Key Evidence from Clinical Trials for Calcipotriol Dipropionate / Betamethasone Foam

What is Calcipotriol Dipropionate / Betamethasone Foam?

Calcipotriol dipropionate / betamethasone foam (trade name Enstilar^®) is a double action spray foam containing calcipotriol, a vitamin D analog, and betamethasone dipropionate, a corticosteroid. Calcipotriol is known as calcipotriene in the United States.

Enstilar is specifically indicated for the current treatment of license plate psoriasis in patients 18 years of age and older.

Enstilar is supplied as a foam. spray for topical administration and applied to affected areas once a day for up to 4 weeks. Treatment is stopped when control is achieved.

The FDA approval of Enstilar foam in 2015 was based on two multicenter, randomized, double-blind trials conducted in patients with plaque psoriasis.

The product is also approved for the treatment of psoriasis in Australia, Canada, the European Union and New Zealand, among other countries.

Clinical studies

Study design

Trial 1 patients (n = 302) were randomly assigned to receive [1]:

• Silage foam (n = 100)
• Betamethasone dipropionate in the same vehicle (n = 101)
• Calcipotriol hydrate in the same vehicle (n = 101).

Trial 2 patients (n = 426) were randomly assigned to receive [2]:

• Silage foam (n = 323)
• Vehicle alone (n = 103).

Disease severity was scored using a 5-point Investigator's Global Assessment (IGA) scale. Treatment success is defined as the proportion of patients at week 4 who were "clear" or "almost clear" according to the IGA. Subjects with "mild" disease in base they were required to be "clear" to be considered a treatment success.

The majority of subjects in both trials (76% and 75%, respectively) had baseline disease of moderate severity, 14% and 15% had mild severity of baseline disease, and 10% had baseline severe disease in both trials. .

The degree of disease involvement assessed by mean body surface area was 7.1% (range 2 to 28%) and 7.5% (range 2 to 30%) in trials 1 and 2, respectively.

In both trials, patients were treated once a day for up to 4 weeks.

Results

Test 1

The percentage of psoriasis patients who achieved treatment success, according to the Investigator's Global Assessment of Severity of Disease, was 45% in the Enstilar foam group, 30.7% for betamethasone dipropionate in vehicle and 14.9% for calcipotriene in the vehicle.

Results for him primary The 'treatment success' (IGA) at week 4 showed Enstilar to be statistically significantly more effective than all included comparators and responses were seen in all categories of disease severity at baseline.

The effect of Enstilar on itching and itch-related sleep loss was investigated in Trial 1 using a visual analog term scale (VAS) ranging from 0 mm (no itching / no loss of sleep) to 100 mm (worst itch you can imagine / worst possible sleep loss).

A statistically significantly greater number of patients in the Enstilar group compared to vehicle achieved a 70% reduction in itching and itch-related sleep loss from day 3 and throughout the treatment period.

Test 2

The percentage of psoriasis patients who achieved treatment success according to the Investigator's Global Assessment of Disease Severity was 53.3% in the Enstilar foam group and 4.8% in the vehicle-only group.

In Trial 2, the effect of Enstilar on scalp psoriasis was investigated as the percentage of patients with “treatment success” according to PGA of the scalp at week 4.

The percentage of subjects with “treatment success” according to the PGA of the scalp at week 4 was 53% in the Enstilar foam group, 47.5% in the betamethasone dipropionate in the vehicle group and 35.6% in calcipotriene in the vehicle-only group. .

Enstilar was statistically significantly more effective compared to calcipotriene and was also associated with a higher treatment success rate than betamethasone dipropionate, but this comparison did not reach statistical significance.

Adverse reactions - trials 1 and 2

The estimation of the frequency of adverse reactions is based on a pooled analysis of data from clinical studies.

Adverse effects associated with the use of Enstilar include the following:

• Irritation at the site of application (uncommon ≥1 / 1,000 to <1/100)
• Application site pruritus (uncommon ≥1 / 1,000 to <1/100)

• Folliculitis (rare ≥1 / 1,000 to <1/100)

• Hypopigmentation (uncommon ≥1 / 1,000 to <1/100)
• Hypercalcemia (rare ≥1 / 1,000 to <1/100)
• Urticaria
• Exacerbation psoriasis (rare ≥1 / 1,000 to <1/100).

Quality of life related to health

Health-related quality of life (HRQoL) measures provide patient-centered assessments of response to treatment.

In the 12-week Phase III PSO-ABLE study, fixed combination calcipotriol 50 μg / g as hydrate (Cal) plus betamethasone 0.5 mg / g as dipropionate (BD) aerosol foam was significantly more effective for the treatment of psoriasis than Cal / BD gel [3].

HRQoL was assessed using the Dermatology Quality of life index (DLQI), The EuroQoL and Psoriasis QoL questionnaires (PQoL-12) at the beginning of the study and at weeks 4, 8 and 12.

Itching, itch-related sleep loss, and impairment of work were also evaluated.

Study design

463 patients were randomized to Cal / BD foam (n = 185), Cal / BD gel, (n = 188) foam vehicle (n = 47), and gel vehicle (n = 43).

Results

Significantly more Cal / BD foam patients achieved DLQI scores of 0/1 at weeks 4 (45.7% vs. 32.4%; p = 0.013) and 12 (60.5% vs. 44.1%; p = 0.003) than Cal / gel patients. BD.

Cal / BD foam significantly improved EQ-5D utility index (0.09 vs 0.03; p <0.001) and PQoL-12 scores (-2.23 vs -2.07; p = 0.029) from baseline to week 4 versus gel Cal / BD.

Itching, itch-related sleep loss, and work impairment improved more with the Cal / BD foam than with the gel.

What is the future potential of Enstilar foam?

• Fixed combination calcipotriol 50 μg / g plus betamethasone 0.5 mg / g (Cal / BD) spray foam is a new topical treatment for psoriasis.
• It is quickly effective, offers greater effectiveness compared to ointment and gel formulations, and has been shown to increase patient treatment satisfaction.
• Topical foam vehicles are innovative alternatives to creams and ointments, addressing some of the challenges for patients experienced with traditional vehicles.
• Well-designed foam vehicles easily spread over large areas of the skin and do not leave a greasy or oily film on the skin after application.
• Although moderate to severe psoriasis is usually treated with systemic or biological therapies, an effective topical treatment can be a cost-saving alternative or an adjunct to systemic therapy.