Medicine (St Vincent's) - Research Publications

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    Safety and Efficacy of Ritlecitinib and Brepocitinib in Alopecia Areata: Results from the Crossover Open-Label Extension of the ALLEGRO Phase 2a Trial.
    King, B ; Guttman-Yassky, E ; Peeva, E ; Banerjee, A ; Zhu, L ; Zhu, H ; Cox, LA ; Vincent, MS ; Sinclair, R (Elsevier BV, 2022-11)
    The 24-week, double-blind period of the ALLEGRO phase 2a trial (NCT02974868) evaluated the safety and efficacy of ritlecitinib (Jak3/tyrosine kinase expressed in the hepatocellular carcinoma inhibitor) and brepocitinib (tyrosine kinase 2/Jak1 inhibitor) in patients with alopecia areata; patients could subsequently continue treatment in a 24-week single-blind extension, followed by a crossover open-label extension, described in this article. Patients who did not achieve ≥30% improvement from baseline in Severity of Alopecia Tool score at the end of the single-blind extension entered a 24-week crossover open-label extension: the ritlecitinib group switched to brepocitinib, and the brepocitinib group switched to ritlecitinib. Eighteen patients switched to brepocitinib, and five switched to ritlecitinib. Six treatment-emergent adverse events were reported by five patients; no new safety risks were observed after crossover. An exploratory efficacy evaluation showed that none of the five patients receiving ritlecitinib in the crossover open-label extension achieved ≥30% improvement from baseline in Severity of Alopecia Tool score or improvement in eyebrow/eyelash assessments. Four of 16 patients receiving brepocitinib achieved ≥30% improvement from baseline in Severity of Alopecia Tool score or better; 4 of 15 and 5 of 12 showed improvement in eyebrow and eyelash assessments, respectively. Although the small number of patients precludes firm conclusions regarding efficacy, the data suggest that some patients with alopecia areata and inadequate response to ritlecitinib after ≥24 weeks show benefit after switching to brepocitinib.
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    Vitamin D status in patients with frontal fibrosing alopecia: A retrospective study.
    Arasu, A ; Meah, N ; Eisman, S ; Wall, D ; Sinclair, R (Elsevier BV, 2022-06)
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    Comparing abrocitinib and dupilumab in the treatment of atopic dermatitis: a plain language summary.
    Bieber, T ; Simpson, EL ; Silverberg, JI ; Thaçi, D ; Paul, C ; Pink, AE ; Kataoka, Y ; Chu, C-Y ; DiBonaventura, M ; Rojo, R ; Antinew, J ; Ionita, I ; Sinclair, R ; Forman, S ; Zdybski, J ; Biswas, P ; Malhotra, B ; Zhang, F ; Valdez, H (Future Medicine Ltd, 2022-01)
    Atopic dermatitis (AD, also called atopic eczema) is a long-term skin disease that causes intensely itchy, red skin. Healthcare providers can prescribe medicated creams and ointments to reduce the signs and symptoms of AD. However, these treatments are not always enough to provide relief. A new medicine called abrocitinib, which is taken every day as a tablet, reduces part of the body's immune response that happens in AD. The clinical study described in this plain language summary, called JADE COMPARE, investigated how well and how safely 16 weeks of treatment with abrocitinib worked in adults with AD compared to placebo ('dummy treatment') and a medicine that is already approved for AD, called dupilumab. The study showed that abrocitinib was better than placebo in improving the signs and symptoms of AD after 16 weeks. In addition, patients who were taking abrocitinib 200 mg for 2 weeks experienced greater relief from itch than patients who were taking abrocitinib 100 mg, placebo, or dupilumab. More people who took abrocitinib 200 mg reported side effects than those taking abrocitinib 100 mg, placebo, or dupilumab, but most of these side effects were mild or moderate. ClinicalTrials.gov NCT number: NCT03720470.
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    Efficiency of Hair Detection in Hair-to-Hair Matched Trichoscopy
    Bokhari, L ; Cottle, P ; Grimalt, R ; Kasprzak, M ; Sicinska, J ; Sinclair, R ; Tosti, A (KARGER, 2022-05-12)
    INTRODUCTION: Precise evaluation of changes in hair count is crucial for monitoring progression of hair loss and the effects of treatment. The focus of this study is the comparison of the various examination and assessment techniques in terms of the precision of hair count change observed in trichoscopy images. METHODS: Controlled hair extraction of the same scalp spot was used to simulate hair loss, and the different examination techniques were performed to detect this change. The investigators who performed the counting were blinded. RESULTS: For trichoscopy images, the average error in determining the terminal hair count change (relative to total hair count) was 9 ± 1% for automatic assessment with manual correction and 0.4 ± 0.2% for hair-to-hair matched images. For phototrichogram, the automatic measurement results were found to deviate from truth on average by 12 ± 2%. The manually corrected hair count results were much closer to the truth with average deviation at the level of 7 ± 1%. The hair-to-hair matched results corresponded to approximately 0.6 ± 0.3% average discrepancy. CONCLUSION: Combination of manually corrected image processing, follicular mapping, and hair-to-hair matching appears to be the most precise way of evaluating the change in hair count over time. These novel techniques should be considered valuable, especially in research and clinical trials.
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    Maintenance, withdrawal, and re-treatment with ritlecitinib and brepocitinib in patients with alopecia areata in a single-blind extension of a phase 2a randomized clinical trial.
    Peeva, E ; Guttman-Yassky, E ; Banerjee, A ; Sinclair, R ; Cox, LA ; Zhu, L ; Zhu, H ; Vincent, M ; King, B (Elsevier BV, 2022-08)
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    Defining Severity in Alopecia Areata: Current Perspectives and a Multidimensional Framework.
    King, BA ; Senna, MM ; Ohyama, M ; Tosti, A ; Sinclair, RD ; Ball, S ; Ko, JM ; Glashofer, M ; Pirmez, R ; Shapiro, J (Springer Science and Business Media LLC, 2022-04)
    Alopecia areata (AA) is an autoimmune disease characterized by nonscarring hair loss. As a clinically heterogeneous disease, various classification systems have evolved for defining its severity. In this high-level review of the literature, we discuss the traditional classification systems for AA severity and their strengths and weaknesses. Most recent classifications have focused on the extent of scalp hair loss as a defining feature, but additional clinical aspects of the disease, including location, pattern, and duration of hair loss as well as impact on the patient's quality of life, are also relevant. These various components have typically been used unidimensionally to classify patients. We propose a multidimensional framework to define AA severity that incorporates multiple patient- and illness-related domains. Using such a framework, dermatologists may better assess the severity of the disease for the individual patient beyond the extent of hair loss.
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    Once-Daily Roflumilast Foam 0.3% Improves Severity and Burden of Itch in Patients With Scalp and Body Psoriasis in a Randomized, Double-blind, Vehicle-Controlled Phase 2b Study
    Moore, A ; Alonso-Llamazares, J ; Bhatia, N ; Devani, A ; Bukhalo, M ; Draelos, Z ; Gooderham, M ; Kempers, S ; Kircik, L ; Papp, K ; Pariser, D ; Sankeva, M ; Sinclair, R ; Zirwas, M ; Feng, A ; Burnett, P ; Higham, R ; Berk, D (National Society for Cutaneous Medicine, 2021-11-05)
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    Advances in hair growth.
    Wall, D ; Meah, N ; Fagan, N ; York, K ; Sinclair, R (Faculty Opinions Ltd, 2022)
    Hair is a deeply rooted component of identity and culture. Recent articles in this series have focused on scientific evidence relating to hair growth and new insights into the pathogenesis and mechanism of hair loss. This article reviews emerging evidence that has advanced our understanding of hair growth in both of these areas to provide a context for outlining current and emerging therapies. These include finasteride, minoxidil, topical prostaglandins, natural supplements, microneedling, low-level laser light, platelet-rich plasma, fractional lasers, cellular therapy, Wnt activators and SFRP1 antagonism.
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    Trichodynia and telogen effluvium in COVID-19 patients: Results of an international expert opinion survey on diagnosis and management.
    Starace, M ; Iorizzo, M ; Sechi, A ; Alessandrini, AM ; Carpanese, M ; Bruni, F ; Vara, G ; Apalla, Z ; Asz-Sigall, D ; Barruscotti, S ; Camacho, F ; Doche, I ; Estrada, BD ; Dhurat, R ; Gavazzoni, MF ; Grimalt, R ; Harries, M ; Ioannidis, D ; McMichael, A ; Melo, DF ; Oliveira, R ; Ovcharenko, Y ; Pirmez, R ; Ramot, Y ; Rudnicka, L ; Shapiro, J ; Silyuk, T ; Sinclair, R ; Tosti, A ; Vano-Galvan, S ; Piraccini, BM (Elsevier BV, 2021-12)
    BACKGROUND: The cutaneous manifestations of COVID-19 may be useful disease markers and prognostic indicators. Recently, postinfectious telogen effluvium and trichodynia have also been reported. OBJECTIVE: To evaluate the presence of trichodynia and telogen effluvium in patients with COVID-19 and describe their characteristics in relation to the other signs and symptoms of the disease. METHODS: Patients with a history of COVID-19 presenting to the clinics of a group of hair experts because of telogen effluvium and/or scalp symptoms were questioned about their hair signs and symptoms in relation to the severity of COVID-19 and associated symptoms. RESULTS: Data from 128 patients were collected. Telogen effluvium was observed in 66.3% of the patients and trichodynia in 58.4%. Trichodynia was associated with telogen effluvium in 42.4% of the cases and anosmia and ageusia in 66.1% and 44.1% of the cases, respectively. In majority (62.5%) of the patients, the hair signs and symptoms started within the first month after COVID-19 diagnosis, and in 47.8% of the patients, these started after 12 weeks or more. LIMITATIONS: The recruitment of patients in specialized hair clinics, lack of a control group, and lack of recording of patient comorbidities. CONCLUSION: The severity of postviral telogen effluvium observed in patients with a history of COVID-19 infection may be influenced by COVID-19 severity. We identified early-onset (<4 weeks) and late-onset (>12 weeks) telogen effluvium.
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    A review of actinic keratosis, skin field cancerisation and the efficacy of topical therapies
    Sinclair, R ; Baker, C ; Spelman, L ; Supranowicz, M ; MacMahon, B (WILEY, 2020-08-25)
    While a wide range of treatments exist for actinic keratosis and skin field cancerisation, the long-term benefits of the most common topical therapies are poorly defined. This report reviews the efficacy of the most commonly used topical therapies to treat regional or field lesions. Limited clinical and histopathological data are available on clearance rates at 12 months post-treatment for the most commonly used agents, with varied outcome measures making any comparison difficult. In general, total field clearance rates at 12 months are suboptimal for the most commonly employed agents. Given the increasing incidence of actinic keratosis and skin field cancerisation due to an ageing population, further research into the efficacy of therapies is critical to guide treatment choice.