New Medicine Report. Pimecrolimus. RED- Hospital only Date of Last Revision 6 th March 2003

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1 New Medicine Report Document Status Pimecrolimus Reviewed by Suffolk D&T RED- Hospital only Date of Last Revision 6 th March 2003 Approved Name Pimecrolimus Trade Name Elidel Manufacturer Novartis Legal Status POM Indication Mild to moderate atopic dermatitis (eczema) in patients aged 2 yrs and over for 1) short term treatment of signs and symptoms and 2) intermittent longterm treatment for prevention of progression to flares Dosage Apply to the affected area twice daily Cost Pimecrolimus 1% cream 30g g tubes of pimecrolimus are also available and 100g tubes will be available later in the year Possible Number of Suffolk 30,000 to 40,000 patients in Suffolk Patients have atopic dermatitis Number Needed to Treat Treatment Alternatives Future Alternatives Possible Future Indications Not calculated Emollients, bath oils & soap substitutes to combat dry skin, topical corticosteroids, oral antihistamines, systemic corticosteroids, ciclosporin tacrolimus Hydrocortisone 1% cream 0.72 Clobetasone 0.05% cream 1.94 Betamethasone 0.1% cream 1.54 Clobetasol 0.05% cream 2.82 Tacrolimus 0.03% Tacrolimus 0.1% (All 30g size taken from BNF 44 th Ed & MIMS Jan 2003) Not known Not known This is an NHS Suffolk document that has been adopted by the WSCCG

2 Reviewer s Comments The prospect of a non-steroidal treatment for atopic dermatitis is welcome. However little evidence has been provided to ensure that this product is both safe and efficacious in the longer term. Whilst there is probably a place for its use in Suffolk it is felt that it should not be seen as first line treatment until further evidence is available. Thus the first instance it may be wise to limit its use to those with severe disease until the safety profile is more established. The product is more costly than current treatments, however its use may be justified in the longer term if the safety profile is found to be good as it is well known that the use of corticosteroids is not without problem. The D&TC should be aware that in January 2002 it classified tacrolimus ointment as RED consultant prescription only. Evidence Reviewed Paper, Review, Abstract etc. Smith K Cambridgeshire Joint Prescribing Group Submission Pimecrolimus Molecule of the month January 2002 Pimecrolimus Pimecrolimus Cream MTRAC Review and Summary Sheet Published MTRAC Nov 2002 Medlineplus Pimecrolimus Elidel Information for USA patients Published Novartis Level of evidence Level of evidence adapted from Quick and Clean : authorative health technology assessment for local health care contracting Andrew Stevens, Duncan Collin-Jones & John Gabbay Health Trends Vol 27 No IV Page 2 of 5 May be freely copied by NHS agencies

3 Review Atopic dermatitis is a chronic inflammatory disease with a lifetime prevalence of 15-20%. It affects all age groups, however prevalence is highest amongst children with 15-20% affected. 80% of patients will present by the age of 5. Tacrolimus ointment was the first topical macrolide immunomodulator for the treatment atopic dermatitis. It is indicated for moderate to severe atopic dermatitis unresponsive to conventional therapy in children over the age of 2 years and adults. Pimecrolimus is the second topical macrolide immunomodulator to be licensed for the treatment of atopic dermatitis. It is indicated for a use in a different patient population to tacrolimus ointment. Pimecrolimus 1% cream can be used on all skin areas including the head, face, neck and intertriginous areas. The therapeutic efficacy of pimecrolimus 1% cream in the management of atopic dermatitis has been evaluated in 2,260 patients aged 2 years and above, in 7 randomised, double blind, vehicle controlled trials - 4 in adults and 3 in children (aged 2-17). Four trials evaluated short-term acute treatment - 2 studies in children over 6 weeks and 2 studies in adults over 3 weeks. In these studies, pimecrolimus 1% cream applied twice daily for up to 6 weeks, significantly reduced the signs and symptoms of atopic dermatitis compared to vehicle. In one dose ranging trial in adults with moderate to severe disease, pimecrolimus 1% cream was less effective than betamethasone valerate 0.1% cream. In the two adults trials, emollients were not allowed to be used during the study period. Three trials have evaluated long-term intermittent use - 1 in children and 2 in adults. Treatment with pimecrolimus 1% cream applied twice daily at the first signs or symptoms of atopic dermatitis, for up to one year, to prevent progression to flare reduced the incidence of disease flare. Conventional therapy was used in the event of a flare. In the adult trial this was emollients and a high potency corticosteroid % prednicarbate. In the children trial it was emollients and a moderately potent or potent corticosteroid - clobetasone 0.05% or hydrocortisone butyrate 0.1% respectively. Those treated with pimecrolimus had reduced topical corticosteroid use compared to vehicle and had a longer mean time to first flare. In the trial conducted in the children, 51.5% using the vehicle alone discontinued therapy compared to 31.6% of those using pimecrolimus. In the adult trial the respective figures were 37.5% and 22.9%. Page 3 of 5 May be freely copied by NHS agencies

4 The unpublished data from a 1-year study in adult patients with moderate to severe disease shows that pimecrolimus 1% cream was less effective in controlling symtoms than potent topical corticosteroid treatment (triamcinolone acetonide 0.1% and hydrocortisone acetate 1%). The long-term effect of pimecrolimus 1% cream on the local skin immune response and on the incidence of skin malignancies is not known. If no improvement occurs after 6 weeks of treatment, or if disease exacerbation occurs, pimecrolimus 1% cream should be discontinued. The Summary of Product Characteristics (SPC) states that it is recommended that pimecrolimus cream should be prescribed by physicians with experience in the topical treatment of atopic dermatitis. Adverse Effects etc. For full information it is important to read the SoPC. The most common adverse events reported in clinical trials were application site reactions - burning, irritation, pruritus & erythema. These generally occurred early in treatment, were mild/moderate and were of short duration. It should not be used on areas affected by acute cutaneous viral infections (e.g. chicken pox, herpes simplex) or clinically infected atopic dermatitis. There may be an increased risk of skin bacterial infections (e.g. impetigo) during treatment. It is suggested that vaccination should take place during a treatment free period. Avoid contact with the eyes & mucous membranes. It should not be used under occlusion. Patients should avoid excessive exposure of the skin to UV light. It should not be used concomitantly with other topical corticosteroids or topical anti-inflammatory products. It should not be used in pregnancy. Breast-feeding mothers may use it, although they must not apply it directly to the breast. Whilst the SoPC in the UK warns against excessive exposure to UV light including the use of a solarium the patient information leaflet in the USA is much more restrictive stating: Avoid sunlight and sun lamps, tanning beds, and treatment with UVA or UVB light. If you need to be outdoors after applying ELIDEL, wear loose fitting clothing that protects the treated area from the sun. Ask your doctor what other type of protection from the sun you should use. Page 4 of 5 May be freely copied by NHS agencies

5 The Medlineplus patient information suggests that patients should stay out of direct sunlight if possible between and They suggest that sunblock and lipsick of at least SPF15 should be worn. Health Economics The prevalence of atopic dermatitis has increased over the past 30 years and now affects 5% of the UK population. Estimates suggest that 15-20% of children aged 7 to 18 years are affected with 2-10% of adults. Most affected individuals develop atopic dermatitis before the age of 5 years. Unfortunately the age breakdown available does not match this but the following table can be constructed: Table 1 to show the various estimates of the prevalence of atopic dermatitis PCT 18% of 0 to 14 years of age 5% of aged 15 years and over Total of Columns 2 & 3 5% of total population Central Ipswich Suffolk Coastal Suffolk West Waveney Total for Suffolk Total for East Commissioning There is a certain discrepancy between the two methods of calculating the prevalence but it can be seen that between 30,000 and 40,000 patients are affected by atopic dermatitis. Not all of these will need treatment with pimecrolimus. Page 5 of 5 May be freely copied by NHS agencies