dermatologic and ophthalmic drugs advisory committee july 12, 2004 1 introduction to psoriasis...
Post on 23-Dec-2015
216 Views
Preview:
TRANSCRIPT
1Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Introduction to PsoriasisIntroduction to PsoriasisIntroduction to PsoriasisIntroduction to Psoriasis
Denise Cook, M.D.Medical Officer
Division of Dermatology and Dental Drug Products
Denise Cook, M.D.Medical Officer
Division of Dermatology and Dental Drug Products
2Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Introduction to PsoriasisIntroduction to PsoriasisIntroduction to PsoriasisIntroduction to Psoriasis
• Prevalence• Genetics and Pathogenesis• Clinical Variants of Psoriasis• State of the Armamentarium
• Prevalence• Genetics and Pathogenesis• Clinical Variants of Psoriasis• State of the Armamentarium
3Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
PrevalencePrevalencePrevalencePrevalence
• Psoriasis occurs in 2% of the world’s population
• Prevalence in the U.S may be as high as 4.6%
• Highest in Caucasians• In Africans, African Americans and
Asians between 0.4% and 0.7%
• Psoriasis occurs in 2% of the world’s population
• Prevalence in the U.S may be as high as 4.6%
• Highest in Caucasians• In Africans, African Americans and
Asians between 0.4% and 0.7%
4Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
PrevalencePrevalencePrevalencePrevalence
• Equal frequency in males and females
• May occur at any age from infancy to the 10th decade of life
• First signs of psoriasis–Females mean age of 27 years–Males mean age of 29 years
• Equal frequency in males and females
• May occur at any age from infancy to the 10th decade of life
• First signs of psoriasis–Females mean age of 27 years–Males mean age of 29 years
5Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
PrevalencePrevalencePrevalencePrevalence
• Two Peaks of Occurrence–One at 20-30 years–One at 50-60 years
• Psoriasis in children–Low – between 0.5 and 1.1% in
children 16 years old and younger–Mean age of onset - between 8 and
12.5 years
• Two Peaks of Occurrence–One at 20-30 years–One at 50-60 years
• Psoriasis in children–Low – between 0.5 and 1.1% in
children 16 years old and younger–Mean age of onset - between 8 and
12.5 years
6Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
PrevalencePrevalencePrevalencePrevalence
• Two-thirds of patients have mild disease• One-third have moderate to severe disease• Early onset (prior to age 15)– Associated with more severe disease– More likely to have a positive family history
• Life-long disease– Remitting and relapsing unpredictably– Spontaneous remissions of up to 5 years have
been reported in approximately 5% of patients
• Two-thirds of patients have mild disease• One-third have moderate to severe disease• Early onset (prior to age 15)– Associated with more severe disease– More likely to have a positive family history
• Life-long disease– Remitting and relapsing unpredictably– Spontaneous remissions of up to 5 years have
been reported in approximately 5% of patients
7Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Genetics and PathogenesisGenetics and PathogenesisGenetics and PathogenesisGenetics and Pathogenesis
• Psoriasis and the Immune System– The major histocompatibility complex
(MHC)• Short arm of chromosome 6
– Histocompatibility Antigens (HLA)• HLA-Cw6• HLA-B13, -B17, -B37, -Bw16
– T-lymphocyte-mediated mechanism
• Psoriasis and the Immune System– The major histocompatibility complex
(MHC)• Short arm of chromosome 6
– Histocompatibility Antigens (HLA)• HLA-Cw6• HLA-B13, -B17, -B37, -Bw16
– T-lymphocyte-mediated mechanism
8Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Psoriasis as a Systemic DiseasePsoriasis as a Systemic DiseasePsoriasis as a Systemic DiseasePsoriasis as a Systemic Disease
• Koebner Phenomenon• Elevated ESR• Increased uric acid levels → gout• Mild anemia• Elevated α2-macroglobulin• Elevated IgA levels • Increased quantities of Immune
Complexes
• Koebner Phenomenon• Elevated ESR• Increased uric acid levels → gout• Mild anemia• Elevated α2-macroglobulin• Elevated IgA levels • Increased quantities of Immune
Complexes
9Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Psoriasis as a Systemic DiseasePsoriasis as a Systemic DiseasePsoriasis as a Systemic DiseasePsoriasis as a Systemic Disease
• Psoriatic arthropathy• Aggravation of psoriasis by systemic
factors–Medication–Focal infections–Stress
• Life-threatening forms of psoriasis
• Psoriatic arthropathy• Aggravation of psoriasis by systemic
factors–Medication–Focal infections–Stress
• Life-threatening forms of psoriasis
10Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Clinical Variants of PsoriasisClinical Variants of PsoriasisClinical Variants of PsoriasisClinical Variants of Psoriasis
11Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Characteristic Lesion of PsoriasisCharacteristic Lesion of PsoriasisCharacteristic Lesion of PsoriasisCharacteristic Lesion of Psoriasis
• Sharply demarcated erythematous plaque with micaceous silvery white scale
• Histopathology–Thickening of the epidermis–Tortuous and dilated blood vessels– Inflammatory infiltrate primarily of
lymphocytes
• Sharply demarcated erythematous plaque with micaceous silvery white scale
• Histopathology–Thickening of the epidermis–Tortuous and dilated blood vessels– Inflammatory infiltrate primarily of
lymphocytes
12Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Psoriatic PlaquePsoriatic PlaquePsoriatic PlaquePsoriatic Plaque
13Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Severity of DiseaseSeverity of DiseaseSeverity of DiseaseSeverity of Disease
• Three Cardinal Signs of Psoriatic Lesions–Plaque elevation–Erythema–Scale
• Body Surface Area
• Three Cardinal Signs of Psoriatic Lesions–Plaque elevation–Erythema–Scale
• Body Surface Area
14Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Chronic Plaque PsoriasisChronic Plaque PsoriasisChronic Plaque PsoriasisChronic Plaque Psoriasis
• Most Common Variant• Plaques may be as large as 20 cm• Symmetrical disease• Sites of Predilection– Elbows– Knees– Presacrum– Scalp– Hands and Feet
• Most Common Variant• Plaques may be as large as 20 cm• Symmetrical disease• Sites of Predilection– Elbows– Knees– Presacrum– Scalp– Hands and Feet
15Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Chronic Plaque PsoriasisChronic Plaque PsoriasisChronic Plaque PsoriasisChronic Plaque Psoriasis
16Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Chronic Plaque PsoriasisChronic Plaque PsoriasisChronic Plaque PsoriasisChronic Plaque Psoriasis
17Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Chronic Plaque PsoriasisChronic Plaque PsoriasisChronic Plaque PsoriasisChronic Plaque Psoriasis
• May be widespread – up to 90% BSA• Genitalia involved in up to 30% of patients• Most patients have nail changes– Nail pitting– “Oil Spots”– Involvement of the entire nail bed• Onychodystrophy• Loss of nail plate
• May be widespread – up to 90% BSA• Genitalia involved in up to 30% of patients• Most patients have nail changes– Nail pitting– “Oil Spots”– Involvement of the entire nail bed• Onychodystrophy• Loss of nail plate
18Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Widespread Chronic Plaque Widespread Chronic Plaque PsoriasisPsoriasis
Widespread Chronic Plaque Widespread Chronic Plaque PsoriasisPsoriasis
19Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Chronic PsoriasisChronic PsoriasisChronic PsoriasisChronic Psoriasis
20Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Psoriasis of the NailPsoriasis of the NailPsoriasis of the NailPsoriasis of the Nail
21Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Psoriasis of the NailPsoriasis of the NailPsoriasis of the NailPsoriasis of the Nail
22Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Symptoms of Chronic Plaque Symptoms of Chronic Plaque PsoriasisPsoriasis
Symptoms of Chronic Plaque Symptoms of Chronic Plaque PsoriasisPsoriasis
• Pruritus• Pain• Excessive heat loss• Patient Complaints–Unsightliness of the lesions–Low self-esteem–Feelings of being socially outcast–Excessive scale
• Pruritus• Pain• Excessive heat loss• Patient Complaints–Unsightliness of the lesions–Low self-esteem–Feelings of being socially outcast–Excessive scale
23Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Guttate PsoriasisGuttate PsoriasisGuttate PsoriasisGuttate Psoriasis
• Characterized by numerous 0.5 to 1.5 cm papules and plaques
• Early age of onset• Most common form in children• Streptococcal throat infection often a
trigger• Spontaneous remissions in children• Often chronic in adults
• Characterized by numerous 0.5 to 1.5 cm papules and plaques
• Early age of onset• Most common form in children• Streptococcal throat infection often a
trigger• Spontaneous remissions in children• Often chronic in adults
24Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Guttate PsoriasisGuttate PsoriasisGuttate PsoriasisGuttate Psoriasis
25Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Life–Threatening Forms of Life–Threatening Forms of PsoriasisPsoriasis
Life–Threatening Forms of Life–Threatening Forms of PsoriasisPsoriasis
• Generalized Pustular Psoriasis• Erythrodermic Psoriasis• Generalized Pustular Psoriasis• Erythrodermic Psoriasis
26Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Generalized Pustular PsoriasisGeneralized Pustular PsoriasisGeneralized Pustular PsoriasisGeneralized Pustular Psoriasis
• Unusual manifestation of psoriasis• Can have a gradual or an acute onset• Characterized by waves of pustules on
erythematous skin often after short episodes of fever of 39˚ to 40˚C
• Weight loss• Muscle Weakness• Hypocalcemia• Leukocytosis• Elevated ESR
• Unusual manifestation of psoriasis• Can have a gradual or an acute onset• Characterized by waves of pustules on
erythematous skin often after short episodes of fever of 39˚ to 40˚C
• Weight loss• Muscle Weakness• Hypocalcemia• Leukocytosis• Elevated ESR
27Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Generalized Pustular PsoriasisGeneralized Pustular PsoriasisGeneralized Pustular PsoriasisGeneralized Pustular Psoriasis
• Cause is obscure• Triggering Factors– Infection– Pregnancy– Lithium– Hypocalcemia secondary to
hypoalbuminemia– Irritant contact dermatitis–Withdrawal of glucocorticosteroids,
primarily systemic
• Cause is obscure• Triggering Factors– Infection– Pregnancy– Lithium– Hypocalcemia secondary to
hypoalbuminemia– Irritant contact dermatitis–Withdrawal of glucocorticosteroids,
primarily systemic
28Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Generalized Pustular PsoriasisGeneralized Pustular PsoriasisGeneralized Pustular PsoriasisGeneralized Pustular Psoriasis
29Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Erythrodermic PsoriasisErythrodermic PsoriasisErythrodermic PsoriasisErythrodermic Psoriasis
• Classic lesion is lost• Entire skin surface becomes
markedly erythematous with desquamative scaling.
• Often only clues to underlying psoriasis are the nail changes and usually facial sparing
• Classic lesion is lost• Entire skin surface becomes
markedly erythematous with desquamative scaling.
• Often only clues to underlying psoriasis are the nail changes and usually facial sparing
30Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Erythrodermic PsoriasisErythrodermic PsoriasisErythrodermic PsoriasisErythrodermic Psoriasis
• Triggering Factors–Systemic Infection–Withdrawal of high potency topical
or oral steroids–Withdrawal of Methotrexate–Phototoxicity– Irritant contact dermatitis
• Triggering Factors–Systemic Infection–Withdrawal of high potency topical
or oral steroids–Withdrawal of Methotrexate–Phototoxicity– Irritant contact dermatitis
31Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Erythrodermic PsoriasisErythrodermic PsoriasisErythrodermic PsoriasisErythrodermic Psoriasis
32Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
State of the ArmamentariumState of the ArmamentariumState of the ArmamentariumState of the Armamentarium
• Wide range of therapies for the treatment of moderate to severe psoriasis
• None induce a permanent remission• All have side effects that can place
limits on their use
• Wide range of therapies for the treatment of moderate to severe psoriasis
• None induce a permanent remission• All have side effects that can place
limits on their use
33Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
State of the ArmamentariumState of the ArmamentariumState of the ArmamentariumState of the Armamentarium
• Therapies–Topical Corticosteroids–Topical Vitamin D3 Analogues–Topical Retinoids–Photo(chemo)therapy–Systemic Therapies•Oral• Parenteral
• Therapies–Topical Corticosteroids–Topical Vitamin D3 Analogues–Topical Retinoids–Photo(chemo)therapy–Systemic Therapies•Oral• Parenteral
34Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Topical CorticosteroidsTopical CorticosteroidsTopical CorticosteroidsTopical Corticosteroids
• High potency and Super potent topical steroids
• These include– Fluocinonide family (cream, ointment,
gel)– Betamethasone dipropionate cream– Clobetasol propionate family (cream,
ointment, gel, foam, lotion)– Diflorasone diacetate ointment– Betamethasone dipropionate ointment
• High potency and Super potent topical steroids
• These include– Fluocinonide family (cream, ointment,
gel)– Betamethasone dipropionate cream– Clobetasol propionate family (cream,
ointment, gel, foam, lotion)– Diflorasone diacetate ointment– Betamethasone dipropionate ointment
35Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Topical CorticosteroidsTopical CorticosteroidsTopical CorticosteroidsTopical Corticosteroids
• Side effects associated with use–Skin atrophy–Burning and stinging–Suppression of the hypothalamic-
pituitary-adrenal (HPA) axis• This may occur after 2 weeks of
use with certain topical corticosteroids
• Side effects associated with use–Skin atrophy–Burning and stinging–Suppression of the hypothalamic-
pituitary-adrenal (HPA) axis• This may occur after 2 weeks of
use with certain topical corticosteroids
36Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Topical Vitamin DTopical Vitamin D33 Analogues AnaloguesTopical Vitamin DTopical Vitamin D33 Analogues Analogues
• Prototype for this group is calcipotriene
• 3 formulations – cream, ointment, and scalp solution
• Former two are approved for plaque psoriasis
• Latter for moderate to severe psoriasis of the scalp
• Prototype for this group is calcipotriene
• 3 formulations – cream, ointment, and scalp solution
• Former two are approved for plaque psoriasis
• Latter for moderate to severe psoriasis of the scalp
37Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Topical Vitamin DTopical Vitamin D33 Analogues AnaloguesTopical Vitamin DTopical Vitamin D33 Analogues Analogues
• Side Effects–Cutaneous•Burning• Stinging• Pruritus• Skin irritation• Tingling of the skin
• Side Effects–Cutaneous•Burning• Stinging• Pruritus• Skin irritation• Tingling of the skin
38Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Topical RetinoidsTopical RetinoidsTopical RetinoidsTopical Retinoids
• Tazarotene Gel and Cream– Available in two strengths• 0.05% and 0.1%
– Side Effects • Pruritus• Burning/Stinging• Erythema• Worsening of psoriasis• Irritation• Skin pain• Hypertriglyceridemia
• Tazarotene Gel and Cream– Available in two strengths• 0.05% and 0.1%
– Side Effects • Pruritus• Burning/Stinging• Erythema• Worsening of psoriasis• Irritation• Skin pain• Hypertriglyceridemia
39Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Topical Tazarotene Topical Tazarotene Topical Tazarotene Topical Tazarotene
• Additional Indications– 0.1% gel - approved for the treatment of
facial acne vulgaris of mild to moderate severity
– 0.1% cream approved as an adjunctive agent for use in the mitigation of facial fine wrinkling, facial mottled hyper- and hypopigmentation, and benign facial lentigines in patients who use comprehensive skin care and sunlight avoidance programs
• Additional Indications– 0.1% gel - approved for the treatment of
facial acne vulgaris of mild to moderate severity
– 0.1% cream approved as an adjunctive agent for use in the mitigation of facial fine wrinkling, facial mottled hyper- and hypopigmentation, and benign facial lentigines in patients who use comprehensive skin care and sunlight avoidance programs
40Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Topical Tazarotene (con’t)Topical Tazarotene (con’t)Topical Tazarotene (con’t)Topical Tazarotene (con’t)
• Both products are pregnancy category X • Are contraindicated in women who are or
may become pregnant• Requirements before and during therapy– A negative pregnancy test 2 weeks prior– Therapy initiated during a normal
menses–Women of childbearing potential should
use adequate birth control
• Both products are pregnancy category X • Are contraindicated in women who are or
may become pregnant• Requirements before and during therapy– A negative pregnancy test 2 weeks prior– Therapy initiated during a normal
menses–Women of childbearing potential should
use adequate birth control
41Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Photo(chemo)therapyPhoto(chemo)therapyPhoto(chemo)therapyPhoto(chemo)therapy
• Two types of phototherapy–Ultraviolet B (UVB)–Ultraviolet A + psoralen (PUVA)
• Two types of phototherapy–Ultraviolet B (UVB)–Ultraviolet A + psoralen (PUVA)
42Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
UVBUVBUVBUVB
• Two types–Broadband UVB–Narrowband UVB (311-313 nm)
• Treatment is time consuming–2-3 visits/week for several months
• Side effect – possibility of experiencing an acute sunburn reaction
• Two types–Broadband UVB–Narrowband UVB (311-313 nm)
• Treatment is time consuming–2-3 visits/week for several months
• Side effect – possibility of experiencing an acute sunburn reaction
43Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
PUVAPUVAPUVAPUVA
• Consists of ingestion of or topical treatment with a psoralen followed by UVA
• Usually reserved for severe, recalcitrant, disabling psoriasis
• Time consuming – 2-3 visits/wk; at least 6 weeks• Precautions– Patients must be protected from further UV
light for 24 hours post treatment– With oral psoralen, wrap around UV-blocking
glasses must be worn for 24 hours post treatment
• Consists of ingestion of or topical treatment with a psoralen followed by UVA
• Usually reserved for severe, recalcitrant, disabling psoriasis
• Time consuming – 2-3 visits/wk; at least 6 weeks• Precautions– Patients must be protected from further UV
light for 24 hours post treatment– With oral psoralen, wrap around UV-blocking
glasses must be worn for 24 hours post treatment
44Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
PUVAPUVAPUVAPUVA
• Side effects with oral psoralen– Nausea– Dizziness– Headache
• Side effects with PUVA– Early• Pruritus
– Late• Skin damage• Increased risk for skin cancer, particularly
squamous cell (SCC) and after 200 - 250 treatments, increased risk for melanoma
• Side effects with oral psoralen– Nausea– Dizziness– Headache
• Side effects with PUVA– Early• Pruritus
– Late• Skin damage• Increased risk for skin cancer, particularly
squamous cell (SCC) and after 200 - 250 treatments, increased risk for melanoma
45Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Contraindications to PUVAContraindications to PUVAContraindications to PUVAContraindications to PUVA
• Patients less than 12 years of age• Patients with a history of light
sensitive disease states• Patients with, or with a history of
melanoma• Patients with invasive SCC• Patients with aphakia
• Patients less than 12 years of age• Patients with a history of light
sensitive disease states• Patients with, or with a history of
melanoma• Patients with invasive SCC• Patients with aphakia
46Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Systemic TherapiesSystemic TherapiesSystemic TherapiesSystemic Therapies
• Oral–Methotrexate –Neoral (cyclosporine)–Soriatane (acitretin)
• Parenteral–Amevive (alefacept)–Raptiva (efalizimab)–Enbrel (etanercept)
• Oral–Methotrexate –Neoral (cyclosporine)–Soriatane (acitretin)
• Parenteral–Amevive (alefacept)–Raptiva (efalizimab)–Enbrel (etanercept)
47Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
MethotrexateMethotrexateMethotrexateMethotrexate
• Folic acid antagonist• Usually reserved for severe,
recalcitrant, disabling psoriasis• Maximum improvement can be
expected after 8 -12 weeks
• Folic acid antagonist• Usually reserved for severe,
recalcitrant, disabling psoriasis• Maximum improvement can be
expected after 8 -12 weeks
48Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Contraindications - MethotrexateContraindications - MethotrexateContraindications - MethotrexateContraindications - Methotrexate
• Nursing mothers• Patients with alcoholism• Alcoholic liver disease• Other chronic liver disease• Patients with overt or laboratory evidence
of immunodeficiency syndromes• Patients who have preexisting blood
dyscrasias
• Nursing mothers• Patients with alcoholism• Alcoholic liver disease• Other chronic liver disease• Patients with overt or laboratory evidence
of immunodeficiency syndromes• Patients who have preexisting blood
dyscrasias
49Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
MethotrexateMethotrexateMethotrexateMethotrexate
• Pregnancy Category X drug product– Contraindicated in pregnant women
with psoriasis– Pregnancy must be excluded in women
of childbearing potential– Pregnancy should be avoided if either
partner is receiving MTX during and for a minimum of 3 months after therapy for male patients and for at least one ovulatory cycle after therapy for female patients
• Pregnancy Category X drug product– Contraindicated in pregnant women
with psoriasis– Pregnancy must be excluded in women
of childbearing potential– Pregnancy should be avoided if either
partner is receiving MTX during and for a minimum of 3 months after therapy for male patients and for at least one ovulatory cycle after therapy for female patients
50Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Methotrexate – Side EffectsMethotrexate – Side EffectsMethotrexate – Side EffectsMethotrexate – Side Effects
• Acute or chronic hepatotoxicity• Hepatic cirrhosis• Leukopenia• Thrombocytopenia• Anemia, including aplastic anemia• Rarely, interstitial pneumonitis• Stomatitis• Nausea/vomiting• Alopecia• Photosensitivity• Burning of skin lesions
• Acute or chronic hepatotoxicity• Hepatic cirrhosis• Leukopenia• Thrombocytopenia• Anemia, including aplastic anemia• Rarely, interstitial pneumonitis• Stomatitis• Nausea/vomiting• Alopecia• Photosensitivity• Burning of skin lesions
51Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
MethotrexateMethotrexateMethotrexateMethotrexate
• Multiple prescreening tests necessary• Recommendations for hepatic monitoring– Periodic LFTs including serum albumin– Liver biopsy• Pretherapy or shortly thereafter• Cumulative dose of 1.5 grams• After each additional 1.0 to 1.5 grams
• Multiple prescreening tests necessary• Recommendations for hepatic monitoring– Periodic LFTs including serum albumin– Liver biopsy• Pretherapy or shortly thereafter• Cumulative dose of 1.5 grams• After each additional 1.0 to 1.5 grams
52Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
NeoralNeoralNeoralNeoral
• Potent Immunosuppressive• Adult, non-immunocompromised
patients with severe, recalcitrant plaque psoriasis
• Maximum efficacy achieved at 16 weeks of therapy
• Potent Immunosuppressive• Adult, non-immunocompromised
patients with severe, recalcitrant plaque psoriasis
• Maximum efficacy achieved at 16 weeks of therapy
53Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Contraindications - NeoralContraindications - NeoralContraindications - NeoralContraindications - Neoral
• Concomitant PUVA or UVB therapy• Methotrexate or other immunosuppressive
agents• Coal tar or radiation therapy• Patients with abnormal renal function• Patients with uncontrolled hypertension• Patients with malignancies• Nursing mothers
• Concomitant PUVA or UVB therapy• Methotrexate or other immunosuppressive
agents• Coal tar or radiation therapy• Patients with abnormal renal function• Patients with uncontrolled hypertension• Patients with malignancies• Nursing mothers
54Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Neoral – Side EffectsNeoral – Side EffectsNeoral – Side EffectsNeoral – Side Effects
• Possibility of Irreversible renal damage• Hypertension• Headache• Hypertriglyceridemia• Hirsutism/hypertrichosis• Paresthesia/hyperesthesia• Influenza-like symptoms• Nausea/vomiting• Diarrhea• Lethargy• Arthralgia
• Possibility of Irreversible renal damage• Hypertension• Headache• Hypertriglyceridemia• Hirsutism/hypertrichosis• Paresthesia/hyperesthesia• Influenza-like symptoms• Nausea/vomiting• Diarrhea• Lethargy• Arthralgia
55Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
NeoralNeoralNeoralNeoral
• Multiple prescreening tests are required
• Tests must continue throughout treatment with dosage adjustment as necessary to prevent end-organ damage
• Multiple prescreening tests are required
• Tests must continue throughout treatment with dosage adjustment as necessary to prevent end-organ damage
56Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
SoriataneSoriataneSoriataneSoriatane
• Oral retinoid approved for the treatment of severe psoriasis in adults
• Significant improvement can be achieved with 8 weeks of therapy
• Oral retinoid approved for the treatment of severe psoriasis in adults
• Significant improvement can be achieved with 8 weeks of therapy
57Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Soriatane - ContraindicationsSoriatane - ContraindicationsSoriatane - ContraindicationsSoriatane - Contraindications
• Patients with severely impaired liver or kidney function
• Patients with chronic abnormally elevated blood lipid values
• Patients who are taking methotrexate• Ethanol use when on therapy and for
2 months following therapy in female patients
• Patients with severely impaired liver or kidney function
• Patients with chronic abnormally elevated blood lipid values
• Patients who are taking methotrexate• Ethanol use when on therapy and for
2 months following therapy in female patients
58Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
SoriataneSoriataneSoriataneSoriatane
• Pregnancy Category X drug product as it is a human teratogen
• Contraindicated in pregnant females or those who intend to become pregnant during therapy or any time up to three years post therapy
• Pregnancy Category X drug product as it is a human teratogen
• Contraindicated in pregnant females or those who intend to become pregnant during therapy or any time up to three years post therapy
59Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Soriatane – Side EffectsSoriatane – Side EffectsSoriatane – Side EffectsSoriatane – Side Effects
• Those associated with retinoid therapy– Cheilitis– Alopecia– Skin peeling– Dry skin– Pruritus– Rhinitis– Xeropthalmia– Arthralgia
• Those associated with retinoid therapy– Cheilitis– Alopecia– Skin peeling– Dry skin– Pruritus– Rhinitis– Xeropthalmia– Arthralgia
60Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Soriatane – Side EffectsSoriatane – Side EffectsSoriatane – Side EffectsSoriatane – Side Effects
• Laboratory Abnormalities– Hypertriglyceridemia (66%)– Decreased HDL (40%)– Hypercholesterolemia (33%)– Elevated liver function tests (33%)– Elevated alkaline phosphatase (10-25%)– Hyperglycemia (10-25%)– Elevated CPK (10-25%)
• Hepatitis and jaundice occurred in < 1% of patients in clinical trials on Soriatane
• Laboratory Abnormalities– Hypertriglyceridemia (66%)– Decreased HDL (40%)– Hypercholesterolemia (33%)– Elevated liver function tests (33%)– Elevated alkaline phosphatase (10-25%)– Hyperglycemia (10-25%)– Elevated CPK (10-25%)
• Hepatitis and jaundice occurred in < 1% of patients in clinical trials on Soriatane
61Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
SoriataneSoriataneSoriataneSoriatane
• Multiple prescreening tests must be obtained
• Continued monitoring throughout therapy necessary with possible dosage adjustment
• Multiple prescreening tests must be obtained
• Continued monitoring throughout therapy necessary with possible dosage adjustment
62Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Parenteral TherapyParenteral TherapyAmeviveAmevive
Parenteral TherapyParenteral TherapyAmeviveAmevive
• Immunosuppressive dimeric fusion protein–Extracellular CD2-binding portion
of the human leukocyte function antigen-3 (LFA-3)–Linked to the Fc portion of human
IgG1
• Immunosuppressive dimeric fusion protein–Extracellular CD2-binding portion
of the human leukocyte function antigen-3 (LFA-3)–Linked to the Fc portion of human
IgG1
63Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
AmeviveAmeviveAmeviveAmevive
• Indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis
• With 12 weeks of therapy, a disease state of clear or almost clear was achieved by 11% (via IV) and 14% (via IM) of patients, respectively
• Indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis
• With 12 weeks of therapy, a disease state of clear or almost clear was achieved by 11% (via IV) and 14% (via IM) of patients, respectively
64Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Amevive – Side EffectsAmevive – Side EffectsAmevive – Side EffectsAmevive – Side Effects
• Dose dependent reduction in circulating CD4+ and CD8+ T lymphocytes–Should not be administered to
patients with low CD4+ counts–CD4+ counts must be monitored
before and weekly throughout therapy
• Dose dependent reduction in circulating CD4+ and CD8+ T lymphocytes–Should not be administered to
patients with low CD4+ counts–CD4+ counts must be monitored
before and weekly throughout therapy
65Dermatologic and Ophthalmic Drugs Advisory Committee Dermatologic and Ophthalmic Drugs Advisory Committee July 12, 2004July 12, 2004
Amevive – Side EffectsAmevive – Side EffectsAmevive – Side EffectsAmevive – Side Effects
• Lymphopenia• Increase risk of malignancies– Skin cancer – BCC and SCC– Lymphoma
• Serious infections requiring hospitalization
• Risk of reactivation of chronic, latent infections
• Hypersensitivity reactions
• Lymphopenia• Increase risk of malignancies– Skin cancer – BCC and SCC– Lymphoma
• Serious infections requiring hospitalization
• Risk of reactivation of chronic, latent infections
• Hypersensitivity reactions
top related