Karen E. Huang MS,a S. Evan Carstensen BS,a and Steven R. Feldman MD PhDa,b,c
BACKGROUND: Acne has a ~90% lifetime prevalence, however the duration of the condition and its treatment is not well characterized. The purpose of this study was to estimate for how long acne patients are treated.
METHODS: Electronic patient records from an academic practice were queried to identify dermatology visits with an acne diagnosis (ICD-9: 706.1) between January 1, 2009 and June 1, 2012. The duration of care for acne treatment was calculated as the time between the earliest and latest visits. Kaplan Meier analyses were used to describe treatment duration.
RESULTS: 1,130 patients had at least one visit acne-related visit to a dermatologist, with 631 (56%) having only one visit and 499 (44%) having multiple visits over the study period. For patients with multiple visits, the mean duration from first to last visit was 0.57 year (95% CI: 0.52, 0.62); 25% ceased visiting in 0.25 year, 50% in 0.40 year, and 75% in 0.64 year.
CONCLUSION: Our study provides a lower limit on the duration of acne treatment. The duration of acne treatment is longer than the duration of typical acne clinical trials. Understanding the duration of the disease can help set patients’ treatment expectations, which may help improve adherence.
J Drugs Dermatol. 2014;13(6):655-656.
Kyle B. Bartlett MD,a Scott A. Davis MA,a and Steven R. Feldman MD PhDa,b,c
BACKGROUND: Thirty to 40% of patients using topical treatments do not comply with their treatment regimen.
OBJECTIVE: To examine how tolerability is assessed, tolerability ratings, and clinical significance of tolerability ratings of topical antimicrobials for acne.
METHODS: A literature search was performed using the terms “tolerability AND acne AND (benzoyl peroxide OR antimicrobial OR clindamycin OR erythromycin OR dapsone OR sulfur OR sulfacetamide).” Inclusion criteria were: 1) evaluation of tolerability, 2) use of an identified topical antimicrobial for acne treatment without combination retinoid use, 3) an original study, in English.
RESULTS: Thirty-four of 132 articles met the inclusion criteria. Tolerability was measured through subject and investigator assessment of specific tolerability parameters and by reporting of adverse events. Nearly all of the acne treatments were well tolerated. Treatment related study discontinuation rates were low and had little to no relation to the degree of tolerability measures.
LIMITATIONS: Patients may be more adherent in clinical trials than in clinical practice. Differences in the measure used to assess tolerability make comparisons difficult.
CONCLUSIONS: Topical antimicrobial acne therapy is generally well tolerated. Discontinuation rates are low under study conditions. Tolerability of topical antimicrobial therapy for acne may not have great clinical significance.
J Drugs Dermatol. 2014;13(6):658-662.
Guy F. Webster MD PhD,a James J. Leyden MD,b and Jason A. Gross PharmDc
BACKGROUND: Isotretinoin-Lidose, the first new formulation of isotretinoin in 30 years, differs from previously approved isotretinoin formulations in that it is less dependent on the presence of fat in the gut for absorption.
OBJECTIVE: Evaluate the safety profiles of isotretinoin-Lidose and food-dependent generic isotretinoin in the largest clinical study with isotretinoin—925 randomized patients from 49 study sites. Determine if the efficacy of this new formulation is noninferior to an existing isotretinoin.
METHODS: Multicenter, double-blind, randomized, parallel-group, noninferiority trial. Study medication was taken with meals twice daily for 20 weeks. Patients were followed for 4 weeks after the last dose. Safety evaluations included recordings of adverse events, assessments for depression, anxiety, emergent psychotic symptoms, and suicidal ideation/behavior, as well as DEXA and X-ray evaluations and changes in bone age. Two co-primary efficacy outcomes were measured to assess noninferiority: a) change in total nodular facial and truncal lesion count at from baseline to week 20 and b) percentage of patients who experienced at least 90% reduction in nodular facial and truncal lesion count from baseline to week 20.
LIMITATIONS: Although isotretinoin-Lidose can be taken without meals, it was given with food because the absorption of both formulations in the study had to be similar to detect noninferiority.
RESULTS: The safety profile of the 2 formulations was comparable. Criteria for noninferiority for both co-primary efficacy outcomes were met based on predetermined margins.
CONCLUSION: Safety and efficacy of isotretinoin-Lidose is similar and noninferior to food-dependent generic isotretinoin, respectively.
J Drugs Dermatol. 2014;13(6):665-670.
Jorge Ocampo-Candiani MD,a Luis Leobardo Velázquez-Arenas MD,a Alberto de la Fuente-García MD,a
Carlos Treviño-Gómezharper MD,b and Arturo Berber MD PhDc
BACKGROUND: Minocycline and lymecycline are used in the treatment of acne, but there is not enough evidence to support superior efficacy of one of them.
METHODS: 170 participants from 14 to 34 years old with mild to moderate facial acne vulgaris were recruited. 84 had 100 mg of minocycline in a single daily dose for 8 weeks and 86 had 300 mg of lymecycline in a single daily dose for 8 weeks. Participants were evaluated at baseline, week 4 and week 8.
RESULTS: 65 minocycline and 60 lymecycline patients were evaluable. The last observation carried forward for the count of non-inflammatory lesions changed from 37.5 ± 17.8 to 37.7 ± 17.8 in the minocycline group and from 36.9 ± 15.5 to 33.4 ± 19.3 in the lymecycline group (no significant changes); corresponding changes in inflammatory lesions were from 19.4 ± 12.4 to 12.2 ± 10.0 in the minocycline group and from 20.1 ± 11.3 to 12.6 ± 8.4 in lymecycline group (P< 0.05 comparing baseline vs. final in both groups). Porphyrin counts varied from 899.5 ± 613.9 to 233.5 ± 219.5 in the minocycline group and from 956.9 ± 661.8 to 411.8 ± 411.5 in the lymecycline group (P<0.05 between the groups at study end). 36 (42.9%) patients receiving minocycline suffered 55 adverse events (22 of them gastrointestinal), while 28 (33.3%) lymecycline patients had 37 adverse events (15 of them gastrointestinal). One patient in the lymecycline group withdrew the study due to gastritis, and one more patient in the same group experienced eosinophilia.
CONCLUSIONS: There were no differences between the groups in non-inflammatory and inflammatory lesion counts, and in the safety profile. Treatment with minocycline induced statistically significant decrease in facial porphyrin counts compared to the group treated with lymecycline (ClinicalTrials.gov number, NCT00988026).
J Drugs Dermatol. 2014;13(6):671-676.
Ashish C. Bhatia MDa,b and Felipe Jimenez PhDc
The biggest hurdle in the treatment of acne vulgaris is patient non-compliance that is due in large part to poor tolerability to common acne medications. As such, new acne treatments must be developed that balance good anti-acne efficacy with excellent tolerability in order to ensure patient adherence and by extension ensure good clinical outcomes. The goal of the present study was to determine the tolerability and efficacy of a novel skin care system, composed of a cleanser, containing 1% salicylic acid and botanical ingredients, and a treatment gel, containing 1% salicylic acid, 10% buffered glycolic acid and botanical ingredients for the treatment of mild acne. In this single-center, open-label clinical study, 25 male and female volunteers used the test cleanser and test gel twice daily over six weeks. Tolerability assessments showed that the skin care regimen was very well tolerated by all study volunteers. Acne severity was significantly reduced by two acne grades at six weeks. Inflammatory lesion counts were significantly reduced, on average, by 59.06% (P≤ 0.0001), 91.62% (P≤ 0.0001), 90.85% (P≤ 0.0001) and by 98.55% (P≤ 0.0001) at weeks 1, 2, 4, and 6, respectively. Non-inflammatory lesion counts were reduced, on average, by 13.54% (ns), 38.95% (P≤ 0.0001), 44.48% (P≤ 0.0001), and by 56.10% (P≤ 0.0001) at weeks 1, 2, 4, and 6, respectively. Standardized photography also demonstrated a progressive reduction in acne lesions over time. In conclusion, results of the present study suggest that the tested skin care regimen offers rapid acne clearance and excellent tolerability that together may help to improve patient adherence as well as treatment outcome.
J Drugs Dermatol. 2014;13(6):678-683.
OBJECTIVE: Compare the safety and efficacy of 1% and 5% silica encapsulated benzoyl peroxide (E-BPO) in patients with papulopustular rosacea.
DESIGN: Multi-centered randomized, double blind, vehicle controlled parallel group, 12 week treatment in 92 patients with papulopustular rosacea. Primary endpoints were dichotomized IGA with success defined as clear/near clear and reduction in inflammatory lesions.
PATIENTS: 92 patients: 74% graded as moderate IGA, 14% severe and 12% mild. The mean inflammatory lesion count was 24.
INTERVENTION: Once daily treatment for 12 weeks with vehicle, 1% or 5% E-BPO.
RESULTS: 1% and 5% E-BPO were superior to vehicle in reducing papulopustular lesions P=0.01 and P=0.02. 5% E-BPO was superior to vehicle for IGA P=0.0013.
J Drugs Dermatol. 2014;13(6):685-688.
Nicole D. Cresce BS,a Scott A. Davis MA,a William W. Huang MD MPH,a Steven R. Feldman MD PhDa,b,c
BACKGROUND: Acne and rosacea cause significant negative impact on quality of life. There is limited information comparing the health-related quality of life (HRQL) impact associated with acne and rosacea to other patient populations.
PURPOSE: We review available literature to assess the HRQL impact of acne and rosacea and compare them with major medical conditions.
METHODS: A PubMed search identified studies that utilized the Short Form 36 (SF-36), the Dermatology Life Quality Index (DLQI), and the willingness-to-pay (WTP) metric to assess the HRQL impact of acne and rosacea. These data were compared to HRQL values for other diseases.
RESULTS: The HRQL impact of acne is similar to asthma, epilepsy, diabetes, back pain, arthritis, and coronary heart disease using SF-36 data. DLQI scores for acne ranged from 2 to 17.7 and for rosacea ranged from 4.3 to 17.3; the DLQI scores for psoriasis ranged from 1.7 to 18.2. WTP data identified ranged widely for both acne and rosacea.
LIMITATIONS: There was limited broadly generalizable data for acne and rosacea.
CONCLUSIONS: Acne and rosacea impact HRQL to a similar degree as other major medical conditions by indirect comparison to psoriasis, a skin condition causing significant disability, and by direct comparison for acne. In the setting of limited health care resources, allocation should be grounded in the evidence that acne and rosacea are not trivial in their effects.
J Drugs Dermatol. 2014;13(6):692-697.
J. Mark Jackson MD,a Joseph Fowler MD,a Angela Moore MD,b Michael Jarratt MD,c Terry Jones MD,d
Kappa Meadows MD,e Martin Steinhoff MD,f Diane Rudisill BSc,g and Matthew Leoni MDg
on behalf of the Brimonidine Phase III Study Group
BACKGROUND: Brimonidine tartrate (BT) 0.5% gel demonstrated significantly greater efficacy versus vehicle gel once-daily for the treatment of moderate to severe erythema of rosacea.
OBJECTIVES: To assess the 30-minute speed of onset of topical BT 0.5% gel in reducing facial erythema in Phase III studies as measured by subject and clinician assessments of erythema.
METHODS: Two Phase III, randomized, controlled studies with identical design in which subjects with moderate erythema of rosacea (study A: n=260; study B: n=293) were randomized 1:1 to apply topical BT 0.5% or vehicle gel once-daily for 4 weeks. Evaluations included severity of erythema based on Clinician’s Erythema Assessment (CEA) and Patient’s Self-Assessment (PSA) prior to study drug application and at 30 minutes after application on days 1, 15, and 29.
RESULTS: 97.7% and 96.6% of subjects reported normal study completion for studies A and B, respectively. The percentage of subjects achieving a 1-grade improvement in both CEA and PSA was significantly increased at 30 minutes post-dosing with BT 0.5% gel compared to vehicle gel on visit days (day 1: 27.9 vs 6.9%, P<0.001; day 15: 55.9 vs 21.1%, P<0.001; Day 29: 58.3 vs 32.0%, P<0.001 for BT 0.5% gel vs vehicle) in study A. Similar results were shown for study B.
CONCLUSIONS: Once-daily topical BT gel 0.5% is not only efficacious at reducing facial erythema but also exhibits response within 30 minutes of application in a significant number of patients throughout both Phase III studies.
J Drugs Dermatol. 2014;13(6):699-704.
Determinants of skin irritability are poorly understood. This study aims to assess differences in cutaneous safety/irritation based on Fitzpatrick skin type among patients with acne treated with tretinoin gel microsphere (TGM).
This was a phase 4, 12-week, prospective, nonrandomized, open-label, multicenter study. Approximately 500 patients with mild to moderate acne were treated with TGM 0.04% or 0.1% and assessed for cutaneous irritation at baseline and weeks 3, 6, and 12.
In this post hoc analysis of patients with Fitzpatrick skin type I-III vs Fitzpatrick skin type IV-VI, there was a general trend toward initial worsening of cutaneous adverse events (AEs) by week 3 across all variables and groups. This was followed by a trend toward improvement and resolution of skin-related AEs from week 3 to week 12 regardless of Fitzpatrick skin type, with a few exceptions. Erythema was the only cutaneous AE that consistently decreased among patients with darker skin. Results from a subsequent 3-group analysis (Fitzpatrick I-II vs Fitzpatrick III-IV vs Fitzpatrick V-VI) generally mirrored those from the 2-group study.
Study limitations include patient nonadherence, lack of a placebo arm, and lack of data regarding the impact of concurrent medications on outcomes. There was no correlation between irritation and Fitzpatrick skin type.
ABBREVIATIONS USED: adverse event (AE), analysis of variance (ANOVA), benzoyl peroxide (BP), case report form (CRF), modified Global Acne Grading Score (mGAGS), tretinoin gel microsphere (TGM)
J Drugs Dermatol. 2014;13(6):706-711.
Elizabeth Farley Prater MD,a Antoinette Day BS,b Mahir Patel MD,c and Alan Menter MDc
BACKGROUND: Efalizumab was voluntarily withdrawn from the market in April 2009 after four cases of Progressive Multifocal Leukoencephalopathy.
OBJECTIVE: To review the baseline characteristics and psoriasis phenotypes of patients with prior excelled response to efalizumab, and to determine the response of these patients to prior as well as subsequent therapies. By defining this subgroup of patients, particularly relating to palmoplantar psoriasis, future therapeutic considerations could be improved.
DESIGN: A retrospective review of 72 patients who were on efalizumab at the time of market withdrawal was conducted. Data was obtained through chart review of patients at a specialty psoriasis clinic in Dallas, TX.
MAIN OUTCOMES AND MEASURES: Patient characteristics, details of efalizumab use, and efficacy of efalizumab compared with other psoriasis treatment modalities.
RESULTS: Of the 72 patients, 24 (33%) were found to have palmoplantar disease. As a group, these patients were older, more likely to be female, and less likely to have a family history of psoriasis. 48 patients (67%) were on one or more systemic and/or biologic medication prior to starting efalizumab. Their BSA improved from 5.45 to 0.8 as a group. Six patients were identified as having failed TNF alpha antagonist treatment prior to starting efalizumab. All responded well to the medication with an average BSA of 0.54. Five of these six patients had evidence of palmoplantar disease prior to starting efalizumab and five of these six patients were female. Eleven patients (15%) experienced neurologic side effects and 13 (18%) had infections while on efalizumab treatment.
LIMITATIONS: This was a retrospective review. Quality of life issues could not always be fully assessed from the data available.
CONCLUSIONS AND RELEVANCE: Efalizumab was effectively utilized in our clinical practice to treat patients with palmoplantar psoriasis, including six patients who had failed prior treatment with one or more TNF alpha antagonist agents.
J Drugs Dermatol. 2014;13(6):712-718.
Marisa Kardos Garshick MD,a Anne Lynn S. Chang MD,b and Alexandra Boer Kimball MD MPHa
OBJECTIVE: Although not well-understood, dermatologic diseases studied in clinical trials often demonstrate substantial response to placebo. The study objective is to determine if optimism, public self-consciousness and other personality traits predict response to placebo or active treatment in a dermatology clinical trial.
METHODS: A questionnaire was mailed to subjects previously enrolled in a two-center rosacea study who had been randomized to either a treatment or placebo gel. The questionnaire included the Revised Life Orientation Test (LOT-R), the Public Self-Consciousness Scale, and questions to assess personality traits.
RESULTS: Forty-seven subjects out of 83 (57%) returned the questionnaire. There was no statistically significant difference in the LOT-R score in those who responded to placebo versus those who did not (18.08 vs 17.92, P= 0.92) nor in those who responded to active treatment versus those who did not (16.27 vs 15.86, P= 0.79). There was no statistically significant difference in public-self consciousness among placebo or active treatment responders versus non-responders (11.75 vs 10.67, P=0.66; 13.55 vs 14.45, P= 0.68). The placebo responders were more likely to report that they were not unusually sensitive to most drugs/medications (X2= 8.33, P= 0.004).
CONCLUSION: Although this pilot study is small, there was no meaningful difference in levels of optimism or public self-consciousness among those who responded to placebo. Placebo responders were more likely to report that they were not sensitive to most drugs/medications, raising the possibility that they are actually less likely to detect when they are on medications.
J Drugs Dermatol. 2014;13(6):719-722.
Itch is a common and troubling symptom of atopic dermatitis.
It is not mediated by histamine, and standard anti-itch therapies, therefore,
have limited benefit for most AD patients. Instead, anti-inflammatory agents
are used to reduce inflammation and therefore improve associated itch. Studies
confirm that long-term use of corticosteroids can lead to a reduction in pruritus.
A pilot study was designed to assess the effects of one week of twice-daily application
of desonide hydrogel 0.05% for the treatment of atopic dermatitis. Active treatment was
associated with significant improvements in IGA scores at day 3 and
day 7 (mean score 0.55, 75.83% improvement from Baseline;
P<.0001) and pruritus VAS scores at day 3 and day 7 (mean 6.35-point,
86.61% reduction in VAS scores; P<.0001). Treatment with the convenient,
hydrating hydrogel formulation is effective and associated with an improvement in subjects’ quality of life.
J Drugs Dermatol. 2014;13(6):725-728.
Margit L.W. Juhász MSca and Ellen S. Marmur MDa,b
Vismodegib is a first-in-class, hedgehog-signal inhibitor that is FDA-approved for use with advanced basal cell carcinomas (BCCs) that cannot be removed by either surgical resection or treated with radiation. Release of the drug was fast-tracked because of need for this type of drug, and its overall efficacy in clinical trial by producing either regression or even resolution of advanced BCCs. Compared to placebo, patients using vismodegib have arrested BCC progression, reduced size of BCC, and decreased recurrence of BCC. Unfortunately, vismodegib has notable adverse effects (especially those of alopecia, gastrointestinal, muscle spasms, and dysguesia) that make dermatologists reluctant to prescribe the drug and patients unwilling to undergo therapy. In this article, we tackle this dilemma by comparing the toxicity profile of vismodegib to the adverse effect profiles of other dermatologic chemotherapeutics, immunomodulators, retinoids, and biologics. Considering that many of these drugs carry their own risks and those drugs used to treat advanced melanoma have similar toxicity profiles to that of vismodegib, we hope dermatologists and patients alike will be more willing to try vismodegib as a treatment option for advanced BCCs in the future.
J Drugs Dermatol. 2014;13(6):729-733.
BACKGROUND: IncobotulinumtoxinA (INCO) was approved for aesthetic use in the United States in 2011. When reconstituted per manufacturer’s instructions, diminished delivery of INCO in US may result.
OBJECTIVE: Investigators sought to determine whether potential loss of decreased motor activity could be demonstrated, using a simple reconstitution technique.
METHODS and MATERIALS: In this 5-patient study, investigators added 2.0 mL of saline to INCO powder at the bottom of the first of 5 vials, swirling gently to dissolve INCO powder at the bottom. Reconstituted INCO was discarded and the cap was replaced. The “empty” vial then received 0.6 mL of saline, and was swirled and inverted 3 times to ensure dissolution. The 0.6 mL from the first vial was added to the second “empty” vial and the process was repeated for the remaining 3 vials (5 vials per patient). Patients were injected from reconstitution of “empty” vials to determine neuromodulatory activity. Pre- and post-treatment patient photographs of maximal contraction were taken.
RESULTS: Markedly diminished maximal frown could be observed in all 5 patients.
CONCLUSION: Improper reconstitution of INCO, or swirling without inversion of the vial following saline injection, can result in significant loss of units of the neurotoxin in the clinical setting.
J Drugs Dermatol. 2014;13(6):735-738.
Brian Berman MD PhD,a Gary Goldenberg MD,b C. William Hanke MD,c Stephen K. Tyring MD PhD,d
Wm Philip Werschler MD,e Kim Mark Knudsen PhD,f Thomas Larsson Dr Med Sci,g and Neil Swanson MDh
INTRODUCTION: Recurrence rates of actinic keratosis (AK) lesions after cryosurgery are high, and this treatment does not address field cancerization. We investigated the efficacy and safety of field treatment of AKs with ingenol mebutate gel following cryosurgery.
METHODS: In this phase 3, randomized, double-blind, vehicle-controlled study (NCT01541553), patients ≥18 years with four to eight clinically typical, visible, discrete AKs within a contiguous 25-cm2 treatment area on the face or scalp underwent cryosurgery followed 3 weeks later by once-daily ingenol mebutate 0.015% or vehicle gel for 3 consecutive days. Endpoints included complete clearance at week 11 and safety and efficacy over 12 months.
RESULTS: In 329 randomized patients, complete clearance rates were greater with ingenol mebutate than vehicle (week 11: 60.5% vs 49.4%; P=.04; month 12: 30.5% vs 18.5%; P=.01). Fewer patients experienced the emergence of new lesions with ingenol mebutate than with vehicle (38.9% vs 51.9%; P=.02). At month 12, mean percentage reduction of AKs was higher with ingenol mebutate than with vehicle (68.2% vs 54.1%; P=.002). The probability of remaining free of lesions was sustained longer with ingenol mebutate compared with vehicle gel: 78% vs 68% at 6 months; 64% vs 57% at 9 months; 55% vs 40% at month 12, respectively. Ingenol mebutate 0.015% gel was well tolerated and no unexpected adverse events occurred; all adverse events resolved within 2 weeks of starting treatment.
CONCLUSIONS: Field treatment with ingenol mebutate 0.015% gel following cryosurgery significantly enhanced clearance of baseline lesions, and was well tolerated. Furthermore, ingenol mebutate 0.015% gel following cryosurgery reduced development of new lesions in the treated field.
J Drugs Dermatol. 2014;13(6):741-747.