Investigator's Global Assessment Research Articles

Predictive Factors for Poor Responders to Tralokinumab in Moderate-to-Severe Atopic Dermatitis: A Real-World Analysis.

Abstracts: Background: Some patients with moderate-to-severe atopic dermatitis (AD) show insufficient response to treatment with tralokinumab, an anti-interleukin-13 antibody. Identifying predictive factors for poor responders to tralokinumab can help optimize treatment strategies for AD patients. Objective: To identify predictive factors for poor responders to tralokinumab, defined as an investigator's global assessment >2 at week 12 or 24. Methods: A prospective study was conducted from October 2023 to August 2024, including 109 Japanese patients with moderate-to-severe AD. Baseline features were compared between poor responders versus responders at week 12 or 24. Results: Poor responders at week 12 showed higher baseline eczema area and severity index (EASI), lactate dehydrogenase (LDH), and eosinophil-to-lymphocyte ratio (ELR) compared with responders. Poor responders at week 24 had older age, longer disease duration, and higher proportions of previous systemic therapies, previous dupilumab, or previous 15 mg upadacitinib treatment, compared with responders. Conclusions: Higher baseline EASI, LDH, and ELR may predict poor response to tralokinumab at week 12. Older age, longer disease duration, and previous usage of systemic therapy, dupilumab, or 15 mg upadacitinib may predict poor response to tralokinumab at week 24. AD patients with the above features may as well avoid tralokinumab treatment.

Needle Radiofrequency Combined with Topical Exosome Therapy for Moderate to Severe Acne

Objective: This case series aims to evaluate the efficacy, patient satisfaction, and safety of combined needle radiofrequency (RF) and topical exosome therapy for moderate to severe acne. Methods: This study involved 22 patients (12 females and 10 males, ages 18–35) with moderate to severe acne who underwent combined needle RF and topical exosome (Xomage, Zishel Bio Inc., Seoul, Republic of Korea) treatments. Each patient completed between 6 and 10 sessions, conducted weekly over three-week intervals. Acne severity was assessed using the Investigator’s Global Assessment (IGA) scale, while patient satisfaction was measured on a 5-point Likert scale. Clinical photographs were taken at baseline and after the final treatment session. Results: All patients showed improvement in acne severity with a mean decrease in IGA score of 2.5 points from baseline to the final assessment. Patient satisfaction was high, with the majority expressing satisfaction in skin texture and acne reduction. Conclusion: Needle RF combined with topical exosome therapy appears to be an effective treatment for reducing acne lesions and improving skin quality, demonstrating a strong safety profile and high patient satisfaction.

Effectiveness and Safety of Dupilumab for Prurigo Nodularis in China: A Multicentric and Observational Study.

The efficacy and safety of dupilumab in patients with refractory prurigo nodularis (PN) is well established in clinical trials, but there is a lack of multicenter data regarding its effectiveness and safety in real-world settings. Patients with moderate-to-severe PN who initiated dupilumab treatment between July 2023 and January 2024, with a follow-up period of at least 16 weeks at 10 hospitals in China were included. We used peak pruritus numeric rating scale (PP-NRS), investigator global assessment (IGA) for PN, and dermatology life quality index for adults or children (DLQI/CDLQI) to assess disease control status and quality of life impairment, and monitored adverse events to assess the safety. A total of 73 PN patients (33 female, 40 male; mean age 45.9 ± 21.5 years) were included. A clinically meaningful improvement of ≥ 4 points in PP-NRS (PP-NRS4) was achieved in 84.9% of patients at Week 12. The percentage of patients achieving IGA 0/1 significantly increasing from 0% to 37.0% and 46.6% at Week 12 and 16, respectively. Patient-reported quality of life outcomes showed substantial improvement, with decreasing from 16.6 ± 6.8 at baseline to 7.2 ± 4.9 at Week 12, 6.4 ± 4.5 at Week 16. The safety profile of dupilumab was favorable, with one patient reporting dry eyes. Dupilumab can effectively improve the pruritus, nodular lesions and quality of life for PN in real-world settings.

Efficacy of diluted botulinum toxin type A (Microbotox) in treatment of mild to moderate acne vulgaris.

Acne vulgaris is a common and challenging condition to treat. To assess the effect of botulinum toxin type A (BTX-A) in the treatment of mild to moderate acne vulgaris. This study included 30 patients with mild to moderate acne vulgaris treated with intradermal injections of diluted BTX-A (microbotox) on the cheek in a regular grid pattern using very small droplets (microbotox). Cases were assessed by acne grading of severity by Investigator's Global Assessment of acne (IGAs) at baseline, at 1month and after 4months follow-up. IGA of acne at baseline ranged between 2 to 3 with a mean of 2.77 ± 0.430 and decreased significantly to 0.93 ± 0.868 after 4months. There were highly statistically significant differences between different follow-up periods according to Investigator's Global Assessment of acne. IGA on acne showed that 6 (20.0%) had fair improvement, 11 (36.7%) had good improvement and 9 (30.0%) demonstrated excellent improvement. Microbotox presents an approach to oily skin and acne vulgaris management. The multifaceted actions of BTX-A offer promising avenues for addressing the complex pathophysiology of this inflammatory condition pending verification by larger controlled multicenter studies.

Biomarkers in Atopic Dermatitis: A Review of the Role of IL-13 and the Impact of Tralokinumab Treatment.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease that can significantly affect quality of life. Presence, severity, and therapeutic response of AD are traditionally reported through clinical assessments including the Eczema Area and Severity Index or Investigator's Global Assessment. These clinical rating scales are visual assessments used in clinical trials to denotate AD severity. Alternatively, biomarkers open the potential to further enhance diagnosis of AD, assess disease status and severity, and potentially enable tailored treatment options for patients. Biomarkers can be classified according to their clinical use, clinical presentation, and underlying/endogenous molecular mechanisms. Specifically, interleukin (IL)-13, which has been shown to be a key biomarker in AD pathogenesis, can be used for prediction of AD development and to monitor clinical severity/response to treatment. Treatment with tralokinumab, a human monoclonal antibody that binds directly to-and subsequently blocks signaling of-IL-13, has been shown to reduce inflammation, re-balance the skin microbiome, and improve the skin barrier in patients with AD. In this review, key AD-related biomarkers, the role of IL-13 in driving AD pathogenesis, and the impact of IL-13 inhibition by tralokinumab on other AD-related biomarkers are discussed.

Real‐life retrospective multicentre study to describe the use of dupilumab in paediatric patients with atopic dermatitis in Spain: Patient profile, effectiveness and safety

AbstractBackgroundDupilumab, inhibiting interleukin 4 and 13, is the first monoclonal antibody licensed for atopic dermatitis (AD) since 6 months of age.ObjectivesThe study describes the patients' profile, the effectiveness and safety in real life of dupilumab in adolescents with moderate‐severe AD and children with severe AD.MethodsNational, multicentre, observational, and retrospective study, based on medical records' data extracted in September 2023. Patients included were adolescents (12–17 years) with moderate‐severe AD (Eczema Area and Severity Index [EASI] ≥ 16) and children (6–11 years) with severe AD (EASI ≥ 21) at the start of dupilumab therapy and treated with dupilumab for at least 3 months.ResultsAmong the 211 analysed patients, at dupilumab treatment onset, 69.6% registered an Investigator's Global Assessment (IGA) = 4, a median Dermatology Life Quality Index (DLQI) = 17, and a median Peak Pruritus Numerical Rating Scale (PP‐NRS) = 8. Atopic comorbidities were present in 69.7% of the patients. Overall, 97.1% of the patients had received systemic treatments before dupilumab, being oral corticosteroids (75.5%) the most frequent. At 16 and 52 weeks, the mean EASI percentage reductions from baseline were −77.5% and −84.7%, respectively, and 71.8% and 82.4% of the patients achieved EASI ≤ 7. A total of 70.5% and 36.5% (16 weeks), and 78% and 48.4% (52 weeks) of the patients had EASI‐75 and EASI‐90, respectively. At week 52, 70% and 87% of the patients achieved a reduction of ≥4 PP‐NRS points and of ≥6 DLQI points, respectively. No serious dupilumab‐related adverse events were reported; 6.2% presented treatment‐related conjunctivitis and 1.4% reported eosinophilia, but without treatment discontinuation.ConclusionsThe study population had a pronounced disease burden as defined by signs, symptoms, quality of life, atopic comorbidities, and the systemic treatments' use prior dupilumab. In a short time (16 weeks), dupilumab treatment demonstrated clinically relevant improvement with an acceptable safety profile, continued over 52 weeks.

Successful Achievement of Demanding Outcomes in Upadacitinib-Treated Atopic Dermatitis Patients: A Real-World, 96-Week Single-Centre Study.

Results from randomized controlled trials of upadacitinib, a Janus kinase (JAK) inhibitor, have led to its approval for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged ≥ 12years. The aim of this study was to report the effectiveness and safety of upadacitinib in real-world settings over a period of 96weeks. This retrospective study included all patients treated with upadacitinib at our centre between April 2022 and September 2024. Clinical and patient-reported outcomes were recorded and assessed at each follow-up visit and included the eczema area severity index (EASI), investigator global assessment (IGA), scoring atopic dermatitis (SCORAD), dermatology life quality index (DLQI) and the worst pruritus numerical scale score (WP-NRS). All drug-related adverse events (AEs) were documented. In total, 36 patients (44.4% female) were retrospectively included. After 4weeks of treatment, the mean EASI was reduced from 29.97 to 3.72 with 83.3/52.8/19.4% achieving EASI75/90/100 respectively. Similar reductions were observed in the DLQI, which was reduced from 20.78 to 2.92, and in the WP-NRS, from 7.78 to 1.31. Further improvements were observed at week16, with a mean EASI of 0.75 and 96.4% of the patients achieving EASI75 and EASI90. At week48 of treatment, EASI75/90/100 were achieved by 100/93.8/81.3% along with a mean DLQI and pruritus NRS of 0.81. All nine patients that reached the 72- and 96-week timepoints had clear skin with no pruritus. Six (16.7%) patients experienced AEs with four of them discontinuing medication; no patient discontinued because of upadacitinib inefficacy. This long-term real-world study of patients with moderate-to-severe AD receiving upadacitinib demonstrated that treatment success (EASI75/90/100) can be achieved in a high proportion of patients by week16 and can be maintained for up to 96weeks along with substantial improvements in pruritus and quality of life.

Lebrikizumab Improves Atopic Dermatitis in Adult and Adolescent Patients With Skin of Color: 16-Week Results From the ADmirable Study

Introduction: Lebrikizumab is a novel monoclonal antibody that binds with high affinity and a slow off-rate to interleukin (IL)-13, thereby blocking the downstream effects of IL13 with high potency. ADmirable (NCT05372419) is an ongoing, open-label, Phase 3b clinical trial of lebrikizumab in patients with moderate-to-severe atopic dermatitis (AD) and skin of color (SoC). These are the first primary results of any Phase 3 clinical trial studying patients with AD and SoC, a historically underrepresented patient population. Methods: At baseline and Week 2, patients received 500-mg lebrikizumab loading doses followed by 250-mg every 2 weeks through Week 16. Concomitant topical therapy was allowed. Patients receiving protocol-defined rescue therapy were discontinued. Key eligibility criteria included: ≥12 years of age, self-reported race other than White, Fitzpatrick Phototype IV-VI, and moderate-to-severe AD. This study includes new objective measures of pigment such as PDCA-Derm™. Endpoints are summarized as observed (primary analysis) and using non-responder imputation/multiple imputation (NRI/MI; supporting analysis). Results: At baseline (N=90), patients had a mean (SD) age of 40.7 (19.6) years, AD disease duration of 19.7 (16.1) years, Eczema Area and Severity Index (EASI) of 26.4 (12.2), and Pruritus Numeric Rating Scale (NRS) of 7.0 (2.2). Forty-three percent of patients were female and 16% were adolescent. Most patients had an Investigator’s Global Assessment (IGA) of 3 (69%). Patients self-reported their race as Black/African American (78%), Asian (11%), American Indian/Alaskan Native (7%), and Native Hawaiian or Other Pacific Islander (4%). Patients had Fitzpatrick Phototypes of IV (43%), V (24%), and VI (32%). At Week 16, 69.2% (54/78) of patients achieved a 75% improvement in EASI (NRI/MI, 66.9%), 44.9% (35/78) achieved a 90% improvement in EASI (NRI/MI, 42.5%), 44.9% (35/78) achieved an IGA 0/1 with ≥2-point improvement (NRI/MI, 44.1%), and 58.1% (36/62) reported ≥4-point Pruritus NRS improvement (NRI/MI, 55.4%). Approximately 50% of patients reported itch improvement within 6 weeks. Using PDCA-Derm™, hypopigmentation and hyperpigmentation improved in 33.3% (4/12) and 63.0% (29/46) of patients, respectively (as observed). Most treatment emergent adverse events (TEAE) were mild-to-moderate in severity. No TEAEs lead to discontinuation and no cases of treatment-related conjunctivitis were reported. No serious adverse events were observed. Conclusion: Lebrikizumab improved signs and symptoms of disease, including post-inflammatory pigment discoloration, in patients with AD and SoC and demonstrated a favorable safety profile.

Lebrikizumab vs Other Systemic Monotherapies for Moderate to Severe Atopic Dermatitis: Network Meta-analysis of Short-term Efficacy

Introduction: Treatment options for moderate-to-severe atopic dermatitis (AD) after inadequate response to topical therapy include biologics and Janus Kinase (JAK) inhibitors. A network meta-analysis (NMA) was conducted to evaluate the short-term efficacy of lebrikizumab relative to other monotherapies approved for moderate-to-severe AD in adults and adolescents (≥12 years). Methods: Data were included from randomized, double-blind, placebo-controlled monotherapy trials of lebrikizumab 250 mg every 2 weeks (Q2W), dupilumab 300 mg Q2W, tralokinumab 300 mg Q2W, abrocitinib 100 or 200 mg daily, baricitinib 2 or 4 mg daily, and upadacitinib 15 or 30 mg daily. Efficacy outcomes included the proportion of patients achieving Eczema Area and Severity Index (EASI) improvement, Investigator Global Assessment of 0 or 1 (IGA 0/1), and ≥4-point improvement in pruritus/itch numeric rating scale (NRS) score at 12 weeks (abrocitinib) or 16 weeks (other treatments). A Bayesian NMA was used to estimate number needed to treat (NNT), odds ratios (ORs), probabilities, and 95% credible intervals (CrI). Results: Twenty-two monotherapy studies involving 8531 patients were identified. For itch improvement, lebrikizumab had lower NNT values (2.90, 95% CrI: 2.26–3.80) than baricitinib 2 mg (11.12, 6.11–29.30) or 4 mg (8.10, 4.42–19.64) and tralokinumab (7.03, 4.81–11.17). Lebrikizumab had comparable NNT values for itch relative to abrocitinib 100 mg (3.50, 2.67–4.91) or 200 mg (2.31, 1.90–2.93), upadacitinib 15 mg (2.57, 2.09–3.29) or 30 mg (2.02, 1.74–2.46), and dupilumab (3.47, 2.78–4.58). NNT values for IGA 0,1 and EASI response were similar, except that upadacitinib 30 mg QD had lower NNT values than biologics at week 16. In pairwise comparisons, lebrikizumab was statistically superior to baricitinib and tralokinumab and comparable to abrocitinib, dupilumab, and upadacitinib 15 mg across all outcomes. Lebrikizumab had statistically inferior outcomes to upadacitinib 30 mg at week 16. Conclusion: Lebrikizumab has comparable or better short-term efficacy relative to other biologics and JAK inhibitors, except for upadacitinib 30 mg. Lebrikizumab may be a highly promising first-line biologic for moderate-to-severe AD, offering patients meaningful symptom relief.

Long-Term Safety and Efficacy with Roflumilast Cream 0.15% in Patients Aged ≥6 Years with Atopic Dermatitis: A Phase 3 Open-Label Extension Trial.

Background: Safety and efficacy of roflumilast cream 0.15% for atopic dermatitis (AD) were demonstrated in two 4-week phase 3 trials. Objective: Evaluate long-term safety, tolerability, and efficacy of roflumilast cream 0.15% in AD. Methods: In this open-label extension (OLE) trial (INTEGUMENT-OLE; NCT04804605), patients aged ≥6 years who completed one of the 4-week phase 3 trials applied roflumilast for up to 52 weeks. After 4 weeks of once-daily application, patients who achieved Validated Investigator Global Assessment for AD (vIGA-AD) of clear (0) switched to twice-weekly (BIW) application to normal-appearing flare-prone areas (proactive treatment). Results: Among 657 patients treated, 36.7% reported adverse events, including 4.7% that were treatment related. Application site pain and stinging/burning that caused definite discomfort at any visit were reported for 0.5% and 0.4%-2.1% of patients, respectively. Patients who achieved vIGA-AD 0 and switched to proactive BIW application maintained vIGA-AD 0/1 (almost clear) for a median of 281 days (Kaplan-Meier estimate). Conclusion: Roflumilast cream 0.15% was well tolerated for up to 56 weeks. BIW application to normal-appearing flare-prone sites maintained improvement in AD signs and symptoms, showing that proactive treatment represents an alternative to the current standard practice of reactive treatment.

A study on the clinical manifestations in lepidopterism.

Exposure to hairs of caterpillars and moths are collectively termed as lepidopterism. Clinical manifestations include cutaneous presentation of localized stinging reaction with wheals or vesiculation, acute urticarial papules and plaques, ophthalmic, oropharyngeal involvement to severe life-threatening anaphylactic reactions with angioedema. In this study we have determined the prevalence of various cutaneous, oropharyngeal and ophthalmic manifestations of lepidopterism at a tertiary health care center. All clinically diagnosed cases of lepidopterism were recruited for the study. Characteristics such as age, sex, history of atopy, presence of direct contact with implicated moth/ caterpillar, symptoms and signs, eye, oropharyngeal involvement and systemic findings were noted. Severity of symptoms and signs were quantified according to the Investigator Global Assessment Scale for Dermatitis. Treatment response were noted. The data was analysed and results tabulated. Out of 32 patients 26 had direct exposure and 6 reported symptoms without direct exposure, Itch and pain, urticaria and excoriations were the most common findings, systemic symptoms though less in occurrence were noted. There is lack of sufficient literature on these findings for comparative analysis. Caterpillar dermatitis can occur without direct contact and can be treated completely thus an astute index of suspicion is essential for prompt diagnosis and treatment.

Orismilast, a PDE4B/D inhibitor, in moderate-to-severe atopic dermatitis: Efficacy and safety from a multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (ADESOS).

Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic therapies with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase-4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD. To evaluate the optimal dose, efficacy and safety of orismilast twice-daily (BID) in patients with moderate-to-severe AD. This 16-week, multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (NCT05469464) included patients from 48 centers in Europe and the United States. Adults with moderate-to-severe AD were given (1:1:1:1) BID orismilast 20, 30, or 40 mg, or placebo. The primary endpoint was percentage change in Eczema Area and Severity Index (EASI); secondary: achievement of a score of Clear (0) or Almost Clear (1) with ≥2-point improvement by Investigator Global Assessment (IGA 0/1); achievement of peak pruritus numerical rating scale (PPNRS) reduction of ≥4 points; and achievement of a reduction in EASI of 75%, 90%, and 100% (EASI75, EASI90, EASI100, respectively) from baseline; all week 16. Overall, 233 patients were randomly assigned to orismilast 20 mg (n=58), 30 mg (n=61), 40 mg (n=59), or placebo (n=55). At week 16, Reductions in EASI (%-point) from baseline to week 16 were seen across orismilast groups and placebo (p>0.05 for orismilast versus placebo). Significantly more patients achieved IGA 0/1 with a ≥2-point improvement with orismilast 20 mg and 40 mg versus placebo (p<0.05). Significantly greater proportions of patients achieving a ≥4-point reduction in PPNRS were demonstrated with orismilast at week 2. The safety profile was consistent with that of the PDE4 class, with no major safety concerns reported. These data support the clinical relevance of selective PDE4B/D inhibition with orismilast, potentially offering a convenient, novel, oral therapy for the treatment of AD.

Meta-analysis of the efficacy and safety of secukinumab in the treatment of moderate to severe psoriasis

Purpose: The purpose of this study is to evaluate the efficacy and safety of secukinumab in the treatment of moderate to severe psoriasis. Methods: This study conducted a comprehensive review using multiple databases, including PubMed, EMBASE, Cochrane Library, ISI Web of Knowledge, and Chinese databases such as the Biomedical Literature Database, Chinese Science and Technology Journal Full-text Database, China Journal Full-text Database, and Wanfang Database. All relevant research published up to April 2024 was included. Two experienced researchers independently performed literature screening, quality assessment, and data extraction, ensuring adherence to predefined inclusion and exclusion criteria. Meta-analysis was conducted using RevMan 5.3 software. Results: A total of 6 studies comprising 2146 patients with moderate to severe psoriasis were selected. Secukinumab significantly outperformed placebo in multiple efficacy metrics, including the Psoriasis Area and Severity Index (PASI) with 75%, 90%, and 100% improvement (PASI 75, PASI 90, and PASI 100), Investigator Global Assessment (IGA) scores of 0 or 1 (IGA 0/1), and Dermatology Life Quality Index (DLQI) scores of 0 or 1 (DLQI 0/1). These differences were statistically significant (P &amp;lt; 0.05). In terms of safety, there was no significant difference in adverse events between the secukinumab and placebo groups (P &amp;gt; 0.05). Conclusion: Secukinumab demonstrates excellent efficacy and safety in treating moderate to severe psoriasis, supporting its strong recommendation for clinical use.

Efficacy and Tolerability of a Novel Cosmetic and Over-the-Counter Facial Acne Regimen Versus a Prescription Treatment.

The SkinMedica Acne Treatment Platform (SM Regimen) was formulated to treat acne without overdrying the skin. We evaluated efficacy and tolerability of the SM Regimen (including a novel 1% salicylic acid Acne Clarifying Cleanser and 2% salicylic acid Acne Treatment Lotion) versus a prescription formulation (Rx Regimen; including adapalene 0.1%/benzoyl peroxide 2.5%) in a diverse population of adults with mild to moderate facial acne. This single-center, double-blind, randomized study enrolled adults (18-45 years) with Fitzpatrick skin types (FST) I-VI. SM Regimen or Rx Regimen was applied topically to the entire face for 12 weeks. Assessments were conducted at 24 and 48 h and 4, 8, and 12 weeks. Subjects (SM Regimen, n = 31; Rx Regimen, n = 23) were primarily female (90.7%) with mean age of 28.6 years; 53.8% had FST IV-VI. Efficacy was comparable between regimens. The SM regimen resulted in significant improvements versus baseline in mean Investigator's Global Assessment of acne severity from 48 h through week 12 (p ≤ 0.001), as well as significant and sustained improvements from baseline in total acne lesion count, global postinflammatory hyperpigmentation/postinflammatory erythema, and oiliness. The SM Regimen was well tolerated at all time points, with mean scores below mild for all parameters; the Rx Regimen caused significantly more tightness/dry feeling at week 4 versus SM Regimen (p = 0.008). Subjects (> 96%) reported high satisfaction with the SM Regimen at all time points. The SM Regimen reduced acne severity and skin oiliness, evening out skin tone without overdrying or irritating the skin.

Assessing eczema severity: A comprehensive review of scoring systems

Eczema, a chronic inflammatory skin condition, requires accurate severity assessment for effective management, and research. This review highlights the importance of various standardized scoring systems used in eczema management including Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), Investigator’s Global Assessment (IGA), Patient-Oriented Eczema Measure (POEM), and Atopic Dermatitis Severity Index (ADSI).These scoring systems evaluate disease extent, severity, and quality of life impact, guiding treatment decisions, monitoring disease progression, and comparing outcomes across studies. Technology integration, including mobile apps and digital platforms, enhances scoring data collection and analysis. Scoring systems play a vital role in eczema management, enabling personalized, evidence-based care, and improving patient outcomes. Continued development and refinement of these tools will help guiding the management of of patients with eczema.

Identification of Early and Late Responders to Anti-IL-13 Antibody Tralokinumab in Atopic Dermatitis: A Real-World Japanese Study.

Background: Tralokinumab, an anti-IL-13 antibody, is an effective treatment for patients with atopic dermatitis (AD). However, predictive factors for responders to tralokinumab remain unclear in real-world practice. Objective: This study aimed to identify predictive factors for early and late responders to tralokinumab treatment. Early responders were defined as patients achieving investigator's global assessment (IGA) 0/1 at week 12, whereas late responders were defined as those without IGA 0/1 at week 12 but achieving IGA 0/1 at week 24. Methods: A prospective study was conducted with 108 Japanese AD patients treated with tralokinumab between October 2023 and August 2024. Patients' background factors and baseline clinical or laboratory indexes were compared between responders and poor responders. Results: Both early and late responders had a higher proportion of systemic therapy-naive patients compared with poor responders. Early responders had higher proportion of females, younger age, shorter disease duration, lower body mass index, and monocyte-to-lymphocyte ratio, whereas late responders had lower immunoglobulin E, thymus and activation-regulated chemokine, platelet-to-lymphocyte ratio, and C-reactive protein compared with poor responders. Conclusions: This study provides valuable insights for optimizing treatment strategies in AD, in selecting patients who may respond to tralokinumab at early or late phases.

Guselkumab for the treatment of moderate-to-severe plaque psoriasis in pediatric patients: results of the phase 3, randomized, placebo-controlled PROTOSTAR study.

No currently approved treatment for pediatric plaque psoriasis selectively targets interleukin (IL)-23. In adults, guselkumab (a selective IL-23 inhibitor targeting the p19 subunit) demonstrated substantial efficacy with a favorable safety profile in treating moderate-to-severe plaque psoriasis. PROTOSTAR (NCT03451851) evaluated the efficacy and safety of guselkumab in pediatric patients with moderate-to-severe plaque psoriasis. This phase 3, randomized, placebo-controlled study enrolled patients ≥6 to <18 years of age with moderate-to-severe plaque psoriasis. In Part 1 (Week [W]0-W16), patients were randomized to receive guselkumab, placebo, or open-label etanercept (active reference arm). At W16, Part 1 patients entered a guselkumab withdrawal/retreatment period or continued/crossed over to receive guselkumab (W16-W52). Co-primary endpoints were Investigator's Global Assessment (IGA) 0/1 and Psoriasis Area and Severity Index (PASI)75 (or United States Food and Drug Administration-required PASI90 co-primary endpoint) responses at W16 of Part 1. Part 2 evaluated continuous open-label guselkumab treatment (W0-W52). Of 92 and 28 patients enrolled in Parts 1 and 2, respectively, 86% and 96% continued treatment through W52. In Part 1, at W16, significantly higher proportions of guselkumab-treated than placebo-treated patients achieved IGA 0/1 (66% vs 16%; P<0.001), PASI75 (76% vs 20%; P<0.001), and PASI90 (56% vs 16%; P<0.01). More than one-third of guselkumab-treated patients achieved clear skin (IGA 0: 39% vs 4% placebo; PASI100: 34% vs 0% placebo; both P<0.01). In Part 2, at W52, 86%, 93%, and 82% of guselkumab-treated patients achieved IGA 0/1, PASI75, and PASI90, respectively. Through W16 of Part 1, 42%, 68%, and 58% of guselkumab-, placebo-, and etanercept-treated patients, respectively, had adverse events (AEs). Rates of AEs with guselkumab were similar through W52 in Parts 1 and 2; common AEs included nasopharyngitis, upper respiratory tract infection, and COVID-19. No serious or opportunistic infections occurred. Guselkumab demonstrated significant and clinically meaningful responses in pediatric patients with moderate-to-severe plaque psoriasis and all co-primary and major secondary endpoints were met. Guselkumab safety outcomes were similar to placebo; no new safety signals were identified. These findings support the use of guselkumab to treat pediatric patients with moderate-to-severe plaque psoriasis.

Effectiveness of potent topical corticosteroids versus mild ones in primary care for children with moderate flare-ups of atopic dermatitis; results of a randomised controlled trial

ObjectiveTo assess the effectiveness of a potent topical corticosteroid (TCS) as an initial treatment in primary care for children with moderate flare-ups of atopic dermatitis (AD), compared to starting on...

A phase 2, randomized, double-blind, vehicle-controlled trial of tapinarof cream in Japanese pediatric patients with atopic dermatitis.

Tapinarof is a nonsteroidal, topical, aryl hydrocarbon receptor agonist approved for the treatment of atopic dermatitis (AD) in Japanese patients aged ≥12 years. We evaluated the efficacy and safety of tapinarof in Japanese pediatric patients aged 2 to 11 years with AD in a phase 2, multicenter, randomized, double-blind, vehicle-controlled trial. Eligible patients (N = 121) were randomized 1:1:1 to receive tapinarof cream 0.5%, tapinarof cream 1%, or vehicle cream once daily for 8 weeks. At week 8, the least-squares mean percent change from baseline in Eczema Area and Severity Index (EASI) score (the primary endpoint) was -81.29% in the tapinarof 0.5% group, -77.62% in the tapinarof 1% group, and - 18.56% in the vehicle group. Reductions in EASI score at week 8 were significantly greater in the tapinarof groups than in the vehicle group (p < 0.0001 for both comparisons). The proportion of patients with ≥75% improvement from baseline in EASI score at week 8 was 77.5% in the tapinarof 0.5% group, 70.7% in the tapinarof 1% group, and 15.0% in the vehicle group. The proportion of patients who achieved an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear) with ≥2-grade improvement from baseline at week 8 was 32.5% in the tapinarof 0.5% group, 43.9% in the tapinarof 1% group, and 17.5% in the vehicle group. No treatment-related serious adverse events (AEs) were reported; all of the AEs were mild or moderate. Common AEs in tapinarof-treated patients included gastroenteritis, application site irritation, and nasopharyngitis. The incidence of trial discontinuations due to AEs was low in tapinarof-treated patients (one patient for each strength). In summary, both strengths of tapinarof cream demonstrated greater efficacy than vehicle cream and were well tolerated in Japanese pediatric patients with AD.

Safety and Efficacy of Anti–IL-23 Monoclonal Antibody QX004N for Patients With Psoriasis

Psoriasis is a chronic, immune-mediated skin disease with an unmet need for biologic treatment options. To assess the safety, pharmacokinetics, and efficacy of QX004N in healthy individuals and patients with moderate to severe plaque psoriasis in China. This randomized clinical trial was composed of 2 parts. Part 1 was a first-in-human, single-ascending-dose, phase 1a clinical trial conducted from November 2, 2021, to January 16, 2023. Part 2 was a double-blind, multiple dose-escalation, phase 1b clinical trial conducted from February 15, 2023, to January 5, 2024, at 5 clinical centers in China, involving patients with moderate to severe plaque psoriasis. In part 1, healthy participants in each cohort were assigned in a 4:1 ratio to receive a single subcutaneous injection of QX004N (ranging from 10 mg to 600 mg) or placebo. In part 2, patients in each cohort were assigned in a 4:1 ratio to receive QX004N or placebo at doses of 150 mg, 300 mg, and 600 mg once every 2 weeks. For part 1, the primary outcome was the safety of a single dose of QX004N in healthy participants, and the secondary outcome was the pharmacokinetic profile. For part 2, the primary efficacy end point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) by week 12; other efficacy end points were considered secondary. The phase 1a clinical trial (part 1) enrolled 55 healthy participants (mean [SD] age, 35.9 [6.0] years; 30 [54.5%] female), and the phase 1b clinical trial (part 2) enrolled 30 patients with moderate to severe plaque psoriasis. The mean (SD) age of QX004N-treated participants in part 2 was 41.4 (7.5) years, and 19 of 24 QX004N-treated participants (79.2%) were male. The mean (SD) age of the placebo cohort in part 2 was 35.3 (8.4) years, and 5 of 6 placebo-treated participants (83.3%) were male. QX004N exhibited linear pharmacokinetics and was tolerated well in both healthy participants and patients with psoriasis. Most adverse events were mild to moderate in severity, with no drug-related serious adverse events reported. The proportion of patients receiving QX004N who achieved PASI 75 at week 12 and PASI 90 (90% improvement in PASI) at week 16 in the 150-mg, 300-mg, and 600-mg cohorts was 100%, significantly higher than that in the placebo cohorts (33.3%). The maximum proportion of patients achieving Investigator's Global Assessment score of 0 or 1 was 100% in the 3 QX004N cohorts. In this randomized clinical trial, QX004N was well tolerated and demonstrated superior efficacy compared to placebo in patients with moderate to severe plaque psoriasis. Chinese Clinical Trial Registry Identifier: CTR20212313 and CTR20223457.