Maximizing Therapy with Mid-Potency Topical Corticosteroids

Author: 
By James Q. Del Rosso, D.O., F.A.O.C.D.

S ince topical corticosteroids were first used in 1952, these agents have maintained a pivotal position in the armamentarium for treatment of multiple corticosteroid-responsive disorders, including eczematous dermatoses, psoriasis vulgaris and seborrheic dermatitis.1

The availability of several topical corticosteroid products with potency ratings ranging from mild to “super potent”, and multiple vehicle formulations, allows for rational selection for treatment of individual disease states and adaptability for use at different anatomic sites.2-4

The effectiveness of topical corticosteroid therapy is highly dependent on proper correlation of the potency and vehicle selected with the relative corticosteroid responsiveness and location of the specific disease under treatment.2-6

Clocortolone pivalate 0.1% (Cloderm Cream) is a mid-potency topical corticosteroid available as an emollient cream approved for use in both adults and children.7 Favorable efficacy and safety of clocortolone pivalate 0.1% cream has been demonstrated in studies inclusive
of >2,500 patients, which have evaluated treatment of multiple corticosteroid-responsive dermatoses in both adult and pediatric populations.

This article offers a review of the available studies with this mid-potency corticosteroid to offer readers a more comprehensive understanding of the safety and efficacy of this therapy, as well as specific conditions successfully treated with this drug.

Structural and Pharmacokinetic Properties
• Structural characteristics of the clocortolone pivalate molecule allow for enhanced corticosteroid receptor binding, optimized potency and increased lipophilicity.3,7,8

• The cutaneous bioavailability of clocortolone pivalate 0.1% emollient cream vehicle has been evaluated in both inflamed and normal human skin through in vivo and in vitro permeation studies.7 Cutaneous drug concentrations assessed in an in vivo human skin study demonstrated 19-fold and 7-fold higher concentrations in the epidermis and dermis, respectively, in inflamed skin compared to normal skin. An in vitro human skin study also demonstrated selective permeability with clocortolone pivalate 0.1% cream.

• Pharmacokinetic studies suggest clocortolone pivalate 0.1% cream preferentially accumulates in the epidermis with lower levels in the dermis, especially in non-inflamed skin. This may correlate with a potential for lower risk of adverse reactions.7,8

• The characteristic of selective permeability suggests greater drug accumulation in diseased skin as compared to surrounding normal tissue and decreased accumulation in actively treated skin as the inflammation associated with disease resolves.

Pharmacodynamic Properties of this Drug
No evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression was observed based on serial measurements of serum 17-ketosteroid and cortisol levels. Ten healthy human subjects applied 30 grams of clocortolone pivalate 0.1% cream twice daily under whole-body plastic sweatsuit occlusion, which was worn for 12 hours daily in a 21-day open trial. Evaluations and serum assays were completed 48 hours before treatment was initiated, then daily for 5 days during the treatment phase, and for 5 days post-therapy.7

Absence of skin irritation was noted in 25 healthy human subjects undergoing application of clocortolone pivalate 0.1% cream after 48-hour patch occlusion in a double-blind study.7 A standard 21-day irritancy study performed in a double-blind fashion in eight healthy human volunteers demonstrated negligible irritancy potential with clocortolone pivalate 0.1% cream.7

No evidence of photoxicity with clocortolone pivalate 0.1% cream was observed on forearm skin in 10 studied healthy human subjects and no evidence of sensitization or photoallergy was noted in 25 healthy male subjects undergoing human draize sensitization with and without ultraviolet light exposure.7

Clinical Efficacy
In the literature, 15 controlled clinical trials have established the efficacy of clocortolone pivalate 0.1% cream when used to treat a variety of steroid-responsive dermatoses.7,8 A compilation of results from representative double-blind, vehicle-controlled trials of patients are summarized in tables 1 through 4.

• Tables 1 and 2 include data for patients with acute and chronic atopic dermatitis/eczema.

• Table 3 highlights data for patients with contact dermatitis (n=44)

• Table 4 focuses on data for patients with seborrheic dermatitis (n=44).

Treating Different Patient Populations
Pediatric Patients. Clocortolone pivalate 0.1% cream has been studied in 83 pediatric patients ranging in age from newborn to 15 years in both an open-label trial (n=39) and in controlled clinical trials (n=44).7

Of the participants, 23 patients were <9 years of age and 18 patients were <4 years of age. Disorders treated included atopic dermatitis/eczema (n=70), psoriasis (n=12) and contact dermatitis (n=1). Efficacy and safety in pediatric patients were both documented. Importantly, cautious use of any topical corticosteroid is recommended with prolonged therapy, especially in cases that appear to be only minimally or partially responsive to treatment, and when extensive body surface area is involved. Topical corticosteroid application should be discontinued upon clearance of disease to avoid potential complications related to unnecessary prolonged application.

Facial Dermatoses. Facial use of clocortolone pivalate 0.1% cream was observed in 147 patients using treatment durations of up to 40 days in clinical trials for atopic dermatitis and seborrheic dermatitis.7 No cases of atrophy, hypopigmentation or striae were reported. One trial of 38 patients assessed efficacy and safety of clocortolone pivalate 0.1% cream applied for facial dermatoses 3 times daily for 21 days.7

Efficacy was favorable with 66% of patients demonstrating good to excellent response and no cases of atrophy, striae or telangiectasia were noted. As stated above, topical corticosteroid application should be discontinued upon clearance of disease to avoid potential complications related to unnecessary prolonged application.

Combination Therapy in Atopic Dermatitis. Topical corticosteroids and topical calcineurin inhibitors (ie. pimecrolimus, tacrolimus) induce their therapeutic effects for eczematous dermatitis through different mechanisms of action. As a result, it is anticipated that combined use of these agents would provide additive or synergistic benefit.

In an investigator-blinded 21-day trial of 57 patients with atopic dermatitis, the concomitant use of clocortolone pivalate 0.1% cream and tacrolimus 0.1% twice daily was compared regarding clinical effectiveness.8

Analysis of results demonstrated superior efficacy and more rapid decrease with the combination regimen in several disease-related sign and symptom study parameters than with either agent alone. Noteworthy was statistically significant reduction in pruritus and burning by day 14 (p=0.016) and at day 21 (p=0.16) with the combination regimen.

Stasis Dermatitis. A case series of patients with lower extremity stasis dermatitis demonstrated that clocortolone pivalate 0.1% cream applied twice daily markedly reduced erythema, burning and stinging within 1 week, with progressive reduction in signs and symptoms observed over 4 weeks of use.9

Complete or nearly complete clearance of stasis dermatitis changes were noted over the 4 week treatment period. In some cases, clocortolone pivalate 0.1% cream was applied under Unna boot occlusion for 1 to 2 weeks, followed by twice daily use; compression stockings were used in some patients.

Tolerability and Safety of Clocortolone Pivalate
In combined clinical data from trials inclusive of 1,038 patients, clocortolone pivalate 0.1% cream was very well tolerated with 96% of patients experiencing no adverse reactions. A subset assessment of 559 patients treated with clocortolone pivalate 0.1% cream experienced a local adverse reaction rate of 4.4% (25/559), characterized primarily as dryness, stinging, burning and/or itching; no systemic adverse effects have been noted.7

Clinical studies for multiple corticosteroid-responsive disease states, such as contact dermatitis, atopic dermatitis, seborrheic dermatitis, psoriasis vulgaris and stasis dermatitis, demonstrate that clocortolone pivalate 0.1% cream is effective and safe when used appropriately. Safety analysis also indicates no reports of cutaneous atrophy, striae or hypopigmentation in the aforementioned clinical trials, including a large subset of patients treated for facial dermatoses (n=147).7

In most studies with clocortolone pivalate 0.1% cream, treatment duration ranged from 14 to 28 days.

In one study of 110 patients with chronic eczematous disease or psoriasis vulgaris, clocortolone pivalate 0.1% cream was used for maintenance therapy over a mean duration of 116.4 days with a conspicuous absence of adverse reactions observed.

As with any therapeutic approach, chronic-intermittent use of clocortolone pivalate 0.1% cream as a maintenance treatment for chronic dermatoses necessitates use for actively present disease coupled with appropriate patient monitoring.

In one 21-day study, 10 healthy human subjects applied 30 grams of clocortolone pivalate 0.1% cream twice daily under whole-body plastic sweat suit occlusion worn 12 hours daily. No evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression was observed based on serial serum measurements of 17-ketosteroid and cortisol levels.

A Round-Up of Data on this Drug
• Clocortolone pivalate 0.1% cream is an effective and safe mid-potency topical corticosteroid as established by multiple clinical studies for corticosteroid-responsive disease states, such as contact dermatitis, atopic dermatitis, seborrheic dermatitis, psoriasis vulgaris and stasis dermatitis.

• Clocortolone pivalate 0.1% cream is FDA-approved for use in both adults and children.

• Combined safety analysis from clinical trials inclusive of 1,038 study participants indicates no reports of cutaneous atrophy, striae or hypopigmentation in patients treated according to individual study protocols with clocortolone pivalate 0.1% cream, including a large subset with facial dermatoses. In the aforementioned clinical trials, clocortolone pivalate 0.1% cream was very well tolerated with 96% of patients experiencing no adverse reactions.

• No evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression was observed in a 21-day study based on serial serum measurements of 17-keto-steroid and cortisol levels in patients treated with 30 grams of clocortolone pivalate 0.1% cream twice daily under whole-body sweatsuit occlusion worn 12 hours daily.

Case Study 1

A 42-year-old female employed as a cashier presented with a 5- to 6-month history of a pruritic eruption on the dorsum of both hands with lichenification noted on the proximal dorsum of the right thumb (photo 1A). No specific causative contactants were identified. Prior treatment with over-the-counter moisturizers was unsuccessful.

Diagnosis: Nummular eczema with lichen simplex and marked pruritus.

Management: Therapy was initiated with use of a gentle liquid cleanser and application of clocortolone pivalate 0.1% cream (Cloderm Cream) twice daily followed by a silicate-based hand protectant containing dimethicone and cyclomethicone formulated in aluminum magnesium hydroxide stearate (Theraseal Hand Protectant).

Response. Marked decrease in pruritus and visible eruption was reported to occur within the first 2 to 3 days. Complete clinical clearance was observed at the first follow-up appointment 3 weeks after initiation of therapy (photo 1B).

Case Study 2

A 7-year-old female presented with a history of atopic dermatitis with a recent intensely pruritic flare on the upper and lower extremities, including both antecubital fossae (photo 2A).

Diagnosis: Atopic dermatitis with exacerbation of eczematous eruption associated with marked pruritus.

Management: In addition to continuing an appropriate skincare regimen with a gentle skin cleanser and non-fragranced moisturizer cream, combination therapy was initiated with clocortolone pivalate 0.1% cream followed by pimecrolimus 1% cream twice daily.

Response. Rapid response to treatment with complete clearance of all signs and symptoms of the disease was observed at follow-up 5 days later (photo 2B). Marked reduction in pruritus, scratching and visible eruption was reported to occur within 2 days. Mild post-inflammatory hypopigmentation was noted at the antecubital fossae, and this progressively resolved within 8 weeks.