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This article discusses the use of tildrakizumab, an interleukin (IL) inhibitor, for the treatment of recalcitrant pityriasis rubra pilaris (PRP). PRP is a rare skin disorder with no approved biologic treatments in Australia. The article presents three cases of PRP that were successfully treated with tildrakizumab, resulting in significant improvements in symptoms and minimal adverse effects. Tildrakizumab is considered a promising therapeutic option for PRP, and further studies are needed to determine its optimal use. [Extracted from the article]

Background: 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. Objectives: To further assess the safety of deucravacitinib over 52 weeks in the pooled population from these two trials. Methods: 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. Results: 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. Conclusions: Deucravacitinib was well‐tolerated with acceptable safety over 52 weeks in patients with psoriasis. [ABSTRACT FROM AUTHOR]

The first-in-class, once daily oral therapy deucravacitinib has been PBS listed in Australia for adults with severe chronic plaque psoriasis. Deucravacitinib represents a new option for treating plaque psoriasis with its unique mechanism of action as a selective tyrosine kinase 2 inhibitor. [ABSTRACT FROM AUTHOR]

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]

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]

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: 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]

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]

A major obstacle toward creating human‐scale artificial tissue models is supplying encapsulated cells with oxygen and other nutrients throughout the construct. In particular, creating channels in hydrogels that match the resolution and density of the smallest blood capillaries (≤10 µm) remains highly challenging. Here, a novel method is demonstrated where polycaprolactone fibers printed using melt‐electrowriting are encapsulated in cell‐laden hydrogels and then physically removed to produce hollow, perfusable channels. This technique produces a range of channel diameters (10–41 µm) with circular cross‐sections and in hydrogels representing various crosslinking mechanisms. The channels can be formed as interconnected grids, hierarchically branched patterns, or stacked in layers with ≈200 µm channel spacing, thus matching average capillary density in the human body. Alternatively, selective removal of fibers from a melt electrowriting grid can generate perfusable channels within a reinforcing fiber network. This method can be performed in the presence of cells, with human fibroblasts exhibiting encapsulated in gelatin methacryloyl showing no detectable cytotoxic effects. This technique is a promising approach for creating perfusable channels with very small diameters within cell‐laden hydrogel matrices, with potential applications including in vitro tissue models and hydrogel microfluidics. [ABSTRACT FROM AUTHOR]

Background Amlitelimab is a fully-human, non-depleting, anti-OX40 ligand (OX40L) monoclonal antibody that binds to OX40L on antigen-presenting cells. Amlitelimab blocks the interaction of OX40L with OX40 on activated T-cells, inhibiting T-cell dependent inflammation without depleting T-cells. Objective To evaluate the efficacy and safety of amlitelimab (Part 1), and explore the maintenance of clinical response over a 28-Week period (Part 2) in patients with moderate-to-severe AD. Methods STREAM-AD (NCT05131477), was a randomized, double-blind, placebo-controlled Phase 2b trial, that included a 24-Week, double-blind, treatment period (Part 1), a 28-Week maintenance/withdrawal period (Part 2), and a 16-Week safety follow-up. In Part 1, adult participants were randomized 1:1:1:1:1 to subcutaneous amlitelimab Q4W (250mg with 500mg loading dose [+ LD], n=77; 250mg, n=78; 125mg, n=77; 62.5mg, n=79) or placebo Q4W (n=79). In Part 2, Clinical responders (defined as those achieving EASI-75 and/or IGA 0/1 at Week-24) in Part 1, were rerandomized 3:1 to withdraw or continue pre-Week 24 Q4W dose (250mg + LD, n=34 [withdrawal]/n=13 [continuing]; 250mg, n=28/n=12; 125mg, n=33/n=12; 62.5mg, n=35/n=7; placebo responders continuing placebo, n=16), and were followed to Week-52 to evaluate maintenance of clinical response. Primary efficacy endpoint was percent change in EASI from baseline at Week-16. Key secondary endpoints were proportion of patients achieving IGA 0/1, EASI-75, PP-RNS≥4. The statistical analysis was performed using two methods: 1) imputing the endpoint as nonresponder after rescue medication use (NRI); and 2) including all measurements regardless of rescue use (treatment policy). Results Out of 390 participants enrolled in Part 1, 190 entered Part 2. In Part 1, all four doses of amlitelimab demonstrated statistically significant improvements in percent change in EASI from baseline to Week-16 vs placebo; the highest response was seen with 250mg + LD group. Clinically meaningful improvements in key secondary endpoints were observed at Week-16, with continued improvements through Week-24. In Part 2, maintenance of EASI-75 and/or IGA 0/1 response at Week-52 was observed in 59%, 63%, 55%, and 66% of clinical responders withdrawn from 250mg + LD, 250mg, 125mg, and 62.5mg, respectively (NRI). Using treatment policy, 77%, 82%, 67%, and 74% maintained response off-drug, respectively. Those continuing amlitelimab treatment had numerically higher maintenance response rates. AD-related biomarkers were reduced during Part 1 and remained decreased over Part 2. Amlitelimab was well tolerated across all dose groups, with no new safety concerns identified during the 52-Weeks. Conclusion Clinically meaningful efficacy with amlitelimab was demonstrated over 52-Weeks, with an acceptable safety profile. Clinical responses were maintained in most patients 28-Weeks after treatment discontinuation. [ABSTRACT FROM AUTHOR]

Introduction Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting 2–7% of adults globally, with 30% experiencing moderate-to-severe disease. Although several treatments for moderate-to-severe AD are available, the efficacy of many treatments has not been compared in head-to-head trials. Objectives Using a network meta-analysis (NMA), we evaluated the relative efficacy between lebrikizumab, an emerging biologic, and approved targeted systemic treatments for AD. Methods Double-blind, randomized, placebo-controlled clinical trials (systemic monotherapy-only) for moderate-to-severe AD in adults (≥18 years) and adolescents (≥12 years to ≤18 years) published before April 2023 were identified in a systematic literature review. Data were extracted for short-term (12–16 weeks) efficacy outcomes (Investigator's Global Assessment [IGA] 0/1 with ≥2-point improvement from baseline and the Eczema Area and Severity Index [EASI]) and patient-reported outcomes (Pruritus Numeric Rating Scale [NRS] with ≥4-point improvement from baseline). Bayesian NMAs were performed using random-effects models, with baseline-risk adjustment. Key estimates from the NMAs included pairwise differences between all treatments and absolute response rates for each treatment. Results Twenty-two clinical trials were included. For % achieving IGA 0/1, at 12–16 weeks, the estimated response rates (posterior median and 95% credible interval) for each of the treatments were: upadacitinib 30 mg 55.8% (43.7–64.2%), upadacitinib 15 mg 41.3% (30.1–50.0%), abrocitinib 200 mg 39.0% (29.8–47.8%), dupilumab 300 mg 31.8% (23.1–38.7%), lebrikizumab 250 mg 31.4% (24.1–39.2%), abrocitinib 100 mg 24.5% (17.5–32.0%), tralokinumab 300 mg 17.3% (12.8–22.2%), baricitinib 4 mg 16.7% (9.8–25.5%), baricitinib 2 mg 15.5% (9.6–22.0%), and placebo 6.0% (4.3–7.3%). Similar trends were observed for the EASI and pruritus NRS responses at 12–16 weeks. Conclusions This 16-week NMA shows that lebrikizumab had a similar response rate to dupilumab, the most widely used targeted systemic therapy for AD, and may represent a valuable treatment option for moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Introduction Atopic dermatitis (AD) is a common, chronic inflammatory disease requiring long-term, continuous therapy, yet in real life, patients may need to temporarily interrupt therapy. Objectives To indirectly compare long-term outcomes with lebrikizumab, tralokinumab, and dupilumab, we present an exploratory efficacy index, which accounts for on-drug and off-drug combined outcomes at Week 52. Methods The data set consisted of patients who, after 16 weeks, responded to treatment, defined as achieving either an IGA 0,1 or EASI 75 score, and who were randomized to receive maintenance dosages of lebrikizumab 250 mg Q4W (ADvocate1; ADvocate2), tralokinumab 300 mg Q2W (ECZTRA1; ECZTRA 2), and dupilumab 300 mg QW, Q2W (SOLO-CONTINUE) or were randomized to withdraw these treatments up to Week 52. The efficacy index is based on a weighted combination of response rates at Week 52, using non-responder imputation results, for IGA 0,1 or EASI 75, for patients who were either in the treatment continuation or the withdrawal arm. Here, we report the efficacy index, in which the weight places equal emphasis on continuing or stopping treatment, and we compare the efficacy index of tralokinumab and dupilumab with lebrikizumab. Results The efficacy index (95% CI) for lebrikizumab, tralokinumab, and dupilumab, respectively, was 53% (45%-61%), 45% (37%-53%), and 34% (28%-40%) with IGA 0,1; 63% (55%-71%), 42% (35%-49%), and 51% (45%-57%) with EASI 75. With IGA 0,1, lebrikizumab was statistically different from dupilumab; with EASI 75, lebrikizumab was statistically different from dupilumab and tralokinumab. Conclusions This novel efficacy index, which accounts for the importance of continuing or stopping therapy after Week 16, may be a useful tool to indirectly compare long-term treatment outcomes. Lebrikizumab's higher efficacy index may translate to improved long-term management of AD. [ABSTRACT FROM AUTHOR]

Background Given the chronic nature of psoriasis and the loss of response that can be observed with therapies over time, it is important to understand the long-term efficacy of new treatments. Objectives To evaluate maintenance of Week 16 responses with bimekizumab (BKZ) treatment through Year 3, in patients with moderate-to-severe plaque psoriasis. Methods Data were pooled from BKZ-treated patients in the 52-week (BE VIVID) and 56-week (BE READY and BE SURE) phase III studies, and their ongoing open-label extension (OLE), BE BRIGHT. Efficacy outcomes are reported through 3 years of BKZ treatment in patients with an efficacy response at Week 16. Missing data were imputed primarily using modified nonresponder imputation (mNRI), with nonresponder imputation and observed case data also reported. Results A total of 989 patients were randomized to BKZ at baseline in BE VIVID, BE READY and BE SURE. At Week 16, 693 patients achieved ≥ 90% reduction from baseline in Psoriasis Area and Severity Index (PASI 90), 503 achieved 100% reduction from baseline in PASI (PASI 100), 694 achieved absolute PASI ≤ 2 and 597 achieved body surface area (BSA) ≤ 1%, and continued into the OLE. Of these, 93.0% maintained PASI 90, 80.8% maintained PASI 100, 94.0% maintained PASI ≤ 2 and 90.3% maintained BSA ≤ 1% responses through to 3 years of BKZ treatment (mNRI). Among Week 16 PASI 90 responders, 96.8% and 72.5% also achieved Investigator's Global Assessment 0/1 and PASI 100 at Week 16, respectively, and 92.2% and 73.4% achieved these responses at Year 3 (mNRI). Among Week 16 PASI 100 responders, 76.3% also achieved Dermatology Life Quality Index (DLQI) 0/1 at Week 16, and DLQI 0/1 response increased with continuous BKZ treatment to 89.0% at Year 3 (mNRI). Conclusions High levels of clinical response were maintained through to 3 years of BKZ treatment in the vast majority of Week 16 responders. Long-term treatment with BKZ was efficacious, with important benefits for health-related quality of life, in patients with moderate-to-severe plaque psoriasis. [ABSTRACT FROM AUTHOR]

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, inhibits cytokine signaling in psoriasis pathogenesis. The objective of this study was to demonstrate deucravacitinib superiority versus placebo and apremilast in moderate to severe plaque psoriasis based on ≥75% reduction from baseline in Psoriasis Area and Severity Index and a static Physician's Global Assessment score of 0 (clear) or 1 (almost clear) with a ≥2-point improvement from baseline at week 16. POETYK psoriasis second trial (NCT03611751), a 52-week, double-blinded, phase 3 trial, randomized patients 2:1:1 to deucravacitinib 6 mg every day (n = 511), placebo (n = 255), or apremilast 30 mg twice a day (n = 254). At week 16, significantly more deucravacitinib-treated patients versus placebo and apremilast patients achieved ≥75% reduction from baseline in Psoriasis Area and Severity Index (53.0% vs 9.4% and 39.8%; P <.0001 vs placebo; P =.0004 vs apremilast) and static Physician's Global Assessment score of 0 or 1 (49.5% vs 8.6% and 33.9%; P <.0001 for both). Efficacy was maintained until week 52 with continuous deucravacitinib. The most frequent adverse event with deucravacitinib was nasopharyngitis. Serious adverse events and discontinuations due to adverse events were infrequent. No clinically meaningful changes were observed in laboratory parameters. The study duration was 1 year. Deucravacitinib demonstrated superiority versus placebo and apremilast and was well tolerated in adults with moderate to severe plaque psoriasis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a chronic skin condition for which a range of systemic treatments have recently been approved. A treat-to-target strategy has been developed previously alongside an algorithm to guide the management of patients with atopic dermatitis. Here, we review the strategy and algorithm in the context of the evolving therapeutic landscape, and identify areas for further refinement and development. [ABSTRACT FROM AUTHOR]

The article discusses scalp pruritus and its treatment. It mentions the common causes for it including seborrhoeic dermatitis that can be controlled by using an antidandruff shampoo alongwith ketoconazole cream, psoriasis that can be controlled by a shampoo having salicylic acid, and lichen simplex chronicus which can be treated by using topical corticosteroid lotions.

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]

This descriptive analysis examines malignancy events reported among guselkumab-treated patients with prior malignancy (excluding NMSC) during VOYAGE 1 and VOYAGE 2 (NCT02207231; NCT02207244). More patients across a broader range of time following cancer remission and longer duration of follow-up are needed to better characterize the safety of guselkumab in patients with prior malignancy. Https://doi.org/10.1093/bjd/ljad081 Dear Editor, The pivotal 5-year VOYAGE 1 and 2 studies of guselkumab in moderate-to-severe psoriasis[1],[2] are among the first studies of biologics to include patients with a history of malignancy, including treated nonmelanoma skin cancer (NMSC) or cervical cancer I in situ i (without evidence of recurrence for >= 3 months) or other malignancy > 5 years before enrolment. [Extracted from the article]

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.

A 70-year-old retired male plumber was admitted with reduced consciousness following a recent onset of confusion and headache. He developed encephalopathy, seizures and myoclonus. He died despite treatment 10 weeks later. This article reports the clinicopathological conference presented at the Edinburgh Clinical Neurology Course 2021. [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]

Evaluate the use of widefield radiation therapy (RT) in the management of extensive skin field cancerization (ESFC) with/without keratinocyte cancer (KC). The National Dermatology Radiation Oncology Registry is a multidisciplinary collaboration (dermatologists and radiation oncologists). It captures disease description, prior therapies, radiation prescription, clinical effect, skin cosmesis scores, and toxicity data. This analysis included 12-month follow-up data on 89 treated fields from a subset of 83 patients. Clinical success (>90% field clearance) was 96% (ESFC, n = 63) and 88% (ESFC with KC, n = 26). Complete lesion response was seen in 96% of evaluable (n = 25) ESFC with KC. Recurrence (4/89 [5%]) and appearance of new lesions (10/89 [11%]) were minimal. Cosmetic outcome was excellent/good in 98% ESFC and 96% ESFC with KC. Grade 1–2 acute radiation dermatitis occurred in up to 80% of treated fields. The frequency of Grade 3 acute skin toxicities was low. Registry data demonstrate the potential for widefield RT to treat patients with significant skin pathology who have exhausted other therapies and require durable, minimally invasive treatment options. At 12 months, observed clinical success rates were higher than those reported for topical interventions for ESFC. Ongoing follow-up is required to determine longer term outcomes. [ABSTRACT FROM AUTHOR]

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Summary: Background: A range of 'field‐directed' treatments is available for the management of extensive skin field cancerization (ESFC), but to date, the only validated objective quantitative tools are limited to assessment of actinic keratoses (AKs) affecting the head. Aims: To develop a versatile quantitative instrument for objective clinical assessment of ESFC and perform initial internal validation across multiple anatomical zones. Methods: The study comprised instrument development, pilot testing and instrument refinement and two rounds of reliability and inter‐rater validation testing. The study was noninterventional and used a convenience sample of de‐identified patient photographs selected based on preset criteria. An expert panel developed the instrument and scoring system via a modified Delphi voting process. A sample of 16 healthcare professionals from multiple specialties undertook the pilot testing, and a panel of seven dermatologists were involved in validation testing. Validation was determined by assessment of overall inter‐rater agreement using Gwet chance‐corrected agreement coefficients (ACs). Results: The instrument produced, called the Method for Assessing Skin Cancer and Keratoses™ (MASCK™), comprises the Skin Field Cancerization Index (SFCIndex), derived from area of skin involvement and AKs (number and thickness), a global assessment score and a cancer‐in‐zone score, and uses Likert scales for quantitative scoring. The SFCIndex is a composite score comprising the number and thickness of AKs multiplied by area of skin involvement. ACs for the SFCIndex components, the overall SFCIndex score and the global assessment score were > 0.80 (rated 'almost perfect') while the AC for the cancer‐in‐zone metric was lower (0.33, rated 'fair'). Internal consistency was demonstrated via positive correlation between the overall SFCIndex score and the global assessment score. Conclusions: Our study found near‐perfect agreement in inter‐rater reliability when using MASCK to assess the severity of ESFC in multiple anatomical sites. Further validation of this novel instrument is planned to specifically assess its reliability, utility and feasibility in clinical practice. [ABSTRACT FROM AUTHOR]

Factors beyond the Psoriasis Area and Severity Index (PASI) contribute to disease severity in psoriasis and potentially affect treatment responses. This subset analysis of data from two phase 3 clinical studies assessed baseline parameters in patients with different degrees of psoriasis severity in order to determine treatment responses to ixekizumab and safety outcomes. This study used integrated data from the UNCOVER-2 and -3 trials involving 2709 patients with chronic plaque psoriasis to assess the efficacy and safety of ixekizumab in three subgroups of patients, defined by PASI > 15 (group 1), PASI > 15 and history of ≥3 non-biologic systemic therapies (group 2), or PASI = 12-15 (group 3). In groups 1 and 2, additional baseline features were identified that could influence treatment responses, including age at disease onset, Dermatology Life Quality Index, and work productivity. Irrespective of subgroup, ixekizumab demonstrated high PASI responses at weeks 12 and 60, which were evident as early as week 2. Adverse events did not differ across subgroups. Our data support the efficacy, early onset of action, and maintained response of ixekizumab as observed in previous trials, and highlight the complexity of comprehensively defining disease severity in psoriasis. [ABSTRACT FROM AUTHOR]

Objectives: Recent studies show that cats could play an important role in the transmission of Leptospira species. There are few reports of leptospirosis on Prince Edward Island (PEI) and none in cats. The objective of this study was to determine the prevalence of serum antibodies against Leptospira serovars and of Leptospira DNA in the urine of a population of free-roaming cats. Methods: Paired blood and urine samples were collected from 200 cats brought to a trap–neuter–return program. Antibody titers against six Leptospira serovars (Bratislava, Canicola, Gryppotyphosa, Hardjo, Pomona, Icterohaemorrhagiae) were determined by microscopic agglutination test. PCR was performed on urine samples to identify urine shedding of Leptospira DNA. Results: Antibodies were detected in 20/200 cats (10%) for at least one serovar, with titers ranging from 1:50 to 1:6400 (all serovars tested, except Hardjo). Urine samples of 7/200 cats (3.5%) were PCR-positive. Conclusions and relevance: Feral cats in PEI had a higher than expected exposure to leptospirosis and can shed DNA from pathogenic Leptospira species in urine. Further studies are needed to determine the prevalence of exposure to leptospirosis in other species on PEI and the potential role of feral cats in transmission of the disease. [ABSTRACT FROM AUTHOR]

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]

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a realworld setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebocontrolled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity Index ≤ 7), symptoms (worst itch score ≤ 4), or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through 1 year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Ciclosporin (CsA) is a systemic immunosuppressive agent indicated for use in the treatment of patients with recalcitrant atopic dermatitis (AD). Studies demonstrate reasonable evidence of benefit compared with placebo. However as biologic agents are under development for use in AD, an assessment of the use, attitude to and safety of CsA is essential in understanding unmet needs in severe AD. We present the results of a survey asking questions relating to initial dose, duration of prescription, precautions and monitoring undertaken during treatment, adverse events seen, and hierarchy of use for systemic agents. This survey was distributed at the annual meeting of the Australasian College of Dermatologists. Twenty-two percent of respondents never prescribe CsA, and 50% prescribe it only 1–2 times per month. When prescribed, the most frequently recommended duration was 6–12 months (24%). Of prescribers, 56% start with a low dose of <3.5 mg/kg daily, and when stratified according to years of experience, a higher proportion of more junior dermatologists commenced with lower doses (p=.028). Regarding side effects, 95% of respondents expressed concern about nephrotoxicity, 37% about hypertension, and 17% infection. The results suggest that although most dermatologists consider CsA to be effective, there are concerns regarding the safety profile. [ABSTRACT FROM AUTHOR]

Biological disease‐modifying agents have increasingly become available for the effective treatment of both cutaneous and non‐cutaneous inflammatory conditions. We report a case of a woman treated successfully for psoriasis and psoriatic arthritis with the IL‐17 inhibitor secukinumab whilst simultaneously being treated for severe asthma and nasal polyps, initially with the IL‐5 inhibitor benralizumab, followed by dupilumab, a monoclonal antibody that targets the IL‐4 receptor alpha subunit which blocks signalling from both IL‐4 and IL‐13. [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]

Sleep disturbance is considered one of the most prevalent symptoms of atopic dermatitis (AD), and is associated with daytime sleepiness, anxiety and depression. In previous phase 3 trials, dupilumab treatment demonstrated signif - icant improvement in objective AD signs and severity of symptoms, including sleep disturbance and mental health symptoms. To investigate the effect of dupilumab for up to 24 weeks on sleep quality, daytime sleepiness, anxiety and depression, using data from the DUPISTAD (NCT04033367) study. The randomized, phase 4 DUPISTAD study, was divided into two 12-week periods: an initial double-blind pla - cebo-controlled period, and a subsequent 12-week open-la - bel extension (OLE) period. The 24-week study enrolled adult patients with moderate-to-severe AD (Eczema Area and Severity Index score ≥12, Peak Pruritus Numeric Rating Scale [NRS] score ≥3, Sleep Disturbance NRS average score ≥5) who showed an inadequate response to topical treat - ments. These patients were randomized 2 :1 to dupilumab 300 mg every 2 weeks (q2w) for both the double-blind and OLE periods or placebo for the initial double-blind period, followed by dupilumab 300 mg q2w for the OLE period. The use of concomitant topical corticosteroids was permitted as needed by both groups throughout the study. Endpoints included mean change from baseline to week 24 for Patient-Reported Outcome Measures Information System (PROMIS) Sleep T-score (standardized score ranging from 30 [best] to 80 [worst], with a mean of 50), Epworth Sleepiness Scale (ESS; scored 0–24; higher values indicate increased daytime sleepiness), and Hospital Anxiety and Depression Scale (HADS; scored 0–21; higher values indicate a worse outcome). Throughout the study, patients also completed a Sleep Diary, recording the NRS of restfulness upon waking up (scored 0–10; lower values indicate a worse outcome). Statistical comparisons were not performed on the data collected during the OLE observation period. A total of 188 patients were enrolled in the study: 127 received continuous dupilumab (dupilumab–dupilumab group) and 61 received placebo to week 12 and then dupilumab to week 24 (placebo–dupilumab group). Baseline demographics and disease characteristics were well balanced. Improvement from baseline in sleep quality, daytime sleepiness, anxiety and depression was observed at week 24 in both groups, as illustrated by the mean change from baseline in PROMIS Sleep T-scores (−12.5 in the dupilumab–dupilumab group and −11.7 in the placebo–dupilumab group), ESS scores (−4.6 in the dupilumab–dupilumab group and −3.7 in the placebo–dupilumab group), HADS anxiety scores (−3.8 in the dupilumab– dupilumab group and −4.4 in the placebo–dupilumab group), HADS depression scores (−4.4 in the dupilumab–dupilumab group and −3.4 in the placebo–dupilumab group), and the NRS of restfulness upon a waking-up item of the Sleep Diary (+3.3 in the dupilumab–dupilumab group and +3.4 in the placebo–dupilumab group). The improvement achieved by the placebo–dupilumab group converged with that of the dupilumab–dupilumab group during the OLE period, as shown by the mean change from week 12 to week 24 in PROMIS Sleep T-score (−3.8), ESS score (−1.9), HADS anxiety score (−1.6), HADS depression score (−0.9) and NRS of restfulness upon a waking-up item of the Sleep Diary (+1.5). The safety profile of dupilumab was consistent with the known safety profile. Dupilumab provided sustained improvement through 24 weeks in patient-reported measures of sleep, daytime sleepiness, anxiety, and depression in adult patients with moderate-to-severe AD. Patients who were switched from placebo to dupilumab at week 12 showed rapid improvement in these parameters after the switch, eventually matching the improvement achieved by patients who received dupilumab from baseline through week 24. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic disease characterized by sleep disturbance, associated with night-time itching and scratching, along with skin pain, resulting in daytime drowsiness, diminished daytime productivity and overall reduced quality of life (QoL) in patients with AD. To report the effect of up to 24 weeks of dupilumab treatment on the QoL of adult patients with moderate-to-severe AD, using data from the DUPISTAD (NCT04033367) study. Phase 4, a randomized DUPISTAD study, comprised two 12-week periods: an initial placebo-controlled double-blind period, and a subsequent 12-week open-label extension (OLE) period. Adult patients with moderate-to-severe AD (Eczema Area and Severity Index score ≥12, Peak Pruritus Numeric Rating Scale [NRS] score ≥3, Sleep Disturbance NRS average score ≥5), showing an inadequate response to topical treatments, were randomized 2:1 to dupilumab 300 mg every 2 weeks (q2w) for both the double-blind and OLE periods or placebo for the initial double-blind period, followed by dupilumab 300 mg q2w for the OLE period. The use of concomitant topical corticosteroids was permitted during the entire course of the study. Endpoints, including Patient-Oriented Eczema Measure (POEM; scored 0–28, with higher values indicating a worse outcome), Dermatology Life Quality Index (DLQI; scored 0–30, with higher values indicating a poorer QoL), Skin Pain and Sensitivity NRS (scored 0–10, where 0=no pain/normal sensitivity and 10=worst possible pain/ extremely sensitive) were assessed from baseline to week 24. The enrolled patients also completed a Work Productivity and Activity Impairment Questionnaire (WPAI-AD), including an NRS rating of the AD-Affected Ability to do Regular Daily Activities other than a Job (scored 0–10, where 0=‘no effect’ and 10=‘prevented me from doing my daily activities’). Formal statistical comparisons were not performed on the data resulting from the OLE period. The DUPISTAD study enrolled a total of 188 patients: 127 patients received dupilumab throughout (dupilumab–dupilumab group), and 61 patients received a placebo and then switched to dupilumab (placebo–dupilumab group). Baseline demographics and disease characteristics were well balanced. Improvement from baseline in AD-related patient-reported QoL indicators and AD symptoms was observed at week 24 in both groups, as illustrated by the mean change from baseline in POEM total scores (−14.6 in the dupilumab–dupilumab group and −15.9 in the placebo–dupilumab group), DLQI scores (−12.6 in the dupilumab–dupilumab group and −13.4 in the placebo–dupilumab group), Skin Pain NRS scores (−4.7 in the dupilumab–dupilumab group and −5.0 in the placebo–dupilumab group), Skin Sensitivity NRS scores (−4.6 in the dupilumab–dupilumab group and −5.0 in the placebo–dupilumab group), and the WPAI-AD NRS of Ability to do Regular Daily Activities scores (−4.2 in the dupilumab–dupilumab group and −3.8 in the placebo–dupilumab group). The placebo– dupilumab group experienced most of this improvement during the OLE period, as illustrated by the mean change from week 12 to week 24 in POEM total score (−11.5), DLQI score (−5.5), Skin Pain NRS score (−3.0), Skin Sensitivity NRS score (−3.0) and the WPAI-AD NRS of Ability to do Regular Daily Activities score (−2.0). The safety profile of dupilumab was consistent with the known safety profile. Dupilumab provided sustained improvements through 24 weeks in AD-related patient-reported measures of QoL and AD symptoms in adults with moderate-to-severe AD. Patients who were switched from placebo to dupilumab at week 12 showed rapid improvement in these parameters after the switch, eventually matching the improvement achieved by patients who received dupilumab from baseline through week 24. [ABSTRACT FROM AUTHOR]