William Abramovits

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles

BACKGROUNDnThe approved imiquimod 5% cream regimen for treating actinic keratoses requires a long treatment time and is limited to a small area of skin.nnnOBJECTIVEnWe sought to evaluate imiquimod 2.5% and 3.75% for short-course treatment of the full face or balding scalp.nnnMETHODSnIn two identical studies, adults with 5 to 20 lesions were randomized to placebo, imiquimod 2.5%, or imiquimod 3.75% (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed at 8 weeks posttreatment.nnnRESULTSnA total of 479 patients were randomized to placebo, or imiquimod 2.5% or 3.75%. Complete and partial clearance (> or =75% lesion reduction) rates were 6.3% and 22.6% for placebo, 30.6% and 48.1% for imiquimod 2.5%, and 35.6% and 59.4% for imiquimod 3.75%, respectively (P < .001 vs placebo, each; P = .047, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion counts were 25.0% for placebo, 71.8% for imiquimod 2.5%, and 81.8% for imiquimod 3.75% (P < .001, each active vs placebo; P = .048 3.75% vs 2.5%). There were few treatment-related discontinuations. Patient rest period rates were 0% for placebo, 6.9% for imiquimod 2.5%, and 10.6% for imiquimod 3.75%.nnnLIMITATIONSnLocal pharmacologic effects of imiquimod, including erythema, may have limited concealment of treatment assignment in some patients.nnnCONCLUSIONSnBoth imiquimod 2.5% and 3.75% creams were more effective than placebo and were well tolerated when administered daily as a 2-week on/off/on regimen to treat actinic keratoses.

Intermittent therapy for flare prevention and long-term disease control in stabilized atopic dermatitis: A randomized comparison of 3-times-weekly applications of tacrolimus ointment versus vehicle

BACKGROUNDnIntermittent dosing of a topical calcineurin inhibitor for preventing atopic dermatitis (AD) disease relapse in patients with stabilized AD has not been evaluated.nnnOBJECTIVEnWe sought to evaluate the long-term efficacy and safety of 3-times-weekly use of tacrolimus ointment in preventing AD disease relapse.nnnMETHODSnAdult and pediatric patients with moderate to severe AD who were clear of disease after up to 16 weeks of treatment with tacrolimus ointment were randomized in a double-blind fashion to 3-times-weekly treatment with either tacrolimus ointment (0.03% or 0.1%) or vehicle for 40 weeks. The primary end point was the number of flare-free treatment days.nnnRESULTSnA total of 125 patients were randomized to tacrolimus and 72 patients to vehicle. The mean number of flare-free treatment days was 177 for tacrolimus and 134 for vehicle (P = .003). Median time to first relapse was 169 days for tacrolimus and 43 for vehicle (P = .037).nnnLIMITATIONSnGeneralizability to all patients seen in clinic may be limited because only patients who responded to tacrolimus ointment in the stabilization phase were randomized into the maintenance phase of the trial.nnnCONCLUSIONSnMaintenance therapy with tacrolimus ointment was associated with significantly more flare-free days compared with vehicle, and a significantly longer time until first disease relapse.

Topical methyl-aminolevulinate photodynamic therapy using red light-emitting diode light for treatment of multiple actinic keratoses: A randomized, double-blind, placebo-controlled study

BACKGROUNDnThe use of light-emitting diode light offers practical advantages in photodynamic therapy (PDT) with topical methyl-aminolevulinate (MAL) for management of actinic keratoses (AK).nnnOBJECTIVEnWe sought to evaluate the efficacy of MAL PDT using red light-emitting diode light.nnnMETHODSnWe 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.nnnRESULTSnMAL 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]).nnnLIMITATIONSnThe study population may not be representative of all patients with AK.nnnCONCLUSIONnMAL PDT using red light-emitting diode light is an appropriate treatment alternative for multiple AK lesions.

CYCLOSPORINE AND TACROLIMUS IN DERMATOLOGY

Immune modulators are being used with increasing frequency in dermatology. This article reviews two such agents, cyclosporine and tacrolimus. Discussion emphasizes the pharmacology, side effects, and uses of these two drugs in dermatologic disorders.

Tacrolimus ointment is more effective than pimecrolimus cream in adult patients with moderate to very severe atopic dermatitis

Objective: To compare the efficacy and safety of tacrolimus ointment 0.1% and pimecrolimus cream 1% in adult patients with moderate to very severe atopic dermatitis (AD). Methods: A total of 281 patients (141 treated with tacrolimus and 140 treated with pimecrolimus) were randomized to a multicenter, investigator‐blinded, 6‐week study. Results: Tacrolimus‐treated patients had significantly greater improvements in the Eczema Area Severity Index score compared with pimecrolimus‐treated patients (mean percent reduction from baseline to study end: 57% vs 39%, respectively; p = 0.0002). Treatment success was also significantly greater among the tacrolimus‐treated patients compared with pimecrolimus‐treated patients (40% vs 22% at study end; p = 0.001), as was the improvement in percentage of total body surface area affected (a reduction of 49% vs 34% at study end; p = 0.01). Both treatment groups had similar improvements in patient assessment of itch. There were no significant differences in the incidences of adverse events, including application‐site burning and application‐site pruritus, the two most commonly reported adverse events. Significantly more pimecrolimus‐treated patients than tacrolimus‐treated patients withdrew from the study due to lack of efficacy (10 vs 1, p = 0.005). Conclusion: Tacrolimus ointment is more effective than pimecrolimus cream in adults with moderate to very severe AD. Both agents have a similar safety profile.

Efficacy of tofacitinib in treatment of alopecia universalis in two patients

Autoimmune‐triggered non‐scarring hair loss is a feature of alopecia areata (AA). Initially patchy and often self‐limited, severe hair loss forms include the complete loss of scalp hair or alopecia totalis (AT) and complete loss of all hair or alopecia universalis (AU). For AT and AU a reliable treatment has remained elusive. The targeted kinase inhibitor tofacitinib, in current use for treatment of other immune diseases, has been hypothesized as a viable option for AA, AT and AU therapy and a few case reports support this.

Sebum, Cosmetics, And Skin Care

Recent contributions to the understanding of the physiology and biochemistry of sebum production and of the lipids on the skin surface are leading to the development of effective strategies to regulate excessive sebum production and its consequences through the use of cosmetics and skin care products.

Comparisons of efficacy and cost-effectiveness of topical immunomodulators in the management of atopic dermatitis

SUMMARY The availability of new topical immunomodulators greatly improves treatment options for patients with atopic dermatitis (AD). Unfortunately, head-to-head studies have not been conducted to allow comparisons in treatment efficacy and cost-effectiveness. The study aims to compare the efficacy and cost-effectiveness of tacrolimus ointment and pimecrolimus cream as monotherapy for the treatment of AD patients with moderate disease, who are not responsive to or not well-controlled with topical corticosteroids. In the absence of head-to-head comparative data, relative treatment efficacy was estimated based on existing outcomes, which were reported in the published literature and data from clinical trials. Comparisons were made between Eczema Area and Severity Index (EASI) scores and converted to disease-controlled days (DCDs) on treatment. Other assumptions about resource utilization, changes in management and patient outcomes were based on opinions of a physician panel and from previously published reports. Medical resources costs were derived from fee schedules and product average wholesale prices (AWPs). A Markov model was developed to determine the cost-effectiveness ratios for each treatment. Sensitivity analyses were conducted for key variables to assess their impact on the results. Study designs and efficacy endpoints differed between tacrolimus and pimecrolimus clinical studies. In tacrolimus studies, a quantitative physician global assessment was performed, which tracked percentage improvement relative to baseline. In contrast, pimecrolimus studies relied on investigator global assessments scored on a Likert scale. Studies of both agents used the Eczema Area and Severity Index (EASI). A comparison of EASI scores for tacrolimus and pimecrolimus found that pimecrolimus was approximately 60% as efficacious as tacrolimus after 2 to 4 weeks of treatment. Based on these efficacy rates, average cost-effectiveness ratios were estimated at

Patient‐reported outcomes from a multicenter, randomized, vehicle‐controlled clinical study of MAS063DP (Atopiclair™) in the management of mild‐to‐moderate atopic dermatitis in adults

7.34 per DCD for tacrolimus and

Sweet's syndrome associated with Staphylococcus aureus.

11.34 per DCD for pimecrolimus. Sensitivity analyses found that pimecrolimus would only be cost-effective if its efficacy approached 90% of tacrolimus efficacy or if the costs of the products were significantly different than current AWPs. Although head-to-head comparative studies have not been completed to date, there are likely to be differences in efficacy between topical immunomodulators. Based on published data, we estimate that the efficacy of pimecrolimus to be 60% of the efficacy of tacrolimus and therefore, tacrolimus to be more cost-effective for the treatment of moderate AD. Sensitivity analyses revealed that pimecrolimus cream would need to be 90% as efficacious as tacrolimus ointment in order to be cost-effective in this patient population.