Dermatology and Therapy最新文献

Introduction: A matching-adjusted indirect comparison (MAIC) was performed comparing the efficacy of delgocitinib and dupilumab in patients with atopic hand eczema (AHE), one aetiological subtype of chronic hand eczema (CHE).

Methods: DELTA 1/2 were phase 3 trials in which adults with moderate to severe CHE received delgocitinib cream 20 mg/g or cream vehicle twice daily for 16 weeks. LIBERTY-AD-HAFT was a phase 3 trial in which patients with moderate to severe AD with hand or foot involvement received subcutaneous dupilumab or placebo every 2 weeks for 16 weeks. An anchored MAIC was conducted using individual patient data (IPD) from DELTA 1/2 and aggregate published data from LIBERTY-AD-HAFT, with vehicle and placebo as the common anchor. IPD from patients with AHE as the primary subtype in DELTA 1/2 were weighted to match age, race, sex and baseline Hand Eczema Severity Index (HECSI) score in LIBERTY-AD-HAFT.

Results: LIBERTY-AD-HAFT included 133 patients (dupilumab, n = 67, placebo, n = 66) while DELTA 1/2 included 345 patients with AHE; the effective sample size after weighted matching was 201 (delgocitinib, n = 128, cream vehicle, n = 73). Anchor-adjusted odds ratios comparing delgocitinib versus dupilumab at week 16 were 1.1 (95% CI: 0.3, 3.4; p = 0.890) for Investigator's Global Assessment for Chronic Hand Eczema / Hand and Foot Investigator's Global Assessment score 0/1, 1.2 (95% CI: 0.4, 3.2; p = 0.773) for HECSI 75 and 1.3 (95% CI: 0.4, 4.9; p = 0.661) for HECSI 90 while response difference for HECSI percent improvement was 11.7% (95% CI: -9.2%, 32.7%; p = 0.273).

Conclusions: Topical delgocitinib and dupilumab in patients with AHE had comparable efficacy, with all results being numerically in favour of delgocitinib, although not statistically significant.

Clinical trial registration: NCT04871711, NCT04872101, NCT04417894.

Introduction: Difamilast is the first selective phosphodiesterase 4 inhibitor approved for atopic dermatitis (AD) in Japan. A phase 3, 52-week, open-label study was conducted to evaluate efficacy and safety of difamilast ointments in Japanese infants with AD aged 3 to < 24 months, because the clinical study in this population has not been conducted.

Methods: Infants (n = 41) received difamilast 0.3% ointment twice daily in a 4-week primary evaluation period, and subsequently received difamilast 0.3% or 1% ointment on the basis of the existing clinical symptoms in a 48-week, long-term extension period.

Results: The response rate in Investigator's Global Assessment score was 56.1% at week 4, and it increased to 75.6% at week 52. The response rate in Eczema Area and Severity Index 75 was 82.9% at week 4, and the approximately same response rate was maintained at 80.5% at week 52. Adverse events (AEs) were reported in 41 (100.0%) infants, most of which were mild or moderate in severity. The most frequently observed AE was nasopharyngitis (82.9%), followed by gastroenteritis (46.3%). The investigational medicinal product-related AE, folliculitis, was reported in one infant (2.4%). No clinically relevant abnormalities were reported in clinical laboratory tests, physical examinations, and vital signs.

Conclusion: Difamilast ointments applied twice daily to Japanese infants with AD aged 3 to < 24 months for up to 52 weeks are effective and well tolerated, indicating a new useful treatment option for this population.

Clinical trial registration: ClinicalTrials.gov identifier NCT05372653.

Introduction: Oral lichen planus (OLP) is a serious chronic inflammatory condition with malignant transformation potential affecting six million Americans which has no US Food and Drug Administration (FDA)-approved therapy. LP-10, a novel liposomal tacrolimus oral rinse, overcomes the poor adherence to oral surfaces and inconsistent drug delivery limitations of existing treatments.

Methods: This phase 2a multicenter dose-ranging study evaluated LP-10 safety and efficacy in symptomatic OLP. Twenty-seven adults (22 female, 5 male) received a 10-mL oral rinse of LP-10 at 0.25 mg, 0.5 mg, or 1.0 mg of tacrolimus, for 3 min twice daily for 4 weeks. Safety assessments included monitoring of adverse events, laboratory studies, and tacrolimus blood levels. Efficacy was measured by investigator global assessment (IGA), reticulation/erythema/ulceration (REU) score, pain/sensitivity numerical rating scale (NRS), OLP symptom severity measure (OLPSSM), and patient global response assessment (GRA).

Results: All participants completed treatment without discontinuation or serious adverse events. Treatment-related treatment-emergent adverse events were mild/moderate (50 mild, 4 moderate). LP-10 demonstrated exceptional pharmacokinetic safety with mean tacrolimus levels remaining < 1.0 ng/mL in 75% of post-baseline measurements; the maximum individual level (4.5 ng/mL) remained well below the toxicity threshold (15 ng/mL) suggesting little absorbance into the blood. All efficacy endpoints showed statistically significant and clinically meaningful improvements at week 4: mean and standard deviation (SD) values for IGA decreased from 3.5 ± 0.51 to 1.8 ± 1.37 (p < 0.0001), pain NRS from 6.8 ± 1.90 to 2.3 ± 2.53 (p < 0.0001), sensitivity NRS from 7.2 ± 1.71 to 2.9 ± 2.29, REU from 26.5 ± 10.4 to 13.2 ± 8.15 (p < 0.0001). Of the 23 participants who responded to the GRA, approximately 78% participants reported that their quality of life was "moderately better" or "very much better" as compared to when they started the study, across all doses. All prior corticosteroid failures (5/5) responded, with benefits sustained through 2-week follow-up.

Conclusions: LP-10 demonstrated excellent safety with minimal systemic absorption and clinically meaningful efficacy, representing substantial improvement over existing therapies for this serious condition with significant unmet medical need. Larger controlled studies are warranted to confirm these promising findings.

Clinical trial registration: NCT06233591.

Introduction: Several treatments are available for actinic keratosis (AK), many of which are hampered by local inflammation, pain, long duration, and slow healing. Indoor daylight photodynamic therapy (idl-PDT) is an effective, well-tolerated, first-line treatment for both AK and field cancerization, but its feasibility is limited by the long time required for illumination (2 h). The objective of our study was to evaluate the efficacy of idl-PDT with an illumination time of 1 h versus 2 h in the treatment of scalp AK.

Methods: We conducted an intrapatient, comparative study of idl-PDT with two illumination durations, 1 h versus 2 h, using methyl aminolevulinate (MAL, Metvix®) and a white light-emitting diode (LED) light (Dermaris®) for the treatment of scalp AK. Patients were evaluated 3 months and 6 months after one session of idl-MAL-PDT for AK response rate, both overall and by AK grade, and tolerability. Physicians' and patients' satisfaction were also investigated.

Results: A total of 55 patients were enrolled with a total of 955 AK (grade I-II). The AK clearance rate was 72.9% in 1 h-half and 71.1% in 2 h-half after 3 months, and 76.2% in 1 h-half and 78.9% in 2 h-half after 6 months. No statistically significant difference in efficacy (overall, grade I and II AK) was observed between the two illumination times, both at 3 and 6 months. The local skin reaction score and pain numeric rating scale (NRS) were very low, and comparable between the two treatment arms. Both physicians and patients expressed very good opinion on effectiveness and cosmetic outcome. Overall, 96.4% of patients would undergo idl-PDT again.

Conclusions: The efficacy of idl-PDT in treating grade I and II AK of the scalp was comparable using 1 h or 2 h as illumination time. Both treatment schedules were well tolerated, with a very high rate of satisfaction from both physicians and patients. This trial was retrospectively registered on the 4th of December 2025.

Trial registration: ClinicalTrials. gov identifier, NCT07290959.

Introduction: Surgical treatment is a key strategy for managing advanced hidradenitis suppurativa (HS), but postoperative recurrence remains a challenge. Understanding recurrence patterns and associated risk factors may help improve outcomes. The objectives were to evaluate surgical outcomes in patients with HS undergoing wide excision, to characterise surgical recurrence patterns, and to identify factors associated with each recurrence type.

Methods: This was a retrospective, observational, single-centre study conducted on patients who underwent HS surgical procedures between 2018 and 2024. Demographic, clinical, surgical and follow-up data were analysed. Recurrence was defined as the reappearance of inflammatory lesions within 1 cm of the surgical scar and subclassified as tunnel or abscess/inflammatory nodule (AN) recurrence.

Results: A total of 165 patients underwent 206 surgical procedures. Wide excision with secondary intention healing was the most common approach. The mean time to complete wound healing was 46.4 days. The overall recurrence rate was 18.5%, with tunnel recurrence in 8.3% and AN recurrence in 10.2%. Tunnel recurrence was associated with Hurley stage III, larger and deeper excisions and higher postoperative IHS4 scores, while AN recurrence was associated with BMI > 30 and preoperative ultrasound assessment. In multivariate analysis of overall recurrence, excised area was the only independent predictor (OR per cm², 1.03; p = 0.020), while poorer preoperative inflammatory control and lack of ultrasound assessment showed trends toward increased risk.

Conclusion: Differentiating between recurrence types may better reflect true surgical failure. Tunnel recurrence should be prioritized when evaluating surgical outcomes. Preoperative ultrasound and postoperative inflammatory control are key factors in minimizing recurrence.

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.

Introduction: Itch and pain are two of the most common and burdensome symptoms for moderate to severe Chronic Hand Eczema (CHE). Here, we assess changes in itch/pain in patients with moderate to severe CHE treated with delgocitinib cream 20 mg/g or cream vehicle for 16 weeks.

Methods: In a pooled DELTA 1 (NCT04871711)/DELTA 2 (NCT04872101) analysis (delgocitinib [n = 639]; cream vehicle [n = 321]; twice-daily), the Hand Eczema Symptom Diary captured patient-reported itch/pain severity on a numeric rating scale. Changes in itch/pain from baseline were assessed daily during week 1 and weekly from week 1 to 16.

Results: In delgocitinib-treated patients, a statistically significant least square mean reduction from baseline was observed for itch from day 1 ([delgocitinib cream/cream vehicle] 0.75/0.32; P < 0.001) and pain from day 3 (0.98/0.58; P = 0.001) after the first application. Among patients with ≥ 4-point baseline itch/pain score, a significantly greater percentage of delgocitinib-treated patients achieved ≥ 4-point reduction from week 2 (14.2%/17.3%) versus cream vehicle (6.3%/6.9%; P < 0.001). Reductions were maintained up to week 16 with delgocitinib cream treatment. Delgocitinib cream was well tolerated.

Conclusion: Early onset of itch/pain reduction was observed within week 1 for delgocitinib-treated patients, thereby providing further support of the use and efficacy of delgocitinib cream in adults with moderate to severe CHE.

Introduction: Biologic therapies have significantly improved treatment options for patients with moderate-to-severe psoriasis. Brodalumab's effectiveness, efficacy, and safety have been demonstrated in clinical trials. Real-world data are now available to confirm these outcomes in diverse populations, including those at higher risk of reduced treatment response.

Methods: This observational, prospective, multicentre study included 143 patients between 2020 and 2022. Baseline data included demographics, medical history, Psoriasis Area and Severity Index (PASI), presence of high-impact areas (HIA), Dermatology Life Quality Index (DLQI), comorbidities, and prior treatments. Follow-up visits (weeks 12-16 and 52) documented PASI, DLQI, and drug survival. The analysis focused on four potential modifiers of treatment response: body mass index (BMI), biologic treatment history, number of HIA, and age.

Results: Brodalumab demonstrated effectiveness and safety in patients with moderate-to-severe psoriasis requiring systemic therapy. Time of exposure to brodalumab was 13 months (52 weeks ± 4). At weeks 12/16, 49.6% achieved PASI 100, sustained in 61.9% at week 52. DLQI scores improved at both follow-ups, with increased proportions achieving DLQI ≤ 1. At week 52, PASI 100 and DLQI ≤ 1 were observed in 62.5% and 73.2% of patients with overweight, 48.6% and 61.8% of patients with obesity, respectively. Among older patients, 60.9% achieved PASI 100 and 65.2% reported DLQI ≤ 1. In patients with ≥ 2 HIA, 60.0% achieved PASI 100 and 68.9% experienced DLQI ≤ 1. Response was favourable across treatment history: 65.5% of bionaïve and 51.7% of bioexperienced patients achieved PASI 100; DLQI ≤ 1 was observed in 75.0% and 64.3%, respectively. Drug survival was high overall (94.6%) and across subgroups (88.3-100%). The safety profile was consistent with clinical trial data.

Conclusion: Real-world data supports brodalumab use as a valuable long-term treatment for HIA and specific subpopulations such as older, bionaïve, bioexperienced, and patients with overweight or obesity. This article is a post hoc analysis of the PSO-TARGET clinical trial (Evaluation of the Sensitivity and Specificity of a Novel Quality of Life Tool to Assess the Treatment Satisfaction in Psoriasis Patients).

Trial registration: ClinicalTrial.gov, NCT04765332.