Understanding the African American facial aesthetic patient

Understanding the African American facial aesthetic patient

Presenters: Boyd C1, Alexis A2, Callender V3, Downie J4, Shumate GT5, Gallagher CJ5

Affiliations: 1BOYD, Birmingham, MI; 2Icahn School of Medicine at Mount Sinai, New York, NY; 3Callender Dermatology and Cosmetic Center, Glenn Dale, MD; 4Image Dermatology, Montclair, NJ; 5Allergan plc, Irvine, CA

Background/Objective: Aesthetic injectors might perceive challenges when addressing the aesthetic needs of African American patients. Understanding the anatomical considerations, facial aging patterns, aesthetic concerns, and treatment preferences might increase the comfort level for the injector and improve outcomes for African American patients. Injectors should also consider any patient misconceptions (e.g., keloid scarring) associated with injection procedures. Accordingly, clinical case studies can provide practical examples of how to implement this knowledge during patient consultation, assessment, and treatment. Two studies were performed to gain insights into self-reported facial aging characteristics and treatment considerations among African American patients.

Methods: Eight-hundred and fifty-nine African American men (145) and women (714) completed an online evaluation in which they assessed their facial features against photonumeric scales depicting degrees of severity for 10 facial characteristics. Four-hundred and one African American women completed a separate online evaluation to identify areas of aesthetic concern, relative prioritization of treatment areas, and attitudes toward injectable treatments. Respondents for both evaluations were naïve to facial aesthetic treatments. A subsequent meeting of experts with significant experience in treating African American patients produced case studies to illustrate the translation of these data to the clinical setting.

Results: In the African American population, moderate-to-severe signs of facial aging were not generally reported until 50 to 79 years of age. At ages 70 to 79 years, over 70 percent were still without moderate-to-severe perioral lines, loss of lip fullness, or midface volume loss. The majority reported having uneven skin tone/color (57%) and dark circles under the eyes (48%). African American patients were most bothered by their tear trough and submental regions. Areas most likely to be prioritized for treatment included tear trough, submental region, and horizontal forehead lines. In contrast, African American patients were less likely to prioritize treatment of perioral lines, lips, temples, and cheeks. African American women reported the lowest consideration rate for injectables (64%), compared to Asian or Hispanic individuals. “Looking good for their age” was the top reason for considering aesthetic treatment, but the cost, perceived safety, and side effects were the largest barriers. Clinical case studies demonstrated practical treatment strategies utilizing commercially available facial aesthetic products.

Conclusion: Across the two research studies, self-reported facial aging characteristics correlated with bothersome areas; both tear trough treatment and submental fat reduction could be seen as entry points for facial aesthetic injectables for this population. An understanding of these objective research findings and practical case studies might increase the comfort level for an injector and improve outcomes for African American patients.

Efficacy, safety, and patient-reported outcomes following onabotulinumtoxinA treatment for moderate-to-severe forehead lines: a pooled analysis of two Phase III pivotal trials

Presenters: De Boulle K1, Fagien S2, Mao C3, Shumate GT3, Gallagher CJ3

Affiliations: 1Aalst Dermatology Clinic, Aalst, Belgium; 2Aesthetic Eyelid Plastic Surgery, Boca Raton, FL; 3Allergan plc, Irvine, CA

Background/Objective: Two pivotal, Phase III studies were conducted to evaluate the safety and efficacy of onabotulinumtoxinA (onabotA) versus placebo (PBO) for treatment of moderate-to-severe forehead lines (FHL).

Methods: In both studies, neurotoxin-naïve subjects were randomized to receive onabotA 40U (frontalis 20U, glabella 20U) or PBO. The second study included an additional treatment arm in which bilateral crow’s feet regions (CFL) were also treated for a total dose of 64U (FHL 20U, GL 20U, CFL 24U) or PBO. After Day 180, all eligible subjects could receive up to two additional open-label onabotA treatments, with assessments to Day 360. Dynamic and static FHL were assessed at all timepoints by both investigator and subject using the Facial Wrinkle Scale with photo numeric guide. Subject satisfaction with treatment was evaluated using the validated Facial Lines Satisfaction Questionnaire (FLSQ).

Results: This pooled analysis comprised 1,178 subjects in the intent-to-treat (ITT) population (onabotA 40U n=608, onabotA 64U n=313; PBO n=257). At maximum eyebrow elevation, Day 30 responder rates for those achieving more than a 2-grade composite FHL improvement based on investigator and subject FWS were 53.1 (40U) and 53.0 (64U) percent, respectively. Responder rates for those achieving more than a 1-grade FHL improvement were 97.9 (40U) and 99.0 (64U) percent, respectively. Percentage of subjects achieving a score of none/mild FHL were 92.3 (40U) and 94.9 (64U) percent, respectively. Of those subjects with at least mild static FHL at baseline, 85.4 (40U) and 84.8 (64U) percent achieved more than a 1-grade improvement at rest. Efficacy and patient satisfaction were comparable across treatment cycles. Based on the FLSQ, 85.6 (40U) and 87.9 (64U) percent of subjects reported being mostly satisfied or very satisfied with the effect treatment had on their forehead lines at Day 60. Across all treatment cycles over 12 months, 25.4 percent of subjects had treatment-related adverse events; of note were brow ptosis (2.6%) and lid ptosis (1.8%). Most frequently reported treatment-emergent adverse events included headache (11.8%), injection site bruising (7.4%), nasopharyngitis (8.3%), and upper respiratory tract infection (4.3%). No new safety signals were detected with repeated upper facial line treatments.

Conclusion: OnabotA significantly improved the appearance of FHL. Treatment of upper facial lines was well tolerated with efficacy and patient satisfaction maintained across repeat treatments.

Reduction of submental fat continues beyond 28 days after ATX-101 treatment: results from a post-hoc analysis

Reduction of submental fat continues beyond 28 days after ATX-101 treatment: results from a post-hoc analysis

Presenters: Dover JS1, Shridharani SM2, Bloom JD3, Somogyi C4, Gallagher CJ4

Affiliations: 1SkinCare Physicians, Chestnut Hill, MA; 2LUXURGERY, New York, NY; 3Main Line Center for Laser Surgery, Ardmore, PA; 4Allergan plc, Irvine, CA

Background/Objective: ATX-101 (deoxycholic acid injection) is approved in the United States, Australia, Canada, and Europe for reduction of submental fat (SMF). When injected into subcutaneous fat, ATX-101 results in adipocytolysis, which induces a localized inflammatory response to clear cellular debris and lipids liberated from the injection site. In ATX-101 clinical trials, subjects received 4 to 6 treatments spaced at intervals of 28 ± 5 days. A post-hoc analysis was conducted to characterize the response after a single ATX-101 treatment using data from a patient experience management study (NCT02007434).

Methods: Adults aged 18 to 65 years with a moderate or large amount of SMF (as assessed via the validated 5-point Clinician-Reported and Patient-Reported SMF Rating Scales) who were dissatisfied with the appearance of their face or chin were enrolled. Subjects were randomized to one treatment with either ATX-101 (area-adjusted dose: 2mg/cm2) or placebo. This post-hoc analysis evaluated efficacy among ATX-101-treated subjects (n=68); subjects with moderate SMF at baseline based on clinician assessment (n=49) received 6mL of ATX-101 while subjects with severe SMF (n=19) received 8mL. Outcomes, evaluated at Days 28 and 84 following ATX-101 treatment, included the percentage of subjects who achieved at least a 1-grade improvement in SMF from baseline based on clinician assessment (CR-1 response), percentage of subjects who achieved at least 1-grade improvement in SMF from baseline based on clinician and subject assessment (composite CR-1/PR-1 response), and mean change in SMF thickness from baseline (measured with calipers).

Results: Most ATX-101-treated subjects were female (62%) and Caucasian (79%). At baseline, 72 percent versus 28 percent of subjects had a moderate versus large amount of SMF, respectively. At Day 28, the CR-1 response rate was 14.1 percent. By Day 84, the CR-1 response rate increased to 47.0 percent. Similarly, the composite CR-1/PR-1 response rate was 7.8 percent at Day 28, and increased to 37.9 percent by Day 84. SMF thickness increased from baseline by 2.1mm at Day 28, which might be related to residual swelling and/or induration within the treatment area. However, SMF thickness decreased from baseline by 1.3mm at Day 84.

Conclusion: Results from this analysis demonstrate that reduction of SMF continues in 2 to 3 months following ATX-101 treatment. Overall, these data provide evidence of a progressive reduction in SMF beyond the 28-day retreatment interval used in the pivotal clinical trials and suggest that benefit might be gained by extending the interval between ATX-101 treatments beyond 28 days.

Funding: Funded by Allergan plc.

Subject satisfaction demonstrated for two on-label injection volumes of abobotulinumtoxinA (ABO) when used to treat moderate-to-severe glabellar lines

Subject satisfaction demonstrated for two on-label injection volumes of abobotulinumtoxinA (ABO) when used to treat moderate-to-severe glabellar lines

Presenters: Cohen J1, Kaufman J2, Peredo M3, Jonas B4, Nogueira A4, Mashburn J4

Affiliations: 1Director of AboutSkin Dermatology and DermSurgery, Greenwood Village and Lone Tree, CO, Associate Clinical Professor, Department of Dermatology, University of Colorado, CO, and Assistant Clinical Professor, Department of Dermatology, University of California Irvine; 2Skin Associates of South Florida, Skin Research Institute, Coral Gables, FL; 3Marina I. Peredo, MD, Smithtown, NY; 4Galderma Laboratories, L.P., Fort Worth, TX

Background/Objective: In the United States (US), glabellar lines (GLs) are most often treated with botulinumtoxin type A (BoNT-A), and satisfaction with treatment is typically measured using patient-reported outcomes. Dysport (abobotulinumtoxinA [ABO]) is approved in the United States for the treatment of GLs and can be injected at two different injection volumes­—0.05mL and 0.08mL. This was a multicenter, randomized, subject- and evaluator-blinded study to evaluate the safety, efficacy, and subject satisfaction of two on-label injection volumes, 0.05mL/injection (Group A) and 0.08mL/injection (Group B), for the treatment of GLs. This report focuses on the subject satisfaction health-related quality of life aspects of the study.

Methods: Subjects with moderate-to-severe GLs at maximum frown were treated with ABO. Subjects were randomized to receive either 0.05mL/injection (Group A) or 0.08mL/injection (Group B), per the approved US label (5 injection points in the glabella area totaling 50U [10U at each injection site] for 1 treatment session). Subjects were given one treatment, then followed for up to four months. Subject assessments were completed before and after treatment.

Results: At 30 days posttreatment, the majority of subjects reported they were satisfied with how attractive they looked (86.7% for Group A, 76.7% for Group B), compared to baseline pretreatment, 20.0 and 36.7 percent, respectively. Subjects also felt more confident after either treatment (90.0% and 80.0% at Day 30, Group A and B, respectively) compared to baseline, 33.3 and 33.3 percent, respectively. At Day 30, subjects also reported an increase in psychological well-being (mean change from baseline 29.5 [P<0.0001] for Group A and 25.0 [P<0.0001] for Group B), being less bothered by their GLs (mean change from baseline 52.2 [P<0.0001] for Group A and 45.7 [P<.0001] for Group B), and looking four years younger than their current age compared to baseline (mean change from baseline -4.4 [P<0.0001] for Group A and -4.3 [P<0.0001] for Group B). These results were mostly maintained through 120 days posttreatment. There were no significant differences between treatment groups.

Conclusion: Subjects treated with two on-label injection volumes of ABO for moderate-to-severe GLs reported high subject satisfaction and increased psychological well-being through Day 120.

Funding: Galderma Laboratories, L.P.

Differential facial aesthetic treatment considerations for skin of color populations: African American, Asian and Hispanic

Differential facial aesthetic treatment considerations for skin of color populations: African American, Asian and Hispanic

Presenters: Boyd C1, Chiu A2, Montes JR3, Narurkar V4; Shumate GT5, Gallagher CJ5

Affiliations: 1BOYD, Birmingham, MI; 2The Derm Institute, Hermosa Beach, CA; 3José Raúl Montes Eyes & Facial Rejuvenation, San Juan, PR; 4Bay Area Laser Institute, San Francisco, CA; 5Allergan plc, Irvine, CA

Background/Objective: By 2050, more than half of the total population in the United States will be of African American, Asian, or Hispanic descent. The unique anatomical needs, aesthetic goals, and cultural considerations for these growing patient populations should be evaluated to optimize treatment expectations and outcomes. A research study was performed to gain insights into the areas of aesthetic concern, relative prioritization of treatment areas, and any barriers to receiving injectables among these populations.

Methods: Four-hundred and one African American, 403 Asian, and 401 Hispanic women living in the United States, aged 30 to 65 years, completed an online evaluation in which questions focused on identifying bothersome facial areas, consideration levels for facial aesthetic treatments, and any barriers to receiving injectables. A maximum difference scaling method was used to identify which of the 15 facial areas would be prioritized for treatment. Respondents were naïve to facial aesthetic treatments but were aesthetically oriented and were considering physician administered aesthetic treatment within the next two years.

Results: The Hispanic population reported the highest consideration rate for injectables (85%), followed by Asian (75%) and African Americans (64%). African American and Hispanics were most bothered by their submental region, whereas Asian respondents were most bothered by the area underneath the eyes (infraorbital area). All skin of color populations prioritized first the periorbital region (infraorbital and crow’s feet areas) followed by the submental area and forehead lines. Relative to the other populations, African American respondents expressed the highest prioritization of the submental region. All respondents then prioritized treatment of glabellar lines, nasolabial folds, and oral commissures. Analysis by increasing Fitzpatrick Type (I–VI) showed an increasing prioritization of the periorbital region and decreasing prioritization of the chin and perioral lines. Most frequently cited barriers to considering injectable treatment included safety and side effects, concern about injecting a foreign substance into the body, and cost.

Conclusion: Understanding the unique aesthetic considerations of a diversifying patient population is imperative. Differences in injectable consideration rates and bothersome areas were apparent across the patient populations evaluated, but there was consensus regarding the facial areas most likely to be prioritized for treatment. An understanding of the differential aging patterns, cultural considerations, and aesthetic goals for each patient population may help optimize treatment expectations and outcomes.

IncobotulinumtoxinA versus onabotulinumtoxinA in the treatment of glabellar facial lines: results from a multicenter, randomized, double-blinded trial

IncobotulinumtoxinA versus onabotulinumtoxinA in the treatment of glabellar facial lines: results from a multicenter, randomized, double-blinded trial

Presenters: Kane MAC1, Gold MH2, Coleman WP III3, Jones DH4, Tanghetti EA5, Alster TS6, Rohrer TE7, Burgess CM8, Shamban AT9

Affiliations: 1Manhattan Eye, Ear & Throat Hospital, New York, NY; 2Tennessee Clinical Research Center, Nashville, TN; 3Tulane Health Sciences Center, New Orleans, LA; 4Skin Care and Laser Physicians of Beverly Hills, Los Angeles, CA; 5Center for Dermatology and Laser Surgery, Sacramento, CA; 6Washington Institute of Dermatologic Laser Surgery, Georgetown University Hospital, Washington, DC; 7Skin Care Physicians, Chestnut Hill, MA; 8Center for Dermatology and Dermatologic Surgery, Washington, DC; 9University of California Los Angeles, Los Angeles, CA

Background/Objective: Botulinum toxin type A is a well-established treatment for glabellar frown lines. Head-to-head comparison studies have demonstrated that incobotulinumtoxinA (Xeomin®) versus onabotulinumtoxinA (Botox®) result in comparable safety and efficacy for both cosmetic and therapeutic uses. In 2011, incobotulinumtoxinA was approved by the United States Food and Drug Administration (FDA) for improvement in the appearance of moderate-to-severe glabellar frown lines with a recommended dosage of 20 units (U).

This is the first large, multicenter, randomized, double-blinded, parallel-group study to compare the efficacy and safety of incobotulinumtoxinA versus onabotulinumtoxinA after a single 20U treatment to improve the appearance of glabellar frown lines.

Primary endpoint was response defined as a 1-point or greater improvement from baseline on the Facial Wrinkle Scale (FWS) at maximum frown one month from treatment.

Methods: Patients were randomized 1:1. Two-hundred and fifty female subjects 18 to 50 years of age (median age was 41 for both groups) with moderate-to-severe GFL on a 4-point FWS at maximum frown were included. Study duration was 120 days for each subject, plus the individual duration of screening (Day ?14 to 0). Eligible subjects received a single injection of the study treatment at Day 0 (baseline). Dose was 20U in both treatment groups; injection volume was 0.5mL.

Results: Primary endpoint was met. Primary efficacy analysis demonstrated equivalence of incobotulinumtoxinA and onabotulinumtoxinA at one month, with 95.7 percent of subjects in the incobotulinumtoxinA group achieving at least a 1-point improvement on FWS and 99.2 percent of subject in that onabotulinumtoxinA group achieving the same. Treatment satisfaction for both groups remained above 90 percent for the entire four-month treatment period. Fourteen (11.5%) subjects treated with incobotulinumtoxinA reported treatment-emergent adverse events (TEAE); 18 (14.1%) of subjects in the onabotulinumtoxinA group reported TEAEs. The most common TEAE among both groups was headache (incobotulinumtoxinA: n=7; onabotulinumtoxinA: n=5).

Conclusion: IncobotulinumtoxinA and onabotulinumtoxinA result in similar efficacy and safety profiles for the treatment of glabellar facial lines.

Funding: This study was funded by Merz North America, Inc.

Microfocused ultrasound in combination with diluted calcium hydroxylapatite for improving skin laxity and the appearance of lines in the neck and décolletage

Presenter: Casabona G

Affiliation: Cosmetic and Surgical Dermatology and Mohs Surgery, Clinica Vida, Sao Paulo, Brazil

Background/Objective: Skin laxity and wrinkling on the neck and décolletage can be age-revealing. The objective of this study was to evaluate the combined use of microfocused ultrasound with visualization (MFU-V) and diluted calcium hydroxylapatite (CaHA) for treating lines and wrinkles of the neck and décolletage.

Methods: Subjects with moderate-to-severe lines on the neck and/or décolletage were retrospectively enrolled. Prior to MFU-V treatment, a topical anesthetic (7% lidocaine, 7% prilocaine) was applied. For both the neck and décolletage, subjects were treated at two depths using the 7MHz transducer at a focal depth of 3.0mm and the 10MHz transducer at a depth of 1.5mm, applying 150 lines for each transducer per site. Immediately after MFU-V, subjects received treatment with CaHA (1.5 ml diluted 1:1 with 1.5 ml of 2% lidocaine solution). For the neck, CaHA was injected subdermally in microdroplets using a fanning technique with a 25G long cannula from four points of entrance starting on top of the lines and extending in a fan shape around the lines to cover the same area as the MFU-V (half a syringe per side). A similar technique was used for décolletage, but with three points of entry. Injections were followed by vigorous massage to ensure that the product was evenly dispersed. Subjects were assessed for skin laxity and wrinkling in the neck and décolletage at baseline and at 90 days (2 blinded, independent evaluators) using three validated scales: Merz Aesthetics Décolleté Scale and Fabi-Bolton Chest Wrinkle Scale (both scales range from 0=no wrinkles, 1=mild wrinkles, 2=moderate wrinkles, 3=severe wrinkles 4=very severe wrinkles); and Allergan Transverse Neck Lines Scale (ranging from 1=no wrinkles to 5=very severe wrinkles. Subject satisfaction was assessed using a 5-point scale (1=very unsatisfied, 2=unsatisfied, 3=neither satisfied nor dissatisfied, 4=satisfied, 5=very satisfied). Pain was assessed and adverse events (AEs) were documented.

Results: At baseline, 24 out of the 42 subjects were given a Grade 2 in the Allergan Transverse Neck Line Scale by Evaluator 1; Evaluator 2 placed 23 out of 42 subjects in the Grade 2 category. None of the subjects achieved a Grade 1 for neck lines at baseline. At 90 days, Evaluators 1 and 2 placed 30 and 27 subjects, respectively, in the Grade 1 category for neck lines. At baseline, 17 out of 18 subjects and 16 out of 18 subjects were given a Grade 2 or higher on the Merz Aesthetics décolletage wrinkles scale. At 90 days, 18 out of 18 subjects achieved a Grade 2 or lower from both evaluators. Using the subject satisfaction scale at baseline, the majority (64.3%) were neither satisfied nor dissatisfied with the neck lines treatment. At Month 3, the majority (54.8%) were very satisfied with the neck lines treatment. At baseline, the majority (66.7%) were neither satisfied nor dissatisfied with the décolletage treatment. At Month 3, 50.0 percent were satisfied and 44.4 were very satisfied with the décolletage treatment. Mild pain was experienced by 90 percent of subjects during the procedure; 10 percent reported no discomfort at all. All subjects experienced bruising, which resolved in three to seven days. No other AEs were reported.

Conclusion: Combining MFU-V with 1:1 diluted CaHA is effective in improving the appearance of neck and décolletage lines and wrinkles. Both procedures were well tolerated, and subject satisfaction was high.

Adapalene 0.3% / benzoyl peroxide 2.5% gel plus oral doxycycline is an effective and safe option for oral isotretinoin candidates with severe inflammatory acne (non-nodulocystic/nonconglobate)

Adapalene 0.3% / benzoyl peroxide 2.5% gel plus oral doxycycline is an effective and safe option for oral isotretinoin candidates with severe inflammatory acne (non-nodulocystic/nonconglobate)

Presenters: Del Rosso J1, Gold LS2, Johnson SM3, Rueda MJ4, Baldwin H5, Lain EL6, Landis M7, Rendon M8, Tanghetti E9, Thiboutot D10, Weiss J11

Affiliations: 1Thomas Dermatology, Las Vegas, N; 2Henry Ford Medical Center, Deptartment of Dermatology, Detroit, MI; 3Johnson Dermatology, Fort Smith, AR; 4Galderma Laboratories, L.P., Fort Worth, TX; 5The Acne Treatment and Research Center, Morristown, NJ; 6Austin Institute for Clinical Research, Pflugerville, TX; 7Forefront Dermatology, Jeffersonville, IN; 8Rendon Center for Dermatology and Aesthetic Medicine, Boca Raton, FL; 9Center for Dermatology and Laser Surgery, Sacramento, CA; 10The Pennsylvania State University College of Medicine, Hershey, PA; 11Gwinnett Dermatology, Snellville, GA

Background/Objective: Acne treatment guidelines suggest combined topical therapy with oral antibiotics or oral isotretinoin (OI) as first-line treatments for severe acne. This study tested the efficacy and safety of a daily regimen of 0.3% adapalene/benzoyl peroxide (ABPO) gel and oral doxycycline 200mg (DOX, two 50mg delayed-release tablets twice-daily) in severe (non-nodulocystic, nonconglobate) inflammatory acne.

Methods: This was a Phase IV, 12-week, single-arm, open-label, multicenter investigational study. Men and women aged 12 years or older with severe inflammatory acne (IGA 4, n=186) and considered OI candidates by the investigator were enrolled. OI candidacy was reevaluated at each study visit. Efficacy endpoints included inflammatory lesion (IL) reduction (Week 12), IGA success (Weeks 4, 8, and 12), percent-reduction in lesions (Weeks 4, 8, and 12), and subject questionnaires (Week 12). Safety assessments included adverse events (AEs) and tolerability.

Results: Mean IL counts were significantly reduced (standard deviation [SD]; baseline, 44.8 (21.73); Week 12, 14.8 (16.11); mean percent-reduction, 66.2% [30.47]; P<.0001). By Week 12, 37.1 percent of subjects achieved IGA Success (n=69, P<0.0001). Most subjects self-reported at least moderate improvement in acne (90.2%) and were “Satisfied” or “Very Satisfied” with the study treatment overall (83.2%). Nearly half (41.9%) of the subjects were no longer considered OI candidates at Week 4. At 12 weeks, just 19.9 percent were still considered OI candidates. Twenty-seven (15.4%) AE were considered to have a reasonable possibility of being treatment-related (gastrointestinal disorders were the most common; n=7, 4.0%). Only four subjects discontinued due to an adverse event, (“skin burning sensation”; 1 mild, 2 moderate, 1 severe; all were considered “possibly related”).

Conclusion: 0.3% A/BPO plus DOX is an effective and safe treatment option for severe inflammatory acne (non-nodulocystic, nonconglobate) before starting OI treatment or as an alternative when OI cannot be used.

Funding/disclosures: This study was sponsored by Galderma Laboratories, L.P. Galderma is the maker of Epiduo Forte Gel. Dr. Rueda is an employee of Galderma. All other authors are advisors or investigators for Galderma.

Efficacy and safety of omalizumab in Japanese and Korean patients with chronic idiopathic/spontaneous urticaria (CIU/CSU): results from the Phase III POLARIS study

Efficacy and safety of omalizumab in Japanese and Korean patients with chronic idiopathic/spontaneous urticaria (CIU/CSU): results from the Phase III POLARIS study

Presenters: Hide M1, Park HS 2, Igarashi A3, Ye YM2, Kim TB4, Yagami A5, Roh JY6, Lee JH7, Fukunaga A8, Khalil S9

Affiliations: 1Department of Dermatology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; 2Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea; 3Department of Dermatology, NTT Medical Center Tokyo, Tokyo, Japan; 4Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 5Department of Allergology, Fujita Health University Second Educational Hospital, Nagoya, Japan; 6Department of Dermatology, Gachon University Gil Medical Center, Incheon, Korea; 7Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea; 8Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan; 9Novartis Pharma AG, Basel, Switzerland

Background/Objective: To date, the effect of omalizumab treatment on CIU/CSU has not been extensively assessed in an Asian population. POLARIS represents the first randomized, double-blind, placebo-controlled clinical trial of omalizumab for CIU/CSU in an Eastern Asian population.

Methods: Efficacy and safety of omalizumab as add-on therapy for treatment of CIU/CSU were evaluated in patients aged 12 to 75 years who were refractory to approved doses of nonsedating H1 antihistamines. This 26-week study comprised a two-week screening, 12-week randomized treatment, and 12-week follow up epochs. Patients (n=218) were randomized 1:1:1 to omalizumab 300mg, 150mg, or placebo by subcutaneous injection every four weeks. Primary outcome was changed from baseline (BL) to Week 12 (W12) in weekly itch severity score (ISS7). Secondary endpoints included change from BL in weekly urticaria activity score (UAS7) and weekly number of hives score (HSS7), proportion of patients achieving a UAS7 score between 0 and 6, and change in the Dermatology Life Quality Index (DLQI). Safety was assessed through the summary of adverse events (AEs).

Results: Most disease characteristics were well balanced across treatment arms. At W12, statistically significant decreases were observed from BL in ISS7 with omalizumab versus placebo (mean changes -10.22 and -8.80 for omalizumab 300mg and 150mg; p<0.001 and p=0.006 vs. placebo [-6.51], respectively). The corresponding mean changes from BL in UAS7 were -22.44 and -18.79 (p<0.001 and p=0.007 vs. placebo [?13.90], respectively). At W12, the proportions of patients treated with omalizumab 300mg or 150mg who achieved UAS7 scores of 6 or less were 57.5 percent and 42.9 percent (p<0.001 and p=0.002 vs. placebo [18.9%]), and for UAS7=0 were 35.6 percent and 18.6 percent (p<0.001 and p=0.013 vs. placebo [4.1%]), respectively. Mean changes in HSS7 at W12 were -12.17 and -10.04 with omalizumab 300mg and 150mg (p<0.001 and p=0.016 vs. placebo [-7.41]), respectively. Mean DLQI changes at W12 from BL were -8.4 and -7.2 with omalizumab 300mg and 150mg (p<0.001 and p=0.011 vs. placebo [-5.3]), respectively. Overall incidence of AEs was similar across treatment arms (54.8%, 57.7%, and 55.4% of subjects with omalizumab 300mg, 150mg, and placebo, respectively). Nasopharyngitis was the most frequently reported AE with all treatments.

Conclusion: POLARIS demonstrated that omalizumab treatment results in significant clinical benefits with no new safety concerns in patients with H1 antihistamine-refractory CIU/CSU in Japan and Korea.

An open-label study evaluating the quality of life, long-term efficacy, and safety of lidose-isotretinoin (ABSORICA®) capsules administered without food in patients with severe recalcitrant nodular acne: interim analysis of 20-week active treatment period

An open-label study evaluating the quality of life, long-term efficacy, and safety of lidose-isotretinoin (ABSORICA®) capsules administered without food in patients with severe recalcitrant nodular acne: interim analysis of 20-week active treatment period

Presenters: Zaenglein A1, Del Rosso J2

Affiliations: 1Department of Dermatology, Pennsylvania State University, Hershey, PA; 2JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV

Background/Objective: Severe acne is known to have a significant adverse effect on self-esteem and quality of life (QoL). Effective treatment of acne with isotretinoin can subsequently improve the patient’s QoL. The timing of QoL improvement over the course of treatment with lidose-isotretinoin has not been established. Isotretinoin products must be taken with a high-fat meal to achieve optimal absorption. Fasted plasma levels of isotretinoin can be nearly 60-percent lower than fed levels. Nonadherence with the food intake requirements can potentially compromise the long-term efficacy of isotretinoin. Absorption of lidose-isotretinoin is less dependent on the amount and/or type of food intake, and it can be taken without meals while still providing a reliable isotretinoin blood concentration. In this study, we evaluated the efficacy and safety of lidose-isotretinoin taken without food by patients with severe recalcitrant nodular acne, as well as assessed their quality of life. Primary objective during the 20-week active treatment period (ATP) was to evaluate the QoL of patients taking lidose-isotretinoin twice daily (bid) without food. Secondary objectives during the ATP were to evaluate the efficacy and safety of lidose-isotretinoin taken twice-daily without food.

Methods: This was a Phase IV, multicenter, single-arm, open-label study conducted in the United States in patients with severe recalcitrant nodular acne (NCT02457520) consisting of two phases: a 20-week (5-month) open-label ATP and a 104-week post-treatment period. Patients were included in the study if they were 12 to 45 years of age with recalcitrant acne severe enough for isotretinoin treatment, including five or more facial nodules. Included patients had no prior exposure to systemic isotretinoin or other systemic retinoid and weighed between 40kg and 110kg. Women included in the study could not be pregnant or breastfeeding; women of childbearing potential had to use two forms of effective contraception simultaneously for one month before the trial, during the trial, and for one month after stopping study medication, or commit to continuous abstinence from heterosexual intercourse.

Dosing during the 20-week ATP to attain target cumulative dose of 120mg to 150mg per kilogram of weight was 0.5mg/kg per day divided into two daily doses for four weeks, followed by 1.0 mg/kg per day divided into two daily doses for 16 weeks. Study medication was taken without food (1 hour before or at least 2 hours after ingestion of food or beverages other than water). Primary efficacy endpoint was the change from baseline to the end of treatment (EOT) in the Acne-QoL score, assessed on a graded scale (overall and by domain). Domains included self-perception, role-social, role-emotional, and acne symptoms. Secondary efficacy endpoints included monthly change from baseline in Acne-QoL scores (overall and by domain) and lesion counts during the ATP and change from baseline to EOT in Investigator’s Global Assessment (IGA) scores. Efficacy evaluation was conducted using the intent-to-treat (ITT) population. Overall Acne-QoL score, each domain score, and the changes from baseline for these scores were summarized using descriptive statistics. Differences between baseline and postbaseline values were analyzed using paired t-tests. Descriptive statistics are provided for mean percentage change from baseline value for inflammatory, noninflammatory, and total lesion counts. Differences between baseline and postbaseline values were analyzed using paired t-tests. Descriptive statistics are provided for IGA observed values.

Results: A total of 201 patients (mean age: 18.7 [range: 12–45] years) were enrolled in the study at 21 sites. Eighty-five percent (n=170/201) of patients completed the 20-week ATP. There was a significant increase in standard deviation (SD) Acne-QoL from baseline to EOT (61.4 [28.4] vs. 99.0 [19.8], P<0.0001). All four domains (self-perception, role-social, role-emotional, acne symptoms) were significantly improved over the course of treatment, with positive improvements beginning at Week 4. Mean (SD) percentage change in inflammatory (-87.2 [22.5]) and noninflammatory lesion (-83.2 [30.3]) counts from baseline to EOT were significant (P<0.0001).

Mean IGA scores improved from baseline by approximately 3.0 points at EOT. A total of 286 adverse events (AEs) was reported in 60.2 percent of patients (121/201). The most common AEs were dry skin (10.9%), dry lips (10.4%), and cheilitis (9.0%)

A total of 166 treatment-related AEs was reported in 46.3 percent of patients (93/201). Twelve severe AEs were reported; five were considered to be treatment-related (nausea [n=2], increased blood cholesterol [n=1], liver function test abnormal [n=1], and headache [n=1]). Psychiatric AEs occurred in 17 patients (8.5%). The psychiatric events reported were depression (4.0%), insomnia (1.0%), and anxiety (1.0%). Abnormal laboratory results occurred in 11 patients (5.5%), including increases in blood triglycerides (3.5%), alanine aminotransferase (1.5%), aspartate aminotransferase (1.5%), and blood cholesterol (1.5%). One serious AE was reported: diabetes mellitus on Study Day 127, severe in intensity and unlikely related to study treatment. Eight patients discontinued the study due to AE (psychiatric events [n=5] and abnormalities in laboratory test results [n=3]). Six additional patients had study drug withdrawn for an AE (psychiatric events [n=4], migraine [n=1], and diabetes mellitus [n=1]).

Conclusion: Twice-daily use of lidose-containing isotretinoin taken without food improved QoL over the 20-week treatment period, with improvement seen as early as Week 4. Clinical efficacy was also demonstrated. AEs were generally consistent with the known safety profile for isotretinoin.

Funding/Disclosures: This study was funded by Sun Pharmaceutical Industries, Inc. Andrea Zaenglein has served as a consultant for Ranbaxy/Sun Pharmaceutical Industries, Inc. James Del Rosso has served as a consultant, speaker, and research investigator for Sun Pharmaceutical Industries, Inc.

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