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Complement inhibition has been identified as a potential therapeutic target for multiple inflammatory disorders including Hidradenitis Suppurativa (HS). It is currently unclear how complement integrates into our current model of molecular pathogenesis in HS and whether it represents a central component of pathogenesis, or a neutrophil‐associated bystander. Levels of C5a in serum and tissue correlate with disease activity and degree of neutrophilic infiltrates in HS. C5a has been associated with Th17 immune axis activation in psoriasis, rheumatoid arthritis and Crohn's disease with strong similarities to TH17 activation in HS. Porphyromonas species (which are identified in the HS microbiome) are able to cleave inactive C5 into C5a implicating the cutaneous microbiome as an activator of complement. C3a and C5a are associated with activation of the NLRP3 inflammasome, implicated in the inflammatory drive in HS. Complement receptors are present upon dendritic cells, monocytes, fibroblasts and adipocytes, which may broaden the potential contribution of complement to multiple aspects of HS pathogenesis. Dysregulation of complement receptor pathways has been documented in obesity, insulin resistance and polycystic ovarian syndrome leading to the possibility that complement may explain the epidemiological associations between these conditions and HS. The therapeutic potential of complement inhibitors in HS may be related to the therapeutic target (complement receptor or complement subunit) and the presence of alternate receptors (such as C5aR2) or ligands (including C3a, PAMPs and DAMPs). Integrating complement into the known pathogenesis of HS may aid in explaining the contradictory results between Phase 2 studies of C5a antagonists. It also allows for the identification of existing knowledge gaps to target further clinical investigation and research. [ABSTRACT FROM AUTHOR]

Summary: Background: Australia has the highest incidence of cutaneous melanoma worldwide. Previous studies have identified some body areas (forearms and dorsal hands) have lower rates of melanoma than expected when compared with other similarly exposed areas, leading to the suggestion that endogenous immunological protective mechanisms in certain body sites may exist. Aims and Methods: We hypothesise that examination of melanoma by body site in a regional Australian setting would demonstrate no significant variation in the incidence of melanoma across highly sun exposed areas including the head and neck and upper limbs. Results were stratified by body site and further examined by univariate correlation analysis by gender, age, body site, Breslow thickness and subtype. Polytomous logistic regression was used to test the difference in risk factors by location of melanoma. Results: A total of 772 melanomas were included in the analysis. Melanomas of the upper limb were more likely to affect females (OR = 2.415 95%CI: 1.433‐4.072) and more likely to be thinner than other body sites. Compared to other international studies, statistically significant decreased rates of melanoma were seen on the upper limb compared to other areas of the body (X2 = 16.29, P < 0.001). Examination of sites of melanoma on the upper limb showed significantly decreased rate on the distal upper limb given relative body surface areas (X2 = 6.30 P = 0.04). Discussion and Conclusions: Our study was limited by its retrospective nature, and the findings require validation in a larger prospective cohort. Further exploration of such mechanisms may lead to new insights into the immunological mechanisms surrounding cutaneous melanoma. [ABSTRACT FROM AUTHOR]

The utility of Strongyloidiasis screening in the setting of Dupilumab therapy is unknown. Our retrospective cohort study identifies a low prevalence of Strongyloidiasis with no cases of disseminated disease in the setting of Dupilumab therapy. Baseline IgE and Eosinophil levels were not associated with Strongyloidiasis and screening is likely of low utility. [ABSTRACT FROM AUTHOR]

Background Several registries for hidradenitis suppurativa (HS) already exist in Europe and the USA. There is currently no global consensus on a core dataset (CDS) for these registries. Creating a global HS registry is challenging, owing to logistical and regulatory constraints, which could limit opportunities for global collaboration as a result of differences in the dataset collected. The solution is to encourage all HS registries to collect the same CDS of information, allowing registries to collaborate. Objectives To establish a core set of items to be collected by all HS registries globally. The core set will cover demographic details, comorbidities, clinical examination findings, patient-reported outcome measures and treatments. Methods Beginning in September 2022, 20 participants – including both clinicians with expertise in HS and patient advocates – from eight countries across three continents participated in a Delphi process consisting of four rounds of voting, with all participants completing each round. A list of potential items for inclusion in the core set was generated from the relevant published literature, including systematic reviews of comorbidities in HS, clinical and examination findings, and epidemiology. For disease severity and progression items, the Hidradenitis SuppuraTiva Core outcome set International Collaboration (HiSTORIC) core set and other relevant instruments were considered for inclusion. This resulted in 47 initial items. Participants were invited to suggest additional items to include during the first round. Anonymous feedback was provided to inform each subsequent round of voting to encourage consensus. Results The eDelphi process established a CDS of 48 items recommended for inclusion in all HS registries globally. Conclusions The routine adoption of this CDS in current and future HS registries should allow registries in different parts of the world to collaborate, enabling research requiring large numbers of participants. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 49-year-old woman with enlarging painless but pruritic perianal plaque 2 cm from the anal verge. Topics include denying a history of genital human papillomavirus or any other sexually transmitted infections; and patient denying bleeding, pain, discomfort or irritation to the plaque from bowel motions or wiping the area.

Defining the health-related quality of life (HRQoL) in patients suffering from the heritable blistering disease epidermolysis bullosa (EB) is important in assessing the efficacy of new treatments. The quality of life in EB questionnaire (QOLEB) is an English 17-item EB-specific HRQoL measurement tool. The aim of this study was to develop a validated and reliable QOLEB in Dutch and assess the HRQoL in Dutch EB patients. The QOLEB was translated to Dutch according to protocol. Fifty-five adult patients across 4 EB subtypes participated. The QOLEB had excellant correlation with the Skindex-29 (ρs = 0.86), good correlation with the SF-36 physical score (ρs = –0.75), and moderate correlation with the SF-36 mental score (ρs = –0.43). The discriminative validity between the 4 different EB subtypes was significant (p = 0.002). The internal consistency was excellent (α = 0.905), and the test–retest reliability strong (ρs = 0.88). In conclusion, the Dutch QOLEB is a reliable and valid instrument for the assessment of the HRQoL in adult EB patients. [ABSTRACT FROM AUTHOR]

An editorial is presented on new paradigms and advances in medical and translational science. Topics include aberrations in cutaneous healing relevant to the mechanistic understanding of chronic wounds; and great potential for collaboration, cooperation, and cross-pollination in skills and knowledge between wound research and dermatology in Australia.

The pathogenesis of hidradenitis suppurativa (HS) centers around Th17/Treg dysfunction illustrated by lesional elevation of IL-17A, IL-6, and other inflammatory mediators resulting in a chronic feed-forward inflammatory cascade. Similar inflammatory mechanisms have been identified in psoriasis and rheumatoid arthritis (RA) in which traditional immunosuppressants (including methotrexate) are routinely used with reasonable levels of disease control. Methotrexate's mechanism of action in these instances includes downregulation of the Th17 axis via alterations in dendritic cell and T-cell activity and maturation. Published data suggest methotrexate in an ineffective therapy in HS, which does not pair with our current understanding of the mechanisms of disease. The reasons behind this, including are discussed. Some HS patients may benefit from drugs such as methotrexate, and acknowledgment of the potential of disease heterogeneity will allow exploration of which factors may enable identification of such individuals. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease presenting with diverse manifestations ranging from nodules and abscesses to draining tunnels. Whether the underlying inflammation from lesions extends to relatively healthy-appearing adjacent perilesional and distant nonlesional skin has not been systematically evaluated. We sought to characterize lesional, perilesional, and nonlesional skin in patients with HS. Skin biopsy samples were collected under ultrasound guidance from patients with active, untreated moderate-to-severe HS. Site-matched control biopsy samples from healthy volunteers were used for comparison. RNA sequencing demonstrated that HS skin clustered separately from healthy control skin, with perilesional and lesion skin clustering together and away from nonlesional skin. Immunohistochemistry analysis identified psoriasiform hyperplasia with keratin 16 positivity in both perilesional and lesional skin, with comparable levels of CD3+, CD11c+, and neutrophil elastase–positive cellular infiltration. There was a marked upregulation of IL-17 signaling in perilesional and lesional skin. HS samples clustered on the basis of expression of lipocalin-2 (LCN2), with samples characterized by high LCN2 expression in the skin exhibiting a differing transcriptomic profile with significantly higher overall inflammation than that of skin characterized by low LCN2 levels. Perilesional HS skin has a transcriptomic and molecular profile comparable to that of lesional skin. HS can be grouped into 2 distinct subtypes based on molecular levels of LCN2 in the skin, with the LCN2-high subtype exhibiting an overall higher inflammatory burden and an upregulation of targetable cytokines. To our knowledge, this is the first study to characterize a unique HS subtype (and a potential endotype) that may guide future therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: The hidradenitis suppurativa (HS) clinical response (HiSCR) has come under scrutiny as several HS clinical trials failed to meet primary endpoints with high placebo responses. This may be due to limitations of the tool and raters' ability to accurately characterize and count lesions, rather than lack of efficacy of the studied drug. Due to HS lesion complexity and potential differences in rater training, it was hypothesized that there would be discrepancies in how providers characterize and count lesions for HS clinical trials. Objective: To evaluate how HS providers and patients name and count HS lesions and to identify discrepancies among providers to initiate the development of consensus‐driven guidance for HS rater training. Methods: An online survey was distributed to the members of HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC). Respondents were asked to classify lesion images composed of multiple and different morphology types and answer questions regarding inclusion of associated dermatological conditions. Results: Forty‐seven HISTORIC members responded (29 providers; 18 patients). There was variability in how respondents classified HS lesions. Of 12 questions containing images, four had ≥50% of respondents choosing the same answer. With an image of a lesion composed of different morphologies, 45% of providers counted it as a single lesion and 45% counted it as multiple distinct lesions. With an image of multiple interconnected draining tunnels, 7% of providers classified it as a single draining tunnel while 79% categorized it as multiple draining tunnels with the number estimated by visual inspection. There was also variability in deciding whether lesions occurring in associated conditions should be considered separately or included in HS lesion counts. Patient responses were also variable. Conclusions: The result of the current study reaffirms the gap in how providers characterize and count HS lesions for clinical trials and the need to develop consensus‐driven rater training related to HS outcome measures. [ABSTRACT FROM AUTHOR]

Background/Objectives: Surgical deroofing is an essential part of ongoing management of Hidradenitis Suppurativa, including persistent lesions non‐responsive to medical therapy. The variables associated with delayed wound healing after surgical deroofing are contradictory within the literature due to the inclusion of heterogeneous surgical intervention methods. We aimed to assess the predictors of time to wound healing after surgical deroofing in HS. Methods: Patients who underwent in‐office surgical deroofing between 2020 and 2024 at a single tertiary HS referral centre were included in analysis. Demographic, disease and blood variables were collected as per standard of care. Statistical analysis was performed using univariate correlation, with multiple regression performed to explore the interactions between variables and identify variables predictive of time to wound healing. Results: A total of 270 individuals were included in the analysis. The median time to wound healing was 9.6 weeks with a range from 4 to 22 weeks. Kaplan–Meier curves demonstrated significant differences with the log rank test when comparing biologic use versus no use, normal versus abnormal CRP and normal versus abnormal haemoglobin. Cox regression analysis identified biologic use with a significant hazard ratio compared to no biologic therapy (HR = 2.512, p < 0.0001) along with baseline CRP (HR = 0.968, p < 0.0001) and baseline haemoglobin (HR = 1.052, p < 0.001). Conclusions: Time to wound healing after in‐office deroofing can be decreased with prior biologic therapy and markers of systemic inflammation in blood are also significantly associated with delays in healing. This correlates well with the existing literature promoting concurrent medical and surgical therapy to improve patient outcomes in HS. [ABSTRACT FROM AUTHOR]

Background: Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory disease with significant impact upon quality of life. Generic quality‐of‐life measures suffer from decreased face validity and content validity, leading to the development of disease‐specific quality‐of‐life measures such as the Hidradenitis Suppurativa Quality of Life (HiSQOL) outcome measure. The aim of this study was to validate the use of the HiSQOL in the Australian population and evaluate the quality‐of‐life impact in HS patients in Australia. Methods: A total of 301 patients were recruited and consented to be involved in this study. All participants were invited to complete the HiSQOL questionnaire along with basic demographic and disease information, the DLQI and HADS anxiety and depression scale. Participants were then asked to repeat the questionnaires 14 days later to assess test–retest reliability. Results: The mean HiSQOL score was 46.5 out of a possible total score of 76 (SD = 24.2) indicating a very large impact on quality of life. Based upon the published validity bands this corresponds to a very large impact on quality of life. Validation statistics indicated a high degree of internal consistency (Cronbach's alpha = 0.956) with expected levels of convergent validity and excellent test–retest reliability (p = 0.95). Multiple regression analysis indicated individuals with a younger age of onset and positive family history had significantly greater quality‐of‐life impact as measured by the HiSQOL. Conclusions: The HiSQOL is a valid, reliable measure for assessing the quality‐of‐life impact of HS. Significant factors influencing quality of life include age of onset and family history. Longitudinal measurements will enable evaluation of the impact of therapy upon QOL in the Australian context. [ABSTRACT FROM AUTHOR]

Background/Objectives: Caucasian and Asian patients with hidradenitis suppurativa demonstrate significant differences with regard to age, gender and body mass index. Demographic characteristics are known to influence the efficacy and drug survival of hidradenitis suppurativa therapeutics including biologic therapies. What remains unknown is the impact of ethnicity upon the efficacy of therapeutics once demographic and disease characteristics have been taken into account. This is an important question given the expansion of biologic therapies for HS into the global patient community. Methods: We assessed 170 patients from a single HS specialist centre in Australia stratified by patient‐identified ethnicity including those identifying as either Caucasian or Asian. Results: Asian patients demonstrated lower BMI, higher rates of smoking and greater odds of Hurley stage 3 disease with tunnels than Caucasian patients in line with the reported literature. There was no significant difference between percentage of individuals achieving HiSCR50 or IHS4‐55 at Week 16. Significant differences were seen in median time to secondary loss of response, and Kaplan–Meier curve analysis showed a significant difference between curves when stratified by patient‐reported ethnicity. Cox regression analysis demonstrated after accounting for age, gender, BMI, smoking and Hurley stage, the significance of ethnicity in influencing time to secondary loss of response disappears. Conclusions: Caucasian or Asian ethnicity does not influence response to adalimumab treatment on patients with hidradenitis suppurativa. [ABSTRACT FROM AUTHOR]

Background Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a considerable disease burden. Existing treatment options are limited and often suboptimal; a high unmet need exists for effective targeted therapies. Objectives To explore the effects of spesolimab treatment in patients with HS. Methods This randomized double-blind placebo-controlled proof-of-clinical-concept (PoCC) study was conducted at 25 centres across 12 countries from 3 May 2021 to 21 April 2022. Patients had moderate-to-severe HS for ≥ 1 year before enrolment. Patients were randomized (2 : 1) to receive a loading dose of 3600-mg intravenous spesolimab (1200 mg at weeks 0, 1 and 2) or matching placebo, followed by maintenance with either 1200-mg subcutaneous spesolimab every 2 weeks from weeks 4 to 10 or matching placebo. The primary endpoint was the percentage change from baseline in total abscess and inflammatory nodule (AN) count at week 12. Secondary endpoints were the absolute change from baseline in the International Hidradenitis Suppurativa Severity Score System (IHS4), percentage change from baseline in draining tunnel (dT) count, the proportion of patients achieving a dT count of 0, absolute change from baseline in the revised Hidradenitis Suppurativa Area and Severity Index (HASI-R), the proportion of patients achieving Hidradenitis Suppurativa Clinical Response (HiSCR50), the proportion of patients with ≥ 1 flare (all at week 12) and patient-reported outcomes. Results In this completed trial, randomized patients (n = 52) received spesolimab (n = 35) or placebo (n = 17). The difference vs. placebo in least squares mean is reported. At week 12, the percentage change in total AN count was similar between treatment arms: –4.1% [95% confidence interval (CI) –31.7 to 23.4]. There was greater numerical improvement in the spesolimab arm, as measured by IHS4 (13.9, 95% CI –25.6 to –2.3); percentage change from baseline in dT count (–96.6%, 95% CI –154.5 to –38.8); and the proportion of patients achieving a dT count of 0 (18.3%, 95% CI –7.9 to 37.5). Spesolimab treatment also improved HASI-R and HiSCR50 vs. placebo. Spesolimab demonstrated a favourable safety profile, similar to that observed in trials in other diseases. Conclusions This exploratory PoCC study supports the development of spesolimab as a new therapeutic option in HS. [ABSTRACT FROM AUTHOR]

Hidradenitis Suppurativa is a chronic inflammatory disease of which the pathogenesis is incompletely understood. Dermal fibroblasts have been previously identified as a major source of inflammatory cytokines, however information pertaining to the characteristics of subpopulations of fibroblasts in HS remains unexplored. Using in silico-deconvolution of whole-tissue RNAseq, Nanostring gene expression panels and confirmatory immunohistochemistry we identified fibroblast subpopulations in HS tissue and their relationship to disease severity and lesion morphology. Gene signatures of SFRP2+ fibroblast subsets were increased in lesional tissue, with gene signatures of SFRP1+ fibroblast subsets decreased. SFRP2+ and CXCL12+ fibroblast numbers, measured by IHC, were increased in HS tissue, with greater numbers associated with epithelialized tunnels and Hurley Stage 3 disease. Pro-inflammatory CXCL12+ fibroblasts were also increased, with reductions in SFRP1+ fibroblasts compared to healthy controls. Evidence of Epithelial Mesenchymal Transition was seen via altered gene expression of SNAI2 and altered protein expression of ZEB1, TWIST1, Snail/Slug, E-Cadherin and N-Cadherin in HS lesional tissue. The greatest dysregulation of EMT associated proteins was seen in biopsies containing epithelialized tunnels. The use of the oral Spleen tyrosine Kinase inhibitor Fostamatinib significantly reduced expression of genes associated with chronic inflammation, fibroblast proliferation and migration suggesting a potential role for targeting fibroblast activity in HS. [ABSTRACT FROM AUTHOR]

The article discusses a real-world cohort analysis that quantifies the time to medical and surgical therapy after the diagnosis of hidradenitis suppurativa (HS) and pilonidal sinus disease (PSD). The study found that individuals with HS were more likely to receive biologics, while those with PSD were more likely to undergo surgical intervention. The results suggest the benefits of early biologic intervention and the integration of these findings into guidelines and models of care. Further research is needed to establish the efficacy of biologic therapy in PSD, especially when combined with surgical therapy. [Extracted from the article]

Hidradenitis suppurativa (HS) is a chronic, inflammatory condition of the pilosebaceous unit. The typical patient with HS is characterized as someone with obesity, who smokes and who has nodules, abscesses and/or draining tunnels predominantly distributed in intertriginous skin. It has been established that lifestyle and genetic factors are the main pathophysiological drivers of HS. In this critical review, we explore the interrelatedness of meta-inflammation, obesity and HS and discuss if and how this relationship may be manipulated for a therapeutic end. [ABSTRACT FROM AUTHOR]

The 2nd Annual Symposium on Hidradenitis Suppurativa Advances (SHSA) took place on 03‐05 November 2017 in Detroit, Michigan, USA. This symposium was a joint meeting of the Hidradenitis Suppurativa Foundation (HSF Inc.) founded in the USA, and the Canadian Hidradenitis Suppurativa Foundation (CHSF). This was the second annual meeting of the SHSA with experts from different disciplines arriving from North America, Europe and Australia, in a joint aim to discuss most recent innovations, practical challenges and potential solutions to issues related in the management and care of Hidradenitis Suppurativa patients. The last session involved clinicians, patients and their families in an effort to educate them more about the disease. [ABSTRACT FROM AUTHOR]

Methods for describing and reporting the clinical and histologic characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. In this study, we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from patients with HS. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help to consistently classify specimens in biobanks on the basis of histologic features and more accurately report and select samples used in translational research projects., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The pathogenesis of hidradenitis suppurativa is complex and multifaceted. Our understanding of disease mechanisms is in constant flux with new genetic, inflammatory, and microbiological insights upending previous paradigms and enlightening us as to the complex connections between different drivers of disease. This updated review integrates novel genetic insights from genome wide association studies, along with novel basic science data from single cell transcriptomic studies and recent interventional translational work to inform our evolving understanding of the disease. The overarching premise is that hidradenitis suppurativa is a chronic autoinflammatory disorder characterized by inflammatory dysregulation in a background of stem cell fate aberrations highly responsive to hormonal and metabolic changes. Genetic drivers are linked to both hair follicle stem cell fate and cellular response to androgen signaling. The complex mixed inflammatory circuits involve both innate and adaptive immunity, with activation of inflammatory fibroblast subsets and tertiary lymphoid organs in chronic disease. Interplay between inflammation, the cutaneous and gut microbiomes are observed both pre- and posttherapy, however causality remain unclear. Metabolic syndrome, sex hormones and insulin resistance are all interlinked, with adipose tissue being a hormonally active organ able to modulate endogenous sources of sex hormones. Future enquiry regarding factors contributing to disease progression and the identification of novel therapeutic targets will aid in more effective therapeutic strategies for management of this burdensome disease., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Pyoderma gangrenosum is a severe ulcerative disease with a great need for novel therapies. A major barrier to the development of novel therapies is a lack of understanding of disease pathogenesis. We present the results of a proof-of-concept open-label clinical trial of IL-23p19 antagonism with tildrakizumab in pyoderma gangrenosum. Gene expression analysis identified proinflammatory genes associated with IFN responses and dendritic cell activity, including IFI27, XBP1, SAA1 LGALS3, and signal transducer and activator of transcription 3 significantly downregulated in lesional tissue after 12 weeks of therapy. Immunohistochemistry confirmed reduction in IL-17A- and IL-17F-positive cells as well as reduction in TNF-a-, C5a-, and IL-1B-positive cells in week 12 samples compared with those at baseline. Significant reduction in serum inflammation was observed through serum proteomics, with IL-8, IL-6, and CASP-8 levels reduced comparable with those in healthy controls at week 12. Clinical outcomes demonstrated significant reduction in ulcer size, pain, itch, and QOL outcomes in line with the molecular findings. Differential expression of key inflammatory cytokines such as IL-8, CXCL5, PD-L1, SPP1, and matrix metalloproteinase 1 was observed in tissue and serum when stratified by clinical responders and nonresponders. These data provide insights into the clinical relevance of alterations in molecular markers in pyoderma gangrenosum and the potential for the identification of clinically relevant biomarkers of disease activity., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors made the following disclosures: J.W.F. has conducted advisory work for Janssen, Boehringer-Ingelheim, Pfizer, Kyowa Kirin, LEO Pharma, Regeneron, Chemocentryx, Abbvie, Azora, Novartis, and UCB, participated in trials for Pfizer, UCB, Boehringer-Ingelheim, Eli Lilly, CSL, and Azora, and received research support from Ortho Dermatologics, Sun Pharma, LEO Pharma, UCB, and La Roche Posay. The remaining authors have no conflicts of interest to disclose.

Competing Interests: Competing interests statement:The authors declare no competing interest.

Importance: The HLA-B*15:02 allele has been associated with an increased risk of carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in specific Asian populations (including Han Chinese, Malaysian, Thai, and Vietnamese individuals). While HLA-B*15:02 genotype testing in Asian populations is recommended by several international prescribing guidelines, it is not subsidized by the Medicare Benefits Schedule in Australia., Objective: To evaluate the cost-effectiveness of HLA-B*15:02 genotyping in Asian Australian patients with epilepsy., Design, Setting, and Participants: A model with components of decision analysis and Markov simulation was developed to simulate clinical trajectories of adult Asian Australian patients with newly diagnosed epilepsy being considered for carbamazepine treatment. Cost-effectiveness and cost-utility analyses over a lifetime time horizon were conducted from the perspective of the Australian health care sector. The study was conducted in May 2023 and data analysis was performed from August 2023 to November 2023., Intervention: No HLA-B*15:02 genotyping and the empirical initiation of treatment with carbamazepine vs HLA-B*15:02 genotyping and the initiation of treatment with valproate in allele carriers., Main Outcomes and Measures: Life-years (LYs), quality-adjusted life-years (QALYs), and costs in 2023 Australian dollars (A$); incremental cost-effectiveness ratios., Results: HLA-B*15:02 screening was associated with an additional mean cost of A$114 (95% CI, -A$83 to A$374; US$76; 95% CI, -US$55 to US$248) and a reduction in 0.0152 LYs (95% CI, 0.0045 to 0.0287 LYs) but improvement by 0.00722 QALYs (95% CI, -0.0247 to -0.01210) compared with no screening, resulting in an incremental cost-effectiveness ratio of A$15 839 per QALY gained (US$10 523 per QALY). Therefore, universal genotyping for Asian Australian individuals was cost-effective compared with current standards of practice at the A$50 000 per QALY willingness-to-pay threshold. Sensitivity analyses demonstrated that the intervention remained cost-effective across a range of costs, utilities, transition probabilities, and willingness-to-pay thresholds. At the A$50 000 per QALY willingness-to-pay threshold, universal screening was the preferred strategy in 88.60% of simulations., Conclusions and Relevance: The results of this economic evaluation suggest that HLA-B*15:02 screening represents a cost-effective choice for Asian Australian patients with epilepsy who are being considered for treatment with carbamazepine.

Hidradenitis suppurativa is a disease in great need of novel therapies. Given the heterogeneous nature of the disease and the variable response to therapies, biomarkers are essential to predict response to therapies and increase our understanding of disease pathogenesis. Our recent phase 2 clinical trial of spleen tyrosine kinase antagonism using fostamatinib in hidradenitis suppurativa demonstrated a 75% clinical response, with the greatest benefit in individuals with elevated serum inflammation and IgG. In this study, we present results of an in-depth serum proteomic analysis in this patient cohort identifying downregulation of IL-12B as well as B-cell-associated proteins CCL19 and CCL20 and IFN-γ-mediated proteins CXCL10 and CX3CL1. Clinical responders demonstrated greater reduction in serum IL-17A, IL-6, IL-8, and CX3CL1 compared with clinical nonresponders. Baseline levels of CCL28 were associated with clinical response to fostamatinib therapy at week 12. Overall, this suggests that fostamatinib, by targeting B-cell receptor and Fc receptor activity in B cells, monocytes, and macrophages, has a significant molecular impact on the inflammatory serum proteome of hidradenitis suppurativa. In addition, potential therapeutic biomarkers may aid in patient selection for targeted therapy., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)