Halobetasol Propionate for the Management of Psoriasis
The use of superpotent topical corticosteroids (TCSs) for the treatment of psoriasis is widely practiced, especially for expedient lesion resolution. However, their continued use in managing this chronic condition is limited because of labelling restrictions, concerns of side effects, and a paucity of data to support long-term management strategies. Halobetasol propionate (HP) is an effective short-term superpotent TCS. A novel HP lotion 0.01% formulation has been developed using a polymeric matrix technology that allows for uniform delivery of optimally sized particles onto the skin surface. The polymeric matrix and emulsion help to keep the skin hydrated and provide more efficient delivery of halobetasol into the epidermis.
Practice Points
- The widespread use of superpotent topical corticosteroids in treating psoriasis is limited by labelling that restricts short-term use, concerns about side effects, and a paucity of clinical data with longer-term use.
- Long-term management and treatment options are required for managing the chronic nature of psoriasis to improve patient satisfaction, adherence, and quality of life.
- A novel formulation of halobetasol propionate lotion 0.01% has been developed using a polymerized matrix with active ingredients and moisturizing excipients suspended in oil droplets.
Comparative Studies With Other TCSs
In comparative studies of patients with severe localized plaque psoriasis, HP ointment 0.05% applied twice daily for up to 4 weeks was significantly superior compared to clobetasol propionate ointment 0.05% for the number of patients with none or mild disease (P=.0237) or comparisons of global evaluation scores (P=.01315) at week 2, or compared to betamethasone valerate ointment 0.1% (P=.02).6 It also was more effective than betamethasone dipropionate ointment 0.05% with healing seen in 40% of patients treated with HP ointment 0.05% within 24 days compared to 25% of patients treated with betamethasone dipropionate ointment 0.05%.8 Patient acceptance of HP ointment 0.05% based on cosmetic acceptability and ease of application was better (very good in 90% vs 80% of patients7) or significantly better compared to clobetasol propionate ointment 0.05% (P=.042 and P=.01915) and betamethasone dipropionate ointment 0.05% (P=.02).8
Evolving Management Strategies
A number of management strategies have been proposed to improve the safety and efficacy of long-term therapy with TCSs, including weekend-only or pulse therapy, dose reduction, rotating to another therapy, or combining with other topical therapies. Maintenance efficacy data are sparse. A small double-blind study in 44 patients with mild to moderate psoriasis was conducted wherein patients were treated with calcipotriene ointment in the morning and HP ointment in the evening for 2 weeks.16 Those patients who achieved at least a 50% improvement in disease severity (N=40) were randomized to receive HP ointment twice daily on weekends and calcipotriene ointment or placebo twice daily on weekdays for 6 months. Seventy-six percent of those patients treated with a HP/calcipotriene pulsed therapy maintained remission (achieving and maintaining a 75% improvement in physician global assessment) compared to 40% of those patients treated with HP only (P=.045). Mild AEs were reported in 4 patients treated with the combination regimen and 1 patient treated with HP only. No AE-related discontinuations occurred.16
In a real-world setting, a maintenance regimen that is less complicated enhances the potential for increased patient adherence and successful outcomes.17 After an initial 2-week regimen of twice-daily HP ointment 0.05% in combination with ammonium lactate lotion in patients with mild to moderate psoriasis (N=55), those rated clear or almost clear (41/55 [74.6%]) entered a maintenance phase, applying ammonium lactate lotion twice daily and either HP or placebo ointment twice daily on weekends. The probability of disease worsening by week 14 was 29% in the HP-treated group compared to 100% in the placebo group (P<.0001). By week 24, 12 patients (29.2%) remained clear or almost clear.17
,Development of HP Lotion 0.01%
There are numerous examples in dermatology where advances in formulation development have made it possible to reduce the strength of active ingredients without compromising efficacy. Formulation advances also afford improved safety profiles that can extend a product’s utility. The vehicle affects not only the potency of an agent but also patient compliance, which is crucial for adequate response. Patients prefer lighter vehicles, such as lotions, over heavy ointments and creams.18,19
Recently, a polymeric honeycomb matrix (carbomer cross-linked polymers), which helps structure the oil emulsion and provide a uniform distribution of both active and moisturizing/hydrating ingredients (ie, sorbitol, light mineral oil, diethyl sebacate) at the surface of the skin, has been deployed for topical delivery of HP (eFigure 1). Ninety percent of the oil droplets containing solubilized halobetasol are 13 µm or smaller, an ideal size for penetration through follicular openings (unpublished data, Bausch Health, 2018).
This polymerized emulsion also forms a barrier by reducing epidermal water loss and improving skin hydration. Skin hydration and barrier protection of the lotion were assessed through corneometry and transepidermal water loss (TEWL) in 30 healthy female volunteers (aged 35–65 years) over 24 hours. The test material was applied to the volar forearm, with an untreated site serving as a control. Measurements using Tewameter and Corneometer were taken at baseline; 15 and 30 minutes; and 1, 2, 3, 8, and 24 hours postapplication. In addition, for the 8-hour study period, 15 patients applied the test material to the right side of the face and completed a customer-perception evaluation. Adverse events were noted throughout and irritation was assessed preapplication and postapplication. There were no AEs or skin irritation reported throughout the study. At baseline, mean (standard deviation [SD]) corneometry scores were 28.9 (2.9) and 28.1 (2.7) units for the test material and untreated control, respectively. There was an immediate improvement in water content that was maintained throughout the study. After 15 minutes, the mean (SD) score had increased to 59.1 (7.1) units in the vehicle lotion group (eFigure 2A). There was no improvement at the control site, and differences were significant at all postapplication assessments (P<.001). At baseline, mean (SD) TEWL scores were 12.26 (0.48) and 12.42 (0.44) g/hm2, respectively (eFigure 2B). There was an immediate improvement in TEWL with a mean (SD) score of 6.04 (0.99) after 8 hours in the vehicle lotion group, a 50.7% change over baseline. There was no improvement at the control site, and differences were significant at all postapplication assessments (P<.001). Customer perception of the novel lotion formulation was positive, with the majority of patients (93%–100%) responding favorably to all questions about the various attributes of the test material (eFigure 3)(unpublished data, Bausch Health, 2018).
