Background The use of light-emitting diode light offers practical advantages in photodynamic therapy (PDT) with topical methyl-aminolevulinate (MAL) for management of actinic keratoses (AK). ...Objective We sought to evaluate the efficacy of MAL PDT using red light-emitting diode light. Methods We conducted a multicenter, double-blind, randomized study. A total of 49 patients with 363 AK lesions had 16.8% MAL cream applied under occlusion for 3 hours, and 47 patients with 360 AK lesions had vehicle cream similarly applied. The lesions were then illuminated (630 nm, light dose 37 J/cm2 ) with repeated treatment 1 week later. Complete lesion and patient (all lesions showing complete response) response rates were evaluated 3 months after last treatment. Results MAL PDT was superior ( P < .0001) to vehicle PDT with respect to lesion complete response (86.2% vs 52.2%, odds ratio 6.9 95% confidence interval 4.7-10.3) and patient complete response (59.2% vs 14.9%, odds ratio 13.2 95% confidence interval 4.1-43.1). Limitations The study population may not be representative of all patients with AK. Conclusion MAL PDT using red light-emitting diode light is an appropriate treatment alternative for multiple AK lesions.
Background: Photodynamic therapy (PDT) is a promising new treatment modality for actinic keratoses. Methyl aminolevulinate (MAL) (Metvix, PhotoCure, Oslo, Norway) leads to selective accumulation of ...photoactive porphyrins in premalignant skin lesions and makes the lesions susceptible to phototoxic effects on illumination with red light.
Objective: This multicenter, randomized, double-blind study compared complete response rates, cosmetic outcome, and patient satisfaction for PDT with cream containing 160 mg/g MAL or placebo cream in the treatment of actinic keratoses.
Methods: After application of the cream under occlusion for 3 hours, the lesions were illuminated by noncoherent red light (570-670 nm, light dose 75 J/cm
2). Treatment was repeated after 1 week and response was assessed 3 months later. A total of 80 patients were randomized into the study, 42 in the active and 38 in the placebo group.
Results: Complete lesion response rate was higher after MAL PDT than placebo, 89% versus 38% per protocol analysis (
P = .001). An excellent or good cosmetic outcome was reported in more than 90% of patients treated with MAL.
Conclusion: In this small study, PDT using topical MAL was a safe and effective treatment for actinic keratoses with excellent cosmetic outcome. It is a promising treatment that could benefit from further study. (J Am Acad Dermatol 2003;48:227-32.)
Topical combination therapy containing a retinoid and an antimicrobial is an effective treatment for acne vulgaris.
To evaluate the efficacy and safety of a new topical formulation containing ...clindamycin phosphate 1.2% and tretinoin 0.025% solubilized in an aqueous-based gel (CT gel).
1,649 participants were randomized 2:2:2:1 to 12 weeks of double-blind treatment with CT gel, clindamycin, tretinoin, or vehicle gel administered once daily.
Significantly more participants achieved 2-grade or greater improvement on the Investigator's Static Global Assessment score with CT gel versus clindamycin, tretinoin, or vehicle gel. CT gel produced a significantly greater reduction in absolute number of total lesions versus all other treatment groups, in total and noninflammatory lesions versus clindamycin, and in total and inflammatory lesions versus tretinoin. Local tolerability was similar to that of tretinoin alone; signs and symptoms of irritation were most notable at week 2. There were no more adverse events with CT gel than with tretinoin gel.
CT gel is more effective than clindamycin or tretinoin monotherapy, with a safety and tolerability profile similar to that of tretinoin.
Treatment of acne vulgaris (acne) with dapsone gel, 5% requires twice-daily dosing, and some patients may not adhere to this regimen.
The objective of this study was to assess the efficacy and safety ...of a new, once-daily formulation of dapsone gel, 7.5%, with a 50% higher dapsone concentration, versus vehicle over 12 weeks in patients with acne.
This 12-week, randomized, double-blind, vehicle-controlled, multicenter clinical trial enrolled patients with moderate acne aged 12 years and older with 20 to 50 inflammatory lesions and 30 to 100 noninflammatory lesions on the face, and an acne grade of 3 (moderate) on the Global Acne Assessment Score (GAAS). Patients were randomized to receive topical dapsone gel, 7.5% or vehicle once daily for 12 weeks. Investigators assessed GAAS success rate (proportion of patients with GAAS of 0 or 1) and percent change from baseline in inflammatory, noninflammatory, and total lesions.
The intent-to-treat population comprised 2102 patients, 1044 in the dapsone gel, 7.5% group and 1058 in the vehicle group. At week 12, 29.9% of patients in the dapsone gel, 7.5% group and 21.2% in the vehicle group (P<.001) had GAAS success. Mean inflammatory lesions decreased by 55.5% and 49.0%, noninflammatory lesions decreased by 44.4% and 38.4%, and total lesions decreased by 48.7% and 42.4% in the dapsone gel, 7.5% and vehicle groups (all P<.001), respectively, at week 12. The incidence of adverse events was similar in the dapsone gel, 7.5% (19.1%) and vehicle (20.6%) groups. Most events in both groups were mild or moderate in severity. Most patients receiving dapsone gel, 7.5% and vehicle had a severity rating of "none" for stinging/burning, dryness, scaling, and erythema scales at all time points.
Dapsone gel, 7.5% applied topically once daily is an effective, safe, and well-tolerated treatment for acne.
J Drugs Dermatol. 2016;15(5):553-561.
Purpose: Actinic keratoses (AKs) exist on a continuum with squamous cell carcinoma and can occur as sub-clinical and clinically visible lesions in cancerized fields on sun-damaged skin. Ingenol ...mebutate effectively treats AKs on areas up to 25 cm
2
, but actinic keratosis can affect larger areas of skin. This trial evaluated systemic exposure and safety of ingenol mebutate gel on larger areas of skin under maximum use conditions.
Methods: Phase I, multicenter, open-label, uncontrolled, non-randomized trial. Patients received ingenol mebutate gel for three consecutive days on approximately 250 cm
2
of sun-damaged skin on the full face (0.027%), the scalp (0.027%), or arm (0.06%).
Results: Of 61 patients, 10 (face =8; arm =2) had ingenol mebutate in whole blood at subnanomolar levels (0.235-0.462 nM). The assayed metabolites were below the lower limit of quantification. Local skin responses increased during Days 1-4 and declined thereafter, approaching baseline by Day 16. Most adverse events were pain/pruritus of mild or moderate intensity.
Conclusions: Subnanomolar systemic exposure to ingenol mebutate was measured after application of the gel to approximately 250 cm
2
on the full face, scalp, or arm under maximum use conditions. No clinically relevant systemic adverse reactions were observed, and local skin responses were manageable.
Objective To examine the efficacy and safety of MAS063DP (Atopiclair) cream in the management of mild to moderate atopic dermatitis in infants and children. Study design One hundred forty-two ...patients aged 6 months to 12 years were administered MAS063DP (n = 72) or vehicle (n = 70) cream 3 times per day to affected areas and sites prone to develop atopic dermatitis. The primary endpoint for efficacy was the Investigator's Global Assessment at day 22. Secondary endpoints included Investigator's Global Assessment at other time-points, patient's/caregiver's assessment of pruritus, onset, duration of itch relief, Eczema Area and Severity Index, subject's/caregiver's assessment of global response, and need for rescue medication in the event of an atopic dermatitis flare. Results MAS063DP cream was statistically more effective ( P < .0001) than vehicle cream for the primary endpoint and all secondary endpoints. Treatment discontinuation as a result of an adverse event occurred in 9.9% of patients using MAS063DP cream and 16% of patients using vehicle cream. Conclusion MAS063DP cream is effective and safe as monotherapy for the treatment of symptoms of mild to moderate atopic dermatitis in infants and children.
Reducing the dosing frequency of topical acne treatments to once daily may improve adherence.
Evaluate pharmacokinetics (PK), safety, and tolerability of 3 formulations of once-daily dapsone gel, ...7.5% and of twice-daily dapsone gel, 5% over 28 days in patients with moderate acne vulgaris.
This phase 1, multicenter, parallel-group study randomized males and females aged 16 to 35 years to 1 of 3 dapsone gel, 7.5% formulations (DAP-11078, DAP-11079, or DAP-11080 double-blind; applied once daily) or to dapsone gel, 5% (investigator-blinded only, applied twice-daily). Blood samples were collected for PK assessments of dapsone and its metabolites, N-acetyl dapsone (NAD) and dapsone hydroxylamine (DHA), before the morning dose on days 1, 7, 14, 18, 21, 26, 27, and 28, and at several follow-up time points (days 29-32). Safety profile assessments included adverse events (AEs), physical examinations, laboratory tests, and local tolerability assessments.
Steady-state dapsone, NAD, and DHA concentrations were reached within 7 days of the first dose in all treatment groups. Daily systemic exposures of the 3 dapsone gel, 7.5% formulations were approximately 25% to 40% lower than that for dapsone gel, 5%, and these differences were statistically significant. Among the 3 dapsone gel, 7.5% formulations, the highest daily exposure of dapsone (per the AUC) was observed with DAP-11080, with respective Cmax and AUC0-24 being approximately 28.6% and 28.7% lower relative to dapsone gel, 5%. Most AEs were mild to moderate in intensity. The safety profiles for all 3 formulations of once-daily dapsone, 7.5% gel and twice-daily dapsone gel, 5% were similar following 28 days of topical administration. All 4 dapsone formulations were well tolerated.
This study demonstrated lower systemic exposure with all 3 once-daily dapsone gel, 7.5% formulations than with twice-daily dapsone gel, 5%. All 4 formulations were well tolerated and demonstrated similar safety profiles.
J Drugs Dermatol. 2016;15(10):1250-1259.
Background Data suggest that photodynamic therapy using topical methyl aminolevulinate (MAL PDT) may be a noninvasive alternative to excisional surgery for nodular basal cell carcinoma (BCC). In the ...studies described here, we investigated the histologic response, tolerability, and cosmetic outcome with MAL PDT for primary nodular BCC (≤ 5 mm in depth).
Methods Two multicenter, randomized, double‐blind studies with similar design and procedures were conducted. After surface debridement and minor tumor debulking, MAL cream 160 mg/g (66 patients with 75 lesions) or placebo cream (65 patients with 75 lesions) was applied for 3 h, followed by illumination with broad‐spectrum red light (75 J/cm2, 570–670 nm). This was repeated 7 days later. Lesions with a partial response (≥ 50% reduction in greatest diameter) at 3 months were re‐treated (21%). Treatment sites were excised at 3 months (clinical nonresponders) or 6 months (clinical responders) after the last treatment.
Results Histologically verified lesion complete response rates were higher with MAL PDT than with placebo 73% (55/75) vs. 27% (20/75). Treatment was most effective for facial lesions (89% complete response). Cosmetic outcome was good or excellent in 98% of evaluable, completely responding lesions treated with MAL PDT.
Conclusion Although longer follow‐up studies are required, these promising data indicate the potential of topical MAL PDT as a noninvasive treatment alternative for nodular BCC.
Tinea cruris, a pruritic superficial fungal infection of the groin, is the second most common clinical presentation for dermatophytosis.
This phase 3 study evaluated the safety and efficacy of ...topical luliconazole cream 1% in patients with tinea cruris.
483 patients were enrolled and 256 male and female patients aged ≥12 years with clinically evident tinea cruris and eligible for modified intent-to-treat analysis were randomized 2:1 to receive luliconazole cream 1% (n=165) or vehicle (n=91) once daily for 7 days. Efficacy was evaluated at baseline and at days 7, 14, 21, and 28 based on mycology (potassium hydroxide, fungal culture) and clinical signs (erythema, scaling, pruritus). The primary outcome was complete clearance at day 28 (21 days posttreatment). Safety evaluations included adverse events and laboratory assessments.
Complete clearance was obtained in 21.2% (35/165) of patients treated with luliconazole cream 1% compared with 4.4% (4/91) treated with vehicle (P<0.001). The safety profile of luliconazole cream 1% was similar to vehicle.
The study was conducted under controlled conditions in a relatively small population.
Luliconazole cream 1% applied once daily for 7 days is more effective than vehicle and well tolerated in patients with tinea cruris.
