Investigator's Static Global Assessment Research Articles

The Relationship between Chocolate Consumption and the Severity of Acne Lesions-A Crossover Study.

The study involved 92 participants with acne who were divided into two groups, A (n = 51) and B (n = 41). In the first week, both groups had to follow an anti-inflammatory diet (AID), then for the next 4 weeks, group A continued on with the AID, and group B followed an AID with chocolate. After this time, group B started a 4-week AID without chocolate, and group A started a 4-week AID with chocolate. The severity of acne lesions was assessed using the Investigator's Static Global Assessment scale, where zero points indicated no lesions and five points indicated severe acne. As a result of the consumption of 50 g of chocolate, a statistically significant intensification of acne lesions was observed in both groups. After 4 weeks of following the chocolate diet, the severity of acne lesions increased from 2.5 ± 0.7 to 3.4 ± 0.8 points (p < 0.0001) in group A, and from 2.4 ± 0.7 to 3.5 ± 0.6 points (p < 0.0001) in group B. Overall, chocolate intake contributed to the exacerbation of acne lesions by one point in 65 participants, by two points in 13 participants and by three points in one participant. The obtained results suggest that daily consumption of 50 g of chocolate with 85% cocoa content, even with an anti-inflammatory diet, may intensify acne lesions in this study group. However, it remains unclear which chocolate components may lead to the exacerbation of acne.

Efficacy and Safety of Crisaborole Ointment 2% in Chinese Patients Aged ≥ 2 Years with Mild to Moderate Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic immuno-inflammatory skin disease. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild to moderate AD. This post hoc analysis assesses the efficacy and safety of crisaborole in Chinese patients aged ≥ 2years with mild to moderate AD. We evaluated the efficacy and safety of crisaborole in Chinese patients from the vehicle-controlled, phase 3 CrisADe CLEAR study. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily, respectively, for 28days. The primary endpoint was percent change from baseline in Eczema Area and Severity Index (EASI) total score at day 29. Key secondary endpoints were improvement in Investigator's Static Global Assessment (ISGA), ISGA success, and change from baseline in weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score. Adverse events were documented. Of 391 patients in the overall study, 237 were from China, 157 assigned to crisaborole and 80 assigned to vehicle. A greater reduction in percent change from baseline in EASI total score at day 29 was shown in the crisaborole vs. vehicle group (least squares mean [LSM]: -66.34 [95% (confidence interval) CI -71.55 to -61.12] vs. -50.18 [95% CI -58.02 to -42.34]). Response rates for achievement of ISGA improvement (43.2% [95% CI 35.4-51.1] vs. 33.4% [95% CI 22.5-44.2]) and ISGA success (31.7% [95% CI 24.3-39.0] vs. 21.5% [95% CI 12.1-30.9]) at day 29 were higher in the crisaborole vs. vehicle group. A greater reduction in change from baseline in weekly average PP-NRS score at week 4 was observed in the crisaborole vs. vehicle group (LSM: -1.98 [95% CI -2.34 to -1.62] vs. -1.08 [95% CI -1.63 to -0.53]). No new safety signals were observed. Crisaborole was effective and well tolerated in Chinese patients aged ≥ 2years with mild to moderate AD. ClinicalTrials.gov, NCT04360187.

Maintenance of Investigator's Static Global Assessment Response with Once-Daily Crisaborole in Participants with Mild to Moderate Atopic Dermatitis.

Treatments for atopic dermatitis (AD) often fail to achieve lasting disease control. In the CrisADe CONTROL phase III study (ClinicalTrials.gov: NCT04040192), participants aged ≥ 3months with mild to moderate AD treated with once-daily (QD) crisaborole, following initial treatment success with crisaborole twice daily (BID), had longer periods of flare-free maintenance, a higher number of flare-free days, and a lower number of flares compared with those who received vehicle. The study was an exploratory analysis of data on the maintenance of response per Investigator's Static Global Assessment (ISGA; ISGA score of 0 [clear] or 1 [almost clear]) during the CrisADe CONTROL study through week 52. Exploratory endpoints were the time to ISGA response during the open-label run-in period, and the maintenance of ISGA response and the severity and duration of flares during the double-blind maintenance period. Outcomes were stratified by age (participants aged 3months to < 12years and ≥ 12years) and duration of crisaborole BID treatment (< 4weeks or ≥ 4weeks) during the open-label run-in period. During the open-label run-in period, the median time to ISGA response was 41.5days. From week 4 to week 52 of the double-blind maintenance period, the proportion of participants who maintained ISGA response was greater with crisaborole versus vehicle, and this difference was statistically significant up to week 36 (P < 0.05). Duration of flare periods during the maintenance period were 54.1 and 54.0days for the vehicle and crisaborole-treated groups, respectively. Numerically fewer crisaborole-treated participants experienced a flare with an ISGA score of ≥ 2 compared with vehicle-treated participants (64.8% vs. 74.4%, respectively). Findings were comparable across most subgroups. Adult and pediatric participants with mild to moderate AD at baseline who had achieved responder criteria (treatment success) with crisaborole BID during the run-in period maintained response per ISGA with crisaborole QD during the double-blind maintenance period through week 52. ClinicalTrials.gov: NCT04040192.

Real-world efficacy of 2% crisaborole ointment on chronic hyperplasia lesions in 49 patients with atopic dermatitis.

Crisaborole, as a phosphodiesterase 4 (PDE4) inhibitor (PDE4i), effectively inhibits inflammatory pathways, showing promising results in atopic dermatitis (AD), particularly in chronic hyperplasia lesions. Based on real-world data from China, this study assesses the effectiveness and safety of 2% PDE4i ointment as monotherapy for chronic hyperplastic AD lesions. A total of 49 AD patients aged 12 and above with chronic hyperplastic lesions and Investigator's Static Global Assessment scores of mild or moderate were enrolled. They received 2% PDE4i ointment twice daily until the lesions completely cleared. The effectiveness endpoints comprised the onset time of pruritus and lesion remission and the time of complete lesion clearance. PDE4i demonstrated high effectiveness with minimal irritation, notable improvement in hyperpigmentation, and early remission of pruritus and lesions. The response varied across age groups; elderly patients experienced quicker pruritus relief compared to adolescents and adults, while adolescents showed earlier lesion remission by about 3 days. No significant difference was observed across age groups in the time for complete lesion clearance. Additionally, AD duration (less or more than 3 years) did not significantly impact pruritus or lesion remission. PDE4i monotherapy is effective and safe for chronic hyperplasia lesions in AD across all age groups, and its effectiveness appears to be independent of AD duration.

Impact of Crisaborole in Treatment-Experienced Patients With Mild-to-Moderate Atopic Dermatitis.

Background: Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of patients with mild-to-moderate atopic dermatitis (AD). Objective: To assess the efficacy and safety of crisaborole in patients with AD who had received prior treatment with (a) corticosteroids (systemic or topical) or topical calcineurin inhibitors (TCIs) or (b) topical corticosteroids (TCSs) or TCIs or (c) who were treatment-naive (TN). Methods: This post hoc analysis comprised patients aged ≥2 years with mild-to-moderate AD. Patients were assigned (2:1) to receive crisaborole or vehicle twice daily for 28 days. Patient response was assessed with the Investigator's Static Global Assessment (ISGA), Dermatology Life Quality Index (DLQI), Children's Dermatology Life Quality Index (CDLQI), and Dermatitis Family Impact (DFI) tools. Safety was also assessed. Results: A significantly higher percentage of patients treated with crisaborole versus vehicle achieved ISGA success regardless of treatment history. Patients treated with crisaborole had significant reductions in DLQI, CDLQI, and DFI scores versus those who received vehicle regardless of treatment history, with the exception of DLQI and DFI scores in the TN group. Crisaborole was well tolerated in all subgroups. Conclusion: Crisaborole demonstrated a favorable efficacy and safety profile in both treatment-experienced and TN patients. ClinicalTrials.gov, NCT02118766 and NCT02118792.

Once-Daily Crisaborole Ointment, 2%, as a Long-Term Maintenance Treatment in Patients Aged ≥ 3 Months with Mild-to-Moderate Atopic Dermatitis: A 52-Week Clinical Study.

Topical treatments for atopic dermatitis (AD) used reactively often fail to achieve lasting disease control; many of these therapies are associated with safety concerns that limit long-term use. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD that has potential as a long-term maintenance therapy. The aim was to evaluate the long-term efficacy and safety of crisaborole once daily (QD) compared to vehicle QD as a maintenance therapy to reduce the incidence of flares in patients with AD who previously responded to crisaborole twice daily (BID). CrisADe CONTROL was a randomized, double-blind, vehicle-controlled, 52-week, phase III study of patients aged ≥3 months with mild-to-moderate AD involving ≥5% treatable body surface area. Eligible patients received crisaborole BID during an open-label run-in period of up to 8 weeks. Responders were randomly assigned in the double-blind maintenance period to receive either crisaborole QD or vehicle QD. Responders were defined as patients who achieved Investigator's Static Global Assessment (ISGA) success (ISGA score of 0 [clear] or 1 [almost clear] with a ≥ 2-grade improvement) and ≥ 50% improvement in Eczema Area and Severity Index total score (EASI-50) from baseline. Patients who experienced a flare (ISGA score ≥2) during the double-blind maintenance period switched to crisaborole BID for up to 12 weeks. During this period, patients were assessed every 4 weeks; if the flare resolved (ISGA score ≤ 1), patients resumed their assigned treatment. The primary endpoint was flare-free maintenance until onset of the first flare. Key secondary endpoints were number of flare-free days, number of flares, and maintenance of pruritus response until onset of the first flare. The incidence of treatment-emergent adverse events was also analyzed. Overall, 497 patients entered the open-label run-in period with crisaborole BID, of which 270 patients were randomized into the 52-week double-blind maintenance period of the study. Of the 270 patients, 135 were randomly assigned to the crisaborole QD group and 135 were randomly assigned to the vehicle QD group. Median time of flare-free maintenance was longer for patients who received crisaborole versus vehicle (111 vs 30 days, respectively; p = 0.0034). The mean number of flare-free days was higher for patients who received crisaborole versus vehicle (234.0 vs 199.4 days, respectively; p = 0.0346). The mean number of flares was lower for patients who received crisaborole versus vehicle (0.95 vs 1.36, respectively; p = 0.0042). No clear trend was observed in maintenance of pruritus response between crisaborole- and vehicle-treated patients. Crisaborole was well tolerated, with no new or unexpected safety findings when used as maintenance treatment. Crisaborole QD was effective and well tolerated for long-term maintenance treatment and flare reduction in adult and pediatric patients with mild-to-moderate AD. ClinicalTrials.gov, NCT04040192, 31 July 2019.

Efficacy and safety of crisaborole ointment in Chinese and Japanese patients aged ≥2 years with mild-to-moderate atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease with a significant impact on the overall wellbeing of patients and their families. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis in multiple countries. However, in the key pivotal trials, a low proportion of the overall patient population was Asian, therefore the safety and efficacy of crisaborole in the Asian population with atopic dermatitis remains unclear. CrisADe CLEAR was a multicenter, randomized, double-blind, vehicle-controlled, phase 3 study (NCT04360187) to assess the efficacy and safety of crisaborole ointment in Chinese and Japanese patients aged ≥2 years with mild-to-moderate atopic dermatitis involving ≥5% treatable body surface area. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. The primary endpoint was percentage change from baseline in the Eczema Area and Severity Index total score at day 29. Additional endpoints were improvement and success per Investigator's Static Global Assessment score at day 29 and change from baseline on the Peak Pruritus Numerical Rating Scale at week 4. Safety was assessed using rates of treatment emergent adverse events, serious adverse events, and clinically significant changes in vital signs and clinical laboratory parameters. Crisaborole-treated patients showed a significantly greater reduction versus vehicle in percentage change from baseline in Eczema Area and Severity Index total score at day 29 (P = 0.0002). Response rates for achievement of Investigator's Static Global Assessment improvement and success at day 29 were significantly higher for patients treated with crisaborole versus vehicle (P = 0.0124 and P = 0.0078, respectively). Crisaborole-treated patients showed a significantly greater reduction versus vehicle in change from baseline on the Peak Pruritus Numerical Rating Scale at week 4 (P = 0.0009). No new safety signals were identified. Treatment with crisaborole was effective and well tolerated in Chinese and Japanese patients with mild-to-moderate atopic dermatitis.

Clindamycin phosphate, tretinoin with benzoyl peroxide versus clindamycin phosphate and tretinoin combination without benzoyl peroxide for the treatment of acne vulgaris

Introduction: Acne vulgaris (AV) is a prevalent skin disorder among adolescents. Affects around 80–90% of adolescents in the Western population. The present study aimed to compare the therapeutic efficacy of Clindamycin phosphate (CLM), Tretinoin (TN) with Benzoyl peroxide (BP) versus clindamycin phosphate and tretinoin combination without Benzoyl peroxide for treatment of AV. Methodology: 250 patients with mild to moderate acne on the face were enrolled in the study and were divided into two groups; group I (n=125); apply CLM 1.2%, TN 0.025%gel with BP 3.75% gel and group II (n=125) apply only CLM 1.2% and TN 0.025% gel without BP 3.75% gel; once daily at night for 4 weeks. The change in acne lesions was recorded every 2 weekly follow-ups using the global acne grading system and non-inflammatory (NI-L), Inflammatory (I-L) lesions count and Investigator's Static Global Assessment grading. Results: The research involved 250 patients split into two groups: 125 patients in group I and 125 patients in group II. After 4 weeks, the group I had a higher mean percent decrease in non-inflammatory, inflammatory, and total lesion count than group II.

Subgroup Analysis of Crisaborole for Mild-to-Moderate Atopic Dermatitis in Children Aged 2 to

ObjectivesThis post hoc analysis of pooled data from two phase III studies (AD-301: NCT02118766; AD-302: NCT02118792) explored the efficacy and safety of crisaborole ointment, 2%, a nonsteroidal phosphodiesterase 4 inhibitor, for the treatment of mild-to-moderate atopic dermatitis (AD) in pediatric patients (aged 2 to < 18 years) only, stratified by baseline characteristics.MethodsPediatric patients with mild or moderate AD per Investigator’s Static Global Assessment (ISGA) and percentage of treatable body surface area (%BSA) ≥ 5 at baseline were assessed. Crisaborole or vehicle (2:1 randomization ratio) was applied twice daily for 28 days. Of the 1313 pediatric patients included in this study, 874 received crisaborole and 439 received vehicle. ISGA success was defined as clear (0) or almost clear (1) with ≥ 2-grade improvement from baseline. Efficacy and safety were stratified by age group, sex, baseline ISGA, baseline %BSA per published severity strata, and prior AD therapy.ResultsOverall, the proportions of crisaborole-treated and vehicle-treated pediatric patients with ISGA success at week 4 were 32.5 and 21.5%, respectively. ISGA success rates at day 29 (week 4) were generally higher in crisaborole-treated (21.9–38.1%) than vehicle-treated (15.7–26.9%) patients across subgroups. Rates of treatment-related application site pain were 2.4–10.1% for crisaborole-treated patients and 0.6–2.2% for vehicle-treated patients across subgroups. No new safety concerns were noted in any patient subgroup.ConclusionCrisaborole improved global disease severity and was reasonably well tolerated across all pediatric baseline characteristic subgroups. Application site discomfort was greater with crisaborole than with vehicle, but few patients discontinued treatment.Clinicaltrials.gov registration numbersNCT02118766; NCT02118792 (registration date: April 21, 2014).Supplementary InformationThe online version contains supplementary material available at 10.1007/s40272-021-00490-y.

Matching-Adjusted Indirect Comparison of Crisaborole Ointment 2% vs. Topical Calcineurin Inhibitors in the Treatment of Patients with Mild-to-Moderate Atopic Dermatitis

IntroductionCrisaborole topical ointment, 2%, is a nonsteroidal, topical anti-inflammatory phosphodiesterase-4 (PDE4) inhibitor that is approved for the treatment of mild-to-moderate atopic dermatitis (AD). The objective of the current analysis was to compare the efficacy of crisaborole 2% relative to pimecrolimus 1%, tacrolimus 0.03% and tacrolimus 0.1% in patients aged ≥ 2 years with mild-to-moderate AD by comparing improvement in Investigator’s Static Global Assessment scores ( (ISGA scores of 0/1 indicating “clear or almost clear”). ISGA was selected as the primary efficacy outcome given the US Food and Drug Administration’s recommendations on the use of ISGA for assessment of global severity in AD and to align with efficacy measurements in the crisaborole registration trials. Safety endpoints could not be analyzed due to differences in outcome definitions across studies.MethodsEfficacy of crisaborole was evaluated using individual patient data (IPD) from two pivotal phase III randomized controlled trials (RCTs), and efficacy of comparators was evaluated using published RCTs included in a previous network meta-analysis. Vehicle controls were not comparable due to differences in ingredients and population imbalance and, therefore, an unanchored matching-adjusted indirect comparison (MAIC) was used, which reweighted IPD for crisaborole to estimate absolute response in comparator populations.ResultsThe odds of achieving an improvement in ISGA score was higher with crisaborole 2% versus pimecrolimus 1% (odds ratio [OR] 2.03; 95% confidence interval [CI] 1.45–2.85; effective sample size = 627, reduced from 1021; p value < 0.001) and for crisaborole 2% versus tacrolimus 0.03% (OR 1.50; 95% CI 1.09–2.05; effective sample size = 311, reduced from 1021; p = 0.012).ConclusionThe unanchored MAIC suggests that the odds of achieving an improvement in ISGA score is greater with crisaborole 2% than with pimecrolimus 1% or tacrolimus 0.03% in patients aged ≥ 2 years with mild-to-moderate AD. These results are consistent with findings from the previously published network meta-analysis, which used a different methodology for performing indirect treatment comparisons.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00646-1.

Efficacy and safety of crisaborole in patients with mild-to-moderate atopic dermatitis and other atopic comorbidities.

Background: Crisaborole is a nonsteroidal anti-inflammatory phosphodiesterase 4 inhibitor that is approved for the treatment of patients with mild-to-moderate atopic dermatitis (AD); however, the efficacy and safety of crisaborole in patients with AD and other atopic comorbidities have not been investigated. Objective: This post hoc pooled analysis of the pivotal phase III studies (CrisADe CORE 1 and CORE 2) assessed the efficacy and safety of crisaborole versus vehicle in patients aged ≥ 2 years with mild-to-moderate AD and other atopic comorbidities. Methods: Patients with mild-to-moderate AD and a medical history of asthma, allergic rhinitis, or food allergies were identified. Efficacy assessments included the proportion of patients who achieved Investigator's Static Global Assessment (ISGA) success at day 29, ISGA clear or almost clear at day 29, and improvement in the Severity of Pruritus Scale score at week 4. Safety was assessed via treatment-emergent adverse events (TEAEs). Results: This analysis included 1522 patients (crisaborole, 1016; vehicle, 506); 26.2, 15.9, and 16.5% had a medical history of asthma, allergic rhinitis, and food allergies, respectively. The mean age was 12.2 years. A significantly greater proportion of patients treated with crisaborole achieved ISGA success at day 29 compared with patients treated with vehicle for most subgroups analyzed. Furthermore, a significantly greater proportion of patients treated with crisaborole achieved ISGA clear or almost clear at day 29 across all subgroups and demonstrated improvement in the Severity of Pruritus Scale score at week 4 versus patients treated with vehicle in most of the subgroups. Overall, most TEAEs were mild or moderate in severity; the most common treatment-related TEAE in patients with atopic comorbidities was application-site pain (crisaborole, 5.1%; vehicle, 1.7%). Conclusion: Crisaborole was efficacious and well tolerated in patients with mild-to-moderate AD and other atopic comorbidities, which suggested that crisaborole should be considered for the management of AD in this population. Clinical Trials NCT02118766 (CrisADe CORE 1) and NCT02118792 (CrisADe CORE 2), <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</ext-link>.

Efficacy and Safety Trends with Continuous, Long-Term Crisaborole Use in Patients Aged ≥ 2 Years with Mild-to-Moderate Atopic Dermatitis

IntroductionAtopic dermatitis (AD) is a chronic inflammatory skin disease often requiring long-term treatment. Crisaborole significantly improved global AD signs and symptoms in 28-day phase 3 studies of patients aged ≥ 2 years with mild-to-moderate AD (Investigator’s Static Global Assessment [ISGA] 2 or 3). A post hoc analysis of a long-term, open-label extension study was conducted to assess efficacy and safety trends of crisaborole in patients stratified by the number of initial consecutive crisaborole treatment cycles, defined as the number of treatment cycles completed before achievement of ISGA 0 (clear)/1 (almost clear).MethodsPatients completing phase 3 studies without drug-related safety issues that precluded further crisaborole treatment were analyzed. Patients with ISGA 0/1 at baseline (the end of a 28-day cycle) did not receive crisaborole for the next 28-day cycle (off-treatment), whereas patients with ISGA ≥ 2 received crisaborole for the next 28-day cycle (on-treatment). Patients were stratified by number of initial consecutive crisaborole treatment cycles. Efficacy was assessed by achievement and maintenance of ISGA 0/1, and safety was assessed by incidence of treatment-emergent adverse events (TEAEs) and treatment-related AEs (TRAEs).ResultsOverall, 418 patients were included in exclusive cohorts based on number of consecutive on-treatment cycles (1 on-treatment cycle, n = 133; 2 consecutive on-treatment cycles, n = 106; 3 consecutive on-treatment cycles, n = 106; 4 consecutive on-treatment cycles, n = 73). After one to four initial consecutive on-treatment cycles, 77.6, 76.3, 59.4, and 43.1% of patients, respectively, achieved ISGA 0/1. Of these patients, 49.5, 37.8, 44.4, and 45.2%, respectively, maintained ISGA 0/1 at the end of a 28-day cycle off-treatment. Incidence of TRAEs was 4.5, 4.7, 3.8, and 1.4% for patients receiving one to four consecutive on-treatment cycles, respectively. One patient discontinued because of AEs.ConclusionThese results support the efficacious and safe continuous, long-term use of crisaborole for the management of mild-to-moderate AD.Trial RegistrationClinicalTrials.gov: NCT02118766, NCT02118792. Video (MP4 1,47,130 kb)Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00584-y.

Novel cannabidiol aspartame combination treatment (JW-100) significantly reduces ISGA score in atopic dermatitis: Results from a randomized double-blinded placebo-controlled interventional study.

Atopic dermatitis (AD) is a common and chronic inflammatory skin disease that erupts periodically. Although the negative impact of the disorder on overall quality of life has been well established, new treatments for AD are still needed. Various studies have reported on cannabidiol's effectiveness in relieving pain and easing inflammation while not presenting major health risks. In this communication, we aim to demonstrate the effectiveness of a novel cannabidiol (CBD) and aspartame formulation, JW-100, in relieving signs and symptoms of AD. We conducted a double-blinded placebo-controlled interventional study randomizing patients to one of three treatment groups: JW-100 (CBD plus aspartame), CBD only, or placebo topical formulations. The Investigator's Static Global Assessment (ISGA) score was used to document any changes in AD resulting from the applied interventions at 14days. Fifty-seven patients completed the trial and were included in the final analysis. The ISGA score of the patients at baseline was 2.56, 2.24, and 2.24, for the JW-100, CBD, and placebo groups, respectively. After two weeks of treatment, the ISGA score reduced by 1.28, 0.81, and 0.71, for the JW-100, CBD, and placebo groups, respectively. The JW-100 cohorts demonstrated statistically significant ISGA score reduction (p=0.042). 50% of patients in the JW-100 group achieved ISGA score of clear or almost clear (0 or 1) with at least a 2-grade improvement from baseline after treatment (p=0.028). Only 20% and 15% of patients in the CBD only and placebo groups reported ISGA score of clear or almost clear (0 or 1). JW-100, a novel topical formulation containing CBD and aspartame, was demonstrated to produce statistically significant improvements in AD following 14days of topical application.

PDG2 Evaluating the Severity of Atopic Dermatitis (AD) in Children and Adults: Mapping of Investigator's Static Global Assessment (ISGA) to Eczema Area and Severity INDEX (EASI) in Phase 3 Studies of Crisaborole, 2%

Severity of AD was measured in 2 phase 3 US studies in patients aged ≥2 years using the Investigator’s Static Global Assessment (ISGA), a 5-point FDA-recommended scale from 0 (clear) to 4 (severe). The Eczema Area and Severity Index (EASI), a validated scale ranging from 0-72, is used globally to assess AD severity in clinical trials. The objective was to translate ISGA scores into EASI scores, thereby aiding in the interpretability of the ISGA. Mapping of ISGA to EASI scores was performed through 70,000 random simulations using published EASI severity strata for global severity states (Leshem Y et al., 2015; Chopra R et al., 2017). ISGA scores were mapped for pooled data from crisaborole, 2%, phase 3 trials CORE-1 (NCT02118766) and CORE-2 (NCT02118792), which evaluated patients aged ≥2 years with mild-to-moderate AD (crisaborole, n=1016; vehicle, n=506; 86% children). Least squares mean (LSM) percentage change from baseline (%CFB; where negative=improving, positive=worsening) in EASI and proportion of patients with 50%, 75%, and 90% improvement (EASI-50, EASI-75, and EASI-90) on day 29 were computed. At day 29, LSM (SE) for %CFB in mapped EASI from Leshem was −43.1% (4.6) (crisaborole) and −5.2% (8.4) (vehicle) (P<0.0001) and from Chopra was −26.3% (17) vs 45.2% (35) (P=0.0671). For proportion of patients with improvement, results for Leshem were: EASI-50, 68.8% (crisaborole) versus 54.0% (vehicle); EASI-75, 54.8% versus 40.5%; EASI-90, 38.9% versus 27.2%; P<0.0001 for each difference. Results for Chopra were: EASI-50, 72.1% (crisaborole) versus 57.6% (vehicle); EASI-75, 63.0% versus 47.8%; EASI-90, 55.0% versus 40.1%; P<0.0001 for each difference. Mapped EASI results were consistent with ISGA findings from the clinical trials. A limitation is that most patients in articles for EASI strata were adults. Mapping of ISGA to EASI scores was investigated using data from clinical trials to present results in terms of the EASI.

Improvement in disease severity and pruritus outcomes with crisaborole ointment, 2%, by baseline atopic dermatitis severity in children and adolescents with mild-to-moderate atopic dermatitis.

Background/ObjectivesCrisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild‐to‐moderate atopic dermatitis (AD). This pooled post hoc analysis of two phase 3 trials (NCT02118766, NCT02118792) assessed improvement and time to improvement in Investigator's Static Global Assessment (ISGA) and Severity of Pruritus Scale (SPS) outcomes in pediatric patients with mild‐to‐moderate AD.MethodsPatients aged ≥2 years were randomly assigned 2:1 to receive twice‐daily crisaborole or vehicle for 28 days. Patients aged 2‐17 years were pooled for this analysis. Proportions of patients and time to achieving ISGA success (clear [0] or almost clear [1] with ≥2‐grade improvement from baseline), ISGA clear/almost clear, ≥1‐grade improvement in ISGA, SPS success (SPS score ≤1 with ≥1‐grade improvement), or ≥1‐grade improvement in SPS score were analyzed and stratified by baseline ISGA.ResultsAt first postbaseline assessment (day 8), significantly higher proportions of crisaborole‐ than vehicle‐treated patients achieved ISGA success, ISGA clear/almost clear, ≥1‐grade ISGA improvement, SPS success, or ≥1‐grade improvement in SPS regardless of baseline ISGA. Differences were significantly greater over time for all outcomes for patients with moderate baseline ISGA and numerically greater for those with mild baseline ISGA. Median times to ISGA and SPS outcomes were shorter for crisaborole versus vehicle.ConclusionImprovement in ISGA and SPS outcomes were observed with crisaborole in pediatric patients with mild‐to‐moderate baseline AD.

Evaluating the Efficacy of Crisaborole Using the Atopic Dermatitis Severity Index and Percentage of Affected Body Surface Area.

Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. This post hoc analysis pools results from 2 phase 3 studies (ClinicalTrials.gov, NCT02118766 [AD-301]; NCT02118792 [AD-302]) to evaluate crisaborole efficacy in patients ≥ 2 years with mild-to-moderate atopic dermatitis (per Investigator’s Static Global Assessment) using the Atopic Dermatitis Severity Index (ADSI) and percentage of treatable body surface area (%BSA). Patients were randomly assigned 2:1 to receive crisaborole (n = 1,016) or vehicle (n = 506) twice daily for 28 days. ADSI scores were the sum of pruritus, erythema, exudation, excoriation, and lichenification severity scores, each graded on a 4-point scale from none (0) to severe (3). Respective mean changes in ADSI score and %BSA at day 29 were (crisaborole vs. vehicle) −3.52 versus −2.42 (p < 0.0001) and –7.43 versus –4.44 (p < 0.0001). Crisaborole was effective in treating mild-to-moderate atopic dermatitis based on ADSI and %BSA.

PDG6 A SYSTEMATIC LITERATURE REVIEW AND NETWORK META-ANALYSIS (NMA) OF CRISABOROLE 2% OINTMENT FOR THE TREATMENT OF MILD-TO-MODERATE ATOPIC DERMATITIS (AD)

To evaluate the comparative efficacy of crisaborole 2% versus other topical pharmacologic therapies among children (≥ 2 years) and adults with mild-to-moderate AD. MEDLINE, Embase, Cochrane, and the Database of Abstracts of Reviews of Effects were searched from inception to 03/04/2019, for randomized clinical trials reporting the efficacy of topical calcineurin inhibitors, topical corticosteroids, or crisaborole. The outcome of interest was treatment success: achieving an Investigator's Static Global Assessment (ISGA) score of 0-1 (clear or almost clear AD) at 28-43 days, with 28-29 day data used preferentially. A Bayesian model adjusting for baseline risk (variation in vehicle response rates) was used; in addition, the model included class effects (tacrolimus and pimecrolimus in one class; crisaborole in its own class). A complementary log-log model accounted for differential follow-up times. 9 RCTs were included in the NMA. The population included both pediatric and adult patients. Patients on crisaborole 2%, tacrolimus 0.03% and 0.1% were significantly more likely to achieve treatment success at 28-43 days versus vehicle with the largest point estimate observed for the crisaborole 2% comparison (hazard ratio [HR]: 2.07 [95% CrI: 1.76; 2.36]). Patients on crisaborole 2% were more likely to achieve treatment success versus pimecrolimus 1% [HR: 1.62 [95% CrI: 1.04; 2.48]. While the point estimates favored crisaborole 2%, there were no significant differences between crisaborole 2%, tacrolimus 0.03% and 0.1% with respect to treatment success at 28-43 days. The baseline risk model found that the relationship between vehicle rate and relative treatment effect versus vehicle was highly significant (slope = -0.89 [95% CrI: -1.26; -0.47]), making results versus vehicle highly sensitive to vehicle rate chosen (not observed versus other active treatments). Crisaborole 2% was superior to vehicle and pimecrolimus 1%, and comparable to tacrolimus 0.03% and 0.1% in achieving treatment success at 28-43 days.

Topical Retinoids in Acne Vulgaris: A Systematic Review

Topical retinoids are a first-line treatment for acne vulgaris. This systematic review aims to evaluate the efficacy, safety, and tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris. A PubMed and Embase search was conducted using the search terms 'adapalene,' 'tretinoin,' 'tazarotene,' and 'acne vulgaris.' Selection of articles fit the following inclusion criteria: clinical trials evaluating both efficacy and safety/tolerability of topical retinoids approved in the United States for the treatment of acne vulgaris and published between January 1, 2008 and September 1, 2018. Exclusion criteria included clinical trials involving 20 subjects or fewer, subjects under 12years of age, and topical retinoid combination therapies with moisturizers or aloe vera. Of 424 search results found, a total of 54 clinical trials were chosen based on selection criteria. Topical retinoids are superior to vehicle in improving Investigator Global Assessment and Investigator's Static Global Assessment (24.1-28.8% and 13.3-17.3%, respectively; p < 0.001). A topical retinoid combined with benzoyl peroxide led to IGA improvement compared with vehicle (26.1-34.9% vs 7-11.8%; p < 0.001) at Week 12. Topical retinoid plus an oral antibiotic was superior to vehicle in reducing lesion counts (64-78.9% vs 41-56.8%, p < 0.001). There was no significant difference in efficacy between tretinoin and tazarotene. Tretinoin 0.05% resulted in 62% of patients experiencing AEs compared with adapalene 0.1% (19%) and adapalene 0.3% (40%). More patients receiving adapalene were tolerant of the AEs compared with tazarotene (55.4% vs 24.4%; p < 0.0012). Topical retinoids are safe and efficacious for the treatment of acne vulgaris. They should be used in combination with benzoyl peroxide to optimize results in patients. The differences in efficacy of topical retinoids appears minor; therefore, the type of topical retinoid is not as important as choosing a particular strength of topical retinoid and combining it with an antimicrobial agent. Adapalene has a superior tolerability profile amongst topical retinoids.

Crisaborole Ointment Improves Quality of Life of Patients with Mild to Moderate Atopic Dermatitis and Their Families

IntroductionThe impact of crisaborole ointment, a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD), on quality of life (QoL) was assessed in two identically designed phase 3 studies (AD-301: NCT02118766; AD-302: NCT02118792, both at http://www.clinicaltrials.gov).MethodsIn both studies, patients aged ≥ 2 years with mild to moderate AD per the Investigator’s Static Global Assessment were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. QoL was assessed using the Children’s Dermatology Life Quality Index (CDLQI) (2–15 years), the Dermatology Life Quality Index (DLQI) (≥ 16 years), and the Dermatitis Family Impact Questionnaire (DFI) (parents/caregivers/family of patients aged 2–17 years). Established QoL score severity bands provided clinical context.ResultsGreater mean improvement in QoL was observed in crisaborole-treated patients than in vehicle-treated patients at day 29 [mean change from baseline (∆BL), CDLQI: − 4.6 vs. − 3.0; P < 0.001; DLQI: − 5.2 vs. − 3.5; P = 0.015]. At baseline, more than half the patients had a “moderate effect” or higher of AD on QoL. At day 29, there was a trend toward more crisaborole- than vehicle-treated patients having “small effect” to “no effect”, The QoL of parents/caregivers/family improved more for crisaborole-treated than for vehicle-treated patients (∆BL, DFI: − 3.7 vs. − 2.7; P = 0.003).ConclusionCrisaborole treatment results in clinically meaningful improvement in QoL for patients and their parents/caregivers/families.Trial RegistrationAD-301: http://www.clinicaltrials.gov, NCT02118766; AD-302: http://www.clinicaltrials.gov, NCT02118792.FundingAnacor Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc., New York, NY.

Magnitude of benefit for topical crisaborole in the treatment of atopic dermatitis in children and adults does not look promising: a critical appraisal.

To assess the efficacy and safety of crisaborole ointment, a phosphodiesterase 4 inhibitor, for the treatment of mild or moderate atopic dermatitis (AD) in two phase III studies (AD-301 and AD-302). Two identically designed multicentre, double-blind randomized controlled trials were conducted in the U.S.A. Participants were randomized 2:1 to receive crisaborole or vehicle treatment. In total 47 and 42 investigational centres were identified for AD-301 and AD-302, respectively. Inclusion criteria were identified as age ≥ 2years, clinical diagnosis of AD (as per the Hanifin and Rajka criteria), ≥ 5% body surface area involvement, and baseline Investigator's Static Global Assessment (ISGA) mild or moderate. Exclusion criteria included previous use of biologics or systemic corticosteroids (within the last 28days) or a topical calcineurin inhibitor/corticosteroid (within the last 14days), and active skin infection. Participants were instructed to apply the study drug twice daily to all lesions identified at baseline, and all new lesions identified after day 1 (with weekly review of application instructions). Bland emollients were permitted to be used on skin not treated with the study drug. The primary outcome was defined as ISGA clear or almost clear at day 29, with a 2-grade or more improvement from baseline. Secondary outcomes included the proportion of patients with an ISGA score of clear or almost clear at day 29, and time to success in ISGA score. Additional outcomes included pruritus severity and signs of AD (erythema, exudation, excoriation, induration/papulation and lichenification), and were measured on a 4-point scale (none, mild, moderate, severe). Adverse events were also recorded. More participants in the crisaborole-treated group achieved ISGA scores of clear or almost clear with ≥ 2-grade improvement than in the vehicle-treated group (AD-301, 32·8% vs. 25·4%, P=0·38; AD-302, 31·4% vs. 18·0%, P<0·001). Greater percentages of clear and almost clear scores were observed in the treatment groups (51·7% vs. 40·6%, P=0·005; 48·5% vs. 29·7%; P<0·001), as well as earlier success in ISGA score and improvement in pruritus (P≤0·001). No serious treatment-related adverse events were identified. Based on the study results, the authors suggest that crisaborole is a safe treatment that improves disease severity, pruritus and clinical signs associated with AD.