Dermatology and Therapy最新文献

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with impaired quality of life and a substantial burden of disease. Lebrikizumab is a monoclonal antibody that selectively binds with high affinity to interleukin-13, thereby inhibiting its cascade signaling and reducing inflammation. Lebrikizumab has demonstrated efficacy and safety in adults and adolescents ≥ 12 years with moderate-to-severe AD in randomized, placebo-controlled, phase 3 clinical trials. Here, we report a case series of four patients with moderate-to-severe AD who transitioned to lebrikizumab treatment in the Czech Republic. All four patients had failed previous targeted therapies (biologics or Janus kinase inhibitors) and/or cyclosporine treatments and presented with associated comorbidities. After 12 to 16 weeks of treatment with lebrikizumab, clinically significant improvements in signs and symptoms (assessed by Eczema Area and Severity Index [EASI], pruritus Numerical Rate Scale, quality of life assessed by the Dermatology Life Quality Index [DLQI], and/or Patient Oriented Eczema Measure [POEM]) were reported. The results of these four clinical cases support the effectiveness observed in randomized clinical trials and suggest that lebrikizumab may be an effective treatment for moderate-severe AD in real-world clinical practice, even in patients with comorbidities who have failed previous advanced treatments.

Introduction: Hair thinning is a prevalent concern influenced by multiple factors including stress, hormonal changes, diet, and lifestyle, with varying impacts across demographic groups. Oral supplements addressing these key root causes through a multi-targeting, patented, botanical-based Synergen Complex have been developed to combat hair thinning across different populations. This study sought to build on existing evidence from previous clinical studies evaluating hair growth and quality by evaluating the effectiveness of these nutraceuticals in enhancing hair fiber diameter, and thus hair strength and length, in adults with thinning hair.

Methods: This 6-month, prospective, open-label study included women, plant-based women, menopausal women, parous women, and men consuming commercially available hair growth nutraceuticals (HGNs) targeted to different demographics (Nutrafol^® Women, Vegan, Balance, Postpartum, and Men). All subjects had hair thinning, self-reported and confirmed by the study dermatologist. Assessments occurred at baseline, day 90, and day 180. Measurements included hair shaft diameter via light microscopy, hair breakage/shedding via a four-region hair pull test, investigator global assessment (IGA) of hair parameters, and subject self-perception questionnaire.

Results: A total of 252 participants enrolled, with 244 completing the study per protocol. Ingestion of the HGNs was associated with a significant increase in hair shaft diameter across all groups by day 180. Hair pull tests showed significant reductions in intact, broken, and total hair shedding overall. In-person IGA was correlated with significant improvements in hair attributes-strength, length, thickness, and overall hair health-across all groups. Self-perception data revealed strong agreement across groups with statements regarding hair improvements by day 180.

Conclusions: This study demonstrates that ingestion of these bio-specific HGNs are associated with significantly enhanced hair shaft diameter and decreased breakage, resulting in longer, stronger hair across their intended populations. These findings support the use of these HGNs for hair thinning, offering alternative options for various populations for improving hair growth and thickness.

Clinicaltrials: gov identifier, NCT06362941.

Introduction: Delays remain in patients receiving effective treatment strategies that have potential to clear their skin of psoriasis, improve their quality of life (QoL) and change the psoriatic disease course, which, if uncontrolled, can irreversibly alter an individual's life course (i.e. cumulative life course impairment [CLCI]). This study explored current international awareness and consideration of the potential impact of psoriasis over the life course within clinical assessments and decisions about its management.

Methods: Cross-sectional surveys collated insights from people with psoriasis and healthcare professionals (HCPs) treating psoriasis (dermatologists and primary care physicians [PCPs]) across 29 countries.

Results: Data were collected from 487 people with psoriasis, 574 dermatologists and 618 PCPs. Despite people with psoriasis highlighting a range of daily activities that are 'very frequently' or 'always' affected by their psoriasis, 37% were never or rarely asked by their HCPs how the disease affects their life. Fewer than half of people with psoriasis had a high understanding of the potential future impact of psoriasis (or CLCI-contributing factors), and 44% were unaware that clear/almost clear skin is now a realistic treatment target. Almost half of HCPs considered psoriasis to be of early onset when it presented at ≤ 15 years of age. Despite HCP awareness of the impact of psoriasis on QoL, many of the contributing factors to CLCI were not addressed routinely in clinical practice nor considered when deciding on treatment; 40% of dermatologists set treatment goals (such as clear skin/almost clear skin/target Dermatology Life Quality Index [DLQI]) sometimes, less frequently, or not at all.

Conclusions: Misalignment exists in the experience of people living with psoriasis versus its assessment in clinical practice. Support is needed for assessment and monitoring of elements that may contribute to CLCI in clinical practice worldwide, to guide early psoriasis treatment decision-making to mitigate the risk for CLCI. Infographic available for this article. INFOGRAPHIC.

Introduction: Lebrikizumab, a human monoclonal antibody that targets interleukin-13, is approved for treating moderate to severe atopic dermatitis in many regions. However, real-world data are lacking and are needed to inform its efficacy and safety in broader populations.

Methods: This retrospective study reviewed the Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) at baseline and 16-20 weeks of 84 consecutive patients who received lebrikizumab subcutaneously at the label dose in a tertiary centre.

Results: EASI scores were available at 16-20 weeks for 72 patients. At this timepoint, 80.6% (58/72) achieved EASI 50, 56.9% (41/72) reached EASI 75, and 27.8% (20/72) attained EASI 90. DLQI was reduced by an average of - 1.5 points at 16-20 weeks. No serious adverse events were reported. Ocular adverse events occurred in 21.4% of the cohort (18/84). Eleven out of 14 patients that previously experienced conjunctivitis with dupilumab or tralokinumab had no recurrence with lebrikizumab.

Conclusion: In this real-world cohort of patients with atopic dermatitis, lebrikizumab demonstrated efficacy comparable to that observed in clinical trials. It may provide an alternative treatment option for individuals who have discontinued other biologics as a result of conjunctivitis.

Introduction: Generalized pustular psoriasis (GPP) is a chronic, systemic neutrophilic inflammatory disease, associated with acute flares and life-threatening complications. Plaque psoriasis, which is clinically and pathologically distinct from GPP, is also associated with mortality. While this has improved with the advent of effective biological therapies, progress in GPP is limited. The objective of this study was to compare all-cause mortality in GPP patients with that of plaque psoriasis patients and the general population.

Methods: Studies reporting mortality in GPP and ≥ 1 comparator group were selected for inclusion in meta-analyses through a systematic literature review and review of unpublished data. Two independent reviewers performed study screening and data extraction. Pooled hazard ratios (HRs) were calculated using random effects models.

Results: Primary meta-analyses included studies in Sweden and the USA, representing 3652, 8308 and 10,102 people with GPP, with plaque psoriasis and in the general population, respectively. All-cause mortality was 1.78 times higher (95% confidence interval [CI]: 1.52-2.09; P < 0.0001) for GPP than for plaque psoriasis and 2.92 times higher (95% CI: 1.12-7.60; P = 0.03) than for the general population. Sensitivity analyses, including studies in Germany and France, confirmed the primary results for GPP versus plaque psoriasis; pooled HRs were 1.79-2.31 (P < 0.01 for all analyses). Effect sizes across all four studies were considerably heterogeneous (I² = 93.58%; Q = 54.93; P < 0.0001). A study in Germany, with significant heterogeneity, possibly due to miscoding issues, was included in a sensitivity analysis for GPP patients versus the general population; the pooled HR reduced to 1.63 (95% CI: 0.45-5.97; P = 0.46), with considerable heterogeneity in effect sizes (I² = 98.35%; Q = 61.42; P < 0.0001).

Conclusion: GPP patients' all-cause mortality is 2-3 times higher than those for plaque psoriasis patients and the general population, highlighting the need for improved management of GPP. This analysis provides a reference point to evaluate changes in mortality following the introduction of targeted treatments.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itch and recurrent lesions that impose clinical and economic burden. The individual and combined contributions of itch intensity and lesion severity to healthcare resource utilization (HCRU) and costs are not well defined. This study characterized real-world clinical phenotypes of moderate-to-severe AD based on itch and lesion severity and quantified their associations with HCRU and healthcare charges.

Methods: A retrospective cohort study was conducted using linked electronic health records and claims data from the OMNY Health Dermatology Platform (January 2022-June 2024). Patients aged ≥ 12 years with moderate-to-severe AD, defined by prescription treatment, were included. Patients were stratified into four clinical phenotypes based on their scores on the Itch Numerical Rating Scale (NRS) and Investigator Global Assessment (IGA): moderate itch and moderate lesions (MI-ML), severe itch and moderate lesions (SI-ML), moderate itch and severe lesions (MI-SL), and severe itch and severe lesions (SI-SL). Annualized all-cause HCRU and total healthcare charges were assessed using multinomial propensity score weighting. Logistic regression identified predictors of high total charges (≥ 90th percentile).

Results: Among 4433 patients with moderate-to-severe AD, phenotype distribution was MI-ML (33%), SI-ML (43%), MI-SL (4%), and SI-SL (21%). While HCRU event rates (hospitalizations, emergency visits) were similar across phenotypes, mean annual total charges differed notably. Compared with MI-ML ($23,697), charges increased with severe itch (SI-ML: + $2197), severe lesions (MI-SL: + $3705), and both severe itch and lesions (SI-SL: + $10,448), driven mainly by pharmacy and outpatient costs. Mean annual charges were highest in SI-SL ($34,145), followed by MI-SL ($27,402), SI-ML ($25,894), and MI-ML ($23,697). Severe itch alone was associated with elevated pharmacy expenditures, whereas severe lesions primarily increased outpatient costs. In multivariable models, biologic use, systemic therapy, and comorbidities were predictors of high total charges.

Conclusion: Both itch intensity and lesion severity independently and additively contributed to HCRU and economic burden of moderate-to-severe AD. Severe itch primarily increased pharmacy spending, while severe lesions drove outpatient costs. The combined phenotype of severe itch and lesions incurred the highest overall charges, underscoring the need for phenotype-informed, comprehensive AD management strategies.

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.