, link plant-forward dietary quality to a lower risk of developing psoriasis and to milder self-reported severity among those affected; higher intake of red/processed meat tracks with worse severity, independent of BMI. Interventional evidence is still limited but informative: a 12-week feasibility trial comparing Mediterranean diet, time-restricted eating and control found improvements in DLQI and symptom indices across arms; weight loss favoured the time-restricted pattern, while perceived wellbeing was strongest with the Mediterranean approach.

Adherence was best for the latter and socially more challenging for evening fasting. Practical takeaways today: prioritise weight management where indicated and offer Mediterranean/plant-forward patterns as safe, feasible and patient-friendly; current evidence is insufficient to recommend high-dose vitamin D or probiotics as routine adjuncts.

Beyond skin clearance, the speakers repeatedly emphasized how systemic inflammation, metabolic comorbidities and mental health interact with psoriasis. Lifestyle measures, together with timely and effective therapy, therefore address not only skin lesions but also broader cardiovascular risk and psychological wellbeing. For clinicians, this reinforces the need to approach psoriasis as a multisystem disease rather than a dermatologic condition alone.

Take-home message

Sources and further reading
  1. Jullien D. Understanding endotypes. Psoriasis session (Session ID D1T03.1A), EADV Congress 2025, Virtual/Amsterdam, 17 Sept 2025, 14:15–14:35 CEST.
  2. Blauvelt A. Towards a cure: hit early, hit hard. Psoriasis session (Session ID D1T03.1B), EADV Congress 2025, Virtual/Amsterdam, 17 Sept 2025, 14:35–14:55 CEST.
  3. Warren RB. Oral treatments in a biologics era. Psoriasis session (Session ID D1T03.1C), EADV Congress 2025, Virtual/Amsterdam, 17 Sept 2025, 14:55–15:15 CEST.
  4. Hall W. Diet and psoriasis. Psoriasis session (Session ID D1T03.1D), EADV Congress 2025, Virtual/Amsterdam, 17 Sept 2025, 15:15–15:35 CEST.
  5. Bissonnette R, Pinter A, Ferris LK, Armstrong A, Zhu H, Su Z, et al. JNJ-77242113 (icotrokinra, JNJ-2113), an orally administered IL-23 receptor antagonist peptide in moderate-to-severe psoriasis: results through week 16. N Engl J Med. 2024;390(6):510-521. doi:10.1056/NEJMoa2308713.
  6. Schäkel K, Reich K, Asadullah K, Aschoff R, Philipp S, Pinter A, et al. Early disease intervention with guselkumab in psoriasis leads to a higher rate of stable complete skin clearance: results from the GUIDE study. J Eur Acad Dermatol Venereol. 2023;37(10):2016-2027. doi:10.1111/jdv.19236.
  7. Eyerich K, Asadullah K, Pinter A, Schäkel K, Philipp S, Reich K, et al. Noninferiority of 16-week vs 8-week guselkumab dosing in super responders: GUIDE trial. JAMA Dermatol. 2024 Jul 10 [Epub ahead of print]. doi:10.1001/jamadermatol.2024.2463.