The Journal of dermatology最新文献

Ixekizumab, an IL-17A monoclonal antibody, is administered in Japan as 160 mg initially, then 80 mg every 2 weeks (Q2W) through Week 12 and every 4 weeks thereafter. Continued Q2W dosing is allowed if response is insufficient at Week 12. This study evaluated long-term effectiveness and factors associated with sustained Q2W dosing in real-world practice. Data from the Western Japan Psoriasis Registry were analyzed for patients treated > 1 year. Outcomes included achievement of body surface area (BSA) ≤ 3% and physician global assessment (PGA) 0/1. Logistic regression adjusted for age, sex, and psoriatic arthritis identified predictors of Q2W maintenance. Among 114 patients (35 for 1 year, 79 for > 1 year; mean duration 35 months), BSA ≤ 3% was achieved by 88.6% and 79.7%, and PGA 0/1 by 82.9% and 75.9%, respectively. Q2W dosing continued in 44 patients (38.6%). Higher body mass index (OR 1.11, 95% CI 1.01-1.23) and prior biologic therapy (OR 2.37, 95% CI 1.01-5.58) were significant predictors; smoking, alcohol, baseline severity, and nail involvement were not. Ixekizumab showed durable effectiveness, and sustained Q2W dosing was a practical option for patients with higher BMI or prior biologic exposure.

Tralokinumab, an anti-IL-13 antibody, is effective for atopic dermatitis (AD); however, its long-term (> 1 year) effectiveness specific to each anatomical site is unknown in real-world settings. To evaluate 72-week effectiveness of tralokinumab on different anatomical sites in AD, we studied 208 patients with moderate-to-severe AD treated with tralokinumab for 72 weeks. Eczema area and severity index (EASI) scores were analyzed on four anatomical sites (head/neck, trunk, upper limbs, and lower limbs). Tralokinumab consistently reduced EASI on all anatomical sites. The achievement rates of EASI 75 and 100 on each site gradually increased from Week 4 to Week 72, and those on lower limbs appeared higher compared to the other sites. The percent reductions of EASI throughout 72 weeks appeared slightly lower on head and neck compared to the other sites. Week 72 achievement rate of EASI 75 on head/neck, trunk, upper limbs, or lower limbs was 80.4%, 80%, 80.3%, or 86.7%, while that of EASI 100 was 37.3%, 25.0%, 27.4%, and 40.0%, respectively. Tralokinumab reduced EASI scores through 72 weeks across different anatomical sites in AD patients. The achievement rates of EASI 75 and 100 appeared slightly higher on lower limbs compared to the other sites.

Real-world data are limited on 2 year effectiveness of tyrosine kinase 2 inhibitor deucravacitinib for psoriasis, especially that stratified by body mass index (BMI) or age. This study is aimed to evaluate 104 week effectiveness of deucravacitinib in patients with psoriasis, stratified by BMI (< 25 versus ≥ 25 kg/m²) or age (< 65 versus ≥ 65 years). We included 127 patients with moderate-to-severe psoriasis who received deucravacitinib 6 mg once daily. Psoriasis area and severity index (PASI) decreased throughout 104 weeks in whole patients. In between-group comparisons, mean percent reduction of PASI did not significantly differ at any time point in either BMI or age stratification. The amount of decreasing PASI and achievement rates of PASI 75, 90, and absolute PASI ≤ 2 through week 16 to 68 were slightly higher in BMI < 25 than in BMI ≥ 25, thereafter inverted order. The achievement rates of PASI 100 or absolute PASI ≤ 1 were higher in BMI < 25 throughout 104 weeks; week 104 PASI 100 or absolute PASI ≤ 1 rates were 16.7% or 54.2% in BMI < 25 while 0% or 40% in BMI ≥ 25, respectively. Percent reduction of PASI and achievement rates of PASI 75 and 90 were slightly higher in age ≥ 65 years than in age < 65 years by week 52, thereafter inverted order. Week 104 achievement rates of PASI 100 or absolute PASI ≤ 1 were 28.6% or 57.1% in age < 65 years while 0% or 46.7% in age ≥ 65 years, respectively. Deucravacitinib reduced PASI throughout 104 weeks in whole patients. Patients with BMI < 25 or age ≥ 65 years might show slightly higher response to deucravacitinib at early time points around 1 year compared to slightly higher response at later time points in those with BMI ≥ 25 or age < 65 years. Patients with BMI ≥ 25 or age ≥ 65 years might have difficulty in keeping PASI 100 through week 104.

We report a case of acute myocarditis in a 25-year-old man with refractory generalized pustular psoriasis (GPP) following treatment with spesolimab, an anti-IL-36 receptor monoclonal antibody. Cardiac magnetic resonance fulfilled the Lake-Louise criteria for myocarditis, and genetic testing revealed a heterozygous pathogenic/likely pathogenic MYH7 variant, suggesting a possible gene-environment-drug interaction. The patient was managed with supportive care and presented no complications. In outpatient evaluation, the patient has remained asymptomatic with no further hospital admissions. This case underscores the need for vigilance regarding cardiac adverse events during IL-36 blockade and highlights the potential role of genetic predisposition in modulating susceptibility to myocardial injury.

Generalized pustular psoriasis (GPP) is a heterogeneous, systemic neutrophilic inflammatory disease, characterized by chronic symptoms and recurrent flares, which can be potentially life-threatening. Spesolimab, an interleukin-36 receptor antagonist, has been approved to treat GPP flares in many countries including Japan. An expanded access program (EAP) in Japan provided early access to spesolimab for patients aged 18-75 years unable to participate in a clinical trial with no other treatment options. Patients received a single dose of 900 mg intravenous spesolimab for flare treatment, with an optional second dose after 1 week if symptoms persisted. Safety was monitored for 16 weeks post-treatment. Eleven patients (54.5% female; 51 years mean age; 26.7 kg/m² mean body mass index) received 23 doses of intravenous spesolimab. Nine patients (81.8%) were diagnosed with GPP for > 5 years. Ten patients (90.9%) had ≥ 1 baseline medical condition. All patients used ≥ 1 concomitant medication prior to or during the spesolimab treatment period, most commonly immunosuppressants and non-steroidal anti-inflammatory agents. Seven patients (63.6%) experienced treatment-emergent adverse events, all of mild or moderate intensity, including skin and subcutaneous tissue disorders, general disorders and administration site conditions. No adverse event led to treatment discontinuation or death. A potential hypersensitivity event (face edema) resolved without intervention and was not considered treatment related. Spesolimab was well tolerated in a heterogeneous patient population with GPP, including those with comorbidities and concomitant medication use. The safety profile of spesolimab aligned with the EFFISAYIL 1 clinical trial results.

Extramammary Paget disease (EMPD) is a rare skin cancer with an estimated incidence rate of 0.13 per 100 000 population/year in Caucasians and 0.28 in Asians. Although distant metastases have been reported in 10%-20% of EMPD cases, standardized systemic chemotherapy has not been established. Prospective clinical trials are essential to establish standard treatments for advanced EMPD. Therefore, this retrospective study examined a substantial number of patients with EMPD to assess the efficacy of systemic chemotherapy. This study included 164 patients with advanced EMPD who underwent treatment at 16 Japanese institutions. Treatment efficacy was evaluated in a cohort of 138 patients, after excluding 26 patients without lesions outside the radical irradiation field from the 164 patients. The efficacy of each treatment was evaluated by determining the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) using Kaplan-Meier analysis. Multivariate analysis was performed to account for potential confounding factors, such as age, sex, and performance status. The patients received the following treatments: docetaxel hydrate (DOC) (65.9%); tegafur/gimeracil/oteracil potassium, DOC (S-1/DOC) (9.8%); fluorouracil and cisplatin (FP) (15.9%); and other drugs (8.5%). DOC is the most commonly used in Japan. The ORRs in the DOC, S-1/DOC, and FP groups were 51.6%, 78.6%, and 27.8%, respectively. Logistic regression analysis revealed that, compared with the DOC group, the odds ratio for the ORR of the S-1/DOC group was 3.29 (95% CI: 1.49-7.25, p = 0.003). However, no significant differences in OS or PFS were observed between the treatment groups (p = 0.122 and p = 0.422, respectively). This study provides valuable information on EMPD and may serve as a useful historical control for the future evaluation of new treatments for EMPD.

Parenteral nutrition (PN) is a critical intervention for patients unable to tolerate enteral nutrition. Commercially available multi-chamber PN formulations are widely used due to their safety and cost-effectiveness. However, hypersensitivity reactions (HSRs), including anaphylaxis, must be carefully considered. Here, we report on a 38-year-old female with intestinal obstruction due to peritoneal dissemination of colon cancer who developed anaphylaxis to a multi-chamber PN formulation. Skin prick and intradermal tests identified the specific chamber as the causative component. PN-related HSRs are rare, but can severely impact nutritional management. Identifying specific allergens is crucial for avoiding unnecessary PN discontinuation. This case highlights the importance of incorporating allergy testing into the management of multi-chamber PN, allowing safe continuation of nutrition and guiding individualized strategies for patients at risk of hypersensitivity.

Alopecia areata (AA) is a chronic autoimmune disorder characterized by refractory non-scarring hair loss. Although baricitinib revolutionized AA management, some severe cases remain refractory. Ritlecitinib, an oral selective dual JAK3 and tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinase inhibitor, is a recently approved therapeutic agent for the treatment of severe AA. Although clinical trials have established the benefit of ritlecitinib, real-world data on its outcome and safety, particularly in patients previously exposed to baricitinib, have been still limited. Accordingly, we conducted a single-center, retrospective study of 22 severe AA patients treated with ritlecitinib 50 mg daily for 24 weeks at Tohoku University Hospital, Japan. Nine patients (41%) were JAK inhibitor (JAKi)-naïve, and 13 (59%) had previously received baricitinib for a median of 19 months. JAKi-naïve patients were significantly younger (median 14 vs. 38 years; p = 0.0143) and had shorter current AA episodes (median 20 vs. 68 months; p = 0.0138), compared with the JAKi-experienced group. Baseline SALT score in each group showed similar distribution. At Week 24, all JAKi-naïve patients achieved SALT₅₀ (a decrease of at least 50% from baseline in the SALT score); 7/9 (78%) attained SALT ≤ 20 and SALT₇₅ (a decrease of at least 75% from baseline in the SALT score). In contrast, among JAKi-experienced patients, only 3/13 (23%) achieved SALT₅₀, and 1/13 (8%) reached SALT₇₅, whereas a reduction in SALT score from baseline was observed in 7 of 13 (54%). Importantly, no patients in both groups experienced SALT worsening or treatment-related adverse events. Our findings highlighted that ritlecitinib is highly effective especially in adolescent JAKi-naïve AA, and although the clinical effect may be limited in JAKi-experienced patients, switching from baricitinib to ritlecitinib remains one of the viable options due to its low risk of disease exacerbation.