膿疱性乾癬（汎発型）

BACKGROUND: We report the first study of anumigilimab, a novel anti-G-CSFR antibody, in patients with neutrophil-driven skin diseases [hidradenitis suppurativa (HS) and palmoplantar pustulosis (PPP)]. METHODS: This phase 1b, open-label, repeat-dose study (NCT03972280) comprised 15-week treatment and 9-week follow-up periods. Enrolled patients had International HS Severity Score System (IHS4) score ≥4 or PPP Area and Severity Index (ppPASI) score ≥12. After ≥10 patients completed anumigilimab 0.3 mg/kg IV at 21-day intervals (Cohort 1), pharmacokinetic/pharmacodynamic modelling determined the Cohort 2 dose (0.6 mg/kg). Primary endpoints were treatment-emergent adverse events (TEAEs). Secondary endpoints were pharmacokinetics and immunogenicity. Exploratory endpoints were pharmacodynamics and clinical response. RESULTS: Of 39 patients (HS, n = 22; PPP, n = 17), 33 patients (84.6%) experienced 198 TEAEs. Sixteen patients (41.0%) experienced 70 anumigilimab-related TEAEs; the most common were fatigue and neutropenia (both n = 7), which resolved spontaneously, and no association between neutropenia and infections was observed. No deaths or serious treatment-related TEAEs occurred. Presence of antidrug antibodies was negligible. Anumigilimab exposure and absolute neutrophil count reduction (pharmacodynamic endpoint) were dose dependent. In signal-finding exploratory analyses, 57.9% of patients with HS (n = 11/19 with data at Week 15) achieved ≥50% HS Clinical Response, IHS4 score decreased by 40.3%, and patients with PPP experienced a 40.4% reduction in ppPASI score. These clinical responses were not dose dependent, possibly due to imbalanced baseline characteristics and small sample size. CONCLUSIONS: Anumigilimab was generally well tolerated in patients with HS or PPP, with no serious treatment-related safety concerns, and demonstrated dose-dependent pharmacology. While clinical responses in HS and PPP were observed, it should be noted that these observations were exploratory and signal-finding in nature. Importantly, the study was not powered to statistically confirm efficacy and lacked a placebo control, underscoring the need for future randomized, placebo-controlled trials to validate these preliminary signal-finding observations.

INTRODUCTION: Atopic dermatitis (AD) and psoriasis are both T-cell-mediated inflammatory skin diseases. While dupilumab effectively treats moderate-to-severe AD, paradoxical psoriasiform eruptions, including rare cases of generalized pustular psoriasis (GPP), have been reported. These reactions often show poor response to conventional therapies, presenting significant therapeutic challenges. We present a case of a 6-year-old child with AD who developed GPP following dupilumab therapy and was successfully treated with upadacitinib. CASE PRESENTATION: A 6-year-old girl with a 5-year history of AD was initiated on dupilumab therapy after an inadequate response to antihistamine treatment. Although initial symptoms improved, the patient rapidly developed GPP-like skin lesions throughout the body on day 11. Despite treatment with high-dose corticosteroids and cyclosporine, the patient experienced recurrent generalized pustules and developed erythrodermic psoriasis-like manifestations. Subsequently, upadacitinib was added at a dose of 15 mg every other day, following which the skin lesions gradually improved and completely resolved within 1 month. During the subsequent 6-month follow-up period on continued medication, no recurrence of skin lesions or adverse events was reported. CONCLUSION: This case provides a reference for the efficacy and safety of upadacitinib in a pediatric patient with AD who developed secondary GPP following dupilumab therapy. Upadacitinib may represent a valuable therapeutic option for dupilumab-associated paradoxical psoriasis (including GPP) in AD patients. Prospective studies are needed to establish its long-term safety and efficacy in this patient population.

INTRODUCTION: This case report describes the clinical course and treatment of generalized pustular psoriasis (GPP) flare with intravenous (i.v.) spesolimab, an anti-IL-36R antibody, and subsequent long-term disease management with subcutaneous (s.c.) spesolimab. CASE PRESENTATION: A 72-year-old female patient had an ongoing GPP flare for 1 month before presenting to the hospital for flare and related multiorgan failure. She was successfully treated with 2 infusions of 900 mg i.v. spesolimab 1 week apart. She then initiated therapy with 300 mg s.c. spesolimab every 4 weeks for the long-term treatment of GPP. Rapid and significant improvement of skin and systemic symptoms was observed within 1 week of receiving i.v. spesolimab. However, the severity of the patient's prolonged flare deteriorated her functional status, and she required rehabilitation post-discharge. At follow-ups, s.c. spesolimab demonstrated favorable efficacy and tolerability, with no flare recurrence. Mild superficial desquamation reappeared in the days before consecutive spesolimab doses, with complete skin recovery achieved post-dose. CONCLUSION: This case underscores the serious complications arising from untreated flare and the need for long-term management of chronic GPP. The patient's ongoing post-flare symptoms highlight the chronicity of GPP, and continuous targeted treatment with spesolimab improved both her symptoms and quality of life.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare and severe inflammatory disease characterized by widespread pustular eruptions and systemic inflammation. OBJECTIVE: To evaluate the clinical characteristics and disease burden of patients with GPP in Taiwan using a national claims database. METHODS: Patients with GPP and no prior diagnosis of psoriasis vulgaris (PV) who experienced an incident flare between January 1, 2017, and September 30, 2020, were identified from Taiwan's National Health Insurance Database. Clinical characteristics, comorbidities, and treatment patterns were described. Recurrent flare frequency, healthcare resource utilization (HCRU) and costs were compared with those of a propensity score-matched PV cohort at a ratio of up to 1:4. Outpatient-managed flares were classified as moderate, whereas hospitalized flares were classified as severe. RESULTS: A total of 245 patients with GPP were included (mean age 51.3 years; 49.8% male). During follow-up, 1,156 moderate-to-severe flares were identified. Compared with matched patients with PV, patients with GPP had a higher recurrent flare rate (rate ratio 1.14; 95% CI 1.06-1.23). Patients with GPP also had greater HCRU, including more outpatient visits (incidence rate ratio [IRR] 1.03 [95% CI 1.01-1.05]), emergency room visits (IRR 1.33, 95% CI 1.19-1.49), and hospital admissions (IRR 1.69 [1.50-1.91]). Median monthly healthcare costs were approximately twice as high among patients with GPP as among matched patients with PV. CONCLUSION: Patients with GPP experienced recurrent flares, greater healthcare utilization, and higher healthcare costs than matched patients with PV, underscoring the substantial real-world clinical and economic burden of GPP.