Secukinumab administration by autoinjector maintains reduction of plaque psoriasis severity over 52 weeks: results of the randomized controlled JUNCTURE trial.

BACKGROUND: User satisfaction is an important factor associated with treatment adherence in chronic diseases including moderate-to-severe psoriasis. OBJECTIVE: To evaluate the efficacy, safety and patient acceptability of 300 and 150 mg secukinumab - a fully human anti-interleukin-17A monoclonal antibody that has demonstrated efficacy in the treatment of patients with moderate-to-severe plaque psoriasis - self-administered by autoinjection. METHODS: Patients with moderate-to-severe plaque psoriasis were randomized to secukinumab 300 mg, secukinumab 150 mg or placebo self-administered by autoinjection at baseline, Weeks 1, 2 and 3 and then every 4 weeks from Week 4 to Week 48. Efficacy responses [≥75/90/100% improvement in Psoriasis Area and Severity Index (PASI 75/90/100) and clear/almost clear skin by Investigator's Global Assessment 2011 modified version (IGA mod 2011 0/1)] were measured at Week 52. Patient-reported usability of the autoinjector was evaluated by the self-injection assessment questionnaire to Week 48. RESULTS: At Week 52 with secukinumab 300 mg, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 81.4/64.1/38.8% and 69.6% of patients, respectively, by multiple imputation. At Week 52 with secukinumab 150 mg, PASI 75/90/100 and IGA mod 2011 0/1 responses were achieved by 75.2/57.4/33.1% and 60.2% of patients, respectively, by multiple imputation. Patient-assessed acceptability of the autoinjector remained high to Week 48. The proportion of patients experiencing adverse events was greater with secukinumab 300 mg (88.6%) than with secukinumab 150 mg (78.7%). CONCLUSION: Self-administration of secukinumab using an autoinjector was associated with robust and sustained efficacy, a good safety profile and high acceptability.

Efficacy, safety and tolerability of topical terbinafine nail solution in patients with mild-to-moderate toenail onychomycosis: results from three randomized studies using double-blind vehicle-controlled and open-label active-controlled designs.

BACKGROUND: Terbinafine nail solution (TNS) was developed for the treatment of onychomycosis. OBJECTIVE: To assess the efficacy of TNS vs. vehicle and amorolfine 5% nail lacquer. METHODS: Subjects with mild-to-moderate toe onychomycosis (25% to ≤75% nail-involvement, matrix uninvolved) were randomized to receive either TNS or vehicle in two double-blind studies, and to TNS or amorolfine in an active-controlled, open-label study. Primary endpoint was complete cure (no residual clinical involvement and negative mycology) at week 52. Secondary endpoints were mycological cure (negative mycology defined as negative KOH microscopy and negative culture) and clinical effectiveness (≤10% residual-involvement and negative mycology) at week 52. RESULTS: Complete cure was not different between TNS vs. vehicle and amorolfine. Mycological cure was higher with TNS vs. vehicle, as was clinical effectiveness with TNS vs. vehicle, and TNS and amorolfine were not different for secondary efficacy endpoints. Patients achieving mycological cure had a better clinical outcome, and efficacy was improved in subjects with milder disease. Post hoc analysis suggests that nail thickness is an important prognostic factor. Moreover, mycological cure may require 6 months of treatment regimen while complete cure and clinical effectiveness may be achievable only after 10 months. A simulation study suggests that longer treatment duration would have resulted in higher complete cure with TNS vs. vehicle. Study treatments were well-tolerated. CONCLUSION: Primary efficacy objectives were not met in the studies reported herein. Possible reasons for failure to achieve significant outcomes include insufficient length of treatment; stringency of primary endpoint and severity of nail involvement of study population.

Susceptibility of dermatophyte isolates obtained from a large worldwide terbinafine tinea capitis clinical trial.

BACKGROUND: Our group, in collaboration with seven other laboratories, has recently developed a method to determine the susceptibility of dermatophytes. OBJECTIVES: The objective of this study was to determine the terbinafine susceptibility profile of dermatophyte isolates obtained from patients with tinea capitis enrolled in two large worldwide clinical trials and to investigate whether these susceptibilities differ by geographical location. Methods Susceptibilities were determined according to the Clinical and Laboratory Standards Institute M38-A2 standard. RESULTS: From a total of 978 baseline dermatophyte isolates, we selected 301 isolates at random. These included: Trichophyton tonsurans (n = 125), Microsporum canis (n = 94), T. violaceum (n = 63) and M. audouinii (n = 19). The terbinafine minimum inhibitory concentration (MIC) range was 0.001-0.25 microg mL(-1), while MIC(50) and MIC(90) ranged between 0.002 and 0.125 microg mL(-1) and 0.03 and 0.25 microg mL(-1), respectively, for all species tested. MIC(50) and MIC(90) varied by individual species; however, there was no difference in terbinafine MIC among the different species isolated from U.S. and non-U.S. sites. CONCLUSION: Terbinafine demonstrates potent antifungal activity against dermatophyte isolates obtained from patients with tinea capitis worldwide.

Non-surgical treatment modalities of facial photodamage: practical knowledge for the oral and maxillofacial professional.

With the increasing interest in cosmetic procedures, oral and maxillofacial surgeons are being asked not only to improve oral health and aesthetics but to extend their expertise to provide advice on improving the overall appearance of the face. For the discerning patient, improving overall facial skin appearance is becoming an integral part of the process of surgical cosmetic procedures. Here, some of the non-surgical options available for the treatment of photodamaged skin are reviewed and an overview of the specific treatments in this category provided. Sun avoidance and protection from harmful rays with appropriate sunscreens are primary to maintaining healthy skin and appearance. Among treatment options, topical treatments with preparations such as retinoids, alpha-hydroxy acids and antioxidants have been shown to provide some benefit and are relatively easy to use albeit with appropriate precautions and professional guidance. As a second-level option, facial rejuvenation procedures such as botulinum toxin injection, soft tissue augmentation with collagen or hyaluronic acid gel, skin resurfacing, use of chemical peels, dermabrasion and laser resurfacing procedures can be used but require administration by qualified practitioners. Overall, these treatments may be used to complement rehabilitative, reconstructive, or cosmetic oral and maxillofacial surgery to further improve and complement surgical results.

Tretinoin cream 0.02% for the treatment of photodamaged facial skin: a review of 2 double-blind clinical studies.

In extensive clinical studies and practical use since its US Food and Drug Administration approval in 1995, tretinoin emollient cream 0.05% has been shown to be safe and effective in the treatment of fine facial wrinkles, mottled hyperpigmentation, and skin roughness. To provide additional prescribing flexibility for various patient needs, a new lower concentration formulation, tretinoin cream 0.02% was chosen for further development. Two multicenter, randomized, double-blind, vehicle-controlled clinical., studies were conducted to evaluate the safety and efficacy of the lower concentration tretinoin formulation in the treatment of moderate-to-severe facial photodamage. Results indicate statistically significant improvement in fine wrinkling, coarse wrinkling, and yellowing with the use of tretinoin cream 0.02% at week-24 end point, compared with placebo. Therapy with tretinoin cream 0.02% was well tolerated overall and demonstrated a favorable safety profile. Both studies demonstrated that tretinoin cream 0.02% is safe and effective for the treatment of moderate-to-severe photodamaged facial skin.

A comparative trial of two retinoids commonly used in the treatment of acne vulgaris.

BACKGROUND: Topical retinoids are highly effective treatments for acne vulgaris. The various formulations and concentrations available allow physicians to tailor therapies to individual patient's needs and minimize the cutaneous irritation that is often observed with the use of these drugs. OBJECTIVE: To compare the efficacy and safety of tretinoin gel microsphere 0.1% with adapalene gel 0.1% in the treatment of acne vulgaris. METHODS: A 12-week double-blind study was conducted, and patients were evaluated at baseline and at weeks 2, 3, 4, 6, 8, 10, and 12. RESULTS: Although the two drugs displayed similar efficacy in the resolution of acne lesions at 12 weeks, a significantly greater reduction in the number of comedones was seen at week 4 among patients treated with tretinoin gel microsphere (p = 0.047). Patients receiving tretinoin gel microsphere had an increased incidence of dryness (weeks 8 and 10) and peeling (weeks 3, 6, 8, and 10) compared with those patients treated with adapalene gel, but the two groups were comparable with respect to erythema, burning/stinging, and itching. CONCLUSION: Both drugs have similar efficacy in the resolution of acne lesions but tretinoin gel microsphere may result in a faster onset of action in the reduction of comedones compared to adapalene.

A comparative evaluation of tretinoin gel microsphere, 0.1%, versus tretinoin cream, 0.025%, in reducing facial shine.

Tretinoin gel microsphere, 0.1%, is a highly effective anti-acne medication formulated with sponge-like microspheres encapsulating the active ingredient, tretinoin. In addition to minimizing cutaneous irritation, this system may also reduce facial shine. This single-center, double-blind, half-face study evaluated the potential of tretinoin gel microsphere, 0.1%, to reduce the appearance of facial shine compared to tretinoin cream, 0.025%. Thirty-five subjects (ages 12 to 24 years) with moderate acne vulgaris and moderate facial oiliness, were evaluated after 4 consecutive days of product use. On sides treated with tretinoin gel microsphere, 0.1%, investigators found significantly reduced facial shine at 3 and 6 hours posttreatment. Subjects' self-evaluations revealed a significant reduction in facial shine at 3 hours posttreatment. Photographic analyses showed reductions in facial shine for both treatments, but decreases were greater on tretinoin gel microsphere, 0.1%-treated sides. Both therapies were well tolerated, and no adverse events occurred. Tretinoin gel microsphere, 0.1%, has the added benefit of reducing the appearance of facial shine, which is a frequent concern in acne patients.