This supplement has been developed in partnership with LEO Pharma. Guidance Update

Transcription

1 This supplement has been developed in partnership with LEO Pharma cpd credits Guidance Update Dermatology Management of plaque psoriasis A focus on calcipotriol and betamethasone cutaneous foam (Enstilar ) Management of plaque psoriasis in primary care by Dr George Moncrieff... p2 Development of a local guideline for the management of psoriasis in primary care by Dr Helen Young... p5 This supplement has been developed in partnership with LEO Pharma. LEO Pharma suggested the topic and authors, commented on the author briefs, and commissioned the production of the supplement. The content has also been checked to ensure its compliance with appropriate regulations and legislation. MGP Ltd has paid the authors honoraria on behalf of LEO Pharma. The views and opinions of the authors are not necessarily those of LEO Pharma or of Guidelines in Practice, its publisher, advisers, or advertisers. No part of this publication may be reproduced in any form without the permission of the publisher. Prescribing information can be found on the back cover. Job code MAT MGP Ltd 2017 Date of preparation: March 2017

2 Management of plaque psoriasis in primary care: a focus on calcipotriol and betamethasone cutaneous foam (Enstilar ) Dr George Moncrieff, GP, Bicester; Chair of the Dermatology Council for England; Committee Member of the Primary Care Dermatology Society Introduction Psoriasis is a chronic, inflammatory skin disease with a wide spectrum of clinical manifestations. It is estimated to affect 2 4% of the population in western countries, 1 so a full-time GP with an average-sized list might have more than 40 affected patients. Psoriasis is uncommon in childhood, affecting around 1 in 200 children under 10 years. Prevalence diminishes beyond the age of 70 years. 2 Psoriasis can relapse and remit over many years and has a major impact on a patient s life beyond the obvious severity of the rash (see paw-2016). It is visible, scaly, itchy, and, at times, painful and debilitating, and can have devastating psychological consequences. Furthermore, recent research suggests that the chronic inflammatory load, especially from psoriatic arthritis, accelerates arteriosclerosis. 3 Diagnosis The diagnosis of chronic stable plaque psoriasis is usually straightforward, and is characterised by plaques of erythematous skin and firm adherent silvery scales, particularly on the extensor surfaces of the limbs and the torso. Atypical patterns can be difficult to diagnose and early referral should be sought where there is doubt about the diagnosis. Other forms of psoriasis that are beyond the scope of this article, such as guttate, flexural (including genital), pustular and facial psoriasis, as well as involvement of the nails, are commonly encountered in primary care and need to be identified. In addition, psoriatic arthritis (PsA) is a destructive condition that can cause permanent damage to the joints with functional disability, 4 and it is essential that we are vigilant for this in primary care. 5,6 Management in primary care The majority of patients with chronic stable plaque psoriasis either self-manage or are cared for exclusively in primary care. It would be hard to overemphasise the importance of asking the patient how their psoriasis affects them and empowering them to respond fully. The Dermatology Life Quality Index (DLQI), developed by the Department of Dermatology, Cardiff University (sites.cardiff.ac.uk/dermatology/quality-of-life/ dermatology-quality-of-life-index-dlqi/), is a quick and effective tool for exploring this. It is crucial to remind the patient that their psoriasis is not contagious, and by touching their skin during examination, you can demonstrate that you do not find their condition offensive. As GPs we are ideally placed to assess important co morbidities such as obesity, smoking, and alcohol, all of which are known to make psoriasis worse. We must also be aware of those medications that can aggravate psoriasis, including antimalarials and lithium, and these should be avoided where possible. Psoriasis is a dry skin condition that is aggravated by harsh detergents, so patients should be advised to avoid soaps, shower gels, and shampoos. Emollients, as part of complete emollient therapy, 7 are as important as they are in the treatment of eczema and their central role is not emphasised adequately in many guidelines, including those from NICE and SIGN. 5,8 The Primary Care Dermatology Society (PCDS) psoriasis guidance (available online at: stresses the importance of prescribing copious emollients for all patients with psoriasis. 9 Guidance NICE Clinical Guideline (CG) 153 on assessment and management of psoriasis includes the following advice on 2

3 Key points Psoriasis is common in the UK, 9 so we need to be confident about managing it in primary care Psoriasis can have a profound effect on the well-being of our patients, way beyond the degree of skin disease Psoriatic arthritis is destructive and needs prompt referral to a rheumatologist to ensure it is fully controlled The DLQI psoriasis assessment survey is a really useful tool for GPs Lifestyle changes really matter in particular, patients with psoriasis should avoid tobacco and obesity Emollients have a central role in the management of psoriasis and patients should avoid soap, shower gel, and shampoo Cal/BD is an effective topical therapy and its use may improve psoriasis in patients and therefore reduce the need for referral to secondary care. DLQI=Dermatology Life Quality Index; Cal/BD=combined calcipotriol monohydrate and betamethasone dipropionate initial topical treatments for psoriasis affecting the trunk and limbs: 8 * offer a potent corticosteroid applied once daily plus vitamin D or a vitamin D analogue applied once daily (applied separately, one in the morning and the other in the evening) for up to 4 weeks as initial treatment for adults with trunk or limb psoriasis if once-daily application of a potent corticosteroid plus oncedaily application of vitamin D or a vitamin D analogue does not result in clearance, near clearance, or satisfactory control of trunk or limb psoriasis in adults after a maximum of 8 weeks, offer vitamin D or a vitamin D analogue alone applied twice daily if twice-daily application of vitamin D or a vitamin D analogue does not result in clearance, near clearance, or satisfactory control of trunk or limb psoriasis in adults after 8 12 weeks, offer either: a potent corticosteroid applied twice daily for up to 4 weeks or a coal tar preparation applied once or twice daily if a twice-daily potent corticosteroid or coal tar preparation cannot be used, or a once-daily preparation would improve adherence in adults, offer a combined product containing calcipotriol monohydrate and betamethasone dipropionate applied once daily for up to 4 weeks. * National Institute for Health and Clinical Excellence (2010) Clinical Guideline 153. Psoriasis: assessment and management. NICE has not checked the use of its content in this publication to confirm that it accurately reflects the NICE publication from which it is taken. In my opinion this advice from NICE does not reflect the particular issues facing GPs. While topical steroids and vitamin D analogues used separately might be a cost-effective choice initially, I consider the dual prescriptions create problems as the patient has two prescription charges to pay, there is increased risk of confusion and therefore non-adherence, a risk of inconsistency in dosing through application of individual preparations, and there is also the potential that they may abandon the vitamin D product altogether if they find it is an irritant. It is well recognised that patients with psoriasis often fail to adhere to their treatment, 10 so a complicated treatment pathway like this is unhelpful, and the guidelines acknowledge that a once-daily therapy is desirable. 5,8 I believe the NICE pathway (available at: pathways.nice.org.uk/pathways/psoriasis) is unnecessarily complicated for both patient and doctor. In the current NICE guideline (CG153, see below left, published before the foam preparation was available), the combination product calcipotriol monohydrate and betamethasone dipropionate (Cal/BD) is not recommended until step three of topical treatments for psoriasis affecting the trunk and limbs. 8 By that stage, some patients may have become bewildered and have lost confidence in their GP s ability to treat their condition, in addition to having paid for several different prescriptions. This is likely to result in a request for referral to see a specialist, which negates any possible savings to the NHS from prescribing the perceived cost-effective treatment. SIGN National Clinical Guideline 121 on Diagnosis and management of psoriasis and psoriatic arthritis, published before the foam preparation of Cal/BD was available, recommends: 5 short-term intermittent use of a potent topical corticosteroid or a combined potent corticosteroid plus calcipotriol ointment to gain rapid improvement in plaque psoriasis (Grade A). This positions Cal/BD as a first-line option in primary care, and is my preferred option for treatment in line with the PCDS guidance, which simply recommends the use of the combination Cal/BD first line. 9 Treatment with Cal/BD In my experience, once-daily Cal/BD combination therapy is more effective than other topical combinations for chronic stable plaque psoriasis. There is some evidence in adults that plaques of psoriasis produce chemicals that aggravate the condition, 11 so early aggressive therapy with a proven effective agent may not only help the patient, but may also assist in preventing their psoriasis becoming more persistent and troublesome. As a consequence, this may avoid the need for referral to secondary care. Combined calcipotriol monohydrate and betamethasone dipropionate preparations are only licensed for use from 18 years of age. They only need to be applied once a day, ideally at bedtime, because of their greasy nature. Patients should be warned that they might cause some initial irritation, but that usually settles and they should expect to see improvement within a month. Skin in the facial and genital areas is very sensitive to corticosteroids and combination Cal/BD should not be used in these areas. 12 A novel formulation of Cal/BD, Enstilar (calcipotriol and betamethasone dipropionate) foam spray, was launched in June 2016 and has been accepted by the Scottish Medicines Consortium for use in NHS Scotland for topical treatment of 3

4 psoriasis vulgaris. 13 The main difference from existing Cal/BD topical preparations for use in adults is that the identical active ingredients are dissolved by the foam propellant and deposited on the plaque in a non-crystalline state, which has been designed, and shown in an animal model, to improve absorption. 14 In the gel and ointment preparations, these ingredients are suspended as crystals. An in vitro study has shown reduced penetration of the constituents of the ointment versus the foam preparation. 15 Early experience with Enstilar has shown significant results and demonstrated visible signs of improvement from week 1 (compared with aerosol foam vehicle: week 1, 8.5 versus 1%; week 2, 26.4 versus 1.9%). 16 Although the psoriasis area severity index (PASI) score is not a tool that is regularly used in primary care, it is an objective composite measure of severity that is used to assess the effectiveness of therapies. It assesses the area of skin involved, degree of redness, and thickness of scale. A study comparing patients randomised to treatment with once-daily Cal/BD aerosol foam, Cal/BD gel, aerosol foam vehicle, or gel vehicle, showed that 50.3% of patients using Cal/BD foam achieved more than a 75% reduction in their disease severity (PASI-75) at just 4 weeks compared with 35.5% of patients using Cal/BD gel. 17 I have only previously seen such an improvement with use of systemic therapies including some of the biologics. Summary When reviewing formularies and implementing guidelines, it can sometimes be hard to justify a treatment that appears to cost more simply because the unit cost of the product is greater. Calcipotriol and betamethasone dipropionate foam spray has been demonstrated to control chronic stable plaque psoriasis quite significantly in over half the patients who use it, 17 and I have seen a dramatic improvement with this treatment in some patients. So, not only does the patient enjoy early marked improvement in their condition, but when the overall costs are taken into consideration, including potentially unnecessary referral to secondary care, it is likely to be a highly cost-effective option. Referral is not only expensive for the CCG, but also may be inconvenient and costly for the patient who has to wait for an appointment and may have to take time off work. In my opinion, Enstilar should therefore have a role as first-line therapy for chronic stable plaque psoriasis (along with emollients) and should be offered to all appropriate patients. Patients with psoriasis should be directed to the outstanding patient support group at The Psoriasis Association ( or by post to The Psoriasis Association, 2 Queensbridge, Northampton NN4 7BF. Tel: ). Using Enstilar Enstilar should be administered by shaking the can vigorously before use and spraying onto the skin from a distance of at least 3 cm. A two-second spray delivers approximately 0.5 g. As a guide, 0.5 g of foam should cover an area of skin roughly corresponding to the surface area of an adult hand. 12 The daily maximum dose should not exceed 15 g. 12 Patients should be warned that, like most sprays, the propellant is inflammable. It should be applied once daily and the patient reviewed at 4 weeks. 12 Review Patients with chronic stable plaque psoriasis, especially those on regular treatment, should be reviewed at least annually. 8 This is an opportunity to ensure they are using their topical treatments optimally, avoiding detergents, and, if necessary, have an in-date NHS prepayment certificate for their prescriptions. The DLQI is a really useful way to monitor the effect the psoriasis is having on their everyday life and can help to disclose early warnings of depression. Any hint of PsA would need prompt referral to a rheumatologist (it is especially important to be vigilant for this within the first 10 years of onset of psoriasis 6 ). The cardiovascular QRISK (qrisk.org/2016/) should be measured and appropriate lifestyle changes discussed (this is particularly important in patients with PsA 3 ). The relatively small number of patients with severe disease that is not controlled by these measures need referral to secondary care for consideration of second-line options. 4 Conflicts of interest The author has acted as a consultant or speaker for LEO Pharma. References 1. Parisi R, Symmons D, Griffiths C, Ashcroft D, on behalf of the Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol 2013; 133 (2): Gelfand J, Weinstein R, Porter S et al. Prevalence and treatment of psoriasis in the United Kingdom: a population-based study. Arch Dermatol 2005; 141: Eder L, Gladman D. Atherosclerosis in psoriatic disease: latest evidence and clinical implications. Ther Adv Musculoskel Dis 2015; 7 (5): Haroon M, Gallagher P, FitzGerald O. Diagnostic delay of more than 6 months contributes to poor radiographic and functional outcome in psoriatic arthritis. Ann Rheum Dis 2013; 10: SIGN. Diagnosis and management of psoriasis and psoriatic arthritis in adults. SIGN 121. SIGN, Available at: sign.ac.uk/guidelines/fulltext/ NICE. Psoriasis. Evidence Update 68. NICE Available at: guidance/cg153/evidence 7. NICE. Atopic eczema in under 12s: diagnosis and management. Clinical Guideline 57. NICE Available at: nice.org.uk/guidance/cg57 8. NICE. Psoriasis: assessment and management. Clinical Guideline 153. NICE Available at: 9. Primary Care Dermatology Society. Psoriasis: an overview and chronic plaque psoriasis. Available at: [Accessed December 2016.] 10. Bewley A, Page B. Maximizing patient adherence for optimal outcomes in psoriasis. J Eur Acad Dermatol Venereol 2011; 25 (Suppl 4): McFadden J, Baker B, Powles A, Fry L. Psoriasis and extra domain A fibronectin loops. Br J Dermatol 2010; 163 (1): LEO Pharma UK. Enstilar summary of product characteristics. April, Available at: Scottish Medicines Consortium. calcipotriol 50 micrograms/g and betamethasone 0.5mg/g cutaneous foam (Enstilar ). SMC No. (1182/16). SMC Available at: Advice/1182_16_calcipotriol_betamethasone_Enstilar 14. Lind M, Troensegaard Nielsen K, Hollesen Schefe L et al. Supersaturation of calcipotriene and betamethasone dipropionate in a novel aerosol formulation for topical treatment of psoriasis provides enhanced bioavailability of the active ingredients. Dermatol Ther (Heidelb) 2016; 6: Koo J, Tyring S, Werschler W et al. Superior efficacy of calcipotriene and betamethasone dipropionate aerosol foam versus ointment in patients with psoriasis vulgaris a randomized phase II study. J Dermatolog Treat 2016; 27 (2): Leonardi C, Bagel J, Yamauchi P 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): King C, Lowson D. Superior efficacy of the fixed combination calcipotriol plus betamethasone dipropionate aerosol foam versus gel, in a subset of patients with mild to moderate psoriasis vulgaris: a sub-analysis of the Phase III PSO-ABLE study. P237, 5th Psoriasis International Network Annual Meeting 5 7 July 2016, Paris.

5 Development of a local guideline for the management of psoriasis in primary care Dr Helen Young, Senior Lecturer and Honorary Consultant in Dermatology, The University of Manchester, Manchester Academic Health Science Centre; Department of Dermatology, Salford Royal Hospital (Hope) Introduction Significant psychological and social consequences of having psoriasis have been identified, and the very high levels of distress in patients with psoriasis are reflected in the numbers of deaths by suicide associated with the disease. 1,2 More recently there has been a paradigm shift in understanding psoriasis as an immune-mediated systemic disease that can occur concurrently with inflammatory diseases, such as psoriatic arthropathy and inflammatory bowel disease, as well as in association with cardiovascular disease and features of the metabolic syndrome. 3,4 The risk of all-cause mortality for patients with psoriasis is elevated compared with people unaffected by the disease. 5 However, as understanding of the pathogenesis of psoriasis has advanced over the past two decades, there has been clearer appreciation of the genetic, cellular, and immunological components of disease expression, which has provided new insight into potential therapeutic targets, including the development of new topical, systemic, and biologic therapies. Patient perceptions and adherence The majority of patients with plaque psoriasis can be managed with topical therapies. 6 However, patients with psoriasis perceive healthcare practitioners as lacking expertise in managing psoriasis and as failing to refer appropriately to specialist care. 7 This means that as a consequence of significant dissatisfaction with NHS services, patients disengage from care, often to the detriment of their own physical and social health. 1,7 Stress is a significant trigger that can exacerbate psoriasis, 3 and it is well understood that psoriasis is a burden for patients. 8 Patients with psoriasis hide their disease from others and actively avoid public places or social situations due to concern about being stigmatised on the basis of their skin condition. 8,9 Use of topical therapies appears to compound these avoidant coping strategies, as a result of the associated smell and staining of clothes. 9 Patients also describe the collection of repeat topical prescriptions and high frequency application of therapy as time-consuming and requiring significant effort. 9 These challenges result in unresolved emotional distress, limited perceived control, and high levels of uncertainty, and they impact significantly on adherence with prescribed medication. 9 Medication adherence is defined as the extent to which the patients behaviour matches agreed recommendations from the prescriber, 10 and it is a major barrier to optimising the efficacy of available therapies, with individuals typically using only half of their prescribed medication. 11 Patients with psoriasis express widespread medication dissatisfaction and experience most adherence difficulties with topical therapies. However, a perceived lack of support from primary care further undermines optimal medication use. 9 Development of the Manchester psoriasis guideline Over a decade ago, an evidence-based clinical guideline for the management of psoriasis in primary care 12 was developed by Professor Chris Griffiths and his dermatology colleagues at the University of Manchester. At that time: 12 most guidelines on the management of psoriasis were aimed primarily at dermatologists and were not suitable for direct translation into primary care local hospital data demonstrated that a substantial proportion of patients with psoriasis could be treated effectively within primary care there was marked variation in the frequency of referrals between practices 5

6 a survey of local GPs suggested that most would prefer to manage psoriasis within primary care, but that few had received adequate training. Therefore the main drivers in developing the guideline were twofold: first, to enhance the management of psoriasis in the primary care setting and, second, to increase the appropriateness of referral to secondary care. 12 The Manchester guideline was produced as a laminated A4 handout with a treatment algorithm on one side and photographic guidance on the diagnosis of psoriasis on the reverse. 12 It was refined after discussion with local GPs, and the quality was assessed using an appraisal tool. 12 In order to facilitate implementation of the guideline, a series of supplementary, outreach, practice-based education and training sessions were offered. 12 A randomised controlled trial was performed to examine whether this initiative resulted in a change in clinical behaviour. 12 The guidelines were welcomed by local GPs and subsequent revised/updated versions have been warmly received. The final study group involved 531 GPs in 225 general practices. 12 This study was the first trial of the effectiveness of a guideline for the management of psoriasis in primary care. The study outcomes were presented locally and nationally and published in the British Journal of Dermatology. 12 Notably, the introduction of the Manchester guideline improved the appropriateness of referral of patients to secondary care, and, importantly, the overall referral rates were not significantly increased. There was a statistically significant difference of 19% in the proportion of patients who were considered to be appropriately referred in the guideline group. 12 The observed decrease in the proportion of inappropriate referrals and the corresponding increase in the proportion of appropriate referrals was considered indicative of an improvement in the management of psoriasis in primary care. 12 Updated guidance on treatment Over the past 10 years the guideline has been updated and revised to reflect the changing landscape of topical therapies for the management of psoriasis. The current version of the guideline is being updated following the launch of an aerosol foam formulation of the fixed calcipotriol and betamethasone (Cal/BD) combination (Enstilar ). Topical formulations of the fixed combination of calcipotriol 50 µg/g (Cal) and betamethasone 0.5 mg/g as dipropionate (BD) are effective first-line treatments for psoriasis. 6 The foam formulation of the fixed Cal/BD combination, developed to improve psoriasis treatment and to offer patients a convenient and easy-to-use topical treatment option, 13 has demonstrated significantly greater efficacy over 4 weeks of treatment than 4 weeks of treatment with Cal/BD ointment, 14 and 8 weeks of treatment with Cal/BD gel, with a comparable tolerability profile. 15 Key points Psoriasis is a complex, long-term condition The majority of patients with psoriasis can be managed in primary care with topical therapy 6 Management outcomes can be enhanced by evidencebased guidelines supplemented by education and training 12 Medication adherence is challenging for patients, especially for those who use topical treatments 9 Novel treatments for psoriasis enhance patient and clinician choice The fixed Cal/BD combination aerosol foam is effective and generally well tolerated by patients with psoriasis. 17 Cal/BD=combined calcipotriol monohydrate and betamethasone dipropionate Patient adherence with topical therapies is greater with once daily than twice-daily treatment. 16 It is also affected by patient perception of effectiveness, the cosmetic properties of the product, and how long it takes to apply. 9 Although further research is required, patient preference data suggest that the fixed Cal/BD combination aerosol foam may address some of these barriers to medication adherence. 17 Summary The healthcare needs of patients with plaque psoriasis are significant and complex. Due to the current downward pressure on referrals to specialist services there is increasing need for effective management of patients with psoriasis in primary care. Evidence based guidelines can facilitate both access to appropriate treatment and the triage of patients to secondary care services. The addition of the fixed Cal/BD combination aerosol foam to the treatment armamentarium increases patient and clinician choice and may improve adherence to topical therapy, which remains a significant issue for patients. Conflicts of interest The author has acted as a consultant or speaker for LEO Pharma and several other pharmaceutical companies. References 1. Cordingley L, Nelson P, Griffiths C, Chew-Graham C; on behalf of the IMPACT (Identification and Management of Psoriasis Associated Comorbidity) programme research team. Beyond skin: the need for a new approach to the management of psoriasis in primary care. Br J Gen Pract 2012; 62 (604): Kurd S, Troxel A, Crits-Cristoph P, Gelfand J. The risk of depression, anxiety and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol 2010; 146 (8): Griffiths C, Barker J. Pathogenesis and clinical features of psoriasis. Lancet 2007; 370: Parisi R, Rutter M, Lunt M et al; on behalf of the Identification and Management of Psoriasis Associated ComorbidiTy (IMPACT) project team. Psoriasis and the risk of major cardiovascular events: cohort study using the clinical practice research datalink. J Invest Dermatol 2015; 135: Springate D, Parisi R, Kontopantelis E et al. Incidence, prevalence and mortality of patients with psoriasis: a U.K. population-based cohort study. Br J Dermatol 2016; [Epub] DOI /bjd Laws P, Young H. Topical treatment of psoriasis. Expert Opin Pharmacother 2010; 11 (12):

7 7. Nelson P, Chew-Graham C, Griffiths C, Cordingley L; on behalf of the IMPACT team. Recognition of need in health care consultations: a qualitative study of people with psoriasis. Br J Dermatol 2013; 168 (2): Fortune D, Main C, O Sullivan T, Griffiths C. Assessing illness-related stress in psoriasis: the psychometric properties of the Psoriasis Life Stress Inventory. J Psychosom Res 1997; 42 (5): Thorneloe R, Bundy C, Griffiths C et al. Non-adherence to psoriasis medication as an outcome of limited coping resources and conflicting goals: findings from a qualitative interview study with people with psoriasis. Br J Dermatol 2016; [Epub] DOI /bjd Horne R, Weinman J, Elliott R, Morgan M. Concordance, adherence and compliance in medicine taking Report for the National Co-ordinating Centre for NHS Service Delivery and Organisation R & D (NCCSDO). 2005, NCCSDO. Available to download at: data/assets/ pdf_file/0007/81394/es pdf 11. Nieuwlaat R, Wilczynski N, Navarro T et al. Interventions for enhancing medication adherence. Cochrane Database Syst Rev 2014; 11. DOI: / CD pub Griffiths C, Taylor H, Collins S et al. The impact of psoriasis guidelines on appropriateness of referral from primary to secondary care: a randomized controlled trial. Br J Dermatol 2006; 155 (2): Koo J, Tyring S, Werschler W et al. Superior efficacy of calcipotriene and betamethasone dipropionate aerosol foam versus ointment in patients with psoriasis vulgaris a randomized phase II study. J Dermatolog Treat 2016; 27 (2): Queille-Roussel C, Olesen M, Villumsen J, Lacour J-P. Efficacy of an innovative aerosol foam formulation of fixed combination calcipotriol plus betamethasone dipropionate in patients with psoriasis vulgaris. Clin Drug Investig 2015; 35: King C, Lowson D. Superior efficacy of the fixed combination calcipotriol plus betamethasone dipropionate aerosol foam versus gel, in a subset of patients with mild to moderate psoriasis vulgaris: a sub-analysis of the Phase III PSO-ABLE study. P237, 5th Psoriasis International Network Annual Meeting 5 7 July 2016, Paris. 16. Zaghloul S, Goodfield M. Objective assessment of compliance with psoriasis treatment. Arch Dermatol 2004; 140: Paul C, Stein Gold L, Cambazard F et al. Calcipotriol plus betamethasone dipropionate aerosol foam provides superior efficacy vs. gel in patients with psoriasis vulgaris: randomized, controlled PSO-ABLE study. JEADV 2016; DOI: /jdv

8 Abbreviated Prescribing Information for Enstilar 50 micrograms/g mg/g cutaneous foam Please refer to the full Summary of Product Characteristics (SmPC) ( before prescribing. Indication: Topical treatment of psoriasis vulgaris in adults. Active ingredients: 50 µg/g calcipotriol (as monohydrate) and 0.5 mg/g betamethasone (as dipropionate). Dosage and administration: Apply by spraying onto affected area once daily. Recommended treatment period is 4 weeks. The daily maximum dose of Enstilar should not exceed 15 g, i.e. one 60 g can should last for at least 4 days. 15 g corresponds to the amount administered from the can if the actuator is fully depressed for approximately one minute. A twosecond application delivers approximately 0.5 g. As a guide, 0.5 g of foam should cover an area of skin roughly corresponding to the surface area of an adult hand. If using other calcipotriol-containing medical products in addition to Enstilar, the total dose of all calcipotriol-containing products should not exceed 15 g per day. Total body surface area treated should not exceed 30%. Safety and efficacy in patients with severe renal insufficiency or severe hepatic disorders have not been evaluated. Safety and efficacy in children below 18 years have not been established. Shake the can for a few seconds before use. Apply by spraying, holding the can at least 3 cm from the skin, in any orientation except horizontally. Spray directly onto each affected skin area and rub in gently. Wash hands after use (unless Enstilar is used to treat the hands) to avoid accidentally spreading to other parts of the body. Avoid application under occlusive dressings since systemic absorption of corticosteroids increases. It is recommended not to take a shower or bath immediately after application. Contraindications: Hypersensitivity to the active substances or any of the excipients. Erythrodermic and pustular psoriasis. Patients with known disorders of calcium metabolism. Viral (e.g. herpes or varicella) skin lesions, fungal or bacterial skin infections, parasitic infections, skin manifestations in relation to tuberculosis, perioral dermatitis, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers and wounds. Precautions and warnings: Adverse reactions found in connection with systemic corticosteroid treatment, e.g. adrenocortical suppression or impaired glycaemic control of diabetes mellitus, may occur also during topical corticosteroid treatment due to systemic absorption. Application under occlusive dressings should be avoided since it increases the systemic absorption of corticosteroids. Application on large areas of damaged skin, or on mucous membranes or in skin folds should be avoided since it increases the systemic absorption of corticosteroids. Due to the content of calcipotriol, hypercalcaemia may occur. Serum calcium is normalised when treatment is discontinued. The risk of hypercalcaemia is minimal when the maximum daily dose of Enstilar (15 g) is not exceeded. Enstilar contains a potent group III-steroid and concurrent treatment with other steroids on the same treatment area must be avoided. Skin on the face and genitals are very sensitive to corticosteroids. Enstilar should not be used in these areas. Instruct the patient in the correct use of the product to avoid application and accidental transfer to the face, mouth and eyes. Wash hands after each application to avoid accidental transfer to these areas. When lesions become secondarily infected, they should be treated with antimicrobiological therapy. However, if infection worsens, treatment with corticosteroids should be discontinued. When treating psoriasis with topical corticosteroids, there may be a risk of rebound effects when discontinuing treatment. Medical supervision should therefore continue in the post-treatment period. Long-term use of corticosteroids may increase the risk of local and systemic adverse reactions. Treatment should be discontinued in case of adverse reactions related to long-term use of corticosteroid. There is no experience with the use of Enstilar in guttate psoriasis. During Enstilar treatment, physicians are recommended to advise patients to limit or avoid excessive exposure to either natural or artificial sunlight. Topical calcipotriol should be used with UVR only if the physician and patient consider that the potential benefits outweigh the potential risks. Enstilar contains butylhydroxytoluene (E321), which may cause local skin reactions (e.g. contact dermatitis), or irritation to the eyes and mucous membranes. Pregnancy and lactation: There are no adequate data from the use of Enstilar in pregnant women. Enstilar should only be used during pregnancy when the potential benefit justifies the potential risk. Caution should be exercised when prescribing Enstilar to women who breast-feed. The patient should be instructed not to use Enstilar on the breast when breast-feeding. Side effects: There are no common adverse reactions based on the clinical studies. The most frequently reported adverse reactions are application site reactions. Calcipotriol: Adverse reactions include application site reactions, pruritus, skin irritation, burning and stinging sensation, dry skin, erythema, rash, dermatitis, psoriasis aggravated, photosensitivity and hypersensitivity reactions, including very rare cases of angioedema and facial oedema. Systemic effects after topical use may appear very rarely causing hypercalcaemia or hypercalciuria. Betamethasone (as dipropionate): Local reactions can occur after topical use, especially during prolonged application, including skin atrophy, telangiectasia, striae, folliculitis, hypertrichosis, perioral dermatitis, allergic contact dermatitis, depigmentation and colloid milia. When treating psoriasis with topical corticosteroids, there may be a risk of generalised pustular psoriasis. Systemic reactions due to topical use of corticosteroids are rare in adults; however, they can be severe. Adrenocortical suppression, cataract, infections, impaired glycaemic control of diabetes mellitus, and increase of intra-ocular pressure can occur, especially after long-term treatment. Systemic reactions occur more frequently when applied under occlusion (plastic, skin folds), when applied on large areas, and during long-term treatment. See SmPC for a full list of side effects. Precautions for storage: Do not store above 30 C. Extremely flammable aerosol. Pressurised container. May burst if heated. Protect from sunlight. Do not expose to temperatures exceeding 50 C. Do not pierce or burn, even after use. Do not spray on an open flame or other ignition source. Keep away from sparks/open flames. No smoking. Legal category: POM. Marketing authorisation number and holder: PL 05293/0008. LEO Pharma A/S, Ballerup, Denmark. Basic NHS price: 39.68/60 g Last revised: May 2016 Further information can be found in the Summary of Product Characteristics or from: LEO Pharma, Horizon, Honey Lane, Hurley, Berkshire SL6 6RJ, UK. medical-info.uk@leo-pharma.com Reporting of Suspected Adverse Reactions Adverse events should be reported. Reporting forms and information can be found at: Adverse events should also be reported to Drug Safety at LEO Pharma by calling +44 (0) or medical-info.uk@leo-pharma.com Registered trademark LEO