Australian consensus: Treatment goals for moderate to severe psoriasis in the era of targeted therapies - Considerations for paediatric patients.

BACKGROUND: 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. 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 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. CONCLUSION: 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.

Network meta-analyses comparing the efficacy of biologic treatments for achieving complete resolution of nail psoriasis at 24-28 and 48-52 weeks.

BACKGROUND: Available network meta-analyses (NMAs) comparing the efficacy of biologics in nail psoriasis (NP) have not included recently approved biologics such as bimekizumab nor have they provided comparisons up to 1 year. OBJECTIVE: We conducted two NMAs that update and extend results from a previous NMA comparing biologics for achieving complete resolution of NP. METHODS: Bayesian NMAs were performed using a generalized linear model with a logit link to model the binary outcome of nail clearance at weeks 24-28 and 48-52. RESULTS: For the NMA at weeks 24-28, which included seven biologics and placebo, the absolute probability of achieving complete resolution of NP was highest for ixekizumab (46.4%; 95% credibility interval [CrI] 35.2-58.0), followed by brodalumab (37.1%; 95% CrI 17.1-62.2) and bimekizumab (30.3%; 95% CrI 12.7-53.9). For the NMA at weeks 48-52, which included six biologics, the absolute probability was highest for ixekizumab (77.2%; 95% CrI 51.1-93.4), followed by adalimumab (75.6%; 95% CrI 61.5-87.3) and brodalumab (71.9%; 95% CrI 38.4-93.2). CONCLUSION: Among biologics included in these two NMAs, ixekizumab has the highest absolute probability of achieving complete resolution of NP. Results may help to inform treatment decisions for patients with NP.

Improving Psychological Health Outcomes in Children with Atopic Dermatitis.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease that usually develops in early childhood. AD has a significant impact on quality of life and psychological health outcomes in both adults and children. There are increased reported rates of psychiatric comorbidities including anxiety, depression, ADHD and suicidal ideation compared to the general population. Primary caregivers of children with pediatric eczema and their families may also have derangements in psychological health and quality of life. A number of interventions exist for AD and address wellbeing outcomes as an important aspect of effective treatment. Methods: A comprehensive literature search was conducted using PubMed/Medline, Embase, the Cochrane Central Register of Controlled Trials in February 2023. Published studies up to April 2023 were included related to interventions for childhood AD that included psychological health or quality of life outcomes. These interventions were stratified according to type and evidence quality. Results: Search strategy revealed a wide variety of interventions with demonstrated improvements in quality of life or wellbeing of patients with pediatric AD or their families. Both pharmacological and non-pharmacological interventions demonstrated effectiveness in improving disease outcomes. Conclusion: A variety of both pharmacological and non-pharmacological interventions may be employed to improve psychological health outcomes in children with AD.

Outcomes in organ transplants from donors with melanoma: a systematic review.

Melanoma transmitted through organ transplantation is an increasingly reported event. Immunosuppression increases the risk of melanoma; however, transmission of malignancy from transplanted organs is a distinct etiology of melanoma occurrence. The risk of transmission of melanoma from an organ donor with melanoma has yet to be determined. The authors aimed to investigate this phenomenon by reviewing the outcomes of patients that received organs from donors with melanoma. A systematic literature review was conducted with emphasis on identifying organ donors with known histories of melanoma and reported information regarding recipients of their organs. The databases PubMed, MEDLINE, Embase, and JBI EBP were searched in January 2023. Search terms included "melanoma," terms for solid organs, "donor," "transplant," "transmission," and their variations as well as terms related to temporal relations. Inclusion criteria were articles that stated outcomes in organ recipients from donors that had a diagnosis of melanoma either pretransplant or postmortem. Reference lists of selected articles were hand searched for further studies. A total of 232 articles were identified from the search parameters. After applying inclusion and exclusion criteria, 13 articles were selected. Hand searching the references of these articles yielded four additional articles. Of the 75 organ recipients that received organs from donors with known melanoma, 43 developed melanoma. While a definitive quantitative risk cannot be ascertained based on our review, the numerous reported cases of melanoma in organ recipients from donors that have melanoma should still be considered by clinicians.

Integrated Safety Analysis on Skin Cancers among Patients with Psoriasis Receiving Ixekizumab in Clinical Trials.

INTRODUCTION: Limited data exist on skin cancer risk in patients with psoriasis using biologics. Here, we report treatment-emergent adverse events (TEAEs) of skin cancer in patients treated with ixekizumab from psoriasis clinical trials. METHODS: Integrated safety databases from 17 clinical trials of adults with moderate-to-severe psoriasis treated with ≥ 1 dose of ixekizumab for ≤ 5 years were used to analyze exposure-adjusted incidence rates (IRs) per 100 patient-years of exposure (PYE) and clinically characterize dermatologist-adjudicated skin cancer TEAEs. RESULTS: Of 6892 patients, 58 presented with ≥ 1 skin cancer TEAE (IR 0.3) with IRs remaining stable with longer ixekizumab exposure. Non-melanoma skin cancer (NMSC) was the most common event (IR 0.3) affecting 55 patients; of those, 44 had basal cell carcinoma (IR 0.2) and 16 had squamous cell carcinoma (IR 0.1). Two treatment-emergent melanoma events were identified; neither were classified as serious AEs. CONCLUSIONS: Incidence of skin neoplasms in patients with psoriasis treated with ixekizumab for ≤ 5 years was low, and among those events, NMSC was most common. Limitations included that longer exposure may be required to confirm risk of skin cancer and that the study exclusion criteria of several studies, which excluded patients with skin cancer events within 5 years prior to baseline, might limit interpretation of skin cancer risk in this cohort. These findings support the safety profile of ixekizumab for patients requiring long-term psoriasis control.

Laser-Assisted Drug Delivery: A Systematic Review of Safety and Adverse Events.

Laser-assisted drug delivery (LADD) is an increasingly studied and applied methodology for drug delivery. It has been used in a wide variety of clinical applications. Given the relatively low barrier to entry for clinicians as well as ongoing research in this area, the authors aimed to review outcomes relating to safety in laser-assisted drug delivery. A systematic review was conducted, with the databases PubMed, Medline and Embase searched in September 2022. Included articles were those that mentioned laser-assisted drug delivery in human subjects that also reported adverse effects or safety outcomes. There were no language-based exclusions. Conference abstracts and literature reviews were excluded. The results were then tabulated and categorized according to the application of LADD. In total, 501 articles were obtained. Following deduplication, screening, and full text review 70 articles of various study designs were included. Common findings were erythema, oedema, pain, and crusting following LADD. Several notably more severe adverse effects such as generalized urticaria, infection, scarring and dyspigmentation were noted. However, these events were varied depending on the clinical use of LADD. Relevant negatives were also noted whereby no studies reported life-threatening adverse effects. Limitations included limited details regarding the adverse effects within the full texts, lack of follow-up, and risk of bias. In conclusion, there were multiple adverse effects that clinicians should consider prior to carrying out LADD, where treatment goals and patient tolerability should be considered. Further evidence is needed to quantitatively determine these risks.

Factors associated with treatment satisfaction in patients with hidradenitis suppurativa: results from the Global VOICE project.

BACKGROUND: Nearly half of patients with hidradenitis suppurativa (HS) report dissatisfaction with their treatment. However, factors related to treatment satisfaction have not been explored. OBJECTIVES: To measure associations between treatment satisfaction and clinical and treatment-related characteristics among patients with HS. METHODS: Treatment satisfaction was evaluated utilizing data from a cross-sectional global survey of patients with HS recruited from 27 institutions, mainly HS referral centres, in 14 different countries from October 2017 to July 2018. The primary outcome was patients' self-reported overall satisfaction with their current treatments for HS, rated on a five-point scale from 'very dissatisfied' to 'very satisfied'. RESULTS: The final analysis cohort comprised 1418 patients with HS, most of whom were European (55%, 780 of 1418) or North American (38%, 542 of 1418), and female (85%, 1210 of 1418). Overall, 45% (640 of 1418) of participants were either dissatisfied or very dissatisfied with their current medical treatment. In adjusted analysis, patients primarily treated by a dermatologist for HS had 1·99 [95% confidence interval (CI) 1·62-2·44, P < 0·001] times the odds of being satisfied with current treatment than participants not primarily treated by a dermatologist. Treatment with biologics was associated with higher satisfaction [odds ratio (OR) 2·36, 95% CI 1·74-3·19, P < 0·001] relative to treatment with nonbiologic systemic medications. Factors associated with lower treatment satisfaction included smoking (OR 0·78, 95% CI 0·62-0·99; active vs. never), depression (OR 0·69, 95% CI 0·54-0·87), increasing number of comorbidities (OR 0·88 per comorbidity, 95% CI 0·81-0·96) and increasing flare frequency. CONCLUSIONS: There are several factors that appear to positively influence satisfaction with treatment among patients with HS, including treatment by a dermatologist and treatment with a biologic medication. Factors that appear to lower treatment satisfaction include active smoking, depression, accumulation of comorbid conditions and increasing flare frequency. Awareness of these factors may support partnered decision making with the goal of improving treatment outcomes. What is already known about this topic? Nearly half of patients with hidradenitis suppurativa report dissatisfaction with their treatments. What does this study add? Satisfaction with treatment is increased by receiving care from a dermatologist and treatment with biologics. Satisfaction with treatment is decreased by tobacco smoking, accumulation of comorbid conditions including depression, and higher flare frequency. What are the clinical implications of this work? Awareness of the identified factors associated with poor treatment satisfaction may support partnered decision making and improve treatment outcomes.

Comparative effectiveness of biologics in clinical practice: week 12 primary outcomes from an international observational psoriasis study of health outcomes (PSoHO).

BACKGROUND: Clinical trials study treatment outcomes under stringent conditions, capturing incompletely the heterogeneity of patient populations and treatment complexities encountered in real-world practice. OBJECTIVES: To compare the effectiveness of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis. METHODS: The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year observational cohort study in adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. Primary study endpoint is the proportion of patients achieving 90% improvement in Psoriasis Area and Severity Index (PASI 90) and/or static Physician Global Assessment (sPGA) 0/1 at Week 12 (W12) in the anti-IL-17A cohort (ixekizumab [IXE], secukinumab) vs. all other approved biologics. Secondary outcomes include the proportion of patients who achieve PASI 75/90/100, absolute PASI scores ≤5, ≤2 and ≤1, Dermatology Life Quality Index (DLQI) score of 0/1 at W12 between the two cohorts and among the individual biologics. Comparative effectiveness analyses were conducted using Frequentist Model Averaging (FMA), a novel causal inference machine learning approach. Missing data for binary outcomes were imputed as non-response. RESULTS: Patient profiles in the anti-IL-17A cohort and other biologics cohort were similar, with more frequent comorbid psoriatic arthritis and less frequent exposure to conventional treatments in the patients receiving anti-IL-17A biologics. At W12, 71.4% of patients who received an anti-IL-17A biologic achieved PASI 90 and/or sPGA 0/1 compared to 58.6% of patients who received other biologics (odds ratios [OR], 1.9; 95% confidence intervals [CI], [1.6, 2.4]). Similar findings were observed for secondary outcomes. CONCLUSIONS: These results reflect the high efficacy and early onset of skin clearance of IL-17A inhibitors observed in randomized clinical trials and confirm the effectiveness of anti-IL-17A biologics in the real-world setting.

Efficacy and Safety of Ixekizumab Versus Adalimumab in Biologic-naïve Patients With Active Psoriatic Arthritis and Moderate-to-severe Psoriasis: 52-week Results From the Randomized SPIRIT-H2H Trial.

Introduction: The randomized, open-label, assessor-blinded, parallel-group SPIRIT-H2H trial (NCT03151551) demonstrated superiority of ixekizumab over adalimumab in simultaneously achieving improvement in joint symptoms (American College of Rheumatology [ACR]50) and skin clearance (Psoriasis Area and Severity Index [PASI]100) in biologic-naïve patients with active psoriatic arthritis (PsA) and plaque psoriasis (PsO) at Week (W) 24. Higher efficacy of ixekizumab versus adalimumab was maintained through W52. Objectives: This analysis investigated efficacy and safety of ixekizumab and adalimumab in the subgroup of patients with PsA and moderate-to-severe PsO through W52. Methods: Efficacy and safety outcomes were analyzed in patients with PsA and moderate-to-severe PsO (PASI ≥ 12, Body Surface Area ≥ 10%, static Physician Global Assessment ≥ 3) through W52. Categorical and continuous outcomes were analyzed using logistic regression models and mixed model for repeated measures, respectively. Results: More ixekizumab-versus adalimumab-treated patients simultaneously achieved PASI100 and ACR50 at W24 (40.8% versus 17.6%, P = 0.015) and W52 (38.8% versus 17.6%, P = 0.026). Likewise, more ixekizumab-versus adalimumab-treated patients achieved PASI100 (59.2% versus 25.5%, P = 0.001) and PASI90 (81.6% versus 60.8%, P = 0.028) through W52, and nail PsO clearance at W24. Joint symptom improvements were comparable between groups. No new safety findings were reported. Conclusions: Ixekizumab had higher efficacy than adalimumab in simultaneous achievement of ACR50 and PASI100 at W24 and W52 in patients with PsA and moderate-to-severe PsO. Ixekizumab-treated patients showed higher response rates for nail PsO clearance and for reporting minimal or no impact on quality of life at W24.

Prevention and management of acneiform rash associated with EGFR inhibitor therapy: A systematic review and meta-analysis.

INTRODUCTION: Epidermal growth factor receptor (EGFR) inhibitors are established therapies for advanced lung, colorectal, and head and neck cancers. They commonly cause acneiform eruptions that affect patient quality of life and may lead to discontinuation of therapy. METHODS: A systematic review and meta-analysis was undertaken to assess strategies for the prevention and reactive management of acneiform rash associated with EGFR inhibitor therapy for advanced lung, colorectal, and head and neck cancers. A systematic Medline, Embase, and EBM Reviews database search was conducted on the 2nd of January 2021. The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement was followed and the studies were critically appraised. Studies were selected if they focused on preventing or treating acneiform eruptions in adults being treated for advanced lung cancer, colorectal cancer, and head and neck cancers with EGFR inhibitors. RESULTS: Oral antibiotics had the greatest efficacy in preventing grade 2 or higher acneiform eruptions with a relative risk reduction of 40% (RR = .6, 95% CI .46-.79, p < .01). Other treatment modalities did not have statistically significant results. Topical antibiotics had a total relative risk reduction of 19% (RR = .81, 95% CI .45-1.48, p = .5). Vitamin K1 cream did not reduce the relative risk (RR = 1.08, 95% CI .45-1.48, p = .50). Sunscreen had a total relative risk reduction of 25% (RR = .75, 95% CI .49-1.14, p = .18). CONCLUSIONS: The results of this meta-analysis reinforce the fact that oral tetracycline antibiotics are the most efficacious prophylactic option for acneiform eruptions in EGFR inhibitors. They should be offered to suitable patients commencing treatment and used with a general skin-care routine involving emollients and avoidance of irritants.

A cross-sectional study of sun-related behaviours in the internet era.

OBJECTIVES: To identify the use and purchasing behavior of sunscreen products over the internet by Australian females, and factors contributing to these. METHODS: A cross sectional study of 1065 Australian female participants aged 18 and over was performed in August 2019, utilizing an online questionnaire to collect descriptive data regarding current demographics and behaviors in sunscreen product use, online sunscreen product purchasing, sunscreen product preferences and barriers to use, and sun exposure behaviors. RESULTS: 57% of 1065 participants have used the internet for sunscreen product recommendations, and 41% have made online purchases of local or international sunscreen products. Participants are more likely to check the ingredients regularly when buying them online (38%) than when purchasing them while overseas (31%).Internet use for sunscreen recommendations and purchasing was significantly impacted by the level of education (p < 0.001), age (<0.001), time in Australia (p < 0.001) and ethnicity (p < 0.001). Checking listed active ingredients when purchasing international sunscreen products online was significantly affected by the level of education (p = 0.02). CONCLUSION: There is a large proportion of Australian women who use the internet for recommendations or purchasing of sunscreen containing products. Active ingredients should be clearly listed when advertised on the internet, especially for international sunscreens.

Indirect comparisons of ixekizumab versus three interleukin-23 p19 inhibitors in patients with moderate-to-severe plaque psoriasis - efficacy findings up to week 12.

BACKGROUND: It is challenging to select the most appropriate biologic treatment for patients with moderate-to-severe plaque psoriasis. OBJECTIVE: To compare speed of onset and level of skin improvement between the interleukin (IL)-17A antagonist ixekizumab and the IL-23 p19 inhibitors guselkumab, tildrakizumab, and risankizumab in patients with moderate-to-severe plaque psoriasis. METHODS: Using data from controlled clinical trials, both adjusted indirect comparisons (AICs) and matching adjusted indirect comparisons (MAICs) were performed to determine the risk difference (RD) between ixekizumab and each IL-23 p19 inhibitor for the proportion of patients with ≥75%/90%/100% improvement compared with baseline in Psoriasis Area and Severity Index (PASI 75/90/100) up to week 12. Placebo, etanercept, or ustekinumab were used as the comparator bridge. RESULTS: In all (M)AICs, RDs generally significantly favored ixekizumab over guselkumab (placebo bridge), tildrakizumab (placebo or etanercept bridge), and risankizumab (placebo or ustekinumab bridge) from the earliest assessment time (≥ week 2) to week 12 when considering PASI 75/90/100 responses. CONCLUSION: Ixekizumab provides a faster onset of effect and earlier clinical benefits than guselkumab, tildrakizumab, or risankizumab in patients with moderate-to-severe psoriasis, as reflected by higher levels of skin improvement than with these IL-23 p19 inhibitors up to week 12.

Hidradenitis suppurativa and association with stroke: systematic review and meta-analysis.

PURPOSE: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful nodules, abscesses, sinus tract formation and scarring. The relationship between HS and strokes is not well established. To assess this potential association, a systematic review and meta-analysis was performed according to PRISMA guidelines. MATERIALS AND METHODS: Electronic searches were performed from six online databases. All eligible case-control studies comparing patients with HS versus non-HS were included. All studies must have included either the proportion of patients with strokes (identified via ICD-9 or ICD-10 codes) in each group, or the summary effect size for association between HS and strokes. Odds ratio (OR) with 95% confidence interval (CI) was used as the effect size. RESULTS: Through our search, we identified six case-control studies for inclusion. From pooled data, we found a significantly higher proportion of strokes in HS cases compared with controls (OR 1.74, 95% CI 1.45-2.09; p < .00001). Limitations included those studies reviewed were observational by design which are susceptible to bias and lack of randomization. CONCLUSION: Our pooled findings demonstrate that the odds of stroke are increased in patients with HS when compared with controls. Dermatologists and other clinicians should be vigilant cerebrovascular risk assessment and risk mitigation in patients with HS.

Network meta-analysis comparing the efficacy of biologic treatments for achieving complete resolution of nail psoriasis.

BACKGROUND: Nail psoriasis (NP) is common and of high importance in patients with psoriasis. Complete resolution of NP at week 24‒26 is an unambiguous nail outcome accessible for indirect treatment comparison of biologics. OBJECTIVE: To evaluate the comparative efficacy of approved biologics in achieving complete resolution of NP at week 24‒26. METHODS: A network meta-analysis (NMA) was conducted to indirectly compare the efficacy of six biologics in achieving complete resolution of NP at week 24‒26 in patients with moderate-to-severe psoriasis and concomitant NP. Complete resolution of NP was defined as a score of zero on the Nail Psoriasis Severity Index (NAPSI), modified NAPSI (mNAPSI) or Physician's Global Assessment of Fingernails (PGA-F). RESULTS: The probability of achieving complete resolution of NP was highest for ixekizumab (46.5%; 95% credibility interval [CrI] 35.1‒58.0; Surface Under the Cumulative RAnking curve [SUCRA] 97%), followed by brodalumab (37.0%; 17.0‒61.0; 79%), adalimumab (28.3%; 24.4‒32.4; 62%), guselkumab (27.7%; 21.1‒35.1; 58%), ustekinumab (20.8%; 10.2‒35.2; 37%), and infliximab (0.8%; 0.0‒8.9; 17%). CONCLUSION: In patients with moderate-to-severe psoriasis and concomitant NP, ixekizumab has the greatest likelihood among approved biologics of achieving complete resolution of NP at week 24‒26. Findings should be interpreted carefully because of inherent study limitations.

Cannabinoids interaction with transient receptor potential family and implications in the treatment of rosacea.

With the recent interest in medical marijuana, research into cannabinoids is regaining wider attention. Cannabinoids are collectively a group of active compounds that can be produced by animals (endocannabinoids), plants (phytocannabinoids), or synthetically. By acting on a number of different receptors like cannabinoids receptors and transient receptor potential ion channel family, cannabinoids are known to modulate cutaneous inflammation, pain, and itch. Rosacea is a highly prevalent disease and can be associated with a significant degree of morbidity associated with its symptom. Transient receptor potential ion channels are known to be triggered in rosacea and may underlie a portion of rosacea's pathophysiology. This article aims to detail the transient receptor potential channel pathways in rosacea and the known effects of cannabinoids on these pathways and further discussing the potential role of cannabinoids in treating rosacea.

Comparing quality of life outcomes of JAK inhibitors and biological treatments for atopic dermatitis: a systematic review and network meta-analysis.

Introduction:Several novel biological agents and janus kinase (JAK) inhibitors are being investigated for efficacy in the management of atopic dermatitis (AD). However, there is a paucity of head-to-head trials comparing agents and their effect on quality of life (QoL).Methods:A systematic review of existing studies was performed, and data was pooled for meta-analysis from eligible studies of novel systemic agents for AD which reported QoL outcomes. Sixteen week least square means differences (LSM) were pooled and compared using network meta-analysis to synthesize direct and indirect comparisons, with 95% credible intervals (Crl) provided.Results:At 16 weeks, Dermatology Life Quality Index outcomes showed dupilumab 300 mg once weekly had the highest improvement versus placebo (LSM -4.63, 95% Crl -5.46,3.79). At 16 weeks, the improvement in Patient Oriented Eczema Measure scores ranked abrocitinib 200 mg daily the highest (LSM -7.62, 95% Crl -10.26; -4.98) and improvement in Hospital Anxiety and Depression Scale ranked dupilumab 300 mg once weekly highest (LSM -2.98, 95% Crl -4.48; -1.47) The improvement in peak pruritus scores ranked lebrikizumab 250 mg fortnightly (LSM -64.90, 95% Crl-84.58; -45.22) highest.Conclusion:The present study suggests that there are various systemic options for AD for which all seem to demonstrate a degree of QoL-related efficacy.