Lyn Guenther MD FRCPC FAAD

Professor of Dermatology, Western University, London ON, Canada
President, Guenther Research Inc., London ON, Canada

Conflict of interest:
Dr. Guenther has been a consultant, speaker, and clinical investigator for Bausch Health.

Introduction

A fixed combination halobetasol propionate and tazarotene lotion was launched in Canada in 2020, to treat moderate to severe plaque psoriasis in adults.1 It contains the super-potent corticosteroid halobetasol propionate (HP) 0.01% and the retinoid (vitamin A derivative) tazarotene (TAZ) 0.045% (HP/TAZ) in a moisturizing base.1 With the use of polymeric emulsion technology, there is uniform distribution of HP and TAZ and excipients on the skin and improved skin moisturization.2 It is a once daily fixed combination lotion that does not drip. Unlike HP cream and ointment which have a 2-week limitation before re-evaluation,3 there is no maximum treatment duration with HP/TAZ lotion. The product is supplied in a 100 g aluminum tube which should last at least 2 weeks.1 The lotion is hydrating and decreases transepidermal water loss.2 The non-medicinal ingredients are: 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 HP/TAZ lotion should not be used in pregnancy or in women who may become pregnant since it contains the retinoid tazarotene and retinoids are teratogenic.1

Background

Topical therapy is the mainstay of treatment for psoriasis. It is more convenient to apply one topical than two which may lead to improved adherence. Topical corticosteroids are most commonly applied, however psoriasis quickly relapses upon discontinuation and they may cause atrophy which is seen clinically as wrinkled or shiny skin.

TAZ is the only topical retinoid approved for use in psoriasis, however TAZ cream and gel are rarely used due to irritation. In an attempt to minimize irritation, TAZ is typically used with a topical corticosteroid.4 The once daily fixed combination HP/TAZ lotion is a convenient formulation that delivers TAZ and a topical corticosteroid.1 TAZ reduces inflammation and keratinocyte hyperproliferation, and normalizes the abnormal differentiation seen in psoriasis.1

In contrast to topical corticosteroids, improvement associated with TAZ therapy often persists after TAZ is stopped.5 Concomitant use of a mid- to higher-potency corticosteroid with tazarotene does not compromise the sustained posttreatment improvement seen with TAZ.6 In addition, use of a mid- to higher-potency corticosteroid with tazarotene halves the rate of burning compared to that seen with tazarotene and placebo.6 TAZ can also minimize corticosteroid induced atrophy. In a 4-week study, the corticosteroid diflorasone diacetate ointment decreased epidermal thickness by 43%, but when it was used with TAZ 0.1% gel, there was only a 28% reduction (p ≤ 0.003).7

Clinical Trials with HP/TAZ Lotion

The fixed combination HP/ TAZ lotion provides synergistic efficacy and greater efficacy than the individual ingredients.8 In a phase 2 multicenter, randomized, double-blind vehicle-controlled study, more participants in the HP/TAZ arm were clear/almost clear with a 2-grade or greater improvement in Investigator Global Assessment (IGA) after 8 weeks of treatment (52.5% vs. 33.3% with HP (p=0.033), 18.6% with TAZ (p<0.001), and 9.7% with vehicle (p<0.001).8,9 Improvement was noted as early as week 2 (the first visit after baseline).10 Itching, dryness and burning/stinging also improved with HP/TAZ at week 2, to a similar degree to that seen with HP but greater degree than that seen with TAZ.10 The improvement with HP/TAZ at week 8 was maintained four weeks after treatment discontinuation.11

In two phase 3 clinical trials, HP/TAZ was more efficacious than vehicle at week 2. After 8 weeks of therapy, 35.8% (study 1) and 45.3% (study 2) were clear/almost clear with at least a 2-grade improvement in IGA.12

HP/TAZ has been used in individuals with skin of colour. In a phase 3 clinical trial, a 58-year-old black man with post-inflammatory hyperpigmentation was almost clear after 4 weeks of treatment and after 8 weeks, the affected body surface area was one half that at baseline. During weeks 2-8, he developed hypopigmentation which resolved 4 weeks after treatment.13

A 1-year open-label phase 3 study involving 555 adults with moderate-to-severe psoriasis affecting 3-12% body surface area (BSA) showed that HP/TAZ can be safely used long-term. In this study, initially patients were treated once daily for 8 weeks, then as needed in 4-week intervals with a maximum of 24 weeks continuous treatment at any point in the study. If an IGA of clear/almost clear (treatment success) was achieved, treatment was discontinued, however if it was not, it was resumed. At some point in the study, 57.8% achieved treatment success.14 Persistence of improvement was noted in many individuals. After treatment discontinuation, 55.3% did not require retreatment for >4 weeks, 28.3% for >8 weeks, 19.5% for >12 weeks, and 12.4% for >16 weeks. More than half of participants had treatment-emergent adverse events (TEAEs) during the 1-year clinical trial, particularly during the first 12 weeks. Seven and one-half percent discontinued the clinical trial due to TEAEs. Mild to moderate application site dermatitis, pruritus, pain and irritation were the most common TEAEs. Skin atrophy led to study discontinuation in one individual and was noted in 0.5% at baseline, 1.7% at week 12, 1.4% at week 24 and 0% at week 52. Striae were noted in 1.1% at baseline, 1.3% at week 12, 0.8% at week 24 and 0.7% at week 52.

Application Counselling: Practical Tips to Optimize Treatment and Minimize Irritation (see Figure 1)

A thin coat, just enough to cover the psoriatic plaques, should be applied once daily, then gently rubbed in. Patients should be shown where the psoriasis lesions are and where they should apply HP/TAZ. Less frequent applications should be considered for patients with sensitive skin (e.g., 1-3 times a week initially), then increasing the frequency as tolerated. If HP/TAZ is to be applied after bathing, the patient should wait until the skin is completely dry before applying.

Remind patients that more medication is not better; more medication is more irritating. A thin coat is all that is required. The medication should not be applied to skin without psoriasis. The medication should be dry before putting on clothes to prevent spread to unaffected skin. 50 g (i.e. one half of a 100 g tube) is the maximum recommended weekly dose.1

Healthcare providers should warn patients that irritation may occur particularly around the plaques. If this happens, before applying HP/TAZ, moisturizer should be applied either all over, OR just around psoriasis lesions and/or the frequency of application of HP/TAZ should be decreased to every 2-3 days until it settles.

Once psoriasis lesions have cleared, HP/TAZ should be discontinued. If the psoriasis lesions cannot be felt when the eyes are closed, it is time to stop. The medication should not be applied to: (1) sensitive areas such as the face, anogenital areas, and intertriginous areas (where two areas of skin touch or rub), (2) sites with erosions, ulcers, or fissures; and (3) skin with eczema. DO NOT use in pregnancy or in women who may become pregnant.1

Figure 1: Application tips for HP/TAZ lotion

Conclusion

HP (a superpotent corticosteroid) /TAZ (a retinoid) is a convenient once daily fixed combination lotion for moderate to severe psoriasis. TAZ minimizes the atrophic potential of HP, and HP reduces the irritancy potential of TAZ. It has synergistic efficacy that is rapid and sustained. Intermittent treatment over 1 year is safe and efficacious. Application counselling improves tolerability and should be offered to all patients.

References



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