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BACKGROUND: Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA. OBJECTIVE: The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA. METHODS: Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg BID, deuruxolitinib 12 mg BID, or placebo for 24 weeks. The primary endpoint was percentage of patients achieving Severity of Alopecia Tool (SALT) score ≤20. A key secondary endpoint was percentage of satisfaction of hair patient-reported outcome (SPRO) responders. RESULTS: Significantly higher proportions of patients taking deuruxolitinib met the primary endpoint (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary endpoints versus placebo, including SPRO (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors. LIMITATIONS: Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation. CONCLUSION: Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.
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BACKGROUND: Dupilumab is approved for moderate-severe atopic dermatitis (AD) in patients aged ≥6 months by the US Food and Drug Administration and Health Canada; however, there are little real-world data because providers have limited practical experience with this recently approved therapy. OBJECTIVES: To describe the real-world effectiveness and safety in patients aged <12 years with moderate-severe AD currently receiving or previously having received dupilumab. METHODS: A multicenter retrospective study was conducted at six Canadian sites. Cases were divided into Group 1 ≤2 years old, Group 2 >2 to <6 years old, and Group 3 ≥6 to <12 years old. Medical history and details of dupilumab treatment were collected. The primary outcome was to measure the improvement in eczema area and severity index. Secondary outcomes examined included the children's dermatology life quality index/infant's dermatitis quality of life, peak pruritus numerical rating scale, and delay to dupilumab access for patients who were considered off-label for dupilumab due to their age. RESULTS: Sixty three pediatric patients (37 males) with moderate-to-severe AD were included; the mean age was 6.4 years old (range: 2-11) when dupilumab treatment was started. Overall, 75% (36/48) achieved EASI-75% and 71% (34/48) achieved EASI-90. EASI-75 and EASI-90 were achieved in 90% (17/19) and 73% (12/19) in patients <6 years old, and 76% (22/29) and 59% (17/29) in patients >6 years old, respectively. No serious adverse events were reported. CONCLUSIONS: Dupilumab is safe and effective for patients under the age of 12. However, even for experienced providers, access to the medication was challenging.
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Anticorpos Monoclonais Humanizados , Dermatite Atópica , Criança , Pré-Escolar , Humanos , Masculino , Canadá , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Feminino , LactenteRESUMO
Generalized pustular psoriasis (GPP) is a rare, immune-mediated inflammatory disease with characteristic cutaneous and systemic manifestations. Mutations in the interleukin-36 receptor antagonist (IL36RN) gene have been implicated in its pathogenesis. Spesolimab is a novel systemic biologic therapy that selectively inhibits interleukin-36. It was recently approved by Health Canada and the US FDA for the treatment of GPP flares in adults. Results from phase 1 and 2 studies have been promising. Herein, we review the efficacy and safety of spesolimab for the treatment of GPP flares, as demonstrated in clinical trials.
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Exantema , Psoríase , Dermatopatias Vesiculobolhosas , Adulto , Humanos , Inibidores de Interleucina , Psoríase/tratamento farmacológico , Interleucinas/genética , Interleucinas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença Aguda , Doença CrônicaRESUMO
BACKGROUND: Characterization of upadacitinib use and switching from dupilumab to upadacitinib among patients with moderate-to-severe atopic dermatitis (AD) is needed. OBJECTIVE: To evaluate the long-term safety and efficacy of continuous upadacitinib 30 mg and switching to upadacitinib after 24 weeks of dupilumab. METHODS: Adults who completed the phase 3b clinical trial of oral upadacitinib 30 mg vs injectable dupilumab 300 mg (Heads Up) and entered a 52-week open-label extension (OLE) (NCT04195698) were included. All patients received 30-mg upadacitinib during the open-label period. We report results of a prespecified interim OLE 16-week analysis. RESULTS: Patients (n = 239) continuing upadacitinib maintained high levels of skin and itch response. Patients (n = 245) switching from dupilumab experienced additional incremental improvements in clinical responses within 4 weeks of starting upadacitinib. Most patients who did not achieve adequate clinical responses with dupilumab did so with upadacitinib. The safety profile of upadacitinib up to 40 weeks (week 16 of OLE) was consistent with previous phase 3 AD studies, with no new safety risks observed. LIMITATIONS: Open-label study design. CONCLUSIONS: Clinical responses are maintained with continuous upadacitinib through 40 weeks and patients regardless of prior dupilumab response experienced improved outcomes when switched to upadacitinib. No new safety risks were observed.
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Dermatite Atópica , Adulto , Humanos , Dermatite Atópica/tratamento farmacológico , Resultado do Tratamento , Método Duplo-Cego , Índice de Gravidade de DoençaRESUMO
Alopecia areata (AA) is a common inflammatory autoimmune disease of the hair which can have a significant negative impact on quality of life (QoL), mental health and productivity. The aim of this scoping review is to elucidate the burden of AA focusing on these three realms. Inclusion criteria included all original manuscripts with no restriction on study type or statistical method written in English (or having an English abstract). For QoL 40 articles were included, 85 for psychiatric comorbidities, and 9 for work/school absenteeism/presenteeism mostly consisting of cross-sectional and observational cohort studies. QoL impairment was detected in over 75% of patients and up to one-third reported extremely severe QoL impairments. Specific QoL dimensions with the greatest impact were embarrassment, social functioning, as well as shopping and/or housework. Cross-sectional studies assessing the psychological burden of adult patients with AA found that the presence of signs of anxiety and/or depression ranged from 30% to 68% and affected all age groups. Rates of work absenteeism and unemployment were significantly higher in AA patients compared to healthy controls. Up to 62% reported making major life decisions including relationships, education and career based on their AA. Additionally, the extensive camouflage techniques and time lost from work led to a strong financial burden for patients and the numerous physician visits added to the healthcare costs. The overall impact of AA stretches much further than simply being an aesthetic concern and can negatively impact every part of an individual's life. An individualized approach and effective treatments will help reduce the psychosocial consequences and distress and return patients to their normal state of health.
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Cytokines in the interleukin (IL)-23/IL-17 axis are central to psoriasis pathogenesis. Janus kinase (JAK) signal transducer and activator of transcription (STAT) regulates intracellular signalling of several cytokines (including IL-12, 23, 22, 6, 17, and interferon (IFN)-γ) in the IL-23/IL-17 axis, and, as a result, has become a therapeutic target for psoriasis treatment. Although several JAK1-3 inhibitors, with varying degrees of selectivity, have been developed for immune-mediated inflammatory diseases, use in psoriasis is limited by a low therapeutic index as anticipated by signals from other disease indications. More selective inhibition of the JAK family is an area of interest. Specifically, selective tyrosine kinase (TYK)2 inhibition suppresses IL-23/IL-17 axis signalling, and at therapeutic doses, has a favorable safety profile compared to therapeutic doses of JAK1-3 inhibitors. Phase III efficacy and safety data for the selective allosteric TYK2-inhibitor, deucravacitinib, in adult patients with moderate-to-severe plaque psoriasis is promising. Furthermore, phase II clinical trials for ropsacitinib (PF-06826647), a selective TYK2 inhibitor, and brepocitinib (PF-06700841), a JAK1/TYK2 inhibitor, have also demonstrated efficacy and an acceptable safety profile in adult patients with moderate-to-severe plaque psoriasis. Other novel TYK2 allosteric inhibitors, NDI-034858 and ESK-001, are currently being investigated in adult patients with plaque psoriasis. This article reviews the details of the JAK-STAT pathway in psoriasis pathophysiology, the rationale for selective targeting of JAKs in the treatment of psoriasis, and provides clinical perspective on clinical trial data for JAK and TYK2 inhibitors.
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Inibidores de Janus Quinases , Psoríase , Adulto , Humanos , Janus Quinases/metabolismo , Janus Quinases/uso terapêutico , Interleucina-17/metabolismo , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Fatores de Transcrição STAT/uso terapêutico , TYK2 Quinase/metabolismo , TYK2 Quinase/uso terapêutico , Psoríase/patologia , Interleucina-23 , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêuticoRESUMO
BACKGROUND: The Psoriasis Longitudinal Assessment and Registry (PSOLAR) is a global, prospective, longitudinal, disease-based registry. It serves as a post-marketing safety commitment with a focus on patients with moderate to severe plaque psoriasis who are candidates for systemic therapy. OBJECTIVES: To describe the baseline disease demographics and clinical characteristics of a Canadian subgroup of participants enrolled in PSOLAR. METHODS: Baseline demographic/disease characteristics, medical histories, and previous psoriasis treatments for Canadian patients in PSOLAR were summarized using descriptive statistics. RESULTS: There were 1896 patients analyzed in the Canadian subgroup at 37 clinical sites, accounting for 15.7% of the global PSOLAR population. Baseline disease and clinical characteristics were as expected for a moderate to severe psoriasis population and were generally similar to the global PSOLAR population. Two distinctions were noted in the Canadian subgroup versus those enrolled globally: a higher proportion of patients were overweight/obese (84.7% vs. 80.4%) and male (61.4% vs. 54.7%). In addition, the Canadian subgroup had numerically higher historical peak disease activity (PGA score 3.35 vs. 3.1) and longer disease duration (22.3 years vs. 17.5 years). Canadian PSOLAR patients reported a variety of comorbidities, including psoriatic arthritis (31.5%), hypertension (34.6%), hyperlipidemia (24.3%), mental illness (24.1%), and inflammatory bowel disease (1.6%). CONCLUSION: The Canadian subgroup of PSOLAR patients was generally similar to those enrolled globally with respect to baseline disease demographics and clinical characteristics. Multiple comorbidities are noted in the Canadian subgroup, underscoring the need for a holistic approach to the treatment of psoriatic patients.
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Artrite Psoriásica , Psoríase , Humanos , Masculino , Estudos Prospectivos , Canadá/epidemiologia , Psoríase/epidemiologia , Psoríase/tratamento farmacológico , Sistema de Registros , Índice de Gravidade de DoençaRESUMO
Atopic dermatitis (AD) is a common, chronic, recurrent, immune-mediated inflammatory skin disease. Targeted treatment options remain limited. Tralokinumab (Adtralza®) is a promising, new systemic therapy that inhibits interleukin-13. It was recently approved by Health Canada and the US FDA for the treatment of moderate-to-severe AD in adults and may be used alone or with topical corticosteroids. Herein, we review the efficacy and safety of tralokinumab in adults, as demonstrated in clinical trials.
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Dermatite Atópica , Humanos , Adulto , Dermatite Atópica/tratamento farmacológico , Resultado do Tratamento , Anticorpos Monoclonais , Pele , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Acne is the most frequent adverse event associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis. OBJECTIVE: To characterize the adverse event of acne associated with upadacitinib. METHODS: This was a post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials of upadacitinib, alone (NCT03569293 and NCT03607422) or in combination with topical corticosteroids (NCT03568318). Data included were from the 16-week placebo-controlled period. RESULTS: Over 16 weeks, 84 of 857 (9.8%), 131 of 864 (15.2%), and 19 of 862 (2.2%) patients randomized to receive upadacitinib 15 mg, upadacitinib 30 mg, and placebo, respectively, experienced acne. All cases of acne, except 1, were mild/moderate in severity; 2 patients discontinued treatment due to moderate acne. Acne occurred at higher rates among younger, female, and non-White patients. Acne required no intervention in 40.5% and 46.6% of patients receiving upadacitinib 15 and 30 mg, respectively; most remaining cases were managed with topical antibiotics, benzoyl peroxide, and/or retinoids. Acne also had no impact on patient-reported outcomes. LIMITATIONS: This study was relatively short in duration and had a small patient population. CONCLUSIONS: Acne associated with upadacitinib for atopic dermatitis treatment is usually mild/moderate in severity and managed with topical therapies or no intervention.
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Acne Vulgar , Dermatite Atópica , Acne Vulgar/induzido quimicamente , Acne Vulgar/tratamento farmacológico , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Peróxido de Benzoíla/uso terapêutico , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Feminino , Compostos Heterocíclicos com 3 Anéis , Humanos , Retinoides/uso terapêutico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Treat-to-target (T2T) recommendations for the use of systemic therapies (including biologics) in patients with moderate-to-severe plaque psoriasis have been published by a few groups of experts worldwide. However, there remains considerable variability in the choice of target severity measure and timing of milestones. To develop consensus recommendations for implementing T2T strategies for the management of moderate-to-severe plaque psoriasis using biologics. An expert group of Canadian dermatologists (the Committee) convened to develop a T2T consensus statement. They held a virtual meeting during which a preliminary set of criteria was created. These criteria were then reviewed, modified, and recirculated until unanimous agreement was achieved. The Committee agreed that defining treatment target is multidimensional and should reflect objective severity measures, as well as clinician and patient-reported outcomes. The Committee unanimously proposes a criterion-based system for determining the achievement of treatment target. The proposed T2T approach presented here provides a clinical framework for defining treatment success, measuring progress toward treatment success, recognizing when treatment modifications are warranted, and recommending treatment optimization strategies.
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Produtos Biológicos , Psoríase , Produtos Biológicos/efeitos adversos , Canadá , Consenso , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
A novel topical corticosteroid, halobetasol propionate (HP) 0.01% lotion (Bryhali™), has recently been introduced for the treatment of plaque psoriasis and corticosteroid-responsive dermatoses in adults. Once daily application of HP 0.01% lotion is indicated for use up to 8 weeks. Treatment success for plaque psoriasis in the pivotal phase 3 clinical trials (defined as an Investigator Global Assessment [IGA] of clear/almost clear [IGA 0/1] with ≥2-grade improvement from baseline) occurred in over one-third of patients by week 8. Treatment-emergent adverse events were typically mild-to-moderate in intensity and usually limited to the application site(s). No treatment-related cases of skin atrophy have been reported from the studies. Counselling should be considered to optimize treatment outcomes.
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Ácidos Nicotínicos , Psoríase , Administração Cutânea , Adulto , Clobetasol/análogos & derivados , Combinação de Medicamentos , Emolientes/uso terapêutico , Emulsões/uso terapêutico , Glucocorticoides/efeitos adversos , Humanos , Imunoglobulina A/uso terapêutico , Ácidos Nicotínicos/efeitos adversos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Creme para a Pele , Resultado do TratamentoRESUMO
OBJECTIVE: To measure the impact juvenile localized scleroderma (jLS) has on family quality of life and to identify predictors of family impact in this population which may inform the development of tailored resources to enhance family functioning for patients with jLS. METHODS: A retrospective cohort study of pediatric patients with jLS and their families was conducted. Five questionnaires were administered at each visit: Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM), PedsQL 4.0 Generic Core Scales (PedsQL-Generic), PedsQL Rheumatology Module (PedsQL-RM), Child Health Assessment Questionnaire (CHAQ), and Children's Dermatology Life Quality Index (CDLQI). Linear mixed models with random intercepts for each patient were used to find relationships between family impact scores and clinically relevant variables over time. Variables of interest included disease activity status, methotrexate use, jLS distribution, and scores for PedsQL-Generic and PedsQL-RM. RESULTS: The median baseline PedsQL-FIM total score was 80.9 (IQR = 76.6-97.4). Adjusting for age and sex, the most significant predictors of family impact were PedsQL-Generic scores and four of five PedsQL-RM dimensions (all P < .001); methotrexate use had borderline significance (P = .06). Family impact increased more significantly over time in older patients. In multivariable modeling, PedsQL-Generic total score and jLS "other" distribution were significant for predicting an increased PedsQL-FIM score (P = .003 and P = .03, respectively). CONCLUSIONS: JLS has a moderate family impact. Family impact is predicted by patients' general and disease-specific health-related quality of life (HRQL) and their jLS subtype. There is a trend toward increased family impact with methotrexate treatment. This study emphasizes the importance of family-centered care in jLS.
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Qualidade de Vida , Esclerodermia Localizada , Idoso , Criança , Humanos , Metotrexato/uso terapêutico , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
A novel fixed combination lotion containing the super-potent corticosteroid halobetasol propionate 0.01% and retinoid tazarotene 0.045% (Duobrii™) has recently been introduced and indicated for the treatment of moderate to severe plaque psoriasis in adults. Studies have shown that there is synergy between the ingredients and that the product can be safely used intermittently for up to 1 year. Treatment success (i.e., Investigator Global Assessment [IGA] of clear/almost clear [IGA 0/1] and at least a 2-grade improvement from baseline) occurred in 58.8% of participants at some point in a 1-year clinical trial. Persistence of treatment success is common after treatment discontinuation. Most treatment-emergent adverse events are application site reactions, mild to moderate in intensity, and occur primarily during the first 12 weeks. Counselling should be considered to optimize treatment outcomes.
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Fármacos Dermatológicos , Psoríase , Administração Cutânea , Adulto , Clobetasol/análogos & derivados , Fármacos Dermatológicos/efeitos adversos , Combinação de Medicamentos , Humanos , Ácidos Nicotínicos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Creme para a PeleRESUMO
BACKGROUND: Psoriasis is a chronic inflammatory disease with clinical manifestations of the skin that affect adults and children. In adults, biologics have revolutionized the treatment of moderate to severe plaque psoriasis where clear or almost clear is a tangible goal. Research on biologics has recently been extended to children. The introduction of these new therapeutic options has outpaced the limited guidelines in this population. OBJECTIVE: To provide a review of current data on biologics, with a proposal for a clinically relevant treatment algorithm on the management of moderate to severe plaque psoriasis in the pediatric population. METHODS: A Canadian panel with expertise in psoriasis, pediatric dermatology, and experience with consensus recommendation processes was selected to review the current landscape of pediatric psoriasis and clinical data on biologics plus identify special considerations for baseline workup and monitoring. Recommendations were reviewed and edited by each expert in an iterative process. CONCLUSION: A treatment algorithm for moderate to severe plaque psoriasis in pediatric patients is presented, incorporating approved biologics. Guidance on baseline screening and ongoing monitoring is also provided. Ultimately, treatment choice depends on the patient and his or her caregiver, with consideration of comorbidities, impact on quality of life, and relevant safety aspects.
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Algoritmos , Produtos Biológicos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Interleucina-12/antagonistas & inibidores , Interleucina-23/antagonistas & inibidoresRESUMO
Generalized pustular psoriasis (GPP) is a severe form of psoriasis, which is rare in pediatric and adult patients. It is characterized by sterile pustular lesions that appear on erythematous skin, associated with systemic features. A recent identification of mutations in the IL36RN gene in some GPP patients has led to a diagnosis of new autoinflammatory disease, interleukin-36-receptor antagonist deficiency (DITRA). DITRA represents an emerging group of autoinflammatory diseases with hyperkeratotic skin involvement, called autoinflammatory keratinization diseases (AIKD). DITRA diagnosis and management are challenging as neither DITRA-specific clinical assessment tools nor treatment trials exist. Autoinflammatory Diseases Activity Index (AIDAI) is a validated tool originally developed to evaluate disease activity and treatment response in other inherited autoinflammatory diseases with systemic and skin involvement. We report the first use of AIDAI in a pediatric DITRA patient with the following goals: (a) to describe the contribution of AIDAI to our patient's management; (b) to identify potential limitations of AIDAI in DITRA; (c) to review literature for current psoriasis assessment tools; and (d) to propose a preliminary DITRA/AIKD disease activity index (DITRA/AIDAI) to be validated in future studies.
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Doenças Hereditárias Autoinflamatórias , Psoríase , Dermatopatias Vesiculobolhosas , Adulto , Criança , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/tratamento farmacológico , Doenças Hereditárias Autoinflamatórias/genética , Humanos , Interleucinas , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , PeleAssuntos
Anticorpos Monoclonais Humanizados , Psoríase , Índice de Gravidade de Doença , Humanos , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Falha de Tratamento , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , IdosoRESUMO
BACKGROUND: Pediatric leukemia cutis (LC) is often difficult to diagnose due to similarity in appearance to other dermatologic diseases. Several case reports and smaller case series have been published in the medical literature, but studies on larger cohorts of children with LC are lacking. OBJECTIVE: This study aimed to better characterize the clinical features, course, and prognosis of LC in the pediatric population. METHODS: We performed a retrospective case series of 31 patients diagnosed with LC at Boston Children's Hospital and the Children's Hospital of Philadelphia. RESULTS: The number and morphology of LC lesions varied among patients, with the head and lower extremities being the most common sites of involvement. Leukemia cutis presented concomitantly with systemic leukemia in the majority of cases. Most cases of LC arose during initial leukemia episodes, rather than with relapsed leukemia. Acute myeloid leukemia was the subtype most frequently associated with LC, followed by acute lymphoblastic leukemia. Diagnosis altered treatment timing and therapeutic decisions. CONCLUSION: Children most often present concomitantly with LC and systemic leukemia. Since the morphology and distribution of LC varies, physicians must maintain a high index of suspicion for this diagnosis, as the presence of LC may change the management of systemic leukemia.