2-grade Improvement Research Articles

Efficacy and Safety of RelabotulinumtoxinA Liquid Botulinum Toxin in the Treatment of Lateral Canthal Lines: Results From the Phase 3 READY-2 Study.

RelabotulinumtoxinA (RelaBoNT-A) is a complex-free, ready-to-use, liquid botulinum toxin A. Efficacy/safety of RelaBoNT-A treatment for lateral canthal lines (LCL). Randomized adults received RelaBoNT-A (30 U/side; n = 230) or placebo (n = 73) during a 6-month, double-blind, Ph3 study (Relabotulinumtoxin Aesthetic Development Study-2 [READY-2]). Primary end points (Month 1, maximum smile) comprised: composite ≥2-grade responder rate using concurrent LCL severity investigator live assessment (LCL-ILA) and subject live assessment (LCL-SLA); LCL-ILA 0 (none)/1 (mild) responder rate. Subject satisfaction and adverse events were also reported. Month 1 composite ≥2-grade responder rates were 51.8% (RelaBoNT-A) and 1.4% (placebo; (p < .001). Month 1 none/mild LCL-ILA responder rates were 87.2% (RelaBoNT-A) and 11.9% (placebo; p < .001). Onset was reported Day 1 by 34%. At Month 6, LCL-ILA responder rates for RelaBoNT-A remained at 23.3% (none/mild) and 35.9% (≥1-grade improvement). Median return to baseline severity was 24.7 weeks; 64% (RelaBoNT-A group) had not returned to baseline at Month 6. RelaBoNT-A satisfaction was high through Month 6 (71%). Mild/moderate treatment-related adverse events occurred in 6.1% (RelaBoNT-A) and 5.5% (placebo). RelaBoNT-A (60 U) treatment provided statistically significant improvement of moderate-to-severe LCL. One-third of subjects reported onset within 1 day and improvements were maintained through Month 6. Treatment satisfaction was high. RelaBoNT-A was well tolerated.

NivobotulinumtoxinA in the Treatment of Glabellar Lines With or Without Concurrent Treatment of Lateral Canthal Lines in Two Phase 3 Clinical Trials.

Botulinum neurotoxins used in aesthetic medicine require reconstitution before administration, which may be inconvenient and present errors among injectors. Evaluate the efficacy and safety of ready-to-use nivobotulinumtoxinA liquid formulation for the treatment of glabellar lines (GL) with/without treatment of lateral canthal lines (LCL). Two multicenter, phase 3, double-blind, randomized trials enrolled participants with moderate-to-severe GL (Study 001) or moderate-to-severe GL+LCL (Study 005). Participants received double-blind nivobotulinumtoxinA (20U) or placebo (Period 1) then ≤2 open-label nivobotulinumtoxinA GL treatments (Period 2) in Study 001 or double-blind nivobotulinumtoxinA 20U (GL), nivobotulinumtoxinA 44U (GL+LCL), or placebo (Period 1) then ≤2 double-blind injections of the same treatment (Period 2) in Study 005. The composite primary endpoint was the proportion of participants achieving ≥2-grade improvement in Facial Wrinkle Scale (FWS) at maximum frown on investigator and participant assessment; co-primary endpoints were investigator- and participant-assessed FWS "none or mild" rating. At Day 30, significantly higher responder rates were observed for the composite primary endpoint with GL treatment alone (Study 001, 46.1%; Study 005, 45.1%) and GL+LCL (Study 005, 41.3%) versus placebo (0%; all P < 0.001). Responder rates of "none or mild" by investigator and participant assessment, respectively, were significantly higher for GL treatment alone (Study 001, 77.2% and 65.0%; Study 005, 74.3% and 68.8%) and GL+LCL (Study 005, 74.0% and 61.2%) versus placebo (all P < 0.001). Adverse events were similar between treatment groups and placebo. Liquid nivobotulinumtoxinA was effective and well tolerated for treating moderate-to-severe GL alone or with LCL.

Efficacy of Ritlecitinib in Patients with Alopecia Areata by Extent of Hair Loss: Results from the Phase 2b/3 and Phase 3 ALLEGRO Clinical Trials

Introduction: Ritlecitinib, a dual JAK3/TEC family kinase inhibitor, demonstrated efficacy and safety in patients ≥12 years old with AA and ≥50% scalp hair loss in the phase 2b/3 ALLEGRO study. This post hoc, pooled analysis of the ALLEGRO-2b/3 and phase 3 ALLEGRO-LT studies evaluated the efficacy of ritlecitinib in patients with alopecia areata (AA) by extent of baseline scalp hair loss through Month 24. Methods: Patients aged ≥12 years with AA and ≥50% scalp hair loss who received ritlecitinib 50 mg daily in ALLEGRO-2b/3 and rolled over to ALLEGRO-LT (continued to receive 50 mg) were included. Outcomes included the proportions of patients achieving response based on Severity of Alopecia Tool [SALT] score ≤20 (≤20% scalp hair loss), ≥2-grade improvement in eyebrow assessment [EBA] score (among patients with abnormal score at baseline), and ≥2-grade improvement in eyelash assessment [ELA] score (among patients with abnormal score at baseline). Patients were stratified by extent of scalp hair loss at baseline, defined as severe AA (SALT score 50-94) or very severe AA (SALT score 95-100), as per the Alopecia Areata Investigator Global Assessment (AA-IGA). Data as observed and imputed (last observation carried forward [LOCF]) are reported at the cutoff date (December 9, 2022). Results: Of 191 patients included, 66 (34.6%) had severe AA and 125 (65.4%) had very severe AA at baseline. At Month 12, 64.4% and 34.3% (observed) and 60.6% and 29.6% (LOCF) of patients with severe AA and very severe AA, respectively, achieved SALT ≤20. At Month 24, these proportions increased to 70.2% and 54.8% (observed) and 63.6% and 36.8% (LOCF), respectively. EBA response was achieved in 54.6% and 46.9% (observed) and 52.8% and 42.4% (LOCF) of patients with severe AA and very severe AA, respectively, at Month 12; at Month 24, the proportions were 60.9% and 56.5% (observed) and 50.0% and 45.8% (LOCF). ELA response was achieved in 60.7% and 40.5% (observed) and 61.3% and 38.0% (LOCF) of patients with severe AA and very severe AA, respectively, at Month 12; at Month 24, the proportions were 70.0% and 45.3% (observed) and 61.3% and 38.0% (LOCF). Conclusion: Ritlecitinib 50 mg daily achieves scalp, eyebrow, and eyelash hair regrowth in patients with severe and very severe AA. Funding: This study was funded by Pfizer Inc

Efficacy and Safety of Ruxolitinib Cream for the Treatment of Moderate to Severe Chronic Hand Eczema: Top-Line Results From a 16-Week, Multicenter, Randomized, Double-Blind Study

Hand eczema is a common inflammatory disorder involving skin of the hands. Chronic hand eczema (CHE) is defined as hand eczema that persists for &gt;3 months or recurs ≥2 times within a 12-month period. The efficacy and safety of ruxolitinib (selective Janus kinase [JAK] 1/JAK2 inhibitor) cream was investigated in adults with moderate to severe CHE in a phase 2, randomized, double-blind, vehicle-controlled study (NCT05906628). Patients aged ≥18 years with a diagnosis of CHE for ≥6 months, an Investigator’s Global Assessment (IGA)-CHE score of 3 or 4, and no current or history (≤5 y) of atopic dermatitis were randomized 1:1 to apply twice-daily 1.5% ruxolitinib cream or vehicle cream for 16 weeks of double-blind treatment. Patients (N=186) had a median (range) age of 50.0 (18–80) years, and 59.7% were female. The median (range) Itch numerical rating scale (NRS) score was 6.6 (2.1–10), and 72.6% of patients had an IGA-CHE score of 3. At Week 16, significantly more patients who applied ruxolitinib cream versus vehicle achieved IGA-CHE treatment success (primary endpoint; 53.2% vs 10.9%; P&lt;0.0001), defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement from baseline. Significantly more patients who applied ruxolitinib cream versus vehicle achieved a ≥4-point improvement from baseline in Itch NRS score (Itch NRS4) at Week 4 (46.7% vs 17.6%; P&lt;0.0001; key secondary endpoint) and Week 16 (52.2% vs 23.1%; P&lt;0.0001; key secondary endpoint). Numerical improvements in Itch NRS4 with ruxolitinib cream versus vehicle were observed at Day 2 with statistically significant improvement observed on Day 7 (27.4% vs 9.0%; P=0.0024; key secondary endpoint). Substantially more patients who applied ruxolitinib cream versus vehicle achieved a ≥75% or ≥90% improvement from baseline in Hand Eczema Severity Index (HECSI) score at Week 16 (80.2% vs 26.9% and 64.0% vs 11.5%, respectively). Ruxolitinib cream was generally well tolerated through Week 16 with no new safety signals; no serious infections, major adverse cardiovascular events, malignancies, or thromboses were observed. Application site reactions were infrequent. No treatment-related grade ≥3 treatment-emergent adverse events (TEAEs) were reported, and no patients discontinued owing to a TEAE. In conclusion, ruxolitinib cream demonstrated significant reductions of CHE signs and symptoms versus vehicle through Week 16 and was generally well tolerated, consistent with the known safety profile. (Funding, Incyte Corporation)

Fixed-Combination Halobetasol Propionate 0.01% and Tazarotene 0.045% Lotion and Halobetasol Propionate 0.01% Lotion for Plaque Psoriasis on Areas With Body Hair: Maintenance of Treatment Effect

Background: Psoriasis on hair-bearing body areas may be difficult to treat with topical therapy, as hair may reduce penetration of active ingredients.1 Patients may also experience disease rebound following cessation of corticosteroid therapy.2,3 An appropriate vehicle for hair-bearing areas may increase penetration, and a combination of corticosteroid and tazarotene may improve maintenance of treatment effect following cessation.4-6 Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) and HP 0.01% lotion are indicated for treatment of plaque psoriasis in adults7,8 and contain a vehicle optimized for penetration.6,9 Previously, a post hoc analysis demonstrated the efficacy and safety of HP/TAZ and HP in treating men with plaque psoriasis on the leg, a representative area with body hair.10 Here, we expand on the previous study by reporting maintenance of efficacy following treatment cessation in this population. Methods: In phase 3 trials, participants with moderate-to-severe plaque psoriasis were randomized to treatment or vehicle once daily for 8 weeks (HP/TAZ, n=276; vehicle, n=142; HP, n=285; vehicle, n=145). Participants were assessed at 2-week intervals and at 4 weeks after treatment cessation (week 12).11,12 In this post hoc analysis, treatment success (≥2-grade improvement in investigator’s global assessment score and score of clear or almost clear); erythema, plaque elevation, and scaling success (≥2-grade improvement for each); and safety were assessed in men with psoriasis on the leg treated with HP/TAZ (n=87) or HP (n=91). Maintenance of effect was defined as the proportion of participants who achieved treatment, erythema, plaque elevation, or scaling success at week 8 and maintained success at week 12. Men were assumed to have leg hair. Treatment comparisons were indirect. Results: Four weeks after treatment cessation, HP/TAZ–treated participants exhibited increased rates of treatment success (week 8, 35.3%; week 12, 37.2%) and erythema success (week 8, 37.4%; week 12, 48.4%), whereas HP-treated participants exhibited decreased rates (treatment success: week 8, 35.5%; week 12, 23.1%; erythema success: week 8, 50.6%; week 12, 36.5%). HP/TAZ–treated participants exhibited less attrition in plaque elevation and scaling success after treatment cessation (week 8, 57.4% and 56.3%; week 12, 55.1% and 55.8%, respectively) versus HP-treated participants (week 8, 53.1% and 61.7%; week 12, 39.8% and 41.6%, respectively). For all outcomes, a greater proportion of participants receiving HP/TAZ achieved maintenance of effect from weeks 8 to 12 compared with participants receiving HP (range: HP/TAZ, 74%-85%; HP, 56%-62%). No new safety signals were identified. Conclusions: Following treatment cessation of HP/TAZ, men with plaque psoriasis on the leg experienced further disease improvement and maintained treatment effects at greater rates than those treated with HP, suggesting that tazarotene combined with HP provides prolonged efficacy in hair-bearing areas.

Tapinarof cream for the treatment of atopic dermatitis: Efficacy and safety results from two Japanese phase 3 trials.

Tapinarof is a nonsteroidal, topical, aryl hydrocarbon receptor agonist. We evaluated the efficacy and safety of tapinarof cream 1% in Japanese patients aged ≥12 years with atopic dermatitis (AD) in two phase 3 trials, ZBB4-1 and ZBB4-2. ZBB4-1 (N = 216) consisted of an 8-week, double-blind, vehicle-controlled treatment period (period 1) and a 16-week extension treatment period (period 2). Patients were randomized 2:1 to tapinarof or vehicle in period 1; subsequently, all patients who enrolled in period 2 received tapinarof. ZBB4-2 (N = 291) was a 52-week, open-label, uncontrolled trial in which all patients received tapinarof. In period 1 of ZBB4-1, the proportion of patients who achieved an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with ≥2-grade improvement from baseline at week 8 (IGA treatment success, the primary end point) was 20.24% in the tapinarof group and 2.24% in the vehicle group (p = 0.0007). The proportion of patients with ≥75% improvement from baseline in Eczema Area and Severity Index (EASI) score at week 8 (EASI-75 response, the key secondary end point) was 40.3% in the tapinarof group and 4.3% in the vehicle group (p < 0.0001). In ZBB4-2, IGA treatment success rate was 28.1% at week 16, 32.3% at week 24, and 41.3% at week 52, and EASI-75 response rate was 53.3% at week 16, 63.7% at week 24, and 76.6% at week 52, indicating that efficacy responses improved over time and were maintained over 52 weeks. Across the two trials, most adverse events (AEs) were mild or moderate; common AEs included folliculitis, acne, and headache. In summary, tapinarof cream 1% was effective and generally safe for up to 52 weeks of treatment in Japanese patients with AD.

Efficacy and Safety of a Fixed-Dose Combination Gel with Adapalene 0.1% and Clindamycin 1% for the Treatment of Acne Vulgaris (CACTUS): A Randomized, Controlled, Assessor-Blind, PhaseIII Clinical Trial.

Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor. To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris. This was a randomized, controlled, assessor-blind, phaseIII study conducted in patients with moderate facial acne vulgaris. A total of 1617 patients were enrolled. At week12, patients in the adapalene-clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (- 66.85%), compared with adapalene alone (- 50.82%) or clindamycin gel alone (- 57.61%). The difference in the least square means of the adapalene-clindamycin gel group and adapalene group, or clindamycin gel group was - 16.08% (95%CI - 19.95% to - 12.21%) and - 9.38% (95%CI - 13.25% to - 5.51%;), respectively. At week12, 19.28% of participants who received adapalene-clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95%CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95%CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups. Adapalene 0.1%-clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris. ClinicalTrials.gov identifier NCT03615768.

Improving Neck and Jawline Aesthetics With OnabotulinumtoxinA by Minimizing Platysma Muscle Contraction Effects: Efficacy and Safety Results in a Phase 3 Randomized, Placebo-Controlled Study.

Platysma prominence (PP) describes the noticeable appearance of the platysma muscle upon contraction, causing less defined jawline contour and vertical neck bands. To assess safety and efficacy of onabotulinumtoxinA for improvement of PP in adults. Participants with moderate-to-severe (Grade 3 to 4) PP at maximum contraction received onabotulinumtoxinA or placebo on Day 1 and were monitored for 120 days. OnabotulinumtoxinA dosage (26, 31, or 36 U) was customized based on baseline PP severity on each side of the neck. Efficacy analyses were conducted in the intent-to-treat (ITT) population (all randomized participants), and modified ITT population (mITT; psychosocially impacted by PP appearance). Results from ITT and mITT populations were comparable. As assessed by investigators, 76.7% of onabotulinumtoxinA mITT participants achieved ≥1-grade improvement versus 21.2% in the placebo group, and 41.0% versus 2.2% (P < 0.0001) achieved ≥2-grade improvement at Day 14. As assessed by participants, 79.9% of onabotulinumtoxinA mITT participants versus 21.8% in the placebo group and 40.8% versus 3.9% (P < 0.0001) achieved ≥1- or ≥2-grade improvement, respectively, at Day 14. OnabotulinumtoxinA responder rates remained higher than placebo through Day 120, gradually declining over time. OnabotulinumtoxinA participants reported significantly higher satisfaction with treatment effect, lower bother from jawline and vertical neck bands, and lower psychosocial impact from PP than placebo at Day 14 (P < 0.0001). OnabotulinumtoxinA effectively improved self-perceived jawline definition and was well tolerated. OnabotulinumtoxinA was well tolerated and effective in improving moderate-to-severe PP, including neck bands and jawline definition.

IncobotulinumtoxinA in the Treatment of Upper Facial Lines: Results From Two Randomized, Double-Blind, Placebo-Controlled, Phase III Studies.

Two randomized, double-blind, placebo-controlled, Phase III studies of incobotulinumtoxinA for treating upper facial lines (UFL; combination of glabellar frown lines [GFL], horizontal forehead lines [HFL] and lateral canthal lines [LCL]) were conducted in the US (ULTRA I: NCT04594213) and Germany (ULTRA II: NCT04622254). To evaluate safety and efficacy of simultaneous intramuscular injections for UFL. Longer-term safety and efficacy were assessed in open-label extension periods (OLEX). Healthy participants (≥18 years) with moderate-to-severe GFL, HFL and symmetrical LCL at maximum contraction on the five-point Merz Aesthetics Scales (MAS) were randomized 2:1:1 to receive up to 64 Units of incobotulinumtoxinA in the main period (MP) for each trial. Treatment groups were: UFL, GFL & HFL (ULTRA I), LCL (ULTRA II) and placebo. Primary efficacy endpoints were the proportions of GFL, HFL and LCL responders, defined as a MAS score for the respective area of 0 (no) or 1 (mild) and ≥2-grade improvement from baseline to Day 30, as assessed by both investigator and participant. Overall, 362 and 368 participants received treatment in ULTRA I and ULTRA II, respectively. In both studies, incobotulinumtoxinA treatment was significantly more effective than placebo with respect to the primary endpoint (p < 0.0001) and key secondary endpoints (p < 0.0001). OLEX results were consistent with those seen in the MP. No new safety findings were identified. In ULTRA I and ULTRA II, safety and efficacy of incobotulinumtoxinA for the simultaneous treatment of moderate-to-severe UFL were demonstrated, with significant improvements across all primary and secondary endpoints versus placebo.

Efficacy and Safety of Ruxolitinib Cream in Atopic Dermatitis Based on Previous Medication History.

For some patients with atopic dermatitis (AD), topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), and systemic therapies are inadequate to control disease or are associated with adverse events (AEs). Ruxolitinib cream monotherapy demonstrated anti-inflammatory and anti-pruritic effects among patients enrolled in two pivotal phase 3 studies (TRuE-AD1/TRuE-AD2); most patients had long-term disease control with as-needed use during the 44-week long-term safety (LTS) period. This post hoc analysis explored efficacy and safety of 1.5% ruxolitinib cream by previous medication use. Patients aged ≥ 12years enrolled in TRuE-AD1/TRuE-AD2 were randomized 2:2:1 to twice-daily 0.75% or 1.5% ruxolitinib cream or vehicle cream for 8 weeks, followed by a 44-week LTS period; patients initially on vehicle were re-randomized 1:1 to either ruxolitinib cream strength. Within 12months of enrollment (N = 1249), previous AD therapies were used by 89.4% of efficacy-evaluable patients applying vehicle or ruxolitinib cream (n = 725); of these, 80.4% received TCS (n = 583), 22.2% TCI (n = 161), 20.3% TCS + TCI (n = 147), and 18.9% systemic therapies (n = 137). Across previous medication subgroups, achievement of Investigator's Global Assessment (IGA)-treatment success (IGA 0/1 with ≥ 2-grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index from baseline, and ≥ 4-point improvement in Itch numerical rating scale score from baseline at Week 8 did not substantially differ among patients who applied ruxolitinib cream. Outcomes were similar to those in the overall study population. At all study visits during the LTS period, > 70% of patients in each subgroup had IGA 0/1 and a low percentage (generally < 3%) of affected body surface area. Treatment-related AEs across subgroups were reported in 7.3% (n = 35/481)to17.4% (n = 19/109) of patients. Continuous-use ruxolitinib cream monotherapy for 8weeks followed by as-needed use was effective and well tolerated, regardless of previous topical or systemic therapy, with outcomes similar to those achieved in the overall study population. ClinicalTrials.gov Identifier, NCT03745638/NCT03745651.

Improvement of platysma prominence with onabotulinumtoxinA: Safety and efficacy results from a randomized, double-blinded, placebo-controlled phase 3 trial

Platysma prominence (PP) refers to the undesirable effects that may occur with platysma muscle contraction. Evaluate safety and efficacy of onabotulinumtoxinA for improving Moderate (Grade 3) to Severe (Grade 4) PP in adults. Participants were randomized 1:1 to receive a total dose of onabotulinumtoxinA 26, 31, or 36 U or placebo on Day 1 and monitored for 120days. Dosage was administered via superficial intramuscular injections into the platysma muscle based on baseline PP severity. At Day 14, 32.3% of onabotulinumtoxinA-treated participants in the intent-to-treat population versus 1.9% who received placebo achieved investigator- and participant-rated Grade 1 or 2 (Minimal or Mild) and ≥2-grade improvement from baseline in PP severity, while 56.9% and 51.7% achieved Grade 1 or 2 on investigator's and participant's assessments, respectively (all P<.0001). OnabotulinumtoxinA-treated participants reported higher satisfaction, less bother from jawline and vertical neck band appearance, and reduced psychosocial impact versus placebo (all P<.0001). Adverse event incidence was similar between onabotulinumtoxinA and placebo. No events of dysphagia or muscular weakness were reported. A single onabotulinumtoxinA treatment was evaluated. OnabotulinumtoxinA showed favorable tolerability and significantly improved PP severityand patient-reported outcomes in participants with moderate-to-severe PP.

Roflumilast Cream, 0.15%, for Atopic Dermatitis in Adults and Children

Safe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates. To evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD. Two phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic Dermatitis (assessed on a 5-point scale ranging from 0 [clear] to 4 [severe]). Patients were randomized 2:1 to receive roflumilast cream, 0.15%, or vehicle cream once daily for 4 weeks. The primary efficacy end point was Validated Investigator Global Assessment for Atopic Dermatitis success at week 4, defined as a score of 0 or 1 plus at least a 2-grade improvement from baseline. Secondary end points included Eczema Area and Severity Index and Worst Itch Numeric Rating Scale. Safety and local tolerability were also evaluated. Among 1337 patients (654 patients in INTEGUMENT-1 and 683 patients in INTEGUMENT-2), the mean (SD) age was 27.7 (19.2) years, and 761 participants (56.9%) were female. The mean body surface area involved was 13.6% (SD = 11.6%; range, 3.0% to 88.0%). Significantly more patients treated with roflumilast than vehicle achieved the primary end point (INTEGUMENT-1: 32.0% vs 15.2%, respectively; P < .001; INTEGUMENT-2: 28.9% vs 12.0%, respectively; P < .001). At week 4, statistically significant differences favoring roflumilast also occurred for the achievement of at least 75% reduction in the Eczema Area and Severity Index (INTEGUMENT-1: 43.2% vs 22.0%, respectively; P < .001; INTEGUMENT-2: 42.0% vs 19.7%, respectively; P < .001). Roflumilast was well tolerated with low rates of treatment-emergent adverse events. At each time point, investigators noted no signs of irritation at the application site in 885 patients who were treated with roflumilast (≥95%), and 885 patients who were treated with roflumilast (90%) reported no or mild sensation at the application site. In 2 phase 3 trials enrolling adults and children, once-daily roflumilast cream, 0.15%, improved AD relative to vehicle cream, based on multiple efficacy end points, with favorable safety and tolerability. ClinicalTrials.gov Identifiers: NCT04773587, NCT04773600.

A Randomized, Evaluator-Blinded, Multicenter Study to Compare Injectable Poly-D,L-Lactic Acid vs Hyaluronic Acid for Nasolabial Fold Augmentation.

Injectable poly-D,L-lactic acid (PDLLA), under the brand name of AestheFill (REGEN Biotech, Inc., Seoul, South Korea), is a biocompatible, biodegradable, and biostimulatory product utilized to correct soft tissue volume loss. Its efficacy and safety have not been fully studied in a large cohort. The aim of the study was to evaluate the efficacy and safety of a novel dermal filler injectable, poly-D,L-lactic acid. This was an evaluator-blinded, multicenter, randomized controlled trial to compare the efficacy and safety of PDLLA vs hyaluronic acid in the correction of the nasolabial fold. Two hundred and sixty patients with moderate to severe nasolabial folds were enrolled and randomized to the treatment group (PDLLA) or control group (hyaluronic acid). Each patient received a PDLLA or hyaluronic acid injection for nasolabial fold augmentation and was followed for 52 weeks. The Wrinkle Severity Rating Scale (WSRS) and Global Aesthetic Improvement Scale (GAIS) were applied to evaluate topical nasolabial fold augmentation and overall improvement, respectively. At 24 weeks, 67.6% of patients in the PDLLA group had an at least 1-grade improvement on the WSRS, compared to 60.9% of patients in the control group with an at least 1-grade improvement on the WSRS (P < .05). At each visit, the PDLLA group showed more improvement on the baseline WSRS than the control group. PDLLA was safe and well tolerated, with no severe adverse events. PDLLA shows noninferior efficacy in correcting nasolabial folds compared to hyaluronic acid.

Efficacy and Safety of Topical Roflumilast for the Treatment of Psoriasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Plaque psoriasis is commonly treated topically with glucocorticoids and vitamin D derivatives. However, potential side effects such as skin atrophy underscore the need for safe and effective alternative topical therapies. Recently, the US Food and Drug Administration (FDA) and Health Canada approved roflumilast 0.3% cream as an option for treating this disease. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of topical roflumilast 0.3% compared with vehicle for plaque psoriasis. PubMed, Embase, ClinicalTrials.gov, and Cochrane databases were searched from inception to 1 May 2024, assessing the outcomes of Investigator's Global Assessment (IGA) or body-IGA success (clear or almost clear status plus an at least 2-grade improvement from baseline), Psoriasis Area and Severity Index (PASI)-50, PASI-75, PASI-90, intertriginous-IGA success (clear or almost clear status on the intertriginous-IGA plus an at least 2-grade improvement from baseline), and adverse events (AEs). Statistical analysis was performed using Review Manager, R software, and RStudio. Heterogeneity was determined using the Cochran Q test and I2 statistics. Four RCTs were included, comprising a total of 1403 patients, of whom 885 (63.1%) received topical roflumilast 0.3% and 518 (36.9%) received vehicle. At week 8, the achievement of IGA or body-IGA success was significantly higher among those treated with topical roflumilast than in the vehicle group [relative risk (RR) 5.07; 95% confidence interval (CI) 3.55-7.23; p < 0.01]. Similar findings were observed at week 8 for PASI-50 (RR 2.73; 95% CI 2.27-3.29; p < 0.01), PASI-75 (RR 4.48; 95% CI 2.26-8.89; p < 0.01), and PASI-90 (RR 5.61; 95% CI 2.57-12.25; p < 0.01). Corresponding outcomes were found at weeks 2, 4, and 6. Additionally, a higher percentage of patients treated with topical roflumilast 0.3% once daily achieved intertriginous-IGA success, compared with those receiving vehicle, at week 8 (71.9% versus 20.5%; RR 3.32; 95% CI 2.11-5.22; p < 0.01), with similar findings at weeks 2, 4, and 6. While a significant difference was observed in the overall incidence of AEs between the topical roflumilast and vehicle groups, there was no difference in treatment-related AEs, serious AEs, or AEs leading to study discontinuation. These findings support the superiority of topical roflumilast 0.3% over vehicle and suggest its use as a valuable asset for the treatment of plaque psoriasis. International Prospective Register of Systematic Reviews (PROSPERO), CRD42023456494.

Tapinarof cream for the treatment of plaque psoriasis: Efficacy and safety results from 2 Japanese phase 3 trials.

Tapinarof is a non-steroidal, topical, aryl hydrocarbon receptor agonist. We evaluated the efficacy and safety of tapinarof cream (1%) in Japanese patients aged ≥18 years with plaque psoriasis in two phase 3 trials, ZBA4-1 and ZBA4-2. ZBA4-1 (N = 158) consisted of a 12-week, double-blind, vehicle-controlled treatment period (period 1) and a 12-week extension treatment period (period 2). Patients were randomized 2:1 to tapinarof or vehicle in period 1; subsequently, all patients who were enrolled in period 2 received tapinarof. ZBA4-2 (N = 305) was a 52-week, open-label, uncontrolled trial in which all patients received tapinarof. In period 1 of ZBA4-1, the proportion of patients who achieved a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear) with ≥2-grade improvement from baseline at week 12 (PGA treatment success, the primary endpoint) was 20.06% in the tapinarof group and 2.50% in the vehicle group (p = 0.0035). The proportion of patients with ≥75% improvement from baseline in the Psoriasis Area and Severity Index (PASI) score at week 12 (PASI75 response, a key secondary endpoint) was 37.7% in the tapinarof group and 3.8% in the vehicle group (p < 0.0001). In ZBA4-2, PGA treatment success rate was 30.0% at week 12, 51.3% at week 24, and 56.3% at week 52, and PASI75 response rate was 50.4% at week 12, 77.5% at week 24, and 79.9% at week 52, indicating that efficacy responses improved over time and were maintained over 52 weeks. Across the two trials, most adverse events (AEs) were mild or moderate; common AEs included folliculitis and contact dermatitis. In summary, tapinarof cream (1%) was efficacious and generally safe for up to 52 weeks of treatment in Japanese patients with plaque psoriasis.

A Review of Current Data on Duration of Effect in Glabellar Lines After Treatment With AbobotulinumtoxinA 50 U.

AbobotulinumtoxinA has become well established as a treatment option for moderate to severe glabellar lines since its first aesthetic approval in 2009. Pivotal trials leading to regulatory approval showed that abobotulinumtoxinA treatment was associated with high responder rates when defined as achievement of none or mild glabellar lines (0 or 1 on the glabellar line severity scale) and a duration of action of up to 5 months. More recently, the goals for treatment of glabellar lines have shifted toward not only achieving a decrease in glabellar line severity but also ensuring that patients are satisfied with their experience. Patients seek an improvement in the appearance of their glabellar lines while maintaining a "natural look," fast onset of effect, and long duration of response. Trial designs have evolved to meet these new targets, including expanding the definition of responders to those having at least 1-grade improvement in the glabellar line severity scale score from baseline coupled with the use of subject satisfaction and psychological well-being questionnaires. The findings demonstrate that abobotulinumtoxinA remains a well-tolerated and consistently effective treatment option associated with a rapid onset of effect, duration of efficacy lasting up to 6 months, and high, long-lasting levels of patient satisfaction.

Tapinarof Cream 1% Once Daily is Efficacious for the Treatment of Atopic Dermatitis in Patients with Skin of Color Down to 2 Years of Age in Two Pivotal Phase 3 Trials

Introduction: Patients with atopic dermatitis (AD) and skin of color can have heterogeneous presentations and treatment responses. In the pivotal phase 3 ADORING 1 and 2 trials, tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) once daily (QD) was significantly efficacious and well tolerated versus vehicle in adults and children down to 2 years of age with AD. Objective: Here, we report analyses of efficacy by skin color in ADORING 1 and 2, based on patients’ self-identified race and investigator-assessed Fitzpatrick skin type. Methods: In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic DermatitisTM (vIGA-ADTM) score of ≥3, an Eczema Area and Severity Index score of ≥6, and body surface area involvement of 5–35% were randomized 2:1 to tapinarof cream or vehicle QD for 8 weeks. The primary efficacy endpoint was a vIGA-ADTM score of 0 (clear) or 1 (almost clear) and ≥2-grade improvement from baseline at Week 8. Secondary endpoints included proportion of patients with a ≥75% improvement in Eczema Area and Severity Index (EASI75). Results: Of the 407 and 406 randomized patients, 8.8–15.3% were Asian, 26.5–35.0% were Black, 44.8–56.8% were White, and 2.7–5.2% were Other groups (American Indian or Alaska Native, Native Hawaiian or Pacific Islander, or multiple races) across trials. Patients with Fitzpatrick skin types IV, V, and VI represented 23.8–25.1%, 20.6–22.2%, and 7.6–8.9%, respectively, of patients (&gt;50% in both trials). Across trials, vIGA-ADTM responses (ranges) for tapinarof versus vehicle were: Asian, 39.5–48.9% vs 3.7–18.5%; Black, 43.1–47.0% vs 17.5–24.1%; White, 49.4–52.1% vs 12.2–14.5%; and Other, 26.0–44.8% vs 0.0–40.2%. EASI75 responses for tapinarof versus vehicle were: Asian, 47.6–76.6% vs 17.7–20.2%; Black, 48.9–55.3% vs 25.7–30.0%; White, 61.4–67.8% vs 19.6–20.7%; and Other, 38.3–63.3% vs 0.0–40.6%. Similarly, high and consistent vIGA-ADTM and EASI75 responses were reported with tapinarof versus vehicle in patients with Fitzpatrick skin types I–III and IV–VI. Conclusion: Tapinarof cream 1% QD was consistently efficacious among all racial groups and Fitzpatrick skin types in adults and children down to 2 years of age with AD, including patients with skin of color, who were highly represented in these trials.

Ruxolitinib Cream in Adolescents/Adults with Atopic Dermatitis Meeting Severity Thresholds for Systemic Therapy: Exploratory Analysis of Pooled Results from Two Phase3 Studies.

Standard therapy for patients with mild to moderate atopic dermatitis (AD) typically includes topical therapies; however, patients with more extensive AD and/or AD refractory to topical therapy may benefit from systemic treatment. Ruxolitinib cream monotherapy has demonstrated superior antipruritic and anti-inflammatory effects versus vehicle in patients with mild to moderate AD, and long-term disease control with as-needed use. Here, efficacy/safety of 1.5% ruxolitinib cream through 52weeks was assessed in a subset of patients with moderate and/or more extensive disease. This post hoc analysis of TRuE-AD1/TRuE-AD2 included patients who, at baseline, had Investigator's Global Assessment (IGA) score of 3, Eczema Area and Severity Index (EASI) ≥ 16, and affected body surface area (BSA) ≥ 10% (higher severity of disease threshold subgroup). Disease control and safety were assessed. Of 1249 patients in the overall population, 78 (6.2%) met all higher severity of disease threshold criteria (continuous-use vehicle-controlled period: 1.5% ruxolitinib cream, n = 32; vehicle, n = 13); 28 and 4 of these patients, respectively, continued as-needed 1.5% ruxolitinib cream during the long-term safety (LTS) period. At week8 (continuous-use), IGA-treatment success (IGA0/1, with ≥ 2-grade improvement from baseline) was achieved by 19/32 (59.4%) patients applying 1.5% ruxolitinib cream versus no patients applying vehicle. In the LTS period, those achieving clear/almost clear skin increased from 19/28 patients (67.9%; continuous-use: week8) to 18/23 patients (78.3%; as-needed use: week52) in patients applying ruxolitinib cream from day1. Ruxolitinib cream was well tolerated, with few application site reactions, regardless of disease severity threshold. Efficacy and safety results were similar to the overall study population. Patients with AD who meet standard disease severity eligibility criteria for systemic therapy may achieve IGA-treatment success with clear/almost clear skin with continuous-use ruxolitinib cream, and maintain long term-disease control with as-needed ruxolitinib cream monotherapy. NCT03745638/NCT03745651.

Safe and Effective Restoration of Jawline Definition With Hyaluronic Acid Injectable Gel VYC-25L: Results From a Randomized Controlled Study.

A well-defined jawline improves overall facial aesthetics, motivating patients to seek jawline augmentation. In this study we evaluated the safety and effectiveness of the hyaluronic acid injectable gel VYC-25L for restoring jawline definition. In a US multicenter, evaluator-blinded study adults with grade 2 (moderate) or 3 (severe) Allergan Loss of Jawline Definition Scale (ALJDS) scores were randomized. Participants were randomized to the VYC-25L treatment group or control group at study onset, with 12-month follow-up. The control group had the option to receive treatment after 6 months (primary endpoint completion). Effectiveness measures included Month 6 ALJDS responders rate (proportion of participants with ≥1-grade improvement from baseline on both sides), FACE-Q Satisfaction With Lower Face and Jawline scores, and Global Aesthetic Improvement Scale (GAIS) responders (improved/much improved) as assessed by the investigator and participants. Injection site responses (ISRs) and adverse events (AEs) were monitored. At Month 6, ALJDS responder rates were 69.0% vs 38.0% in the VYC-25L treatment (n = 157) and control (n = 49) groups, respectively (P = .0001). In the VYC-25L treatment group, FACE-Q scores improved by a mean of 45.9 points from baseline at Month 6 (P < .0001). Furthermore, 88.4% and 89.0% of participants in the VYC-25L treatment group were GAIS responders at Month 6 by participant and investigator assessment, respectively. Most ISRs were mild or moderate and resolved within 2 weeks. Most treatment-related AEs were mild and resolved within 1 week. VYC-25L safely and effectively restores jawline definition through 1 year.

Efficacy and Safety of RelabotulinumtoxinA, a New Ready-to-Use Liquid Formulation Botulinum Toxin: Results From the READY-1 Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial in Glabellar Lines.

RelabotulinumtoxinA (RelaBoNT-A, Galderma, Uppsala, Sweden) is an innovative, ready-to-use liquid botulinum toxin A, produced with PEARL (precipitation-free extraction and activity-preserving refined liquid) manufacturing technology, which yields a potent, complex-free formulation. In the READY-1 study, efficacy and safety outcomes following a single RelaBoNT-A treatment for glabellar line correction were examined. Adults with moderate to severe glabellar lines received RelaBoNT-A (50 U) or placebo in a 3:1 randomized, 6-month, phase 3, multicenter, double-blind study. Primary endpoints (examined at Month 1, maximum frown) comprised the composite ≥2-grade response, defined as ≥2-grades improvement from baseline on concurrent investigator (glabellar line investigator live assessment; GL-ILA) and participant (glabellar line subject live assessment; GL-SLA) severity scales (US endpoint), and the investigator-reported responder rate for participants scored as 0 (none) or 1 (mild) (GL-ILA scale only; EU endpoint). Participant satisfaction and treatment-emergent adverse events (TEAEs) were reported. Overall, 297 adults were randomized and treated. Month 1 composite ≥2-grade responder rate was 82.9% (RelaBoNT-A, n = 199) vs 0% (placebo, n = 67; P < .001). Month 1 investigator-reported none or mild responder rate was 96.3% (RelaBoNT-A) vs 4.5% (placebo; P < .001). GL-ILA scores remained higher with RelaBoNT-A (23.6% [none or mild]; 58.1% [≥1-grade improvement]) vs placebo (1.5%; 10.4%, respectively) through Month 6 (P < .001). In the Kaplan-Meier analysis, 75% still showed GL-ILA and GL-SLA improvements from baseline at 169 days (end of study). Participants reported onset of effect from Day 1 (39%) and satisfaction with natural-looking results (96.8%; Month 1). RelaBoNT-A-related TEAEs were low (3.6%) and typically mild. A single RelaBoNT-A treatment was effective and demonstrated a favorable safety profile. RelaBoNT-A provided significant improvements in glabellar line severity, high satisfaction, rapid onset, and enduring effectiveness throughout the 6-month study period.