Dermatology and Therapy最新文献

Introduction: Patients with moderate-to-severe atopic dermatitis (AD) who discontinue dupilumab need additional therapeutic options. Lebrikizumab's distinct mechanism of action may provide that alternative treatment. We evaluated efficacy and safety of lebrikizumab in adults and adolescents with moderate-to-severe AD previously treated with dupilumab.

Methods: In the open-label ADapt trial, patients who discontinued dupilumab due to inadequate response, adverse events (AEs)/intolerance, or other reasons received lebrikizumab 250-mg every 2 weeks (Q2W) following 500-mg loading dose at baseline/week 2, through week 16, with optional topical therapy. From weeks 16-24, responders (≥ 75% improvement in Eczema Area and Severity Index [EASI 75] or Investigator's Global Assessment score 0/1 with ≥ 2-point improvement from baseline) received lebrikizumab every 4 weeks; inadequate responders continued lebrikizumab Q2W. The primary endpoint was EASI 75 at week 16 in the intent-to-treat population; EASI 75 was also analyzed by reason for dupilumab discontinuation. Secondary and exploratory efficacy endpoints were assessed throughout.

Results: Among the 86 patients enrolled, primary reasons for stopping dupilumab were inadequate response (n = 48, 55.8%), AEs/intolerance (n = 14, 16.3%), and other reasons (n = 24, 27.9%). Fifty-nine patients (68.6%) completed week 16; 52 patients (60.5%) completed week 24. At weeks 16 and 24, respectively, response rates were 57.4% (35/61) and 60.0% (33/55) for EASI 75; 53.2% (25/47) and 61.5% (24/39) for Pruritus Numeric Rating Scale ≥ 4-point improvement; and 83.0% (44/53) and 83.0% (39/47) for Dermatology Life Quality Index ≥ 4-point improvement. Most treatment-emergent AEs were mild/moderate. Serious AEs and discontinuations due to AEs were reported by 2 (2.3%) and 5 (5.8%) patients, respectively. Of the 10 patients who discontinued dupilumab due to eye-related events, facial dermatitis, or inflammatory arthritis, none reported similar events with lebrikizumab.

Conclusion: Results suggest that lebrikizumab provides meaningful improvements in skin clearance, itch, and quality of life in dupilumab-experienced patients with moderate-to-severe AD, with a safety profile consistent with other lebrikizumab phase 3 trials.

Trial registration: ClinicalTrials.gov identifier, NCT05369403.

Introduction: Psoriasis is a chronic inflammatory skin disease with a global prevalence of 1-5%, however its clinical and demographic profile in Kenya remains underexplored. This article describes the establishment of the Kenyan Psoriasis Registry at Moi Teaching and Referral Hospital in Eldoret, Kenya.

Methods: 214 subjects were enrolled between October 2024 and August 2025 at Moi Teaching and Referral Hospital. Both healthy controls and patients with psoriasis completed enrollment surveys and physical exams, and donated saliva samples.

Results: The initial cohort of 214 subjects (108 patients with psoriasis, 106 healthy controls) provides valuable insights into the demographics, clinical profiles, quality of life, and mental health characteristics of patients with psoriasis in Kenya. The mean age of psoriasis onset was 30.4 years, and mean age of diagnosis by a medical provider was 38.9 years old. 13.9% of patients with psoriasis reported a positive family history of psoriasis, and 9.3% of patients with psoriasis reported a diagnosis of psoriatic arthritis. The mean psoriasis area and severity index was 9.9 and mean Investigator Global assessment score was 3.0. Examination of treatment patterns revealed that moisturizers, prescription topical medications, and methotrexate were commonly tried while only 9.3% of individuals had ever received a biologic therapy. Patients with psoriasis reported significantly worse sleep disturbance, quality of life, and mental health compared to healthy controls.

Conclusion: This data highlights the unique characteristics of patients with psoriasis in Kenya. The Kenyan Psoriasis Registry continues to enroll patients and conduct yearly follow-ups, aiming to deepen the understanding of psoriasis in this population. These findings underscore the need for targeted research and advocacy to improve psoriasis care in Kenya.

Chronic spontaneous urticaria (CSU) is a mast cell-driven disease that affects approximately 1% of the population. Second-generation non-sedating H₁-antihistamines (H1AH) are considered the first-line treatment; however, a substantial proportion of patients remain refractory and require alternative therapeutic approaches, including anti-IgE antibodies or other agents that inhibit mast cell activation and degranulation. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are widely used for the treatment of type 2 diabetes mellitus and obesity and are known to reduce cardiovascular risk as well as comorbidities such as kidney disease and depression. In addition, GLP-1RAs have been reported to improve several autoimmune and autoinflammatory disorders, including dermatoses such as psoriasis, hidradenitis suppurativa, and atopic dermatitis. Several mechanisms have been proposed to explain the immunomodulatory effects of GLP-1RAs, including their influence on cytokine networks and immune cells, particularly mast cells. We report two female patients, aged 44 and 45 years, with long-standing CSU inadequately controlled on high-dose H1AH, who were initially prescreened for participation in a clinical trial with barzolvolimab. Before trial enrollment, both initiated GLP-1RA therapy (semaglutide or tirzepatide) for metabolic indications. Remarkably, both patients achieved complete resolution of CSU within 3 weeks of GLP-1RA initiation, with remission persisting for over 6 months. These observations suggest a potential immunometabolic mechanism linking GLP-1 signaling and mast cell activation, highlighting a novel therapeutic avenue for antihistamine-resistant CSU.

Introduction: Alopecia areata (AA) is an autoimmune disease characterized by nonscarring hair loss. Ritlecitinib, an oral JAK3/TEC family kinase inhibitor, inhibits cytokines that may be involved in humoral and cellular immunity and is approved to treat severe AA in patients aged ≥ 12 years. This sub-study of a phase 3 study evaluated primary immune responses to the meningococcal groups A, C, Y, and W-135 oligosaccharide diphtheria CRM₁₉₇ conjugate (MenACWY-CRM) vaccine and secondary immune responses to tetanus toxoid booster (Tdap) in patients with AA receiving ritlecitinib.

Methods: Adult participants in the ALLEGRO-LT study (NCT04006457) receiving open-label ritlecitinib 50-mg once-daily for ≥ 6 months were eligible. Participants received a single-dose of 0.5-mL Tdap booster alone or in combination with a single dose of 0.5-mL MenACWY-CRM vaccine. Blood samples were collected at baseline pre-vaccination and 1 month post-vaccination.

Results: Overall, 17 participants received Tdap vaccination, of whom 13 also received meningococcal vaccination. At month 1 post-vaccination, 62.5% (10/16) of participants exhibited a tetanus booster response. All participants (16/16) achieved anti-tetanus antibody levels of 1.0 IU/mL and 0.1 IU/mL; 50% (8/16) showed a > fourfold increase from baseline. For the MenACWY-CRM vaccine, 20% (1/5) and 40% (2/5) of participants achieved human serum bactericidal activity titer for serogroup C ≥ 1:8 and ≥ 1:4, respectively. The geometric mean titer of antibodies for serogroup C increased from baseline (n = 12) to month 1 (n = 11). In total, three adverse events (AEs) occurred in three participants. No vaccine-related AEs, serious AEs, or permanent discontinuations due to AEs were reported.

Conclusions: Primary and secondary immune responses to the meningococcal and tetanus vaccines were observed in patients with AA during chronic ritlecitinib therapy, although the study was limited by the small sample size. The vaccines were well tolerated, no vaccine-related AEs were reported, and there was no exacerbation of underlying disease.

Trial registration: ClinicalTrials.gov identifier, NCT04006457.

Introduction: Postherpetic neuralgia (PHN) is a chronic neuropathic pain condition that disproportionally affects older adults. First-line oral treatments often yield suboptimal relief and may cause systemic side effects and drug-drug interactions. Effective topical treatments offer the potential to address this significant unmet medical need in PHN. This CASPAR analysis evaluated real-world effectiveness and safety of the high-concentration capsaicin patch (HCCP) in patients with PHN.

Methods: Real-world data were evaluated for a large PHN cohort extracted from the German Pain e-Registry as part of the retrospective, noninterventional, multicohort CASPAR study. Patients received one to four HCCP treatments over 12 months. Patient-reported outcomes included average pain intensity (API), quality of life (QoL), sleep impairment, mood, concurrent pain medications, and safety.

Results: This analysis included 961 patients with PHN (mean age: 63.8 years, female: 69.7%; mean pain duration: 3.3 years) receiving one (n = 187), two (n = 209), three (n = 207), or four HCCP treatments (n = 358). Mean 24-h API decreased from 61.8 at baseline to 46.8 by month 3 (P < 0.001), and to 31.8 at month 12 (P < 0.001). Patients receiving four treatments had the greatest API reductions (63.7 at baseline versus 19.6 at month 12; P < 0.001), whereas improvements were lost in those who discontinued treatment. While ≥ 30% API response rates were similar across treatment groups at month 3 (25.6-30.7% of patients), those receiving additional treatments showed continued improvement, peaking at 99.7% by month 12 after four HCCP treatments. Trends were similar for other patient-reported outcomes, including QoL, sleep, and mood. Concomitant pain medication use decreased over time. Most adverse drug reactions were mild and application site-specific.

Conclusions: HCCP is an effective and well-tolerated topical treatment for patients with PHN, including older adults. After one treatment, improvements were noted in API, QoL, sleep, and mood outcomes, alongside decreased concomitant pain medication use, with progressive improvements following additional treatments. A Graphical Abstract is available for this article.

Introduction: Atopic dermatitis (AD) is a complex disease with clinical heterogeneity. Nemolizumab is a novel interleukin (IL)-31 receptor alpha inhibitor that has demonstrated efficacy in managing moderate-to-severe AD. However, there are no head-to-head trials that compare nemolizumab with other anti-IL-4/13 monoclonal antibodies (mAbs). To support clinical decision-making, the comparative efficacy and safety of nemolizumab versus other advanced systemic therapies, in combination with topical treatments, were estimated using network meta-analyses (NMAs).

Methods: Randomized controlled trials (RCTs) investigating advanced systemic therapies for moderate-to-severe AD in adolescents (12-17 years) and adults (≥ 18 years) were identified through a systematic literature review (searches conducted 31 March 2025, CRD42023492392). The trial results were analyzed in fixed- and random-effects Bayesian NMA models. Outcomes included ≥ 75% improvement in the Eczema Area Severity Index (EASI-75), an Investigator's Global Assessment (IGA) score of 0 or 1 (IGA success), treatment-emergent adverse events, and discontinuations due to adverse events. Analyses for all endpoints were conducted at week 16. This publication presents a targeted comparison of licensed anti-IL mAbs.

Results: Twenty-two RCTs were included in the NMA. When measuring response through EASI-75 and IGA success, no statistically significant differences were observed between nemolizumab and all other anti-IL mAbs in CsA-experienced adults or CsA-naïve adolescents. In CsA-naïve adults, only lebrikizumab demonstrated statistically superior efficacy against nemolizumab. Nemolizumab demonstrated a comparable safety profile with other available treatments.

Conclusions: The results of this study suggest that compared with other anti-IL mAb therapies for the treatment of moderate-to-severe AD, nemolizumab has similar efficacy in achieving EASI-75 and IGA success, and a comparable safety profile. This is in addition to nemolizumab's well-demonstrated efficacy in improving itch. Nemolizumab may be particularly beneficial in clinical settings where patients and physicians are seeking to manage AD with a well-tolerated therapeutic.

Cutaneous T cell lymphomas (CTCL) are non-Hodgkin T cell malignancies defined by malignant T cell transformation and accumulation in the skin. Limited understanding of CTCL pathogenesis, including the role of the tumor microenvironment, hinders effective treatment. Emerging evidence implicates the skin microbiota as a key modulator of disease, with microbial dysbiosis contributing to progression and representing a novel therapeutic target. This review synthesizes findings from 37 rigorously selected studies, outlining current knowledge of the CTCL-associated microbiome, mycobiome, and virome. It evaluates therapeutic strategies aimed at microbial colonization, emphasizing the potential of modulating host-microbe interactions. Additionally, we provide comprehensive clinical insight into the indications for microbial-modulating strategies of the microbiota in CTCL.

Introduction: Fractional microneedle radiofrequency (FMRF) and poly-L-lactic acid (PLLA) each promote dermal remodeling through distinct mechanisms and have demonstrated efficacy as monotherapies for atrophic acne scars (AAS). The objective of this study is to evaluate the efficacy and safety of combining FMRF with transdermal PLLA delivery compared with sterile water in Asian patients with moderate-to-severe AAS.

Methods: In this randomized, split-face, evaluator-blinded clinical trial, 24 participants underwent two monthly FMRF sessions. Immediately after each session, a reconstituted PLLA suspension was applied to one facial half for transdermal delivery through the FMRF-created microchannels, while sterile water was applied to the contralateral side. Outcomes were assessed using three-dimensional imaging (Antera® 3D), standardized photography, and patient self-assessments over a 6-month follow-up. Safety was monitored throughout the study.

Results: PLLA-treated sides demonstrated statistically significant improvements in skin texture and scar volume at 6 months compared with baseline and with control sides (p < 0.05). Patient-reported outcomes paralleled objective findings, with a higher proportion of participants reporting > 75% improvement on the PLLA-treated side. Adverse events were of low incidence, transient, self-limited, and no serious complications occurred.

Conclusions: Combining FMRF with transdermal PLLA delivery is a safe and effective approach for moderate-to-severe AAS in Asian patients. The combination produced progressive, sustained, and clinically meaningful improvements compared with FMRF alone.

Trial registration: Thai Clinical Trials Registry: TCTR20250803007.