Evaluating Risankizumab's Long-Term Effects in Psoriasis Using Optical Coherence Tomography.

Psoriasis is a common, chronic inflammatory skin disease which typically follows a relapsing and remitting course, and is associated with joint disease in approximately 25% of patients.1 The significant reduction in quality of life and the psychosocial disability suffered by patients underline the need for prompt, effective treatment, and long-term disease control (reviewed2, 3). Localized, limited disease can usually be managed satisfactorily with topical agents. Those with moderate to severe disease often require systemic treatment. Phototherapy and traditional 'standard' systemic therapies, while often effective, can be associated with long-term toxicity; some are expensive, and some patients have treatment-resistant disease.4 Also, phototherapy is not available to many due to geographical, logistical or other constraints. Patients themselves demonstrate high levels of dissatisfaction with standard approaches to treatment.5, 6 Biologic therapies for psoriasis utilize molecules designed to block specific molecular steps important in the pathogenesis of psoriasis and now comprise a number of well-established, licensed, treatment options for patients with severe disease. Since 2005, when the British Association of Dermatologists (BAD) first published guidance on the use of biologic therapies in psoriasis,7 much has changed. There is a substantial body of new evidence pertinent to the clinical use of these treatments, the U.K. National Institute for Health and Clinical Excellence (NICE) has approved the use of a number of biologic therapies in severe chronic plaque psoriasis and the BAD Biologic Interventions Register (BADBIR) has been successfully launched. Despite these developments, use of biologic therapy in clinical practice remains limited in the U.K., with a shortfall in funding cited as a significant obstacle to prescribing in approximately 40% of units recently surveyed.8 These guidelines have been revised and updated in accordance with a predetermined scope. This is based on the original scope used in 2005, and extended to include additional areas of practice. Recommendations in this guideline supersede those in the 2005 guideline. The overall objective of these guidelines is to provide up-to-date, evidence-based recommendations on use of biologic therapies (infliximab, adalimumab, etanercept, ustekinumab) in adults and children with all types of psoriasis and, where relevant, psoriatic arthritis, for clinical staff involved in the care of patients treated with biologic therapies. Efalizumab remains in the scope of the guideline in relation to safety only, given that the European Medicines Agency has withdrawn the marketing authorization of this drug because of concerns over the development of progressive multifocal leukoencephalopathy (PML). This guidance does not cover agents licensed outside the U.K. (alefacept) or use of biologic therapies for indications other than psoriasis and psoriatic arthritis. The guideline working group represents all relevant stakeholders including dermatologists, nurses, rheumatologists and patients. Draft guidance was made available for consultation and review by patients, the BAD membership and the British Dermatological Nursing Group (BDNG). Advice relating to tuberculosis was reviewed and approved by the British Thoracic Society. The guideline has been developed using the BAD's recommended methodology9 and with reference to the AGREE (Appraisal of Guidelines Research and Evaluation) instrument.10 Recommendations were developed for implementation in the National Health Service using a process of considered judgment based on the evidence and an awareness of the European product licence of the various treatments. Cochrane, EMBASE and Medline databases were searched between 1990 and June 2009 for clinical trials involving adalimumab, efalizumab, etanercept, infliximab and ustekinumab using an agreed protocol. Two reviewers screened all titles and abstracts independently, and full papers of relevant material were obtained. In relation to efficacy, only randomized controlled trials (RCTs) of high quality (1+ or more; see Appendix 1) were included for chronic plaque psoriasis, whereas in other clinical phenotypes, given the paucity of published data, all data were included. Data from each paper were extracted by two members of the guideline group using standardized literature evaluation forms in order to create evidence tables. Evidence on safety was extracted from literature on use of biologic agents for any indication in view of the relatively limited data specifically relating to use in psoriasis. The methodological limitations of the safety analysis are detailed in section 15. The guideline was peer reviewed by the Clinical Standards Unit of the BAD (made up of the Therapy & Guidelines and Audit & Clinical Standards Subcommittees) prior to publication. These guidelines have been prepared on behalf of the BAD and reflect the best data available at the time the report was prepared. Caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations in this report. It may be necessary or even desirable to depart from the guidelines in the interests of specific patients and special circumstances. Just as adherence to guidelines may not constitute defence against a claim of negligence, so deviation from them should not necessarily be deemed negligent. This field of psoriasis biologic therapeutics is in a rapid phase of development, and revision of the scope and content of the guidelines will therefore occur on an annual basis. Where necessary, the guideline will be updated via the BAD website, and a fully revised version is planned for 2012. Most patients with moderate to severe disease achieve satisfactory disease control (i.e. significant or complete clearing of disease) in the short term with at least one of the systemic agents currently available.4 Long-term disease control frequently requires some form of continuous therapy and consequent, predictable risks of toxicity. At present, the risks and benefits of biologic therapies relative to standard systemic therapy are largely unknown. Widespread use of these agents in uncomplicated moderate to severe psoriasis is inappropriate and is not supported by the licensed indications for these drugs. Eligibility criteria should encompass both objective measures of disease severity and the impact the disease has on quality of life. All existing disease severity assessment tools are imperfect11-13 and most require some training to complete. The Psoriasis Area and Severity Index (PASI) is a measure of disease severity in chronic plaque psoriasis12 and has been chosen for the purposes of this guideline as it has been widely used in clinical trials including those investigating biologic therapies, and has also been adopted by NICE. A PASI score of ≥ 10 (range 0–72) has been shown to correlate with a number of indicators commonly associated with severe disease such as need for hospital admission or use of systemic therapy,14 and reflects the minimal level of disease severity required for patient inclusion in most of the clinical trials of biologic therapies to date. Where the PASI is not applicable (e.g. pustular psoriasis), body surface area (BSA) affected should be used, with severe disease defined as > 10% BSA affected.14 The Dermatology Life Quality Index (DLQI) is a validated tool for the measurement of quality of life across all skin diseases, including psoriasis, and has been used in both trial and clinical practice settings.13, 15 A score of > 10 (range 0–30) has been shown to correlate with at least 'a very large effect' on an individual's quality of life.12, 14, 16 When using the PASI and DLQI to determine whether or not a patient should be considered for biologic therapy, clinicians should take into account the applicability of these measures to each individual patient. There are circumstances where the use of these tools fails to give a sufficiently accurate assessment of the clinical situation. With respect to the PASI, this is especially pertinent in patients with localized disease that involves special 'high-impact' sites (genitalia, hands, feet, head and neck) where highly significant functional and/or psychosocial morbidity may exist with a PASI < 10. The DLQI may be a poor indicator of emotional disabilities resulting from psoriasis and the validity of the DLQI (and of other quality of life measures) may also be undermined due to linguistic or other communication difficulties.13 Patients with psoriasis may be considered eligible to receive treatment with any of the licensed biologic interventions when they fulfil the eligibility criteria set out below. However, the decision to proceed with treatment must be made in collaboration with the patient and include a careful assessment of the associated risks and benefits17 Eligibility criteria To be considered eligible for treatment, patients must have severe disease as defined in (a) and fulfil one of the clinical categories outlined in (b): (a) Severe disease defined as a PASI score of 10 or more (or a BSA of 10% or greater where PASI is not applicable) and a DLQI > 10. In exceptional circumstances (for example, disease affecting high-impact sites with associated significant functional or psychological morbidity such as acral psoriasis), patients with severe disease may fall outside this definition but should be considered for treatment (Strength of recommendation D; level of evidence 3) AND (b) Fulfil at least one of the following clinical categories (Strength of recommendation D; level of evidence 3, and formal consensus) where phototherapya and alternative standard systemic therapyb are contraindicated or cannot be used due to the development of, or risk of developing, clinically important treatment-related toxicity. are intolerant to standard systemic therapy are unresponsive to standard systemic therapyb have significant, coexistent, unrelated comorbidity which precludes use of systemic agents such as ciclosporin or methotrexate have severe, unstable, life-threatening disease Eligibility criteria for patients with skin and joint disease patients with active psoriatic arthritis or skin disease that fulfils defined British Society for Rheumatology (BSR)18 or BAD guideline criteria, respectively patients with severe skin psoriasis and psoriatic arthritis who have failed or cannot use methotrexate may need to be considered for biologic treatment given the potential benefit of such treatment on both components of psoriatic disease aPhototherapy may be inappropriate in patients (i) who have exceeded safe exposure limits (150–200 treatments for PUVA, 350 treatments for narrowband UVB19, 20), (ii) who are nonresponsive or relapse rapidly, (iii) who have a history of skin cancer or repeated episodes of severe sunburn, (iv) who are intolerant of UV exposure, especially if skin phototype I (sun-sensitive), or (v) for logistical reasons bStandard systemic therapy includes ciclosporin (2·5 mg kg−1 daily; up to 5 mg kg−1 daily), and in men, and women not at risk of pregnancy, methotrexate [single dose (oral, subcutaneous, intramuscular) of 15 mg weekly; max 25 mg weekly] and acitretin (25–50 mg daily) An adequate response to treatment is defined as either (i) a 50% or greater reduction in baseline PASI (PASI 50 response) (or % BSA where the PASI is not applicable) and a 5-point or greater improvement in DLQI4, 21-23or (ii) a 75% reduction in PASI score compared with baseline (PASI 75 response). Initial response to therapy should be assessed at time points appropriate for the drug in question (Table 1). For patients on tumour necrosis factor (TNF) antagonist treatment with psoriasis and psoriatic arthritis, treatment may be continued if there has been a sufficient response in at least one of these components (see BSR guidelines18 for definition of disease response in psoriatic arthritis). TNF is a proinflammatory cytokine produced by a wide variety of cell types including keratinocytes. It plays a central role in the pathogenesis of psoriasis, psoriatic arthritis and a number of other disease states. TNF is released from cells as a soluble cytokine (sTNF) following cleavage from its cell surface-bound precursor (transmembrane TNF, tmTNF). Both sTNF and tmTNF are biologically active, and bind to either of two distinct receptors: TNF receptor 1 (TNFR1, p55) and TNF receptor 2 (TNFR2, p75). This leads to NF-κB activation (which promotes inflammation) and/or cell apoptosis. In addition, tmTNF can itself act as a ligand (via a process of reverse signalling) to induce cell activation, cytokine suppression or apoptosis of the tmTNF-bearing cell. Soluble forms of the TNF receptors also exist and, by binding and neutralizing sTNF, may act as natural TNF antagonists. There are currently two approved groups of biologic agents that target TNF: anti-TNF monoclonal antibodies (adalimumab and infliximab), and sTNF receptors (etanercept). Infliximab is a chimeric human–murine monoclonal antibody (∼ 25% mouse-derived protein) whereas adalimumab is fully human. Etanercept is a genetically engineered fusion protein composed of a dimer of the extracellular portions of human TNFR2 (p75) fused to the Fc domain of human IgG1. All three agents specifically bind both soluble and transmembrane forms of TNF and act by (i) blocking TNFR-mediated mechanisms and (ii) inducing tmTNF (reverse-signalling) events. Etanercept also binds members of the lymphotoxin family [LTα3 (also known as TNF-β) and LTα2β1] although the biological significance of this is unclear. Aside from the latter, there are important differences between the three agents with respect to pharmacokinetics, immunogenicity and structure-based mechanisms of action (only some of which are completely understood).24 It is likely that these differences, in the context of the highly complex biology of TNF, account for observed differences in the efficacy and adverse events profile of TNF antagonists. Lymphocyte function-associated antigen-1 (LFA-1) is a cell surface protein that binds to intracellular adhesion molecule (ICAM) 1–3 and plays a key role in T-lymphocyte recirculation, trafficking to sites of inflammation, antigen presentation by dendritic cells and other activated cells including keratinocytes, and T-cell costimulation. Efalizumab is a recombinant humanized IgG1 monoclonal antibody that binds specifically to the CD11a subunit of LFA-1, which by interfering with LFA-1/ICAM binding inhibits several key steps important in the pathogenesis of psoriasis including T-cell migration into the skin and T-cell activation. More recently, in vivo data have shown that efalizumab induces a state of reversible T-cell 'hyporesponsiveness' including downregulation of a number of T-cell surface molecules unrelated to LFA-1 both in the circulation and in psoriatic plaques.25, 26 Interleukin (IL)-12 and IL-23 are heterodimeric cytokines secreted by activated antigen-presenting cells, and share a common protein subunit, p40. Of relevance to psoriasis, IL-12 activates CD4 and natural killer cells to induce expression of type 1 cytokines (TNF and interferon-γ) while IL-23 stimulates survival and proliferation of a subset of T cells that produce IL-17 (Th17 cells). Recent immunological27 and genetic studies indicate a central role for IL-23 in the pathogenesis of psoriasis.28Ustekinumab is a fully human IgG1κ monoclonal antibody which acts as an IL inhibitor by binding with high affinity and specificity to the p40 protein subunit. It thus prevents IL-12 and IL-23 from binding to their IL-12Rβ1 receptor protein expressed on the surface of immune cells. Three large RCTs demonstrate that etanercept is effective in chronic plaque psoriasis.29-31 Onset of action is slower than that seen with the monoclonal antibodies, with clinically significant improvement in disease severity scores evident between 4 and 8 weeks after initiation of treatment.30 Response is dose related, with 34% (25 mg biweekly) and 48% (50 mg biweekly) of patients achieving PASI 75 by 12 weeks (Table 2). Continuing therapy up to 6 months improves response rates further (43% and 57% for 25 mg biweekly and 50 mg biweekly, respectively).29, 30, 32 While there are no RCT data establishing efficacy beyond 6 months, data from a 2-year, open-label etanercept 50 mg biweekly extension study32 (following the phase III study reported by Tyring et al.31) suggest that efficacy is maintained for up to 1 year, with approximately 75% of patients maintaining their PASI 75 response over the ensuing year. Overall, continuous therapy provides better disease control and higher levels of patient satisfaction compared with interrupted therapy. When treatment is stopped, disease relapses slowly: median time to disease relapse as defined by loss of PASI 50 in those who achieved PASI 75 after 24 weeks of continuous etanercept 25 or 50 mg biweekly, was 85 and 91 days, with no evidence of disease PASI scores were with the of patients achieving efficacy after 12 further weeks (i.e. and of PASI 75 achieved this level of efficacy on Aside from objective measures of disease improvement studies also report associated clinically in quality of life reduction in and and of patients in analysis of two of these RCTs that response rates in those over were the as those although in the group were The 25 mg and 50 mg are given that their are that the number of patients achieving PASI 75 at 12 weeks following etanercept 50 mg an RCT compared with was with that seen in other RCTs investigating etanercept 25 mg biweekly and that no significant differences were observed in PASI or DLQI in a of patients open-label etanercept 25 mg biweekly and etanercept 50 mg In the RCTs the of adverse events or adverse events in patients etanercept was no greater than in the control patients, with the of in each treatment RCT has shown efficacy of etanercept 25 mg compared with acitretin mg kg−1 at 24 weeks (see the role of TNF in levels of TNF in patients, and the used for etanercept, response rates may occur in patients, with This is in by published RCT and data cited in the study by et The of etanercept and methotrexate has been shown to be more effective in arthritis than either with no significant additional toxicity. data suggest that the of methotrexate may also etanercept efficacy in psoriasis. A RCT the efficacy and safety of etanercept (25 mg biweekly) in patients on and reported of patients or at 24 weeks on therapy, as compared with those in methotrexate was A reported both efficacy with the of methotrexate in patients on etanercept and loss of efficacy on of methotrexate from patients on Data from a RCT reported that the of etanercept 25 mg with acitretin mg kg−1 is as effective as etanercept 25 mg and that both these interventions are more effective that acitretin These data suggest that in the short term at the may additional efficacy as there is no additional associated toxicity. The patient in the cited RCTs may not be of patients likely to be treated in clinical practice as to the studies required patients only to be considered or have or systemic therapy. However, objective disease severity criteria were the as those currently recommended by the BAD and and PASI scores on to studies were higher from 16 to studies of practice report response rates in patients who have failed systemic therapies, all of which that data from the RCTs can be to clinical 50 There is a of long-term RCT data beyond 6 months, and only limited data on the two published studies one is and both report following one of treatment RCT data indicate that 50 mg biweekly is more effective than 25 mg biweekly, but there are no trial data whether the dose to 50 mg biweekly in patients who to achieve or adequate on 25 mg biweekly results in disease This is especially pertinent given guidance which currently limits treatment to the 25 mg biweekly dose (see Etanercept is licensed for use in moderate to severe psoriasis at either 50 or 25 mg biweekly for the first months, and 25 mg biweekly for up to 24 therapy beyond 24 weeks may be appropriate for some patients has approved use of etanercept in severe plaque psoriasis to defined disease at the 25 mg biweekly dose only, and not the 50 mg dose effective, with therapy to be continued only in those patients achieving disease response at months (Table 1). Etanercept is recommended for the treatment of patients with severe psoriasis who fulfil the disease severity criteria to section (Strength of recommendation level of evidence Etanercept therapy may be at either 50 or 25 mg and disease response assessed at months (Strength of recommendation level of evidence The of which dose to use will on clinical disease body and, in the U.K., the dose that will be (Strength of recommendation level of evidence Patients on etanercept 25 mg may to to etanercept 50 mg as these two are in of efficacy (Strength of recommendation level of evidence In patients who treatment may be continued to clinical although long-term data on efficacy are limited to 2 (Strength of recommendation level of evidence may be risk of disease although there may be a response on therapy (Strength of recommendation level of evidence may be recommended in clinical where it is required for associated or to efficacy (Strength of recommendation level of evidence Three large indicate that infliximab therapy is highly effective in chronic plaque psoriasis (Table Onset of action is with evidence of significant improvement the first 2 weeks of treatment and benefit by 10 when of patients achieve PASI 75 (Table (and in DLQI of This response is largely maintained over time with and achieving PASI 75 at 6 and 12 months, respectively (Table 2). of efficacy with development of antibodies to which in of patients continuous therapy and 5 mg following a standard 2 and 6 continuous therapy at 5 mg kg−1 8 weeks achieved to relapse in the by loss of PASI was as and in the of although data were not An that 50% patients relapse of PASI by There are no published trial data beyond 1 year. study assessed disease using the Psoriasis Severity Index to a a improvement in from baseline was observed at 10 with a of improvement reported at This was maintained of patients with complete of disease the target continued to between weeks 24 and 50 and There are no RCT data on use of methotrexate in with infliximab in psoriasis. In both and psoriatic arthritis, with methotrexate is a licensed and response rates and are at least in these disease levels of infliximab have been reported with methotrexate which may in of mg also the of antibodies to The patient in the cited RCTs may not be of patients likely to be treated in clinical practice. The PASI at baseline was ≥ 10 in all the studies However, of systemic therapy was not an in that most studies required patients to be for systemic therapy and/or failed A of patients in the study by et indicate that baseline PASI > and the of treatments two or more systemic therapies, or biologic no on treatment The of the study investigating continuous infliximab therapy is in that study at patients randomized to receive therapy receive infliximab at PASI 75 was not and in both were reported as Infliximab is licensed for use mg kg−1 8 in moderate to severe plaque psoriasis. has approved use of infliximab in patients with severe (PASI ≥ DLQI ≥ with treatment beyond 10 weeks recommended only in those who achieve response Infliximab is recommended for the treatment of patients with severe psoriasis who fulfil the disease severity criteria to section (Strength of recommendation level of evidence Infliximab therapy should be at a dose of 5 mg kg−1 at weeks 2 and 6 and disease response assessed at months (Strength of recommendation level of evidence In patients who mg should be given at to disease control although long-term data are available only up to 1 (Strength of recommendation level of evidence therapy should be given the associated risk of and disease control (Strength of recommendation level of evidence may be recommended in clinical where it is required for associated to efficacy or to the development of antibodies to infliximab (Strength of recommendation D; level of evidence 3) Three large RCTs demonstrate that adalimumab is a highly effective treatment for chronic plaque psoriasis (Table Onset of action is with significant in disease severity evident 2 weeks of treatment and disease response seen between weeks 12 and Response is dose with of patients achieving PASI 75 at 12 with adalimumab mg other (i.e. the licensed dose for psoriasis), and achieving PASI 75 with adalimumab mg relevant in quality of life indicators are also In one a subset of patients who failed to achieve PASI 50 following at least 24 weeks of adalimumab other was to the dose for the of the study 40% of this PASI 50 that dose may further data are available up to 1 year, with no evidence of significant loss of response over time in those patients who and are continued on of response on treatment was also in the phase of the study reported by et those who maintained PASI 75 by were to receive either or a further weeks of adalimumab While time to relapse was not of patients PASI 50 response relative to baseline with a of a in PASI score relative to compared with relapse in those on adalimumab by of this patients who

BackgroundChronic plaque psoriasis is a common immune-mediated dermatosis that often requires long-term systemic therapy in patients with moderate to severe disease. Methotrexate has been a cornerstone of systemic treatment for decades; however, concerns regarding delayed onset of action, cumulative toxicity, and the need for close laboratory monitoring have driven interest in newer targeted oral therapies. Tofacitinib, an oral Janus kinase (JAK) inhibitor, modulates multiple cytokine signaling pathways implicated in psoriasis pathogenesis, though comparative data from the Indian population remain limited.ObjectivesThe present study aimed to compare the efficacy, time to response, relapse rates, and safety profile of oral tofacitinib versus oral methotrexate in patients with moderate to severe chronic plaque psoriasis.MethodsThis prospective, randomized, open-label comparative study was conducted over 18 months (August 2023 to January 2025) at Great Eastern Medical School & Hospital, a tertiary care teaching hospital in South India. Adult patients with biopsy-proven chronic plaque psoriasis of at least three months’ duration, a Psoriasis Area and Severity Index (PASI) score greater than 10, and body surface area involvement exceeding 10% were enrolled. Forty-two eligible patients were randomized into two groups: Group A (n = 21) received oral tofacitinib 5 mg twice daily, while Group B (n = 21) received oral methotrexate 10 mg once weekly with folic acid supplementation. Clinical assessment using PASI was performed at baseline and at two, four, eight, 12, and 16 weeks. Treatment efficacy, PASI 75 and PASI 90 responses, time to PASI 75, relapse, and adverse events were analyzed.ResultsBoth treatment groups demonstrated a progressive and statistically significant reduction in mean PASI scores over the 16-week treatment period, with no statistically significant difference in mean PASI reduction between the two groups at individual follow-up visits. Tofacitinib showed a faster onset of action, with a higher proportion of patients achieving PASI 75 by week 12 (57.1%), whereas methotrexate demonstrated a higher cumulative PASI 75 response by week 16 (71.4%). Achievement of PASI 90 at week 16 was significantly higher in the tofacitinib group compared to the methotrexate group (57.1% vs. 19.0%; p < 0.05). Relapse was observed more frequently in the methotrexate group, although this difference did not reach statistical significance. Mild elevation of liver enzymes was the most commonly observed adverse effect in both groups, and no serious adverse events were recorded.ConclusionOral tofacitinib and methotrexate are both effective systemic therapies for moderate to severe chronic plaque psoriasis. Tofacitinib offers the advantage of faster and deeper clinical clearance, while methotrexate demonstrates comparable efficacy over a longer treatment duration. Tofacitinib may be considered a useful oral alternative in patients requiring rapid disease control.

Introduction The Psoriasis Longitudinal Assessment and Registry (PSOLAR; NCT00508547) is a large, international, prospective, longitudinal, disease-based registry that enrolled patients with psoriasis (PsO) who were receiving, or were candidates for, systemic therapy. The aims of the Registry are to assess the long-term safety and improve understanding of real-world biologic use in patients with PsO. Objective The objective of this analysis is to describe real-world effectiveness of guselkumab in patients with psoriasis. Methods Disease characteristics, absolute Psoriasis Area and Severity Index (PASI) score, percentage of body surface area (BSA) involvement, and change from baseline in PASI score and BSA through two years are reported for patients with PsO treated with guselkumab (GUS). Some patients initiated GUS ahead of enrolment in the registry. Results As of 12 July 2024, 2198 patients who initiated GUS prior to, or at, enrolment were included with a mean (standard deviation [SD]) duration of follow-up of 3.02 (1.08) years. Of these, 1184 (53.9%) were from North America, 672 (30.6%) were from Europe and 342 (15.6%) were from the Asia-Pacific region. Through 2 years of treatment, 244 (11.1%) patients withdrew from the registry, with the most common reason for withdrawal being patient choice (n=96, 39.3%) and 48 (19.7%) patients being lost to follow-up. Most patients had plaque PsO (2140, 97.4%) with a mean (SD) baseline PASI score of 6.0 (7.02) and a mean (SD) BSA involvement of 8.9% (12.72%). At baseline, 427 (21.1%) patients had a PASI score of 0, 188 (9.3%) had PASI &gt;0–&lt;1, 199 (9.8%) had PASI ≥1–&lt;2, 160 (7.9%) had PASI ≥2–&lt;3, 231 (11.4%) had PASI ≥3–&lt;5 and 816 (40.4%) had PASI ≥5. Approximately 1 in 4 GUS patients had a PASI score of &gt;10 (n=496; 24.5%). At Month 6, the mean (SD) change from baseline in PASI score was −4.5 (7.06) and the mean (SD) change from baseline in %BSA was −6.6 (12.41), corresponding to a mean (SD) absolute PASI score of 1.6 (3.10) and a mean (SD) BSA of 2.3% (5.81%), respectively. Improvements were maintained through 1 year of therapy; at Month 12, the mean (SD) change from baseline in PASI score was −4.4 (6.96) and in %BSA was −6.8 (12.26), corresponding to mean (SD) absolute PASI score of 1.5 (2.74) and a mean (SD) BSA of 1.9% (4.79%). Improvements were maintained through 2 years of treatment, with a mean (SD) absolute PASI score of 1.5 (3.13) and a mean (SD) BSA of 2.1% (6.08%), respectively. Conclusion: Patients in this large real-world registry experienced improvements in PsO severity while receiving treatment with GUS. Improvements were maintained through 2 years of treatment, supporting the use of GUS as a highly effective long-term option for patients with PsO.

PV058 / #431Poster Topic:AS06 - ComorbiditiesBackground/PurposeRetinopathy is a common ocular manifestation in SLE, and it is often caused by microangiopathy resulting from immune complex deposition, leading to vasculitis and thrombosis in the retinal microcirculation. Antiphospholipid antibodies (aPL) are present in around 30% of SLE patients, with 10% developing antiphospholipid syndrome (APS). Retinal involvement in APS can manifest as arterial and venous thrombosis. While macrovascular involvement manifests with prominent symptoms such as amaurosis fugax or transient diplopia, microvascular involvement may remain asymptomatic and manifest at the retinal level with microhaemorrhages, microaneurysms, and cotton-wool spots. This study aimed to evaluate the association between aPL positivity and preclinical retinal vascular changes in SLE patients.MethodsThis cross-sectional, two-center study included 112 SLE patients and 134 healthy controls recruited from Hospital Clinic de Barcelona and Policlinico Tor Vergata in Rome. Patients underwent ophthalmological evaluations, including visual acuity measurement, slit-lamp biomicroscopy, intraocular pressure measurement, and fundus examination. Retinal structural changes, such as macular thickness (MT) and retinal nerve fiber layer (RNFL) thickness, were assessed using spectral-domain optical coherence tomography (SD-OCT). Retinal vascular changes, including vessel density (VD), vascular perfusion (VP), and foveal avascular zone (FAZ), were evaluated using OCT angiography (OCTA). Statistical analysis was performed to compare differences between SLE subgroups stratified based on aPL positivity or the presence of APS.This cross-sectional, two-center study included 112 SLE patients and 134 healthy controls recruited from Hospital Clinic de Barcelona and Policlinico Tor Vergata in Rome. Patients underwent ophthalmological evaluations, including visual acuity measurement, slit-lamp biomicroscopy, intraocular pressure measurement, and fundus examination. Retinal structural changes, such as macular thickness (MT) and retinal nerve fiber layer (RNFL) thickness, were assessed using spectral-domain optical coherence tomography (SD-OCT). Retinal vascular changes, including vessel density (VD), vascular perfusion (VP), and foveal avascular zone (FAZ), were evaluated using OCT angiography (OCTA). Statistical analysis was performed to compare differences between SLE subgroups stratified based on aPL positivity or the presence of APS.ResultsOCTA analysis revealed decreased vascular parameters in SLE patients compared to controls in both cohorts. Specifically, the Barcelona cohort showed significant reductions in VD and VP (Table 1), while the Rome cohort showed significant reductions in parafoveal superficial VD. No clear association was found between aPL positivity and alterations in OCTA vascular parameters in SLE patients. However, a possible correlation between aPL positivity and variations in RNFL thickness was observed in both cohorts (Table 2 and Table 3).Table 1.Spectral-domain Optical Coherence Tomography (SD-OCT) and Angiography by Optical Coherence Tomography (OCTA) parameters at Barcelona cohort, right eyea.Table 2.Spectral-domain Optical Coherence Tomography (SD-OCT) and Angiography by Optical Coherence Tomography (OCTA) parameters at Barcelona cohort, by antiphospholipid antibodies, right eyea.Table 3.Spectral-domain Optical Coherence Tomography (SD-OCT) and Angiography by Optical Coherence Tomography (OCTA} parameters at Rome cohort, by antiphospholipid antibodies, right eyea.ConclusionsWhile SLE patients exhibited significant alterations in vascular OCTA parameters compared to healthy controls, the study did not find a definitive association between aPL positivity and changes in OCTA parameters in SLE patients. However, the study suggests a potential correlation between aPL positivity and variations in RNFL thickness in both cohorts. Further studies are needed to confirm these results and understand their biological significance.

Evaluating psoriasis severity: limitations of the PASI and advantages of the overall lesional assessment

Tildrakizumab is an anti–interleukin-23 p19 monoclonal antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis. This analysis evaluated real-world effectiveness and safety of tildrakizumab for 28 weeks. In this Phase 4 study (NCT03718299), adults with moderate-to-severe plaque psoriasis received tildrakizumab 100 mg subcutaneously at week 0, week 4, and every 12 weeks thereafter. Clinical improvement was assessed from Psoriasis Area and Severity Index (PASI) score change from baseline; disease activity from body surface area (BSA) percentage affected, static Physician's Global Assessment (sPGA), and sPGA x BSA; and safety from adverse events (AEs). At week 28, 52/55 enrolled patients were assessed. Mean (standard deviation [SD]) PASI score decreased significantly (P<0.001) from 11.6 (7.1) at baseline to 1.8 (3.0; 82.1% improvement) at week 28; 55.8% of patients achieved PASI 90 response. From baseline to week 28, mean (SD) BSA decreased significantly from 14.5% (11.5%) to 2.9% (6.4%), sPGA from 3.2 (0.6) to 1.2 (0.9), and BSA x sPGA from 47.0 (41.5) to 6.8 (20.3; all P<0.001). Serious AEs were infrequent. No treatment-emergent AEs were considered related to tildrakizumab. Conclusions: Real-world tildrakizumab treatment significantly improved clinical status and reduced disease activity, with no new safety concerns. Heim J, Gabriel Vasquez J, Schenkel B, et al. Real-world effectiveness and safety of tildrakizumab in patients with moderate- to-severe psoriasis: week 28 interim analysis of a phase 4 study. J Drugs Dermatol. 2023;22(8):754-760. doi:10.36849/JDD.7471.

Product of the Physician Global Assessment and body surface area: A simple static measure of psoriasis severity in a longitudinal cohort

Background There are limited randomized controlled trials of oral vitamin D supplementation in psoriasis, especially in Asia, and the results are inconclusive. Objective To investigate the clinical effect of oral vitamin D supplementation on psoriasis. Methods Patients with psoriasis were randomized to receive vitamin D2 60,000 IU or similar-looking placebo pills once every 2 weeks for 6 months. The primary outcome was improvement of the Psoriasis Area and Severity Index (PASI) score at 3 and 6 months after treatment. Serum levels of 25(OH)D, calcium, phosphate, parathyroid hormone, and C-reactive protein and adverse events were monitored. The chi-square test, Fisher's exact test, Student's t-test, and Spearman's correlation analysis were used in statistical analysis. Results Of 50 subjects screened, 45 were eligible and randomized to the oral vitamin D2 group (n=23) or placebo group (n=22). At enrollment, the mean PASI score was 4.45, and 26.7% of patients had vitamin D deficiency. At 3 months, the oral vitamin D2 group had significantly higher PASI improvement than the placebo group (mean PASI improvement: 1.43 versus [vs.] -0.33, p-value=0.034; mean %PASI improvement: 34.21% vs. -1.85%, p-value=0.039). The mean serum 25(OH)D level was significantly higher in the oral vitamin D group than in the placebo group (27.4 vs. 22.4 ng/mL, p-value=0.029). Serum 25(OH)D concentrations were significantly inversely correlated with PASI scores at the 6-month follow-up. No major adverse event was observed overall. Conclusion Oral vitamin D2 supplementation in patients with psoriasis increased the serum vitamin D level and significantly improved the treatment outcome without increasing adverse events. Trial Registration This trial is registered with Thai Clinical Trials Registry TCTR20180613001.

Introduction Data on real-world experiences for patients treated with ixekizumab is currently limited. Objectives Describe characteristics of ixekizumab-treated psoriasis patients and provide evidence of clinical outcomes using disease severity scores Body Surface Area (BSA) and Psoriasis Area and Severity Index (PASI) in the real world. Methods Chart review was performed for adult patients treated with ixekizumab at a single Canadian dermatology clinic (February 2017–August 2018). The cohort was stratified into responders (patients who remained on ixekizumab) and non-responders (patients who discontinued ixekizumab). Subgroup analyses were performed for responders to assess clinical improvement stratified by previous biologic exposure. Results Thirty-eight patients were included (mean observational time 32 weeks). At baseline, mean PASI and BSA were 10.8 and 11.6%, respectively. Mean changes in PASI and BSA were –7.8 and –6.7%, respectively, at week 4. PASI 100 was achieved in 70% of patients. Significant differences in mean change of BSA were seen between bio-naïve and bio-experienced patients. Conclusion This analysis represents the first investigation of early clinical outcomes in a small cohort of Canadian patients treated with ixekizumab. Overall, complete and rapid skin clearance was observed. Future studies including more patients and longer follow-up time are crucial to confirm these findings.

For adult patients with plaque psoriasis, limited information exists on switching between classes from an IL-23 inhibitor (IL-23i) to bimekizumab. We conducted a real-world, multicentre, retrospective study of bimekizumab following IL-23i exposure. Twenty-three subjects with prior exposure to an IL-23i were identified. Effectiveness outcomes included Investigator Global Assessment (IGA), psoriasis area and severity index (PASI), body surface area (BSA), and IGA × BSA scores. Safety was assessed via treatment-related adverse events (AEs). For 23 patients included, the mean age was 43 (range: 20–73) years, with 56.5% (13/23) being male. Prior IL-23i exposures included guselkumab only (52.2%, 12/23), risankizumab only (21.7%, 5/23), and both guselkumab and risankizumab (26.1%, 6/23). Reasons for discontinuation included lack of efficacy (95.7%, 22/23) and persistent psoriatic arthritis (4.3%, 1/23). Primary non-response to prior IL-23i was defined as lack of IGA 0/1 and/or 75% improvement in PASI (PASI75) at Week 16, whereas secondary non-response to prior IL-17i was defined as loss of IGA 0/1 and/or PASI75 response at any point afterwards. At Weeks 52 ± 6: IGA 0/1 was achieved by 66.7% (12/18); mean PASI, BSA, and IGA × BSA improvements from baseline were 69.6% (8.5–0.8), 71.8% (8.2–0.7%), and 74.6% (22.6–1.4), respectively; 65.2% (15/23), 56.5% (13/23), and 47.8% (11/23) achieved PASI75, 90% improvement in PASI (PASI90), and 100% improvement in PASI (PASI100), respectively; 78.3% (18/23), 69.6% (16/23), and 65.2% (14/23) achieved absolute PASI scores &amp;lt;3, &amp;lt;2, and &amp;lt;1; and 73.9% (17/23) achieved BSA &amp;lt;1%. In prior IL-23i primary non-responders (n = 6), 83.3% (5/6) achieved IGA 0/1 and/or PASI90 and 50% (3/6) achieved PASI100 with bimekizumab at Week 52 ± 6. In prior IL-23i secondary non-responders (n = 12), 66.7% (8/12) achieved IGA 0/1 and/or PASI90 and 50% (6/12) achieved PASI100 with bimekizumab at Week 52 ± 6. Four treatment-related AEs occurred (17.4%, 4/23), including oral candidiasis (8.7%, 2/23) and bacterial folliculitis (4.3%, 1/23). There were 3 (13%) treatment-related discontinuations [lack of efficacy (n = 2); AE: anxiety (n = 1)]. While our real-world results of patients with prior IL-23i exposure demonstrated lower achievement of effectiveness endpoints (IGA 0/1: 66.7%; PASI90: 56.5%; PASI100: 47.8%) at Week 52 ± 6 as compared with clinical trials, the discrepancy between clinical trials and this study may be explained by a more difficult-to-treat population with multiple biologic failures (56.5% utilized &amp;gt;3 biologics and 26.1% used several IL-23i). Our real-world study also included patients with &amp;gt;1 biologic failure, while Phase III clinical trials excluded this population. Our results highlight the long-term utility of bimekizumab in the setting of prior IL-23i exposure. Study limitations include its small sample and retrospective nature.

Purpose Psoriasis is a common, chronic epidermal hyperplastic and inflammatory skin disease. Studies have shown that the reduction of skin‐derived glucocorticoids (GC) may be one of the pathogenic factors of psoriasis. However, the clinical significance of the glucocorticoid receptor (GR) in patients with psoriasis remains unclear. This study aims to investigate the immunohistochemical expression of GR in psoriatic lesional tissues and its quantitative correlation with psoriasis severity, as well as to clarify the direction of this association (positive or negative). Methods Skin tissue and corresponding patient information were collected from 15 patients with chronic eczema (CE), 15 patients with lichen planus (LP), 26 patients with psoriasis, and 15 healthy adults. The skin tissue was embedded in paraffin and sectioned, followed by immunohistochemical staining using a GR antibody. The clinicopathological data were then correlated with the staining results. Disease severity was assessed using the Psoriasis Area and Severity Index (PASI), body surface area (BSA), Investigator’s Global Assessment (IGA), and Dermatology Life Quality Index (DLQI) scoring systems. Results We compared GR levels in skin tissues among healthy adults and patients with psoriasis, CE, and LP. Compared with normal skin tissues, GR levels were reduced in lesional skin of both CE and LP, with an even more pronounced decrease observed in psoriasis tissues ( p &lt; 0.01). Among the three psoriasis subtypes (ordinary psoriasis [psoriasis], pustular psoriasis [PP], and psoriatic arthritis [PA]), GR expression was the highest in the lesional skin of PA patients, exceeding that found in psoriasis patients, while expression was lower in PP lesions ( p &lt; 0.01). Strong positive correlation was found between PASI and BSA ( r = 0.8). In comorbidity analysis, psoriasis with obesity (PO) showed increased GR levels ( p &lt; 0.01), whereas psoriasis associated with hyperuricemia (PH) did not, confirming GR as a reliable diagnostic marker for psoriasis despite comorbidities. Conclusion GR level shows promise as an immunohistochemical biomarker for identifying psoriasis and assessing its severity. While comorbidities like obesity may affect its utility as a diagnostic marker, in the case of hyperuricemia, GR levels remain a reliable indicator.

Survivin, an inhibitor of apoptosis protein (IAP), has been implicated in endothelial cell stability, through inhibition of apoptosis and in cell proliferation. To evaluate the effect of antitumour necrosis factor (TNF)-alpha therapy on survivin expression in psoriasis skin at 0, 2 and 12 weeks after infliximab therapy. Skin biopsies were obtained from 16 patients; 11 also had arthritis with active skin/joint disease. Clinical scores [Psoriasis Area and Severity Index (PASI), involved body surface area (BSA), Disease Activity Score (DAS28) and Health Assessment Questionnaire] were recorded. Inflammatory infiltration and survivin protein expression were examined and graded by immunohistochemical staining, and mRNA levels were determined by real-time polymerase chain reaction. Survivin mRNA and protein were demonstrated in all baseline lesional biopsies. Survivin mRNA and protein expression was significantly greater in lesional compared with nonlesional baseline skin (P < 0.05). Differential cellular localization of survivin was demonstrated with cytoplasmic survivin protein expression localized to the perivascular/endothelial regions and strong nuclear staining localized in the basal layer of the epidermis. Infliximab produced a dramatic clinical response in skin and joints (P < 0.05), paralleled by significant reduction in the inflammatory infiltrate and survivin protein expression (P < 0.05) which was reflected at the mRNA level where expression was significantly reduced by week 12 (P < 0.01). Survivin protein levels before and after treatment significantly correlated with PASI (r = 0.478, P < 0.05) and BSA scores (r = 0.528, P < 0.024). PASI strongly correlated with BSA (r = 0.949, P < 0.0001) and DAS28 (r = 0.717, P < 0.002) scores. Survivin correlates with disease activity in patients with psoriasis and is significantly downregulated following anti-TNF-alpha treatment. Understanding the role of IAPs in cell survival/antiapoptosis and proliferation mechanisms may provide important insights into downstream therapeutic targeting in inflammation.

Background Psoriasis is a chronic, immune-mediated inflammatory disease primarily affecting the skin and joints, but it also induces systemic inflammation that disrupts metabolic processes. This systemic involvement contributes to a myriad of comorbidities, including diabetes, dyslipidemia, hypertension, obesity, cardiovascular disease, and psoriatic arthritis. Objective This study aimed to examine the relationship between psoriasis and the development of dyslipidemia and, ultimately, cardiovascular diseases. Materials and methods A comparative cross-sectional study was conducted with a total of 164 individuals (82 psoriasis cases and 82 controls) within a study period of two years (June 2022 to June 2024). The severity of psoriasis was calculated using the psoriasis area and severity index (PASI) score. Fasting lipid levels and electrocardiography (ECG) were done for patients who consented. Results Among 82 cases, the mean PASI score was 6.89, with the majority (37, 45.1%) having mild psoriasis. The prevalence of dyslipidemia was significantly higher in psoriasis patients (61, 74.3%) compared to controls (34, 41.4%), with the majority (26, 31.71%) having elevated low-density lipoprotein (LDL) levels. The most commonly observed ECG change among psoriasis patients was rhythm abnormalities (17, 20.7%), followed by conduction block (6, 7.3%) and ischemic changes (5, 6.1%), with ECG changes being more prevalent in cases (33, 40.24%) than controls (25, 30.49%), but with no statistical significance. Conclusion The higher prevalence of dyslipidemia, particularly elevated LDL levels, highlights the need for cardiovascular risk assessment in psoriasis patients. Although ECG changes were observed, their relevance to psoriasis needs to be further studied. Overall, this study emphasizes the importance of comprehensive management strategies addressing both dermatological manifestations and associated systemic conditions to improve patient outcomes in psoriasis.

Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.5 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies and postmarketing reports from regulatory agencies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis.