This is the current release of the guideline.

Level of evidence grades (I-III) and strength of recommendations (A-C) are defined at the end of the "Major Recommendations" field.

General Recommendations for the Treatment of Psoriasis

Topical treatments are appropriate for patients who are candidates for localized therapy but may not be practical as monotherapy for most patients who are candidates for systemic and/or phototherapy (Pariser et al., 2007), where traditional systemic treatments, including methotrexate, cyclosporine (CyA), narrowband (NB) and broadband ultraviolet light B (UVB), psoralen plus ultraviolet A (PUVA), oral retinoids, and the newer biologic agents are prescribed.

1. UVB is safe, effective, and cost-effective. NB UVB is more effective than broadband UVB. Up to 20 to 25 NB UVB treatments, given 2 to 3 times a week, are usually required for significant improvement. Treatment can be offered in the office or at home; home UVB reduces the inconvenience of patients having to travel a long distance for treatment. Other forms of UV exposure, including sun exposure, may offer benefit in select patients.
2. PUVA therapy is very effective in the majority of patients, with potential for long remissions. However, long-term PUVA treatment in Caucasians is associated with an increased risk of squamous cell carcinoma and possibly malignant melanoma. PUVA induces photoaging and other skin changes including lentigines. Ingestion of psoralen may also produce nausea. Oral psoralen is contraindicated in pregnancy. NB-UVB therapy avoids some of the adverse side effects of PUVA, while being slightly less effective than PUVA.
3. Methotrexate, although effective in the majority of patients, has the potential for hepatotoxicity and is contraindicated in the following clinical scenarios: pregnancy; individuals with renal impairment, hepatitis, or cirrhosis; alcoholics; unreliable patients; and patients with leukemia or thrombocytopenia. In addition, drug interactions are common. Methotrexate is an immunosuppressive agent. In patients treated with methotrexate, drug interactions are common with resultant bone-marrow suppression a concern. Methotrexate may induce pneumonitis. Methotrexate is a teratogen, an abortifacient, and decreases sperm count. Prior guidelines suggest a liver biopsy after 1.5-g cumulative dose (Roenigk et al., 1988).
4. CyA, another immunosuppressive medication, works rapidly and is effective in the majority of patients. However, impaired renal function, hypertension, concerns about lymphoma, and a potential increase in cutaneous malignancies are known adverse effects after long-term treatment with CyA. CyA is thus best used interventionally in short-term courses of 3 to 4 months. There are also numerous potential drug interactions with CyA. Guidelines exist for reducing the CyA dose in patients who develop hypertension or elevations in creatinine.
5. Acitretin is an effective systemic agent for the treatment of psoriasis that is not immunosuppressive. Because it is teratogenic and should not be used in women who are pregnant, breast-feeding, or may become pregnant within 3 years of discontinuing acitretin, its use is substantially limited in female patients of childbearing potential. Mucocutaneous side effects are frequent. Dyslipidemia may also ensue and require dose reduction or treatment with lipid-lowering agents. Hepatotoxicity rarely arises during therapy. Acitretin is frequently used in combination therapy with UVB or PUVA.
6. Biologic agents are proteins that can be extracted from animal tissue or produced by recombinant deoxyribonucleic acid (DNA) technology and possess pharmacologic activity. Five biologic agents are currently Food and Drug Administration (FDA) approved for psoriasis. Their safety and efficacy are discussed in detail in the original guideline document.

Treatment of Psoriasis with Biologics

Refer to the original guideline document for general recommendations for all patients who will be treated with biologics including T-cell inhibitors and tumor necrosis factor (TNF) inhibitors.

Biologics that Target Pathogenic T Cells

Recommendations for Alefacept

• Indication: moderate to severe psoriasis
• Dosing: 15 mg every week given as an intramuscular injection for 12 weeks, with a 12-week follow-up nontreatment period
• Short-term Results: 21% of patients achieved a 75% improvement in the Psoriasis Area and Severity Index (PASI-75) at week 14
• Long-term Results:
  • Associated with long remissions in a subset of responders
  • Prior response to alefacept is a likely marker of future treatment response; thus, patients responding to the first course of therapy may be treated long-term with repeated 12-week courses of alefacept -- at a minimum of 24-week intervals
• Toxicity: excellent safety profile in clinical trials
• Baseline Monitoring: CD4 count
• Ongoing Monitoring: biweekly CD4 count required; hold dose for counts <250
• Pregnancy Category: B
• Contraindications: human immunodeficiency virus (HIV) infection

Recommendations for Efalizumab

• Indication: moderate to severe psoriasis
• Dosing: 0.7 mg/kg first dose followed by 1.0 mg/kg/week subcutaneously
• Short-term Response: 27% of patients achieve a 75% improvement in the Psoriasis Area and Severity Index score (PASI-75) at 3 months)
• Long-term Response: 44% to 50% of patients achieved and maintained a PASI-75 response in a 3-year open-label study that only enrolled responders
• Toxicities:
  • Flu-like symptoms frequently occur initially and generally disappear after the third week of treatment
  • Thrombocytopenia, hemolytic anemia, pancytopenia, and peripheral demyelination have all been reported
• Other Issues:
  • Small percentage of patients may develop rebound or flare
  • Do not discontinue treatment abruptly unless essential
  • Not effective in psoriatic arthritis; flares and new-onset psoriatic arthritis have been reported in a subset of patients
• Baseline Monitoring: complete blood count (CBC)
• Ongoing Monitoring:
  • CBCs monthly for the first 3 months and at periodic intervals thereafter
  • Liver function test (LFT) and a periodic history and physical examination are recommended while on treatment
• Pregnancy Category: C

Table: The Strength of Recommendations for the Treatment of Psoriasis Using Biologics That Target Pathogenic T Cells

General Recommendations for Tumor Necrosis Factor (TNF) Inhibitors

• Anti-TNF agents are contraindicated in patients with active, serious infections
• Tuberculosis testing (purified protein derivation [PPD]) should be performed on all patients who will be treated with TNF inhibitors as there are reports of tuberculosis reactivation in patients treated with this class of drug. (Desai & Furst, 2006)
• Do not use with live vaccines; biologically inactive or recombinant vaccines may be considered, although the immune response of these vaccines could be compromised
• Because there is an association between anti-TNF therapy and demyelinating diseases (i.e., multiple sclerosis [MS]), TNF inhibitors should not be used in patients with MS or other demyelinating diseases; first-degree relatives of patients with MS have an increased risk of developing MS, with a sibling relative risk of between 18 and 36, evidence strongly suggesting that TNF inhibitors should not be used in first-degree relatives of patients with MS.
• Because there have been reports of new onset and worsening of congestive heart failure (CHF) in patients treated with TNF inhibitors, caution should be used when considering TNF inhibitor use in patients with CHF; it is recommended that patients with New York Heart Association class III or IV CHF avoid all use of TNF inhibitors and patients with class I or II CHF undergo echocardiogram testing; if the ejection fraction of these patients is <50%, then TNF inhibitor treatment should potentially be avoided. (Desai & Furst, 2006)
• Hepatitis B reactivation after treatment with TNF inhibitors has been reported; in the appropriate clinical setting, patients should be screened for hepatitis B infection.

Recommendations for Adalimumab

• Indications: moderate to severe psoriatic arthritis, moderate to severe psoriasis, adult and juvenile rheumatoid arthritis (as young as age 4 years), ankylosing spondylitis, and Crohn's disease
• Dosing for Psoriasis: 80 mg the first week, 40 mg the second week, followed by 40 mg every other week given subcutaneously
• Short-term Results: 80% of patients achieve PASI-75 at 12 week
• Long-term Results: 68% of patients achieve 75% improvement in the Psoriasis Area and Severity Index score (PASI-75) at 60 weeks
  • Small percentage of patients lose efficacy with continued use
• Toxicities:
  • Moderately painful injection site reactions are noted
  • Rare reports of serious infections (i.e., tuberculosis and opportunistic infections) and malignancies
  • There are rare reports of drug-induced, reversible side effects including lupus without renal or central nervous system (CNS) complications, cytopenia, multiple sclerosis (MS), and exacerbation of and new onset of congestive heart failure (CHF)
• Baseline Monitoring:
  • Purified protein derivation (PPD) is required
  • Liver function test (LFT), complete blood count (CBC), and hepatitis profile
• Ongoing Monitoring:

  Periodic history and physical examination are recommended while on treatment

  Consider a yearly PPD, and periodic CBC and LFT

• Pregnancy Category: B

Recommendations for Etanercept

• Indications: moderate to severe psoriasis, moderate to severe psoriatic arthritis, adult and juvenile rheumatoid arthritis (as young as 4 years), and ankylosing spondylitis
• Dosing: 50 mg twice/week given subcutaneously for 3 months followed by 50 mg once/week
• Short-term Results: 49% of patients given 50 mg twice/week achieved a PASI-75 at 12 weeks; 34% of patients given 25 mg twice/week achieved a PASI-75 at 12 weeks
• Step-down Results: 54% of patients whose dose was decreased from 50 mg twice/week to 25 mg twice/week achieved a PASI-75 at 24 weeks; 45% of patients whose dose remained at 25 mg twice/week achieved a PASI-75 at 24 weeks
• Toxicities:
  • Mildly pruritic injection site reactions may occur
  • Rare cases of serious infections (i.e., tuberculosis) and malignancies
  • There are also rare cases of drug-induced, reversible side effects including lupus without renal or central nervous system (CNS) complications, cytopenia, multiple sclerosis (MS), and exacerbation and new onset of congestive heart failure (CHF)
• Baseline Monitoring:
  • Purified Protein Derivation (PPD) is required
  • Liver function test (LFT) and complete blood count (CBC)
• Ongoing Monitoring:
  • Periodic history and physical examination are recommended while on treatment
  • Consider yearly PPD, and periodic CBC and LFT
• Pregnancy Category: B
• Contraindications: sepsis

Recommendations for Infliximab

• Indications: severe psoriasis, moderate to severe psoriatic arthritis, adult rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, and Crohn's disease
• Dosing: 5 mg/kg dose infusion schedule at week 0, 2, and 6 and then every 6 to 8 weeks; dose and interval of infusions may be adjusted as needed
• Short-term Response: 80% of patients achieved a PASI-75 at week 10, 50% PASI improvement noted by week 2
• Long-term Response: 61% of patients achieved a PASI-75 at week 50
• Toxicities:
  • Infusion reactions and serum sickness can occur -- more commonly in patients who have developed antibodies
  • The incidence of infusion reactions may be reduced by concurrent administration of methotrexate
  • Rare cases of serious infections (i.e., tuberculosis) and malignancies including hepatosplenic T-cell lymphoma (in children); there are rare reports of drug-induced, reversible side effects including lupus without renal or central nervous system (CNS) complications, cytopenia, multiple sclerosis (MS), and exacerbation of and new onset of congestive heart failure (CHF)
• Baseline Monitoring:
  • Purified Protein Derivation (PPD) is required
  • Liver function test (LFT), complete blood count (CBC), and hepatitis profile
• Ongoing Monitoring:
  • Periodic history and physical examination are recommended while on treatment
  • Consider a yearly PPD, and periodic CBC and LFT
• Pregnancy Category: B
• Contraindications: infliximab at doses >5 mg/kg should not be given to patients with New York Heart Association functional class III or IV CHF

Table: The Strength of Recommendations for the Treatment of Psoriasis Using Tumor Necrosis Factor Inhibitors

Definitions:

Levels of Evidence

1. Good-quality patient-oriented evidence.
2. Limited-quality patient-oriented evidence.
3. Other evidence including consensus guidelines, opinion, or case studies.

Strength of Recommendations

1. Recommendation based on consistent and good quality patient-oriented evidence.
2. Recommendation based on inconsistent or limited quality patient-oriented evidence.
3. Recommendation based on consensus, opinion, or case studies.

A decision tree for the treatment of psoriasis with or without psoriatic arthritis is provided in the original guideline document.

The type of supporting evidence is identified and graded for selected recommendations (see "Major Recommendations").

Not applicable: The guideline was not adapted from another source.

2008 May

American Academy of Dermatology - Medical Specialty Society

American Academy of Dermatology operational funds and member volunteer time supported the development of this guideline.

American Academy of Dermatology Work Group

Work Group Members: Alan Menter, MD, Chair, Baylor University Medical Center, Dallas; Alice Gottlieb, MD, PhD, Department of Dermatology, Tufts-New England Medical Center, Tufts University School of Medicine, Boston; Steven R. Feldman, MD, PhD, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem; Abby S. Van Voorhees, MD, Department of Dermatology, University of Pennsylvania; Craig L. Leonardi, MD, Saint Louis University; Kenneth B. Gordon, MD, Division of Dermatology, Evanston Northwestern Healthcare and Department of Dermatology, Northwestern University, Fienberg School of Medicine, Chicago; Mark Lebwohl, MD, Department of Dermatology, Mount Sinai School of Medicine, New York; John Y. M. Koo, MD, Department of Dermatology, University of California - San Francisco; Craig A. Elmets, MD, Department of Dermatology, University of Alabama at Birmingham; Neil J. Korman, MD, PhD, Murdough Family Center For Psoriasis, Department of Dermatology, University Hospitals Case Medical Center, Cleveland; Karl R. Beutner, MD, PhD, Anacor Pharmaceuticals Inc, Palo Alto; Reva Bhushan, PhD, American Academy of Dermatology, Schaumburg

Alan Menter: MD, Chair, Psoriasis Work Group. Dr Menter served on the Advisory Board and was a consultant, investigator and speaker for Abbott Labs, Amgen, and Centocor, receiving grants and honoraria; served on the Advisory Board and was an investigator and consultant for Cephalon and UCB, receiving grants and honoraria; was a consultant, investigator, and speaker for Warner Chilcott and Wyeth, receiving honoraria; served on the Advisory Board and was an investigator for Galderma and Genentech, receiving grants and honoraria; was a consultant and investigator for Allergan and Astellas, receiving grants and honoraria; as an investigator for Collagenex, CombinatoRx, Dow, Ferndale, Leo, Medicis, Photocure, Pierre Fabre, 3M Pharmaceuticals and XOMA, receiving grants; and was an investigator for Connetics, receiving grants and honorarium.

Alice Gottlieb, MD, PhD: Dr Gottlieb served as a speaker for Amgen Inc and Wyeth Pharmaceuticals; has current consulting/advisory board agreements with Amgen Inc, Centocor, Inc, Wyeth Pharmaceuticals, Celgene Corp, Bristol Myers Squibb Co, Beiersdorf, Inc, Warner Chilcott, Abbott Labs, Roche, Sankyo, Medarex, Kemia, Celera, TEVA, Actelion, UCB, Novo Nordisk, Almirall, Immune Control, RxClinical, Dermipsor Ltd, Medacorp, DermiPsor, Can-Fite, Incyte; and has received research/educational grants from Centocor, Amgen, Wyeth, Immune Control, Celgene, Pharmacare, Incyte. All income has been paid to her employer directly.

Steven R. Feldman, MD, PhD: Dr Feldman served on the Advisory Board and was investigator and speaker for Galderma, Stiefel, Warner Chilcott, Abbott Labs and Astellas, receiving grants and honoraria; served on the Advisory Board for Photomedex, receiving stock options; served on the advisory board and was speaker for National Psoriasis Foundation, receiving honoraria; and was an investigator and speaker for Amgen, Centocor and Genentech, receiving grants and honoraria.

Abby S. Van Voorhees, MD: Dr Van Voorhees served on the Advisory Board, was an investigator and speaker for Amgen and Genentech, receiving grants and honoraria; investigator for Astellas, IDEC and Roche, receiving grants; Advisory Board and investigator for Birstol Myers Squibb and Warner Chilcott, receiving grants and honoraria; Advisory Board and was speaker for Abbott Labs and Centocor, receiving honoraria; served on the Advisory Board for Connetics, receiving honoraria; was consultant for Incyte and Xtrac and VGX and has received honoraria from Synta for another function. Dr. Van Voorhees' spouse is an employee with Merck receiving a salary, stock and stock options.

Craig L. Leonardi, MD: Dr Leonardi served on the Advisory Board and was consultant, investigator, and speaker for Abbott Labs, Amgen, Centocor, Genentech, receiving honoraria, other financial benefit, and grants for Amgen and Genentech; was speaker for Warner Chillcott receiving honoraria; was on the Advisory Board and was investigator for Serano receiving honoraria and other financial benefit; was investigator for Astellas, Biogen, Bristol Myers, Allergun, Fujisawa, CombinatorRx, and Vitae receiving other financial benefit.

Kenneth B. Gordon, MD: Dr Gordon served on the Advisory Board and was consultant, investigator, and speaker for Abbott Labs, Amgen, and a consultant and investigator for Centocor, receiving grants and honoraria; and was investigator for Genentech, receiving grants.

Mark Lebwohl, MD: Dr Lebwohl served on the Advisory Board and was consultant, investigator, and speaker for Abbott Labs, Amgen, Centocor, Galderma, Genentech, and Warner Chilcott, receiving honoraria and grants; served on the Advisory Board and was consultant, investigator, and speaker for Stiefel, receiving honoraria; was consultant and investigator for Astellas, receiving grants and honoraria; was consultant for Biogen, UCB and Isotechnika, receiving honoraria; was on the Advisory Board and was consultant and investigator for Novartis, receiving grants and honoraria; and had an "other" relationship with PharmaDerm receiving grants and honoraria.

John Y. M. Koo, MD: Dr Koo served on the Advisory Board, was speaker, consultant, and investigator for Amgen, Abbott Labs, Astellas, Warner Chilcott, and Galderma, receiving grants and honoraria; was investigator for Genentech, receiving grants; and was an Advisory Board consultant and investigator for Teikokio, receiving compensation.

Craig A. Elmets, MD: Dr Elmets has served on the Advisory Board and was investigator for Amgen and Abbott Labs, receiving grants and honoraria; was consultant for Astellas, receiving honoraria; and was an investigator for Genentech and Connetics, receiving grants.

Neil J. Korman, MD, PhD: Dr Korman has served on the Advisory Board and was investigator and speaker for Abbott Labs, Genentech and Astellas, receiving grants and honoraria; served on the Advisory Board and was investigator for Centocor, receiving grants and residency/fellowship program funding; and was investigator and speaker for Amgen, receiving grants and honoraria.

Karl R. Beutner, MD, PhD: Chair, Clinical Research Committee. Dr Beutner was an employee of Anacor, receiving salary, stock and stock options and had other relationships and received stock from Dow Pharmaceutical Sciences.

Reva Bhushan, PhD: Dr. Bhushan had no relevant conflicts of interest to disclose.

This is the current release of the guideline.

None available

None available

This NGC summary was completed by ECRI Institute on June 30, 2008. The information was verified by the guideline developer on July 16, 2008. This summary was updated by ECRI Institute on October 30, 2008 following the U.S. Food and Drug Administration advisory on Raptiva (efalizumab).

The American Academy of Dermatology Association places no restriction on the downloading, use, or reproduction of its guidelines.