Diagnostic and Treatment Options for Psoriasis & Psoriatic Arthritis CME Activity Vital Issues in Medicine
This continuing medical education activity is sponsored by Vital Issues in Medicine and is supported by an educational grant from Abbott Laboratories 1
Learning Objectives Upon completion of this activity, participants should be able to:
•
Recognize the clinical presentation of psoriasis and psoriatic arthritis (PsA) based on signs, symptoms, lab and x-ray findings, and locations on the body
•
Describe different treatment approaches for mild (localized) and moderate/severe psoriasis, as well as barriers to effective treatment
•
Distinguish PsA from rheumatoid arthritis (RA) and osteoarthritis (OA)
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Learning Objectives (cont.) Upon completion of this activity, participants should be able to:
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Identify appropriate biological therapies for patients with psoriatic disease
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Review the safety and efficacy of systemic agents in treatment of psoriasis and PsA
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Review the safety and efficacy of T-cell inhibitors and tumor necrosis factor (TNF-α) antagonists, as well as pros and cons of their use in short- and long-term management of psoriasis and PsA
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Demographics of Psoriasis
• Affects up to 7.5 million people in the U.S. • Mean age of presentation: 28 yrs • 10-15% present during childhood
• 10-30% of cases evolve into psoriatic arthritis (PsA)
• Psoriasis typically precedes PsA • Populations of more severe psoriasis patients have higher prevalence of PsA Helliwell PS, Wright V. Psoriatic arthritis: clinical features. In: Klippel J, Dieppe P, eds. Rheumatology. St. Louis, Mo: Mosby Co; 2000:6.21.21-26.21.28. Gladman DD. Rheum Dis Clin North Am. 1998;24:829-844. Salonen D. Presented at: EADV; 2003. Gelfand JM, et al. J Am Acad Dermatol. 2005;53:573. National Psoriasis Foundation. www.psoriasis.org. Accessed February 22, 2007.
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Pathophysiology of Psoriasis Pathophysiology1,2
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Proliferation of T cells is activated through genetically mediated mechanisms1 ! at least 9 distinct genetic loci identified
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This results in abnormally prolonged immune response in focal epidermal and dermal regions and lymph nodes1
Potential triggers3
• • • •
Emotional stress Injury to skin Some types of infection Reactions to certain drugs (eg, lithium, β-blockers, steroid withdrawal)
1. Mease P. Ann Rheum Dis. 2004;63:755-758. 2. Krueger JG. J Am Acad Dermatol. 2002;46:1-23. 3. National Psoriasis Foundation. www.psoriasis.org. Accessed February 22, 2007. 5
Psoriasis Severity Mild Psoriasis
• • •
Low body surface area (BSA) of involvement Requiring no therapy, or either intermittent topical or local therapies for adequate control and patient satisfaction Minimal impact on quality of life
Moderate to Severe Psoriasis
• • • •
Greater BSA of involvement or Refractory to either topical or local therapies Significant impact on quality of life Requires either phototherapy or systemic therapy (including biologic therapy)
National Psoriasis Foundation. Mease PJ, Gladman DD, Krueger GG. Ann Rheum Dis. 2005;64:ii1-ii2.
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Psoriasis Undertreatment
• Nearly 40% of psoriasis patients receive no treatment
• 73% of patients with moderate psoriasis and 57% of patients with severe psoriasis receive topical treatment only
* Psoriasis severity was assessed using patient-reported affected body surface area (BSA) and was defined as mild (10% BSA) National Psoriasis Foundation. Mease PJ, Gladman DD, Krueger GG. Ann Rheum Dis. 2005;64:ii1-ii2.
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Diagnosis of Psoriasis
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Examination and Assessment
• Conduct history and full skin examination and
determine if mild or moderate to severe disease
• Assess joint involvement • Devise plans for therapeutic intervention and patient education (including advocacy for drug access, if necessary)
• Consider need for consultation National Psoriasis Foundation. Facts: Psoriasis. Available at: http://www.psoriasis.org/facts/psoriasis. Accessed February 16, 2007.
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Important Aspects of Patient History • • • • •
Determine family history of psoriasis or PsA Age of onset of first lesion or joint disease Perceived severity Previous therapies and responses Triggers (eg, streptococcal infection, drugs, stress)
•
Comorbidities (eg, obesity, dyslipidemia, hypertension, insulin resistance)
•
Rule out subtle psoriasis in patients with inflammatory arthritis devoid of skin findings 10
Subtypes of Psoriasis • • • • • •
Plaque psoriasis ! ~80-90% of cases; well-demarcated, indurated, erythematous lesions covered by silvery white scale; often pruritic and bleeds Inverse ! lesions are inflamed and located in the axillae, groin, inframammary areas, gluteal cleft, and skin folds; typically lacks the scale seen in plaque psoriasis Pustular ! pus-filled vesicles surrounded by erythema; may solely exist on the hands and/or feet; can be localized or generalized Guttate ! discrete, small erythematous papules diffusely distributed on the trunk and extremities; usually post-infection Erythrodermic ! severe erythema involving a majority of the body surface area; less scale than plaque type psoriasis Palmo-plantar psoriasis ! psoriasis limited to the hands and feet, without pustules
National Psoriasis Foundation. Facts: Psoriasis. Available at: http://www.psoriasis.org/facts/ psoriasis. Accessed February 16, 2007. Griffiths CE, Christophers E, Barker JN, et al. Br J Dermatol. 2007;156:258-262.
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Psoriasis Cutaneous Features
Chronic plaque psoriasis
Guttate
Scalp
Palmo-plantar plaque psoriasis 12
Psoriasis Cutaneous Features (cont.)
Inverse Psoriasis
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Psoriasis Cutaneous Features (cont.)
Pustular psoriasis 14
Psoriasis of the Nails
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Treatment of Psoriasis
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Major Treatment Approaches Topical treatments
• • • • • •
Corticosteroids Vitamin D analogs Retinoids Tar Anthralin Calcineurin inhibitors
American Academy of Dermatology. Available at http://www.aad.org. Accessed February 23, 2007. National Psoriasis Foundation. Available at: http://www.psoriasis.org/facts/psoriasis. Accessed February 16, 2007. Lebwohl M, Freeman AK, Chapman MS, et al. J Am Acad Dermatol. 2004;141:1152-1153. Gribetz C, Ling M. Lebwohl M, Pariser D, et al. J Am Acad Dermatol. 2004;51:731-738.
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Major Treatment Approaches (cont.) Systemic Therapies
• • • • •
Oral retinoids (eg, acitretin) Cyclosporine Methotrexate (MTX) TNF-α inhibiting biologic T-cell inhibiting biologic
American Academy of Dermatology. Available at http://www.aad.org. Accessed February 23, 2007. National Psoriasis Foundation. Available at: http://www.psoriasis.org/facts/psoriasis. Accessed February 16, 2007.
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Major Treatment Approaches (cont.) Phototherapy
• • • •
Psoralen UVA (PUVA) Broadband UVB Narrowband UVB 308-nm Excimer Laser
American Academy of Dermatology. Available at http://www.aad.org. Accessed February 23, 2007. National Psoriasis Foundation. Available at: http://www.psoriasis.org/facts/psoriasis. Accessed February 16, 2007.
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Non-Biologics Modalities Conventional systemic drugs
•
Advantages
• • • •
•
Extensive experience over many years of use Effective in many patients Well-defined adverse event profile Lower cost
Disadvantages
•
Potentially serious adverse effects:
• Methotrexate: hepatotoxicity and bone marrow suppression, • •
• •
pulmonary toxicity, teratogenic Cyclosporine: renal toxicity and hypertension Acitretin: teratogenic, lipid abnormalities and rare liver toxicity
More fastidious monitoring requirements Numerous drug/drug interactions
Krueger JG. J Am Acad Dermatol. 2002;46:1-23.
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Non-Biologics Modalities (cont.) Ultraviolet Phototherapy
•
Advantages
• • • •
•
Extensive experience over many years of use Effective for many patients Minimal adverse event profile No systemic toxicity (UVB)
Disadvantages
•
Requires patients to travel to physician's office 2-3 times weekly
• •
Cost of multiple weekly co-pays Potential long-term negative effects of UV exposure ! skin cancer 21
Biologic Agents
• Adalimumab* • Alefacept • Efalizumab • Etanercept • Infliximab *Not FDA-approved for the treatment of psoriasis; filed April 2007. Graves JE, Nunley K, Heffernan MP, et al. J Am Acad Dermatol. 2007;56:e55-79.
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T-cell Inhibitors: MOA
• Alefacept and Efalizumab •
Inhibit co-stimulatory signals between antigenpresenting cells and T cells
•
Additional potential mechanisms of action:
• Alefacept ! induction of apoptosis of memory effector T cells
• Efalizumab ! interferes with ability of lymphocytes to leave blood vessels and enter tissues
Mease P. Bull Hosp Jt Dis. 2006;64(1-2):25-31.
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TNF-α Inhibitors: MOA
• Adalimumab, Etanercept, Infliximab •
Bind to and inhibit TNF-α and therefore multiple key steps in psoriatic pathophysiology
•
Effectively treat both skin and joint disease
• •
Comparable efficacy in psoriatic arthritis Varying efficacy in psoriasis may be related to pharmacokinetic differences
Mease P. Bull Hosp Jt Dis. 2006;64(1-2):25-31.
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Treatment with Biologics • •
Biologics possibly offer safer, more effective long-term management than non-biologics Determine proper candidates based on:
• Severity of psoriasis • Presence and severity of psoriatic arthritis • Medical history (comorbidities, pregnancy, etc.) • Response to other therapies (topicals, conventional systemics, ultraviolet phototherapy) • Patient’s tolerance of risk and route of administration • Access to medications (ie, insurance coverage)
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Typical Biologic Dosing Regimens •
Adalimumab—40 mg every other week, administered subcutaneously
•
Alefacept—course of 12 weekly 15-mg IM injections; ≥12 week hiatus between courses
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Efalizumab—following an initial dose of 0.7 mg/kg, 1 mg/kg subcutaneously every week
•
Etanercept
•
•
Psoriasis: 50 mg once weekly, after an initial 3 months of 50 mg twice weekly
•
PsA: 50 mg once weekly
Infliximab—5 mg/kg IV infusion at baseline, week 2, and week 6, and every 8 weeks thereafter; more frequent dosing and higher doses may be necessary
Graves JE, Nunley K, Heffernan MP, et al. J Am Acad Dermatol. 2007;56:e55-79.
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Efficacy Data for Biologics in Treatment of Psoriasis
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Psoriasis Area and Severity Index (PASI) Score Calculation Region
Involvement*
Area
Severity† Redness
Thickness
Scale
0.1
x
3
x
2
0
1
(0.9)
0.2
x
3
x
2
1
2
(3.0)
0.3
x
2
x
2
2
2
(3.6)
0.4
x
3
x
3
2
3
(9.6)
*0
1.0
= None 1 =
