RESUMO
Psoriasis is a chronic complicated inflammatory skin disease. Genital, nail, and scalp lesions with psoriasis are difficult-to-treat and significantly impair patients' quality of life (QOL). Deucravacitinib, a selective oral tyrosine kinase 2 (TYK2) inhibitor, may act as a novel therapeutic option that improves these challenging manifestations. A retrospective study was conducted from January 2023 and February 2024 on 70 psoriasis patients treated with deucrabacitinib 6 mg. We evaluated the achievement rates of genital physician's global assessment (genital-PGA) 0/1, PGA of fingernails (PGA-F) 0/1, scalp-specific PGA (ss-PGA) 0/1, whole-body static PGA (sPGA) 0/1, and dermatology life quality index (DLQI) 0/1 at weeks 4, 16, and 24. Deucravacitinib improved genital, nail, and scalp lesions as well as systemic eruption and QOL in patients with psoriasis. Deucravacitinib may act as a promising treatment option for these difficult-to-treat lesions with psoriasis.
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Recently, the pathomechanisms of various skin diseases have been progressively elucidated [...].
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Dermatopatias , Humanos , Dermatopatias/genética , Dermatopatias/metabolismoRESUMO
Bimekizumab, which suppresses both interleukin (IL)-17A and IL-17F, has recently been approved as a biologic for psoriasis. We aimed to evaluate the real-world effectiveness and safety of bimekizumab for psoriasis and to identify predictive factors for its treatment responsiveness. We analyzed 36 Japanese patients with psoriasis (19 with psoriasis vulgaris and 17 with psoriatic arthritis) from May 2022 to September 2023. All patients received bimekizumab (320 mg every 4 weeks) until week 16. Seventeen patients (43.2%) had experienced bio-switch. The median (interquartile range) baseline total psoriasis area and severity index (PASI) was 6 (3.2-20.0). Total PASI rapidly and significantly decreased at week 4 by a median 79.8% from baseline, and gradually decreased thereafter. The PASI on the trunk, and upper and lower limbs rapidly and significantly decreased at week 4 compared to baseline and plateaued thereafter. The neutrophil-to-lymphocyte ratio and neutrophil number significantly decreased at week 16 compared to baseline. At weeks 4, 8, 12, and 16, the achievement rate of absolute PASI ≤2 was 72.2%, 80.6%, 92.9%, and 96.4%, respectively; that of absolute PASI ≤1 was 41.7%, 61.3%, 85.7%, and 82.1%; that of PASI 75 was 55.5%, 52.9%, 69.7%, and 75.8%; that of PASI 90 was 36.1%, 50.0%, 57.6%, and 62.9%; and that of PASI 100 was 19.4%, 38.2%, 51.5%, or 57.6%, respectively. Linear multivariate regression analysis revealed that younger age was associated with a higher percentage reduction of total PASI at weeks 4 and 8. There were no serious or fatal adverse events during treatment. In conclusion, bimekizumab rapidly and remarkably reduced the total PASI together with high achievement rates of absolute PASI ≤1 and ≤2, and with favorable safety in real-world clinical practice. Younger age may be a predictive factor for a good treatment response to bimekizumab.
Assuntos
Psoríase , Índice de Gravidade de Doença , Humanos , Masculino , Feminino , Psoríase/tratamento farmacológico , Psoríase/imunologia , Psoríase/diagnóstico , Psoríase/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto , Japão , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Neutrófilos/imunologia , Idoso , Interleucina-17/antagonistas & inibidores , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , População do Leste AsiáticoRESUMO
BACKGROUND: Previous clinical trials presented efficacy and safety of Janus kinase 1 inhibitor upadacitinib through 52 weeks for moderate-to-severe atopic dermatitis (AD). OBJECTIVES: To assess the effectiveness and safety of upadacitinib through 48 weeks in real-world clinical practice for Japanese AD patients (aged ≥12 years). METHODS: This retrospective study included 287 patients with moderate-to severe AD treated with 15 mg (n = 216) or 30 mg (n = 71) of upadacitinib daily. Effectiveness was assessed using eczema area severity index (EASI) scores, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and investigator's global assessment (IGA). Safety was evaluated through the incidence of treatment-emergent adverse events. RESULTS: From baseline, EASI, ADCT, PP-NRS, and IGA rapidly reduced at week 4, and the reduction was maintained until week 48 of treatment with upadacitinib at both doses. Achievement rates of EASI 75, EASI 90, and EASI 100 at week 48 were 63.5, 30.2, and 7.9 in 15 mg group, and 77.4, 54.8, and 3.2% in 30 mg group, respectively. Acne and herpes zoster were frequent, but no serious adverse events occurred. CONCLUSIONS: Upadacitinib was therapeutically effective and tolerable for moderate-to-severe AD through 48 weeks in real-world clinical practice.
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Dermatite Atópica , Compostos Heterocíclicos com 3 Anéis , Índice de Gravidade de Doença , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Dermatite Atópica/tratamento farmacológico , Relação Dose-Resposta a Droga , População do Leste Asiático , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/administração & dosagem , Inibidores de Janus Quinases/uso terapêutico , Japão , Estudos Retrospectivos , Resultado do Tratamento , CriançaRESUMO
BACKGROUND: Deucravacitinib is a selective oral tyrosine kinase 2 (TYK2) inhibitor recently approved for psoriasis. OBJECTIVES: We aimed to evaluate the real-world effectiveness and safety of deucravacitinib for psoriasis. METHODS: We analyzed 33 Japanese patients with psoriasis (23 with plaque psoriasis, eight with psoriatic arthritis, and two with erythrodermic psoriasis) from January 2023 to October 2023. All patients received deucravacitinib 6 mg daily until week 16. RESULTS: At week 8, 12, or 16, the achievement rate of PASI 75 was 60.9%, 73.9%, or 78.3%, that of PASI 90 was 13.0%, 39.1%, or 52.2%, that of PASI 100 was 0%, 8.7%, or 13.0%, that of absolute PASI ≤2 was 34.8%, 65.2%, or 78.3%, respectively. The achievement rate of dermatology life quality index 0/1 at week 16 was 42.9%. Fourteen patients (42%) complained pruritus. Peak pruritus-numerical rating scale in patients with pruritus decreased by median [interquartile] 71.4 [50-80] % of baseline at week 2. Adverse events occurred in 18.2% of patients, which were mild and manageable. CONCLUSIONS: Deucravacitinib for patients with psoriasis was well-tolerated and gave favorable therapeutic effects in the real-world practice. Deucravacitinib treatment rapidly reduced pruritus.
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Anticorpos Monoclonais Humanizados , Compostos Heterocíclicos , Psoríase , Humanos , Japão , Anticorpos Monoclonais Humanizados/uso terapêutico , Resultado do Tratamento , Índice de Gravidade de Doença , Psoríase/terapia , Prurido/tratamento farmacológico , Prurido/etiologiaRESUMO
Clinical trials and real-world studies have shown the effectiveness of upadacitinib for treating rash and pruritus in patients with atopic dermatitis (AD). This study aimed to determine whether the early reduction in rash or pruritus at week 12 of upadacitinib treatment could be maintained at later treatment stages. This retrospective study involved 227 and 73 patients with moderate-to-severe AD treated with 15 and 30 mg upadacitinib daily, respectively. The eczema area and severity index (EASI) scores, peak pruritus numerical rating scale (PP-NRS), and investigator's global assessment (IGA) were analyzed. At week 12, patients were divided into achievers and non-achievers of EASI 75, 90, 100, absolute EASI ≤ 2, IGA0/1, PP-NRS4, or absolute PP-NRS ≤ 1. Achievement rates for each endpoint were assessed at later time points (weeks 24, 36, and 48) in both groups. Week 12 achievers largely maintained their endpoint achievements until week 48, regardless of dosage (15 mg or 30 mg). Week 12 non-achievers saw an increasing achievement rate of EASI 75 until week 48. The initial reduction in rash and pruritus at week 12 persisted until week 48 with upadacitinib treatment, suggesting potential benefits for patients requiring prolonged treatment despite not achieving EASI 75 at week 12.
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BACKGROUND: Atopic dermatitis is characterized by persistent eczema and pruritus. Janus kinase inhibitors, including upadacitinib, are effective treatments for moderate-to-severe atopic dermatitis. If patients do not respond well to a certain dose of a Janus kinase inhibitor, increasing the dose may improve their treatment responsiveness. OBJECTIVES: We assessed the outcomes of a dose increase in upadacitinib from 15 mg to 30 mg for Japanese patients with moderate-to-severe atopic dermatitis. METHODS: In 23 patients who showed insufficient responses to upadacitinib 15-mg treatment, the dose of upadacitinib was increased to 30 mg. We evaluated total Eczema Area and Severity Index (EASI), EASI on the head and neck, trunk, upper, or lower limbs, EASI of erythema, edema/papulation, excoriation, or lichenification, and Peak Pruritus Numerical-Rating Scale at baseline (onset of upadactinib 15 mg), week 0 (time of increase), and weeks 4 and 12 after the increase. RESULTS: Total EASI, EASI on each anatomical site, EASI of each clinical sign, and Peak Pruritus Numerical-Rating Scale were markedly reduced at weeks 4 or 12 compared with week 0. After the dose increase, the achievement rates of EASI 75 and EASI 90 significantly improved; EASI 75 4.3%, 68.2%, and 66.7%; EASI 90 0%, 18.2%, and 38.1% at weeks 0, 4, and 12, respectively. CONCLUSIONS: These results suggest that upadacitinib 30 mg can ameliorate rash and pruritus insufficiently improved by upadacitinib 15 mg, and that the dose increase to 30 mg may be considered as a treatment option for patients with atopic dermatitis with a limited response to upadacitinib 15 mg.
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Dermatite Atópica , Eczema , Compostos Heterocíclicos com 3 Anéis , Inibidores de Janus Quinases , Humanos , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Japão , Índice de Gravidade de Doença , Método Duplo-Cego , Prurido , Inibidores de Janus Quinases/efeitos adversos , Resultado do TratamentoRESUMO
Background: Atopic dermatitis (AD) is a chronic skin disease characterized by type 2-skewed immune responses, and significantly influenced by cytokines dependent on Janus kinases (JAKs). Upadacitinib, a JAK1 inhibitor, is effective for moderate-to-severe AD. This study aims to identify biomarkers that reflect long-term therapeutic effects of upadacitinib 15 mg or 30 mg. Methods: A retrospective study from August 2021 to July 2023 included 213 AD patients treated with upadacitinib 15 mg and 70 AD patients with 30 mg. We analyzed eczema area and severity index (EASI), peak pruritus-numerical rating scale (PP-NRS), serum immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), and total eosinophil count (TEC) at weeks 0, 4, 12, 24, 36, and 48 of treatment. Results: Both treatments with upadacitinib 15 mg and 30 mg significantly reduced EASI and PP-NRS scores over week 4 to 48 compared to baseline. Upadacitinib 15 mg or 30 mg treatment significantly decreased TEC compared to baseline through week 4 to 36 or week 4 to 48, respectively. The percent reduction of TEC correlated with those of EASI and PP-NRS through week 4 to 48 of treatment with upadacitinib 15 mg, or through week 12 to 48 with 30 mg, respectively. After adjusting for % reductions of other laboratory markers, the significance of correlations was preserved at weeks 36 and 48 of 15 mg treatment, while at weeks 4 and 36 of 30 mg treatment. Conclusion: The % reduction of TEC correlated with those of EASI and PP-NRS during upadacitinib treatment, indicating its potential as a biomarker reflecting treatment responses to upadacitinib in AD patients. However, the variability of significant correlation during treatment indicates that further inspection is needed for its usefulness in monitoring responses to upadacitinib treatment for AD.
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Biomarcadores , Dermatite Atópica , Eosinófilos , Compostos Heterocíclicos com 3 Anéis , Humanos , Adolescente , Adulto , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Masculino , Feminino , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Estudos Retrospectivos , Biomarcadores/análise , Eosinófilos/citologia , Contagem de Células Sanguíneas , Análise MultivariadaRESUMO
BACKGROUND: Janus kinase 1 inhibitor upadacitinib is therapeutically effective for atopic dermatitis (AD). However, predictive factors for high responders to upadacitinib have not been established in real-world clinical practice. OBJECTIVES: To identify predictive factors for responders to upadacitinib 15 mg or 30 mg, defined as achievers of investigator's global assessment (IGA) 0/1 with ≥ 2-point improvement from basal IGA. METHODS: A retrospective study was conducted from August 2021 to July 2023 on 159 AD patients treated with upadacitinib 15 mg and 52 patients with 30 mg. Patients in each group were categorized into responders (achievers of IGA 0/1 at week 12) and non-responders (non-achievers). We compared baseline values of clinical and laboratory parameters between responders and non-responders. Logistic regression analysis was used to detect variables predicting responders. Receiver-operating characteristic curves were used for evaluating prediction capabilities of the variables. RESULTS: In logistic regression analysis, responders to 15 mg upadacitinib were associated with lower total EASI and higher age whereas responders to 30 mg were associated with lower LDH and lower IgE. CONCLUSIONS: Lower total EASI and higher age may predict responders to upadacitinib 15 mg while lower IgE and lower LDH may predict responders to 30 mg.
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Dermatite Atópica , Compostos Heterocíclicos com 3 Anéis , Humanos , Dermatite Atópica/tratamento farmacológico , Estudos Retrospectivos , Imunoglobulina A , Imunoglobulina E , Resultado do Tratamento , Índice de Gravidade de Doença , Método Duplo-CegoRESUMO
BACKGROUND: Though Janus kinase inhibitors such as upadacitinib rapidly relieve itch in atopic dermatitis (AD) patients, how early itch relief impacts later skin clearance is not examined. OBJECTIVES: This study aims to determine if early itch relief by upadacitinib could predict complete skin clearance in later phases. METHODS: This retrospective study involved 105 patients with moderate-to-severe AD treated with upadacitinib 15 mg/day. Eczema area and severity index (EASI), atopic dermatitis control tool, and achievement rate of EASI 100 were evaluated at weeks 4, 12, and 24. The threshold of early peak pruritus-numerical rating scale (PP-NRS) predicting later skin clearance was assessed by area under the receiver-operating characteristic curve, and predictors for EASI 100 achievement were determined by logistic regression analysis. RESULTS: The rate of achieving EASI 100 at week 24 was extremely higher in patients who achieved week 2 PP-NRS ≤ 1 (42.9%) than in non-achievers (1.4%). The logistic regression analysis showed that the achievement of week 2 PP-NRS ≤ 1 and low body mass index were associated with achievement of EASI 100 at weeks 12 and 24. CONCLUSIONS: The achievement of week 2 PP-NRS ≤ 1 may predict later skin clearance in upadacitinib treatment.
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Dermatite Atópica , Humanos , Dermatite Atópica/complicações , Dermatite Atópica/tratamento farmacológico , Estudos Retrospectivos , Pele , Compostos Heterocíclicos com 3 Anéis , Prurido/tratamento farmacológico , Prurido/etiologia , Difenidramina , Índice de Gravidade de Doença , Resultado do Tratamento , Método Duplo-CegoRESUMO
Psoriasis is a complex, chronic inflammatory skin disease that significantly impacts patients' quality of life (QOL), especially in cases of genital, nail, and scalp psoriasis. Bimekizumab is an inhibitor of interleukin (IL)-17A and IL-17F and used for the treatment of psoriasis. The aim of this retrospective study was to evaluate the effectiveness of bimekizumab through in treating genital, nail, and scalp lesions with psoriasis over 24 weeks. The study was conducted from May 2022 and February 2024 on 52 psoriasis patients treated with bimekizumab. The therapeutic effects of bimekizumab were evaluated by the achievement of Physician's Global Assessment (PGA) rates of 0/1 on the genitals (genital-PGA), fingernails (PGA-F), scalp-specific PGA (ss-PGA), static PGA (sPGA), and the Dermatology Life Quality Index (DLQI) at weeks 4, 16, and 24. Bimekizumab treatment significantly improved genital, nail, and scalp lesions with psoriasis. At week 24, the achievement rate of genital-PGA 0/1, PGA-F 0/1, ss-PGA 0/1 was 96.2%, 66.7%, or 93.9%, and that of sPGA 0/1 or DLQI 0/1 was 93.9% or 83.3%, respectively. Bimekizumab was effective for genital, nail, and scalp lesions with psoriasis, difficult-to-treat lesions, and simultaneously improved QOL in a real-world clinical practice.
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Vitiligo is an autoimmune skin disease with acquired depigmentation. Dietary habits may modulate the pathogenesis of vitiligo. We evaluated dietary habits in adult Japanese patients with nonsegmental vitiligo, and compared their results with those of age- and sex-matched controls. We also examined the relationship between dietary habits and Vitiligo Area Scoring Index (VASI), or vitiligo on different anatomical sites. The intakes of energy, nutrients, and foods in the participants were analyzed using a brief-type self-administered diet history questionnaire. Patients with vitiligo showed higher body mass index (BMI) and lower intakes of manganese, vitamin D, pulses, and confection, compared with controls. Multivariate logistic regression analysis showed that vitiligo was associated with high BMI. VASI was higher in males than in females, and negatively correlated with age or intakes of potatoes and vegetables other than green/yellow vegetables. Linear multivariate regression analysis showed that high VASI was associated with younger age. Multivariate logistic regression analysis showed that moderate to severe vitiligo (VASI ≥ 4.25) was associated with male sex and longer disease duration. Multivariate logistic regression analyses showed the following association with vitiligo on respective anatomical sites: high intake of eggs and dairy products and high VASI on the head or neck, high intake of oils and fats and high VASI on the trunk, high intake of cereals and high VASI on the upper limbs, male sex and high VASI on the lower limbs, and high BMI and high VASI on the hands or feet. In conclusion, the control of obesity might have prophylactic or therapeutic effects on vitiligo.
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Vitiligo , Adulto , Feminino , Humanos , Masculino , Vitiligo/patologia , Japão/epidemiologia , Comportamento Alimentar , Vitaminas/uso terapêutico , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Basal cell carcinoma (BCC) is the most common cutaneous malignancy. BCCs occur mainly in exposed areas, such as the face and scalp. Therefore, surgical resection with narrow margins is highly desirable. However, narrow margins may increase the risk of positive histopathological margins. Outcomes for such treatment might be unfavorable, but evidence for such a conclusion is lacking. METHODS: Between April 2015 and November 2023, a total of 230 Japanese cases with BCC which underwent surgical resection with 2-mm, 3-mm, or 5-mm margins were followed in our hospital. We conducted a retrospective review that focused on the recurrence rate and histopathological margins. RESULTS: Recurrence was recorded if the follow-up time was longer than 3 months. One of the 198 cases (0.5%) developed a recurrence. The mean lateral and deep histopathological margins were 2,525.4 µm (30.8-14,034.6 µm) and 3,409 µm (199.9-16,523.6 µm), respectively. Recurrence rate was associated with tumor size and clinical tumor border. However, histopathological margin was not associated with recurrence rate, even when it was less than 1,000 µm. CONCLUSIONS: A narrow histopathological margin is acceptable for surgical resection of BCC in Japanese patients.
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Carcinoma Basocelular , Margens de Excisão , Recidiva Local de Neoplasia , Neoplasias Cutâneas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Basocelular/cirurgia , Carcinoma Basocelular/patologia , População do Leste Asiático , Seguimentos , Japão , Estudos Retrospectivos , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Resultado do TratamentoRESUMO
Tumor necrosis factor (TNF) inhibitors, including adalimumab, are widely used to treat refractory psoriatic arthritis (PsA). Although isoniazid chemoprophylaxis is generally effective in preventing reactivation of latent tuberculosis infection (LTBI), prophylactic measures do not fully protect against development of active tuberculosis. We report a rare case of active tuberculosis despite chemoprophylaxis for LTBI in a patient receiving adalimumab for PsA. A 60-year-old Japanese woman who had received a diagnosis of psoriasis at age 35 years presented with arthralgia of the right hand, which she first noticed 2 months previously. Physical examination showed scattered erythematous papules and plaques with scales on her trunk, extremities, and scalp. Her right metacarpophalangeal and proximal interphalangeal joints were swollen and painful, and her right wrist and elbow were painful. PsA was diagnosed and adalimumab was initiated. Because an interferon-γ release assay (IGRA) showed a borderline result at screening, isoniazid was administered as chemoprophylaxis for LTBI. At 22 months after initiation of adalimumab, IGRA was positive and chest CT disclosed centrilobular nodules in both lungs and swelling of multiple lymph nodes. Culture of sputum at 24 months demonstrated Mycobacterium tuberculosis. Active tuberculosis was diagnosed, and treatment with a combination of isoniazid, rifampicin, ethambutol hydrochloride, and pyrazinamide was started. To ensure timely diagnosis and treatment of active tuberculosis, a tuberculosis expert should be consulted at an early stage, with regular screening and monitoring.