Drugs for acne, rosacea and psoriasis

Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Drugs for Acne, Rosacea and Psoriasis p Important Copyright Message The Medical Letter® publications are protected by US and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with US and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 FORWARDING OR COPYING IS A VIOLATION OF US AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 11 (Issue 125) January 2013 www.medicalletter.org Take CME exams Tables Some Topical Antibiotics for Acne Some Oral Antibiotics for Acne Some Retinoids for Acne Some Topical Corticosteroids Some Systemic Drugs for Psoriasis Page Page Page Page Page Drugs for Acne, Rosacea and Psoriasis Related article(s) since publication ACNE The pathogenesis of acne is multifactorial: follicular hyperkeratinization, bacteria, sebum production, androgens, and inflammation all play a role The grampositive microaerophilic bacteria Propionibacterium acnes promote development of acne lesions by secreting chemotactic factors that attract leukocytes to the follicle, causing inflammation TOPICAL THERAPY — Salicylic Acid – Widely available OTC, topical salicylic acid is a well-tolerated keratolytic agent that can be used alone or in combination with other agents, such as benzoyl peroxide Benzoyl Peroxide – The oxidizing agent benzoyl peroxide is available in a wide variety of OTC and prescription preparations Its effect is primarily due to its antibacterial activity against P acnes Benzoyl peroxide is most useful for treatment of mild to moderate acne It is often used in combination with topical or oral antibiotics, or with a retinoid such as adapalene.1 Skin irritation and bleaching (skin or fabric) can occur and may be intolerable for some patients Contact dermatitis can also occur Antibiotics – The topical antibacterial drugs clindamycin and erythromycin are commonly used to treat mild to moderate acne Both have antibacterial and anti-inflammatory properties Products containing sulfur and/or sulfacetamide are sometimes used, but clinical data supporting their efficacy are limited Topical antibiotics are generally safe and well tolerated, but bacterial resistance has occurred, especially to erythromycin Concomitant use of topical antibiotics and benzoyl peroxide may be effective against resistant P acnes Skin irritation may occur, but is typically milder than with retinoids.2 Dapsone, an antimicrobial drug used orally to treat leprosy, Pneumocystis pneumonia and toxoplasmosis, Table Some Topical Antibiotics for Acne Drug Some Formulations Usual Dosage Cost/Size1 Clindamycin – generic Cleocin T (Pfizer) generic Evoclin (Stiefel) Clindamycin/benzoyl peroxide generic Benzaclin (Valeant) generic Duac (Stiefel) Acanya (Valeant) Erythromycin – generic Erythromycin/benzoyl peroxide generic Benzamycin (Valeant) Azelaic acid – Azelex (Allergan) 1% gel, soln, lotion, pads Twice daily 1% foam Once daily $38.75/30 63.88/30 143.77/50 190.49/50 g g g g 1%/5% gel Twice daily 1.2%/5% gel Once daily in the evening 1.2%/2.5% gel 2% gel, soln, pads Once daily Twice daily 107.62/25 187.70/25 166.05/45 188.37/45 258.29/50 12.52/30 g g g g g g 3%/5% gel Twice daily Dapsone – Aczone (Allergan) 20% cream Twice daily 89.74/46.6 g 282.38/46.6 g 199.91/30 g 5% gel Twice daily 172.50/30 g Wholesale acquisition cost (WAC) of the listed size tube, bottle or jar When multiple formulations are listed, the cost of the gel is provided Source: PricePointRx™ December 7, 2012 Reprinted with permission by FDB All rights reserved ©2012 http://www.firstdatabank.com/support/drugpricing-policy.aspx Actual retail prices may be higher Federal copyright law prohibits unauthorized reproduction by any means and imposes severe fines Drugs for Acne, Rosacea and Psoriasis Table Some Oral Antibiotics for Acne Drug Usual Dosage Some Adverse Effects Cost1 Doxycycline – generic Vibramycin extended-release – generic Doryx Minocycline – generic Minocin extended-release – generic Solodyn Erythromycin6 – generic Trimethoprim/sulfamethoxazole – generic Bactrim6 20-100 mg bid Photosensitivity, GI upset, vaginal candidiasis $4.002,3 120.003 422.40 525.00 17.60 307.80 277.025 705.305 153.60 4.002 155.40 150 mg once daily 50-100 mg bid Vertigo, skin discoloration, GI upset, vaginal candidiasis mg/kg once daily4 500 mg bid 160/800 mg bid GI upset, drug interactions Bone marrow suppression, rash Wholesale acquisition cost (WAC) of 30 days’ treatment with the lowest dosage Source: PricePointRx™ December 7, 2012 Reprinted with permission by FDB All rights reserved ©2012 http://www.firstdatabank.com/support/drug-pricing-policy.aspx Actual retail prices may be higher Cost of 30 days’ treatment with the generic drug from large discount pharmacies Cost based on a dose of 50 mg twice daily Extended-release minocycline (Solodyn, and generics) is available in 45-, 90- and 135-mg tablets In addition, Solodyn is available in 55-, 65-, 80-, 105-, and 115-mg tablets Cost of 30 days’ treatment at 90 mg/day Not FDA-approved for acne is FDA-approved in a 5% gel formulation (Aczone) for treatment of acne Application of both dapsone and benzoyl peroxide at the same time can cause temporary yellow or orange discoloration of the skin and facial hair Azelaic Acid – An anti-keratinizing agent with antibacterial and anti-inflammatory activity, azelaic acid (Azelex for acne; Finacea for rosacea) is less irritating than benzoyl peroxide Hypopigmentation can occur, particularly in people with dark skin It is classified as category B (no evidence of risk in humans) for use during pregnancy Retinoids – Topical retinoids such as tretinoin, adapalene and tazarotene can be used to treat both inflamed and noninflamed acne lesions, alone or in combination with antibiotics, or for maintenance treatment Many dermatologists now use them as first-line treatment All topical retinoids normalize keratinization and appear to have anti-inflammatory effects It is not clear that any one of these agents is more effective than any other Retinoid/antimicrobial combinations are more effective than either component alone,1,3 but simultaneous application of tretinoin and benzoyl peroxide can cause oxidation of tretinoin and loss of its effectiveness Adverse effects typically associated with topical retinoids, including dry skin, scaling, photoirritation, erythema, burning and pruritus, vary with the formulation, concentration and frequency of application Tazarotene gel may be more irritating than adapalene Retinoids are teratogens; even though only small amounts are absorbed systemically, tretinoin and adapalene are classified as category C (risk cannot be ruled out) for use during pregnancy Tazarotene is classified as category X and is contraindicated during pregnancy SYSTEMIC THERAPY — Oral Antibiotics – Tetracyclines, such as doxycycline and minocycline, and erythromycin are generally prescribed for moderate to severe inflammatory acne unresponsive to topical drugs They are usually taken for months, which can lead to development of bacterial resistance Trimethoprim/sulfamethoxazole can be used in patients who not tolerate or respond to other oral antibiotics Tetracyclines, in addition to their antibacterial activity, may have anti-inflammatory effects An extendedrelease formulation of minocycline is available for once-daily treatment of acne; whether it is less likely than standard minocycline to cause vertigo remains to be established.4,5 Drug-induced lupus has occurred with long-term use of minocycline for treatment of acne Tetracyclines should not be used during pregnancy Isotretinoin – The oral retinoid isotretinoin is the most effective drug available for treatment of severe nodulocystic acne It inhibits P acnes colonization by reducing sebum production and has keratinolytic and antiinflammatory effects Isotretinoin can completely clear severe nodulocystic lesions, in many cases leading to remission that can persist for years after treatment is stopped A new isotretinoin product (Absorica) has recently been approved in the US; unlike other formulations, which are taken with a meal, Absorica can be taken with or without food.6 Mucocutaneous adverse effects of isotretinoin include cheilitis, epistaxis, dry skin, alopecia, eczema, skin fragility and photosensitivity Depression, suicidal ideation, myalgia, hypertriglyceridemia, hepatitis, pancreatitis and pseudotumor cerebri can occur Isotretinoin is a potent human teratogen; it is regulated by iPLEDGE, a computer-based risk management program (www.ipledgeprogram.com) designed to prevent fetal exposure to the drug Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 125) • January 2013 Drugs for Acne, Rosacea and Psoriasis Table Some Retinoids for Acne Drug Some Formulations Topical Retinoids Adapalene – generic Differin (Galderma) Tazarotene – Tazorac (Allergan) Tretinoin – generic 0.1%, 0.3% gel, 0.1% cream 0.1%, 0.3% gel, 0.1% cream, 0.1% lotion 0.1% gel, cream 0.01%, 0.025% gel 0.025%, 0.0375%, 0.05%, 0.075%, 0.1% cream Atralin (Valeant) 0.05% gel Avita (Mylan) 0.025% gel, cream Retin-A (Valeant) 0.01%, 0.25% gel 0.025%, 0.05%, 0.1% cream Retin-A Micro (Valeant) 0.04%, 0.1% gel Retinoid/Antimicrobial Combinations Epiduo (Galderma) 0.1% adapalene/2.5% benzoyl peroxide gel Veltin (Stiefel) 0.025% tretinoin/1.2% clindamycin phosphate gel Ziana (Medicis) 0.025% tretinoin gel/1.2% clindamycin phosphate gel Oral Retinoids Isotretinoin Absorica (Ranbaxy) 10, 20, 30, 40 mg caps Amnesteem (Mylan) 10, 20, 40 mg caps Claravis (Barr) 10, 20, 30, 40 mg caps Myorisan (VersaPharma) 10, 20, 40 mg caps Sotret (Ranbaxy) 10, 20, 30, 40 mg caps Usual Dosage Cost/Size1 Once daily at bedtime $158.00/45 328.15/45 224.15/30 73.03/45 53.45/45 g g g g g Once daily in the evening 253.58/45 171.72/45 213.52/45 215.65/45 369.11/35 g g g g g Once daily Once daily in the evening 242.10/45 g 159.84/30 g Once daily at bedtime 229.86/30 g Once daily in the evening Once daily at bedtime Once daily at bedtime Once daily in the evening Once daily at bedtime 0.5-1 mg/kg/d in divided doses for 15-20 wks 1416.822 551.262 710.702 550.502 600.482 Wholesale acquisition cost (WAC) of one tube or bottle of the listed size in the lowest available strength When multiple formulations are listed, the cost of the gel is provided Source: PricePointRx™ December 7, 2012 Reprinted with permission by FDB All rights reserved ©2012 http://www.firstdatabank.com/ support/drug-pricing-policy.aspx Actual retail prices may be higher Cost of 30 days’ treatment at 60 mg/day Oral Contraceptives – Acne in women is often treated with oral contraceptives Estrogen decreases formation of ovarian and adrenal androgens and suppresses sebum secretion.7,8 topical drugs The most effective drug available for inflammatory acne is isotretinoin; it can clear severe recalcitrant nodular acne, but has many adverse effects ROSACEA Spironolactone (Aldactone, and generics) – The antiandrogen aldosterone receptor antagonist spironolactone is used off-label to treat acne in women It has been useful in some patients with resistant disease.9 Hyperkalemia and menstrual irregularity can occur It is classified as category C (risk cannot be ruled out) for use during pregnancy PHOTOTHERAPY — Blue light, infrared lasers, photodynamic therapy and other light-based therapies may be effective for short-term treatment of acne, but their long-term efficacy and how they compare with conventional drugs are unclear.10 CHOICE OF DRUGS — Topical salicylic acid and benzoyl peroxide, both available OTC, may be used first for treatment of acne For mild to moderate acne, benzoyl peroxide is often combined with a topical antibiotic A topical retinoid is now often used first-line to treat all patients with acne Combinations of retinoids with topical antibiotics are more effective than either component alone, particularly for patients with pustular lesions Oral antibiotics are generally prescribed for moderate to severe acne unresponsive to This common, chronic inflammatory facial eruption of unknown cause is characterized by erythema, telangiectasia and recurrent, progressive crops of acneiform papules and pustules, usually on the central part of the face Some patients develop cystic nodules, granulomas and tissue hypertrophy, which may lead to rhinophyma (a bulbous nose) Blepharitis and conjunctivitis are common Keratitis and corneal scarring occur rarely Rosacea is more prevalent in women, but rhinophyma occurs more frequently in men TOPICAL THERAPY — It may take 4-6 weeks of treatment with topical drugs for improvement to become visible Metronidazole (Metrogel, and generics) and azelaic acid (Finacea for rosacea; Azelex for acne) are the standard topical antimicrobials used to treat the papules and pustules of rosacea; they appear to be about equally effective, but few well-controlled comparative trials have been published Benzoyl peroxide, erythromycin, clindamycin, sulfacetamide/sulfur and 5% permethrin (to treat Demodex mites, which have been implicated in the pathogenesis of rosacea) have been used The topical retinoids used to treat Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 125) • January 2013 Drugs for Acne, Rosacea and Psoriasis acne are also sometimes used to treat rosacea An investigational 0.5% gel formulation of the alpha2agonist brimonidine tartrate, which is available in an ophthalmic formulation for treatment of glaucoma, was effective in a randomized, vehicle-controlled study for treatment of moderate to severe erythema of rosacea.11 SYSTEMIC THERAPY — Oral Antibiotics – Systemic antibiotic therapy tends to be effective for treatment of papules, pustules, erythema and ocular inflammation, but not for telangiectasia, rhinophyma or the flushing that nearly always accompanies rosacea Effective treatment often requires a prolonged course (months or sometimes years) of an oral antibiotic, such as doxycycline The antibiotic dose can often be reduced when papules and pustules improve Low-dose (40 mg) doxycycline (Oracea, and generics) once daily has been shown to be effective and safe for treatment of rosacea, but it is expensive.12 Oral metronidazole (Flagyl, and generics) is also effective for rosacea, but it has some unpleasant side effects, such as metallic taste Isotretinoin – Patients with severely inflamed rosacea, or those whose disease has a marked nodulocystic component, can be treated (off-label) with low doses of isotretinoin (0.1-0.5 mg/kg/day) for 6-8 months; as with acne, careful monitoring is necessary in women of childbearing age (see page 2) Significant reductions in erythema, papules and telangiectasia occur after about months of treatment; no other pharmacologic treatment has been reported to reduce telangiectasia LIGHT-BASED THERAPY — In small clinical trials, light and laser therapies were effective in decreasing the severity of telangiectasia and erythema in patients with rosacea Long-term studies are lacking.13 Adverse effects have included purpura and hyperpigmentation CHOICE OF DRUGS — Topical antimicrobials such as metronidazole and azelaic acid are generally tried first for treatment of rosacea, sometimes in combination with oral antimicrobials, which can produce a more rapid response Topical retinoids are used for patients who not respond to topical antimicrobials Isotretinoin is generally reserved for patients with severe inflammatory nodulocystic disease PSORIASIS This common chronic condition, characterized by erythematous plaques covered by silvery scales, takes many forms, including arthritis.14 TOPICAL THERAPY — Corticosteroids – Topical corticosteroids are the most widely used drugs for treatment of mild to moderate psoriasis They are listed according to potency in Table Ointments are generally the most effective Foams and sprays can be applied to large areas, but the alcohol base found in many of them may cause burning in patients with sensitive skin Super-high-potency topical corticosteroids, such as clobetasol propionate 0.05%, have been shown to induce adrenal suppression when applied to large body surface areas, but clinically significant adrenal insufficiency is rare Local cutaneous adverse effects such as atrophy of the dermis and epidermis, telangiectasia and irreversible striae can occur when these agents are used for prolonged periods of time, when too much is applied, or when corticosteroid-sensitive areas such as the face and intertriginous regions are treated, but usually not when applied to active lesions of psoriasis Calcipotriene – The vitamin D3 analog calcipotriene (Dovonex, and others)15 is about as effective as a medium-potency corticosteroid for topical treatment of plaque psoriasis Calcipotriene inhibits epidermal proliferation and stimulates cellular differentiation It is generally well tolerated, but burning and itching can occur Hypercalcemia has been reported Calcitriol – A second vitamin D3 analog, calcitriol (Vectical)16 is indicated for topical treatment of mild to moderate plaque psoriasis in adults In clinical trials, the drug was modestly effective Skin discomfort, pruritus and erythema can occur, but are generally mild Tazarotene – An acetylenic retinoid, tazarotene (Tazorac) has been effective for treatment of psoriasis, and in some patients the therapeutic effect may persist after the treatment is stopped Erythema, burning, pruritus and peeling can occur with tazarotene gel The cream formulation is better tolerated, but peeling has been more frequent Even though systemic absorption is minimal, the drug is contraindicated during pregnancy Calcipotriene/Betamethasone Dipropionate – This once-daily combination ointment (Taclonex) is more effective than either component alone for treating plaque psoriasis and has been well tolerated.17 A suspension formulation that can be used on the scalp (Taclonex Scalp) contains the same active ingredients and is also applied once daily PHOTOTHERAPY — UVB phototherapy is used when the disease is widespread or unresponsive to top- Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 125) • January 2013 Drugs for Acne, Rosacea and Psoriasis Table Some Topical Corticosteroids Drug Vehicle Cost1 Drug Super-High Potency Betamethasone dipropionate augmented 0.05% oint, gel $75.56 Clobetasol propionate 0.05% generic Clobex (Galderma) Olux (Stiefel) Fluocinonide 0.1% Vanos (Medicis) Halobetasol propionate 0.05% generic Ultravate (Ranbaxy) High Potency Amcinonide 0.1% Betamethasone dipropionate 0.05% augmented Betamethasone dipropionate 0.05% Desoximetasone 0.25% generic Topicort (Taro) cream, oint, gel soln, lotion shampoo foam lotion shampoo spray foam 9.11 22.84 311.08 124.81 338.80 451.75 266.05 223.12 cream 187.36 cream, oint 40.30 137.72 oint cream oint 324.002 51.22 75.30 cream, oint cream, oint 70.40 103.62 Desoximetasone 0.05% gel 122.58 Diflorasone diacetate 0.05% oint 75.84 Fluocinonide 0.05% oint, gel soln cream 16.06 44.26 8.76 Halcinonide 0.1% Halog (Ranbaxy) Mometasone 0.1% cream, oint oint Triamcinolone acetonide 0.5% oint Medium-High Potency Amcinonide 0.1% 100.36 30.52 16.36 cream lotion 110.05 271.44 Betamethasone dipropionate 0.05% cream 62.74 Betamethasone valerate 0.1% oint 30.53 Desoximetasone 0.05% cream 99.88 Diflorasone diacetate 0.05% cream 112.82 Fluocinonide emollient 0.05% cream 7.45 Fluticasone propionate 0.005% generic Cutivate (PharmDerm) oint 22.97 69.40 Triamcinolone acetonide 0.1% oint 9.00 Triamcinolone acetonide 0.5% cream Vehicle Cost1 Medium Potency Betamethasone valerate 0.12% Luxiq (Stiefel) foam 185.89 Fluocinolone acetonide 0.025% oint 56.42 Hydrocortisone valerate 0.2% generic Westcort (Ranbaxy) Mometasone furoate 0.1% oint oint cream 119.38 179.98 32.74 cream 6.30 Triamcinolone acetonide 0.1% Triamcinolone acetonide 0.05% generic Trianex (Upsher-Smith) Medium-Low Potency Betamethasone dipropionate 0.05% Betamethasone valerate 0.1% Desonide 0.05% Fluocinolone acetonide 0.025% Flurandrenolide 0.05% Cordran (Aqua) Cordran SP (Aqua) Fluticasone propionate 0.05% generic Cutivate (PharmaDerm) Hydrocortisone butyrate 0.1% generic Locoid (Onset) Locoid Lipocream Hydrocortisone valerate 0.2% Prednicarbate 0.1% Triamcinolone acetonide 0.025% Triamcinolone acetonide 0.1% Low Potency Alclometasone dipropionate 0.05% Betamethasone valerate 0.1% Clocortolone 0.1% Cloderm (Promius) Desonide 0.05% generic Desonate (Bayer) Verdeso (Stiefel) Fluocinolone acetonide 0.01% Triamcinolone acetonide 0.025% 17.44 23.003 188.624 oint lotion 38.742 cream oint cream 25.04 21.92 56.58 lotion cream 180.00 155.00 cream 22.97 113.14 cream oint soln cream, oint cream cream cream, oint oint lotion 42.94 42.94 34.58 108.58 150.08 24.06 31.93 9.92 34.33 cream, oint 27.02 lotion 60.002 cream 108.30 cream lotion gel foam cream soln cream lotion 25.32 122.34 346.772 162.43 74.84 150.00 7.32 29.56 Lowest Potency (may be ineffective for some indications) Hydrocortisone 0.5% Hydrocortisone 1.0% Hydrocortisone 2.5% cream cream, oint lotion cream, oint lotion 4.995 7.995 8.995 4.90 29.74 Wholesale acquisition cost (WAC) When multiple formulations are listed, the price of the first formulation is provided (30 g of cream, ointment or gel, 50 or 60 mL for lotion, solution or spray, 118 mL for shampoo, and 50 g for foam) Source: PricePointRx™ December 7, 2012 Reprinted with permission by FDB All rights reserved ©2012 http://www.firstdatabank.com/support/drug-pricing-policy.aspx Actual retail prices may be higher Cost of 60 g Cost of a 430-g jar Cost of an 85-g tube Available without a prescription Cost from CVS.com (December 12, 2012) Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 125) • January 2013 Drugs for Acne, Rosacea and Psoriasis Table Systemic Drugs for Psoriasis Table 5 Some Systemic Agents for Psoriasis Drug Usual Dosage Methotrexate – generic 7.5-25 mg/wk PO in a single dose or in divided doses over 36 hours 2.5-4 mg/kg/day PO in divided doses Cyclosporine – generic Neoral (Novartis) Acitretin – Soriatane (Stiefel) Biologics Adalimumab – Humira (Abbott) Etanercept – Enbrel (Amgen/Pfizer) Infliximab – Remicade (Janssen) Golimumab – Simponi (Centocor) Ustekinumab – Stelara (Janssen) 25-50 mg/day PO 80 mg x 1, then 40 mg SC q2wks 50 mg SC twice/wk x 12 wks, then once/wk mg/kg IV weeks 0, 2, then q8 wks 50 mg SC once/month 45 mg SC weeks and 4, then q12 wks2 Cost1 $2.46 3.90 65.59 899.40 1024.31 527.59 3095.88 2218.84 6035.95 Wholesale acquisition cost (WAC) for weeks’ treatment at the lowest dosage (cyclosporine cost based on a dose of 175 mg/day) Source: PricePointRx™ December 7, 2012 Reprinted with permission by FDB All rights reserved ©2012 http://www.firstdatabank.com/support/ drug-pricing-policy.aspx Actual retail prices may be higher Dose for patients weighing 100 kg is 90 mg ical agents Narrow-band UVB is more effective than broad-band UVB Oral or topical psoralens combined with UVA radiation (PUVA) is also effective for treating psoriasis, but it increases the risk of skin cancer The excimer laser has been safe and effective for localized disease and is FDA-approved for this indication.18 SYSTEMIC THERAPY — Methotrexate – In low doses (7.5-25 mg per week), methotrexate is effective in many patients with psoriasis It is indicated for the control of severe psoriasis refractory to topical treatments and phototherapy It is also used for patients with psoriatic arthritis and those with disfiguring lesions Hepatotoxicity is the most common serious adverse effect of methotrexate The drug is teratogenic and is contraindicated in pregnancy After stopping it, men should wait at least months and women should wait one ovulatory cycle before attempting to conceive The drug is immunosuppressive and should not be used in patients with active infections Methotrexateinduced pneumonitis is rare, but can be fatal Macrocytic anemia, leukopenia and thrombocytopenia can occur Liver function and blood counts should be monitored Cyclosporine – Cyclosporine (Neoral, and generics) has been as effective as methotrexate in treating moderate to severe psoriasis; in one study, relative reductions in Psoriasis Area Severity Index (PASI) scores were 64% for methotrexate and 72% for cyclosporine at 16 weeks.19 The doses of cyclosporine used for this indication (2.5-4 mg/kg/day in divided doses) have generally been safe, but nephrotoxicity can occur Cyclosporine interacts with many other drugs.20 Acitretin – Use of acitretin (Soriatane), an oral retinoid, in a dose of 25-50 mg/day can reduce the area and severity of psoriasis, but with significant mucocu- taneous toxicity Use of lower doses may reduce its toxicity Synergism has been reported when acitretin was combined with UVB radiation or with PUVA As with other systemic retinoids, acitretin frequently causes cheilitis, hair loss, dry skin and desquamation Increases in aminotransferase activity occur in about one-third of patients; this usually returns to normal even when treatment is continued, but symptomatic retinoid hepatitis can occur, and rarely progresses to cirrhosis Decreased HDL cholesterol, hypertriglyceridemia, skeletal hyperostosis, conjunctivitis, corneal erosions and opacities, iritis and decreased visual acuity can also occur Acitretin is a long-lasting teratogen; patients should not become pregnant or donate blood for at least years after discontinuing the drug Biologic Agents – These expensive drugs might be more effective than methotrexate or acitretin for treatment of psoriasis, but only one comparative trial has been published It showed greater efficacy with adalimumab (Humira) than with methotrexate over a 16-week period.21,22 The long-term safety of these agents, particularly the possibility of inducing malignancy or auto-immune disease, has been a concern, but some long-term results are available now and indicate an acceptable safety profile.23 TNF Inhibitors – Etanercept (Enbrel), a TNF inhibitor made from the fusion of two naturally occurring TNF-receptors, binds TNF with greater affinity than natural receptors, resulting in a reduction in inflammatory activity In one double-blind study, the percentage of patients achieving 75% improvement in PASI scores was 49% at 12 weeks and 59% at 24 weeks with 50 mg twice weekly.24 In a double-blind, randomized clinical trial, etanercept significantly reduced disease severity in children and adolescents with moderate to severe plaque psoriasis.25 It has been Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 125) • January 2013 Drugs for Acne, Rosacea and Psoriasis effective and well tolerated in plaque psoriasis involving the scalp.26 The drug is FDA-approved for use in both plaque psoriasis and psoriatic arthritis Infliximab (Remicade), an intravenous monoclonal chimeric TNF inhibitor, is effective for treatment of psoriasis with about 75% of patients achieving a 75% reduction in PASI scores after injections over a 10week period.27 The drug has been approved by the FDA for both psoriasis and psoriatic arthritis Adalimumab (Humira) is a fully human monoclonal antibody that binds TNF and is approved for psoriasis and psoriatic arthritis In a 52-week multicenter study of 1212 patients randomized to receive adalimumab 40 mg or placebo every other week, 71% of adalimumabtreated and 7% of placebo-treated patients achieved 75% improvement in PASI scores by week 16.28 Golimumab (Simponi) is a once-monthly, subcutaneously administered TNF inhibitor approved for use in psoriatic arthritis In a randomized, placebo-controlled trial, a 20% improvement in American College of Rheumatology criteria (ACR 20) occurred at week 14 in 51% of patients receiving golimumab 50 mg and in 9% of those receiving placebo.29 Adverse Effects – Serious infections, including bacterial sepsis and reactivation of tuberculosis and hepatitis B virus, have been reported with all the TNF inhibitors, particularly in the first 2-7 months of treatment These drugs should not be given to patients with active localized or chronic infections Screening for exposure to tuberculosis is now recommended before starting anti-TNF therapy Lymphoma and other malignancies have been reported with use of these drugs in patients with rheumatoid arthritis, but a cause-andeffect relationship has not been established They generally should not be used in patients with a recent malignancy Exacerbations and new onset of heart failure have occurred Adalimumab and infliximab have been associated with development of auto-antibodies, including anti-nuclear antibodies and anti-dsDNA antibodies, and the induction of a lupus-like syndrome Pancytopenia and demyelinating disorders such as multiple sclerosis have been reported These agents are classified as category B (no evidence of risk in humans) for use during pregnancy IL-12/23 ANTIBODIES — Ustekinumab (Stelara), a human monoclonal antibody against interleukins 12 and 23, is the only drug in its class to be approved for the treatment of psoriasis.30 In a double-blind study, 1230 patients with moderate-to-severe psoriasis were randomly assigned to receive ustekinumab 45 mg or 90 mg SC at weeks and 4, and then every 12 weeks, or placebo A total of 273 patients (66.7%) receiving ustekinumab 45 mg, 311 (75.7%) receiving ustekinumab 90 mg, and 15 (3.7%) receiving placebo achieved the primary endpoint of 75% improvement in PASI scores Serious adverse effects occurred in patients (2.0%) in the 45-mg group, in (1.2%) in the 90-mg group, and in (2.0%) in the placebo group.31 Briakinumab, an investigational IL-12/23 inhibitor, showed greater efficacy than methotrexate or etanercept in treatment of moderate to severe psoriasis,32,33 but was withdrawn from development because of concerns about an increased incidence of cardiovascular adverse effects with these agents.34,35 INVESTIGATIONAL ORAL DRUGS — Apremilast, an oral phosphodiesterase-4 inhibitor, has improved psoriasis symptoms in some patients.36,37 Tofacitinib (Xeljanz), an oral Janus kinase (JAK) inhibitor, was recently approved for use in rheumatoid arthritis38 and is also being studied in patients with psoriatic arthritis.39 CHOICE OF DRUGS — Mild to moderate psoriasis is generally treated with topical corticosteroids Calcipotriene and tazarotene are topical alternatives Phototherapy is used when the disease is widespread or unresponsive to topical agents Systemic agents, including biologic drugs, are usually reserved for patients with moderate to severe disease or those with psoriatic arthritis 10 11 12 13 14 15 Adapalene-benzoyl peroxide (Epiduo) for acne Med Lett Drugs Ther 2009; 51:31 W Ting Randomized, observer-blind, split-face study to compare the irritation potential of topical acne formulations over a 14-day treatment period Cutis 2012; 90:91 Clindamycin-tretinoin (Veltin Gel) for acne Med Lett Drugs Ther 2010; 52:102 Extended-release minocycline (Solodyn) for acne Med Lett Drugs Ther 2006; 48:95 SE Garner et al Minocycline for acne vulgaris: efficacy and safety Cochrane Database Syst Rev 2012; Aug 15 (8):CD002086 Isotretinoin (Absorica) for acne Med Lett Drugs Ther 2013; 55: in press AO Arowojolu et al Combined oral contraceptive pills for treatment of acne Cochrane Database Syst Rev 2012; 7:CD004425 EA Arrington et al Combined oral contraceptives for the treatment of acne: a practical guide Cutis 2012; 90:83 CB Turowski and WD James The efficacy and safety of amoxicillin, trimethoprim-sulfamethoxazole, and spironolactone for treatmentresistant acne vulgaris Adv Dermatol 2007; 23:155 HC Williams et al Acne vulgaris Lancet 2012; 379:361 J Fowler et al Once-daily topical brimonidine tartrate gel 0.5% is a novel treatment for moderate to severe facial erythema of rosacea: results of two multicentre, randomized and vehicle-controlled studies Br J Dermatol 2012; 166:633 Low-dose doxycycline (Oracea) for rosacea Med Lett Drugs Ther 2007; 49:5 KJ Butterwick et al Laser and light therapies for acne rosacea J Drugs Dermatol 2006; 5:35 FO Nestle et al Psoriasis N Engl J Med 2009; 361:496 Calcipotriene for psoriasis Med Lett Drugs Ther 1994; 36:70 Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 125) • January 2013 Drugs for Acne, Rosacea and Psoriasis 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 Calcitriol (Vectical) for mild to moderate plaque psoriasis Med Lett Drugs Ther 2009; 51:70 A betamethasone-calcipotriene combination for psoriasis Med Lett Drugs Ther 2006; 48:55 T Mudigonda et al A review of targeted ultraviolet B phototherapy for psoriasis J Am Acad Dermatol 2012; 66:664 VM Heydendael et al Methotrexate versus cyclosporine in moderateto-severe chronic plaque psoriasis N Engl J Med 2003; 349:658 C Ryan et al The use of cyclosporine in dermatology: part II J Am Acad Dermatol 2010; 63:949 JH Saurat et al Efficacy and safety results from the randomized controlled comparative study of adalimumab vs methotrexate vs placebo in patients with psoriasis (CHAMPION) Br J Dermatol 2008; 158:558 J Schmitt et al Efficacy and tolerability of biologic and nonbiologic systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials Br J Dermatol 2008; 159:513 MH Rustin Long-term safety of biologics in the treatment of moderate-to-severe plaque psoriasis: review of current data Br J Dermatol 2012; 167 (suppl 3):3 CL Leonardi et al Etanercept as monotherapy in patients with psoriasis N Engl J Med 2003; 349:2014 AS Paller et al Etanercept treatment for children and adolescents with plaque psoriasis N Engl J Med 2008; 358:241 J Bagel et al Moderate to severe plaque psoriasis with scalp involvement: a randomized, double-blind, placebo-controlled study of etanercept J Am Acad Dermatol 2012; 67:86 A Menter et al A randomized comparison of continuous vs intermittent infliximab maintenance regimens over year in the treatment of moderate-to-severe plaque psoriasis J Am Acad Dermatol 2006; 56:31 A Menter et al Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial J Am Acad Dermatol 2008; 58:106 A Kavanaugh et al Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: twenty-four-week efficacy and safety results of a randomized, placebo-controlled study Arthritis Rheum 2009; 60:976 Ustekinumab (Stelara) for psoriasis Med Lett Drugs Ther 2010; 52:7 KA Papp et al Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2) Lancet 2008; 371:1675 K Reich et al A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis N Engl J Med 2011; 365:1586 BE Strober et al Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis Br J Dermatol 2011;165:661 C Ryan et al Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials JAMA 2011; 306:864 T Tzellos et al Re-evaluation of the risk for major adverse cardiovascular events in patients treated with anti-IL-12/23 biological agents for chronic plaque psoriasis: a meta-analysis of randomized controlled trials J Eur Acad Dermatol Venereol 2012; March (epub) K Papp et al Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial Lancet 2012; 380:738 KA Papp et al Efficacy and safety of apremilast in subjects with moderate to severe plaque psoriasis: results from a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dosecomparison study J Eur Acad Dermatol Venereol 2012 Oct (epub) Tofacitinib (Xeljanz) for rheumatoid arthritis Med Lett Drugs Ther 2013; 55: in press KA Papp et al Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study Br J Dermatol 2012; 167:668 2012 Year-End Index: For an electronic copy of the 2012 Index, go to: www.medicalletter.org/downloads/tgindex2012.pdf Treatment Guidelines ® from The Medical Letter EDITOR IN CHIEF: Mark Abramowicz, M.D EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School EDITOR: Jean-Marie Pflomm, Pharm.D ASSISTANT EDITORS, DRUG INFORMATION: Susan M Daron, Pharm.D., Corinne Z Morrison, Pharm.D CONSULTING EDITORS: Brinda M Shah, Pharm.D., F Peter Swanson, M.D CONTRIBUTING EDITORS: Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical School Eric J Epstein, M.D., Albert Einstein College of Medicine Jane P Galiardi, M.D., M.H.S., F.A.C.P., Duke University School of Medicine Jules Hirsch, M.D., Rockefeller University David N Juurlink, BPhm, M.D., PhD, 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Participants will be able to select and prescribe, or confirm the appropriateness of the prescribed usage of the drugs and other therapeutic modalities discussed in Treatment Guidelines with specific attention to clinical evidence of effectiveness, adverse effects and patient management Upon completion of this program, the participant will be able to: Explain the current approach to the management of acne, rosacea and psoriasis Discuss the pharmacologic options available for treatment of these common skin conditions and compare them based on their efficacy, dosage and administration and potential adverse effects Determine the most appropriate therapy given the clinical presentation of an individual patient Privacy and Confidentiality: The Medical Letter guarantees our firm commitment to your privacy We not sell any of your information Secure server software (SSL) is used for commerce transactions through VeriSign, Inc No credit card information is stored IT Requirements: Windows 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Call us at 800-211-2769 or 914-235-0500 or e-mail us at: custserv@medicalletter.org Questions start on next page Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 125) • January 2013 DO NOT FAX OR MAIL THIS EXAM To take CME exams and earn credit, go to: medicalletter.org/CMEstatus Issue 125 Questions The mechanism of action of benzoyl peroxide in acne is primarily: a anti-inflammatory b antibacterial c keratolytic d all of the above Issue 125 A 16-year-old girl who has been taking tretinoin for acne tells you that it does not seem be clearing her skin You could tell her that: a adapalene is more effective, but also more irritating b tazarotene is less effective c a combination of tretinoin and an antibiotic may be more effective d all of the above Issue 125 A topical retinoid can be used to treat: a inflamed acne lesions b noninflamed acne lesions c rosacea d all of the above Issue 125 The most effective drug available for treatment of severe, nodulocystic acne is: a isotretinoin b minocycline c tretinoin d prednisone Issue 125 The standard topical antimicrobials used to treat the papules and pustules of rosacea are: a erythromycin and clindamycin b minocycline and azithromycin c tetracycline and benzoyl peroxide d metronidazole and azelaic acid Issue 125 Oral antibiotics are effective in rosacea for treatment of: a telangiectasia b rhinophyma c flushing d none of the above Issue 125 Treatment with isotretinoin can lead to significant reductions in the erythema, papules and telangiectasia of rosacea after about: a weeks b months c months d months Issue 125 Light-based therapy of rosacea can cause: a hyperpigmentation b hypopigmentation c melanoma d non-melanoma skin cancer Issue 125 Side effects of super-high potency topical corticosteroids can include: a adrenal suppression b atrophy of the dermis c telangiectasias d all of the above Issue 125 10 A 36-year-old man with plaque psoriasis that has not responded to topical treatment asks you to discuss the choice between methotrexate and cyclosporine You could tell him that: a methotrexate can cause liver damage b cyclosporine can cause kidney damage c cyclosporine has been as effective as methotrexate in treating moderate to severe psoriasis d all of the above Issue 125 11 As a group, TNF inhibitors have achieved a 75% reduction in PASI score in about: a 30-50% of patients b 50-75% c 70-90% d 95% Issue 125 12 Side effects of TNF inhibitors have included: a sepsis b reactivation of TB c lymphoma (possibly) d all of the above Issue 125 ACPE UPN: 0379-0000-12-125-H01-P; Release: December 2012, Expire: December 2013 Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 125) • January 2013 ... Antibiotics for Acne Some Oral Antibiotics for Acne Some Retinoids for Acne Some Topical Corticosteroids Some Systemic Drugs for Psoriasis Page Page Page Page Page Drugs for Acne, Rosacea and Psoriasis. .. Letter • Vol 11 ( Issue 125) • January 2013 Drugs for Acne, Rosacea and Psoriasis Table Systemic Drugs for Psoriasis Table 5 Some Systemic Agents for Psoriasis Drug Usual Dosage Methotrexate –... plaque psoriasis. 25 It has been Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 125) • January 2013 Drugs for Acne, Rosacea and Psoriasis effective and well tolerated in plaque psoriasis