Real-world Performance of a New Strategy for Off-Label Use of Guselkumab in Moderate to Severe Psoriasis: Super-Responder Patients as the Epitome of Efficacy and Optimisation.

BACKGROUND: Guselkumab is a drug used to treat moderate to severe plaque psoriasis. However, real-life clinical data on its off-label use are limited, especially regarding the optimal drug dosage regimen for different patient profiles. OBJECTIVE: The main objective of this real-world, single-centre, retrospective study was to identify the off-label guselkumab dosing regimen used in clinical practice. The study also aimed to evaluate the drug's efficacy, safety, and survival, as well as the proportion of super-responders (SR) based on a newly proposed definition. METHODS: The study included 69 patients who started treatment with guselkumab between March 2019 and July 2021. Patients were followed up until April 2022, during which time their efficacy, safety, persistence, and use of guselkumab were recorded. Patients were aged ≥  18 years and had moderate to severe plaque psoriasis. RESULTS: The mean disease duration was 18.6 years, and 59% of patients had received at least one biologic treatment before guselkumab with a mean of 1.3 biologics per patient. The initial absolute Psoriasis Area and Severity Index (PASI) was 10.1 and decreased to 2.1 between Week 11-20 without significant changes in the PASI value throughout the 90 weeks of follow-up. The cumulative probability of drug survival was 93.5% at Week 52. No differences were found in terms of efficacy and survival associated with the off-label drug dosage regimens compared to the doses described in the Summary of Product Characteristics (SmPC). The greatest adjustments in the drug administration regimen were achieved in the subgroups of bio-naïve and SR patients, with a reduction in the number of administrations by 40% and 47% compared to the regimen described in the SmPC. Super-response to guselkumab was mainly associated with patients naïve to previous biologic treatment. CONCLUSION: The study demonstrated that off-label use of guselkumab was safe and effective in real-life clinical practice. The findings suggest that adjustments to the drug administration regimen may be necessary to optimise its use in different patient profiles, especially in SR and bio-naïve patients. Further studies are needed to confirm these findings.

Subacute cutaneous lupus erythematosus following ribociclib therapy for metastatic breast cancer.

INTRODUCTION: Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) has been associated with drugs with different mechanisms of action, including anti-hypertensives, tumour necrosis factor-α inhibitors and even some chemotherapy medicines. In the last years, a few reports have been described in patients treated with cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib. CASE REPORT: Here, we describe a case of DI-SCLE in association with ribociclib and exemestane in a woman diagnosed with metastatic breast cancer. MANAGEMENT AND OUTCOME: Topical mometasone was prescribed for two weeks with complete resolution of lesions, also abemaciclib was substituted for ribociclib, and the patient had stable disease with no relapse of DI-SCLE. DISCUSSION: To our knowledge, this is the first report of ribociclib-induced SCLE but based on the DI-SCLE reported cases associated others CDK4/6 inhibitors, the role of this family of drugs in dermatopathology must be further investigated.

Identifying biomarkers of treatment response to ciclosporin in atopic dermatitis through multiomic predictive modelling: DERMATOMICS study protocol.

INTRODUCTION: There is a need to optimise the management of atopic dermatitis (AD), improving the efficacy of treatments and reducing the toxicity associated with them. Although the efficacy of ciclosporine (CsA) in the treatment of AD has been thoroughly documented in the literature, the optimal dose has not been yet established. The use of multiomic predictive models of treatment response could optimise CsA therapy in AD. METHODS AND ANALYSIS: The study is a low-intervention phase 4 trial to optimise the treatment of patients with moderate-severe AD requiring systemic treatment. The primary objectives are to identify biomarkers that could allow for the selection of responders and non-responders to first-line treatment with CsA and to develop a response prediction model to optimise the CsA dose and treatment regimen in responding patients based on these biomarkers. The study is divided into two cohorts: the first comprised of patients starting treatment with CsA (cohort 1), and the second, of patients already receiving or who have received CsA therapy (cohort 2). ETHICS AND DISSEMINATION: The study activities began following authorisation by the Spanish Regulatory Agency (AEMPS) and the Clinical Research Ethics Committee of La Paz University Hospital approval. Trial results will be submitted for publication in an open access peer-reviewed medical speciality-specific publication.Trial registration of this study can be located at the EU Clinical Trials Register, available from https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en. Our clinical trial was registered in the website before the enrolment of the first patient complying with European regulations. EU Clinical Trials Register is a primary registry according the WHO. Once our trial was included in a primary and official registry, in order to extend the accessibility to our research, we also registered it retrospectively in clinicaltrials.gov; however, this is not mandatory as per our regulation. TRIAL REGISTRATION NUMBER: NCT05692843.

An Emollient PLUS Balm Is Useful for the Management of Xerosis in Patients Treated for Cancer: A Real-World, Prospective, Observational, Multicenter Study.

INTRODUCTION: Xerosis is a common skin side effect of current anticancer therapies, including chemotherapy, targeted therapy, radiotherapy, and hormonotherapy. We evaluated the effectiveness of an emollient PLUS containing an Aquaphilus dolomiae extract (ADE-G1) for the management of xerosis in adult patients treated for cancer. METHODS: This real-world, prospective, observational, multicenter study involved 319 xerotic cancer patients, who were prescribed the study product according to the usual practice of their physician. The practitioner assessed xerosis severity and objective clinical signs, and the patients assessed subjective clinical signs and the impact of their skin condition on their quality of life, at inclusion and after around 4 weeks of use. Overall effectiveness and tolerance were assessed at the end of the study. Clinical success was defined by the combination of several of these effectiveness outcomes. RESULTS: Daily application of the emollient PLUS reduced xerosis severity in 62.7% of patients (p < 0.0001). The mean total severity scores for objective and subjective clinical signs were reduced by 67.7% and 57.4% (p < 0.0001), respectively, compared with baseline. The mean Dermatology Life Quality Index (DLQI) score also significantly improved at the end of follow-up (-56.6%, p < 0.0001). The product was rated as "effective" or "very effective" by the physician for over 80% of patients, regardless of the initial severity grade of xerosis. Overall clinical success was achieved in 73.7% of patients. A trend toward higher effectiveness and clinical success was observed in patients under hormonotherapy. The study product was well tolerated, regardless of the anticancer therapy being received. CONCLUSION: This study shows that the emollient PLUS containing ADE-G1 is an effective treatment for xerosis in cancer patients, regardless of the initial grade of xerosis and the anticancer treatment received.

High prevalence of cryofibrinogenemia in patients with chilblains during the COVID-19 outbreak.

BACKGROUND: Many cutaneous manifestations have been described in possible association with the COVID-19 pandemic, including acral lesions resembling chilblains. The underlying pathomechanisms of COVID-19 chilblains are not fully understood. The aim of this study was to describe the clinical, pathological, and laboratory findings of a series of patients who developed chilblains during the COVID-19 outbreak and to investigate the possible factors that could be involved in the pathogenesis of these lesions. METHODS: We conducted a prospective cohort study that included 54 patients who presented with chilblains during the highest peak in the incidence of COVID-19 in Cantabria (northern Spain). Skin biopsies were performed on 10 of these patients who presented with recent lesions. Laboratory investigations, including immunological analysis, serological studies, and the assessment of cryoproteins, were also performed. RESULTS: Most patients presented erythematous plaques located on the toes and/or purpuric macules located on the feet. Histopathological findings were compatible with those of idiopathic chilblains. Immunohistochemical evaluation showed C3d and C4d deposits in the vessel walls in seven cases. The autoimmunity panel was negative in most of our series. Cryoprotein testing showed positive cryofibrinogen in two-thirds (66.7%) of the patients assessed. On follow-up, most patients presented almost complete resolution, although six patients required prednisone and antiaggregant drug treatment. CONCLUSIONS: This study shows, for the first time to our knowledge, a high prevalence of cryofibrinogenemia in patients with chilblains during the COVID-19 pandemic. Cryofibrinogenemia could be implicated in the pathogenesis of chilblains related to COVID-19.

Mucositis Secondary to Chlamydia pneumoniae Infection: Expanding the Mycoplasma pneumoniae-Induced Rash and Mucositis Concept.

The term Mycoplasma pneumoniae-induced rash and mucositis (MIRM) was recently proposed to identify the mucocutaneous condition secondary to M. pneumoniae infection that had historically been regarded among the more confusing pathologies of erythema multiforme and Stevens-Johnson syndrome. Based on a number of previous reports, these syndromes require differentiation since they have different prognoses and specific treatment requirements. We report a case of oral and genital erosions that strongly resembled MIRM without rash but were found to be secondary to a Chlamydia pneumoniae infection. After a thorough review of the literature on this subject, we propose that C. pneumoniae should also be considered a potential causative agent of MIRM and that this term should be amended to include C. pneumoniae infection.

Efficacy of botulinum toxin in pachyonychia congenita type 1: report of two new cases.

Pachyonychia congenita (PC) is a rare genodermatosis caused by a mutation in keratin genes, which can lead to hypertrophic nail dystrophy and focal palmoplantar keratoderma (predominantly plantar), amongst other manifestations. Painful blisters and callosities, sometimes exacerbated by hyperhidrosis, are major issues that can have a significant impact on patient quality of life. Many alternative treatments for this condition have been applied with variable and partial clinical response, but a definitive cure for this disease has yet to be discovered. After obtaining informed consent, two patients with genetically confirmed PC type 1 were treated with plantar injections of botulinum toxin type A. Both patients showed a marked improvement in pain and blistering with an average response time of one week, a six-month mean duration of effectiveness, and a lack of any side effects or tachyphylaxis.

Vascular Tumor on the Forehead of an HIV Patient.

Cirsoid aneurysm is a small vascular proliferation characterized by small to medium-sized channels with features of arteries and veins, that present as small, blue or red asymptomatic papule. We report a case of a crisoid aneurysm on the forhead of an HIV patient that suggested a Kaposi sarcoma as a differential diagnosis.

Diffuse Reactive Angioendotheliomatosis Secondary to the Administration of Trabectedin and Pegfilgrastim.

Diffuse dermal angiomatosis is a rare benign condition considered a variant of reactive angioendotheliomatosis, usually related to vascular disease such as arteriovenous fistula or severe peripheral vascular disease. The most frequent clinical manifestations range from a solitary erythematous patch to an indurated plaque that may ulcerate. A clinical case of a 60-year-old woman who developed generalized livedoid lesions 2 days after the administration of intravenous trabectedin and subcutaneous pegfilgrastim for a recidivant myxoid liposarcoma has been reported. A biopsy of the skin lesions showed a pronounced proliferation of vessels in the upper dermis that was diagnosed as diffuse dermal angiomatosis.