Fixed Combination Halobetasol Propionate and Tazarotene Lotion for Plaque Psoriasis

Lyn Guenther, MD, FRCPC, FAAD^1,2; Andrei Metelitsa, MD, FRCPC, FAAD^3-5; Vimal H. Prajapati, MD, FRCPC, DABD^4-9

¹Western University, London, ON, Canada
²The Guenther Dermatology Research Centre, London, ON, Canada
³Beacon Dermatology, Calgary, AB, Canada
⁴Division of Dermatology, Department of Medicine, University of Calgary, Calgary, AB, Canada
⁵Probity Medical Research, Calgary, AB, Canada
⁶Skin Health & Wellness Centre, Calgary, AB, Canada
⁷Dermatology Research Institute, Calgary, AB, Canada
⁸Section of Community Pediatrics, Department of Pediatrics, University of Calgary, Calgary, AB, Canada
⁹Section of Pediatric Rheumatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada

Conflict of interest:
Dr. Guenther has been a consultant, speaker, and clinical investigator for Bausch Health. Dr. Metelitsa has been a speaker for Bausch Health. Dr. Prajapati has been an advisor, consultant, speaker, and clinical investigator for and has received educational grants from Bausch Health.

Abstract:
A novel fixed combination lotion containing the super-potent corticosteroid halobetasol propionate 0.01% and retinoid tazarotene 0.045% (Duobrii™) has recently been introduced and indicated for the treatment of moderate to severe plaque psoriasis in adults. Studies have shown that there is synergy between the ingredients and that the product can be safely used intermittently for up to 1 year. Treatment success (i.e., Investigator Global Assessment [IGA] of clear/almost clear [IGA 0/1] and at least a 2-grade improvement from baseline) occurred in 58.8% of participants at some point in a 1-year clinical trial. Persistence of treatment success is common after treatment discontinuation. Most treatment-emergent adverse events are application site reactions, mild to moderate in intensity, and occur primarily during the first 12 weeks. Counselling should be considered to optimize treatment outcomes.

Key Words:
Duobrii, halobetasol, tazarotene, fixed combination, psoriasis, topical, corticosteroid, retinoid

Introduction

The US FDA and Health Canada approved in 2019 and 2020, respectively, a once daily fixed combination lotion containing the super-potent corticosteroid halobetasol propionate (HP) 0.01% and the retinoid tazarotene (TAZ) 0.045% (Duobrii™, HP/TAZ) delivered by polymeric emulsion technology. It is more convenient to apply 1 topical than 2, which may improve adherence. The product is supplied in a 100 g aluminum tube for treating moderate to severe plaque psoriasis in adults.¹

Unlike other lotions, Duobrii™ does not drip. The product improves delivery of HP and TAZ compared to HP 0.05% and TAZ 0.1% creams, increases skin moisturization and decreases transepidermal water loss.² Non-medicinal ingredients include carbomer copolymer type B, carbomer homopolymer type A, diethyl sebacate, edetate disodium dihydrate, light mineral oil, methylparaben, propylparaben, purified water, sodium hydroxide, sorbitan monooleate and sorbitol solution 70%.¹ Since retinoids are teratogenic, Duobrii™ should not be used in pregnancy or women who may become pregnant.¹

Background

Topical therapy is used for all severities of psoriasis, although severe disease is often also treated with systemic therapy. Topical corticosteroids are the mainstay of treatment, however psoriasis quickly recurs when they are discontinued and they may cause atrophy. According to the product monograph of Ultravate® cream and ointment which contain HP 0.05%, they should be applied twice daily or as directed by the patient’s physician for a maximum of 50 g/week.³ The duration of treatment is a maximum of 2 weeks without patient re-evaluation.³ Since psoriasis is a chronic condition, it is preferable to have a topical product without the requirement for re-evaluation after 2 weeks.

TAZ, the only topical retinoid approved for use in psoriasis, is associated with persistence of improvement after treatment discontinuation, however its use is limited by irritation.⁴ TAZ is a synthetic acetylenic retinoid which is a prodrug. Its free-acid active metabolite, tazarotenic acid, binds to the nuclear retinoic acid receptors (RAR) beta (RAR-β), and the predominant subtype gamma (RAR-γ), in the epidermis.⁵ In psoriasis, it reduces inflammation and keratinocyte hyperproliferation, and normalizes differentiation.⁵

Treatment Rationale for Combination Halobetasol/Tazarotene Lotion

After 12 weeks of use, once daily TAZ 0.05% and 0.1% creams have comparable efficacy to twice daily fluocinonide 0.05% cream, however the psoriasis recurs more quickly after fluocinonide discontinuation.⁴ In an attempt to minimize adverse effects and enhance efficacy, TAZ is usually used with a mid- or higher potency corticosteroid.⁶ Concomitant use of midor higher potency corticosteroid with TAZ does not compromise the sustained posttreatment improvement seen with TAZ.⁷ The rates of burning were less than half as frequent when TAZ was used with the mid-potency corticosteroid mometasone furoate 0.1% cream or high-potency corticosteroid fluocinonide 0.05% cream versus placebo.⁷ In a 4-week study, the steroid diflorasone diacetate 0.05% ointment reduced epidermal thickness by 43%, however when used in combination with TAZ 0.1% gel, there was only a 28% reduction (p≤0.003).⁸

Supporting Evidence from Clinical Trials (Table 1)

The fixed combination HP/TAZ lotion is more efficacious than the individual ingredients with a synergistic benefit.⁹ In a phase 2 multicenter, randomized, double-blind vehicle-controlled clinical trial, an Investigator Global Assessment (IGA) of clear/almost clear (IGA 0/1) with at least a 2-grade improvement from baseline at week 8 was seen in 52.5% treated with HP/TAZ, 33.3% with HP (p=0.033), 18.6% with TAZ (p<0.001), and 9.7% with vehicle (p<0.001).10 At week 2, baseline itching, dryness and burning/stinging also improved, similar to the improvement seen with HP and greater than that seen with TAZ.¹¹ Four weeks after treatment discontinuation, the improvement associated with HP/TAZ at week 8 was maintained.¹²

Two phase 3 multicenter, randomized, double-blind, vehicle-controlled clinical trials showed that by 2 weeks, HP/TAZ was more efficacious than vehicle. By week 8, 35.8% (study 1) and 45.3% (study 2) achieved IGA 0/1 with at least a 2-grade improvement from baseline.¹³

HP/TAZ may be a treatment option for individuals with skin of color. In a phase 3 clinical trial, a 58-year-old black male with post-inflammatory hyperpigmentation developed hypopigmentation from weeks 2-8, which returned to normal 4 weeks after treatment.¹⁴

In a 1-year phase 3 open-label long-term clinical trial of 555 adults with psoriasis and an IGA score of 3 (moderate) or 4 (severe) affecting 3-12% body surface area (BSA) at baseline, patients were treated once daily for 8 weeks, then as needed in 4-week intervals if an IGA of 0/1 (treatment success) was not achieved. There was a maximum of 24 weeks continuous treatment at any point in the study. Treatment success was achieved by 57.8% at some point during the study.¹⁵ No retreatment for >4 weeks was required in 55.3%, for >8 weeks in 28.3%, for >12 weeks in 19.5%, and for >16 weeks in 12.4%. Treatment-emergent adverse events (TEAEs) occurred in more than half of participants during the 1-year clinical trial, especially during the first 12 weeks. Most were mild to moderate in intensity. The most common TEAEs were application site dermatitis, pruritus, pain and irritation. Skin atrophy was present in 0.5% at baseline, 1.7% at week 12, 1.4% at week 24 and 0% at week 52. It led to study discontinuation in 1 participant. Striae occurred in 1.1% at baseline, 1.3% at week 12, 0.8% at week 24 and 0.7% at week 52. Folliculitis was present in 0.4% at baseline, 1.5% at week 12, 1.1% at week 24 and 0% at week 52. The discontinuation rate due to TEAEs was 7.5%.

Table 1: Summary of phase 2 and 3 12-week clinical trials with published data

† Treatment success was defined as an Investigator Global Assessment (IGA) score of clear or almost clear (IGA 0/1) with at least a 2-grade improvement from baseline.
BSA, body surface area; HP/TAZ, halobetasol propionate 0.01%-tazoretene 0.045%; HP, halobetasol propionate 0.01%; TAZ, tazarotene 0.045%; ↑/↓ , % change (increase/decrease) in BSA

Dosage and Duration

The usual adult dose is a once daily thin coat rubbed in gently to psoriatic plaques until control is achieved.¹ HP/TAZ may be used less frequently and on and off if redness, peeling or tenderness develop.¹ The maximum weekly amount to be used is 50 g which is one half of a 100 g tube.¹ There is no maximum treatment duration.¹

Counselling: Practical Tips to Optimize HP/TAZ Treatment and Minimize Irritation (Figure 1)

The fixed combination HP/TAZ medication should be applied once daily and rubbed in gently to skin affected with psoriasis, avoiding unaffected skin. It is important to show patients where the psoriasis lesions are and where to apply the medication. Less frequent applications (e.g., one, two, or three times per week) then increasing the frequency as tolerated may be considered, particularly in patients with sensitive skin. A thin coat of the medication should be applied, just enough to cover the psoriasis lesions. It is important to remind patients that more is not better as this can lead to irritation. After bathing, it is important to dry the skin with psoriasis before applying the medication. Failure to do so may result in redness, peeling and/or tenderness. The medication should be allowed to dry before putting on clothes. This prevents inadvertent spread onto unaffected skin. Patients should stop applying the medication when they cannot feel the psoriasis lesions anymore when their eyes are closed. The medication should not be applied to: (1) sensitive sites such as the face, anogenital region, and intertriginous areas (where two areas of skin touch or rub); (2) sites with erosions, ulcers, or fissures; and (3) sites also affected by eczema.¹ One 100 g tube should last at least 2 weeks.

Patients should be warned that sometimes the area around the psoriasis lesions can get irritated with redness, dryness, peeling and tenderness. If patients experience irritation, they should apply moisturizer either all over or just around psoriasis lesions before applying the HP/TAZ medication and/or reduce the frequency of application of the HP/TAZ medication to every 2nd or 3rd day until it settles.

Figure 1: Application tips for HP/TAZ lotion

Conclusions

The once daily fixed combination HP/TAZ lotion is convenient and provides synergistic benefit that is rapid and sustained for moderate to severe plaque psoriasis. Intermittent treatment over 1 year when the IGA is not clear/almost clear is safe and maintains efficacy supporting long-term use of HP/TAZ. The atrophic potential of HP is minimized with TAZ and the irritancy potential of TAZ is minimized with HP. Counselling with application tips should be considered for all patients.