Psoriasis is a chronic inflammatory condition that can significantly impair quality of life. Enstilar®, a topical treatment, contains betamethasone and calcipotriol in a cutaneous foam formulation
Psoriasis is a chronic inflammatory condition that can significantly impair quality of life. Enstilar®, a topical treatment, contains betamethasone and calcipotriol in a cutaneous foam formulation
Rod Tucker BPharm PhD
Researcher, Robert Gordon University, Aberdeen, UK
Psoriasis is a chronic inflammatory skin condition, which according to the psoriasis association, affects up to 3% of the UK population.1 While not life-threatening, it is associated with a significant impairment in quality of life,2 impacting on work, family, sexual relations and physical and emotional well-being.3 Focus-group work with patients suggests that the itching associated with psoriasis is the most important, severe and troublesome symptom of their condition.4
Psoriasis places a large economic burden on society with one estimate of costs due to absenteeism from work in the UK being £1.03 billion per year.5 Moreover, it is estimated that between 6% and 42% of patients with psoriasis will develop an inflammatory arthritis known as psoriatic arthritis.6
Cause of psoriasis
The precise cause of psoriasis remains unclear but is likely to result from a complex interplay between genetic and immune-related factors. In the epidermis, the normal 28-day life span of keratinocytes is reduced to four to five days. This results in immature keratinocyte cells accumulating on the surface of the skin, becoming visible as silvery-white scales.
The trigger for psoriasis is unknown but recent research suggests that dysregulation of the immune system is a major factor as proven by the efficacy of the biologic drugs (which target immune cells) used to treat more severe disease. Furthermore, psoriasis is associated with several co-morbidities such as ischaemic heart disease, diabetes and hypertension.
There is currently no cure for psoriasis and the disease follows a relapsing-remitting pattern, requiring effective self-management by the patient. There are several variants, but the most common, affecting the majority of patients, is plaque psoriasis. Clinically, this presents as well-demarcated round to oval plaques with a silvery white adherent scale. Typically, these plaques will develop on extensor surfaces such as the elbows, knees and lower back, although many patients will also suffer with scalp psoriasis.
Up to 80% of patients with plaque psoriasis have mild to moderate disease that is amenable to treatment with topical therapies.7
Defining disease severity
There are no universally accepted classifications of disease severity. According to the National Psoriasis Foundation, severity can be defined in terms of the total body surface area (BSA) affected.8 The surface area of a single hand (that is, flat palm and five fingers) of the affected person, represents about 1% of the skin. Using this measure, mild psoriasis affects less than 3% BSA (for example, only the elbows) and moderate psoriasis, between 3 and 10% BSA (that is, elbows and knees). Another commonly used measure is the Psoriasis and Severity Index (PASI).
This tool assesses the level of psoriasis at different parts of the body and then computes an overall severity score. The maximum value is 72 with values >10 representing moderate disease and PASI scores <10 representing mild disease.
However, PASI and BSA assessments fail to recognise the impact of psoriasis on quality of life which is normally evaluated with the Dermatology Quality of Life Index (DLQI).9
Disease severity has recently been defined by a European consensus group using all three measures. Severity is dichotomised into either mild or moderate to severe. Mild psoriasis is defined when all three measures have a value <10 and moderate to severe where all measures are >10.10 Nevertheless, in clinical trials, disease severity is often measured using PASI values and treatment success defined, for example, as a PASI75 (that is, a 75% improvement from baseline in PASI score). Another commonly used tool is the Investigator/Physician Global Assessment (IGA/PGA), which is illustrated in Table 1.
Topical therapies for mild to moderate psoriasis
There have been various treatments for psoriasis over the last two centuries including coal tar, dithranol and tazarotene (topical retinoid). Today, the majority of patients with mild to moderate disease are managed with topical steroids, vitamin D analogues (for example, calcipotriol, calcitriol) or a combination of the two.
The most recent systematic reviews of topical therapies for psoriasis are a Cochrane review11 and the guideline from the National Institute for Health and Care Excellence (NICE).12
The conclusions of the Cochrane review are summarised in Figure 1 and represent an estimate of the degree of improvement achieved by the different therapies based on a six-point improvement scale.
Figure 1. Effect of topical therapies on psoriasis based on a six-point improvement scale.
The data in Figure 1 suggest that Dovobet® is the most effective treatment option in primary care. Such an approach allows for targeting different aspects of the disease. For instance, vitamin D analogues restore normal keratinocyte development while topical steroids treat the underlying inflammation. Although NICE agreed that combination therapy is more effective, it recommended that patients receive and apply the individual components separately (for example, morning and evening) rather than as a combined product.
The only topical combination therapy previously available was calcipotriol and the potent steroid, betamethasone, launched in the UK in 2002 under the brand name Dovobet® (LEO Pharma). The product was originally available as an ointment but a gel formulation was launched in 2011 and an applicator device containing the gel was launched in 2015.
In May 2016, LEO Pharma launched a formulation called Enstilar®. Rather than a gel or ointment, Enstilar® is a cutaneous foam formulation containing the same two ingredients as Dovobet®.
Enstilar® clinical studies
To date there have been five clinical studies with Enstilar® and these are summarised in Table 2. The primary outcome in four of the studies was the proportion of patients who achieved ‘clear’ or ‘almost clear’ (compared with baseline) after four weeks of treatment for those with moderate/severe psoriasis and ‘clear’ for patients with mild disease according to the PGA scale.
Other outcomes considered were a modified (excluding the head) PASI score and one of the studies used a total clinical score, TCS (which was a composite measure of erythema, scaling and lesional thickness (each scored from 0–3) and a 100mm visual analogue scale measuring itch severity over the previous 24 hours. Some trials also reported patient global assessment (PaGA).
Adverse effects
In the trial by Lebwohl,13 the incidence of adverse effects was similar for all active groups (10–13%) and were of mild to moderate intensity and included medication residue and application site pain experienced by one to three patients. A similar level of adverse events was reported in the paper by Koo et al.14
An example of the impact of Enstilar® on psoriasis is shown in Figure 2.
Figure 2. Change in disease severity after four weeks’ treatment with Enstilar®. Data from the PSO-FAST study, reference 16. Reproduced with permission from LEO Pharma.
Place in therapy
The results in Table 2 suggest that the difference in efficacy between Enstilar® and a potent topical steroid, betamethasone are marginal13 in the treatment of both body and scalp psoriasis. However, the data in studies 3 and 5, in which Enstilar® is compared with the two currently available Dovobet® products, suggest that the new formulation has a greater efficacy.
Conclusions
The introduction of Enstilar® allows healthcare professionals to work towards achieving the vision of the NICE guidance, which suggests that professionals “…take into account patient preference, cosmetic acceptability, practical aspects of application and the site(s) and extent of psoriasis to be treated.”
Increasing the range of formulations available with different aesthetic qualities, allows for greater patient choice, which may impact on adherence and ultimately improve disease outcomes.
Key points
- Psoriasis is a chronic inflammatory skin condition affecting up to 3% of the population in the UK.
- It is not life threatening but has a huge negative impact on quality of life.
- Psoriasis presents clinically as silvery-white scales, typically affecting the elbows, knees, scalp and lower back.
- Available evidence suggests that the combination of a potent topical steroid and a vitamin D analogue is the most effective therapy.
- Enstilar® is a new topical foam formulation containing the potent steroid betamethasone and calcipotriol. Enstilar® appears to be more efficacious than currently available combination products in the UK
References
- Psoriasis Association. About Psoriasis. www.psoriasis-association.org.uk/pages/view/about-psoriasis (accessed September 2016).
- Langley RGB et al. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis 2005;64(Suppl 2):18−23.
- Kimball AB et al. The psychosocial burden of psoriasis. Am J Clin Dermatol 2005;6(6):383−92.
- Globe D et al. The impact of itch symptoms in psoriasis: results from physician interviews and patient focus groups. Health Qual Life Outcomes 2009;7:62−72.
- Bajorek Z et al. The impact of long term conditions on employment and the wider UK economy. The Work Foundation, Feb 2016. www.theworkfoundation.com/Reports/397/The-impact-of-long-term- conditions-on-employment-and-the-wider-UK-economy (accessed September 2016).
- Gladman DD et al. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis 2005;64 (Suppl 2:ii):14−17.
- Menter A et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 3. Guidelines of care for the management and treatment of psoriasis with topical therapies. J Am Acad Dermatol 2009;60:643−59.
- National Psoriasis Foundation. About psoriasis. www.psoriasis.org/about-psoriasis (accessed September 2016).
- Dermatology Quality of Life Indexhttp://sites.cardiff.ac.uk/dermatology/quality-of-life/dermatology-quality-of-life-index-dlqi/ (accessed September 2016).
- Mrowietz U et al. Definition of treatment goals for moderate to severe psoriasis: a European consensus. Arch Dermatol Res 2011;303(1):1−10.
- Mason AR et al. Topical treatments for chronic plaque psoriasis. Cochrane Database Sys Rev 2013; Issue 3. Art. No.: CD005028.
- National Institute for Health and Care Excellence. Psoriasis: assessment and management. NICE guideline CG153. www.nice.org.uk/guidance/CG153/chapter/1-Guidance#topical-therapy (accessed September 2016).
- Lebwohl M et al. Fixed combination aerosol foam calcipotriene 0.005% (Cal) plus betamethasone dipropionate 0.064% (BD) is more efficacious than Cal or BD aerosol foam alone for psoriasis vulgaris: A randomised, double-blind, multicenter, three-arm, Phase 2 study. J Clin Aesthet Dermatol 2016;9(2):34−41.
- Koo J et al. Superior efficacy of calcipotriene and betamethasone dipropionate aerosol foam versus ointment in patients with psoriasis vulgaris – a randomised phase II study. J Dermatolog Treat 2016;27(2):120–7.
- Queille-Roussel C et al. Efficacy of an innovate aerosol foam formulation of fixed combination calcipotriol plus betamethasone dipropionate in patients with psoriasis vulgaris. Clin Drug Invest 2015;35:239–45.
- Leonard C et al. Efficacy and safety of calcipotriene plus betamethasone dipropionate aerosol foam in patients with psoriasis vulgaris – a randomised phase III study (PSO-FAST). J Drugs Dermatol 2015;14(12):1468−77.
- Paul C et al. Calcipotriol plus betamethasone dipropionate aerosol foam provides superior efficacy vs. gel in patients with psoriasis vulgaris: randomised, controlled PSO-ABLE study. J Eur Acad Dermatol Venereol 2016; Aug 17 [Epub ahead of print]
