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.

Video: The Pathogenesis of Atopic Dermatitis

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Head-to-Head in Psoriasis: Brodalumab vs Ustekinumab

It has been unusual for companies to risk direct comparisons of new agents with recent vintage competitors, but that is beginning to happen in the crowded market for biologic agents in psoriasis.  It is also important to note that the trend toward a higher bar for efficacy assessment of treatments for this disease is continuing with a 100% reduction in the psoriasis area-and-severity index score (PASI 100) being used as the benchmark for efficacy.

In two phase III studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomized to brodalumab, ustekinumab, or placebo.

The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with the primary endpoint being the percent of patients achieving at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician’s global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to PASI 100.

At week 12, PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (AMAGINE-2, 44% vs 22%; AMAGINE-3, 37% vs 19%; P<0.001).

Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo and mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo (Lebwohl, 2015).

References

Lebwohl M, Strober B, Menter A, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;373:1318-28.

Lasers: Red vs Blue in PDT

Its Blue

A study reported late last year was carried out to determine whether prior microneedling would enhance the penetration of topical aminolevulinic acid HCl (Levulan) and thus enhance photodynamic therapy (PDT) and possibly also result in a better cosmetic outcome vs PDT alone in patients with AKs.

In this trial, 20 patients each with ≥4 non-hyperkeratotic AKs on each side of their faces were randomized to receive multiple passes with a microneedling device on one side of their faces, followed by application of aminolevulinic acid HCl to the entire face.

The aminolevulinic acid HCl was allowed to incubate for 1 hour and this was followed by exposure to blue light (Blu U) for 1000 seconds.

For the 19 patients who completed 4 months of follow-up, the mean AK reduction on the microneedling side was 89.3% vs 69.5% on the PDT alone side. In addition, 13 of the 19 patients had a noticeable improved cosmetic appearance on the microneedled side of the face (Spencer, 2016).

No, Its Red

Aminolevulinic acid hydrochloride (BF-200 ALA, Ameluz) was recently approved by the United States Food and Drug Administration for PDT using the BF-RhodoLED lamp, a narrowband, red light illumination source, for lesion-directed and field-directed treatment of AKs of mild-to-moderate severity on the face and scalp.

This approval was based on results from 779 patients with 4-8 mild to moderate AK lesions. The results obtained from these studies demonstrated that BF-200 ALA was significantly superior to the standard of care, with a complete patient response rate of 91% when paired with BF-RhodoLED PDT lamp (CenterWatch, 2017).

In addition, BF-200 ALA showed positive long-term effects with low recurrence over the course of 12 months (Dirschka, 2013).

In a pivotal phase III trial performed on entire treatment fields, BF-200 ALA demonstrated long-lasting skin rejuvenation effects in sun-damaged, but asymptomatic, skin regions (CenterWatch, 2017; Reinhold, 2016).

References

CenterWatch. Ameluz (aminolevulinic acid hydrochloride). 2017. Available at: http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100150/ameluz-aminolevulinic-acid-hydrochloride

Dirschka T, Radny P, Dominicus R, et al. Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photodynamic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis. Br J Dermatol. 2013;168:825-36.

Reinhold U, Dirschka T, Ostendorf R, et al. A randomized, double-blind, phase III, multicentre study to evaluate the safety and efficacy of BF-200 ALA (Ameluz(®) ) vs. placebo in the field-directed treatment of mild-to-moderate actinic keratosis with photodynamic therapy (PDT) when using the BF-RhodoLED lamp. Br J Dermatol. 2016;175:696-705.

Spencer JM, Freeman SA. Microneedling Prior to Levulan PDT for the Treatment of Actinic Keratoses: A Split-Face, Blinded Trial. J Drugs Dermatol. 2016;15:1072-4.

5-Fluorouracil (5-FU): 4% vs 5% for the Treatment of Actinic Keratosis

While oxymetazoline HCl cream, 1% and bromocriptine gel, 0.33% were not compared in a head-to-head trial, this has been done for 4% 5-FU in an aqueous vehicle cream containing peanut oil (Tolak) vs 5% 5-FU in a vanishing cream (Efudex) in patients with actinic keratosis (AKs).

In a 4-week, double-blind, multicenter non-inferiority study that included 841 subjects, 4% 5-FU cream administered once daily was compared with 5% 5-FU cream twice daily with 100% and 75% clinical clearance of AK’s assessed as the study endpoint.

4% 5-FU achieved 100% clearance in 80% of patients and 75% clearance in 100% of patients compared with 75% and 95%, respectively, with 5% 5-FU.

Skin irritation occurred in 30% of patients treated with 4% 5-FU vs 60% with 5% 5-FU.

It was also noted that the peanut oil component of the 4% 5-FU preparation is safe even in peanut-allergic patients.

Thus, 4% 5-FU is non-inferior to 5% 5-FU with better tolerability and permits once-daily administration which may result in better adherence to therapy (Dohil, 2016).

References

Dohil MA. Efficacy, safety, and tolerability of 4% 5-fluorouracil cream in a novel patented aqueous cream containing peanut oil once daily compared with 5% 5-fluorouracil cream twice daily: meeting the challenge in the treatment of actinic keratosis. J Drugs Dermatol. 2016;15:1218-1224.

Oxymetazoline Hydrochloride 1% Cream for Rosacea

Oxymetazoline hydrochloride (HCl) cream, 1% (RHOFADE), an alpha-1A-adrenoceptor agonist and a partial agonist at the alpha-2 receptor, was approved in January of 2017 and is indicated for the treatment of persistent facial erythema associated with rosacea in adults. Nasal sprays containing a lower concentration of oxymetazoline HCl have been used off-label to treat rosacea for many years, and oxymetazoline hydrochloride (HCl) cream, 1% is the first approved treatment using this compound (Smith, 2017).

In two clinical trials, once-daily application of oxymetazoline hydrochloride (HCl) cream, 1% reduced persistent facial erythema associated with rosacea through 12 hours.  After 29 days of treatment, patients achieving clinical success at 12 hours were 15% vs 6% for placebo in one study and 12% vs 6% in the second trial (RHOFADE PI, 2017).

Oxymetazoline HCl cream, 1% is not the first adrenergic agent approved for the treatment of rosacea. Brimonidine topical gel, 0.33% (MIRVASO) is an alpha-adrenergic agonist indicated for the topical treatment of persistent facial erythema of rosacea in adults that has been available since 2013 (MIRVASO PI, 2016).

Which of these two preparations is a better choice for your patient?  There is no head-to-head comparison of these treatments, so it is hard to know. Combined assessment of results from different studies (for example, with network meta-analyses) has now become a fairly common approach for comparing treatments that have never been tested vs each other, but that has not been accomplished for these drugs.  A look at the labels for the two agents suggests that effect sizes for oxymetazoline HCl cream, 1% and bromocriptine gel, 0.33% are very similar, but that application site erythema may occur more often with bromocriptine gel, 0.33% than with oxymetazoline HCl cream, 1% (RHOFADE PI, 2017; MIRVASO PI, 2016).

References

MIRVASO (brimonidine) topical gel. 2016. Available at: http://www.galdermausa.com/PI/MirvasoPI.pdf

RHOFADE (oxymetazoline hydrochloride) cream, for topical use. 2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208552s000lbl.pdf

Obiltoxaximab: A Monoclonal Antibody for Cutaneous Anthrax

You should certainly hope that you will never have to use it, but it is still important to know about obiltoxaximab (Anthim), a monoclonal antibody administered by injection, that has been approved for treating inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs in adult and pediatric patients.

It is also approved for prophylaxis of inhalational anthrax when alternatives are not available or appropriate (Kaufman, 2016).

Why should dermatologists care? Because the most common type of human anthrax is the cutaneous form. Other forms of human anthrax (gastrointestinal, inhalational, or injectional) are rare (Kajfasz, 2014).

It is expected that the main use of obiltoxaximab is likely to be in the setting of bioterrorism, but it might also be effective for the rare patient in your practice with cutaneous anthrax.

References

Kaufman MB. Pharmaceutical Approval Update. P T. 2016;41:355-6.

Kajfasz P, Bartoszcze M, Borkowski PK, Basiak W. Retrospective review of the case of cutaneous anthrax-malignant pustule from 1995 in 15-year old girl. Przegl Epidemiol. 2014;68:657-9.