Topical Corticosteroid Drug Class Review (October 2012).pdf

Drug Class Review

Topical Corticosteroids

84:06 Anti-inflammatory Agents (Skin and Mucous Membrane)

Alclometasone

Amcinonide

Betamethasone

Clobetasol

Clocortolone

Desonide

Desoximetasone

Diflorasone

Fluocinolone

Fluocinonide

Flurandrenolide

Fluticasone

Halcinonide

Halobetasol

Hydrocortisone

Mometasone

Prednicarbate

Triamcinolone

Final Report

October 2012

Review prepared by:

Melissa Archer, PharmD, Clinical Pharmacist

Gary Oderda, PharmD, MPH, Professor

University of Utah College of Pharmacy

Copyright 2012 by University of Utah College of Pharmacy

Salt Lake City, Utah. All rights reserved.

2

Table of Contents:

Executive Summary ........................................................................................................................ 3

Introduction ..................................................................................................................................... 5

Disease Overview....................................................................................................................... 5

Table 1. Topical Corticoid Skin Disease Responsiveness .................................................... 6

Table 2. Comparison of the Topical Corticosteroids ............................................................ 8

Pharmacology/Pharmacokinetics ............................................................................................ 13

Table 3. Potency of Topical Corticosteroid Agents ............................................................ 13

Methods......................................................................................................................................... 14

Clinical Efficacy ........................................................................................................................... 15

How do the topical corticosteroids compare with each other for reducing anti-inflammatory

symptoms? ............................................................................................................................... 15

Are there patient subgroups for which one of the topical corticosteroids is more effective or

associated with fewer adverse effects? ................................................................................... 16

Adverse Drug Reactions ............................................................................................................... 17

How does the safety of the topical corticosteroids compare with each other? ....................... 17

Summary ....................................................................................................................................... 17

References ..................................................................................................................................... 19

3

Executive Summary

Introduction: Eighteen topical corticosteroid agents are currently available for use in the United

States and are indicated in the treatment of corticosteroid-responsive inflammation associated

with dermatoses. The topical agents are available as creams, foams, gels, lotions, ointments,

shampoos, solutions and rectal products. Each of the agents has varying potencies and rates of

skin penetration and, subsequently, different clinical uses.

Topical corticosteroids may be used to treat inflammation associated with a number of

dermatologic disorders: eczema, psoriasis, lichen planus, bullous pemphigoid, vasculitis, and

granuloma annulare. Efficacy of the topical corticosteroids can vary depending on the skin

disorder being treated. In general, treatment of inflammation associated with skin infections is

determined by clinical judgment based upon location of infection, prior treatment, and

complicating conditions (bacterial or fungal growth, age of patient, location of infection).

Clinical Efficacy: The comparative clinical evidence available for the topical corticosteroids is

limited. The majority of the evidence evaluates the agents in placebo-controlled trials in the

treatment of inflammation associated with psoriasis. The limited data demonstrate comparable

clinical efficacy for the potent and very-potent topical corticosteroid agents in psoriasis. Limited

evidence also suggests efficacy for potent and mid-strength topical corticosteroids in the

treatment of inflammation associated with chronic dermatitis. According to both comparative

evidence and clinical experience, topical corticosteroids are useful treatments for dermatologic

conditions and success of treatment can vary depending on an accurate diagnosis, steroid

potency, agent delivery vehicle, frequency of application, duration of treatment, and adverse

effects.

Special Populations: Very little evidence is available for use of topical corticosteroids in

pediatric patients, the geriatric population, and in pregnant women. Pediatric and geriatric

patients may be at increased risk of adverse events due to characteristics that increase penetration

of the topical agents including: reduced ability to metabolize potent glucocorticoids rapidly and

thinner skin. Some evidence suggests topical corticosteroid use in pregnant may be harmful to

the fetus. Overall, caution should be used when using topical corticosteroids in children, the

geriatric population, or pregnant women.

Adverse Drug Reactions: The topical corticosteroids are associated with both local and

systemic adverse events. Rate of adverse events tends to increase with increase in potency and

duration of use of the corticosteroid. Local adverse effects include: skin atrophy, acneiform

reactions, hypertrichosis, pigment changes, cutaneous infections, and allergic reactions. Systemic

adverse effects include: suppression of the hypothalamicpituitaryadrenal axis, ocular effects,

and metabolic effects. Long-term use of topical steroids should be limited and highly potent

formulations should only be used intermittently. Laboratory tests should be performed if

systemic absorption of corticosteroids is suspected.

4

Summary: Overall, selection of a topical glucocorticoid preparation should be based on both

patient-related and drug-related factors including age of the patient, the extent and location of the

body surface area to be treated and the presence or absence of skin inflammation.

5

Introduction

The topical corticosteroid agents are available as creams, foams, gels, lotions, ointments,

shampoos, solutions and rectal products. Eighteen topical corticosteroid agents are currently

available for use in the United States: alclometasone, amcinonide, betamethasone, clobetasol,

clocortolone, desonide, desoximetasone, diflorasone, fluocinolone, fluocinonide, flurandrenolide,

fluticasone, halcinonide, halobetasol, hydrocortisone, mometasone, prednicarbate, and

triamcinolone.1, 2

Hydrocortisone is available as an over-the-counter product and in rectal

formulations for the treatment of mild or moderate acute ulcerative colitis.1, 2

All of the topical

corticosteroid agents are indicated in the treatment of corticosteroid-responsive inflammation

associated with dermatoses including, but not limited to, seborrheic or atopic dermatitis,

neurodermatitis, anogenital pruritus, and psoriasis.1-4

A number of combination corticosteroid

products are available for use in the united states: betamethasone/clotrimazole,

betamethasone/calcipotriene, fluocinolone/hydroquinone/tretinoin, hydrocortisone/acyclovir,

hydrocortisone/ bacitracin/neomycin/polymyxin B, hydrocortisone/iodoquinol,

hydrocortisone/neomycin/polymyxin B, hydrocortisone/urea, and triamcinolone/nystatin.1, 2

Table 2 compares all of the available topical corticosteroid agents.

The topical corticosteroids agents have varying potencies and therefore have different

indications and uses.3-6

The topical products exhibit minimal absorption and have few systemic

adverse reactions or drug interactions. Limited data is available comparing the efficacy and/or

safety of the topical corticosteroid agents. In general, treatment of inflammation associated with

skin infections is determined by clinical judgment based upon location of infection, prior

treatment, and complicating conditions (bacterial or fungal growth, age of patient, location of

infection).3, 4

This is a report of the available data evaluating the topical corticosteroid agents in

the treatment of corticosteroid-responsive inflammation associated with dermatoses.

Disease Overview

Topical corticosteroids are indicated in the symptomatic treatment of inflammatory skin

disorders, or dermatoses, including eczema, psoriasis, lichen planus, bullous pemphigoid,

vasculitis, granuloma annulare, and acne.3-7

Efficacy of the topical corticosteroids can vary

depending on the skin disorder being treated. See Table 1 for a comparison of topical

corticosteroid disease responsiveness. In general, the topical corticosteroids are most effective in

the symptomatic treatment of psoriasis (intertriginous), seborrheic dermatitis, intertrigo, and

atopic dermatitis in children.3-6

Systemic corticosteroids tend to be more effective in treating

most dermatologic inflammations but the topical agents are often preferred as they are associated

with fewer systemic adverse effects.3, 4

Systemic adverse events associated with steroid use

include adrenal suppressive effects and metabolic adverse reactions.1, 2

While all corticosteroids

are effective in treating inflammation, they are not curative.3, 4

The cause of underlying skin

disorder should be identified and treated or eliminated in addition to treatment of the

inflammatory symptoms.7

6

Individual topical corticosteroid preparations can vary in anti-inflammatory activity as a

result of the potency, the vehicle, frequency of application, the site of application, the disease,

the individual patient, and whether or not an occlusive dressing is used.3, 4, 7

For example,

occlusive vehicles, like ointments, can increase anti-inflammatory activity as they provide

increased skin hydration and increased skin permeability. Covering the skin with an occlusive

dressing can also drastically increase anti-inflammatory activity. The solubility of the topical

agents can affect penetration into the epidermis; propylene glycol is a solvent found in many

topical glucocorticoid preparations that tends to increase the potency of the corticosteroid agent.

Peanut oil is added to some topical agents to form a preparation that is thinner and easier to apply

while maintaining the hydrating properties. Creams have increased amounts of petrolatum, are

less oily, and may be more cosmetically appealing but less hydrating. Lotions, solutions, and gels

have less penetration but may be more useful in treating diseases in hair-bearing areas, such as

the scalp. Other formulations, like foams or sprays, may increase convenience.3, 4, 7

For all topical corticosteroid agents there are general principles recommended when

initiating therapy.1-4, 7

All agents should be initiated at the lowest potency sufficient to treat the

inflammation and used for the shortest duration possible. In general, highly responsive skin

diseases respond well to less-potent topical corticosteroids, while the least responsive skin

diseases often require higher-potency agents. For example, very potent corticosteroid agents are

usually required for hyperkeratotic or lichenified dermatoses. If a large area is to be treated, a

low to medium potency agent should be used. Low-potency agents should be used for disease on

the face or intertriginous areas.1-4

Overall, topical corticosteroids are effective in treating

inflammation related to many skin diseases but they are not curative and they are associated with

adverse events which limit their use.7

Table 1. Topical Corticoid Skin Disease Responsiveness7

Responsiveness Skin disease

Highly responsive Psoriasis (intertriginous)

Atopic dermatitis (children)

Seborrheic dermatitis

Intertrigo

Moderately responsive Psoriasis

Atopic dermatitis (adults)

Nummular eczema

Primary irritant dermatitis

Papular urticaria

Parapsoriasis

Lichen simplex chronicus

Least responsive Palmoplantar psoriasis

Psoriasis of nails

Dyshidrotic eczema

Lupus erythematosus

Pemphigus

Lichen planus

7

Granuloma annulare

Necrobiosis lipoidica diabeticorum

Sarcoidosis

Allergic dermatitis, acute phase

Insect bites

8

Table 2. Comparison of the Topical Corticosteroids1, 2

Product Dosage Forms Labeled Uses Dose

Range

(mg),

Adults

Absorption Generic Available

Alclometasone (Aclovate) Topical cream: 0.05% (15 g, 45 g,

60 g)

Topical ointment: 0.05% (15 g, 45

g, 60 g)

Treatment of inflammation of

corticosteroid-responsive dermatosis

Apply 2-3

times/day

~3% absorbed systemically after 8

hours when applied to intact skin

Yes

Amcinonide (Amcort, others) Topical cream: 0.1% (15 g, 30 g,

60 g)

Topical: 0.1% (60 mL)

Relief of the inflammatory and pruritic

manifestations of corticosteroid-

responsive dermatoses

Apply 2-3

times/day

Adequate through intact skin;

increases with skin inflammation or

occlusion

Yes

Betamethasone (Celestone; Celestone

Soluspan; Diprolene; Diprolene AF;

Luxiq)

Topical foam aerosol: 0.12% (50 g,

100 g)

Topical cream: 0.05% (15 g, 45 g,

50 g); 0.1% (15 g, 45 g)

Topical gel: 0.05% (15 g, 50 g)

Topical lotion: 0.05% (30 mL, 60

mL); 0.1% (60 mL)


g, 50 g); 0.1% (15 g, 45 g)

Inflammatory dermatoses such as

seborrheic or atopic dermatitis,

neurodermatitis, anogenital pruritus,

psoriasis, inflammatory phase of xerosis

Apply 1-2

times/day

Dependent on formulation, amount

applied and nature of skin at

application site

No: Foam

Betamethasone/clotrimazole (Lotrisone) Topical cream: 0.05/1% (15 g, 45

g)

Topical lotion: 0.05/1% (30 mL)

Topical treatment of various dermal

fungal infections (including tinea pedis,

cruris, and corpora in patients 17 years

of age)

Apply 2

times/day



application site

Yes

Betamethasone/calcipotriene (Taclonex

Scalp; Taclonex)

Topical ointment: 0.064/0.005%

(60 g, 100 g)

Topical suspension: 0.064/0.005%

(60 mL)

Treatment of psoriasis vulgaris

Unlabeled: Treatment of corticosteroid-


Apply 1

times/day



application site

No

9

Clobetasol (Clobex; Cormax; Olux-

E; Olux; Temovate E; Temovate)


100 g)


45 g, 60 g)

Topical gel: 0.05% (15 g, 30 g, 60

g)


mL)


g, 45 g, 60 g)

Topical shampoo: 0.05% (118 mL)

Topical solution: 0.05% (25 mL,

50 mL); spray (59 mL, 125 mL)

Short-term relief of inflammation of

moderate-to-severe corticosteroid-


Apply 2

times/day

Percutaneous absorption is variable

and dependent upon many factors

including vehicle used, integrity of

epidermis, dose, and use of occlusive

dressings

No: spray

Clocortolone (Cloderm) Topical cream: 0.1% (30 g, 45 g,

75 g, 90 g)

Inflammation of corticosteroid-


Apply 1-4

times/day

Percutaneous absorption is variable

and dependent upon many factors

including vehicle used, integrity of

epidermis, dose, and use of occlusive

dressings; small amounts enter

circulatory system via skin

No

Desonide (Desonate; DesOwen;

LoKara; Verdeso)


100 g)

Topical cream: 0.05% (15 g, 60 g)

Topical gel: 0.05% (60 g)


mL, 118 mL)


g)

Treatment of inflammatory and pruritic

manifestations of corticosteroid

responsive dermatosis and mild-to-

moderate atopic dermatitis

Apply 2-3

times/day



application site; may be increased with

inflammation or occlusion

No : Foam; Gel

Desoximetasone (Topicort; Topicort

LP)

Topical cream: 0.05% (15 g, 60 g);

0.25% (15 g, 60 g, 100 g)

Topical gel: 0.05% (15 g, 60 g)

Topical ointment: 0.05% (60 g);

0.25% (15 g, 60 g)

Relieves inflammation and pruritic

symptoms of corticosteroid-responsive

dermatosis

Apply 2

times/day

May be increased with occlusion,

inflammation, or vary with site of

application

Yes

Diflorasone (ApexiCon E; ApexiCon) Topical cream: 0.05% (15 g, 30 g,

60 g)


g, 60 g)

Relieves inflammation and pruritic

symptoms of corticosteroid-responsive

dermatosis

Apply 1-4

times/day

Negligible, around 1% reaches dermal

layers or systemic circulation;

occlusive dressings increase

absorption percutaneously

Yes

10

Fluocinolone (Capex; Derma-

Smoothe/FS)

Topical cream: 0.01% (15 g, 60 g);

0.025% (15 g, 60 g)

Topical oil: 0.01% (118 mL)


g)

Topical shampoo: 0.01% (120 mL)

Topical solution: 0.01% (60 mL)

Relief of susceptible inflammatory

dermatosis [low, medium corticosteroid];

dermatitis or psoriasis of the scalp;

atopic dermatitis in adults and children

3 months of age

Apply 1-4

times/day

Dependent on strength of preparation,

amount applied, nature of skin at

application site, vehicle, and use of

occlusive dressing; increased in areas

of skin damage, inflammation, or

occlusion

No; Shampoo

Fluocinolone/hydroquinone/tretinoin

(Tri-Luma)

Topical cream, topical:

0.01%,/4%/0.05% (30 g)

Short-term treatment of moderate-to-

severe melasma of the face

Apply

once daily

Minimal No

Fluocinonide (Vanos) Topical cream: 0.05% (15 g, 30 g,

60 g, 120 g); 0.1% (30 g, 60 g, 120

g)

Topical gel: 0.05% (15 g, 30 g, 60

g)


g, 60 g)

Topical solution: 0.05% (20 mL,

60 mL)

Anti-inflammatory, antipruritic;

treatment of plaque-type psoriasis (up to

10% of body surface area) [high-potency

topical corticosteroid]

Apply 2-4

times/day

Dependent on strength of product,

amount applied, and nature of skin at

application site; ranges from ~1% in

areas of thick stratum corneum (palms,

soles, elbows, etc) to 36% in areas of

thin stratum corneum (face, eyelids,

etc); increased in areas of skin

damage, inflammation, or occlusion

Yes

Flurandrenolide (Cordran; Cordran

SP)


60 g)


mL, 120 mL)

Topical tape: 4 mcg/cm2 (24 inch,

80 inch)


responsive dermatoses [medium potency


Apply 2-3

times/day

Adequate with intact skin; repeated

applications lead to depot effects on

skin, potentially resulting in enhanced

percutaneous absorption

No

Fluticasone (Cutivate) Topical cream: 0.05% (15 g, 30 g,

60 g)


g)


g, 60 g)

Relief of inflammation and pruritus

associated with corticosteroid-responsive

dermatoses; atopic dermatitis

Apply 1-2

times/day

5% (increased with inflammation) Yes

Halcinonide (Halog) Topical cream: 0.1% (30 g, 60 g,

216 g)


g)


responsive dermatoses [high potency


Apply 1-3

times/day

Percutaneous absorption varies by

location of topical application and use

of occlusive dressings

No

11

Halobetasol (Halonate; Ultravate) Topical cream: 0.05% (15 g, 50 g)


g)

Relief of inflammatory and pruritic

manifestations of corticosteroid-response

dermatoses [super high potency topical

corticosteroid]

Apply 1-2

times/day

Percutaneous absorption is dependent

on several factors, including epidermal

integrity (intact vs abraded skin),

formulation, and the use of occlusive

dressings;

12

Hydrocortisone/ bacitracin/neomycin/polymyxin B

(Cortisporin Ointment; Neo-Polycin

HC)

Ophthalmic ointment: 10 mg/400

u/3.5 mg/10,000 u per g (3.5 g)

Topical ointment: 10 mg/400 u/3.5

mg/5000 u per g (15 g)

Prevention and treatment of susceptible

inflammatory conditions where bacterial

infection (or risk of infection) is present

Apply 2-4

times/day

Varies No: topical

ointment

Hydrocortisone/iodoquinol (Alcortin A;

Dermazene)

Topical cream: 1%/1% (30 g)

Topical gel: 2%/1% (2 g)

Treatment of eczema (including

impetiginized, nuchal, and nummular);

acne urticaria; anogenital pruritus, atopic

dermatitis, chronic infectious dermatitis;

chronic eczematoid otitis externa;

folliculitis, intertrigo; lichen simplex

chronicus; moniliasis; mycotic

dermatoses; neurodermatitis (localized or

systemic); pyoderma, stasis dermatitis

Apply 3-4

times/day

Varies No: gel

Hydrocortisone/neomycin/polymyxin B

(Cortisporin; Cortomycin)

Topical cream: 5 mg/3.5

mg/10,000 u per g (7.5 g)

Steroid-responsive inflammatory

condition for which a corticosteroid is

indicated and where bacterial infection or

a risk of bacterial infection exists

Apply 1-4

times/day

Varies No

Hydrocortisone/urea (Carmol-HC) Topical cream: 1%/10% ((28 g) Inflammation of corticosteroid-


Apply 2-4

times/day

Varies No

Mometasone (Elocon) Topical cream: 0.1% (15 g, 45 g)


mL)


g)

Relief of the inflammatory and pruritic

manifestations of corticosteroid-

responsive dermatoses (medium potency

topical corticosteroid)

Apply

once daily

Ointment: 0.7%; increased by

occlusive dressings

Yes

Triamcinolone (Kenalog; Oralone;

Pediaderm TA; Trianex; Triderm;

Zytopic)

Topical aerosol spray: 0.2 mg/

spray (63 g, 100 g)


454 g); 0.1% (15 g, 30 g, 80 g, 85

g, 454 g); 0.5% (15 g)

Topical lotion: 0.025% (60 mL);

0.1% (60 mL); 0.1%


g, 454 g); 0.05% (430 g); 0.1% (15

g, 80 g, 454 g); 0.5% (15 g)

Topical oral paste: 0.1% (5 g)

Oral topical: Adjunctive treatment and

temporary relief of symptoms associated

with oral inflammatory lesions and

ulcerative lesions resulting from trauma

Topical: Inflammatory dermatoses

responsive to steroids

Apply 1-4

times/day

Topical corticosteroids are absorbed

percutaneously. The extent is

dependent on several factors,

including epidermal integrity (intact vs

abraded skin), formulation, and the use

of occlusive dressings.

No: spray

Triamcinolone/nystatin Topical cream: 0.1%/100,000 u (15

g, 30 g, 60 g)

Topical ointment: 0.1%/100,000 u

(15 g, 30 g, 60 g)

Treatment of cutaneous candidiasis Apply 2-4

times/day

Varies Yes

13

Pharmacology/Pharmacokinetics

Corticosteroids regulate the inflammatory process by binding to the

glucocorticoid receptor in the cytosol and translocating to the region of the corticosteroid

responsive element where it either stimulates or inhibits transcription of adjacent genes.3,

4, 7 This gene activity can result in many specific and nonspecific effects, including anti-

inflammatory, antiproliferative, immunosuppressive, and vasoconstrictive effects. More

specifically, corticosteroids exert their anti-inflammatory effects by binding to the

glucocorticoid receptor and inhibiting the release of phospholipase A2, an enzyme

implicated in the formation of leukotrienes, prostaglandins, and other arachidonic acid

pathway derivatives.1, 2

Corticosteroids also regulate the inflammatory process by

inhibiting transcription factors, decreasing the release of interleukin-1 (IL-1), and

preventing phagocytosis.3, 4, 7

In general, corticosteroids have a basic structure with one five-membered ring

attached to three six-membered rings, containing a total of 17 carbon atoms.3, 4, 7

Adding

or altering any of the functional groups can influence anti-inflammatory potency,

mineralocorticoid activity, and adverse effects. For example, fluorinated corticosteroids

tend to have greater genetic activity and demonstrate more potent anti-inflammatory

effects. The development of topical corticosteroids has focused on improving or

optimizing potency while minimizing unwanted atrophic and adrenal suppressive adverse

effects. Some of the newer agents, such as fluticasone or mometasone, retain high anti-

inflammatory activity when applied topically but are quickly broken down into inactive

metabolites in an effort to avoid both local and systemic adverse effects.3, 4, 7

Potency and penetration varies between agents. Factors that influence potency

include the delivery vehicle, the site of application, and whether or not an occlusive

dressing is used.3, 4, 7

See table 3 for a comparison of potency for the topical

corticosteroids. Penetration of topical glucocorticoids varies depending on the thickness

of the stratum corneum and the vascular supply to the area being treated. Penetration of a

topical steroid through an area of thin stratum corneum, like the eyelid and/or scrotum, is

up to 40 times greater than penetration through an area of thick stratum corneum, like the

palms and soles. Penetration is also increased with inflamed and/or moist skin.3, 4

Potent

topical steroids should not be used in the areas with the highest level of penetration, such

as the eyelids.1, 2

Overall, selection of a topical glucocorticoid preparation should be

based on both patient-related and drug-related factors including age of the patient, the

extent and location of the body surface area to be treated and the presence or absence of

skin inflammation.7

Table 3. Potency of Topical Corticosteroid Agents7

Class Agent

Class 1 Very potent Betamethasone dipropionate 0.05%

Clobetasol propionate 0.05%

Diflorasone diacetate 0.05%

Fluocinonide 0.1%

14

Flurandrenolide 4mcg/cm2

Halobetasol propionate 0.05%

Class 2 Potent Amcinonide 0.1%

Desoximetasone 0.25%; 0.05%

Fluocinonide 0.05%

Halcinonide 0.1%

Mometasone furoate 0.1%

Class 3 Upper midstrength Betamethasone valerate 0.1%

Fluticasone propionate 0.005%

Triamcinolone acetonide 0.5%

Class 4 Midstrength Betamethasone valerate 0.12%

Clocortolone pivalate 0.1%

Desoximetasone 0.05%

Fluocinolone acetonide 0.025%

Flurandrenolide 0.05%

Hydrocortisone probutate 0.1%

Hydrocortisone valerate 0.2%

Mometasone furoate 0.1%

Prednicarbate 0.1%


Class 5 Lower midstrength Fluocinolone acetonide 0.01%

Hydrocortisone butyrate 0.1%


Class 6 Mild strength Alclometasone dipropionate 0.05%

Desonide 0.05%

Class 7 Least potent Other topical agents with hydrocortisone

Methods

A literature search was conducted to identify articles addressing each key

question, searching the MEDLINE database (1950 2012), the Cochrane Library, and

reference lists of review articles. For the clinical efficacy section, only clinical trials

published in English and indexed on MEDLINE prior to 10/2012, evaluating efficacy of

the topical corticosteroid agents with reduction of symptoms as the endpoint are included.

Trials evaluating the topical corticosteroid agents as monotherapy or combination therapy

where adjunctive medications remained constant throughout the trial are included. Trials

comparing monotherapy with combination regimens are excluded. The following reports

were excluded (note: some were excluded for more than 1 reason):

Individual clinical trials which evaluated endpoints other than reduction of symptoms,

such as bioequivalence8, patient preference

9, pharmacokinetics

10-12, adherence

13,

delivery vehicles14-16

, vasoconstrictive properties17

, and bioavailability.17-19

15

Individual trials comparing the topical corticosteroid agents where adjunctive

medications were not constant20-29

, in dose-finding or formulation studies18, 19, 30-40

or

in healthy volunteers.41-44

Individual clinical trials evaluating topical corticosteroid agents or formulations not

currently available in the US45-47

or clinical trials without access to the full article.48, 49

Clinical Efficacy

How do the topical corticosteroids compare with each other for reducing anti-

inflammatory symptoms?

Very limited data is available comparing the efficacy of the topical corticosteroid

agents. In a recent publication in the Journal of the American Academy of Dermatology

(2009)50

a number of placebo- or vehicle-controlled trials51-61

were identified and

evaluated for the efficacy of topical corticosteroids in the treatment of psoriasis and

psoriatic arthritis. According to the data, topical corticosteroids are effective in treating

inflammation associated with psoriasis. The evidence, based on double-blind, placebo-

controlled trials, is limited by differences in study design, patient populations, and end

points. Although limited, the authors note, placebo- and vehicle-controlled trials are the

best evidence currently available to evaluate the efficacy of topical corticosteroids. One

meta-analysis27

evaluating placebo-controlled trials is also available for evaluation. The

trials also evaluated corticosteroid efficacy in the treatment of plaque psoriasis.

According to the data, topical corticosteroids are more effective than placebo and very-

potent corticosteroids tended to demonstrate small clinical benefits over potent

corticosteroids.

Two comparative trials62, 63

evaluating the efficacy of betamethasone dipropionate

0.05% lotion compared to clobetasol propionate 0.05% solution are available for

evaluation. Again, the efficacy of the topical corticosteroid agents was evaluated in the

treatment of moderate-to-severe scalp psoriasis. According to the data, the two agents

were equally effective in treatment of disease-related inflammation. Conflicting evidence

suggests betamethasone provides a faster onset of relief than clobetasol while clobetasol

may be associated with few adverse events. Three additional comparative trials are

available for evaluation; however, only the abstracts are available for these trials.

According to limited data gathered from published abstract information, clobetasol

propionate 0.05% cream, halobetasol propionate 0.05% cream, desoximetasone 0.05%

gel and fluocinonide 0.05% gel demonstrate equal efficacy in the treatment of psoriasis.64,

65 Hydrocortisone butyrate 0.1% cream, fluticasone propionate 0.05% cream,

prednicarbate 0.1% cream, and mometasone furoate 0.1% cream are all equally effective

in the treatment of chronic dermatitis.66

Overall, comparative clinical evidence for the topical corticosteroids is limited.

The majority of the evidence evaluates the agents in the treatment of inflammation

associated with psoriasis. The limited data demonstrate comparable clinical efficacy for

the potent and very-potent topical corticosteroid agents in psoriasis. Limited evidence

16

also suggests efficacy for potent and mid-strength topical corticosteroids in the treatment

of inflammation associated with chronic dermatitis. According to both comparative

evidence and clinical experience, topical corticosteroids are useful treatments for

dermatologic conditions and success of treatment can vary depending on an accurate

diagnosis, steroid potency, agent delivery vehicle, frequency of application, duration of

treatment, and adverse effects.7

Are there patient subgroups based on demographics (e.g., age, racial groups,

gender) or comorbidities for which one of the topical corticosteroids is more

effective or associated with fewer adverse effects?

Geriatric Patients

In general, topical corticosteroids are safe and effective in the geriatric population

when a low-potency preparation is used for short periods of time. Elderly patients may

have thin skin, which can lead to increased penetration of topical glucocorticoids and

increase in both systemic and local adverse events. They are also more likely to have

preexisting skin atrophy secondary to aging which can compound the skin atrophy

adverse events seen with chronic topical corticosteroid use.3, 4, 7

Pediatric Patients

In general, topical corticosteroids are safe and effective in children when a low-

potency preparation is used for short periods of time. Children, especially infants, may be

at an increased risk for absorbing topical corticosteroids as they have a higher ratio of

skin surface area to body weight. Other factors that can increase penetration in children

include a reduced ability to metabolize potent glucocorticoids rapidly, thinner skin

(particularly in premature infants), and occlusion of the steroid by a diaper. Excess

penetration of topical corticosteroids can result in an addisonian crisis, growth

retardation, and death.3, 4, 7

Pregnancy

Human studies using topical glucocorticoids in pregnancy are not available. The

majority of topical corticosteroids are rated by the US Food and Drug Administration as

category C drugs in pregnancy, which implies caution should be used.1, 2

Studies in

animals are available and suggest topical steroids are systemically absorbed and may

cause fetal abnormalities. One systematic review of the safety of topical corticosteroids in

pregnancy is available. According to the review, the available evidence is unable to

detect an association between topical corticosteroid use and congenital abnormalities,

preterm delivery, or stillbirth. A small cohort study of participants from a single

maternity center is also available. According to the limited data from the small trial,

17

highly potent corticosteroids may be associated with low birth weight but further

investigation is required.3, 4, 7

Adverse Drug Reactions

How does the safety of the topical corticosteroids compare with each other?

The topical corticosteroids are associated with both local and systemic adverse

events.3, 4, 7

Rate of adverse events tends to increase with increase in potency and duration

of use of the corticosteroid. Local adverse effects are more prevalent than systemic

reactions. Local adverse events result from the antiproliferative effects of these agents

and include: skin atrophy, acneiform reactions (development or exacerbation of

dermatoses), hypertrichosis, pigment changes, exacerbating and/or masking cutaneous

infectious diseases, and allergic reactions.1, 2

Elements found in topical corticosteroids

that may cause an allergic reaction include: propylene glycol, sorbitan sesquioleate,

methylchloroisothiazolinone or methylisothiazolinone, lanolin, parabens, or

formaldehyde releasing preservatives (imidazolidinylurea/diazolidinylurea).3, 4, 7

Usually, up to 99% of the topical corticosteroid is cleared from the skin and only

1% is therapeutically active and only a very small portion of that, if any, is systemically

absorbed.3, 4, 7

Penetration can vary depending on striatum thickness, frequency of

application, and use of an occlusive barrier. Systemic adverse effects that can result from

topical corticosteroid use include: suppression of the hypothalamicpituitaryadrenal axis

(or iatrogenic Cushing syndrome/Addison crisis), development of glaucoma or vision

loss, and metabolic effects (i.e. hyperglycemia, diabetes mellitus, hypokalemia, femoral

avascular necrosis).1, 2

Continued use of topical corticosteroids may also lead to

tachyphylaxis.3, 4, 7

Long-term use of topical steroids should be limited.1, 2

Highly potent formulations

should only be used for two to three weeks or intermittently.3, 4, 7

When disease control is

achieved, a less potent compound should be used and frequency of application should be

reduced. Topical corticosteroids should not be used on ulcerated, atrophic, or infected

skin. Caution should be used when using corticosteroids on certain body areas (e.g.,

intertriginous areas) or in pediatric/geriatric populations. Laboratory tests should be

performed if systemic absorption of corticosteroids is suspected.1-4, 7

Summary

Eighteen topical corticosteroid agents are currently available for use in the United

States and are indicated in the treatment of corticosteroid-responsive inflammation

associated with dermatoses. The topical agents are available as creams, foams, gels,

lotions, ointments, shampoos, solutions and rectal products. Each of the agents has

varying potencies and rates of skin penetration and, subsequently, different clinical uses.

In general, treatment of inflammation associated with skin infections is determined by

18

clinical judgment based upon location of infection, prior treatment, and complicating

conditions (bacterial or fungal growth, age of patient, location of infection).

The comparative clinical evidence available for the topical corticosteroids is

limited. The majority of the evidence evaluates the agents in the treatment of

inflammation associated with psoriasis. The limited data demonstrate comparable clinical

efficacy for the potent and very-potent topical corticosteroid agents in psoriasis. Limited

evidence also suggests efficacy for potent and mid-strength topical corticosteroids in the

treatment of inflammation associated with chronic dermatitis. According to both

comparative evidence and clinical experience, topical corticosteroids are useful

treatments for dermatologic conditions and success of treatment can vary depending on

an accurate diagnosis, steroid potency, agent delivery vehicle, frequency of application,

duration of treatment, and adverse effects.

The topical corticosteroids are associated with both local and systemic adverse

events. Rate of adverse events tends to increase with increase in potency and duration of

use of the corticosteroid. Local adverse effects include: skin atrophy, acneiform reactions,

hypertrichosis, pigment changes, cutaneous infections, and allergic reactions. Systemic

adverse effects include: suppression of the hypothalamicpituitaryadrenal axis, ocular

effects, and metabolic effects. Long-term use of topical steroids should be limited and

highly potent formulations should only be used intermittently. Caution should be used

when using topical corticosteroids in children, the geriatric population, or pregnant

women. Laboratory tests should be performed if systemic absorption of corticosteroids is

suspected.

Overall, selection of a topical glucocorticoid preparation should be based on both

patient-related and drug-related factors including age of the patient, the extent and

location of the body surface area to be treated and the presence or absence of skin

inflammation.

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