Linda Stein Gold

Guidelines of care for the management of acne vulgaris

Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence.

Consensus Guidelines for the Management of Plaque Psoriasis

The Canadian Guidelines for the Management of Plaque Psoriasis were reviewed by the entire National Psoriasis Foundation Medical Board and updated to include newly approved agents such as ustekinumab and to reflect practice patterns in the United States, where the excimer laser is approved for psoriasis treatment. Management of psoriasis in special populations is discussed. In the updated guidelines, we include sections on children, pregnant patients or pregnant partners of patients, nursing mothers, the elderly, patients with hepatitis B or C virus infections, human immunodeficiency virus-infected patients, and patients with malignant neoplasms, as well as sections on tumor necrosis factor blockers, elective surgery, and vaccinations.

Long-term Follow-up Study of Ingenol Mebutate Gel for the Treatment of Actinic Keratoses

IMPORTANCE Ingenol mebutate is the active agent (a macrocyclic diterpene ester) in the sap of the plant Euphorbia peplus. This herb has been used as a traditional remedy for several different skin lesions, including skin cancers. OBJECTIVE To assess 12-month recurrence rates and safety associated with ingenol mebutate gel treatment in patients who previously had achieved complete clearance of actinic keratoses. DESIGN AND SETTING The treatment area was observed for recurrence for 12 months after the original study. Patients were treated in an outpatient setting. PARTICIPANTS Patients received ingenol mebutate gel, 0.015%, daily for 3 consecutive days for actinic keratoses on the face or scalp or ingenol mebutate gel, 0.05%, daily for 2 consecutive days for actinic keratoses on the trunk or extremities. Study participants had achieved complete clearance in a prespecified 25-cm2 area at day 57 of their original trial. MAIN OUTCOME MEASURES Recurrence rates and safety were assessed. RESULTS In total, 108 patients with complete clearance of face or scalp lesions in the original trial and 76 patients with complete clearance of trunk or extremity lesions in the original trial were enrolled in the 12-month observational follow-up study. Of these, 100 patients (face or scalp) and 71 patients (trunk or extremities) completed all 12 months. The sustained lesion reduction rates compared with baseline were 87.2% for the face or scalp and 86.8% for the trunk or extremities. The estimated median times to recurrence were 365 days (face or scalp) and 274 days (trunk or extremities). There were no safety concerns during the follow-up period. CONCLUSION AND RELEVANCE Ingenol mebutate gel applied as field therapy for 2 or 3 consecutive days to treat actinic keratoses produced clinically relevant sustained clearance and long-term lesion reduction. TRIAL REGISTRATION clinicaltrials.gov Identifiers: NCT00953732, NCT00952783, and NCT00989313.

Synergistic efficacy of adapalene 0.1%-benzoyl peroxide 2.5% in the treatment of 3855 acne vulgaris patients

Abstract The adapalene-benzoyl peroxide (adapalene-BPO) combination gel is efficacious and safe in the treatment of acne vulgaris. We aimed in this pooled analysis to determine whether the adapalene-BPO combination demonstrates synergistic efficacy. Data were pooled and analyzed from three double-blind controlled studies, in which patients were randomized to receive adapalene-BPO, adapalene, BPO or vehicle once daily for 12 weeks. Efficacy assessments included percent reduction in lesion counts and Investigators Global Assessment (IGA) success. Benefit of each treatment relative to vehicle was calculated by subtracting the vehicle result from the efficacy result. Synergy was defined as the benefit of the combination greater than the sum of benefits of adapalene and BPO monotherapies. Adapalene-BPO was significantly more efficacious than its monotherapies in decreasing lesion counts as early as week 1 and throughout the study (p < 0.05). Synergy in total lesion count reduction was observed up to week 8, contributing 48.7% of the benefit of adapalene-BPO relative to vehicle in decreasing total lesions at week 1. Synergy of the combination in IGA success was observed at weeks 1, 4, 8 and 12. In conclusion, the fixed-dose adapalene-BPO combination gel provides synergistic and significantly greater efficacy than its monotherapies in the treatment of acne vulgaris.

Long-term safety of crisaborole ointment 2% in children and adults with mild to moderate atopic dermatitis

Background: Long‐term topical treatment is often required for atopic dermatitis (AD), a chronic inflammatory skin disease. Objective: To assess the long‐term safety results from a multicenter, open‐label, 48‐week safety study (AD‐303) of patients (N = 517) ≥2 years of age with mild to moderate AD who continued crisaborole treatment, a topical phosphodiesterase‐4 inhibitor, after completing a 28‐day phase 3 pivotal study (AD‐301, AD‐302). Methods: Global disease severity was assessed in patients every 4 weeks, and if assessed as mild or greater, a 28‐day treatment period with crisaborole applied twice daily was initiated. Adverse events (AEs), including treatment‐emergent AEs (TEAEs), and serious AEs were analyzed. Results: During the pivotal studies and AD‐303, 65% of patients reported ≥1 TEAE, most of which were mild (51.2%) or moderate (44.6%) and considered unrelated to treatment (93.1%). The frequency and severity of TEAEs were consistent. The most frequently reported treatment‐related AEs (overall, 10.2%) were dermatitis atopic (3.1%), application‐site pain (2.3%), and application‐site infection (1.2%). Nine patients (1.7%) discontinued the long‐term study because of TEAEs. Limitations: Long‐term efficacy was not analyzed. Conclusion: Crisaborole ointment had a low frequency of treatment‐related AEs over 48 weeks of treatment of patients with AD.

Addressing the Immunopathogenesis of Atopic Dermatitis: Advances in Topical and Systemic Treatment

▪ Abstract Several immunologic mediators—phosphodiesterase (PDE), interleukin (IL), small molecules, and Janus kinase—have been implicated in the pathogenesis of atopic dermatitis, and evidence has shown that blocking these mediators can help modify the disease process. Several new topical medications have been developed that target the enzyme PDE; crisaborole was recently approved by the US Food and Drug Administration (FDA) for the treatment of atopic dermatitis, and phase II studies have been completed on OPA‐15406. The phase III clinical trial results of the systemic medication dupilumab, an inhibitor of the IL‐4 receptor a subunit (which inhibits both IL‐4 and IL‐13 signaling), are currently being reviewed by the FDA.

Antifungal Drugs for Onychomycosis: Efficacy, Safety, and Mechanisms of Action.

In 1996, oral terbinafine joined itraconazole and fluconazole on the short list of systemic medications that could be used to treat onychomycosis (although fluconazole was not approved for this indication by the US Food and Drug Administration [FDA], it was commonly used for this purpose). In 1999, ciclopirox was the first topical treatment to be FDA approved. The addition of the topical antifungal agents efinaconazole and tavaborole in 2014 expanded the roster of medications available to more effectively manage onychomycosis in a wide range of patients, including those for whom comorbid conditions, concomitant medications, or patient preference limited the use of systemic antifungals.

Cost-Effectiveness of Ivermectin 1% Cream in Adults with Papulopustular Rosacea in the United States.

BACKGROUND Papulopustular rosacea is a chronic skin disease involving central facial erythema in combination with papules and pustules. Papulopustular rosacea is treated with topical, systemic, or a combination of topical and systemic therapies. Currently approved topical therapies include azelaic acid gel/cream/foam twice daily (BID) and metronidazole cream/gel/lotion BID. Ivermectin 1% cream once daily (QD) is a new topical agent for the treatment of papulopustular rosacea that has been approved for the management of inflammatory lesions of rosacea and offers an alternative to current treatments. OBJECTIVE To evaluate the cost-effectiveness of ivermectin 1% cream QD compared with current topical treatments in order to understand the cost of adding ivermectin as a treatment option that would bring additional clinical benefit for adults with papulopustular rosacea in the United States. METHODS The cost-effectiveness of ivermectin 1% cream QD was compared with metronidazole 0.75% cream BID and azelaic acid 15% gel BID for adults in the United States with moderate-to-severe papulopustular rosacea using a Markov cohort state transition structure with 2 mutually exclusive health states (rosacea and no rosacea) and 5 phases. Patients could succeed or fail to respond to treatment and experience a relapse after treatment success. The model took a health care payer perspective (direct medical costs of topical and/or systemic therapy plus health care costs for physician and specialist visits) and used a 3-year time horizon. The model was run for a cohort of 1,000 patients. Costs (2014 U.S. dollars) and benefits (disease-free days and quality-adjusted life-years [QALYs]) were discounted at a rate of 3% per annum. Cost-effectiveness was determined by the incremental cost-effectiveness ratio (ICER) and measured in terms of incremental cost per QALY gained (estimated from health state utilities for patients with and without rosacea). Univariate and probabilistic sensitivity analyses (PSA) were conducted to assess the robustness of model outcomes. RESULTS Compared with metronidazole 0.75% cream BID, ivermectin 1% cream QD was associated with higher costs but provided greater clinical benefit, with an ICER of

Greater improvement in quality of life outcomes in patients using fixed-combination calcipotriol plus betamethasone dipropionate aerosol foam versus gel: results from the PSO-ABLE study.

13,211 per QALY gained. For a cohort of 1,000 patients, ivermectin 1% cream QD provided an additional 72,922 disease-free days (200 years) over a 3-year period compared with metronidazole 0.75% cream BID, leading to a lower cost per disease-free day for ivermectin 1% cream QD (

Atopic dermatitis progression: evaluating intervention strategies.

4.54) compared with metronidazole 0.75% cream BID (