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The 2016 edition of the annual MauiDerm meeting had a wide variety of ical and scientific data presented not only at the podium, but in its poster essions as well. A wide range of clinically relevant material was presented in oster format. For those of you who were not on hand to review the posters and discuss them with their authors, we have compiled and indexed selected posters from the 2016 meeting. It is my hope that you will find the posters informative and thought provoking.
For an alphabetical index organized by poster title or author, please see page 22 of this supplement.
Efficacy and Safety of Once-Daily Dapsone Gel 7.5% for Treatment of Adolescents and Adults with Acne Vulgaris: First of Two Identically Designed, Large, Multicenter, Randomized, Placebo-Controlled Trials
Presenters: 1Linda F. Stein Gold, MD; 2Michael T. Jarratt, MD; 3Alicia D. Bucko, DO; 4Steven K. Grekin, DO; 5Joshua M. Berlin, MD; 6Michael Bukhalo, MD; 7Jonathan S. Weiss, MD; 8David Berk, MD; 8Joan-En Chang-Lin, PhD; 8Vince Lin, PhD; 8Alexandre Kaoukhov, MD
Affiliations: 1Henry Ford Medical Center, Detroit, MI; 2DermResearch, Inc., Austin, TX; 3Academic Dermatology Associates, Albuquerque, NM; 4Grekin Skin Institute, Warren, MI; 5Dermatology Associates, PA, of the Palm Beaches, Boynton Beach, FL; 6Altman Dermatology Associates, Arlington Heights, IL; 7Gwinnett Dermatology, PC, Snellville, GA; 8Allergan plc, Irvine, CA
Objective: Treatment of acne vulgaris with dapsone gel 5% requires twice-daily dosing. This first of two studies assessed efficacy and safety of a once-daily formulation of dapsone gel 7.5% (DAP) versus vehicle (VEH) over 12 weeks in patients with acne.
Methods: This randomized, double-blind, multicenter study enrolled 2,102 patients (≥12y) with 20 to 50 inflammatory lesions, 30 to 100 noninflammatory lesions, and a moderate grade (3) on the Global Acne Assessment Score (GAAS). Investigator-assessed efficacy measures at Week 12 were GAAS success rate (GAAS = 0 or 1) and percent change from baseline in inflammatory, noninflammatory, and total lesions.
Results: At Week 12, for DAP versus VEH, respectively, GAAS success rate was 29.9 percent versus 21.2 percent, mean inflammatory lesions decreased by 55.5 percent versus 49.0 percent, mean noninflammatory lesions decreased by 44.4 percent versus 38.4 percent, and mean total lesions decreased by 48.7 percent versus 42.4 percent (all P<0.001). AE incidence was 19.1 percent for DAP and 20.6 percent for VEH. Most AEs in both groups were mild to moderate in severity. Most patients receiving DAP and VEH had a severity rating of “none” on stinging/burning, dryness, scaling, and erythema scales at all time points.
Conclusion: Dapsone gel 7.5% applied topically once daily is an effective, safe, and well-tolerated topical acne treatment.
Efficacy and Safety of Once-Daily Dapsone Gel 7.5% for Treatment of Adolescents and Adults with Acne Vulgaris: Second of Two Identically Designed, Large, Multicenter, Randomized, Placebo-Controlled Trials
Presenters: 1Lawrence F. Eichenfield, MD; 2Ted Lain, MD; 3Ellen H. Frankel, MD; 4Terry M. Jones, MD; 5Joan-En Chang-Lin, PhD; 5David Berk, MD; 5Shiling Ruan, PhD; 5Alexandre Kaoukhov, MD
Affiliations: 1University of California, San Diego and Rady Children’s Hospital, San Diego, CA; 2Private Practice, Austin, TX; 3RISkinDoc, Cranston, RI; 4Dermatologe, Bryan, TX; 5Allergan plc, Irvine, CA
Purpose: Acne treatment with dapsone gel 5% requires twice-daily dosing. This second of two studies assessed efficacy and safety of a new once-daily formulation of dapsone gel 7.5% (DAP) versus vehicle (VEH) over 12 weeks in patients with moderate acne.
Methods: This randomized, double-blind, multicenter study enrolled 2,238 patients (≥12y) with 20 to 50 inflammatory lesions, 30 to 100 noninflammatory lesions, and a moderate grade (3) on the Global Acne Assessment Score (GAAS). Investigator-assessed efficacy measures at Week 12 were GAAS success rate (GAAS=0 or 1) and percent change from baseline in inflammatory, noninflammatory, and total lesions.
Results: At Week 12, for DAP versus VEH, respectively, GAAS success rate was 29.8 percent versus 20.9 percent mean inflammatory lesions decreased by 53.8 percent versus 47.3 percent, mean noninflammatory lesions decreased by 45.9 percent versus 40.4 percent and mean total lesions decreased by 48.9 percent versus 43.2 percent (all P<0.001). AE incidence was 17.6 percent for DAP and 17.1 percent for VEH. Most AEs in both groups were mild to moderate in severity. Most patients receiving DAP and VEH had a severity rating of “none” for stinging/burning, dryness, scaling, and erythema scales at all time points.
Conclusion: Dapsone gel 7.5% applied topically once daily is an effective, safe, and well-tolerated topical acne treatment.
Age and Gender as Predictors of Treatment Outcomes with Once-Daily Dapsone 7.5% Topical Gel for Acne Vulgaris
Presenters: 1Zoe Diana Draelos, MD; 2David A. Rodriguez, MD; 3Steven E. Kempers, MD; 4Suzanne Bruce, MD; 5Marina I. Peredo, MD, PC; 6Jeanine Downie, MD; 7Joan-En Chang-Lin, PhD; 7David R. Berk, MD; 7Shiling Ruan, PhD;7Alexandre Kaoukhov, MD
Affiliations: 1Dermatology Consulting Services, High Point, NC; 2Dermatology Associates and Research, Coral Gables, FL; 3Associated Skin Care Specialists, Fridley, MN; 4Suzanne Bruce and Associates, PA, Houston, TX; 5Private Practice, Smithtown, NY; 6Image Dermatology, Montclair, NJ; 7Allergan, Inc., Irvine, CA
Introduction: A new, once-daily topical dapsone gel 7.5% (DAP) was developed to simplify topical anti-inflammatory acne treatment relative to twice-daily Aczone® Gel 5%. Pooled data from two identical Phase 3 randomized, double-blind, vehicle (VEH)-controlled trials of DAP for acne assessed the effects of age, gender, and race on treatment outcomes.
Methods: Patients with moderate acne (20–50 inflammatory lesions, 30– 100 noninflammatory lesions, and Global Acne Assessment Score [GAAS] of 3) were randomized to once-daily treatment for 12 weeks with DAP or VEH. Co-primary efficacy measures were GAAS responder rates (GAAS-RR; no or minimal lesions at Week 12) and changes in inflammatory and noninflammatory lesions. In the pooled analysis, efficacy variables were analyzed by age group (12–17y [adolescents] and ≥18y [adults]), gender, and race (Caucasian and non-Caucasian).
Results: Overall, the intent-to-treat analysis included 4,340 patients (DAP, n=2,162; VEH, n=2,178); 50.5% were adults, 55.8% were female, and 57.4% were Caucasian. At baseline, all but one had a GAAS of 3; mean inflammatory and noninflammatory lesion count was 29.4 and 47.2, respectively. Significant improvements (P<0.001) for DAP versus VEH on co-primary outcomes were observed at Week 12. GAAS-RR was significantly greater (P<0.001) for DAP (29.8%) versus VEH (21.1%). Significantly greater (P<0.001) percent reductions for DAP versus VEH, respectively, were seen in inflammatory (-54.6% vs. -48.1%), noninflammatory (-45.1% vs. -39.4%), and total (-48.8% vs. -42.8%) lesions. In all subgroups, greater improvements with DAP versus VEH were noted in GAAS-RR and change in all lesion counts. Greater improvements in all outcome measures were seen in adults versus adolescents and in females versus males; results for Caucasians and non-Caucasians were similar. For GAAS-RR, DAP treatment (P<0.001), age (P<0.001), and gender (P=0.029) were significant predictors of improvement, based on logistic regression. For inflammatory and noninflammatory lesions, respectively, DAP treatment (P<0.001 for both), age (P<0.001 for both), and gender (P<0.001 and P≤0.025) were significant predictors of improvement, based on analysis of covariance. Incidence of adverse events was similar between subgroups of age, gender, and race and between treatment groups.
Conclusion: Once-daily DAP improved acne severity versus VEH for all subgroups. Improvements were greater in adults versus adolescents and in females versus males. Results were similar for Caucasians and non-Caucasians.
Activity of Dapsone versus Community and Hospital Bacterial Pathogens from the CANWARD Study
Presenters: 1George G. Zhanel, MD; 2James Q. Del Rosso, DO
Affiliations: 1Department of Medical Microbiology and Infectious Diseases College of Medicine, Faculty of Health Sciences, University of Manitoba and Canadian Antimicrobial Resistance Alliance, Winnipeg, Canada; 2Touro University College of Oseopathic Medicine, Henderson, NV, and Las Vegas Skin and Cancer Clinics/West Dermatology Group, Las Vegas, NV
Background: Topical dapsone gel is a sulfone antibiotic approved for acne treatment. No microbiology studies were conducted during dapsone gel clinical trials and it is unclear whether 1) dapsone has antimicrobial activity with clinical relevance in dermatology and 2) dapsone could affect the normal microbiome of facial skin where it is usually applied. This study assessed in vitro activity of dapsone versus Gram-positive and Gram-negative bacterial pathogens obtained from patients with infections.
Methods: CANWARD is a national surveillance system of antibiotic resistance in Canada. Antimicrobial susceptibility was assessed using CLSI broth microdilution method. Fifteen centers collected 3,511 isolates from blood, respiratory tract, urine, and wounds. MIC panels were prepared at the Health Sciences Centre in Winnipeg, Canada.
Results: Dapsone demonstrated relatively poor activity versus Gram-negative bacilli with most MIC50, MIC90 in the range of 512µg/mL and >512μg/mL, respectively. In contrast, dapsone demonstrated activity versus Gram-positive cocci, such as Staphylococcus, Streptococcus, and Enterococcus: several strains of S. epidermidis had MICs of 32 and 64μg/mL; there were strains of E. faecalis with MICs of 8, 16, 32, and 64μg/mL; and several strains of S. agalactiae and S. pyogenes demonstrated dapsone MICs of 4 to 64μg/mL.
Conclusion: Dapsone has demonstrated antimicrobial activity in vitro. Whether this activity is part of the mechanism of action of topical dapsone in acne remains unknown. There are few cutaneous pharmacokinetic data including skin concentration data in the literature about dapsone; however, topical dapsone as a 2% nanoemulsion has shown very high (1196–3837.34μg/cm2) local skin concentrations. At these levels, topical dapsone would be expected to affect the skin flora of patients with acne (especially Gram-positive cocci, such as Staphylococcus and Streptococcus). These concentrations are multiple times higher (20x–1000x) than the dapsone MICs found of many MSSA, MRSA, S. epidermidis, S. agalactiae and S. pyogenes; any of which may be present on the skin of acne patients. Whether this results in resistance to dapsone (i.e., in Gram-positive cocci, such as Staphylococcus and Streptococcus) or more importantly results in resistance to chemically unrelated antimicrobials is currently unknown.
Evolution of Acne Assessments and Impact on Acne Medications: An Evolving, Imperfect Paradigm
Presenters: 1Linda Stein Gold, MD; 2Jerry Tan, MD; 3Leon Kircik, MD; 4Marie-Jose Rueda, MD
Affiliations: 1Department of Dermatology, Henry Ford Hospital, Detroit, MI; 2University of Western Ontario and Windsor Clinical Research Inc., Ontario, Canada; 3Indiana University Medical Center, Indianapolis, IN; 4Galderma Laboratories, L.P., Fort Worth, TX
Background: Outcomes for success in acne trials include statistically significant differences from baseline between treatment arms in lesion counts (comedonal, inflammatory, and/or total) and in categorical improvement in investigator global assessments (IGA). However, IGA scales are not standardized and there have been important differences in clinical trial endpoints..
Objectives: We evaluated differences in outcome measures and definition of success in acne trials and their impact on FDA approval and indications for acne medications.
Methods: Review of acne clinical trial literature, prescribing information, and regulatory guidelines for currently approved acne medications in the United States.
Results: The impression of overall acne severity is subjective and arises from a composite of lesion size/density/type plus lesion distribution and intensity of involvement at affected sites. Numerous IGA scales exist, which are similar on cursory evaluation, but have a number of important variations. Scales vary in number of categories (4–7), inclusion of skin discoloration (erythema present or not), guidance about area of involvement (e.g., <half, >half, whole face), or overall quantity of lesions present (rare, some, few, many). One scale defines “clear” as including rare open and closed comedones. Finally, most scales mix inflammatory and noninflammatory lesions, yet it is very uncommon for these lesions to respond to an acne therapy in the same fashion over the same time frame. There are also differences in definitions of global success: Two grade improvement or achievement of clear/almost clear. Outcome success may not be accurately translated into corresponding terminology for indications, as most currently approved acne drugs are indicated in the United States “for treatment of acne vulgaris,” which at times is independent of efficacy shown on specific lesion types and inclusion severity in clinical trials.
Conclusion: Variability in investigator global assessment scales and definitions of success confound comparison of acne trial results. Harmonization and standardization of these factors will facilitate meta-analytics and treatment selection in patient care. Outcome measure success has not consistently been incorporated into acne medication indications.
ATX-101 (Deoxycholic Acid Injection) is Safe and Effective in Men: Results from a Pooled Analysis of the REFINE Trials
Presenters: 1,2Vince Bertucci; 3Jean Carruthers; 4Joel Schlessinger; 5Todd M. Gross; 5Paul F. Lizzul; 5,6Frederick C. Beddingfield, III; 5Christine Somogyi
Affiliations: 1Division of Dermatology, University of Toronto, Toronto, ON, Canada; 2Bertucci MedSpa, Woodbridge, ON, Canada; 3Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada; 4Skin Specialists, P.C., Omaha, NE; 5Allergan plc, Irvine, CA; 6David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Background: ATX-101 (deoxycholic acid injection) is a first-in-class injectable treatment for submental fat (SMF) reduction. Because a strong chin and defined jawline are often associated with authority, self-confidence, and trustworthiness in men, and because submental fullness can give the appearance of being overweight and/or older, this new injectable treatment may be of interest to men. This post-hoc analysis examined the efficacy and safety of ATX-101 in men who participated in the Phase 3 REFINE trials.
Methods: REFINE-1 (NCT01542034) and REFINE-2 (NCT01546142) were identical double-blind, placebo-controlled trials conducted in the United States and Canada. Adults with moderate (grade 2) or severe (grade 3) SMF (based on both investigator and subject assessment using the Clinician-Reported SMF Rating Scale [CR-SMFRS] and Patient-Reported SMF Rating Scale [PR-SMFRS], respectively) who were dissatisfied with their submental region were randomized to ATX-101 2mg/cm2 or placebo for up to six treatments. The co-primary endpoints, composite ≥1-grade and ≥2-grade response based on both CR-SMFRS and PR-SMFRS were evaluated at 12 weeks after last treatment. Secondary endpoints were change in the psychological impact of SMF (using the Patient-Reported SMF Impact Scale [PR-SMFIS]) and percentage achieving a prespecified reduction in submental volume by magnetic resonance imaging (MRI) in a subset of subjects. Satisfaction with the appearance of their face/chin and with treatment were assessed using the Subject Self-Rating Scale (SSRS) and Subject Global Question (SGQ-3), respectively.
Results: Of the 1,022 subjects enrolled in the REFINE trials, 156 (15.3%) were men (ATX-101, n=80; placebo, n=76). The mean (SD) age of the men was 47.0 (10.5) years with mean (SD) body mass index of 29.6 (3.5) kg/m2. Overall, 91.7 percent of men were white, 60.3 percent were CR-SMFRS grade 3, 35.9 percent were PR-SMFRS grade 3, and 74.4 percent were Fitzpatrick skin type I–III. The co-primary endpoints (composite ≥1-grade and ≥2-grade response) in men receiving ATX-101/placebo were: 64.4%/8.6% (p<0.001) and 9.6%/0 (p=0.014), respectively. Overall, 32.5 percent of ATX-101–treated men were MRI responders versus 2.9 percent of placebo-treated men (p<0.001). At baseline, men demonstrated psychological impact from their SMF, with PR-SMFIS scores of 6.9 and 6.8 (10=most impacted) in the ATX-101 and placebo groups, respectively. The mean change from baseline in PR-SMFIS at 12 weeks after last treatment was -3.0/-0.9, respectively (p<0.001). Most men were satisfied with their face/chin and treatment; 79.2 percent of ATX-101–treated subjects versus 22.9 percent of placebo-treated subjects were SSRS responders (p<0.001) and 71.4 percent versus 24.3 percent, respectively, were satisfied with treatment based on SGQ-3 (p<0.001). Overall, 96.3 percent of ATX-101–treated men and 78.9 percent of placebo-treated men reported an adverse event (AE); most AEs were localized to the treatment area, mild/moderate, and transient. The most common AEs in men receiving ATX-101/placebo were: edema (swelling), 90.0%/38.2%; anesthesia (numbness), 75.0%/2.6%; bruising (hematoma), 67.5%/42.1%; and pain, 63.8%/22.4%.
Conclusion: This post-hoc analysis of pooled REFINE data illustrates that ATX-101 effectively reduced SMF in men with ≥50-percent reduction in the psychological impact of SMF. Importantly, men were satisfied with their face/chin and with treatment. Overall, the ATX-101 treatment effect and safety profile observed in men was similar to that seen in women.
Changes in Skin Laxity Among Responders to ATX-101 (Deoxycholic Acid Injection) in the REFINE Trials
Presenters: 1Sabrina Fabi; 2Zoe Draelos; 3,4Steven H. Dayan; 5Todd M. Gross; 5Paul F. Lizzul; 5,6Frederick C. Beddingfield, III; 5Christine Somogyi
Affiliations: 1Private practice, San Diego, CA; 2Private practice, High Point, NC; 3University of Illinois, Chicago, IL; 4Private practice (SDMD), Chicago, IL; 5Allergan plc, Irvine, CA; 6David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Background: ATX-101(deoxycholic acid injection) was recently approved as a pharmacologic treatment for submental fat (SMF) reduction. When injected into subcutaneous fat, ATX-101 causes adipocytolysis (targeted destruction of fat cells) and an expected local tissue response which may involve collagen production (neocollagenesis). Data from clinical trials, including the two Phase 3 REFINE trials, demonstrated that ATX-101 significantly reduced SMF based on investigator and subject assessment as well as objective assessment via magnetic resonance imaging (MRI; evaluated in a subset of subjects). In a pooled analysis of the REFINE data, 68.2 percent of ATX-101–treated subjects and 20.5 percent of placebo-treated subjects (p<0.001) had a composite ≥1-grade response based on both investigator and subject evaluation. The MRI response rate (prespecified reduction in submental volume) was 43.3 percent and 5.3 percent in ATX-101–treated and placebo-treated subjects, respectively (p<0.001). A composite ≥2-grade response based on both investigator and subject evaluation was seen in 16.0 percent and 1.5 percent of subjects, respectively (p<0.001). In theory, SMF reduction could result in worsened skin laxity, as seen in some patients undergoing liposuction for SMF removal. However, skin laxity was unchanged or improved in 93.4 percent of ATX-101–treated subjects in the REFINE trials despite significant SMF reductions. To further explore the effect of SMF reduction with ATX-101 treatment on skin laxity, a post-hoc analysis was conducted to evaluate the change in skin laxity among treatment responders in the REFINE trials.
Methods: REFINE-1 and REFINE-2 were identical randomized, double-blind, placebo-controlled trials (NCT01542034 and NCT01546142). Adults with moderate or severe SMF (based on both investigator and subject assessment) who were dissatisfied with their submental region were enrolled. Skin laxity was assessed as a safety measure using the 4-point Submental Skin Laxity Grade (SMSLG) scale (1=none) and subjects with severe skin laxity were excluded.
Results: Among ATX-101-treated subjects with a composite ≥1-grade response (n=328), skin laxity was improved in 22.9 percent, unchanged in 70.1 percent, and worse in 7.0 percent. In ATX-101–treated MRI responders (n=86), skin laxity was improved in 27.9 percent, unchanged in 65.1 percent, and worse in 7.0 percent. In ATX-101–treated subjects who achieved a composite ≥2-grade response (n=79), skin laxity was improved in 24.1 percent, unchanged in 70.9 percent, and worse in 5.1 percent. In placebo-treated subjects with a composite ≥1-grade response (n=95), skin laxity was improved in 33.7 percent, unchanged in 61.1 percent, and worse in 5.3 percent. Too few placebo-treated subjects achieved a MRI response or composite ≥2-grade response for meaningful assessment of skin laxity.
Conclusion: In ATX-101-treated subjects from the REFINE trials who responded to treatment (regardless of the efficacy measure), skin laxity infrequently worsened, and in most subjects was unchanged or improved. Importantly, a rating of unchanged or improved occurred in the setting of SMF volume loss wherein one might expect worsening of skin laxity. We hypothesize that the controlled inflammatory response following ATX-101 treatment may induce neocollagenesis, which could play a role in skin retracting as SMF is reduced. The multiple injections used in the treatment procedure may also have contributed a modest degree to improvements in skin laxity in both treatment groups.
Safety and Efficacy of ATX-101 (Deoxycholic Acid Injection) for Reduction of Submental Fat: Results from a Multicenter, Open-Label Phase 3b Trial
Presenters: 1Kenneth R. Beer; 2,3Susan H. Weinkle; 4,5Sue Ellen Cox; 6Mark G. Rubin; 7Jeffrey M. Adelglass; 8Paul F. Lizzul; 8Todd M. Gross; 8,9Frederick C. Beddingfield, III; 8Christine Somogyi
Affiliations: 1Beer Surgical, Aesthetic and General Dermatology, West Palm Beach, FL; 2University of South Florida, Tampa, FL; 3Private Practice, Bradenton, FL; 4University of North Carolina, Chapel Hill, Chapel Hill, NC; 5Aesthetic Solutions, Chapel Hill, NC; 6Lasky Skin Center, Beverly Hills, CA; 7SKINTASTIC Medical & Surgical Rejuvenation Center, Plano, TX; 8Allergan plc, Irvine, CA; 9David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
Background: ATX-101 (deoxycholic acid injection) was recently approved in the United States and Canada as an injectable treatment for submental fat (SMF) reduction. This Phase 3b trial (NCT01426373) evaluated the safety and efficacy of ATX-101 in subjects followed for up to 12 months after last treatment.
Methods: Overall, 165 adults with SMF graded as moderate to extreme on validated Clinician- and Patient-Reported SMF Rating Scales (CR-SMFRS and PR-SMFRS, respectively) were enrolled. Subjects received up to a maximum of six treatments of ATX-101 (2mg/cm2). Efficacy endpoints, evaluated at 12 weeks and 12 months after last treatment, included percent of subjects who achieved a ≥1-grade improvement in SMF severity based on CR-SMFRS or PR-SMFRS (CR-1 or PR-1 response); mean reduction in the psychological impact of SMF (assessed using the Patient-Reported Submental Fat Impact Scale [PR-SMFIS]); mean percent reduction in SMF via calipers; and percent of subjects satisfied with their face/chin (assessed using the Subject Self-Rating Scale [SSRS]). Safety was monitored, including spontaneous adverse event (AE) reports and skin laxity (using the Submental Skin Laxity Grading [SMSLG] Scale). Impact of treatment on work and social/leisure activities was evaluated by subject questionnaire.
Results: At 12 weeks after last treatment, 87 percent of subjects achieved a CR-1 response and 84 percent achieved a PR-1 response; of these responders, 90 percent and 81 percent maintained their CR-1 and PR-1 response, respectively, at 12 months after last treatment. At baseline, subjects reported marked psychological impact of SMF (mean PR-SMFIS: 7.0/10 [10=worst impact]). The psychological impact of SMF was reduced by 61 percent at 12 weeks after last treatment (mean change from baseline:-4.3), which was maintained at 12 months after last treatment (-4.2). By caliper assessments, SMF was reduced by 27 percent at 12 weeks after last treatment; this reduction was maintained at 12 months after last treatment (31%). At 12 weeks after last treatment, 88 percent of subjects were satisfied with their face/chin; 85 percent were still satisfied at 12 months after last treatment. AEs were reported in 97 percent of subjects; most were related to the treatment area (bruising, numbness, pain, swelling), mild/moderate, transient, and resolved. The incidence of AEs decreased over subsequent treatments. At 12 months after last treatment, 93 percent of subjects had stable or improved skin laxity. Questionnaire results showed that a majority of subjects chose not to forgo work or social/leisure activities in the immediate post-treatment period.
Conclusion: ATX-101 treatment reduced SMF and the psychological impact of SMF without worsening skin laxity. SMF reductions and subject satisfaction achieved at 12 weeks after last treatment were maintained over 12 months of follow-up. ATX-101 exhibited a safety profile expected for a facial injectable with most AEs related to the treatment area. For most subjects, downtime was minimal and occurred most commonly after the first treatment.
Retrospective Safety Study of Combining Micro-Focused Ultrasound with Visualization (MFU-V) with Neurotoxins and Fillers (HA and CaHA)
Presenters: 1William P. Werschler, MD, FAAD, FAACS; 2Sabrina G. Fabi, MD, FAAD, FAACS; 3Jeremy B. Green, MD, FAAD; 4Daniel C. Mills II, MD, FACS; 5Robert Weiss, MD
Affiliations: 1Spokane Dermatology Clinic/Premier Clinical Research; 2Cosmetic Laser Dermatology; 3Skin Research Institute; 4Aesthetic Plastic Surgery Institute; 5Laser Skin and Vein
Objectives: To evaluate micro-focused ultrasound with visualization (MFU-V) for its potential interaction with botulinum toxin A (BoNTA) and/or permanent and temporary dermal fillers
Methods: One hundred one subjects were enrolled in this retrospective, two-year chart review. Treatment dates, volume of product used, and treatment areas were collected. Subjects underwent a combination treatment with MFU-V and BoNTA injection, hyaluronic acid (HA) dermal filler, and/or calcium hydroxylapatite (CaHA) dermal filler within six months of MFU-V. Treatments were in the face and/or neck regions. Data on other aesthetic procedures were also captured.
Results: Male (n=4) and female (n=96) subjects were enrolled. The average age was 55.32. Of the 101 subjects receiving MFU-V, 81 percent also received either HA/CaHA, two percent received both HA/CaHA and BoNTA injection, and 18 percent received BoNTA. Of the 83 receiving HA/CaHA, 69 percent received HA and 31 percent received CaHA. Fifty-nine percent of subjects received treatments/procedures beyond MFU-V and products detailed above. Seven adverse events were reported in seven subjects. Three adverse events were related to the MFU-V treatment, three to HA/CaHA, and one to a combination of MFU-V, BoNTA injection, hyaluronic acid with Gram-positive bacterial proteins and hyaluronic acid. Adverse events were bruising/purpura x 4, swelling, paresthesia, and HSV outbreak. HSV outbreak was related to combination therapy. Adverse events were mild in nature with the exception of one “moderate” bruising (related to MFU-V). Minor medical interventions were undertaken to resolve six of the adverse events with one not requiring intervention.
Conclusion: Safety data has shown that there are no serious adverse events or increase in adverse events and suggests that the safety profile of MFU-V combined with other aesthetic products is similar to that of the individual treatment/product.
Multicenter Pivotal Study of the Safety and Effectiveness of a Tissue Stabilized-Guided Subcision Procedure for the Treatment of Cellulite- Interim 3 Year Update
Presenter: Joel Cohen, MD
Investigators: Michael S. Kaminer, MD; Deanne M. Robinson, MD; William P. Coleman III, MD; Robert A. Weiss, MD; W. Patrick Coleman IV, MD
Background: Tissue release (subcision) for cellulite has been practiced for decades with limited success. A novel procedure has been developed which stretches and stabilizes tissue while providing integrated anesthesia delivery and precise depth control of minimally invasive tissue release. The purpose of this study was to determine the safety and efficacy of a new tissue stabilized-guided subcision (TS-GS) system for the treatment of cellulite.
Design: A pivotal prospective multi-centered safety and effectiveness study enrolled 55 subjects. Subjects served as their own controls, underwent a single treatment, and were followed at regular intervals out to three years. Safety was assessed and effectiveness was evaluated by blinded, independent physician evaluators using randomized (before/after) professional photographs and a novel, validated 5-point severity scale.
Results: Treatments were well-tolerated with minor expected side effects that resolved quickly. Improvement was rapid and pronounced. Fifty-two subjects completed two-year follow-ups. Two-year average reduction in cellulite severity was 2.0 points (p<0.0001) and masked evaluator improvement was 98 percent. At two years, evaluators rated 100 percent of subjects as having noticeable improvement, and 96 percent of subjects were either satisfied or very satisfied. Forty-five subjects have completed three-year follow-ups with 93 percent either satisfied or very satisfied.
Conclusion: Tissue release at precise depths leads to significant, lasting improvement in cellulite. The results of this study showed a single treatment with a novel TS-GS release system improved the appearance of cellulite on the thighs and buttocks through two years of follow-up with minimal adverse effects. This study supported the FDA- clearance of the device as an effective and safe treatment for the long-term improvement in the appearance of cellulite of the buttocks and thighs with no diminishment of benefit for up to two years. Three-year data will be available and presented.
A Double-blind, Randomized Study to Compare Microcyn Scar Management HydroGel, K103163, and Kelo-cote Scar Gel for Hypertrophic or Keloid Scars
Presenters: 1Alicia D. Bucko, DO, CPI, JD; 2Zoe Draelos, MD; 3Janet C. Dubois, MD; 4Terry M. Jones, MD
Affiliations: 1Academic Dermatology Associates, Albuquerque, NM; 2Dermatology Consulting Services, High Point, NC; 3DermResearch, Inc., Austin, TX; 4J&S Studies, Inc. College Station, TX
Introduction: Microcyn Scar Management HydroGel was developed to improve the appearance of scars and relieve the itching and pain associated with scars. This randomized, double-blind study compared the efficacy, safety and tolerability of Microcyn scar gel with that of a comparator device, Kelo-cote scar gel, for the management of hypertrophic or keloid scars.
Methods: At four sites, 44 adults (aged 18–65 years) were randomized 1:1 to Microcyn scar gel or comparator. Each subject had a target linear or widespread hypertrophic or keloid scar resulting from a wound that had healed 3 to 12 months earlier. Subjects applied treatment thrice daily for eight weeks. Endpoints included the Vancouver Scar Scale (VSS), subject-rated pain and itch assessment, subject satisfaction, and investigator global assessment (IGA).
Results: The vascularity, pliability, and height of target scars, as measured by the VSS, improved consistently over the course of the study. At Day 56, the mean total VSS had decreased by 2.10 and 1.28 in the Microcyn scar gel and comparator groups, respectively, and this improvement continued to the end-of-study visit at 16 weeks with decreases of -2.70 and -1.83 in the Microcyn scar gel and comparator groups. Pain and itch decreased (improved) in both groups with greater improvement with Microcyn scar gel; however, no notable differences were observed. The IGA of efficacy was good/very good in six (30%) subjects at Day 56 and 11 (55%) subjects at Day 112 with Microcyn scar gel, which compares favorably with five (28%) subjects at both timepoints with the comparator. Subject global satisfaction was similar between treatment groups and at various timepoints. Adverse events were reported in 18 percent of subjects on Microcyn scar gel and 35 percent on the comparator. Most were mild to moderate and not related to treatment.
Conclusion: This randomized, double blind study demonstrated that Microcyn scar gel performed better than the comparator gel for the management of hypertrophic or keloid scars. Both treatments were well tolerated.
Regression Analysis of Local Skin Responses to Predict Clearance of Actinic Keratoses on the Face in Patients Treated with Ingenol Mebutate Gel
Presenters: 1S Jim On; 2Kim Mark Knudsen; 2T Skov; 1Mark Lebwohl
Affiliations: 1Department of Dermatology, Mount Sinai School of Medicine, New York, NY; 2LEO Pharma A/S, Ballerup, Denmark
Introduction: Ingenol mebutate gel is a topical field treatment for actinic keratosis (AK). The treatment elicits application site reactions in most patients. This analysis explores the relationship between the severity of the local skin reactions (LSRs) and efficacy, as expressed by percentage reduction from baseline of AKs.
Materials and Methods: The analysis included 218 subjects from two of the pivotal Phase 3 trials with ingenol mebutate gel, 0.015%, who were treated for AK on the face. Subjects had 4 to 8 AKs within a 25cm2 area and were treated with ingenol mebutate gel, 0.015%, once daily for three days. Severity of LSRs was assessed on Days 4, 8, 15, 29, and 57. Efficacy was assessed on Day 57. Erythema, flaking/scaling, crusting, swelling, pustulation/vesiculation, and erosion/ulceration (LSRs) were assessed on a 5-point scale from 0 to 4 yielding a maximum composite score of 24. The analysis models the AK count at Day 57 with the LSR score on Day 4 for each subject as independent variable. A negative binomial regression was applied for modeling subjects’ eight-week AK count with the number of baseline lesions as offset variable and anatomic location and study site as explanatory factors. This extension of the Poisson regression model for over-dispersed count outcomes is used to account for a correlation in clearance between AK lesions within a subject. The expected percent reduction in AK count across 57 days can be derived from this model. The modeling results were used to calculate 90-percent prediction interval for the AK reduction as a function of the composite LSR score.
Results: Composite LSR scores assessed on Day 4 were predictive of efficacy. For example, at a composite score of 10, the model predicts that the subject was 90-percent certain to experience at least 50-percent reduction in the lesion count. Higher LSRs predicted greater rates of response. At low scores, the LSR had no predictive value, i.e., it neither predicted treatment success nor treatment failure.
Conclusion: Composite LSR scores were predictive of efficacy at high scores and had little predictive power at low scores.
Efficacy and Safety of Dupilumab for Moderate-to-Severe Atopic Dermatitis in Adults: A Pooled Analysis of Two Phase 2 Clinical Trials
Presenters: 1Kim Papp; 2Eric Simpson; 3Lisa Beck; 4Diamant Thaci;5Thomas Bieber; 6Andrew Blauvelt; 7Howard Sofen; 8Richard Wu; 8Neil Graham; 9Gianluca Pirozzi; 10E Rand Sutherland; 8Marius Ardeleanu
Affiliations: 1K. Papp Clinical Research and Probity Medical Research, Waterloo Ontario, Canada; 2Oregon Health & Science University, Portland, OR; 3Department of Dermatology, University of Rochester Medical Center, Rochester, NY; 4Comprehensive Center for Inflammation Medicine, University Medical School Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; 5Department of Dermatology and Allergy, University of Bonn, Bonn, Germany; 6Oregon Medical Research Center, Portland, OR; 7Department of Medicine/Dermatology, UCLA School of Medicine, Los Angeles, CA; 8Regeneron Pharmaceuticals, Tarrytown, NY; 9Sanofi, Bridgewater, NJ; 10Sanofi, Cambridge, MA
Background: Atopic dermatitis (AD) is characterized by Th2 inflammation (interleukin [IL]-4 and IL-13). Dupilumab, a fully-human monoclonal antibody directed against IL-4Rα, blocks biological actions of IL-4 and IL-13
Objectives: To evaluate efficacy of dupilumab 300mg weekly in adults with moderate-to-severe AD using pooled data from two Phase 2 trials (NCT01548404; NCT01859988).
Methods: Adults with moderate-to-severe AD were enrolled in a 12 week (Study 1117) or 16-week dose-ranging study (Study 1021). Both studies were randomized, double-blind, and placebo-controlled, with once-weekly subcutaneous placebo or dupilumab. Efficacy outcomes included absolute and percent change in Eczema Area and Severity Index (EASI) and SCORing Atopic Dermatitis (SCORAD); patients who achieved EASI improvement ≥50 percent (EASI-50) and ≥75 percent (EASI-75); and patients who achieved Investigator’s Global Assessment (IGA) score of 0 (“clear”) or 1 (“almost clear”). This analysis reflects pooled efficacy and safety results after 12 weeks of treatment. Analysis of covariance (treatment and baseline as covariates) was used to compare changes and percent changes; chi-square test was used for proportions. Safety was assessed.
Results: The pooled population consisted of placebo (n=115) or dupilumab 300mg (n=118) treated patients; demographic and clinical characteristics were balanced between treatment groups. At 12 weeks, dupilumab resulted in EASI change (mean±SD) of 21.1±12.0 from baseline values (29.3±12.4), compared with placebo ( 6.9±14.0 from baseline of 31.9±13.7; P<0.0001); percent change was greater with dupilumab, -73.9 percent versus -22.9 percent (P<0.0001). Significantly higher proportions of dupilumab-treated patients achieved EASI-50 compared with placebo (85.6% vs. 32.2%; P<0.0001), EASI-75 (61.0% vs. 13.9%; P<0.0001), and IGA ≤1 (36.4% vs. 3.5%; P<0.0001). Change in SCORAD from baseline was -37.0±18.8 and 10.9±19.6 for dupilumab (baseline 65.8±13.0) and placebo (baseline 68.1±13.5), respectively (P<0.0001); percent change was -56.6 percent dupilumab versus -15.7 percent placebo (P<0.0001). The pooled incidence of adverse events (AEs) through 12 weeks was 80.9 percent with placebo and 81.4 percent with dupilumab, and the three most common AEs (MedDRA Preferred Term) in the dupilumab group were nasopharyngitis, (32.2% dupilumab; 22.6% placebo), headache (14.4% dupilumab; 7.8% placebo), and conjunctivitis (9.3% dupilumab; 1.7% placebo).
Limitations: To enable pooling of data from two studies with different double-blind treatment durations, data from Study 1021 was truncated at 12 weeks. Safety is reported through Week 12 in both studies and does not include post-treatment AEs. These studies did not include patients with mild AD.
Conclusion: In adults with moderate-to-severe AD, dupilumab significantly improved clinical outcomes relative to placebo; the safety profile in these studies was acceptable and consistent with previous studies.
Data first presented at the 23rd World Congress of Dermatology; June 8–13, 2015; Vancouver, Canada.
Efficacy of CeraVe Itch Relief Lotion and Cream on Itch Relief in Patients with Atopic Dermatitis
Presenters: 1Matthew J. Zirwas, MD, FAAD; 2Laurence Dryer, PhD; 2Sylvia Barkovic, BA
Affiliations: 1Ohio Contact Dermatitis Center, Columbus, OH; 2Valeant Pharmaceuticals North America LLC, Irvine, CA.
Objectives: To evaluate the speed of onset and duration of relief of two ceramide-containing formulations with 1% pramoxine hydroxide (CeraVe Itch Relief Lotion and Cream) in patients with atopic dermatitis (AD), including those with active flare.
Methods: Double-blind, split-body, randomized, monadic study in 34 male and female subjects, ages 11+ years, with history of AD. Itch severity was assessed on a 10-point scale (where 0=none and 7–9=severe). Single applications of ceramide-containing lotion or cream incorporating 1% pramoxine hydrochloride applied to opposite sides of the body, following a 3- or 7-day washout period (for moisturizers/OTC products or prescription AD medications, respectively). Itch relief assessed at baseline, 2 and 5 minutes, 1, 4, and 8 hours post-application. Efficacy and aesthetic attributes were assessed at the same timepoints.
Results: Relief of itching was rapid and long-lasting with significant reductions in severity after two minutes, and continued improvement over the eight-hour test period (P<0.001 versus baseline at all timepoints). Mean itch severity scores reduced progressively from 6 (moderate) at baseline to 1–2 (mild) after eight hours, with all patients experiencing relief from itching. Rapid and long-lasting relief to dry, itchy, irritated skin; and relief from associated pain and discomfort were confirmed through patient self-assessment. Both formulations were non-greasy, absorbed quickly and easily, and were non-irritating.
Limitations: Results are based on a single application.
Conclusion: Ceramide-containing lotion or cream containing 1% pramoxine provides both rapid and long-lasting relief of itching following a single application in patients with AD with or without active flare. Both formulations were well-tolerated with aesthetic appeal.
Results From Two Phase 3 Studies in Children and Adults With Mild-to-Moderate Atopic Dermatitis Treated With Crisaborole Topical Ointment, 2%, a Novel Nonsteroidal, Topical Anti-Inflammatory, Phosphodiesterase 4 Inhibitor
Presenters: 1AS Paller; 2,3WL Tom; 4MG Lebwohl; 5RL Blumenthal; 6,7M Boguniewicz; 8RS Call; 2,3LF Eichenfield; 9DW Forsha; 10WC Rees; 11EL Simpson; 12LF Stein Gold; 13AL Zaenglein; 5LT Zane; 14AA Hebert
Affiliations: 1Northwestern University, Feinberg School of Medicine, Chicago, IL; 2Rady Children’s Hospital, San Diego, CA; 3University of California, San Diego, La Jolla, CA; 4Icahn School of Medicine at Mount Sinai, New York, NY; 5Anacor Pharmaceuticals, Inc., Palo Alto, CA; 6National Jewish Health, Denver, CO; 7University of Colorado School of Medicine, Denver, CO; 8Clinical Research Partners, Richmond, VA; 9Jordan Valley Dermatology & Research Center, West Jordan, UT; 10PI-Coor Clinical Research, Burke, VA; 11Oregon Health and Science University, Portland, OR; 12Henry Ford Health System, Detroit, MI; 13Pennsylvania State University, Hershey, PA; 14University of Texas Health Science Center Houston, Houston, TX
Objectives: Atopic dermatitis (AD) is an inflammatory skin disease affecting children and adults, and up to 90 percent of patients present with mild-to-moderate AD. Crisaborole Topical Ointment, 2% (Anacor Pharmaceuticals, Palo Alto, CA) is an investigational, nonsteroidal, topical, anti-inflammatory, phosphodiesterase 4 inhibitor. Two Phase 3 studies (NCT02118766, NCT02118792) were conducted to evaluate Crisaborole Topical Ointment, 2% in mild-to-moderate AD.
Methods: Patients ≥2 years old with mild-to-moderate AD affecting ≥5% of body surface area (BSA) were enrolled in two multicenter, double-blind, vehicle-controlled studies of identical design. Patients were randomized 2:1 to receive crisaborole or vehicle twice daily for 28 days and were evaluated on Days 8, 15, 22, and 29. The primary endpoint defined success in the Investigator’s Static Global Assessment (ISGA) as “clear/0”or “almost clear/1” with ≥2-grade improvement from baseline at Day 29. Secondary endpoints measured the percentage of patients achieving “clear/0” or “almost clear/1” on ISGA and time to success in ISGA goal.
Results: Studies 1 and 2 enrolled 503:256 and 513:250 crisaborole/vehicle patients, respectively. There were no significant differences in key baseline characteristics across all groups/studies (pooled data: mean age ~12 years, mean BSA ~18%, ISGA ~60% “moderate/3” and ~40% “mild/2”). More patients achieved success in ISGA with crisaborole than vehicle at Day 29 (Study 1: 32.8% vs. 25.4%, P=0.038; Study 2: 31.4% vs. 18.0%, P<0.001), with a greater percentage of “clear/0” or “almost clear/1” ISGA scores (51.7% vs. 40.6%, P=0.005; 48.5% vs. 29.7%, P<0.001). Patients achieved success in ISGA goals earlier when treated with crisaborole than vehicle (P<0.001). Treatment-related adverse events (AEs) were mostly mild and included application site pain (pooled data, crisaborole vs. vehicle: 4.4% vs. 1.2%) and upper respiratory tract infection (3.0% vs. 3.0%). Discontinuation rates due to AEs were 1.2% for both crisaborole and vehicle.
Conclusion: Crisaborole Topical Ointment, 2%, demonstrated favorable efficacy and safety in two large Phase 3 studies and may represent a safe and efficacious treatment for patients as young as two years with mild-to-moderate AD.
An In Vitro Study Demonstrating Nail Penetration of Tavaborole from Tavaborole Topical Solution, 5% through Multiple Layers of Nail Polish
Presenters: 1Boni E. Elewski; 2Dina Coronado; 2Sanjay Chanda; 2Tejal Merchant; 2Huiming Lin; 2Lee T. Zane; 3Tracey Vlahovic
Affiliations: 1Department of Dermatology, University of Alabama, Birmingham, AL; 2Anacor Pharmaceuticals, Inc., Palo Alto, CA; 3Temple University School of Podiatric Medicine, Philadelphia, PA
Introduction: Onychomycosis is a common infection of the fingernails and toenails resulting in thickening, discoloration, and deformity of the nail plate. Onychomycosis may have a significant psychological impact on individuals affected by this condition. Tavaborole Topical Solution, 5% (tavaborole, Anacor Pharmaceuticals, Inc., Palo Alto, CA) is a novel, boron-based pharmaceutical approved by the US FDA in July 2014 for the treatment of toenail onychomycosis caused by Trichophyton rubrum and T. mentagrophytes.
Objective: The objective of this study was to evaluate the nail penetration properties of Tavaborole Topical Solution, 5% through multiple layers of nail polish.
Methods: Human cadaver fingernails from eight female donors were mounted on Vertical Diffusion Cells and randomized to four groups representing different nail polish application practices (for each, N=7); Tavaborole Topical Solution, 5% was applied daily (25µL/cm2) to each nail for 14 days.
Results: Mean (standard deviation) cumulative penetration of tavaborole from Tavaborole Topical Solution, 5% through nails after 14 days of dosing:
Unpainted nails: 565.91.
Nail penetration was measured by monitoring the rate of drug appearance each day in the receiving medium. Approximately 24 hours after each dose, the receiving medium from each cell was removed and replaced with fresh solution. Prior to each subsequent daily dose, the nails were cleaned with a cotton swab moistened with water. Aliquots of each receiving medium sample were analyzed using high performance liquid chromatography.
Conclusion: Tavaborole Topical Solution, 5% can penetrate through up to four layers of nail polish.
Efficacy and Safety of Adalimumab versus Methotrexate Treatment in Pediatric Patients with Severe Chronic Plaque Psoriasis: Results from the 16-Week Randomized, Double-Blind Period of a Phase 3 Study
Presenters: 1Kim Papp, MD; 2Diamant Thaci, MD2; 3Danielle Marcoux, MD; 4Lisa Weibel, MD; 5Kristina Unnebrink, PhD; 6David A Williams, MD
Affiliations: 1Probity Medical Research, University of Western Ontario, Waterloo, ON, Canada; 2Comprehensive Center for Inflammation Medicine, University Medical School Schleswig Holstein, Campus Lübeck, Germany; 3CHU Sainte-Justine Montreal, Quebec, Canada; Montreal, QC, Canada; 4Pediatric Dermatology Department, University Children’s Hospital, Zurich, Switzerland; 5AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany; 6AbbVie Inc., North Chicago, Illinois
Introduction: This study (clinicaltrials.gov NCT01251614) evaluated safety and efficacy of TNF-alpha inhibitor adalimumab (ADA) versus methotrexate (MTX) treatment in pediatric patients with chronic plaque psoriasis. Results from the 16-week initial treatment period (Period A) are presented.
Methods: This multi-site international study included four periods. Period A: 16-week double-blind treatment; 1:1:1 randomization to initial 0.8mg/kg ADA up to 40mg, then every other week from Week 1; initial 0.4mg/kg ADA up to 20mg, then every other week from Week 1; or 0.1 to 0.4mg/kg MTX weekly up to 25mg/week. Period B: treatment withdrawal for treatment responders. Period C: ADA retreatment. Period D: 52-week treatment and follow-up. Eligibility included patient age-range 4 to 18 years, Physician’s Global Assessment (PGA) ≥4 or; body surface area involved >20% or; Psoriasis Area Severity Index (PASI) >20; or PASI >10 plus at least one of the following: active psoriatic arthritis unresponsive to NSAIDS, clinically relevant facial, genital, or hand and/or foot involvement, or Children’s Dermatology Life Quality Index >10. Primary efficacy endpoints, ≥PASI75 response and PGA clear or minimal (0/1) at Week 16 (ADA–0.8mg/kg vs. MTX), were evaluated for the intent-to-treat population; patients with missing data were imputed as nonresponders. Safety was evaluated for all patients who received at least one dose of study drug.
Results: Of 114 enrolled (MTX n=37, ADA–0.4mg/kg n=39, ADA-0.8mg/kg n=38), 57 percent were female; 90 percent were white. Mean age was 13.0 years (SD 3.76), range 5 to 18. Body mass index (BMI) distribution by age- and sex-adjusted percentiles was 4.4 percent (<5th, underweight), 59.6 percent (5th to <85th, normal weight), 14.9 percent (85th to ≥95th, overweight), 21.1 percent (≥95th, obese). A statistically significantly higher proportion of ADA–0.8mg/kg patients achieved PASI75 response at Week 16 (22/38, 57.9%) versus MTX patients (12/37, 32.4%; [95% CI: -47.2][-3.7] p=0.027). Approximately 20 percent more ADA-0.8mg/kg patients achieved PGA 0/1 response at Week 16 (23/38, 60.5%) versus MTX patients (15/37, 40.5%; [95% CI: -42.2][2.2] p=0.083). Treatment-emergent adverse events (TEAEs) were reported by 73.7 percent (84/114) in Period A: 75.7 percent (28/37) MTX; 76.9 percent (30/39) ADA–0.4mg/kg; 68.4 percent (26/38) ADA–0.8mg/kg. TEAEs of infection were reported by 54.1 percent (20/37) MTX; 56.4 percent (22/39) ADA–0.4mg/kg; 47.4 percent (18/38) ADA–0.8mg/kg; serious TEAEs were reported by only the ADA–0.4mg/kg patients, 7.7 percent (3/39) during Period A.
Limitation: The number of enrolled patients was low.
Conclusion: After 16 weeks of treatment, adalimumab 0.8mg/kg every-other-week demonstrated significant and clinically meaningful efficacy outcomes over methotrexate in this population. Adalimumab treatment had a similar safety profile to methotrexate, and no new safety risks were identified.
The Aerosol Foam Formulation Of Fixed Combination Calcipotriene Plus Betamethasone Dipropionate Is Efficacious In Patients With Psoriasis Vulgaris: Pooled Data From Three Randomized Controlled Studies
Presenters: 1Linda Stein Gold; 2Mark Lebwohl; 3Alan Menter; 4John Villumsen; 4Monika Rosén; 5John Koo
Affiliations: 1Henry Ford Health System, Detroit, MI; 2Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; 3Baylor University Medical Center, Dallas, TX; 4LEO Pharma A/S, Ballerup, Denmark; 5Department of Dermatology, University of California, San Francisco, CA
Background: An innovative alcohol-free aerosol foam formulation of calcipotriene 0.005% (Cal)/betamethasone dipropionate 0.064% (BD) was developed as a new treatment option for patients with psoriasis. Phase 2/3 studies have shown that the aerosol foam formulation is efficacious for the treatment of psoriasis vulgaris.
Objective: Data from three Phase 2/3 studies were pooled to increase the precision in the estimate of the effect size and to evaluate the efficacy of Cal/BD aerosol foam for 4 weeks in patients with psoriasis.
Methods: The three pooled studies enrolled patients aged ≥18 years with mild–severe psoriasis of the body (NCT01536886, NCT01536938, NCT01866163); each study evaluated Cal/BD aerosol foam versus different comparators. All analyses were descriptive. Primary endpoint: proportion of patients clear/almost clear with ≥2-step improvement in disease severity at Week 4 (according to physician’s global assessment; defined as treatment success). Additional endpoints: proportion of patients with treatment success at Week 1; modified (excluding head) psoriasis area and severity index (mPASI) at Weeks 1 and 4. Tertiary endpoints: proportion of patients with ≥75% reduction in mPASI (PASI75) at Week 4; change in itch (according to visual analog scale [VAS]) at Weeks 1 and 4. Missing values were imputed by last-observation-carried-forward, except for itch.
Results: Overall, 1,104 patients were randomized across the three studies to Cal/BD aerosol foam (n=564), Cal aerosol foam (n=101), BD aerosol foam (n=101), aerosol foam vehicle (n=152), Cal/BD ointment (n=135), or ointment vehicle (n=51). All patients were included in the full efficacy analysis set (intent-to-treat population). Overall completion rate was 95 percent. At Week 4, 51 percent of patients using Cal/BD aerosol foam achieved treatment success, a higher proportion than all other treatment groups (Cal/BD ointment, 43%; BD aerosol foam, 31%; Cal aerosol foam, 15%; aerosol foam vehicle, 5%; ointment vehicle, 8%); treatment success rate was also superior for Cal/BD aerosol foam at Week 1. Greater percentage mean decreases in mPASI with Cal/BD aerosol foam were noted versus all other treatments at Week 1 (Cal/BD aerosol foam, 39%; Cal/BD ointment, 31%; BD aerosol foam, 32%; Cal aerosol foam, 27%; aerosol foam vehicle, 22%; ointment vehicle, 27%) as well as Week 4 (71%, 63%, 53%, 43%, 32% and 33%, respectively). Week 4 PASI75 rates were also greater (51%, 41%, 34%, 18%, 7% and 10%, respectively). Cal/BD aerosol foam was efficacious irrespective of baseline disease severity (treatment success: 30% mild; 59% moderate; 33% severe baseline disease) and on all body areas assessed (i.e., arms, legs, and trunk). Cal/BD aerosol foam treatment resulted in substantial alleviation of itch at Week 1 (change in itch VAS: -30); itch relief further increased at Week 4 (change in itch VAS: -41).
Limitations: As each clinical study evaluated Cal/BD aerosol foam versus different comparators, pooling resulted in unequal patient numbers across treatment groups; this must be considered during data interpretation.
Conclusion: Cal/BD aerosol foam was significantly more effective than Cal/BD ointment and each of its individual active ingredients for the treatment of psoriasis vulgaris, resulting in a greater reduction in disease severity and a rapid, effective relief of itch.
Efficacy of Secukinumab in Patients with Plaque Psoriasis: Area Under the Curve of Treatment Response Rates
Presenters: 1April W. Armstrong; 2Steven R. Feldman; 3Neil J. Korman; 4Xiangyi Meng; 4Adriana Guana; 4Judit Nyirady; 4Vivian Herrera; 4Yang Zhao
Affiliations: 1University of Colorado Denver School of Medicine, Aurora, CO; 2Wake Forest University School of Medicine, Winston-Salem, NC; 3University Hospitals Case Medical Center, Cleveland, OH; 4Novartis Pharmaceuticals Corporation, East Hanover, NJ
Background: Assessment of how therapies achieve cumulative disease control over time is critical. In two Phase 3, 52-week trials (ERASURE and FIXTURE), secukinumab—a human, anti–interleukin-17A, monoclonal antibody—was an effective treatment for moderate-severe chronic plaque psoriasis. Pooled analysis of these trials was performed to explore the cumulative efficacy of secukinumab by assessing area-under-the-curve (AUC) of percentage of treatment responders according to Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores.
Methods: All patients who stayed on the same active treatment for 52 weeks were included. Active treatments were subcutaneous secukinumab 300mg (n=568) or 150mg (n=570) at Weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks, and subcutaneous etanercept 50mg twice weekly for 12 weeks and then once weekly (n=323). Total AUCs over the 52-week period by percentage of PASI-75/90/100 and DLQI-0/1 (no impact on patient quality of life) responders—measuring overall controlled disease time—were determined using all responder numbers at all scheduled visits.
Results: Total AUCs for patients who received secukinumab 300 and 150mg, and etanercept, respectively, were: 3857.8, 3286.9, and 2628.1 (PASI-75); 3017.7, 2212.2, and 1531.8 (PASI-90); 1677.0, 978.9, and 452.5 (PASI-100); and 3029.8, 2492.2, and 1991.4 (DLQI-0/1). Total AUC ratios for secukinumab 300 and 150mg, respectively, versus etanercept were 1.47 and 1.25 (PASI-75); 1.97 and 1.44 (PASI-90); 3.71 and 2.16 (PASI-100); and 1.52 and 1.25 (DLQI-0/1). Total AUC ratios for secukinumab 300 versus 150mg were 1.17 (PASI-75), 1.36 (PASI-90), 1.71 (PASI-100), and 1.22 (DLQI-0/1).
Conclusion: In patients with moderate-severe plaque psoriasis, greater AUCs by PASI-75/90/100 and DLQI-0/1 responders were achieved with secukinumab 300mg, followed by secukinumab 150mg and etanercept. This analysis suggests that secukinumab 300mg resulted in the best overall disease control over time.
DFD-01, a Class 3/4 Betamethasone Dipropionate 0.05% Emollient Formulation Demonstrates Similar Efficacy to a Class 1 Topical Steroid for the Treatment of Moderate Psoriasis
Presenters: 1Linda Stein Gold; 2David Pariser; 3J. Mark Jackson
Affiliations: 1Henry Ford Medical Center, Detroit, MI; 2Virginia Clinical Research, Inc., Norfolk, VA; 3University of Louisville, Louisville, KY
Introduction: Topical steroids are routinely used for the treatment of mild-to-moderate psoriasis. Steroids are classified according to potency with Class 1 (or super potent) steroids having historically demonstrated the highest efficacy. Research into the site of steroid action within the skin has driven development of novel vehicles to ensure the steroid reaches and remains within the dermis and epidermis and minimizes permeation into the systemic system. DFD-01, a Class 3/4 emollient spray formulation of 0.05% betamethasone dipropionate is compared here with a Class 1 augmented betamethasone dipropionate 0.05% steroid lotion (Diprolene [AugBD]) for the treatment of moderate plaque psoriasis.
Methods: Data from two Phase 3, randomized, clinical trials enrolling adults with moderate plaque psoriasis (Investigator Global Assessment [IGA]=3; 10 to 20% BSA) were pooled. Subjects were randomized to receive DFD-01, AugBD, or Vehicle Spray (DFD-01 Vehicle). Products were applied twice daily to all affected areas on the body excluding face, scalp, and intertriginous areas for 14 or 29 days. AugBD was only applied for 14 days, as per labelling. Treatment success was defined as an IGA=0 or 1 and ≥2-grade improvement from baseline. Other measures of efficacy included the reduction in total sign score (TSS) for a target lesion (TSS=the sum of erythema, plaque and elevation scores), individual sign scores, the percentage of subjects who achieved ≥50% reduction in TSS (TSS50) and TSS≤1 for any sign. Analysis was by Fisher’s exact test.
Results: Overall, 356 subjects received DFD-01, 90 AugBD, and 182 vehicle. Pooled IGA results showed that DFD-01 and AugBD demonstrated similar treatment success throughout the comparative treatment period, while DFD-01 was significantly superior to vehicle at Day 8, 15, and 29 (p≤0.010). Reduction in TSS showed consistent improvement with both DFD-01 and AugBD, with DFD-01 showing slightly higher rates of improvement. The percentage of subjects achieving a TSS of ≤1 for all of the three signs was significantly higher for DFD-01 than Diprolene at Day 4 and Day 15 (p≤0.033) and was significantly higher for DFD-01 than vehicle for all timepoints (p≤0.009). Pooled TSS50 results showed similar trends in efficacy, with 50 percent of DFD-01 subjects achieving TSS50 at Day 15 versus 41 percent of AugBD subjects. Erythema, scaling, and plaque elevation were all improved with both DFD-01 and AugBD with individual sign scores of 0 (clear) achieved in significantly more DFD-01 subjects versus vehicle at Day 15 and Day 29 (p≤0.007).
Conclusion: The medium potency, Class 3/4 DFD-01 showed similar clinical efficacy to the super potent, Class 1 AugBD on global measures of IGA, TSS, and TSS50 for the treatment of moderate plaque psoriasis. DFD-01’s novel formulation appears to confer the efficacy of a Class 1 steroid despite its vasoconstrictor assay classification of Class 3/4.
Financial disclosures/funding: Promius Pharma, Princeton, NJ.
Secukinumab in Psoriasis: Relationship Between Clinical-and Patient-Reported Outcomes Using Clinical Trial Data from the ERASURE and FIXTURE Trials
Presenters: 1Alice B Gottlieb; 2Bruce Strober; 3Mark Lebwohl; 4Roland Kaufmann; 5David Pariser; 6Redzinaldas Narbutas; 7Judit Nyirady; 7Yang Zhao; 8Lori D McLeod; 8Dawn Odom; 9Boni E Elewski
Affiliations: 1Tufts Medical Center, Boston, MA; 2University of Connecticut Health Center, Farmington, CT; Probity Medical Research, Waterloo, ON, Canada; 3Icahn School of Medicine at Mount Sinai, New York, NY; 4Department of Dermatology, Venereology and Allergology, Goethe-University, Frankfurt, Germany; 5Eastern Virginia Medical School, Norfolk, VA; 6Vilnius University Hospital Clinic, Vilnius, Lithuania; 7Novartis Pharmaceuticals Corporation, East Hanover, NJ; 8RTI Health Solutions, Research Triangle Park, NC; 9University of Alabama at Birmingham, Birmingham, AL.
Background: Secukinumab, a fully human anti-interleukin 17A monoclonal antibody, was evaluated in ERASURE and FIXTURE, two Phase 3 multicenter double blind versus placebo clinical studies, for efficacy and safety in subjects with moderate-to-severe plaque psoriasis. Data from these trials provided an opportunity to evaluate the relationship between traditional clinical outcomes and patient-reported symptoms.
Methods: Patients aged ≥18 years were randomized 1:1:1 in ERASURE to receive subcutaneous treatment with secukinumab 300mg, secukinumab 150mg, or placebo; and 1:1:1:1 in FIXTURE, which included etanercept 50mg twice weekly. The co-primary endpoints were the Psoriasis Area and Severity Index (PASI) and Investigator’s Global Assessment Mod 2011 Rating Scale (IGA mod 2011). Symptom response was evaluated using the patient-completed Psoriasis Symptom Diary (PSD), which measures psoriasis-related disease characteristics, which subjects have reported as important and relevant to their disease and treatment. Correlation coefficients were calculated at baseline, Week 12, and change from baseline to Week 12 between the PSD weekly itching, pain, and scaling scores and the PASI and IGA mod 2011 scores. Logistic regression evaluated the relationship between itching, pain, and scaling response (improvement of at least 2.2 points for itching and pain and 2.3 points for scaling), and percent change in PASI at Week 12.
Results: Approximately 40 percent of patients completed the voluntary PSD. For the pooled analysis (ERASURE n=187, FIXTURE n=266) of secukinumab data, correlation coefficients at baseline were positive but low in magnitude (0.11–0.21) and positive and stronger at Week 12 (0.32–0.52). The change from baseline to Week 12 correlation coefficients (0.18–0.30) were positive but lower in magnitude than Week 12 values. Most coefficients were significant (P<0.001). The logistic models showed that the percent change in PASI score was a significant predictor of PSD response. The likelihood of a response for psoriasis-related itching, pain, and scaling at Week 12 increased from 77.7, 65.9, and 77.7 percent with a 75% PASI change between baseline and Week 12 to 85.9, 72.6, and 86.1 percent with a 90% PASI change.
Conclusion: PASI 90 provides greater symptom response as measured by the PSD than PASI 75. It is important to evaluate both patient-reported outcomes and clinical endpoints to understand the full benefits of a psoriasis treatment.
Financial disclosures/funding: Sponsored by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
DFD-01 A Novel Emollient Spray Formulation of 0.05% Betamethasone Dipropionate Effectively Treats Plaque Psoriasis on Knees and Elbows
Presenters: 1Leon Kircik; 2Jerry Bagel
Affiliations: 1Mount Sinai School of Medicine, New York, NY; 2Psoriasis Treatment Center of Central NJ, East Windsor, NJ.
Introduction: Topical therapies for psoriasis have remained largely unchanged for decades, but remain an important first-line treatment and are often used in combination with other therapies for more severe disease. Topical steroids are effective, but can be associated with the potential to cause systemic side effects. DFD-01 is a novel emollient spray formulation of 0.05% betamethasone dipropionate. This formulation is designed to penetrate the outer stratum corneum and be retained within the dermis and epidermis, the sites of T cell activity that drive the disease process. Plaque psoriasis affecting knees and elbows is notoriously difficult to treat. So much so, that these lesions are often excluded from psoriatic clinical trial assessments. This analysis compares the efficacy of a Class 3/4 betamethasone (DFD-01) and a Class 1 betamethasone (Diprolene, AugBD) on knee and elbow plaques in subjects with moderate plaque psoriasis.
Methods: Two Phase 3 clinical trials randomized adults with moderate psoriasis (Investigator Global Assessment [IGA]=3; 10 to 20% BSA) to DFD-01, AugBD, or vehicle. Products were applied twice daily to all affected areas for 14 or 28 days. AugBD was applied for 14 days, per labelling. A target plaque, from either the elbow or knee of each subject was assessed. Success was assessed as (1) a score of 0 or 1 (reducing the plaque to “clear” or “slight to mild”) for erythema, scaling, and plaque elevation; and (2) total sign score (TSS) ≤1 for all three signs (erythema, scaling, or plaque elevation) for a particular target lesion. Treatment success was analyzed post-hoc using Fisher’s exact test.
Results: Of the 628 subjects enrolled in these trials, 37.9 percent had a target lesion located on their elbow or knee selected for assessment (DFD-01, n=133; AugBD, n=32; Vehicle, n=71). Subanalysis of the pooled data shows that DFD-01 showed similar efficacy on hard-to-treat knee and elbow lesions as those treated with AugBD. In each measured outcome—erythema, scaling, plaque elevation, and TSS—results were superior with DFD-01 compared with AugBD at Day 4, although not significantly so. Day 15 success was seen in erythema (66.2% DFD-01 vs. 62.5% AugBD), scaling (70.7% DFD-01 v.s 62.5% AugBD), plaque elevation (65.4% DFD-01 vs. 62.5% AugBD), and TSS (53.4% DFD-01 vs. 43.8% AugBD). From Day 8, DFD-01 reduced erythema and scaling in significantly more subjects than vehicle (p≤0.003) and reduced plaque elevation in more subjects from Day 15 (p<0.001). DFD-01 and AugBD also demonstrated comparative efficacy for lesions located on the trunk or extremities, with the exception of DFD-01 improving erythema in significantly more subjects than AugBD on Day 4 (p=0.024).
Conclusion: DFD-01 effectively improved hard-to-treat lesions on knees and elbows. Improvements were seen in erythema, plaque elevation and, in particular, scaling. Responses were similar to those seen for lesions on the trunk and extremities.
Financial disclosures/funding: Promius Pharma, Princeton, NJ
Apremilast for the Treatment of Psoriasis and Psoriatic Arthritis: Management of Gastrointestinal Adverse Effects
Presenters: 1Abraham BP; 2Shah K; 2Levi E; 3Sellin JH
Affiliations: 1Houston Methodist – Weill Cornell, Houston, TX; 2Celgene Corporation, Warren, NJ; 3Baylor College of Medicine, Houston, TX
Objective: Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, works intracellularly to regulate inflammatory mediators involved in the pathogenesis of psoriasis and psoriatic arthritis (PsA). Diarrhea and nausea are among the most common gastrointestinal adverse events (AEs) associated with PDE4 inhibitors. Here, we review the occurrence of diarrhea and nausea events thought to be drug related in the apremilast clinical trial program and provide practical clinical strategies for managing these events based on the literature on the management of drug-induced gastrointestinal symptoms and clinical experience.
Methods: The safety and tolerability of oral apremilast 30mg twice daily have been evaluated in two Phase 3 clinical trials in patients with moderate-to-severe plaque psoriasis (ESTEEM 1 [NCT01194219] and ESTEEM 2 [NCT01232283]) and three Phase 3 clinical trials in patients with active PsA (PALACE 1 [NCT01172938], PALACE 2 [NCT01212757], and PALACE 3 [NCT01212770]); details of these studies have been published. No protocol definition for diarrhea or nausea was provided for these studies; frequency and specific stool characteristics (e.g., using the Bristol Stool Chart) were not assessed. Instead, diarrhea and nausea were documented from patients’ reports and characterized as mild, moderate, or severe according to patients and reporting investigators.
Results: In the pooled clinical studies, most gastrointestinal AEs reported with oral apremilast 30mg twice-daily treatment occurred early, were mild in severity, and resolved without intervention or dose modification. Patients treated with this dosing experienced diarrhea (16.5–17.8%) and/or nausea (15.1–16.6%) during the 0- to 16-week placebo-controlled periods. The majority of diarrhea or nausea events occurred within the first two weeks of treatment. Diarrhea and nausea were predominantly mild or moderate in nature. Most cases tended to resolve over time with continued dosing and without intervention; when treatment was used, loperamide was the most common agent used to manage gastrointestinal symptoms.
Conclusion: Diarrhea and nausea are common AEs associated with apremilast treatment; they generally occur early, are mild in severity, and resolve without intervention. If needed, a number of non-pharmacologic and pharmacologic measures, based on the literature for drug-induced gastrointestinal symptoms, could be considered to manage gastrointestinal AEs in the short term with the goal of optimizing long-term treatment outcomes. We suggest counseling patients and setting expectations before treatment initiation to maximize treatment success. Non-pharmacologic measures should be considered first, including ensuring adequate hydration; taking medication with food (if not contraindicated); eating smaller, more frequent meals; and avoiding foods or drinks that exacerbate gastrointestinal symptoms. If symptoms persist, over-the-counter antidiarrheal or anti-nausea medications are options to consider; prescription agents for diarrhea or nausea are also available if needed.
Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Moderate-to-Severe Plaque Psoriasis: Pooled 16-Week Efficacy in Patient Subgroups (ESTEEM 1 and 2)
Presenters: 1Neil J. Korman, MD; 2Yves Poulin, MD; 3Christopher E. M. Griffiths, MD; 4Sergio Chimenti, MD; 5Howard Sofen, MD; 6Sandra Philipp, MD; 7ChiaChi Hu, EdM, MS; Robert M. Day, PhD; 8Giampiero Girolomoni, MD
Affiliations: 1University Hospitals Case Medical Center, Cleveland, OH; 2Centre de Recherche Dermatologique du Québec métropolitain, Québec, QC, Canada; 3The Dermatology Centre, The University of Manchester, Manchester, UK; 4University of Rome Tor Vergata, Rome, Italy; 5Department of Medicine/Dermatology, UCLA School of Medicine, Los Angeles, CA; 6Charité Campus Mitte, Universitaetsmedizin Berlin, Berlin, Germany; 7Celgene Corporation, Warren, NJ; 8University of Verona, Verona, Italy
Background: ESTEEM 1 and 2 evaluated the efficacy and safety of apremilast (APR) in patients with moderate-to-severe plaque psoriasis. This analysis evaluated APR efficacy in specified subpopulations.
Methods: In ESTEEM 1 and 2, patients with moderate-to-severe plaque psoriasis (PASI ≥12, BSA ≥10%, sPGA ≥3) were randomized (2:1) to APR 30mg BID (APR30) or placebo (PBO). At Week 16, all PBO patients switched to APR30 through Week 32. This was followed by a randomized treatment withdrawal phase up to Week 52. Subgroup analyses were based on baseline demographics (e.g., gender, race, age, body weight, body mass index), baseline disease characteristics (e.g., disease duration, history of nail, scalp, and palmoplantar psoriasis), and prior psoriasis therapies. Using data pooled from ESTEEM 1 and 2, efficacy was evaluated at Week 16 by baseline PASI score (≤20, >20) and number/type of prior and failed psoriasis therapies (including phototherapy, conventional systemics, biologics, or TNF blockers).
Results: The pooled analyses included 1,255 patients who entered the PBO-controlled phase (PBO: n=419; APR30: n=836). At Week 16, PASI-75 responses (primary end point) were significantly greater with APR30 (ESTEEM 1: 33.1%; ESTEEM 2: 28.8%) versus PBO (ESTEEM 1: 5.3%; ESTEEM 2: 5.8%; P<0.0001). The primary end point analysis consistently demonstrated the treatment benefit of APR30, relative to PBO, across multiple demographic and disease characteristic subgroups, including baseline disease severity (moderate vs. severe psoriasis) and whether or not patients had been treated previously with systemic (including biologics) psoriasis treatments. Although not significant, there were trends for higher PASI-75 responses in patients with PASI scores ≤20 at baseline and patients who had not received prior systemic therapies. Subpopulation analyses of sPGA 0 (clear) or 1 (almost clear) achievement and PASI-50 responses had similar findings
Conclusion: In pooled analyses of PASI-75, PASI-50, and sPGA responses at Week 16 in ESTEEM 1 and 2, APR30 was effective across subgroups regardless of baseline demographics or prior psoriasis therapy.
Safety of Apremilast and Etanercept Compared With Placebo in Patients With Moderate to Severe Psoriasis: Results From the LIBERATE Study
Presenters: 1Melinda Gooderham, MD; 2Jennifer Soung, MD; 3Lawrence Green, MD; 4Matthias Augustin, MD, PhD; 5Zuoshun Zhang, PhD; 5Kamal Shah, MD; 5Joana Goncalves, MD; 6Kristian Reich, MD
Affiliations: 1Skin Centre for Dermatology and Probity Medical Research, Peterborough, ON, Canada; 2University of California, Irvine, CA; 3George Washington University School of Medicine, Washington, DC; 4Institute for Health Services, Research in Dermatology and Nursing – IVDP, University Medical Center of Hamburg Eppendorf Augustin, Hamburg, Germany; 5Celgene Corporation, Warren, NJ, USA; 6SCIderm Research Institute and Dermatologikum Hamburg, Hamburg, Germany
Background: The Phase 3b LIBERATE (Evaluation in a Placebo-Controlled Study of Oral Apremilast and Etanercept in Plaque Psoriasis) double-blind, double-dummy study evaluated efficacy and safety of apremilast (APR) or etanercept (ETN) versus placebo (PBO) in biologic-naive patients with moderate-to-severe plaque psoriasis.
Methods: In this study patients were randomized (1:1:1) to PBO, APR 30mg BID (APR30), or ETN 50mg QW (ETN50) through Week 16; thereafter, patients receiving PBO (PBO/APR30) or ETN50 (ETN50/APR30) switched to APR30 through Week 104. Patients in the APR30 group continued treatment (APR30/APR30) through Week 104. Adverse events (AEs) were assessed for Weeks 0 to 16 and Weeks 16 to 32.
Results: 250 randomized patients received ≥1 dose of study drug and were included in the safety analysis (PBO n=84; APR30 n=83; ETN50 n=83). The most common AEs (≥5% of patients) were headache, nausea, diarrhea, upper respiratory tract infection (URTI), tension headache, and nasopharyngitis. Across all subgroups: severe or serious AEs were reported in ≤3 patients and ≤3 patients discontinued due to AEs. For Weeks 0 to 16, serious infections were pneumonia n=1 APR30, n=1 ETN50; no serious infections were reported for Weeks 16 to 32. No malignancies were reported. History of depression was reported at baseline in 9.5, 16.9, and 7.2 percent of patients, respectively, in the PBO, APR30, and ETN50 arms. Rates of depression and depressed mood with APR30 were low, occurring in patients with a prior history or with depression at baseline (Weeks 0–16, depression n=1 APR30; Weeks 16–32, depression n=1; depressed mood, n=1 APR30/APR30). Suicidal ideation (n=1 PBO/APR30) was reported for Weeks 16–32. At Week 16, mean percent change from baseline in weight was +0.17%, -0.81%, and +1.44% with PBO, APR30, and ETN50, respectively. At Week 32, mean percent change from baseline in weight was -0.52%, -0.78%, and +0.09% with PBO/APR30, APR30/APR30, and ETN50/APR30, respectively.
Conclusion: The safety profile of APR30 was acceptable in patients with moderate-to-severe plaque psoriasis. No new safety or tolerability issues were observed between Week 16 and Week 32 in patients who switched from ETN50 to APR30 at Week 16.
Secukinumab Exhibits Low Immunogenicity During 104 Weeks of Treatment in Subjects with Moderate-to-Severe Plaque Psoriasis
Presenters: 1Reich K; 2A Blauvelt A; 3Warren RB; 4Szepietowski JC; 5Sigurgeirsson B; 6Langley RGB; 7Tyring S; 8Messina I; 8Fox T; 8Papavassilis C; 8Bruin G
Affiliations: 1Dermatologikum Hamburg and Georg-August-University Göttingen, Hamburg, Germany; 2Oregon Medical Research Center, Portland, OR; 3The Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester, UK; 4Wroclaw Medical University, Wroclaw, Poland; 5Hudlæknastöðin Smaratorg 1 201 Kópavogur, Iceland; 6Dalhousie University, Halifax, Nova Scotia, Canada; 7University of Texas Health Science Center & Center for Clinical Studies, Houston, TX; 8Novartis Pharma AG, Basel, Switzerland.
Introduction and Objectives: Secukinumab, a human monoclonal antibody (mAb) that selectively targets interleukin (IL)-17A, is highly efficacious in the treatment of moderate-to-severe psoriasis, starting at early time points, with a sustained effect and a favorable safety profile. Biologic drugs can induce anti-drug antibodies (ADA) that may affect pharmacokinetics, diminish response, or cause hypersensitivity. This trial is a 4-year extension of two 1-year secukinumab Phase 3 studies in moderate-to-severe psoriasis, ERASURE and FIXTURE. Here, we evaluated the immunogenicity of secukinumab at Week 104 of treatment in this extension study.
Methods: Subjects completing either core study with at least a partial response (Psoriasis Area and Severity Index [PASI] ≥50) to secukinumab at Week 52 were eligible for inclusion. PASI 75 responders in each secukinumab dose group of the core studies were randomized 2:1 to continue the same doses of secukinumab (300mg or 150mg) or receive placebo (300mg placebo or 150mg placebo) every four weeks. Subjects who relapsed in the two placebo arms were retreated with secukinumab. Partial responders (PASI ≥50 but <75) from the core studies continued the same secukinumab doses. Blood samples obtained at Week 52, Week 76, and Week 104 were assayed for ADA. Presence of treatment-emergent ADA (TE-ADA) was defined as a positive ADA signal detected in post-treatment samples from subjects with a negative signal at baseline in the core studies. Confirmed TE-ADA samples were analyzed for neutralizing potential
Results: TE-ADA were detected in 6/1,142 (0.53%) subjects tested; one in the 300mg arm, three in the 150mg arm (one partial responder), and two in the 150mg placebo arm (one relapsed and regained response following retreatment). Two subjects, one each in the 300mg and 150mg placebo treatment groups, tested positive for neutralizing antibodies at Week 76. Among the six subjects with TE-ADA, four later reverted to a seronegative state during therapy. TE-ADA, including in the two subjects with neutralizing antibodies, were not associated with loss of response or hypersensitivity reactions, and pharmacokinetics (PK) were normal in subjects for whom data were available and assessable (3/6). In terms of overall efficacy, secukinumab 300mg was consistently more efficacious than 150mg, with strong sustained efficacy to Week 104. Immunogenicity findings were consistent with the overall Phase 3 psoriasis program, which had a TE-ADA incidence of 0.4%.
Conclusion: TE-ADA and neutralizing antibodies were reported rarely with secukinumab treatment out to two years (104 weeks) and were not associated with loss of secukinumab efficacy or other issues of clinical concern.
Financial disclosures/funding: This research was funded by Novartis Pharma AG, Basel, Switzerland.
Secukinumab Delivers Greater Improvement in Health-Related Quality of Life Compared to Ustekinumab in Subjects With Moderate-to-Severe Plaque Psoriasis: 16-Week Data From the CLEAR Study
Presenters: 1Thaci D; 2Blauvelt A; 3Reich K; 4Tsai TF; 5Vanaclocha F; 6Kingo K; 7Ziv MI; 8Pinter A; 9Hugot S; 10You R; 11Augustin M; 9Milutinovic M
Affiliations: 1Comprehensive Center for Inflammation Medicine, University Hospital Schleswig-Holstein, Lubeck, Germany; 2Oregon Medical Research Center, Portland, OR; 3Dermatologikum Hamburg and Georg-August-University Göttingen, Göttingen, Germany; 4Deparment of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; 5Servicio de Dermatología, Hospital 12 de Octubre, Madrid, Spain; 6Department of Dermatology and Venereology, Tartu University, Tartu, Estonia; 7Dermatology Department, Ha’Emek Medical Center, Afula, Israel; 8Klinik fur Dermatologie, Venerologie und Allergologie, Universitätsklinikum Frankfurt, Frankfurt, Germany; 9Novartis Pharma AG, Basel, Switzerland; 10Novartis Beijing Novartis Pharma Co. Ltd, Shanghai, China; 11University Medical Center, Hamburg, Germany.
Introduction and Objectives: Secukinumab, a human anti– interleukin (IL)-17A monoclonal antibody (mAb), has been previously reported to be superior to etanercept in achieving strong responses with a favorable safety profile in moderate-to-severe plaque psoriasis. In the ongoing CLEAR study, which is a multicenter, double-blind, parallel-group, active comparator-controlled Phase 3b study comparing efficacy/safety of secukinumab versus ustekinumab (an anti-IL-12/23 mAb) in adults with moderate-to-severe plaque psoriasis, superior efficacy was reported for secukinumab versus ustekinumab, with a superior Psoriasis Area and Severity Index (PASI) 90 response in the secukinumab arm at Week (Wk) 16. Here, we report the 16-week Patient Reported Outcomes (PROs) from the CLEAR study.
Methods: Subjects were randomized 1:1 to receive subcutaneous injection of secukinumab (300mg) or ustekinumab (per label, for subjects ≤100kg, 45mg; >100kg, 90mg). In both treatment arms, randomization was stratified by body weight (≤100 and >100kg). Secukinumab was administered at baseline, Weeks 1, 2, 3, and 4, and then every four weeks from Week 8 to 48; ustekinumab at baseline and Week 4, then every 12 weeks from Week 16 to 40. Exploratory objectives included assessing the effects of both treatments on health-related quality of life (HRQoL), including changes in the Dermatology Life Quality Index (DLQI; maximum range of 0–30), patient assessment of psoriasis symptoms (pain, itching, and scaling; using a numeric rating scale of 0–10), and, for subjects with psoriatic arthritis (PsA), the Health Assessment Questionnaire-disability index (HAQ-DI; maximum range of 0–3).
Results: At each assessed time-point post baseline (Weeks 4, 8, 12, and 16), significantly more subjects achieved a DLQI score of 0 or 1 (i.e., no impact of skin problems on HRQoL) with secukinumab versus ustekinumab (at Week 16: 71.9 and 57.4%, respectively; P<0.0001). The total DLQI change from baseline (percentage and absolute change) was significantly greater with secukinumab versus ustekinumab at all time-points (P≤0.002). Improvements in psoriasis symptoms were greater for subjects on secukinumab at all time-points (Weeks 1, 2, 3, 4, 8, 12, and 16). At Week 16, subjects on secukinumab had mean decreases of 81 percent in pain, 79.5 percent in itching, and 86.3 percent in scaling scores, and these differences were significantly greater versus ustekinumab (P<0.05 for each). In subjects with PsA, the proportion achieving a decrease of at least 0.3 (minimum clinically important difference) in their HAQ-DI score was greater with secukinumab (34.9%) versus ustekinumab (26.5%).
Conclusion: The superior 16-week efficacy of secukinumab versus ustekinumab in subjects with moderate-to-severe plaque psoriasis also translates into greater improvements in patient HRQoL.
Financial disclosures/funding: This research was funded by Novartis Pharma AG, Basel, Switzerland.
Secukinumab Administration by Prefilled Syringe Maintains Efficacy in Moderate-to-Severe Plaque Psoriasis Over 100 Weeks: Results of the FEATURE Trial
Presenters: 1Blauvelt A; 2Gottlieb AB; 3Tyring S; 4You R; 5Papanastasiou P; 5Fox T; 5Papavassilis C for the FEATURE Study Group
Affiliations: 1Oregon Medical Research Center, Portland, OR; 2Tufts Medical Center, Boston, MA; 3University of Texas Health Science Center/Center for Clinical Studies, Houston, TX; 4Beijing Novartis Pharma Ltd., Shanghai, China; 5Novartis Pharma AG, Basel, Switzerland
Introduction and Objectives: Plaque psoriasis is a chronic disease; therefore, sustaining treatment benefits is important. Secukinumab, a human monoclonal antibody (mAb) that selectively targets interleukin (IL)-17A, has been demonstrated to be highly efficacious in the treatment of moderate-to-severe psoriasis, with a sustained effect and a favorable safety profile. The FEATURE study examined secukinumab efficacy and safety when self-administered using a prefilled syringe (PFS). Here, data from up to two years (100 weeks) of treatment are reported.
Methods: In this Phase 3 trial, subjects were randomized 1:1:1 to secukinumab 300mg, 150mg, or placebo. Treatments were self-administered using a PFS at Weeks 0, 1, 2, 3, and 4, then every four weeks until Week 12 (placebo) or secukinumab until Week 208. Placebo group non-responders were re-randomized to secukinumab 300mg or 150mg after Week 12. Co-primary endpoints were secukinumab Psoriasis Area and Severity Index (PASI) 75 and Investigator’s Global Assessment 2011 modified version (IGA mod 2011 0/1) clear/almost clear response rates at Week 12 compared to placebo. Secondary endpoints included PASI 90 and PASI 100. Here, Week 100 interim efficacy analyses were performed using multiple imputation (MI) methods on data from 86 subjects who received 300mg secukinumab and 88 subjects who received 150mg secukinumab at any point during the study.
Results: Week 12 and 52 data were reported previously. Secukinumab was superior to placebo at Week 12 with respect to PASI 75 response and IGA mod 2011 0/1 response, with substantial PASI 75, 90, and 100 responses maintained to Week 52. At Week 100, median treatment exposure at any dose was 624 (33–763) days for 274.3 subject-years overall experience. Week 100 analysis in all subjects receiving secukinumab from Week 0 or Week 13 showed PASI 90 response for 59.7 percent of subjects with 300mg and 41.3 percent with 150mg secukinumab. At Week 100, 40.8 and 22.2 percent of subjects had PASI 100 with secukinumab 300mg and 150mg, respectively. PASI 75 responses were seen in 79.6 percent of subjects with secukinumab 300mg and in 58.4 percent receiving secukinumab 150mg, and IGA mod 2011 0/1 scores were recorded for 55.2 and 41.1 percent of subjects receiving secukinumab 300mg and 150mg, respectively. No new or unexpected safety signals were observed to Week 100.
Conclusion: Substantial and durable PASI 90 and PASI 100 responses at Week 100 were achieved using long-term administration of secukinumab by PFS. The safety profile of secukinumab was consistent with previous studies, with no new or cumulative safety findings seen.
Financial disclosures/funding: This research was funded by Novartis Pharma AG, Basel, Switzerland.
Secukinumab is Predominantly Prescribed at the Recommended 300mg Dose to Psoriasis Patients in the United States
Presenters: 1Jashin J. Wu; 2Yang Zhao; 2Yufeng Li; 2Huanxue Zhou; 3Xing Liu; 2Melody Tran; 2Vivian Herrera
Affiliations: 1Department of Dermatology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA; 2Novartis Pharmaceuticals Corporation, East Hanover, NJ; 3KMK Consulting, Morristown, NJ
Background: Secukinumab is a novel, fully human monoclonal antibody indicated for the treatment of moderate-to-severe plaque psoriasis and has been available to US patients since March of 2015. According to the US product label, the recommended dose is 300mg. For some patients, a dose of 150mg may be acceptable.
Methods: Secukinumab Service Request Forms (SRFs) jointly filled by physicians and patients for initial secukinumab prescription from March 1, 2015, to May 31, 2015, were analyzed. All patients provided written informed consent. Information on the prescribed secukinumab dose and patient characteristics was analyzed descriptively.
Results: The analysis included 5,050 secukinumab SRFs completed by 1,989 unique physicians. Patients were from all regions of the United States: Northeast (14.5%), Midwest (20.2%), South (45.6%), and West (19.7%). The patient sample was roughly balanced by sex (females, 45.7%; males, 53.8%; missing data, 0.5%) and distributed across a wide range of age groups: 18–24 years (2.6%), 25–34 (10.6%), 35–44 (20.4%), 45–54 (25.1%), 55–64 (25.2%), 65+ (16.2%). 2,494 patients (49.4%) had previously used a biologic (missing or unknown for rest of data), with 60 percent (1,486) using two or more biologics. Overall, the initial secukinumab dose was 300mg for 99.9 percent of the patients (5,046) and 150mg for only four patients (0.1%). A majority of the SRFs requested the autoinjector pen as the injection device (4,543; 90.0%) rather than the pre-filled syringe (507; 10.0%).
Conclusion: Using a large number of secukinumab SRFs filled by US patients and their physicians distributed from all regions, this analysis found that secukinumab is predominantly prescribed at the recommended 300mg dose. Therefore, secukinumab is being prescribed in accordance with the product label.
Financial disclosures/funding: This study was funded by Novartis Pharmaceuticals Corporation.
Pregnancy Outcomes in the Tofacitinib Psoriasis Safety Database up to April 2014
Presenters: 1Steven Feldman; 2Alexandra B. Kimball; 3Richard B. Warren; 4Don Frazier; 4James Proulx; 5Amy Marren
Affiliations: 1Department of Dermatology, Wake Forest University School of Medicine, Winston Salem, NC; 2Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA; 3University of Manchester, Manchester, UK; 4Pfizer Inc, Groton, CT; 5Pfizer Inc, Collegeville, PA
Introduction: Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis. No adverse fetal effects were observed in preclinical studies with exposures corresponding to the human dose tofacitinib 10mg twice daily; at approximately >10 and 100-fold this exposure, tofacitinib was teratogenic (visceral and skeletal abnormalities) in rabbits and rats, and decreased the number of viable pups in rats. There are no well-controlled tofacitinib studies in pregnant women; the psoriasis clinical development program excluded pregnant patients and required contraception use. If a patient became pregnant, treatment discontinuation was mandatory. Pregnancies were followed up to investigate occurrence of any adverse outcomes.
Objective: To understand potential effects of tofacitinib on pregnancy outcomes in patients with psoriasis.
Methods: Cases were identified from Pfizer’s internal safety database, including all tofacitinib exposure in clinical studies through April 2014. Cases included females administered study medication at time of conception and/or fetuses exposed to study medication through maternal or paternal exposure. Pregnancy outcomes were categorized as healthy newborns, spontaneous abortion, medical termination, pending, or lost to follow-up.
Results: In total 16 female patients, aged 19 to 40 years, became pregnant while on study drug over the course of 5,203.6 patient-years of tofacitinib exposure. Most patients were treated with tofacitinib at the time of conception and early gestation. There were no cases of fetal demise or birth defects reported among these 16 patients; four abortions (1 spontaneous, 3 elective) were reported. All other patients had healthy newborns (6), had not yet reported pregnancy outcome (5), or were lost to follow-up (1). There were 42 cases of paternal exposure to tofacitinib: 13 healthy newborns, 5 spontaneous abortions, 19 pending outcome, and 5 lost to follow-up.
Conclusion: No pregnancies resulting in birth defects or fetal demise were reported among cases of maternal tofacitinib exposure. Pregnancy outcomes reported here were generally similar to those reported with biologic psoriasis therapies, and in tofacitinib-treated patients with rheumatoid arthritis.
Secukinumab Safety and Tolerability in Patients with Active Psoriatic Arthritis and Psoriasis: Results from a Pooled Safety Analysis
Presenters: 1Mease P; 2McInnes IB; 3Gottlieb AB; 4Widmer A; 5Pricop L; 4Mpofu S
Affiliations: 1Swedish Medical Center and University of Washington, Seattle, WA; 2University of Glasgow, Glasgow, UK; 3Tufts Medical Center, Boston, MA; 4Novartis Pharma AG, Basel, Switzerland; 5Novartis Pharmaceuticals Corporation, East Hanover, NJ
Introduction and Objectives: Secukinumab, a human anti– interleukin (IL)-17A monoclonal antibody (mAb), has been shown to improve the signs and symptoms of psoriasis (PSO) and psoriatic arthritis (PsA). Here, we describe the safety profile of secukinumab from a large cohort of patients with PSO and patients with PsA, using pooled data from Phase 3 studies.
Methods: Safety data were pooled from five double-blind, randomized, placebo-controlled Phase 3 studies in patients with PSO (ERASURE [NCT01365455], FIXTURE [NCT01358578], SCULPTURE [NCT01406938], FEATUR [NCT01555125], and JUNCTURE [NCT01636687]), and two double-blind, randomized, placebo-controlled Phase 3 studies in patients with active PsA (FUTURE 1 [NCT01392326] and FUTURE 2 [NCT01752634]). In the FUTURE 1 study, patients received 10mg/kg secukinumab i.v. loading followed by s.c. maintenance dosing (75mg or 150mg). In all other studies, patients received s.c. loading and maintenance with secukinumab (300, 150, or 75mg). All randomized patients were included in the pooled safety analysis. Data were pooled at the patient level, and safety analyses were performed for the entire treatment period (≥52 weeks for FUTURE 1; Week 52 for ERASURE, FIXTURE, SCULPTURE, FEATURE, and JUNCTURE; ≥24 weeks for FUTURE 2).
Results: 3,928 patients received ≥1 dose of secukinumab (3,225 patient-years of exposure, respectively). Baseline demographics, disease/medical history, and concomitant medications were similar between the pooled secukinumab and placebo populations. Exposure-adjusted incidence rates for adverse events (AEs)/serious adverse events (SAEs) across the entire safety period (mean exposure: 299.8 days secukinumab; 105.7 days placebo) were, 240.5/7.9 and 329.6/9.9 per 100 patient-years with secukinumab and placebo, respectively; 115 (2.9%) patients discontinued secukinumab treatment due to AEs. There were four deaths in secukinumab-treated patients: one due to intracranial hemorrhage; one due to cardio-respiratory arrest; one due to alcohol intoxication; and one of unknown cause. There were two (0.05%) cases of suicidality with secukinumab: one attempted suicide and one case of suicidal ideation. Nasopharyngitis and upper respiratory tract infections were the most frequently reported AEs with secukinumab. The incidence of inflammatory bowel disease (IBD)/Crohn’s, infections, neutropenia, major adverse cardiac events (MACE), and malignancy with secukinumab was low.
Conclusion: Secukinumab was well-tolerated in a large cohort of 3,928 patients across seven Phase 3 studies with PsA and PSO. The safety profile was consistent with previous reports.
Financial disclosures/funding: This research was funded by Novartis Pharma AG, Basel, Switzerland.
Long-term Use of Once-daily Brimonidine Gel 0.33% for Treating Facial Erythema of Rosacea, Improved Quality of Life, and Decreased Basal Levels of Erythema
Presenters: 1Jonathan Weiss, MD; 2Angela Moore, MD; 3Steven Kempers, MD; 4George Murakawa, MD; 5Amanda Tauscher, MD; 6Leonard Swinyer, MD; 7Matthew Leoni, MD; 8Gregor Schaefer, MD
Affiliations: 1Gwinnett Clinical Research, Snellville, GA; 2Arlington Center for Dermatology, Arlington, TX; 3Minnesota Clinical Study Center, Fridley, MN; 4Dermcenter PC, Troy, MI; 5Compliant Clinical Research, Olathe, KS; 6Dermatology Research Center, Salt Lake City, UT; 7Galderma R&D, Princeton, NJ; 8Galderma SAS, Paris, France
Objectives: Investigate safety and efficacy of 12 months of once-daily topical brimonidine gel 0.33% for facial erythema of rosacea treatment. Compare pre- and post-treatment subject social life questionnaire responses. Observe treatment effect on pre-application erythema and telangiectasia.
Materials and Methods: Once-daily application of topical brimonidine gel 0.33% was investigated in a 12-month, open-label, 27-center, US study of moderate-to-severe erythema of rosacea. There were no facial lesions of rosacea or concomitant medication restrictions. Pre-application erythema and telangiectasia severity were assessed at baseline, Week 1, and Months 1, 3, 9, and 12. Social life impact questionnaires were completed at baseline and every third month.
Results: Two-hundred and seventy-nine subjects completed the study. Compared to baseline, one-grade pre-application erythema improvements were 69.6 percent (Patient’s Self-Assessment) and 66.0 percent (Clinician’s Erythema Assessment). At study end, 44.0 percent of subjects exhibited one-grade improvement in pre-application telangiectasia compared to baseline. Social life impact questionnaire responses indicated that treatment improved subject perception of social life impact of rosacea.
Conclusion: Pre-application erythema severity was lower after 12 months of study treatment in subjects with moderate-to-severe erythema of rosacea. Telangiectasia scores also improved and fewer patients reported negative social life impact compared to baseline.
A Randomized, Double-blind, Vehicle-controlled, Parallel Group Study of the Dose-response Profile of A-101 Solution in Subjects with Seborrheic Keratosis of the Face
Presenters: Diane S. Berson, MD; Stuart D. Shanler, MD; Christopher V. Powala; Brian B. Beger
Clinical Trial Investigators: Andrew Blauvelt, MD; Michael Jarrett, MD; Andrew Pollack, MD; David Wilson, MD. All received remuneration from Aclaris Therapeutics as investigators.
Background: Seborrheic keratosis (SK) is one of the most common cutaneous lesions and affects over 83 million Americans. Treatment options, such as cryosurgery, electrosurgery, curettage, or surgical excision are employed; however, pain during treatment, long-term pigmentary changes (particularly hypopigmentation), and/or scarring at the treatment site are common. A-101 Solution, an investigational new drug, is a patented, proprietary, topical formulation of stabilized hydrogen peroxide with a surface tension reducing agent, which may offer a safe, noninvasive approach to removing SK lesions. The main objective of this study was to evaluate the dose-response relationship of two concentrations of the active ingredient when A-101 Solution is applied to target SK lesions on the face compared with a matching vehicle.
Methods: This randomized, multi-center, double-blind, vehicle-controlled study, enrolled subjects having one SK lesion on the face for treatment with A-101 40% Solution, A-101 32.5% Solution, or vehicle. Eligible subjects were at least 18 years of age and had one clinically typical stable SK on the face that was graded as 2 or 3 on the Physician Lesion Assessment (PLA) scale, a validated 4-point assessment scale. Study medication was applied to subjects at the baseline visit with a re-treatment 21 days later for lesions with a PLA score >0. The study included a no-treatment follow-up period of 84 days.
Results: 116 of 119 subjects randomized completed the study. In the primary analysis, a pairwise comparison between vehicle and each active medication group based on mean change from baseline in PLA score at each visit, A-101 Solution achieved statistical significance in reducing SK lesions in a dose-related fashion beginning at Day 22 and at all other visits through the end of the study, Day 106 (p<0.001). In the secondary responder analysis, the percentage of subjects achieving clear (PLA = 0) was 59.5 percent in the A-101 40% Solution group, 46.2 percent in the A-101 32.5% Solution group, and 2.5 percent in the vehicle group (p<0.0001). Primarily mild, transient local skin reactions were observed and reported. No hypopigmentation was observed in any of the treatment groups at Day 106. No subjects in the study experienced serious AEs that were deemed related to study medication.
Conclusion: A-101 Solution was clinically and statistically effective in treating SK lesions on the face with A-101 40% Solution being more effective than A-101 32.5% Solution. A-101 Solution had a favorable safety and tolerability profile at both concentrations when applied up to two times to SK lesions on the face.
Financial disclosures/funding: Aclaris Therapeutics.
Patient-reported Impact of Chronic Hives Relative to Psoriasis in the US
Presenters: 1Susan Gabriel; 2Jeffrey Vietri; 1Meryl Mendelson; 1Haijun Tian; 3Maria-Magdalena Balp; 4Mark Lebwohl
Affiliations: 1Novartis Pharmaceuticals Corporation, East Hanover, NJ; 2Kantar Health, Horsham, PA; 3Novartis Pharma AG, Basel, Switzerland; 4Mount Sinai Hospital, New York, NY
Background: Chronic idiopathic urticaria (CIU) is associated with impaired health outcomes, but few studies place the burden in the context of dermatological conditions where disease impact is better understood.
Objective: To assess the burden of CIU according to patient-reported outcomes using psoriasis (PsO) of varying severity as a benchmark.
Methods: Data came from the 2010–2012 US National Health and Wellness Surveys (NHWS). A diagnosis of chronic urticaria (CU; ≥6 weeks) served as proxy for CIU (the most common type of CU) since CIU was not specifically assessed in NHWS. Respondents diagnosed with PsO were analyzed by self-reported body surface area (BSA), with <2–3% classified as mild (category varied by data year), ≤10% moderate, and >10% severe. Severity was not assessed for CU. Measures included health-related quality of life (SF-12v2/SF-36v2 mental and physical component summary scores [MCS and PCS][respectively], SF-6D health utility), psychological complaints, the Work Productivity and Activity Impairment questionnaire and healthcare visits.
Results: A total of 747 respondents reported CU, and 5,107 reported PsO (n=3,468 mild, n=1,336 moderate, and n=303 severe). MCS scores among patients with CU (44.7), moderate and severe PsO (44.7 and 44.3) indicated lower mental health status than the US norm (50). PCS scores indicated physical health status was lower still: 43.8 for CU, and 46.5, 44.1, and 40.3 for mild, moderate, and severe PsO, respectively. The mean SF-6D score of patients with CU (0.67) was similar to patients with moderate PsO (0.72, 0.67, and 0.65 for mild, moderate, and severe PsO, respectively). Depression was reported by 39 percent of patients with CU, and 26 percent, 32 percent, and 33 percent of patients with mild, moderate, and severe PsO, respectively. Anxiety was reported by 42 percent of patients with CU, and 29 percent, 36 percent, and 30 percent of patients with mild, moderate, and severe PsO; and sleep difficulties by 50 percent for CU, and 38 percent, 44 percent, and 47 percent for mild, moderate, and severe PsO.
Patients lost substantial work productivity, with mean overall work impairment of 29 percent for CU, and 19 percent, 27 percent, and 31 percent for mild, moderate, and severe PsO, respectively. Mean activity impairment was also substantial, 39 percent for CU, 28 percent, and 37 percent, and 43 percent for mild, moderate, and severe PsO, respectively. These patients were also frequent users of healthcare, with a mean of 7.1 visits in the past six months for CU and 5.2, 5.6, and 6.6 visits for mild, moderate, and severe PsO, respectively.
Conclusion: The average patient with CU in the survey had impairments to health-related quality of life, work, and non-work activities similar to the average patient with moderate PsO. High levels of depression, anxiety, and overall healthcare use among patients with CU suggest a need for better management of this disease.
Financial disclosures/funding: This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, and Genentech, Inc., South San Francisco, CA.
A Randomized, Double-blind, Vehicle-controlled, Parallel Group Study of the Dose-response Profile of A-101 Solution in Subjects with Seborrheic Keratosis of the Face.....S20
A Double-blind, Randomized Study to Compare Microcyn Scar Management HydroGel, K103163, and Kelo-cote Scar Gel for Hypertrophic or Keloid Scars.....S8
Activity of Dapsone versus Community and Hospital Bacterial Pathogens from the Canward Study.....S4
Age and Gender as Predictors of Treatment Outcomes with Once-Daily Dapsone 7.5% Topical Gel for Acne Vulgaris.....S4
An In Vitro Study Demonstrating Nail Penetration of Tavaborole from Tavaborole Topical Solution, 5% through Multiple Layers of Nail Polish.....S11
Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Moderate-to-severe Plaque Psoriasis: Pooled 16-Week Efficacy in Patient Subgroups (ESTEEM 1 and 2).....S15
Apremilast for the Treatment of Psoriasis and Psoriatic Arthritis: Management of Gastrointestinal Adverse Effects.....S15
ATX-101 (Deoxycholic Acid Injection) is Safe and Effective in Men: Results from a Pooled Analysis of the REFINE Trials.....S5
Changes in Skin Laxity Among Responders to ATX-101 (Deoxycholic Acid Injection) in the REFINE Trials.....S6
DFD-01, a Class 3/4 Betamethasone Dipropionate 0.05% Emollient Formulation Demonstrates Similar Efficacy to a Class 1 Topical Steroid for the Treatment of Moderate Psoriasis.....S13
DFD-01 A Novel Emollient Spray Formulation of 0.05% Betamethasone Dipropionate Effectively Treats Plaque Psoriasis on Knees and Elbows.....S14
Efficacy and Safety of Adalimumab versus Methotrexate Treatment in Pediatric Patients with Severe Chronic Plaque Psoriasis: Results from the 16-Week Randomized, Double-Blind Period of a Phase 3 Study.....S11
Efficacy and Safety of Dupilumab for Moderateto-severe Atopic Dermatitis in Adults: A Pooled Analysis of Two Phase 2 Clinical Trials.....S9
Efficacy and Safety of Once-daily Dapsone Gel 7.5% for Treatment of Adolescents and Adults with Acne Vulgaris: First of Two Identically Designed, Large, Multicenter, Randomized, Placebo-Controlled Trials.....S3
Efficacy and Safety of Once-daily Dapsone Gel 7.5% for Treatment of Adolescents and Adults with Acne Vulgaris: Second of Two Identically Designed, Large, Multicenter, Randomized, Placebo-Controlled Trials.....S3
Efficacy of CeraVe Itch Relief Lotion and Cream on Itch Relief in Patients with Atopic Dermatitis.....S10
Efficacy of Secukinumab in Patients with Plaque Psoriasis: Area Under the Curve of Treatment Response Rates.....S13
Evolution of Acne Assessments and Impact on Acne Medications: An Evolving, Imperfect Paradigm.....S5
Long-term Use of Once-daily Brimonidine Gel 0.33% for Treating Facial Erythema of Rosacea, Improved Quality of Life, and Decreased Basal Levels of Erythema.....S20
Multicenter Pivotal Study of the Safety and Effectiveness of a Tissue Stabilized-Guided Subcision Procedure for the Treatment of Cellulite-Interim 3 Year Update.....S8
Patient-reported Impact of Chronic Hives Relative to Psoriasis in the US.....S21
Pregnancy Outcomes in the Tofacitinib Psoriasis Safety Database up to April 2014.....S19
Regression Analysis of Local Skin Responses to Predict Clearance of Actinic Keratoses on the Face in Patients Treated with Ingenol Mebutate Gel.....S9
Results From Two Phase 3 Studies in Children and Adults With Mild-to-moderate Atopic Dermatitis Treated with Crisaborole Topical Ointment, 2%, a Novel Nonsteroidal, Topical Anti-Inflammatory, Phosphodiesterase 4 Inhibitor....S10
Retrospective Safety Study of Combining Micro-Focused Ultrasound with Visualization (MFU-V) with Neurotoxins and Fillers (HA and CaHA).....S7
Safety and Efficacy of ATX-101 (Deoxycholic Acid Injection) for Reduction of Submental Fat: Results from a Multicenter, Open-Label Phase 3b Trial.....S7
Safety of Apremilast and Etanercept Compared with Placebo in Patients with Moderate to Severe Psoriasis: Results From the LIBERATE Study.....S16
Secukinumab Administration by Prefilled Syringe Maintains Efficacy in Moderate-to-se vere Plaque Psoriasis Over 100 Weeks: Results of the FEATURE Trial.....S18
Secukinumab Delivers Greater Improvement in Health-related Quality of Life Compared to Ustekinumab in Subjects With Moderate-tosevere Plaque Psoriasis: 16-Week Data From the CLEAR Study.....S17
Secukinumab Exhibits Low Immunogenicity During 104 Weeks of Treatment in Subjects with Moderate-to-severe Plaque Psoriasis.....S17
Secukinumab in Psoriasis: Relationship Between Clinical- and Patient-reported Outcomes Using Clinical Trial Data from the ERASURE and FIXTURE Trials.....S14
Secukinumab is Predominantly Prescribed at the Recommended 300mg Dose to Psoriasis Patients in the United States.....S18
Secukinumab Safety and Tolerability in Patients with Active Psoriatic Arthritis and Psoriasis: Results from a Pooled Safety Analysis.....S19
The Aerosol Foam Formulation Of Fixed Combination Calcipotriene Plus Betamethasone Dipropionate Is Efficacious In Patients with Psoriasis Vulgaris: Pooled Data From Three Randomized Controlled Studies.....S12
BEDDINGFIELD III FC.....S6,S7
BERK D....S3, S4
CHANG-LIN J.....S3, S4
COLEMAN III WP.....S8
COLEMAN IV P.....S8
DEL ROSSO JQ.....S5
KAOKHOV A.....S3, S4