Search

Copyright of British Journal of Dermatology is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Although there are several highly effective treatments for severe psoriasis, many of them have to be given by injection and they are ineffective in some patients. Tofacitinib is a new oral (taken by mouth) drug which inhibits an enzyme, Janus kinase. It has proved beneficial in diseases called rheumatoid arthritis and ulcerative colitis, and its use has been studied in psoriasis. The authors, based in Europe, North and South America and Japan, have reviewed 6 clinical trials assessing the benefits and risks of tofacitinib treatment in patients with moderate or severe plaque psoriasis. The data collected comprise over 5,000 patient years. Patients received either 5mg or 10mg twice daily and were reviewed after 4 months and after a year. The drug was generally well tolerated, with side effects similar to the "biologic treatments" currently available for moderate to severe psoriasis, although there was a slightly higher rate of herpes zoster (shingles) infection, especially in the higher dose. The higher dose was more effective, and overall there was considerable improvement in the patient's quality of life, with improvement in the appearance of skin and nails and rapid reduction of itching. The authors conclude that the drug is effective and has an acceptable safety profile. As yet there is only one published trial comparing its efficacy with a biologic treatment (etanercept) and further comparisons with established drugs are desirable. However many patients would prefer to take a drug orally rather than by injection; injection reactions are a significant problem with biologic treatments. Linked Article: Strober et al. Br J Dermatol 2019; 180:67–75 [ABSTRACT FROM AUTHOR]

The article presents case study of a 62-year-old man presented with recurrent anogenital herpes simplex virus type 2-related pseudotumours. Topics discussed include known to be infected with human immunodeficiency virus type 1, fibrous chorion with plasma cell infiltrate and dense lymphocytic shown from histopathological examination, and introduction of lenalidomide due to lack of neurotoxicity of thalidomide and efficacy of antiherpetic drugs.

A letter to the editor about the efficacy of treatment with a recombinant interleukin-1 receptor antagonist for deficiency of interleukin-36 receptor antagonist (DITRA), a form of generalized pustular psoriasis (GPP), is presented.

The article presents a case of progressive multifocal leucoencephalopathy (PML) occurring in a 48-year old man treated for Sézary syndrome, a leukaemic variant of primary cutaneous T-cell lymphoma (CTCL). The man had a history of tonsil carcinoma, treated 5 years previously with combined surgery, radiation and chemotherapy. It also highlights the effectiveness of interferon alfa which was used to treat the patient.

Background Decision-making is a complex process. The aim of our study was to assess factors associated with the choice of the first biological treatment in patients with moderate-to-severe psoriasis. Methods Data on all patients included in the French prospective, observational, cohort, Psobioteq and initiating a first biologic prescription between July 2012 and July 2016 were analysed. Demographic information and clinical features were collected during routine clinical assessments by the dermatology team at the recruiting centres using a standardized case report form. The primary outcome was the nature of the first biologic treatment. Four groups were identified as follows: adalimumab, etanercept, ustekinumab and infliximab groups. Factors associated with the choice of the first biological agent were determined by a multinomial logistic regression model adjusted on year of inclusion. Results The study population included the 830 biological-naïve patients who initiated a first biological agent. The mean age was 46.6 years (± SD 13.9), and 318 patients (38.3%) were female. The most commonly prescribed biologic was adalimumab: 355 (42.8%) patients, then etanercept ( n = 247, 29.8%), ustekinumab ( n = 194, 23.4%) and infliximab ( n = 34, 4.0%). In the multinomial logistic regression analysis, patients were significantly more likely to receive adalimumab if they had a severe psoriasis as defined by baseline PASI or if they had psoriatic arthritis compared to etanercept ( aOR, 0.42; 95% CI, 0.16-1.07) and ustekinumab ( aOR, 0.15; 95% CI, 0.04-0.52). Patients were significantly more likely to receive ustekinumab ( aOR, 2.39; 95% CI, 1.04-5.50) if they had a positive screening for latent tuberculosis compared to adalimumab. Younger patients were also more likely to receive ustekinumab. Patients with chronic obstructive pulmonary disease were more likely to be prescribed ustekinumab or etanercept compared to adalimumab. There was a trend in favour of etanercept prescription in patients with cardiovascular comorbidities, metabolic syndrome and in patients with a history of cancer. Conclusion We identified patient- and disease-related factors that have important influence on the choice of the first biological agent in clinical practice. Clinicians appear to have a holistic approach to patient characteristics when choosing a biological agent in psoriasis. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about adult Kawasaki disease complicated by pancreatitis.

Presents a letter to the editor concerning the putative preferential usage of Vβ8 and Vβ12 gene segments by malignant cells in the cutaneous infiltrate of patients with mycosis fungoides.

Background: Biologics are the cornerstone of treatment of patients with moderate‐to‐severe plaque psoriasis and switches between biologics are frequently needed to maintain clinical improvement over time. Objectives: The main purpose of this study was to describe precisely switches between biologics and how their pattern changed over time with the recent availability of new biologic agents. Methods: We included patients receiving a first biologic agent in the Psobioteq multicenter cohort of adults with moderate‐to‐severe psoriasis receiving systemic treatment. We described switches between biologics with chronograms, Sankey and Sunburst diagrams, assessed cumulative incidence of first switch by competing risks survival analysis and reasons for switching. We assessed the factors associated with the type of switch (intra‐class – i.e. within the same therapeutic class ‐ vs. inter‐class) in patients switching from a TNF‐alpha inhibitor using multivariate logistic regression. Results: A total of 2153 patients was included. The cumulative incidence of switches from first biologic was 34% at 3 years. Adalimumab and ustekinumab were the most prescribed biologic agents as first and second lines of treatment. The main reason for switching was loss of efficacy (72%), followed by adverse events (11%). Patients receiving a TNF‐alpha inhibitor before 2016 mostly switched to ustekinumab, whereas those switching in 2016 or after mostly switched to an IL‐17 inhibitor. Patients switching from a first‐line TNF‐alpha inhibitor before 2016 were more likely to switch to another TNF‐alpha inhibitor compared with patients switching since 2018. Patients switching from etanercept were more likely to receive another TNF‐alpha inhibitor rather than another therapeutic class of bDMARD compared with patients switching from adalimumab. Conclusion: This study described the switching patterns of biologic treatments and showed how they changed over time, due to the availability of the new biologic agents primarily IL‐17 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Acral pustular disease within the pustular psoriasis/psoriasis‐like spectrum mainly includes palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH). Scarce data argue for a distinction between these two entities, but no study has compared the clinical and epidemiologic characteristics of ACH and PPP. Objectives: We aimed to perform a comparative description of the epidemiological and clinical characteristics of PPP and ACH in a multicentre retrospective cohort. Methods: In this multicentre national retrospective cohort study, we compared the epidemiological characteristics, comorbidities and psoriasis characteristics of patients with PPP and ACH. Results: A total of 234 patients were included: 203 (87%) with PPP, 18 (8%) with ACH and 13 (6%) with both, according to 2017 ERASPEN criteria. As compared with ACH, PPP was associated with female sex, smoking activity and higher median BMI (P = 0.01, P = 0.02 and P = 0.05 respectively). A family background of psoriasis was more frequent in PPP than ACH. Age of onset of palmoplantar disease was similar between PPP and ACH patients, median age 44 and 48 years respectively. Peripheral joint inflammatory involvement was the only rheumatic disease associated with ACH. The association with another psoriasis type was similar in PPP and ACH (57.6% and 61.1% respectively). Conclusion: Our study confirms in a large PPP cohort the predominance of females and a high prevalence of smoking and elevated body mass index but also shows an association of these features in PPP as compared with ACH. In addition, it highlights peripheral arthritis as the only arthritis endotype associated with ACH. Increased knowledge of the immunogenetic backgrounds underlying these two entities is warranted to better stratify pustular psoriasis or psoriasis‐like entities for precision medicine. [ABSTRACT FROM AUTHOR]

Summary: Background: Risankizumab has demonstrated efficacy and safety in patients with moderate‐to‐severe plaque psoriasis in randomized clinical trials. Objectives: To evaluate safety data from risankizumab psoriasis phase I–III clinical trials. Methods: Short‐term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long‐term safety was evaluated using integrated data from 17 phase I–III completed and ongoing trials. Results: Short‐term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient‐years (PY) of exposure, respectively]. Long‐term analyses included 3072 risankizumab‐treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure‐adjusted adverse event rates did not increase with long‐term treatment (318 vs. 171 events per 100 PY for short‐ and long‐term analyses). With long‐term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients. Conclusions: Risankizumab demonstrated a favourable safety profile over short‐ and long‐term treatment in patients with moderate‐to‐severe psoriasis. Whatis already known about this topic? In clinical trials of patients with moderate‐to‐severe plaque psoriasis, risankizumab, a selective interleukin‐23 inhibitor, was well tolerated and efficacious. Whatdoes this study add? In this comprehensive evaluation of risankizumab safety in patients with moderate‐to‐severe psoriasis, adverse event rates were comparable between risankizumab (n = 1306, 402 patient‐years) and placebo (n = 300, 92 patient‐years) in the short‐term (16‐week) analysis set, and were consistent with those in the long‐term analysis (n = 3072, 7927 patient‐years of risankizumab exposure).These findings are consistent with the known safety profile of risankizumab and support its long‐term use in moderate‐to‐severe psoriasis. Linked Comment: S. Mirali et al. Br J Dermatol 2022; 186:394–395. Plain language summary available online [ABSTRACT FROM AUTHOR]

Prof. Warren reports grants and personal fees from Abbvie, grants and personal fees from Celgene, grants and personal fees from Eli Lilly, grants and personal fees from Novartis, personal fees from Sanofi, grants and personal fees from UCB|, grants and personal fees from Almirall, grants and personal fees from Amgen, grants and personal fees from Janssen, grants and personal fees from Leo, grants and personal fees from Pfizer, personal fees from Arena, personal fees from Avillion, personal fees from Bristol Myers Squibb, personal fees from Boehringer Ingelheim, outside the submitted work. We are grateful to all the patients who have contributed to PsoProtect I Me i , the professional and patient organisations who supported or promoted PsoProtect I M i e and for the input of Prof Lars Iversen, Prof Nick Reynolds, Prof Joel Gelfand, Ms Christine Janus and Ms Melissa Sweeney through their vital contributions. Dr. Di Meglio reports grants and personal fees from UCB, personal fees from Novartis, personal fees from Janssen, outside the submitted work. [Extracted from the article]

Summary: Background: Registry data suggest that people with immune‐mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID‐19) outcomes compared with patients receiving no systemic treatments. Objectives: We used international patient survey data to explore the hypothesis that greater risk‐mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. Methods: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk‐mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed‐effects model. Results: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk‐mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35–1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23–1·56). Shielding was associated with established risk factors for severe COVID‐19 [male sex (OR 1·14, 95% CI 1·05–1·24), obesity (OR 1·37, 95% CI 1·23–1·54), comorbidity burden (OR 1·43, 95% CI 1·15–1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27–1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36–1·80). Modest differences in the proportion shielding were observed across nations. Conclusions: Greater risk‐mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID‐19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence‐based patient communication on risk‐mitigation strategies and may help inform updated public health guidelines as the pandemic continues. What is already known about this topic? At the beginning of the coronavirus disease 2019 (COVID‐19) pandemic, patients with immune‐mediated inflammatory diseases (IMIDs) on targeted systemic therapies were considered to be at higher risk of severe COVID‐19.Subsequent clinician‐reported registry data suggest that targeted systemic therapy use is associated with fewer adverse COVID‐19 outcomes compared with no systemic therapy. What does this study add? We characterize shielding behaviour in 3720 patients with IMIDs from a global self‐report survey.Use of targeted systemic therapy associates with increased shielding behaviour, compared with standard systemics or no therapy, as do demographic risk factors for severe COVID‐19 including male sex and obesity.Greater risk‐mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID‐19 outcomes.Behaviour variation across treatment groups reinforces the need for clear, evidence‐based patient communication on risk‐mitigation strategies.These data may help to inform updated public health guidelines as the pandemic continues. Linked Comment: G. Becher and A.D. Burden. Br J Dermatol 2021; 185:7–8. [ABSTRACT FROM AUTHOR]

Background: In 2018 in France, overall mean health‐related out‐of‐pocket (OOP) expenditures were 214.00€/year/patient. Aim: To evaluate OOP expenditures for psoriasis patients in France. Methodology: Observational, cross‐sectional, non‐comparative, multicentre study in 3000 patients with clinically confirmed psoriasis who responded to a specific digital questionnaire collecting demographic and socio‐economic characteristics, assessing the 3 domains (severity, psychosocial impact and past history and interventions) of the patient's Simplified Psoriasis Index (sa‐SPI) and expenditures to manage psoriasis, including OOP. Multivariate linear regression was conducted to search for factors associated with higher OOP. Results: In total, 2681 patients completed the questionnaire and, of those, 2562 provided clinically validated data. Overall, 60% were women; the mean age was 49.4 ± 14.8 years. 30% of the patients declared that they suffered from psoriatic arthritis. The final mean sa‐SPI core was 10.86 ± 9.70. Of these 2562 patients, 243 (9.5%) had severe, 442 (17.3%) moderate and 1877 (73.3%) mild psoriasis. In addition, 932 (36.4%) patients reported facial involvement, 724 (28.25%) genital impairment and 1124 (43.8%) lesions on the limbs. Mean OOP expenditures to manage psoriasis per patient were 531.00€, 439.74€ ± 939.85€ for patients with mild, 791.06€ ± 1367.67€ with moderate and 1077.64€ ± 1680.14€ for patients with severe psoriasis. For patients with psoriasis in the genital area, the median amount of expenditures (251.17€; CI95% [138.35;363.99]) was significantly higher than that for the face (183.85€; CI95% [78.76;288.94]) or limbs (199.96€; CI95% [93.77;306.15); (P < 0.001). More than 90% of the patients had OOP expenditures for over‐the‐counter products (97.5%) and alternative care (92.0%), especially for emollients and/or hydrating products. Conclusion: In France, in 2019, OOP expenditures to manage psoriasis were on average more than twice as high as the overall mean health‐related OOP expenditures estimated by the French Health Agency in 2018. These results should lead health authorities to review certain standards of healthcare reimbursement. [ABSTRACT FROM AUTHOR]

A commonly used assessment is the Psoriasis Area and Severity Index (PASI), with an absolute value of 10 or more indicating severe disease.1 How patients perceive the severity of psoriasis and physicians' evaluations may be discordant, especially when lesions involve visible areas or are associated with itching. [Extracted from the article]

Summary: Background: Although existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been investigated in patients with moderate‐to‐severe chronic plaque psoriasis. Objectives: To consider the benefits and risks of tofacitinib in patients with moderate‐to‐severe psoriasis. Methods: Data were pooled from one phase II, four phase III and one long‐term extension study comprising 5204 patient‐years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of 'clear' or 'almost clear', ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure. Results: Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients' quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID. Conclusions: Tofacitinib has a benefit–risk profile in moderate‐to‐severe psoriasis consistent with that of other systemic treatments. What's already known about this topic? Psoriasis is a chronic, systemic inflammatory disease, which has a significant impact on patients' health‐related quality of life.Although several existing psoriasis treatments are efficacious and well tolerated in many patients, some patients require treatment switching, and a proportion of patients remain untreated or undertreated.Potential challenges to the use of existing therapies include safety issues and limited efficacy in some patients with conventional oral psoriasis treatments, inconvenience of topical treatments and the requirement for parenteral administration of biologics. What does this study add? Consistent efficacy and a safety profile consistent with that seen in rheumatoid arthritis, psoriatic arthritis and ulcerative colitis were demonstrated for oral tofacitinib in patients with moderate‐to‐severe psoriasis.Tofacitinib has a benefit–risk profile in patients with moderate‐to‐severe psoriasis that is consistent with that of other systemic psoriasis treatments. Linked Comment: Fleming. Br J Dermatol 2019; 180:13–14. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Between February 2011 and November 2018, we enrolled 25 patients including 13 women with PV (21) and GPP (4) at baseline, with a median age of 38 years, consulting for 31 flares with RTI symptoms. Overall, 21 of 25 patients had at least one positive multiplex PCR viral test, with I Rhinovirus i and I Coronavirus i as the most frequently detected pathogens, while only two of 25 bacterial swabs were positive (one each for I Staphylococcus aureus i and I Streptococcus dysgalactiae i ). All patients reported history of previous acute psoriasis flares following RTI, including two patients with GPP/DITRA sharing the homozygous c.80T>C; p.Leu27Pro severe mutation.[6] No genetic abnormality was detected in I IL36RN i , I CARD14 i and I AP1S3 i in other patients. [Extracted from the article]

Background Limited information is available regarding factors associated with long-term drug survival of infliximab for psoriasis in real life. Objectives The main aim pf this study was to identify predictors of long-term (>12 months) drug survival among patients treated with infliximab for psoriasis in a real-world clinical setting. Methods Retrospectively collected data, relating to disease, patient characteristics and treatment procedures, in a multicentre observational cohort of patients with moderate-to-severe plaque psoriasis treated with infliximab at eight university hospitals, 120 of whom maintained a response to infliximab for more than 12 months, were compared with prospectively collected data in the same centres from 54 patients who experienced secondary loss of response within a 12-month period. Results Mean duration of drug survival of infliximab in patients with long-term drug survival was 41.12 months ± 20.64 SD vs. 8.5 months ± 2.43 SD in patients with a secondary loss of response. Multivariate analysis identified greater disease severity at treatment onset ( PASI score >12) ( OR = 5.18, 95% CI: 1.60-16.77, P = 0.006), high levels of initial psoriasis clearance ( PASI-90 reduction or equivalent) ( OR = 18.50, 95% CI: 4.56-74.45, P = 0.0001) and combination with methotrexate ( OR = 13.15, 95% CI: 1.46-118.79, P = 0.022) as independent predictors of long-term drug survival and sustained efficacy of infliximab. Conclusion Positive predictors for long-term drug survival of infliximab in real life were identified. Their impact on treatment management should be addressed in further prospective trials. [ABSTRACT FROM AUTHOR]

The article discusses research that assessed the efficacy of anti-tumor necrosis factor (TNF)-alpha drugs in patients with hidradenitis suppurativa (HS). Topics covered include the initial characteristics of HS patients treated with an anti-TNF-alpha drug, factors associated with a complete or partial response to first-line anti-TNF-alpha therapy, and the modest and inconsistent efficacy of the therapy for moderate-to-severe HS.

Background: Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis.Methods: In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician's global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100).Results: At week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P=0.08 for the comparison with ustekinumab) and 27% in AMAGINE-3 (P=0.007). Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. Through week 52, the rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab.Conclusions: Brodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.). [ABSTRACT FROM AUTHOR]

Introduction: Risankizumab has demonstrated a favourable safety profile in patients with psoriatic disease (moderate-to-severe psoriasis [PsO] and psoriatic arthritis [PsA]). We evaluated the long-term safety of risankizumab in psoriatic disease., Methods: Long-term safety was evaluated by analysing data from 20 (phase 1-4) clinical trials for plaque PsO and four (phase 2-3) trials for PsA. Treatment-emergent adverse events (TEAEs) and AEs in areas of special interest were reported among patients receiving ≥ 1 dose of risankizumab. Exposure-adjusted event rates were presented as events (E) per 100 patient-years (PY)., Results: The long-term safety data analyses included 3658 patients with PsO (13,329.3 PY) and 1542 patients with PsA (3803.0 PY). The median (range) treatment duration for patients with PsO and PsA was 4.1 (0.2-8.8) years and 2.8 (0.2-4.0) years, respectively. In the PsO population, rates of TEAEs, serious AEs and AEs leading to discontinuation were 145.5 E/100 PY, 7.4 E/100 PY and 1.9 E/100 PY, respectively; in the PsA population, these rates were 142.6 E/100 PY, 8.6 E/100 PY, and 1.8 E/100 PY, respectively. The rates of serious infections (excluding COVID-19-related infections) in the PsO and PsA populations were 1.2 and 1.4 E/100 PY, respectively. The rates of opportunistic infections (excluding tuberculosis and herpes zoster) were low (< 0.1 E/100 PY) in both populations. The rates of both nonmelanoma skin cancer (NMSC) and malignant tumours excluding NMSC were 0.6 and 0.5 E/100 PY in PsO and PsA, respectively, which are within the benchmarks of prior epidemiological studies. Adjudicated major cardiovascular event rates were 0.5 E/100 PY in PsO and 0.3 E/100 PY in PsA, which are within the epidemiologic reference benchmarks for both indications. No additional safety concerns were identified with this long-term exposure., Conclusions: The results support the favourable safety profile of risankizumab for long-term treatment of psoriatic disease with no new safety concerns and similar safety profiles among both PsO and PsA populations., (© 2024. The Author(s).)

Psoriasis is a multifactorial, chronic inflammatory skin disease with unresolved questions on its primary events. Iron overload has been described in the epidermis of psoriasis patients, but its relevance remains unknown. We found that the key iron regulatory hormone hepcidin was highly expressed in the epidermis of psoriasis patients, especially the pustular variants resistant to treatments. In a murine model of acute skin inflammation, keratinocyte-derived hepcidin was required for iron retention in keratinocytes, leading to hyperproliferation of the epidermal layer and neutrophil recruitment, two main features of psoriatic skin lesions. Keratinocytes overexpressing hepcidin were sufficient to elicit these psoriasiform features in a transgenic mouse model. Furthermore, transcriptome analysis of these keratinocytes revealed canonical pathways found in human psoriasis, pointing to a causal role for hepcidin in the pathogenesis of the disease. Altogether, our data suggest that hepcidin could be an actionable target for skin psoriasis treatment, in addition to current therapeutics, or targeted as maintenance therapy during remission to prevent recurrence., (© 2024. The Author(s).)

EFFISAYIL 1 was a randomized, placebo-controlled study of spesolimab, an anti-IL-36 receptor antibody, in patients presenting with a generalized pustular psoriasis flare. Treatment with spesolimab led to more rapid pustular and skin clearance versus treatment with placebo in approximately half of the patients. In this study, we present histologic, transcriptomic, and proteomic analyses of lesional and nonlesional skin and whole-blood samples collected from EFFISAYIL 1. Treatment with spesolimab led to a transition toward a nonlesional profile, with a downregulation of gene expressions in the skin of IL-36 transcripts (IL36α, IL36β, IL36γ) and those associated with neutrophil recruitment (CXCL1, CXCL6, CXCL8), proinflammatory cytokines (IL6, IL19, IL20), and skin inflammation (DEFB4A, S100A7, S100A8). Changes were manifest at week 1 and sustained to week 8. At the systemic level, reductions in serum biomarkers of inflammation (IL-17, IL-8, IL-6) were sustained until 12 weeks after spesolimab treatment. Considerable overlap was observed in the spesolimab-induced changes in gene and protein expressions from skin and blood samples, demonstrating the molecular basis of the effects of spesolimab on controlling local and systemic inflammation. Data are consistent with the mode of action of spesolimab, whereby inhibition of the IL-36 pathway leads to subsequent reductions in the key local and systemic pathologic events associated with generalized pustular psoriasis flares., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Generalized pustular psoriasis (GPP) lacks internationally accepted definitions and diagnostic criteria, impeding timely diagnosis and treatment and hindering cross-regional clinical and epidemiological study comparisons., Objective: To develop an international consensus definition and diagnostic criteria for GPP using the modified Delphi method., Evidence Review: The rarity of GPP presents a challenge in acquiring comprehensive published clinical data necessary for developing standardized definition and criteria. Instead of relying on a literature search, 43 statements that comprehensively addressed the fundamental aspects of the definitions and diagnostic criteria for GPP were formulated based on expert reviews of 64 challenging GPP cases. These statements were presented to a panel of 33 global GPP experts for voting, discussion, and refinements in 2 virtual consensus meetings. Consensus during voting was defined as at least 80% agreement; the definition and diagnostic criteria were accepted by all panelists after voting and in-depth discussion., Findings: In the first and second modified Delphi round, 30 (91%) and 25 (76%) experts participated. In the initial Delphi round, consensus was achieved for 53% of the statements, leading to the approval of 23 statements that were utilized to develop the proposed definitions and diagnostic criteria for GPP. During the second Delphi round, the final definition established was, "Generalized Pustular Psoriasis is a systemic inflammatory disease characterized by cutaneous erythema and macroscopically visible sterile pustules." It can occur with or without systemic symptoms, other psoriasis types, and laboratory abnormalities. GPP may manifest as an acute form with widespread pustules or a subacute variant with an annular phenotype. The identified essential criterion was, "Macroscopically visible sterile pustules on erythematous base and not restricted to the acral region or within psoriatic plaques.", Conclusions and Relevance: The achievement of international consensus on the definition and diagnostic criteria for GPP underscores the importance of collaboration, innovative methodology, and expert engagement to address rare diseases. Although further validation is needed, these criteria can serve as a reference point for clinicians, researchers, and patients, which may contribute to more accurate diagnosis and improved management of GPP.