Landmark Studies of Recent Years (2023–2025)

Psoriasis research has picked up pace. This section highlights the most significant studies published in 2023-2025, explaining why each matters and what new knowledge it introduced.

27.1 The 109-Loci GWAS Meta-Analysis (Dand et al., 2025)

Study: Identification of 109 psoriasis susceptibility loci, including 46 novel loci, by multi-ancestry genome-wide meta-analysis. Dand N, et al. Nature Communications. 2025;16:2051. Read it: Nature Communications

Why it matters: This is the largest genetic study of psoriasis ever conducted, analysing 36,466 psoriasis cases and 458,078 controls across 18 genome-wide association studies. It nearly doubled the number of known psoriasis risk loci from ~63 to 109, including 46 entirely novel genetic associations.

New knowledge: The study provided genetic proof that the IL-23/IL-17 axis is the central pathogenic pathway in psoriasis, not just a clinical observation but confirmed at the level of DNA. It also revealed new pathway involvement, including type I interferon signalling, NF-κB regulation, and skin barrier function genes. For patients, the most exciting part is what comes next: validation of existing biologic targets at a genetic level, and a foundation for future pharmacogenomic approaches that could match you to the right drug based on your individual genetic profile.

27.2 The STEPIn Trial — Early Intervention as Disease Modification (Iversen et al., 2023; Conrad et al., 2023)

Study: Secukinumab demonstrates superiority over narrow-band ultraviolet B phototherapy in new-onset moderate to severe plaque psoriasis patients: Week 52 results from the STEPIn study. Iversen L, Conrad C, Eidsmo L, et al. JEADV. 2023;37(5):1004–1016. Read it: JEADV (Wiley)

Why it matters: STEPIn was the first clinical trial ever designed to test whether treating psoriasis aggressively and early, within the first year of disease onset, could modify the long-term course of the disease rather than just manage symptoms. This is a paradigm shift: the question moved from “how do we control this disease?” to “can we prevent it from becoming chronic in the first place?”

New knowledge: At week 52, over 90% of patients treated with secukinumab (an IL-17A inhibitor) achieved PASI 90, far outperforming phototherapy. Even more striking, epigenetic analysis of skin biopsies from STEPIn participants showed that patients treated within the first year of disease had their DNA methylation patterns (epigenetic “scarring” that locks cells into an inflammatory state) reversed to normal levels after 12 months of treatment. In preliminary conference data (not yet peer-reviewed), Conrad et al. reported at EADV 2023 that patients who had the disease for more than 5 years before treatment still had residual epigenetic scarring even after therapy. This suggests a “window of opportunity” in early psoriasis where aggressive treatment could potentially prevent permanent immune reprogramming of the skin.

The GUIDE trial is now investigating a similar approach using guselkumab (an IL-23 inhibitor) with treatment tapering.

27.3 The GUIDE Trial — Super-Responders and Treatment Tapering (Eyerich et al., 2024)

Study: Early disease intervention with guselkumab in psoriasis leads to a higher rate of stable complete skin clearance (‘clinical super response’). Eyerich K, et al. JAMA Dermatology. 2024;160(8):953–963. Read it: JAMA Dermatology

Why it matters: The GUIDE trial introduced the concept of “clinical super-responders,” patients who achieve complete skin clearance that remains stable even when treatment is reduced or withdrawn. This addresses a critical question: can we eventually stop biologic therapy in some patients?

New knowledge: Interim results showed that patients with shorter disease duration (≤2 years) were significantly more likely to achieve and maintain complete skin clearance than patients with longer disease histories. This reinforces the STEPIn findings and supports the hypothesis that early, aggressive treatment may prevent the establishment of tissue-resident memory T cells and epigenetic changes that drive chronic, relapsing disease.

27.4 Bimekizumab Phase 3 Trials — Dual IL-17 Blockade (Warren et al., 2021–2023; BE SURE, BE READY, BE RADIANT, BE BRIGHT)

Study: Bimekizumab versus adalimumab in plaque psoriasis. Warren RB, et al. N Engl J Med. 2021;385(2):130–141 (BE SURE). Extended data published through 2023. Read it: NEJM

Why it matters: Bimekizumab was the first biologic to simultaneously block both IL-17A and IL-17F, testing the hypothesis that IL-17F, previously considered less important than IL-17A, also contributes meaningfully to psoriatic inflammation.

New knowledge: The BE SURE and BE READY trials demonstrated that dual IL-17A/F blockade produces among the highest rates of complete skin clearance (PASI 100) of any therapy studied to date. The BE RADIANT trial provided head-to-head evidence that bimekizumab was superior to secukinumab (an IL-17A-only inhibitor) in achieving PASI 100 at week 16 (61% vs 49%) (Reich et al., 2021), directly demonstrating the clinical benefit of additionally blocking IL-17F. Responses held through 3 years in the BE BRIGHT extension study (Strober et al., 2023). Bimekizumab received FDA approval in October 2023. Its success confirmed that IL-17F is a non-redundant driver of psoriatic inflammation and that blocking both IL-17 family members provides additional clinical benefit over blocking IL-17A alone.

27.5 Cochrane Network Meta-Analysis of Systemic Therapies (Sbidian et al., 2023)

Study: Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Sbidian E, Chaimani A, et al. Cochrane Database Syst Rev. 2023;7:CD011535. Read it: Cochrane Library

Why it matters: This is the gold standard of evidence synthesis, a Cochrane network meta-analysis, and provides the most comprehensive comparison of all systemic psoriasis therapies ever conducted. Clinical guidelines worldwide rely on it when ranking treatment options.

New knowledge: The analysis established the efficacy hierarchy of psoriasis biologics. IL-23 inhibitors (risankizumab, guselkumab) and IL-17 inhibitors (ixekizumab) ranked at the top for achieving PASI 90. It confirmed that newer biologics targeting IL-23 and IL-17 are substantially more effective than older TNF-α inhibitors and conventional systemics, while maintaining favourable safety profiles. Bimekizumab was not included in this analysis (its pivotal trials were too recent for the review’s inclusion window) but has since demonstrated comparable or superior efficacy in head-to-head trials (Section 27.4). This evidence has driven the global shift toward IL-23 inhibitors as first-line biologic therapy.

27.6 Oral IL-23 Receptor Antagonist — Icotrokinra Phase 3 (ICONIC-LEAD, 2025)

Study: Oral Icotrokinra for Plaque Psoriasis in Adults and Adolescents. Bissonnette R, Soung J, Hebert AA, et al. N Engl J Med. 2025;393(18):1784-1795. Read it: NEJM | PubMed

Why it matters: Icotrokinra is a first-in-class oral peptide that selectively blocks the IL-23 receptor. If approved, it would be the first pill to offer the efficacy profile of an injectable IL-23 inhibitor, potentially eliminating the need for injections entirely for many patients with moderate-to-severe psoriasis.

New knowledge: Phase 3 data showed that nearly half of patients achieved completely clear skin (IGA 0) at week 24 with a once-daily pill. Johnson & Johnson has initiated the first-ever head-to-head trial comparing an oral drug (icotrokinra) against an injectable biologic (ustekinumab), seeking to prove that a pill can match or surpass a biologic injection. This could fundamentally shift how psoriasis is treated, removing a major barrier (injection aversion) that prevents some patients from starting biologic therapy.

27.7 Zasocitinib Phase 3 — Next-Generation Oral TYK2 Inhibitor (Takeda, December 2025)

Study: Phase 3 pivotal studies of zasocitinib (TAK-279) in moderate-to-severe plaque psoriasis. Topline results announced December 2025. Phase 2b published: Tehlirian C, et al. JAMA Dermatology. 2024. Read it: Takeda press release | Phase 2b (PubMed)

Why it matters: Zasocitinib is a next-generation TYK2 inhibitor, more selective and potent than the first-in-class deucravacitinib (Sotyktu). The Phase 3 results test whether a second-generation oral TYK2 inhibitor can close the efficacy gap between pills and injectable biologics.

New knowledge: Both pivotal studies met all primary and all 44 ranked secondary endpoints, including PASI 90 and PASI 100, demonstrating complete skin clearance with a once-daily pill. These results approach injectable biologic-level efficacy. This confirmed that the TYK2 pathway, once considered “undruggable,” can be effectively targeted orally, opening the door to an era where high-efficacy psoriasis treatment may no longer require injections.

27.8 Biologics Reduce Psoriatic Arthritis Development (Floris et al., 2025)

Study: Treatment of psoriasis with different classes of biologics reduces the likelihood of peripheral and axial psoriatic arthritis development. Floris A, et al. Rheumatology. 2025;64:1131–1137. Read it: Oxford Academic

Why it matters: Approximately 30% of psoriasis patients develop psoriatic arthritis (PsA), often years after skin disease onset (Griffiths et al., 2021). This study is among the first to demonstrate that treating psoriasis with biologics doesn’t just clear skin. It may actually prevent joint disease.

New knowledge: Patients treated with IL-17 and IL-23 inhibitors had a significantly reduced likelihood of developing both peripheral and axial psoriatic arthritis compared to untreated patients or those on conventional therapies. This supports the “psoriatic march” hypothesis (Section 14.7) and carries major clinical implications: early, effective biologic treatment of skin psoriasis may prevent the downstream organ damage that occurs when systemic inflammation goes unchecked.

27.9 Hepcidin and Iron Dysregulation — A Novel Pathogenic Mechanism (2024)

Study: Skin hepcidin initiates psoriasiform skin inflammation via Fe-driven hyperproliferation and neutrophil recruitment. Abboud E, Chrayteh D, Boussetta N, et al. Nature Communications. 2024;15(1):6718. Read it: Nature Communications | PMC

Why it matters: Researchers have proposed that hepcidin, a hormone that regulates iron metabolism, when produced abnormally in the skin, may be a root cause of psoriatic inflammation. This is a completely novel angle that falls outside the traditional IL-23/IL-17 paradigm.

New knowledge: If confirmed in larger studies, iron dysregulation in the skin could represent an entirely new therapeutic target. This finding reminds us that while the IL-23/Th17 axis is the dominant framework, psoriasis pathogenesis may involve additional mechanisms that current therapies don’t address.

27.10 Somatic Mutations Ruled Out (2023)

Study: Effects of psoriasis and psoralen exposure on the somatic mutation landscape of the skin. Olafsson S, Rodriguez E, Lawson ARJ, et al. Nature Genetics. 2023;55(11):1892-1900. Read it: Nature Genetics | PubMed

Why it matters: One longstanding hypothesis was that psoriasis might be driven by somatic mutations (random DNA changes that accumulate in skin cells over a lifetime), similar to how cancer develops. If true, this would have fundamentally changed how we understand the disease.

New knowledge: Comprehensive genetic analysis showed that somatic mutations are not linked to either the development or the spread of psoriatic plaques. This conclusively rules out a cancer-like mutational model and confirms that psoriasis is driven by immune dysregulation acting on genetically predisposed but otherwise normal skin cells, reinforcing the rationale for immune-targeting therapies.

27.11 Deucravacitinib — First TYK2 Inhibitor (POETYK PSO-1 and PSO-2, 2022)

Study: Trial of Deucravacitinib versus Placebo and Apremilast in Moderate to Severe Plaque Psoriasis. Armstrong AW, et al. N Engl J Med. 2023;388(8):666–678. Read it: NEJM | PubMed

Why it matters: Deucravacitinib (Sotyktu) was the first oral drug to selectively inhibit TYK2, a specific member of the Janus kinase family involved in IL-23, IL-12, and type I interferon signalling. Unlike older JAK inhibitors (tofacitinib, baricitinib) that broadly suppress multiple JAK enzymes and carry cardiovascular and thromboembolic safety signals, deucravacitinib targets only TYK2 through its regulatory (pseudokinase) domain, offering a more selective mechanism. It received FDA approval in September 2022.

New knowledge: The POETYK PSO-1 and PSO-2 trials demonstrated that deucravacitinib achieved PASI 75 in approximately 53-59% of patients at week 16, significantly outperforming both placebo and apremilast (the only other oral targeted therapy). While these response rates fall below injectable biologics, deucravacitinib established that the TYK2 pathway is a viable oral drug target and opened the door for next-generation TYK2 inhibitors like zasocitinib (Section 27.7) that aim to close the efficacy gap with biologics.

27.12 Spesolimab — First Approved Therapy for GPP Flares (Effisayil 1, 2021)

Study: Trial of Spesolimab for Generalized Pustular Psoriasis. Bachelez H, et al. N Engl J Med. 2021;385(26):2431–2440. Read it: NEJM | PubMed

Why it matters: Generalised pustular psoriasis (GPP) is rare and potentially life-threatening, yet it had no specifically approved treatment until spesolimab (Spevigo). Before this, GPP flares were managed with off-label use of drugs developed for plaque psoriasis, often with poor results. Spesolimab is a monoclonal antibody that blocks the IL-36 receptor, targeting the distinct inflammatory pathway that drives GPP (Section 7.3). It received FDA approval in September 2022.

New knowledge: The Effisayil 1 trial showed that a single intravenous dose of spesolimab cleared pustules in 54% of patients within one week, compared to 6% on placebo. This trial validated IL-36 as the dominant cytokine pathway in GPP (distinct from the IL-23/IL-17 axis of plaque psoriasis) and demonstrated that targeting it could rapidly control a previously uncontrollable disease. The Effisayil 2 trial subsequently showed that subcutaneous spesolimab prevented GPP flares over 48 weeks (Bachelez et al., 2024).

27.13 Tapinarof — A New Topical Mechanism (PSOARING 1 and 2, 2022)

Study: Two Phase 3 Trials of Tapinarof Cream for the Treatment of Plaque Psoriasis. Lebwohl M, et al. N Engl J Med. 2022;387(11):983–994. Read it: NEJM | PubMed

Why it matters: Tapinarof (Vtama) was the first topical aryl hydrocarbon receptor (AhR) agonist approved for psoriasis (May 2022), representing an entirely new mechanism of action in a therapeutic space long dominated by corticosteroids and vitamin D analogues. It offered something no topical steroid can: no duration-of-use restrictions and a “remittive effect” where skin improvement continues after treatment stops.

New knowledge: The PSOARING trials demonstrated a unique post-treatment durability: patients who achieved clear or almost-clear skin maintained that response for a median of approximately 4 months after stopping the cream. This “remittive effect” was unprecedented for a topical agent and suggests that tapinarof may modulate the underlying immune response rather than simply suppressing symptoms. Section 23 covers the clinical details of tapinarof use.