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Background Methods Results Conclusion Treatment goals have been established in Australia to facilitate the management of adults with moderate to severe psoriasis. The Australasian College of Dermatologists sought to determine if and how these adult treatment goals could be modified to accommodate the needs of paediatric and adolescent patients.A modified Delphi approach was used. Comprehensive literature review and guideline evaluation resulted in the development of statements and other questions to establish current clinical practices. Two rounds of anonymous voting were undertaken, with a collaborative meeting held in between to discuss areas of discordance. Overall, consensus was defined as achievement of ≥75% agreement in the range 7–9 on a 9‐point scale (1 strongly disagree; 9 strongly agree).Consensus was achieved on 23/29 statements in round 1 and 17/18 statements in round 2. There was a high level of concordance with treatment criteria in the adult setting. The limitations of applying assessment tools developed for use in adult patients to the paediatric setting were highlighted. Treatment targets in the paediatric setting should include objective metrics for disease severity and psychological impact on the patients and their family, and be based on validated, age‐appropriate tools.While the assessment, classification and management of moderate to severe psoriasis in paediatric patients aligns with metrics established for adults, it is vital that nuances in the transition from childhood to adolescence be taken into account. Future research should focus on psoriasis severity assessment scales specific to the paediatric setting. [ABSTRACT FROM AUTHOR]

This article discusses the use of dupilumab, a medication, for the treatment of chronic actinic dermatitis (CAD), a rare photosensitive disorder that primarily affects older men. The article presents two case studies of patients with CAD who were successfully treated with dupilumab, showing significant improvement in their symptoms. The article also reviews existing literature on the use of dupilumab for CAD and suggests the need for further studies to confirm its effectiveness. The document is a case series that includes information on patients with various medical conditions and the treatments they received, predominantly male patients treated with medications like hydroxychloroquine, methotrexate, and mycophenolate mofetil. The document also provides information on abbreviations used and conflicts of interest of the authors. Ethical approval was not required for this case series, and patient consent was obtained for the use of their information and images. [Extracted from the article]

Background: Over the last decade, the treatment landscape for moderate–severe psoriasis has rapidly evolved. The Australasian College of Dermatologists sought to review and update previously published treatment goals for moderate–severe psoriasis. Methods: A modified Delphi approach was used. Comprehensive literature review and guideline evaluation resulted in the development of statements and other questions to establish current clinical practices. Two rounds of anonymous voting were undertaken, with a collaborative meeting held in between to discuss areas of discordance. Overall, consensus was defined as achievement of ≥75% agreement in the range 7–9 on a 9‐point scale (1 strongly disagree; 9 strongly agree). Results: Consensus was achieved on 26/29 statements in round 1 and a further 20 statements in round 2. There was strong agreement to expanding the classification/definition of psoriasis severity by including a choice of metrics, incorporating quality of life measures, and widening the scope of high‐impact sites. Consensus was also reached on revised treatment response criteria, which were then incorporated into a new treatment algorithm. There was discordance with the current requirement to undertake a trial with established systemic agents before accessing targeted therapy. Conclusion: The ability of new targeted treatment options to change the narrative in psoriasis patient care can only be properly realised if challenges to timely and equitable access are addressed. The proposed framework for the assessment, classification and management of moderate–severe psoriasis aligns with international recommendations. Its adoption into Australian clinical practice is hoped to improve treatment outcomes and patients' satisfaction with their care. [ABSTRACT FROM AUTHOR]

Background/Objectives: Dupilumab‐associated ocular surface disease (DAOSD) is of particular relevance in patients with atopic dermatitis (AD). Guidance on DAOSD assessment and management in the Australian setting is needed to reduce its impact and minimise disruption to treatment. Methods: A systematic review of the literature was undertaken to identify data pertaining to the incidence, pathophysiology, risk factors and management of DAOSD. A critical review of this literature was used to inform a decision framework for dupilumab‐prescribers and develop a graded severity scoring tool to guide appropriate management options. Results: DAOSD typically emerges within 4 months of commencing dupilumab and the occurrence of new events diminishes over time. The reported incidence varies widely depending on the nature and source of the data: 8.6–22.1% (clinical trials programme), 0.5–70% (real‐world data; differences in study size, duration of follow‐up, ophthalmologist intervention, use of prophylaxis). Occurrence increases with AD severity and in patients with prior history of ocular disease; pathophysiology is still to be fully characterised. Management options have evolved over time and include lubricants/artificial tears, corticosteroids, calcineurin inhibitors, antihistamines, anti‐inflammatory agents and antimicrobial agents. Current therapies aim to resolve symptoms or reduce severity to levels sufficiently tolerable to enable continuation of dupilumab therapy. Conclusions: Recommendations for DAOSD assessment and management include identification of high‐risk patients, vigilance for red flags (keratoconus, herpetic and bacterial keratitis), regular assessment of symptom severity (before and during dupilumab therapy), conservative management of mild DAOSD by the prescribing physician and ophthalmologist referral for collaborative care of moderate–severe DAOSD and high‐risk patients. [ABSTRACT FROM AUTHOR]

Background: Drug survival measures the rate and duration of adherence to a given therapeutic agent and evaluates its long‐term effectiveness, safety, and real‐world utility. The SUSTAIN study sought to establish the drug survival and effectiveness of secukinumab for patients with severe chronic plaque psoriasis (CPP) in the Australian clinical setting. Methods: Data of all patients (aged ≥18 years) from Australasian Psoriasis Registry (APR) treated with secukinumab were analysed. The primary objective was to describe the drug survival of secukinumab at 9 months. Key secondary objectives included drug survival of secukinumab at 3, 6, 15, and 21 months, stratified by biologic‐naïve vs biologic‐experienced patients; proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75/90/100 responses; and changes in health‐related quality of life over time utilising the Dermatology Life Quality Index (DLQI). Results: Of 294 patients included in this analysis, 110 (37.4%) were biologic‐naïve and 184 (62.6%) biologic‐experienced. Kaplan–Meїer drug survival rates in biologic‐naïve vs biologic‐experienced patients were 0.92 vs. 0.86 (9 months) and 0.82 vs. 0.68 (21 months), respectively. The proportion of patients with PASI 75/90/100 responses for biologic‐naïve vs. biologic‐experienced was 100/87.7/38.4 vs 98.5/61.5/27.2 (9 months) and 100/81.0/41.7 vs. 98.4/62.0/24.2 (21 months), respectively. The mean (standard deviation [SD]) DLQI in biologic‐naïve vs. experienced patients was 2.2 (4.1) vs. 3.1 (5.2) (9 months) and 1.4 (2.5) vs. 3.1 (5.3) (21 months). No new safety signals were observed. Conclusions: Secukinumab demonstrated high drug survival and sustained effectiveness in Australian real‐world setting, in biologic‐naïve and biologic‐experienced patients with severe CPP. [ABSTRACT FROM AUTHOR]

Background: Psoriasis imposes a disease burden that can have a profound negative impact on patients' quality of life (QoL). HOPE was the first non‐interventional study conducted in patients with severe chronic plaque psoriasis in Australia that evaluated health‐related QoL in response to treatment with secukinumab. Methods: HOPE was a prospective, open‐label, single‐arm, multicentre, non‐interventional, exploratory study in patients with severe chronic plaque psoriasis in Australia. The study investigated the change in QoL, using the Dermatology Life Quality Index (DLQI), Assessment Quality of Life‐8 Dimension questionnaire (AQoL‐8D) and Psoriasis Area and Severity Index (PASI), and safety profile in response to treatment with secukinumab 300 mg SC weekly for 4 weeks followed by monthly maintenance for 58 weeks. Results: At Week 14, the mean percentage reduction in total DLQI score from baseline was −82.4% (n = 65), which indicates a substantial improvement in QoL. This level of improvement was sustained up to Week ≥58, with a mean percentage change of −87.4%. The mean percentage change from baseline for AQoL‐8D weighted total score decreased from Week 14 (41.1%) to Week 58 (35.2%), indicating an improvement in patients' QoL. A high proportion of patients achieved PASI 75/90/100 responses at Week 14 (97.0%/71.2%/34.8%), with rates sustained up to Week ≥58 (100%/87.9%/43.1%). The safety profile of secukinumab was favourable, with no cumulative or unexpected safety concerns. Conclusion: Secukinumab treatment demonstrated a striking improvement in patients' QoL in the HOPE study, the first real‐world study in patients with severe chronic plaque psoriasis in the Australian clinical setting. [ABSTRACT FROM AUTHOR]

Introduction: Secukinumab has demonstrated sustained long-term efficacy with a favourable safety profile in various manifestations of psoriatic disease. We investigated effectiveness and safety of secukinumab, other biologics and conventional systemic therapies in patients with chronic plaque psoriasis in a real-world setting. Methods: REALIA was a non-interventional, multicentre, prospective, parallel group study. Eligible patients were ≥ 18 years old with chronic plaque psoriasis commencing a new treatment with a biologic agent or conventional systemic therapies. Results: At baseline, 541 patients were divided into three cohorts based on treatment initiated: conventional systemics (173), secukinumab (184) and other biologics (184). A significantly higher proportion of patients achieved almost clear to clear skin based on physician's judgement in secukinumab versus conventional systemics at month 3 (64.7% versus 22.8%, P < 0.001) and month 6 (61.8% versus 20.8%, P < 0.001). At month 12, clear to almost clear skin was achieved by 52.1% of the patients in secukinumab versus 35.8% in conventional systemics (P = 0.066). The proportion of patients achieving Psoriasis Area Severity Index (PASI) 90 on conventional systemics, secukinumab and other biologics was 18.8%, 59.7% and 40.0% at month 3 and 35.3%, 60.8% and 50.0% at month 12, respectively. Secukinumab patients showed significantly higher change in PASI total score from baseline versus conventional systemics at month 3 {least squares [LS] mean [standard error (SE)]: −14.49 [0.648] versus −8.48 [1.149], P < 0.001} and numerically higher [LS mean (SE): −13.60 (0.475) versus −10.84 (1.733), P = 0.122] at month 12. The proportion of patients with Dermatology Life Quality Index 0/1 score on conventional systemics, secukinumab and other biologics was 22.6%, 65.0% and 41.6% at month 3 and 32.0%, 63.5% and 41.3% at month 12, respectively. Safety profile was comparable across cohorts. Conclusions: Secukinumab is effective and well tolerated in patients with chronic plaque psoriasis in a real-world setting in an Asia-Pacific and Middle East population, and these results are in agreement with clinical outcomes of secukinumab reported in randomised clinical trials. Trial registration number: 170803-001645. [ABSTRACT FROM AUTHOR]

The aim of this article is to provide education to clinicians about certain barriers restricting the use of advanced targeted treatments in Australian health care. For illustrative purposes, the article focuses on dermatological conditions, but the content is relevant to all specialties that treat inflammatory and chronic diseases. Barriers to care discussed result in a lower than necessary standard of care for patients in Australia despite important advancements in medicine. [ABSTRACT FROM AUTHOR]

Background: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. This study investigated the efficacy and safety of bimekizumab in patients with moderate to severe plaque psoriasis, the effects of treatment withdrawal, and two maintenance dosing schedules over 56 weeks.Methods: BE READY was a phase 3, multicentre, randomised, double-blind, placebo-controlled trial done at 77 sites (hospitals, clinics, private doctor's practices, and dedicated clinical research centres) in nine countries across Asia, Australia, Europe, and North America. Adult patients aged 18 years or older with moderate to severe plaque psoriasis were stratified by region and previous biologic exposure, and randomly assigned (4:1) to receive bimekizumab 320 mg every 4 weeks or placebo every 4 weeks by use of interactive response technology. Coprimary endpoints were the proportion of patients achieving 90% or greater improvement from baseline in the Psoriasis Area Severity Index (PASI90) and the proportion of patients achieving a score of 0 (clear) or 1 (almost clear) on the five-point Investigator's Global Assessment (IGA) scale at week 16 (non-responder imputation). Bimekizumab-treated patients achieving PASI90 at week 16 were re-allocated (1:1:1) to receive bimekizumab 320 mg every 4 weeks, every 8 weeks, or placebo for weeks 16-56. Efficacy analyses were done in the intention-to-treat population; the safety analysis set comprised all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT03410992), and is now completed.Findings: Between Feb 5, 2018, and Jan 7, 2020, 435 patients were randomly assigned to receive either bimekizumab 320 mg every 4 weeks (n=349) or placebo every 4 weeks (n=86). Coprimary endpoints were met: at week 16, 317 (91%) of 349 patients receiving bimekizumab 320 mg every 4 weeks achieved PASI90, compared with one (1%) of 86 patients receiving placebo (risk difference 89·8 [95% CI 86·1-93·4]; p<0·0001); and 323 (93%) of 349 patients receiving bimekizumab 320 mg every 4 weeks achieved an IGA score of 0 or 1 versus one (1%) of 86 patients receiving placebo (risk difference 91·5 [95% CI 88·0-94·9]; p<0·0001). Responses were maintained through to week 56 with bimekizumab 320 mg every 8 weeks and every 4 weeks. Treatment-emergent adverse events in the initial treatment period (up to week 16) were reported in 213 (61%) of 349 patients receiving bimekizumab 320 mg every 4 weeks and 35 (41%) of 86 patients receiving placebo every 4 weeks. From week 16 to week 56, treatment-emergent adverse events were reported in 78 (74%) of 106 patients receiving bimekizumab 320 mg every 4 weeks, 77 (77%) of 100 patients receiving bimekizumab 320 mg every 8 weeks, and 72 (69%) of 105 patients receiving placebo.Interpretation: Bimekizumab showed high levels of response, which were durable over 56 weeks, with both maintenance dosing schedules (every 4 weeks and every 8 weeks). Moreover, bimekizumab was well tolerated, with no unexpected safety findings. Data presented here further support the therapeutic value of bimekizumab and inhibition of IL-17F in addition to IL-17A for patients with moderate to severe plaque psoriasis.Funding: UCB Pharma. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of guselkumab on work productivity, including absenteeism and presenteeism, in psoriasis patients with and without depression/anxiety. Methods: VOYAGE 2 is a randomized, double-blind, placebo-controlled, and comparator-controlled, phase 3 trial that compared guselkumab with adalimumab in patients with moderate-to-severe psoriasis. Absenteeism was evaluated among patients who reported that their skin prevented work/study based on the Dermatology Life Quality Index (DLQI) work/study domain (score = 3) at baseline. Presenteeism was assessed by summarizing mean changes in four Work Limitations Questionnaire (WLQ) domain scores at week 24. Analyses were compared between treatments and stratified by depression/anxiety status at baseline. Results: At week 24, 82.1% and 50.0% in the guselkumab and adalimumab groups, respectively, reported a DLQI work/study score = 0 (no effect of skin on work/study) (p <.001). Mean changes (improvements) were greater in guselkumab-treated versus adalimumab-treated patients in the work limitations domains of Physical Demands (−6.9 vs. −3.3, p <.05), Mental-Interpersonal (−6.3 vs. −3.2, p <.06), and Output Demands (−6.2 vs. −2.2, p <.05). Improvements were consistent in patients with and without depression/anxiety. Conclusions: Psoriasis patients treated with guselkumab had significantly better improvements in absenteeism and presenteeism compared with those treated with adalimumab, regardless of depression/anxiety status. [ABSTRACT FROM AUTHOR]

Unhealthy weight gain and diabetes are global challenges that threaten not only the well-beings of hundreds of millions of persons but also the global economy. The authors in this article describe two overlapping stories, one is about a 150-year-old diet, known as the Banting Diet, which is similar to the Atkins or Keto Diet, and the other is about a provider-patient relationship story that helped the patient make lifestyle modifications that were effective in significant weight loss, improved quality of life, and reduced need for exogenous insulin for Type 2 diabetes. Both of the stories are from England but might be useful worldwide. [ABSTRACT FROM AUTHOR]

Objectives: To conduct initial assessment of the early arthritis for psoriatic patients (EARP) questionnaire for Australian, Korean and Chinese populations using translated and linguistically validated versions. To measure the proportion of patients with psoriatic arthritis (PsA) among patients with psoriasis who attended dermatology clinics. Methods: Questionnaires were translated and culturally validated into Australian English, Korean and Chinese. A multicenter, observational, descriptive estimate of the proportion of patients with PsA among patients with psoriasis attending dermatology clinics in Australia, Korea and China was conducted. Initial assessments included evaluations of floor and ceiling effects, internal consistency (using Cronbach's alpha), test‐retest reliability (using intraclass coefficient), and correlations between EARP score and rheumatology findings. If the initial EARP score was ≥3, patients were assessed by a rheumatologist for PsA within 3 months of their retest questionnaire. Results: Two hundred and fifty patients participated. Translated EARP questionnaires showed satisfactory internal consistency and test‐retest reliability. A potential floor effect was observed for the Chinese and Korean versions. Cronbach's alpha was 0.885 (Australian), 0.776 (Korean) and 0.789 (Chinese), indicating acceptable internal consistency. Intraclass correlation coefficients were 0.89 (Australian), 0.86 (Korean) and 0.87 (Chinese), indicating acceptable test‐retest reliability. EARP summary scores had weak to moderate linear correlation with the relevant PsA assessments. Overall, 32 (12.8%) patients were diagnosed with PsA based on Classification for Psoriatic Arthritis (CASPAR) score. Conclusion: The Australian, Korean, and Chinese versions of the EARP questionnaire are suitable for the early detection of PsA symptoms in patients with psoriasis by dermatologists working in specialist dermatology clinics. Trial registration: NCT02470481. [ABSTRACT FROM AUTHOR]

Solar urticaria (SU) is a rare form of urticaria with a pathogenesis that is poorly understood. It affects all skin types, can be difficult to diagnose, and is challenging to manage effectively. We conducted a retrospective review of patients with SU in our institution. A total of 83 patients (56 females) were identified as having SU. The mean age was 32 years (7–74) at first development of symptoms/signs of SU. Pruritus was the most common symptom reported (79%). Of the 60 patients who underwent monochromator testing at least once, 35 had SU confirmed with most reacting to visible light and UVA, or to UVA alone. Antihistamines and sun avoidance remain the mainstay treatment for SU but other treatments, including omalizumab, are of potential interest in treating patients with recalcitrant SU. The characterisation of this large case series of patients may help dermatologists recognise and manage this rare disorder appropriately. [ABSTRACT FROM AUTHOR]

Abstract Introduction Genital psoriasis (GenPs) is common and distressing for patients, but is often not discussed with physicians, and no previous clinical trials have assessed the effects of biologics specifically on GenPs and its associated symptoms. Aim To report results for novel patient-reported outcomes (PROs) for the assessment of symptoms and the sexual impact of GenPs before and after treatment in the IXORA-Q study. Methods IXORA-Q (NCT02718898) was a phase III, randomized, double-blind, placebo-controlled study of ixekizumab (80 mg/2 weeks after 160-mg initial dose) vs placebo for GenPs. Men and women ≥18 years old with moderate-to-severe GenPs and body surface area (BSA) ≥1% were assessed through 12 weeks. Main Outcome Measure GenPs symptoms were assessed using the 8-item Genital Psoriasis Symptoms Scale (GPSS), Genital Psoriasis Sexual Frequency Questionnaire (GenPs-SFQ), and Genital Psoriasis Sexual Impact Scale (GPSIS) (validation data presented in the supplemental materials), and the Dermatology Life Quality Index (DLQI) item 9. Results For patients receiving ixekizumab (N = 75) vs placebo (N = 74), statistically significant improvement in GenPs symptoms were seen from week 1 onward (GPSS total and individual items, all P <.005). Sexual activity avoidance owing to GenPs symptoms (GPSIS) decreased significantly with ixekizumab from week 4 onward (all P <.005), whereas impact of sexual activity on GenPs improved significantly with ixekizumab at weeks 2–8 (all P < 0.05). Ixekizumab resulted in significant improvement vs placebo by week 1 onward in limitations on frequency of sexual activity owing to GenPs (GenPs-SFQ item 2). Sexual difficulties caused by skin (DLQI item 9) decreased significantly with ixekizumab from week 2 onward (all P <.001). Clinical Implications Both GenPs symptoms and impact on sexual activity improved rapidly and significantly with ixekizumab vs placebo through 12 weeks in patients with moderate-to-severe GenPs and BSA ≥1%. Strength & Limitations To our knowledge, this is the first phase III, randomized, placebo-controlled, double-blinded clinical trial to evaluate the effect of any treatment on the symptoms and sexual impact related to GenPs. The study did not include an active comparator owing to the lack of any well-established treatment for moderate-to-severe GenPs, and the period assessed herein was of relatively short duration. Conclusion These validated PRO measures may aid in future clinical studies of GenPs and in facilitating discussions of GenPs symptoms and their impact between patients and clinicians. Yosipovitch G, Foley P, Ryan C. Ixekizumab improved patient-reported genital psoriasis symptoms and impact of symptoms on sexual activity vs placebo in a randomized, double-blind study. J Sex Med 2018;15:1645–1652. [ABSTRACT FROM AUTHOR]

Background: Calcipotriol 50 µg/g and betamethasone 0.5 mg/g dipropionate (Cal/BD) aerosol foam formulation provides greater effectiveness and improved patient preference compared with traditional Cal/BD formulations for the topical treatment of plaque psoriasis.Objective: To determine the cost-effectiveness of Cal/BD foam compared with Cal/BD gel from the Australian perspective.Methods: A Markov model was developed to evaluate the cost-effectiveness of topical Cal/BD foam and gel for the treatment of people with plaque psoriasis. Treatment effectiveness, safety, and utilities were based on a randomized control trial, resource use was informed by expert opinion, and unit costs were obtained from public sources. Outcomes were reported in terms of 1-year costs, quality-adjusted life years, and incremental cost-effectiveness ratios. All costs were reported in 2017 Australian Dollars.Results: The model showed that patients using Cal/BD foam had more QALYs and higher costs over 1 year compared with patients using Cal/BD gel, resulting in a cost of $13,609 per QALY gained at 4-weeks. When 4 weeks of Cal/BD foam was compared with 8 weeks of Cal/BD gel treatment, Cal/BD foam was $8 less expensive and resulted in 0.006 more QALYs gained. Sensitivity analyses showed that, compared with Cal/BD ointment, Cal/BD foam was associated with an incremental cost of $15,091 per QALY gained.Conclusion: Cal/BD foam is the most cost-effective Cal/BD formulation for the topical treatment of patients with plaque psoriasis. [ABSTRACT FROM AUTHOR]

Background:Actinic keratosis (AK) is a common skin condition, for which topical therapies are frequently prescribed. This review summarises current understanding of patient adherence and persistence to topical AK treatment by identifying literature relating to measures of adherence and persistence and influencing factors. Methods:A multi-database literature search was conducted (2004–2015) using key search terms. Supplementary searches of pivotal clinical trials and reference lists of eligible papers were also conducted. Results:Non-adherence and non-persistence rates varied between real-world studies (10–63% and 23–31%, respectively), with combined non-adherence and non-persistence reported as high as 88%. Methods to calculate adherence and persistence differed between studies. Adherence and persistence were generally higher in clinical trials than clinical practice. Key contributing factors to non-adherence and non-persistence to AK treatment were identified as: treatment duration, severity and persistence of local skin responses and patient confusion over treatment regimens. Conclusion:The review highlighted a significant evidence gap regarding adherence and persistence to topical AK therapies. Combined, non-adherence and non-persistence may be as high as 88% in clinical practice, highlighting the importance of incorporating contributing factors to patient non-adherence into treatment decisions. [ABSTRACT FROM PUBLISHER]

Pruritus and skin discomfort/pain negatively impact health-related quality of life (HRQoL). The effects of apremilast, an oral phosphodiesterase 4 inhibitor, on pruritus, skin discomfort/pain, and patient global assessment of psoriasis disease activity (PgAPDA) were assessed in patients with moderate/severe chronic plaque psoriasis in the phase 3 ESTEEM trials. Significant improvements in pruritus and skin discomfort/pain observed at Week 2 with apremilast versus placebo (both studies, p < 0.0001) were sustained through Week 32. Among apremilast-treated patients, improvements in pruritus visual analog scale (VAS) scores correlated with Dermatology Life Quality Index scores (rs = 0.55 [Week 16]; rs≥ 0.51 [Week 32]; both studies, p < 0.001). PgAPDA correlated with improvements in pruritus (rs≥ 0.56 [Week 16]; rs≥ 0.53 [Week 32]; both studies, p < 0.001) and skin discomfort/pain (rs ≥ 0.54 [Week 16]; rs≥ 0.53 [Week 32]; both studies, p < 0.001) VAS scores. Apremilast provided rapid and sustained improvement in pruritus and skin discomfort/pain, symptoms not typically captured in psoriasis assessments (e.g., PASI) that contribute significantly to patients' disease severity and HRQoL perceptions. [ABSTRACT FROM AUTHOR]

SUMMARY Solar urticaria is an uncommon disorder characterized by pruritus, erythema and whealing commencing within minutes of exposure to ultraviolet (UV) and visible light, and generally resolves in a few hours. We describe a 28-year-old woman who developed pruritus and erythema 5 min after sun exposure while on tetracycline for treatment of perioral dermatitis. Phototesting elicited urticarial reactions in the UVA, UVB and visible spectra. Repeat phototesting after cessation of tetracycline was negative. This report documents the first case of solar urticaria induced by tetracycline. [ABSTRACT FROM AUTHOR]

Basal cell carcinomas ( BCCs) account for around 80% of non-melanoma skin cancer. Australia has the highest incidence of BCC globally and the rates continue to increase in both Australia and New Zealand. BCC causes significant morbidity, placing an enormous burden on the healthcare system. Treatment of patients with advanced BCC can be particularly challenging. A panel of UK experts recently defined advanced disease as BCC that in which current treatment modalities are considered potentially contraindicated by clinical or patient-driven factors. Research has found that mutations in the hedgehog signalling pathway underpin the pathogenesis of the vast majority of sporadic BCC, as well as Gorlin syndrome. The first-in-class oral small molecule hedgehog pathway inhibitor - vismodegib-is now approved in a number of countries for use in locally-advanced and metastatic BCC and has resulted in improved outcomes in the majority of patients treated. With a number of similar agents in the pipeline, research is now focusing on identifying mechanisms that may contribute to resistance to this agent in some lesions. [ABSTRACT FROM AUTHOR]

Abstract: The prevalence, associations, and natural history of pain in multiple sclerosis (MS) are poorly understood. The objective of this work was to study the prevalence of pain syndromes in MS both cross-sectionally, and longitudinally during the MS disease course. We systematically identified prospective studies detailing pain prevalence in definite MS. We used pooled prevalence estimates, explored heterogeneity using meta-regression, and analysed prevalence during the disease course using both estimates at disease milestones and longitudinal studies. Twenty-eight articles (7101 subjects) describing overall pain, or pain syndromes, met inclusion criteria. Pooled overall pain prevalence (17 studies, 5319 subjects) was 63% (95% confidence interval [CI] 55–70%). Marked heterogeneity in this estimate was not significantly explained by selected study design variables (use of outpatient sample, timeframe prior to study over which pain was assessed) or sample demographic variables (mean Expanded Disability Status Scale, mean disease duration, proportion of female sex, and proportion with progressive MS). We quantified prevalence of headache (43%; 95% CI 33–52%), neuropathic extremity pain (26%; 95% CI 7–53%), back pain (20%; 95% CI 13–28%), painful spasms (15%; 95% CI 8.5–23%), Lhermitte sign (16%; 95% CI 10–25%), and trigeminal neuralgia (3.8%; 95% CI 2–6%) in included studies. Prevalence of pain at MS disease milestones (prior to onset, at onset, and at relapse) and during longitudinal follow-up was poorly described. Pain is common in MS, as are specific pain syndromes. The clinical associations and natural history of pain in MS require clarification. Future study could be enhanced by standardised study design. [Copyright &y& Elsevier]

Geographically weighted spatial statistical methods are a family of spatial statistical methods developed to address the presence of non-stationarity in geographical processes, the so-called spatial heterogeneity. While these methods have recently become popular for analysis of spatial data, one of their characteristics is that they produce outputs that in themselves form complex multi-dimensional spatial data sets. Interpretation of these outputs is therefore not easy, but is of high importance, since spatial and non-spatial patterns in the results of these methods contain clues to causes of underlying non-stationarity. In this article, we focus on one of the geographically weighted methods, the geographically weighted discriminant analysis (GWDA), which is a method for prediction and analysis of categorical spatial data. It is an extension of linear discriminant analysis (LDA) that allows the relationship between the predictor variables and the categories to vary spatially. This produces a very complex data set of GWDA results, which include on top of the already complex discriminant analysis outputs (e.g. classifications and posterior probabilities) also spatially varying outputs (e.g. classification function parameters). In this article, we suggest using geovisual analytics to visualise results from LDA and GWDA to facilitate comparison between the global and local method results. For this, we develop a bespoke visual methodology that allows us to examine the performance of global and local classification method in terms of quality of classification. Furthermore, we are also interested in identifying the presence (or absence) of non-stationarity through comparison of the outputs of both methods. We do this in two ways. First, we visually explore spatial autocorrelation in both LDA and GWDA misclassifications. Second, we focus on relationships between the classification result and the independent variables and how they vary over space. We describe our visual analytic system for exploration of LDA and GWDA outputs and demonstrate our approach on a case study using a data set linking election results with a selection of socio-economic variables. [ABSTRACT FROM PUBLISHER]

Background/Objectives Internationally, the understanding of psoriasis has advanced in recent years to the point now where it is no longer considered a benign or cosmetic skin condition but a systemic, immune-mediated disease associated with significant comorbidities and considerable detriment to quality of life. The aim of this study was to gain a better understanding of the physical, psychosocial and medical burden of psoriasis on Australian adults and the impact on health status. Methods Two large-scale multi-centre cross-sectional studies of Australian adults with psoriasis were conducted during 2010 and 2011, with the participation of a national patient representative group ( Psoriasis Australia). The studies were based on detailed questionnaires that were self-completed by individuals with psoriasis. Results A total of 362 and 330 completed surveys were received in 2010 and 2011, respectively. A significant physical, psychosocial and medical burden was reported by the respondents. It was noteworthy that patients reported actively concealing their disease from the general public (83%), work colleagues (65%), friends (58%), employers (49%), family (40%), close friends (39%) and spouse/partner (20%). The mean five-dimension European quality of life ( EQ- 5D) score for the 2011 cohort was 0.73, representing a significant impact on their HRQoL. The presence of comorbidities, found in three-quarters of the cohort, was associated with an even greater detriment to their HRQoL (mean score 0.64). Conclusions Psoriasis imposes a significant psychosocial burden on the lives of patients, including a profound impact upon their personal and professional relationships, social interactions and quality of life, to a degree comparable to other serious chronic conditions. This study highlights the importance of collaboration between primary and specialist health-care providers in developing patient management strategies that address the spectrum of physical and psychological manifestations associated with psoriasis. [ABSTRACT FROM AUTHOR]

The article presents a case study of Lesley Ruth Hampton, a 42-year-old woman who died from complications of multiple sclerosis (MS) in hospital. Some of the challenges faced by Lesley in end-of-life care for progressive neurological disease are described. The article discusses the need for end-of-life care for those living with incurable progressive neurodegenerative diseases in Great Britain today and some of the initiatives undertaken by the government to improve the situation.

The article presents a guide to treatment of Actinic keratoses (AK), also known as solar keratosis, with 5-fluorouracil (5-FU) cream. It informs that (AK) is a common condition that develops as scaly lesions on chronically sun-exposed skin. It notes that 5-FU 4 percent, or 0.5 percent in combination with salicylic acid, offer effective field treatment options for AKs. It also highlights the importance of being aware of the expected clinical course and common local inflammatory skin reactions.

Background Psoriasis is a chronic skin disease that can impact heavily on a patient’s well-being. Efalizumab, a unique, targeted, biological therapy, has demonstrated efficacy in treating moderate-to-severe, chronic plaque psoriasis with ≤36 months of continuous therapy. The objective of this Extended Access Program (EAP) was to evaluate further the benefit of efalizumab as long-term therapy in a real-world clinical setting. Methods After an initial conditioning dose of efalizumab (0.7 mg/kg subcutaneously), a weekly dose of efalizumab (1.0 mg/kg) was administered for ≤21 months. Patients with reduced Psoriasis Area and Severity Index (PASI) scores (≥50%, or a score ≤8) at month 3 entered the long-term maintenance treatment period. Results In total, 101 patients (>18 years) with severe plaque psoriasis enrolled on the EAP, of these 93 (92.1%) met all the inclusion criteria. After 3 months of treatment, 84/101 (83.2%) patients had evaluable data and entered the maintenance period. After 3 months, 57/84 (67.9%) patients had achieved PASI-50. Using an intent-to-treat analysis, after 21 months of treatment, PASI-75 and PASI-50 were achieved by 43/101 (42.6%) and 69/101 (68.3%) of patients, respectively. Efalizumab was generally well tolerated during the 21 months of continuous therapy. Conclusion Efalizumab, 1.0 mg/kg/week, is effective and well tolerated in a ‘real world’ clinical setting, providing enduring reduction of psoriasis symptoms for up to 21 months. [ABSTRACT FROM AUTHOR]

Background Data suggest that photodynamic therapy using topical methyl aminolevulinate (MAL PDT) may be a noninvasive alternative to excisional surgery for nodular basal cell carcinoma (BCC). In the studies described here, we investigated the histologic response, tolerability, and cosmetic outcome with MAL PDT for primary nodular BCC (≤ 5 mm in depth). Methods Two multicenter, randomized, double-blind studies with similar design and procedures were conducted. After surface debridement and minor tumor debulking, MAL cream 160 mg/g (66 patients with 75 lesions) or placebo cream (65 patients with 75 lesions) was applied for 3 h, followed by illumination with broad-spectrum red light (75 J/cm2, 570–670 nm). This was repeated 7 days later. Lesions with a partial response (≥ 50% reduction in greatest diameter) at 3 months were re-treated (21%). Treatment sites were excised at 3 months (clinical nonresponders) or 6 months (clinical responders) after the last treatment. Results Histologically verified lesion complete response rates were higher with MAL PDT than with placebo [73% (55/75) vs. 27% (20/75)]. Treatment was most effective for facial lesions (89% complete response). Cosmetic outcome was good or excellent in 98% of evaluable, completely responding lesions treated with MAL PDT. Conclusion Although longer follow-up studies are required, these promising data indicate the potential of topical MAL PDT as a noninvasive treatment alternative for nodular BCC. [ABSTRACT FROM AUTHOR]

Actinic Prurigo (AP), an uncommon idiopathic photodermatosis, presents a distinct clinical picture and can be severely debilitating. The clinical features, investigation and treatment of AP are reviewed. We report the experience of an Australian photobiology unit with this condition. [ABSTRACT FROM AUTHOR]

Solar keratosis is a common problem encountered by dermatologists, particularly in Australia. Solar keratosis is most commonly found on sun-exposed areas such as the scalp, face and forearms. UV radiation is thought to be the major aetiological factor, with age, immunosuppression and human papillomavirus being important contributing factors. Solar keratosis usually presents as a discrete, variably erythematous and irregular lesion with a scaly surface. Although the exact rate of malignant transformation to squamous cell carcinoma is unknown, the majority of squamous cell carcinomas appear to arise from within solar keratosis. For this reason, solar keratosis is commonly treated and, consequently, an increasing number of therapeutic options is now available. Traditional therapies, such as liquid nitrogen cryotherapy, are still popular, but newer choices, such as photodynamic therapy and imiquimod cream, are now providing further options with similar efficacy and superior adverse effect profiles, albeit at a higher cost. [ABSTRACT FROM AUTHOR]

The article focuses on the studies related to the efficacy of methyl aminolaevulinate (MAL) photodynamic therapy (PDT) in basal cell carcinoma (BCC) and solar keratoses (SK). It states that PDT requires the application of an agent such as MAL to the lesion. It says that in Australia and the U.S., there were two studies that compared the response rates of nodular BCC. It mentions the randomized trial in Europe that compared the efficacy of single-cycle MAL PDT with cryotherapy double freeze-thaw.

A retrospective study was performed to analyse the clinical and photobiological features and therapeutic outcomes of 44 patients with chronic actinic dermatitis who were evaluated over an 8.3-year period. The study population comprised 37 men and seven women with a mean age of 62.7 years (range 26–85 years). The most common abnormal phototest results were decreased minimal erythema doses to both UVA and -B (73.8%), and to UVA alone (14.3%). Twenty-six patients (78.8%) had at least one allergic, photoallergic or combined allergic/photoallergic reaction. A total of 139 positive contact or photocontact reactions were recorded (mean 4.2 per patient). Most commonly, treatment consisted of photoprotection, topical corticosteroids and episodic use of systemic agents, in particular azathioprine. [ABSTRACT FROM AUTHOR]

Linear porokeratosis is a distinctive variant of porokeratosis with malignant transformation, a known but infrequently reported complication. We report a case of linear porokeratosis on the right leg of a 57-year-old man present since infancy that, over a 2-year period, developed tow squamous cell carcinomas within the lesion. concurrent right inguinal lymphadenopathy was demonstrated on biopsy to be reactive in nature. [ABSTRACT FROM AUTHOR]

SUMMARY Actinic prurigo (AP) is a rare acquired idiopathic photodermatosis, reported most often in American Indians, but also in Caucasian and Asian populations. The skin lesions in AP predominantly affect exposed sites but may involve covered areas, and often result in postinflammatory scarring. The diagnosis of AP can be difficult and relies on a combination of history, clinical experience and investigations including phototesting and human leucocyte antigen typing. Twenty-one patients (17 women, four men) diagnosed with AP at the photobiology clinic at St Vincent’s Hospital Melbourne were reviewed in this retrospective study. The mean age of patients at presentation to the clinic was 25 years, with the mean age of onset being 14 years. Phototesting was undertaken in 20 patients, with 12 (60%) having reduced and eight (40%) normal minimal erythema doses. Human leucocyte antigen typing indicated 18 patients (85.7%) were DR4 positive, with further subtyping of the DR4 allele establishing that 15 patients (71.4%) were DRB1*0407 positive and that two (9.5%) were DRB1*0401 positive. This condition is often recalcitrant, with treatment options including photoprotection, topical and oral corticosteroids, antimalarials, phototherapy and thalidomide. [ABSTRACT FROM AUTHOR]

SUMMARYActinic prurigo is an uncommon and usually persistent idiopathic photodermatosis with typical human leukocyte antigen (HLA) associations (HLA-DR4, particularly subtypes DRB1*0407 and DRB1*0401). Although its mechanism of action is not clearly understood, thalidomide has been shown to be particularly efficacious in treating actinic prurigo, among other conditions. A 31-year-old Australian woman who had suffered actinic prurigo for most of her life was treated with two courses of thalidomide (50–100 mg nocte) over consecutive summers. Remission was observed after cessation of the second course of thalidomide and had continued 4 years later. Abnormalities in the cutaneous response to ultraviolet radiation at the time of diagnosis, detected by monochromator phototesting, reverted to normal following treatment. [ABSTRACT FROM AUTHOR]

Reports on the advances in the understanding of dermatological conditions that have allowed dermatologists to refine treatments. Expansion of laser therapy in dermatology; Photodynamic therapy; Treatment of dermatological problems using narrowband ultraviolet Beta light; Discussions on Kaposi's sarcoma and human herpesvirus 8.

As with adults, paediatric patients may benefit from a number of advanced targeted therapies for inflammatory skin disease. This brief report aims to be an accessible reference tool with respect to regulatory approval and reimbursement of these treatments within Australia. [ABSTRACT FROM AUTHOR]

The article focuses on the clinical efficacy of methyl aminolaevulinate (MAL) photodynamic therapy (PDT) in basal cell carcinoma (BCC) and solar keratosis. Two studies in Australia and the U.S. have compared nodular BCC complete response rates with MAL PDT and placebo PDT. In the Australian study, as tumour depth increased efficacy diminished; in the U.S. where debulking was somewhat more aggressive, no loss of efficacy with increasing depth was observed. However, this finding does suggest that the procedure may be best used for thin nodular BCC.

The article analyses the clinical efficacy of methyl aminolaevulinate photodynamic therapy in basal cell carcinoma (BCC) and solar keratosis. Photodynamic therapy (PDT) using methyl aminolaevulinate 160 mg/g cream has recently been approved in Australia for the treatment of thin or non-hyperkeratotic and non-pigmented solar keratoses on the face and scalp when other registered therapies are unacceptable. PDT is a simple, doctor-controlled procedure with an established treatment protocol and which allows multiple lesions to be treated during the same session. It is well tolerated, with predictable local phototoxic adverse events, high patient acceptance and has superior cosmetic outcome.

A 23-year-old man presented with the onset of a widespread pruritic eruption 4 days after ingestion of an Ecstasy tablet for the first time. The rash was characterized by small papules up to 10 mm in diameter distributed in a guttate pattern over most of his body and displaying the Köbner phenomena. Histology diagnosed a psoriasiform drug eruption. The eruption was not responsive to the initial treatment of topical betamethasone dipropionate 0.1% ointment and oral prednisolone. Prompt resolution was achieved with narrowband UVB treatment and avoidance of rechallenge. [ABSTRACT FROM AUTHOR]

This article focuses on the clinical efficacy of methyl aminolaevulinate photodynamic therapy (PDT) in basal cell carcinoma and solar keratosis. PDT using methyl aminolaevulinate 160 mg/g cream has recently been approved in Australia for the treatment of thin or non-hyperkeratotic and non-pigmented solar keratoses on the face and scalp when other registered therapies are unacceptable, and for the primary treatment of superficial and/or nodular basal cell carcinoma where surgery is considered inappropriate.

Pityriasis rubra pilaris (PRP) is a group of uncommon chronic inflammatory skin conditions with unclear pathophysiology and etiology. To date there is limited published literature and no clinical guidelines for the management of PRP. Infliximab, alone or in combination, is the most widely published successful treatment for adults and etanercept for pediatric populations. We present a case series of patients diagnosed with PRP. Retrospective data were collected from a tertiary Australian dermatology department between January 2010 and December 2019 on patients with PRP. Electronic medical records and pathology database were searched. A total of 13 patients were included. Twelve of the 13 patients used topical agents and three patients attempted narrow‐band ultraviolet B phototherapy. All patients received acitretin as first line systemic agent with the dose varying from 10 to 50 mg daily. Six patients treated with acitretin reported adverse events, requiring dose reduction or cessation. Of the nine patients who did not receive a biologic agent, complete clearance of PRP was achieved in five cases. At least one biologic agent was used in four cases with two experiencing a marked improvement. Overall, complete clearance was achieved in six patients. PRP continues to be a challenge to treat with many treatment options used with variable efficacy. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterised by neuroinflammation and neurodegeneration. Fatigue and depression are common, debilitating, and intertwined symptoms in people with relapsing-remitting MS (pwRRMS). An increased understanding of brain changes and mechanisms underlying fatigue and depression in RRMS could lead to more effective interventions and enhancement of quality of life. To elucidate the relationship between depression and fatigue and brain connectivity in pwRRMS we conducted a systematic review. Searched databases were PubMed, Web-of-Science and Scopus. Inclusion criteria were: studied participants with RRMS (n ≥ 20; ≥ 18 years old) and differentiated between MS subtypes; published between 2001-01-01 and 2023-01-18; used fatigue and depression assessments validated for MS; included brain structural, functional magnetic resonance imaging (fMRI) or diffusion MRI (dMRI). Sixty studies met the criteria: 18 dMRI (15 fatigue, 5 depression) and 22 fMRI (20 fatigue, 5 depression) studies. The literature was heterogeneous; half of studies reported no correlation between brain connectivity measures and fatigue or depression. Positive findings showed that abnormal cortico-limbic structural and functional connectivity was associated with depression. Fatigue was linked to connectivity measures in cortico-thalamic-basal-ganglial networks. Additionally, both depression and fatigue were related to altered cingulum structural connectivity, and functional connectivity involving thalamus, cerebellum, frontal lobe, ventral tegmental area, striatum, default mode and attention networks, and supramarginal, precentral, and postcentral gyri. Qualitative analysis suggests structural and functional connectivity changes, possibly due to axonal and/or myelin loss, in the cortico-thalamic-basal-ganglial and cortico-limbic network may underlie fatigue and depression in pwRRMS, respectively, but the overall results were inconclusive, possibly explained by heterogeneity and limited number of studies. This highlights the need for further studies including advanced MRI to detect more subtle brain changes in association with depression and fatigue. Future studies using optimised imaging protocols and validated depression and fatigue measures are required to clarify the substrates underlying these symptoms in pwRRMS. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Two phase 3 trials, POETYK PSO‐1 and PSO‐2, previously established the efficacy and overall safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in plaque psoriasis.To further assess the safety of deucravacitinib over 52 weeks in the pooled population from these two trials.Pooled safety data were evaluated from PSO‐1 and PSO‐2 in which patients with moderate‐to‐severe plaque psoriasis were randomized 1:2:1 to receive oral placebo, deucravacitinib or apremilast.A total of 1683 patients were included in the pooled analysis. Adverse event (AE) incidence rates were similar in each treatment group, serious AEs were low and balanced across groups, and discontinuation rates were lower with deucravacitinib versus placebo or apremilast. No new safety signals emerged with longer deucravacitinib treatment. Exposure‐adjusted incidence rates of AEs of interest with placebo, deucravacitinib and apremilast, respectively, were as follows: serious infections (0.8/100 person‐years [PY], 1.7/100 PY, and 1.8/100 PY), major adverse cardiovascular events (1.2/100 PY, 0.3/100 PY, and 0.9/100 PY), venous thromboembolic events (0, 0.2/100 PY, and 0), malignancies (0, 1.0/100 PY and 0.9/100 PY), herpes zoster (0.4/100 PY, 0.8/100 PY, and 0), acne (0.4/100 PY, 2.9/100 PY, and 0) and folliculitis (0, 2.8/100 PY, and 0.9/100 PY). No clinically meaningful changes from baseline in mean levels, or shifts from baseline to CTCAE grade ≥3 abnormalities, were reported in laboratory parameters with deucravacitinib.Deucravacitinib was well‐tolerated with acceptable safety over 52 weeks in patients with psoriasis. [ABSTRACT FROM AUTHOR]

Background: Guselkumab effectively treats moderate-to-severe psoriasis. Objectives: Results of continuous guselkumab treatment through 4 years from VOYAGE 2 are presented. Methods: At baseline, 992 patients were randomized to receive guselkumab 100 mg every 8 weeks, placebo, or adalimumab 40 mg every 2 weeks. Placebo-treated patients crossed over to guselkumab at week 16. Weeks 28–76 incorporated randomized withdrawal, and all patients received open-label guselkumab through to week 204. Efficacy was analyzed using pre-specified treatment failure rules (patients were considered nonresponders after discontinuing due to lack of efficacy, worsening of psoriasis, or use of a prohibited treatment). There was no missing data imputation after treatment failure rules. Safety was analyzed through 4 years. Results: The proportions of guselkumab-treated patients who achieved and maintained designated clinical responses at weeks 100 and 204, respectively, were as follows: at least a 75% improvement in Psoriasis Area and Severity Index from baseline (PASI 75): 94.1% and 92.3%; PASI 90: 79.1% and 79.7%; PASI 100: 48.4% and 51.0%; Investigator's Global Assessment (IGA) score of 0/1: 83.1% and 81.9%; IGA score of 0: 52.7% and 52.7%; Dermatology Life Quality Index score of 0/1: 70.2% and 69.1%; Psoriasis Symptoms and Signs Diary (PSSD) symptom score of 0: 35.7% and 39.7%; PSSD sign score of 0: 22.0% and 27.2%; ≥ 5% improvement in Short Form-36 (SF-36) physical component score: 48.8% and 45.0%; ≥ 5% improvement in SF-36 mental component score: 45.1% and 43.2%; Hospital Anxiety and Depression Score (HADS)-anxiety score ≥ 8: 22.9% and 21.7%; and HADS-depression score ≥ 8: 16.6% and 21.0%. Similar findings were reported for the adalimumab → guselkumab group. No new safety signals were identified. Conclusions: High efficacy levels were maintained from week 100 through to week 204 with continuous guselkumab treatment, across multiple endpoints, in VOYAGE 2. Guselkumab was well tolerated. Clinical Trial Registration: NCT02207244. [ABSTRACT FROM AUTHOR]

Introduction/Background Targeting and binding OX40 ligand (OX40L) expressed on antigen-presenting cells may inhibit the persistent immune response that drives atopic dermatitis (AD) pathophysiology. Amlitelimab (SAR445229; KY1005) is a potential first-in-class, fully human, non-depleting anti-OX40L monoclonal antibody that blocks OX40L-OX40 interactions and has shown efficacy and an acceptable safety profile in a Phase 2a trial in adults with moderate-to-severe AD. Here, we present 24-week efficacy and safety results (Part 1) from an ongoing dose-ranging Phase 2b trial. The study remains blinded to individual patient data (Part 2 ongoing). Objectives: To evaluate the efficacy and safety of amlitelimab in adults with moderate-to-severe AD. Methods: STREAM-AD (NCT05131477) is a 52-week, randomised, double-blinded, placebo-controlled Phase 2b monotherapy trial. This study is designed with 2 parts (double-blind throughout): a 24-week treatment period (Part 1, completed and presented here) and a 36-week maintenance/withdrawal period (Part 2, ongoing). Adults (18 to <75 years; n=390) with moderate-to-severe AD were randomised 1:1:1:1:1 to receive subcutaneous amlitelimab Q4W (250 mg with 500 mg loading dose [LD], n=77; 250 mg without LD, n=78; 125 mg without LD, n=77; or 62.5 mg without LD, n=79) or placebo Q4W (n=79). The primary endpoint was percentage change in Eczema Area and Severity Index (EASI) from baseline at Week 16. Key secondary endpoints included percentage change in EASI at Week 24 and percentage of patients with at least 75% reduction from baseline in EASI (EASI-75), percentage of patients with Investigator Global Assessment response of 0 (clear) or 1 (almost clear) and a reduction from baseline of ≥2 points (IGA 0/1), and proportion of patients with a weekly average reduction of Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 points from baseline. The primary efficacy analysis included all randomised patients who completed Week 24 or discontinued treatment or study prior to Week 24 visit (n=390), whereas the safety analysis included all treated patients (n=388). Results: Treatment with amlitelimab resulted in statistically significant improvements in percentage change in EASI from baseline to Week 16 compared to placebo for all four doses studied. The 250 mg with LD group had the numerically highest response versus placebo at Week 16, with a least-squares mean change from baseline of -32.1% (95% CI: -43.9, -20.3; P<0.0001); the remaining groups without LD had the following responses versus placebo: 250 mg, -27.3 (95% CI: -39.1, -15.6; P<0.0001); 125 mg, -22.2 (95% CI: -34.0, -10.4; P=0.0002); and 62.5 mg, -30.2 (95% CI: -41.9, -18.5; P<0.0001). There were also clinically meaningful improvements in all key secondary efficacy outcome measures, with all amlitelimab dose groups demonstrating nominally significant (P<0.05) efficacy versus placebo for EASI-75, IGA 0/1, and PP-NRS =4, except 250 mg (no LD) in IGA 0/1 at Week 16 (P=0.0562). Continued improvements were generally observed through Week 24 in primary and key secondary efficacy outcomes. Amlitelimab was well tolerated across all dose groups, with no safety concerns identified. Conclusions: In this dose-ranging Phase 2b trial of amlitelimab in adults with moderate-to-severe AD, amlitelimab demonstrated clinically meaningful efficacy over 24 weeks with an acceptable safety profile across all four dose groups. [ABSTRACT FROM AUTHOR]

Introduction: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for treatment of moderate-to-severe plaque psoriasis. Our objective was to evaluate the long-term efficacy and safety of ixekizumab in moderate-to-severe plaque psoriasis through 5 years. Methods: Data were integrated from the UNCOVER-1 and UNCOVER-2, randomized, double-blinded, phase-3 trials. Patients who continuously received the labeled ixekizumab dose, were static Physician's Global Assessment (sPGA) (0,1) responders at Week 12 and completed 60 weeks of treatment could enter the long-term extension (LTE) period. Patients could escalate to every-2-week dosing per investigator opinion. Efficacy and health outcomes included proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1) and (0), absolute PASI ≤ 5/ ≤ 3/ ≤ 2/ ≤ 1 and Dermatology Life Quality Index (DLQI) (0,1). Results exclude patients who escalated to every-2-week dosing. A modified non-responder imputation method was used to account for missing data. Supplemental analyses include patients who escalated to every-2-week dosing and observed and multiple imputation results. Exposure-adjusted safety outcomes are also reported. Results: Of 206 patients who entered the LTE periods, 172 completed treatment. At Week 60, PASI 75/90/100 responses were 94.7%, 85.0% and 62.1%, respectively, and at year 5 were 90.3%, 71.3% and 46.3%, respectively. Similarly, meaningful responses were achieved for the other efficacy and health measures. Among patients with PASI 100 through 5 years, 92% achieved DLQI (0,1), indicating no impact of skin disease on quality of life. During the LTE period, exposure-adjusted incidence rates were 31.4 per 100 patient-years for treatment-emergent adverse events and 6.8 per 100 patient-years for serious adverse events. No deaths were reported. No new or unexpected safety findings were noted. Conclusions: The results demonstrate 80 mg ixekizumab maintains long-term efficacy and a safety profile consistent with previous data in patients with moderate-to-severe plaque psoriasis through 5 years of treatment. Trial Registration: ClinicalTrials.gov identifier, UNCOVER-1: NCT01474512, UNCOVER-2: NCT01597245. [ABSTRACT FROM AUTHOR]