New-Onset Vitiligo During Guselkumab Therapy for Psoriasis.

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

Background/Objectives: Psoriasis is an immune-mediated disease influenced by genetic predisposition, environmental triggers, and metabolic comorbidities. Biologic therapies have markedly improved disease control; however, variability in patient response remains insufficiently understood. The aim of the study is to evaluate whether CARD14 mutations and the season of treatment initiation influence the efficacy of biologic therapy in psoriasis. We also examined the potential interactions between CARD14 status, seasonality, drug class, and nutrition status on short-term clinical outcomes. Methods: This retrospective study included 72 patients receiving biologic therapy within the Polish NHF B.47 program. Clinical endpoints (PASI, BSA, DLQI) were assessed at baseline and after 1, 4, 7, and 10 months. CARD14 genotyping was performed using Sanger sequencing. Patients were stratified according to mutation status, season of therapy initiation (warm vs. cold), drug class, and BMI category. Statistical analyses included t-tests, chi-square, ANOVA, and MANOVA. Results: The CARD14 rs34367357 mutation was associated with earlier disease onset (15.6 vs. 22.7 years, p = 0.0134) and higher DLQI baseline (p = 0.0265) but did not significantly impact treatment response. Therapy initiated during the warm season (April–September) led to greater PASI improvement (p < 0.0001). Obesity was associated with reduced response (p = 0.02385). Drug class and interaction effects were not statistically significant. Conclusions: Our findings suggest that seasonal timing, nutritional status, and genetic background may modulate the efficacy of biologic therapies in psoriasis. Although not statistically conclusive, the potential interaction between CARD14 rs34367357 and seasonality warrants further investigation.

Psoriasis is one of the most common dermatoses with a heterogeneous pathogenesis which can be successfully exploited therapeutically as it is increasingly well understood. Topical therapy is the gold standard for psoriasis patients with mild disease courses and for complementary and maintenance treatment in moderate and severe forms. However, while new systemic therapies are rapidly implemented in the daily routine as our pathomechanistic understanding of psoriasis evolves, the development of topical psoriasis therapies stagnates. Modern topical treatments though would require not only new active substances but also improved galenics. Due to their unique ability to directly exert biological functions, but also to deliver drugs in optimal concentrations, enabling increased therapeutic efficacy, reduced adverse effects and improved patient compliance, nanoparticles may represent ideal drug carriers for local therapeutics in psoriasis. In recent years, a series of reports added important insights into the biology of skin-nanoparticles interactions and on how they impact the epidermal and dermal inflammatory compartments in vitro and in psoriasis plaques. Furthermore, by targeting anti-inflammatory substances to specific skin compartments, nanotechnological advances offer the exciting opportunity to fine-tune skin inflammation at molecular and cellular levels, paving the road to a high-precision, skin-directed topical therapy in psoriasis. However, nanoparticle-based therapies have not yet found their way into clinical routine in dermatology. We here resume the current advances in the research of nanoparticles and skin inflammation in general and psoriasis in particular and discuss how this promising technology should develop in order to fulfil the requirements of an optimal skin therapy.

Despite recent advancements in psoriasis treatment, challenges in management persist. Recently, there has been a rising interest amongst patients in complementary and alternative medicines (CAM), driven by the desire for more natural, holistic approaches and dissatisfaction with conventional treatments. Up to 41% of patients with psoriasis reported using alternative therapies and 39.5% use complementary therapies (Murphy EC, Nussbaum D, Prussick R, Friedman AJ (2019) Use of complementary and alternative medicine by patients with psoriasis. J Am Acad Dermatol 81:280-283). Despite their rapidly growing prevalence, literature on CAM therapies for psoriasis is lacking, making their recommendation difficult. Since the last systematic review on this topic published in 2018, evidence for new alternative therapies has emerged, promoting a further investigation of their efficacy (Gamret AC, Price A, Fertig RM, Lev-Tov H, Nichols AJ (2018) Complementary and Alternative Medicine Therapies for Psoriasis: A Systematic Review. JAMA Dermatol 154:1330-1337). This systematic review aims to compile recent literature on the most studied alternative therapies for psoriasis and further discuss their effectiveness in order to counsel clinicians in guiding patients on the use of these non-standard approaches. A literature search was conducted in the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov databases for randomized controlled trials (RCT) on complementary and alternative therapies in psoriasis from March 2018 through April 2024, resulting in 12 studies being included in this review. The preliminary results for many treatments such as curcumin, dietary modification and additions, indigo naturalis, meditation, acupuncture, and balneotherapy showed positive clinical effects. However, additional well-designed randomized trials are needed to confirm the potential beneficial effects and to establish safety of use.

The tendencies for an increase in the prevalence of moderate and severe psoriasis forms leading to a patient’s disability require close attention to the possibilities of improving the methods of therapy for this disease. One of these areas is intravenous laser blood irradiation (ILBI) used in addition to traditional therapy and promotes the intensification of immune and a number of other processes in the organs and systems of the body. The paper analyzes the main prospects and possibilities of using the method of laser blood irradiation (LBI), describes the main effects occurring in the body, and characterizes the results of using ILBI. LBI is noted to be highly effective in the therapy of psoriasis, painless, and versatile. This method can be used in people of different ages.

Journal Article Corrected proof Seeking new topical therapies in psoriasis Get access Dominika Kwiatkowska, Dominika Kwiatkowska Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, Poland https://orcid.org/0000-0003-3268-012X Search for other works by this author on: Oxford Academic Google Scholar Adam Reich Adam Reich Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, Poland Correspondence: Adam Reich. Email: adi_medicalis@go2.pl https://orcid.org/0000-0002-5573-1754 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad233, https://doi.org/10.1093/bjd/ljad233 Published: 07 July 2023 Article history Received: 30 June 2023 Accepted: 04 July 2023 Published: 07 July 2023 Corrected and typeset: 08 August 2023

Background. Currently, psoriasis is the most common skin disease, its prevalence reaches 5% and this pathology often occurs together with arterial hypertension. Both arterial hypertension and psoriasis contribute to the remodeling of the cardiovascular system. As is known, myocardial remodeling is a substrate for electrical instability of the myocardium. Objective. The aim of the study was to study the parameters of the signal-averaged electrocardiogram in men with stage 2 arterial hypertension with concomitant vulgar psoriasis in the progressive stage, and to evaluate the parameters of the signal-averaged electrocardiogram against the background of psoriasis therapy. A total of 86 men with stage 2 arterial hypertension with a progressive stage of vulgar psoriasis with a severe and moderate course were examined. Signal-averaged ECG was recorded before psoriasis therapy was prescribed and after 6 months of systemic and topical psoriasis therapy. Results. A statistically significant moderate positive correlation was found between the severity of psoriasis vulgaris (according to the PASI index) and such an SU-ECG indicator as the duration of the filtered QRS complex (r = 0.32; p = 0.005), a statistically significant weak negative correlation of the PASI index with the root-mean-square amplitude of the last 40 ms of the filtered QRS complex (r = -0.27; p = 0.012). Patients with severe psoriasis had more pronounced changes in cardiac electrophysiology, in the form of more frequent recording of late ventricular potentials χ2 = 4.07; p = 0.044, a longer duration of the filtered QRS complex (p = 0.01). Systemic and topical therapy of concomitant psoriasis in patients with arterial hypertension leads to a decrease in the frequency of recording late ventricular potentials, and in patients who had severe psoriasis before the start of treatment, late potentials were recorded significantly more often after 6 months of therapy (χ2 = 3.88; p = 0.049) than in patients with initially moderate-severe psoriasis.

Psoriasis is a chronic, immune-mediated skin condition that often requires lifelong treatment. Many patients report dissatisfaction with traditional nonbiologic therapies because they are ineffective for their psoriasis, are associated with side effects, or impact negatively on quality of life. The aim of this article is to review the effect on patient quality of life of traditional nonbiologic psoriasis therapies and to discuss the impact of biologic psoriasis therapies on patient satisfaction. A review of the literature is presented. Traditional nonbiologic psoriasis therapies can negatively impact quality of life due to a variety of factors including inconvenience and toxicity. Biologic agents have been developed that target the immunopathogenesis of psoriasis. Based on favorable efficacy and safety results in clinical trials, some of these agents are now approved for clinical use. Evidence suggests that patients receiving biologic therapies experience significant improvements in health-related quality of life. Biologic agents offer new hope for patients with psoriasis that their chronic condition can be controlled in a manner that improves their quality of life and may lead to high levels of satisfaction with their treatment.

Real-world evidence regarding biologic therapy in geriatric psoriasis is limited, particularly concerning systemic inflammatory burden and infection-related safety. This study evaluates the clinical efficacy of biologic therapy and its impact on systemic inflammatory indices while emphasizing safety related to hepatitis B virus (HBV) serology and tuberculosis screening. We conducted a retrospective analysis of eighty biologic-naïve patients aged 65 years and older with plaque psoriasis undergoing biologic therapy. Patients were categorized by biologic class: tumor necrosis factor-α (TNF-α) inhibitors, interleukin-17 inhibitors, an interleukin-12/23 inhibitor, and interleukin-23 inhibitors. The primary outcomes included changes in Psoriasis Area and Severity Index (PASI) scores and blood count-derived inflammatory indices over time (baseline and 6 months). Secondary outcomes encompassed changes in HBV serologic status and QuantiFERON-TB (QFT) results. Data analysis utilized longitudinal mixed-effects models for repeated measures. Blood count-derived inflammatory indices, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), were assessed at baseline and 6 months, alongside HBV serology and QFT results. PASI scores demonstrated significant improvement over time (P < 0.001), with no notable differences among biologic classes after adjusting for baseline covariates. Significant time effects were observed for all inflammatory indices (all P < 0.001), with significant group × time interactions noted for SII and NLR (both P < 0.05). Variability in HBV serologic markers and QFT results was observed during follow-up; however, no cases of active tuberculosis or clinically overt hepatitis were identified. In conclusion, biologic therapy led to substantial clinical improvement in geriatric psoriasis, accompanied by reductions in systemic inflammatory indices over a 6-month period, without evidence of clinically overt hepatitis or active tuberculosis during follow-up.

The use of biologic therapy has increased over the past decade well beyond primary autoimmune diseases. Indeed, a recent trial using an anti-IL-1beta antibody reduced second myocardial infarction (MI) in those who have had MI. Psoriasis is a chronic inflammatory disease often treated with biologics when severe, is associated with increased risk of MI, in part driven by high-risk coronary plaque phenotypes by coronary computed tomography angiography (CCTA). We hypothesized that we would observe a reduction in inflammatory-driven phenotypes of coronary plaque, including non-calcified coronary plaque burden and lipid-rich necrotic core in those treated with biologic therapy after one-year compared with non-biologic therapy. In a prospective, observational study, 290 participants were recruited from 1 January 2013 through 31 October 2018 with 215 completing one-year follow-up. Of the 238, 121 consecutive participants who were biologic treatment naïve at baseline were included. A blinded reader (blinded to patient demographics, visit and treatment) quantified total coronary plaque burden and plaque subcomponents (calcified and non-calcified) in the three main coronary vessels >2 mm using dedicated software (QAngio, Medis, Netherlands). Psoriasis patients were middle-aged [mean (standard deviation) age, 50.5 (12.1) years], mostly male (n = 70, 58%) with low cardiovascular risk by Framingham score [median (interquartile range, IQR), 3 (1-6)] and had moderate to severe skin disease at baseline [median (IQR) Psoriasis Area Severity Index, PASI, 8.6 (5.3-14.0)]. Biologic therapy was associated with a 6% reduction in non-calcified plaque burden (P = 0.005) reduction in necrotic core (P = 0.03), with no effect on fibrous burden (P = 0.71). Decrease in non-calcified plaque burden in the biologic treated group was significant compared with slow plaque progression in non-biologic treated (Δ, -0.07 mm2 vs. 0.06 mm2; P = 0.02) and associated with biologic treatment beyond adjustment for traditional cardiovascular risk factors (β = 0.20, P = 0.02). In this observational study, we demonstrate that biologic therapy in severe psoriasis was associated with favourable modulation of coronary plaque indices by CCTA. These findings highlight the importance of systemic inflammation in coronary artery disease and support the conduct of larger, randomized trials.

Fumaric acid esters (FAE) are effective against psoriasis vulgaris and monomethylfumarate (MMF) is believed to be the most bioactive metabolite of this medication. Earlier we found that the beneficial effects of FAE medication are accompanied by a downregulation of type 1 cytokine production by T-helper (Th) lymphocytes, which are important as they maintain a type 1 cytokine [interferon (IFN)-gamma, interleukin (IL)-2] environment in the skin lesions of psoriasis vulgaris patients and once maximal beneficial effects are obtained type 2 cytokine production is also decreased. In vitro MMF selectively induced type 2 cytokine production by primed Th lymphocytes, whereas type 1 cytokine production by and profileration of T lymphocytes were unaffected. As dendritic cells (DCs) present in these skin lesions play a key role in the activation of Th lymphocytes, we investigated the effects of MMF on monocyte-derived DC differentiation. Monocytes were differentiated into immature (i) DCs by cytokines with or without MMF. To establish whether these cells were differentiated into iDCs, we analysed the expression of cell surface molecules on these cells and the capacity to capture antigens using flow cytometry. Next, we determined whether these MMF-incubated (MMF-)iDCs could be matured by lipopolysaccharide (LPS) and whether MMF affected this responsiveness as well. For this purpose we measured cytokine production by these LPS-stimulated cells (MMF-DCs) using enzyme-linked immunosorbent assays as well as their ability to activate naive Th lymphocytes. The presence of MMF during the differentiation of monocytes into iDCs resulted in cells that retained low levels of CD14 and hardly expressed CD1a. Upon maturation, these MMF-iDCs upregulated CD83 and costimulatory molecules and HLA-DR on their surface, indicating that these cells respond to LPS, albeit less than control iDCs. In addition, in response to LPS, MMF-iDCs did not decrease the capacity to capture antigens when compared with control iDCs. MMF-DCs hardly produced IL-12p70 and IL-10 and low levels of tumour necrosis factor (TNF)-alpha, whereas IL-8 produced by MMF-DCs and control DCs did not differ. Moreover, MMF-DCs were less able to induce IFN-gamma production by naive Th lymphocytes compared with control DCs. The production of IL-4 and IL-10 by naive Th lymphocytes cocultured with MMF-DCs did not differ from that by T cells cocultured with control DCs. MMF inhibited the monocyte-derived DC differentiation resulting in cells that cannot be appropriately matured to DCs. Consequently, these MMF-DCs are less effective than control DCs in stimulating type 1 cytokine, but not type 2 cytokine production, in Th lymphocytes. This general immunomodulatory effect may in part explain the beneficial effects of FAE therapy in psoriasis.

Psoriasis is a chronic, recurrent and inflammatory skin disease. Although conventional immunosuppressants can ameliorate psoriatic symptoms, it tends to relapse over time. Previous studies have shown that exosomes from both immune and non-immune cells participate in psoriatic immunopathology. The biologically active cargoes in exosomes accelerate psoriasis progression by altering gene profiles and signaling pathways of neighboring cells. On the other hand, exosomes can be utilized as drug delivery platforms for psoriasis treatment. Especially, engineered exosomes may serve as drug delivery systems for effective delivery of proteins, nucleic acids or other drugs due to their low immunogenicity, good stability and ability to fuse with target cells. Therefore, investigation into the mechanisms underlying intercellular communications mediated by exosomes in skin lesions likely helps design drugs for therapy of psoriasis. In this review, we have summarized recent advances in the biogenesis of exosomes and their potential roles in the pathogenesis and treatment of psoriasis and further discussed their challenges and future directions in psoriasis treatment. In particular, this review highlights the immunoregulatory function of exosomes derived from immune or non-immune cells and exosome-based therapeutic applications in psoriasis, including their drug delivery systems. Thus, this review may help accelerate applications of exosomes for drug delivery and treatment of psoriasis.

COBRA Trial Opens Door to All-Topical Therapy in Psoriasis

Hepatotoxicity is a major concern with methotrexate (MTX) therapy for psoriasis. Guidelines to help ensure safe use of MTX in this patient population are revisited periodically as new data become available. Much focus has been dedicated to establishing pre-treatment and monitoring protocols to detect MTX-induced hepatic injury. Here we review past and current guidelines, risk factors, population characteristics, and surveillance techniques with regard to MTX hepatotoxicity in psoriasis patients.

Introduction Significant advances in psoriasis treatment have taken place since the introduction of biologics. Tumor necrosis factor inhibitors were the first class of biologics approved and at that time greatly improved psoriasis treatment. However, newer biologics, directed to interleukin(IL)-23/IL-17 pathways central to psoriasis pathogenesis, have improved complete or nearly complete clearance rates and are characterized by an excellent safety profile. Real-world setting experiences have generally confirmed the results of clinical trials, but real-world data regarding newer biologics is relatively scarce. Areas covered We provide an extensive review of real-world survival of biologic treatments for moderate to severe psoriasis. Expert opinion There is growing and consistent evidence of higher drug survival of IL-23 inhibitors, possibly due to their favorable efficacy and safety profiles, dosing convenience and persistence of response despite treatment interruption; eventual confirmation of their potential role as modifiers of the natural history of psoriasis might provide additional reasons for therapeutic persistence of this class of biologics.