Spesolimab is an anti-interleukin-36 receptor monoclonal antibody approved to treat generalised pustular psoriasis (GPP) flares. We aimed to assess the efficacy and safety of spesolimab for GPP flare ...prevention.
This multicentre, randomised, placebo-controlled, phase 2b trial was done at 60 hospitals and clinics in 20 countries. Eligible study participants were aged between 12 and 75 years with a documented history of GPP as per the European Rare and Severe Psoriasis Expert Network criteria, with a history of at least two past GPP flares, and a GPP Physician Global Assessment (GPPGA) score of 0 or 1 at screening and random assignment. Patients were randomly assigned (1:1:1:1) to receive subcutaneous placebo, subcutaneous low-dose spesolimab (300 mg loading dose followed by 150 mg every 12 weeks), subcutaneous medium-dose spesolimab (600 mg loading dose followed by 300 mg every 12 weeks), or subcutaneous high-dose spesolimab (600 mg loading dose followed by 300 mg every 4 weeks) over 48 weeks. The primary objective was to demonstrate a non-flat dose-response curve on the primary endpoint, time to first GPP flare.
From June 8, 2020, to Nov 23, 2022, 157 patients were screened, of whom 123 were randomly assigned. 92 were assigned to receive spesolimab (30 high dose, 31 medium dose, and 31 low dose) and 31 to placebo. All patients were either Asian (79 64% of 123) or White (44 36%). Patient groups were similar in sex distribution (76 62% female and 47 38% male), age (mean 40·4 years, SD 15·8), and GPP Physician Global Assessment score. A non-flat dose-response relationship was established on the primary endpoint. By week 48, 35 patients had GPP flares; seven (23%) of 31 patients in the low-dose spesolimab group, nine (29%) of 31 patients in the medium-dose spesolimab group, three (10%) of 30 patients in the high-dose spesolimab group, and 16 (52%) of 31 patients in the placebo group. High-dose spesolimab was significantly superior versus placebo on the primary outcome of time to GPP flare (hazard ratio HR=0·16, 95% CI 0·05–0·54; p=0·0005) endpoint. HRs were 0·35 (95% CI 0·14–0·86, nominal p=0·0057) in the low-dose spesolimab group and 0·47 (0·21–1·06, p=0·027) in the medium-dose spesolimab group. We established a non-flat dose-response relationship for spesolimab compared with placebo, with statistically significant p values for each predefined model (linear p=0·0022, emax1 p=0·0024, emax2 p=0·0023, and exponential p=0·0034). Infection rates were similar across treatment arms; there were no deaths and no hypersensitivity reactions leading to discontinuation.
High-dose spesolimab was superior to placebo in GPP flare prevention, significantly reducing the risk of a GPP flare and flare occurrence over 48 weeks. Given the chronic nature of GPP, a treatment for flare prevention is a significant shift in the clinical approach, and could ultimately lead to improvements in patient morbidity and quality of life.
Boehringer Ingelheim.
In the registration trial of risankizumab for patients with moderate‐to‐severe psoriasis in Japan, similar Psoriasis Area Severity Index (PASI) responses were observed for 75 mg or 150 mg ...risankizumab at most time points up to 52 weeks, except for PASI 100 at week 16. The use of 75 mg risankizumab offers an attractive option considering the high cost of risankizumab. However, it is unknown whether patients with mild‐to‐moderate psoriasis respond similarly, and the efficacy data of non‐Japanese patients is also lacking. We retrospectively included 30 consecutive Chinese patients receiving half‐dose (75 mg) risankizumab as scheduled up to 52 weeks. Compared with biologic‐experienced group, biologic‐naive group had a significantly higher PASI 50/75/90/100 achievement (p = 0.0098/0.0039/0.0016/0.0054) at week 52. PASI 50/75/90/100 curves in biologic‐naive group (p = 0.0117/0.0239/0.0143/0.0269) were also significantly higher when analysed generalized estimating equations (GEE) model. Though there was no statistically significant difference in terms of PASI 50/75/90/100 responses at any time points between those with body weight ≦ 65 kg and those >65 kg, a tendency of secondary failure was noted in those >65 kg from week 40 onwards. Patients who were both biologic‐naive and weighed ≦ 65 kg achieved sustained PASI 50/75/90 responses from week 16/28/40 onwards, respectively, indicating that they could be considered as potential candidates for 75 mg risankizumab. Though PASI 75 curve in patients without diabetes mellitus (DM) surpassed that in patient without DM, curves of other parameters did not reach significance when analysed by GEE model. There was no HBV, HCV or TB reactivation, nor other new safety signals during the 52‐week observational period. Providing risankizumab with flexible dosing options is beneficial in clinical practice considering the high cost of this medication.
Psoriasis is associated with multiple co-morbid medical conditions. The purpose of this study is to evaluate the relationships between psoriasis and cardiovascular disease, psoriatic arthritis, ...mental health conditions, and immune-mediated diseases, respectively. A literature search was performed during the study period January 1, 2015 to December 18, 2018. Of 2,499 records identified, 28 met our criteria selection and were included in this review. The relationships between psoriasis and these multiple comorbid disease conditions are discussed and are important to consider when developing the treatment plan and overall management of patients with psoriasis. Early recognition and treatment of comorbid disease conditions is important to help improve the quality of life for these patients.
HLA-Cw1 and Psoriasis Huang, Yi-Wei; Tsai, Tsen-Fang
American journal of clinical dermatology,
05/2021, Volume:
22, Issue:
3
Journal Article
Peer reviewed
Open access
Psoriasis is a chronic inflammatory skin condition with regional and ethnic differences in its prevalence and clinical manifestations. Human leukocyte antigen (HLA)-Cw6 is the disease allele ...conferring the greatest risk to psoriasis, but its prevalence is lower in Asian individuals. Recent studies have found associations between HLA-Cw1 and some Asian populations with psoriasis, especially Southern Chinese. HLA-Cw6 was associated with type I early-onset psoriasis, guttate psoriasis, Koebner phenomenon, and better response to methotrexate, interleukin (IL)-12/23, IL-17, and IL-23 targeting drugs. In contrast, HLA-Cw1 positivity has been associated with erythrodermic psoriasis, pustular psoriasis, and the axial type of psoriatic arthritis. Furthermore, HLA-Cw1 was more frequently associated with high-need patients who did not respond to conventional therapies. No known trigger factor nor autoantigen has been identified for HLA-Cw1 positivity. However, HLA-Cw1 has been linked to some viral agents. For example, cytotoxic T lymphocytes recognize multiple cytomegalovirus pp65-derived epitopes presented by HLA alleles, including HLA-C*01:02. In addition, cytomegalovirus can lead to severe exacerbation of psoriatic skin disease. The proposed interaction between viral infection, HLA-Cw1, and psoriasis is through the killer cell immunoglobulin-like receptors of natural killer cells. Given the diverse nature of psoriasis pathogenesis and the difference in HLA-Cw prevalence in different racial groups, more studies are needed to confirm the role of HLA-Cw1 in psoriasis.
Angiotensin II receptor blockers (ARBs) are commonly used for cardiovascular diseases, especially for patients who can't tolerate the side effects of cough and angioedema caused by angiotensin ...converting enzyme inhibitors (ACEIs). However, the evidence of using ARBs in dermatology is mostly anecdotal and limited to case reports or small case series. Here we present a narrative review focusing on the therapeutic use of ARBs in dermatology and adverse cutaneous reactions due to the administration of ARBs.
Since human skin is the primary interface responding to external mechanical stimuli, extrinsic forces can disrupt its balanced microenvironment and lead to cutaneous lesions. We performed this review ...to delve into the pathological effects of mechanical pressure on skin from the cellular perspective. Fibroblasts of different subsets act as heterogeneous responders to mechanical load and express diverse functionalities. Keratinocytes relay mechanical signals through mechanosensitive receptors and the ensuing neurochemical cascades to work collaboratively with other cells and molecules in response to pressure. Mast cells release cytokines and neuropeptides, promoting inflammation and facilitating interaction with sensory neurons, while melanocytes can be regulated by pressure through cellular and molecular crosstalk. Adipocytes and stem cells sense pressure to fine-tune their regulations of mechanical homeostasis and cell differentiation. Applying mechanical pressure to the skin can induce various changes in its microenvironment that potentially lead to pathological alterations, such as ischemia, chronic inflammation, proliferation, regeneration, degeneration, necrosis, and impaired differentiation. The heterogeneity of each cellular lineage and subset from different individuals with various underlying skin conditions must be taken into consideration when discussing the pathological effects of pressure on the skin. Thus, elucidating the mechanotransduction and mechanoresponsive pathways from the cellular viewpoint is crucial in diagnosing and managing relevant dermatological disorders.
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