Halobetasol Propionate 0.01% Lotion for Plaque Psoriasis and Corticosteroid-Responsive Dermatoses

Abrahim Abduelmula, BScN¹; Brian D. Rankin, PhD²; Ronald Vender, MD^3,4;
Jensen Yeung, MD^5-8; Alim R. Devani, MD^9-11; Vimal H. Prajapati, MD^9-14

¹Faculty of Medicine, University of Western Ontario, London, ON, Canada
²Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
³Department of Dermatology, McMaster University, Hamilton, ON, Canada
⁴Dermatrials Research Inc. & Venderm Innovations in Psoriasis, Hamilton, ON, Canada
⁵Division of Dermatology, Department of Medicine, University of Toronto, ON, Canada
⁶Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada
⁷Sunnybrook Health Sciences Centre, Toronto, ON, Canada
⁸Probity Medical Research, Waterloo, ON, Canada
⁹Dermatology Research Institute, Calgary, AB, Canada
¹⁰Skin Health & Wellness Centre, Calgary, AB, Canada
¹¹Probity Medical Research, Calgary, AB, Canada
¹²Division of Dermatology, Department of Medicine, University of Calgary, Calgary, AB, Canada
¹³Section of Community Pediatrics, Department of Pediatrics, University of Calgary, Calgary, AB, Canada
¹⁴Section of Pediatric Rheumatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada

Conflict of interest:
Abrahim Abduelmula and Brian D. Rankin have no relevant disclosures. Ronald Vender has been an advisor, consultant, speaker, and/or investigator for AbbVie, Actelion, Amgen, Astellas, Celgene, Dermira, Eli Lilly, Galderma, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, and Takeda. Jensen Yeung has been an advisor, consultant, speaker, and/or investigator for AbbVie, Allergan, Amgen, Astellas, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, GSK, Janssen, LEO Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, Valeant, and Xenon. Alim R. Devani has been an advisor, consultant, speaker, and/or investigator for AbbVie, Amgen, AnaptysBio, Arcutis, Arena, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Incyte, Janssen, LEO Pharma, Medexus, Nimbus Lakshmi, Novartis, Pediapharm, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Tribute, UCB, and Valeant. Vimal H. Prajapati has been an advisor, consultant, speaker, and/or investigator for AbbVie, Actelion, Amgen, AnaptysBio, Aralez, Arcutis, Arena, Aspen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Concert, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Homeocan, Incyte, Janssen, LEO Pharma, Medexus, Nimbus Lakshmi, Novartis, Pediapharm, Pfizer, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Tribute, UCB, and Valeant. Funding sources: None.

Abstract:
A novel topical corticosteroid, halobetasol propionate (HP) 0.01% lotion (Bryhali™), has recently been introduced for the treatment of plaque psoriasis and corticosteroid-responsive dermatoses in adults. Once daily application of HP 0.01% lotion is indicated for use up to 8 weeks. Treatment success for plaque psoriasis in the pivotal phase 3 clinical trials (defined as an Investigator Global Assessment [IGA] of clear/almost clear [IGA 0/1] with ≥2-grade improvement from baseline) occurred in over one-third of patients by week 8. Treatment-emergent adverse events were typically mild-to-moderate in intensity and usually limited to the application site(s). No treatment-related cases of skin atrophy have been reported from the studies. Counselling should be considered to optimize treatment outcomes.

Key Words:
Bryhali™; halobetasol; topical; therapeutics; corticosteroid; psoriasis; clinical trial

Introduction

Topical corticosteroids are a mainstay in the management of plaque psoriasis and other corticosteroid-responsive dermatoses. Bryhali™ is a super-potent topical corticosteroid lotion with halobetasol propionate (HP) 0.01% as the active ingredient. It was approved by the US FDA in 2018 for plaque psoriasis and by Health Canada in 2021 for both plaque psoriasis and corticosteroid-responsive dermatoses. Available in 45 g, 60 g, and 100 g tubes containing 0.1 mg of HP 0.01% per gram, HP 0.01% lotion is applied once daily to affected areas (maximum dose of 50 g per week).^1,2 It has a safety profile allowing for extended use up to 8 weeks without physician re-evaluation (provided there are observed improvements in the condition being treated).³ Non-medicinal ingredients of this product 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%. No data is currently available for its use in pediatric or pregnant patients; therefore, HP 0.01% lotion has not been approved for utilization in children/adolescents (<18 years of age), nor is it recommended in pregnant women.¹

Background

Plaque psoriasis and certain corticosteroid-responsive dermatoses, such as atopic dermatitis, are chronic, immunemediated, inflammatory skin diseases that vary in severity. Topical corticosteroids are used across all severities, although moderate-to-severe disease often requires the addition of phototherapy or systemic therapies.⁴ Despite their efficacy, these conditions can quickly recur if treatment is discontinued; however, extended use of topical corticosteroids can also result in adverse events (AEs) that are either local (e.g., skin atrophy, folliculitis, striae, and telangiectasia) or systemic (e.g., hypothalamic-pituitary-adrenal [HPA] axis suppression).⁵

HP 0.05% cream or ointment (Ultravate^®) is a commonly prescribed topical corticosteroid applied once or twice daily per physician direction (maximum dose of 50 g per week).⁶ According to the product monograph, patients should limit use to a maximum of 2 weeks unless re-evaluated by a physician. However, considering the chronic nature of plaque psoriasis and many other corticosteroid-responsive dermatoses, such as atopic dermatitis, this limited treatment duration can become an issue for long-term utilization and compliance.⁶ Studies on HP 0.01% lotion have shown that despite demonstrating comparable efficacy to HP 0.05% cream, the safety profile allows it to be used for intervals longer than 2 weeks without the need for physician re-evaluation at 2 weeks.⁷

HP is a water-insoluble synthetic corticosteroid thought to act via the induction of lipocortins, a group of phospholipase A2 inhibitory proteins. It is theorized that these proteins act on pro-inflammatory mediators, such as prostaglandins and leukotrienes, via inhibition of the precursor arachidonic acid.⁸ HP has anti-inflammatory, anti-proliferative, antipruritic, and vasoconstrictive effects.^1,7

The once daily HP 0.01% lotion is formulated with proprietary PRISMATREX™ technology, a novel polymeric emulsification system that features oil droplets containing the active ingredient and other hydrating/moisturizing excipients dispersed evenly in an oil-in-water emulsion and separated by a 3-dimensional mesh matrix.^1,9 This allows for uniform distribution and enhanced penetration when applied onto the skin surface. The latter may provide rationale for the comparable efficacy of HP 0.01% lotion and HP 0.05% cream despite a 5-fold difference in the concentration of HP.⁷

Supporting Evidence from Clinical Trials (Table 1)

Table 1

Plaque Psoriasis

In a phase 2 multicenter, randomized, double-blind, vehicle-controlled clinical trial (n=150), the efficacy and safety of HP 0.01% lotion (n=60) versus HP 0.05% cream (n=57) was evaluated in adult patients with moderate-to-severe plaque psoriasis (Investigator Global Assessment [IGA] score: moderate [3] or severe [4]; affected body surface area [BSA]: 3% to 12%).⁷ At week 2: the primary endpoint of an IGA score of clear or almost clear (IGA 0/1) with ≥2-grade improvement from baseline (treatment success) was achieved by 30.0% and 31.6% of patients treated with HP 0.01% lotion and HP 0.05% cream, respectively (p=0.854); a 2-grade improvement from baseline in the 3 key signs of plaque psoriasis—erythema, elevation, and scaling—at the target lesion site (treatment success for specific psoriasis signs) was achieved by 38.3%, 40.0%, and 43.3% of patients treated with HP 0.01% lotion versus 31.6%, 36.8%, and 47.4% of patients treated with HP 0.05% cream, respectively (p=0.446, p=0.727, and p=0.663, respectively); and BSA improved by 22.3% with HP 0.01% lotion versus 20.9% with HP 0.05% cream (p=0.787). Both HP 0.01% lotion and HP 0.05% cream were more effective than vehicle at all time points, with HP 0.01% lotion demonstrating greater efficacy than HP 0.05% cream for patients with more severe disease (IGA=4) at baseline. Safety evaluation revealed AEs of treatment-related dermatitis (n=1) and severe itching (n=1) with HP 0.01% lotion as well as treatment-related severe itching (n=2) and severe burning/ stinging (n=1) with HP 0.05% cream. No treatment-related cases of skin atrophy, folliculitis, striae, or telangiectasia were observed in either treatment group.⁷ In summary, HP 0.01% lotion was comparable to HP 0.05% cream in terms of overall treatment success, treatment success for specific psoriasis signs at the target lesion site, and reduction in BSA, with both treatments demonstrating a favorable safety profile.

In a pooled analysis of 2 phase 3 multicenter, double-blind, randomized, parallel-group clinical trials (n=430), the efficacy and safety of HP 0.01% lotion (n=285) versus vehicle (n=145) was evaluated in adult patients with moderate-to-severe plaque psoriasis (IGA score: 3 or 4; affected BSA: 3% to 12%).⁹ At week 8: the primary endpoint of treatment success was achieved by 36.5% (Study 1) and 38.4% (Study 2) of patients treated with HP 0.01% lotion versus 8.1% (Study 1) and 12.0% (Study 2) of patients treated with vehicle (p<0.001 for both comparisons versus vehicle), with HP 0.01% lotion demonstrating statistically significant superiority over vehicle as early as week 2 (Study 1) and week 4 (Study 2); HP 0.01% lotion achieved treatment success for specific psoriasis signs at the target lesion site in 46.7% (Study 1) and 56.3% (Study 2) of patients for erythema, 52.5% (Study 1) and 62.7% (Study 2) of patients for elevation, as well as 54.9% (Study 1) and 63.1% (Study 2) of patients for scaling (p<0.001 for all comparisons versus vehicle); BSA improved by 34.2% (Study 1) and 36.2% (Study 2) with HP 0.01% lotion (p<0.001 for both comparisons versus vehicle), with HP 0.01% lotion demonstrating statistically significant superiority over vehicle as early as week 2 (both Study 1 and Study 2); mean Dermatology Life Quality Index (DLQI) score was reduced by 57.7% (Study 1) and 58.7% (Study 2) with HP 0.01% lotion (p=0.001 and p=0.004, respectively, versus vehicle); mean IGAxBSA composite score (calculated by multiplying the IGA by the BSA; range: 9-48) was reduced by 49.5% with HP 0.01% lotion versus 13.4% with vehicle (p<0.001), with HP 0.01% lotion demonstrating statistically significant superiority over vehicle as early as week 2; and the proportion of patients achieving ≥50%, ≥75%, and ≥90% reduction in IGAxBSA composite score from baseline (IGAxBSA-50, IGAxBSA-75, and IGAxBSA-90, respectively) was 56.8%, 39.3%, and 19.3% with HP 0.01% lotion versus 17.2%, 9.7%, and 2.8% with vehicle (p<0.001 for all comparisons versus vehicle).^3,9 Safety evaluation revealed similar rates of AEs between the treatment groups: 21.5% with HP 0.01% lotion and 23.9% with vehicle. Most AEs (90.2%) were mild-to-moderate in intensity. No cases of treatment-related skin atrophy, folliculitis, or striae were reported.¹⁰ There was one AE of telangiectasia with HP 0.01% lotion, not deemed to be treatment-related. In summary, HP 0.01% lotion was superior to vehicle in terms of overall treatment success, treatment success for specific psoriasis signs at the target lesion site, reduction in BSA, as well as improvements in mean DLQI and mean IGAxBSA composite scores, with HP 0.01% lotion demonstrating a favorable safety profile.

Corticosteroid-Response Dermatoses

There are no clinical trials investigating the efficacy and safety of HP 0.01% lotion for corticosteroid-responsive dermatoses.

Dosage and Administration

The on-label recommendation is to apply a thin layer of Bryhali™ once daily to areas affected by plaque psoriasis or other corticosteroid-responsive dermatoses until disease control is achieved.¹ The total amount used should not exceed 50 g per week due to the concern for HPA axis suppression. Uninterrupted treatment beyond 8 weeks is not recommended.¹

Counselling: Practical Tips to Optimize Use

A thin layer of HP 0.01% lotion should be applied, just enough to cover the areas affected by plaque psoriasis or other corticosteroid-responsive dermatoses. It is essential to rub in gently and inform patients that applying excessive amounts will not improve treatment efficacy. If HP 0.01% lotion is applied after bathing, the treatment site(s) should be dry before application.

It is also important to allow sufficient time for the medication to dry before putting clothes on to prevent inadvertent spread onto unaffected skin. HP 0.01% lotion should not be used with occlusive dressings unless recommended by a physician. It is for external use only and must be kept away from the eyes, nose, mouth, and other mucosal sites. HP 0.01% lotion should not be applied to the scalp or sensitive sites, such as the face, groin, and axillae, nor on ulcers or wounds.¹ It is also advised to avoid application on areas affected by untreated bacterial, tubercular, fungal and viral infections involving the skin.¹

Conclusion

Once daily application of HP 0.01% lotion (Bryhali™) is a convenient topical therapy with comparable efficacy to HP 0.05% cream (Ultravate^®), despite a 5-fold difference in concentration of HP. One of the main advantages is its ability to be used safely for up to 8 weeks without concern for AEs (especially skin atrophy) and the requirement for physician re-evaluation (provided there are observed improvements in the condition being treated). Counselling with application tips should be considered for all patients.

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