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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

1. Some Topical Antibiotics for Acne 2. Some Oral Antibiotics for Acne 3. Some Retinoids for Acne 4. Some Topical Corticosteroids 5. Some Systemic Drugs for Psoriasis Page Page Page Page Page 1 2 3 5 6

Drugs for Acne, Rosacea and Psoriasis

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
Table 1. Some Topical Antibiotics for Acne
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) Dapsone Aczone (Allergan)

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,

Some Formulations
1% gel, soln, lotion, pads 1% foam 1%/5% gel 1.2%/5% gel 1.2%/2.5% gel 2% gel, soln, pads 3%/5% gel 20% cream 5% gel

Usual Dosage
Twice daily Once daily Twice daily Once daily in the evening Once daily Twice daily Twice daily Twice daily Twice daily

$38.75/30 63.88/30 143.77/50 190.49/50 107.62/25 187.70/25 166.05/45 188.37/45 258.29/50 12.52/30 g g g g g g g g g g

89.74/46.6 g 282.38/46.6 g 199.91/30 g 172.50/30 g

1. 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. 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 2. Some Oral Antibiotics for Acne
Doxycycline generic Vibramycin extended-release generic Doryx Minocycline generic Minocin extended-release generic Solodyn Erythromycin6 generic Trimethoprim/sulfamethoxazole generic Bactrim6

Usual Dosage
20-100 mg bid 150 mg once daily 50-100 mg bid 1 mg/kg once daily4 500 mg bid 160/800 mg bid

Some Adverse Effects

Photosensitivity, GI upset, vaginal candidiasis Vertigo, skin discoloration, 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

GI upset, drug interactions Bone marrow suppression, rash

1. 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. Actual retail prices may be higher. 2. Cost of 30 days treatment with the generic drug from large discount pharmacies. 3. Cost based on a dose of 50 mg twice daily. 4. 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. 5. Cost of 30 days treatment at 90 mg/day. 6. 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 do 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 ( 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 3. Some Retinoids for Acne
Topical Retinoids Adapalene generic Differin (Galderma) Tazarotene Tazorac (Allergan) Tretinoin generic

Some Formulations

Usual Dosage
Once daily at bedtime Once daily in the evening Once daily at bedtime Once daily at bedtime Once daily in the evening Once daily at bedtime Once daily in the evening Once daily Once daily in the evening Once daily at bedtime

$158.00/45 328.15/45 224.15/30 73.03/45 53.45/45 253.58/45 171.72/45 213.52/45 215.65/45 369.11/35 g g g g g g g g g g

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) Amnesteem (Mylan) Claravis (Barr) Myorisan (VersaPharma) Sotret (Ranbaxy)

242.10/45 g 159.84/30 g 229.86/30 g

10, 20, 30, 40 mg caps 10, 20, 40 mg caps 10, 20, 30, 40 mg caps 10, 20, 40 mg caps 10, 20, 30, 40 mg caps

0.5-1 mg/kg/d in 2 divided doses for 15-20 wks

1416.822 551.262 710.702 550.502 600.482

1. 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. support/drug-pricing-policy.aspx. Actual retail prices may be higher. 2. 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 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

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 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 brimonide 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 2 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 do 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 4. 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 4. Some Topical Corticosteroids
Super-High Potency Betamethasone dipropionate augmented 0.05% Clobetasol propionate 0.05% generic

oint, gel


Medium Potency Betamethasone valerate 0.12% Luxiq (Stiefel) Fluocinolone acetonide 0.025% Hydrocortisone valerate 0.2% generic Westcort (Ranbaxy) Mometasone furoate 0.1% 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



foam oint oint oint cream cream oint

185.89 56.42 119.38 179.98 32.74 6.30 23.003 188.624 38.742 25.04 21.92 56.58 180.00 155.00 22.97 113.14 42.94 42.94 34.58 108.58 150.08 24.06 31.93 9.92 34.33 27.02 60.002 108.30 25.32 122.34 346.772 162.43 74.84 150.00 7.32 29.56 4.995 7.995 8.995 4.90 29.74

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) Desoximetasone 0.05% Diflorasone diacetate 0.05% Fluocinonide 0.05%

cream, oint, gel soln, lotion shampoo foam lotion shampoo spray foam cream cream, oint

9.11 22.84 311.08 124.81 338.80 451.75 266.05 223.12 187.36 40.30 137.72 324.002 51.22 75.30

lotion cream oint cream lotion cream cream

oint cream oint

cream, oint cream, oint gel oint oint, gel soln cream cream, oint oint oint cream lotion cream oint cream cream cream oint oint cream

70.40 103.62 122.58 75.84 16.06 44.26 8.76 100.36 30.52 16.36 110.05 271.44 62.74 30.53 99.88 112.82 7.45 22.97 69.40 9.00 17.44

Halcinonide 0.1% Halog (Ranbaxy) Mometasone 0.1% Triamcinolone acetonide 0.5% Medium-High Potency Amcinonide 0.1% Betamethasone dipropionate 0.05% Betamethasone valerate 0.1% Desoximetasone 0.05% Diflorasone diacetate 0.05% Fluocinonide emollient 0.05% Fluticasone propionate 0.005% generic Cutivate (PharmDerm) Triamcinolone acetonide 0.1% Triamcinolone acetonide 0.5%

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%

cream oint soln cream, oint cream cream cream, oint oint lotion cream, oint lotion cream cream lotion gel foam cream soln cream lotion cream cream, oint lotion cream, oint lotion

Lowest Potency (may be ineffective for some indications) Hydrocortisone 0.5% Hydrocortisone 1.0% Hydrocortisone 2.5%

1. 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. Actual retail prices may be higher. 2. Cost of 60 g. 3. Cost of a 430-g jar. 4. Cost of an 85-g tube. 5. Available without a prescription. Cost from (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. 5. Some Systemic Agents for Psoriasis
Methotrexate generic Cyclosporine generic Neoral (Novartis) Acitretin Soriatane (Stiefel) Biologics Adalimumab Humira (Abbott) Etanercept Enbrel (Amgen/Pfizer) Infliximab Remicade (Janssen) Golimumab Simponi (Centocor) Ustekinumab Stelara (Janssen)

Usual Dosage
7.5-25 mg/wk PO in a single dose or in 3 divided doses over 36 hours 2.5-4 mg/kg/day PO in 2 divided doses 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 5 mg/kg IV weeks 0, 2, 6 then q8 wks 50 mg SC once/month 45 mg SC weeks 0 and 4, then q12 wks2

$2.46 3.90 65.59 899.40 1024.31 527.59 3095.88 2218.84 6035.95

1. Wholesale acquisition cost (WAC) for 1 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. drug-pricing-policy.aspx. Actual retail prices may be higher. 2. Dose for patients weighing <100 kg; dose for patients >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 3 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 2 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 3 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 3 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 0 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 8 patients (2.0%) in the 45-mg group, in 5 (1.2%) in the 90-mg group, and in 8 (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.
1. 2. 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 2 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.

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Treatment Guidelines from The Medical Letter Vol. 11 ( Issue 125) January 2013

Drugs for Acne, Rosacea and Psoriasis

16. 17. 18. 19. 20. 21. 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 1 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 8 (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 3 (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:

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, Sunnybrook Health Sciences Centre Richard B. Kim, M.D., University of Western Ontario Hans Meinertz, M.D., University Hospital, Copenhagen Sandip K. Mukherjee, M.D., F.A.C.C., Yale School of Medicine Dan M. Roden, M.D., Vanderbilt University School of Medicine Esperance A. K. Schaefer, M.D., M.P.H., Harvard Medical School F. Estelle R. Simons, M.D., University of Manitoba Neal H. Steigbigel, M.D., New York University School of Medicine Arthur M.F. Yee, M.D., Ph.D., F.A.C.R, Weill Medical College of Cornell University SENIOR ASSOCIATE EDITORS: Donna Goodstein, Amy Faucard ASSOCIATE EDITOR: Cynthia Macapagal Covey EDITORIAL FELLOW: Jennifer Y. Lin, M.D., Harvard Medical School MANAGING EDITOR: Susie Wong ASSISTANT MANAGING EDITOR: Liz Donohue PRODUCTION COORDINATOR: Cheryl Brown EXECUTIVE DIRECTOR OF SALES: Gene Carbona FULFILLMENT AND SYSTEMS MANAGER: Cristine Romatowski DIRECTOR OF MARKETING COMMUNICATIONS: Joanne F. Valentino VICE PRESIDENT AND PUBLISHER: Yosef Wissner-Levy Founded in 1959 by Arthur Kallet and Harold Aaron, M.D. Copyright and Disclaimer: The Medical Letter is an independent nonprofit organization that provides healthcare professionals with unbiased drug prescribing recommendations. The editorial process used for its publications relies on a review of published and unpublished literature, with an emphasis on controlled clinical trials, and on the opinions of its consultants. The Medical Letter is supported solely by subscription fees and accepts no advertising, grants or donations. No part of the material may be reproduced or transmitted by any process in whole or in part without prior permission in writing. The editors do not warrant that all the material in this publication is accurate and complete in every respect. The editors shall not be held responsible for any damage resulting from any error, inaccuracy or omission. Subscription Services Subscriptions (US):
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Treatment Guidelines from The Medical Letter Vol. 11 ( Issue 125) January 2013