ABSTRACT
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.
Subject(s)
Botulinum Toxins, Type A/administration & dosage , Foot Dermatoses/drug therapy , Keratoderma, Palmoplantar/drug therapy , Nails, Malformed/drug therapy , Pachyonychia Congenita/drug therapy , Skin/drug effects , Adult , DNA Mutational Analysis , Female , Foot Dermatoses/genetics , Foot Dermatoses/pathology , Genetic Predisposition to Disease , Humans , Injections, Intradermal , Keratin-6/genetics , Keratoderma, Palmoplantar/genetics , Keratoderma, Palmoplantar/pathology , Male , Mutation, Missense , Nails, Malformed/genetics , Nails, Malformed/pathology , Pachyonychia Congenita/genetics , Pachyonychia Congenita/pathology , Phenotype , Remission Induction , Skin/pathology , Time Factors , Treatment OutcomeABSTRACT
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.
Subject(s)
Antibodies, Monoclonal , Psoriasis , Humans , Off-Label Use , Retrospective Studies , Treatment Outcome , Severity of Illness Index , Double-Blind Method , Psoriasis/diagnosis , Psoriasis/drug therapyABSTRACT
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.
Subject(s)
Cyclosporine , Dermatitis, Atopic , Humans , Biomarkers , Cyclosporine/therapeutic use , Dermatitis, Atopic/drug therapy , Multiomics , Retrospective Studies , Clinical Trials, Phase IV as TopicABSTRACT
BACKGROUND: The Spanish Melanoma Group (GEM) developed a national registry of patients with melanoma infected by SARS-CoV-2 ("GRAVID"). METHODS: The main objective was to describe the COVID-19 fatality rate in patients with melanoma throughout the pandemic, as well as to explore the effect of melanoma treatment and tumor stage on the risk of COVID-19 complications. These are the final data of the register, including cases from February 2020 to September 2021. RESULTS: One hundred-fifty cases were registered. Median age was 68 years (range 6-95), 61 (40%) patients were females, and 63 (42%) patients had stage IV. Thirty-nine (26%) were on treatment with immunotherapy, and 17 (11%) with BRAF-MEK inhibitors. COVID-19 was resolved in 119 cases, including 85 (57%) patients cured, 15 (10%) that died due to melanoma, and 20 (13%) that died due to COVID-19. Only age over 60 years, cardiovascular disorders, and diabetes mellitus increased the risk of death due to COVID-19, but not advanced melanoma stage nor melanoma systemic therapies. Three waves have been covered by the register: February-May 2020, August-November 2020, and December 2020-April 2021. The first wave had the highest number of registered cases and COVID-19 mortality. CONCLUSION: Tumor stage or melanoma treatments are non-significant prognostic factors for COVID-19 mortality. During the pandemic in Spain there was a downward trend in the number of patients registered across the waves, as well as in the severity of the infection. GOV IDENTIFIER: NCT04344002.
Subject(s)
COVID-19 , Diabetes Mellitus , Melanoma , Female , Humans , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Male , COVID-19/epidemiology , SARS-CoV-2 , Melanoma/complications , Melanoma/therapy , RegistriesABSTRACT
BACKGROUND: Verrucous carcinoma (VC) of the anogenital area is an uncommon variant of squamous cell carcinoma (SCC). Its treatment is not standardized, but surgical excision must be performed if possible. The traditional approach does not distinguish between conventional SCC and VC, despite the extremely low metastatic potential of VC. Accordingly, most patients reported in the literature have been treated with radical surgery, including regional lymphadenectomy. METHODS: We report two cases in order to describe the oncologic, functional, and esthetic results achieved by Mohs micrographic surgery (MMS) in the treatment of this disease. RESULTS: Good functional and esthetic results were achieved in both patients. No local or nodal relapses were detected during the respective 12- and 27-month follow-ups. CONCLUSIONS: Early recognition of VC and the proper evaluation of deep biopsies will avoid misdiagnosis as SCC and may prevent the occurrence of unnecessary disfiguring interventions. The MMS technique may be considered as a surgical approach in genitoanal VC, although further research is required to confirm this.