The treatment of psoriasis has undergone dramatic changes since the early days of coal tar and sunlight. Although these modalities are still utilized, newer genetically engineered drugs are utilized with increasing success.
Prognosis Treatment Commonly Used Terms Internet Links
PROGNOSIS CHARACTERIZATION Conversion of a psoriatic plaque to a squamous cell carcinoma is extremely rare and may be related to a tumor suppressor pathway discussed in the pathogenesis section
- The risk of mortality in patients with psoriasis: results from a population-based study.
MSCE, Department of Dermatology, University of Pennsylvania School of Medicine, 2 Maloney Bldg, 3600 Spruce St, Philadelphia, PA 19104, USA.
- Arch Dermatol. 2007 Dec;143(12):1493-9. Abstract quote
OBJECTIVE: To determine the risk of mortality in patients with psoriasis.
DESIGN: Cohort study.
SETTING: General practitioners participating in the General Practice Research Database in the United Kingdom, 1987-2002.
PATIENTS: Mild psoriasis, defined as any patient with a diagnostic code of psoriasis but no history of systemic therapy; severe psoriasis, any patient with a diagnostic code of psoriasis and a history of systemic therapy consistent with severe psoriasis. The unexposed (control) population was composed of patients with no history of a psoriasis diagnostic code. Control patients were selected in a 5:1 ratio from the same practice and date in practice as the patients with psoriasis.
MAIN OUTCOME MEASURE: Hazard ratio (HR) of time to death using Cox proportional hazards models adjusted for age and sex. RESULTS: There was no overall effect of mild psoriasis on mortality (HR, 1.0; 95% confidence interval [CI], 0.97-1.02), whereas patients with severe psoriasis demonstrated an increased overall mortality risk (HR, 1.5; 95% CI, 1.3-1.7). The association of severe psoriasis with mortality persisted after adjustment for risk factors for mortality (HR, 1.4; 95% CI, 1.3-1.6) and after exclusion of patients with inflammatory arthropathy (HR, 1.5; 95% CI, 1.3-1.8). Male and female patients with severe psoriasis died 3.5 (95% CI, 1.2-5.8) and 4.4 (95% CI, 2.2-6.6) years younger, respectively, than patients without psoriasis (P < .001).
CONCLUSION: Severe but not mild psoriasis is associated with an increased risk of death.
N Engl J Med 1997;336:1041
N Engl J Med 1990;322:1053
PUVA therapy may increase risk of development of SCCA and melanoma but these skin cancers do not occur in continuity with the psoriatic plaques but occur on the scrotum and other sites not typically involved by psoriasis
The course of chronic plaque-type psoriasis in placebo groups of randomized controlled studies.
Spuls PI, Witkamp L, Bossuyt PM, Bos JD.
Departments of Dermatology and Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
Arch Dermatol. 2004 Mar;140(3):338-44. Abstract quote
OBJECTIVE: To determine the outcome in placebo-treated patients with plaque-type psoriasis.
Data Sources Online search of MEDLINE and EMBASE until January 2001 and the Cochrane Library (2001, issue 1), supplemented by references, reviews, guidelines, and textbooks.
Study Selection Randomized controlled induction of remission trials of patients with chronic plaque-type psoriasis with systemic treatments with a placebo group not treated with antipsoriatic medication. Identified studies were examined by 2 independent reviewers. Through MEDLINE, 290 studies could be identified. Twenty-seven placebo-controlled studies were included (488 patients).
Data Extraction Two independent reviewers extracted data on first author, year of publication, design, comparison, placebo treatment, number of patients, treatment duration, type of psoriasis and baseline severity in the placebo group, mean relative change in outcome measures, and/or percentage of patients with worsening of psoriasis; no change; minimal, moderate, or good improvement; or complete clearance.
Data Synthesis Owing to substantial heterogeneity and differences in the way outcomes were reported, no summary estimates could be obtained. The outcome of placebo treatment was poor in most studies. Some reported a mean relative change of 11% to 47%. The highest percentages of patients ended up in the worsening, no change, or minimal improvement categories. Also, complete clearance was possible. No explanation for the differences in outcome between placebo groups could be found. Description of placebo groups was often insufficient.
CONCLUSIONS: The effect of treatment in placebo groups varied across studies in an unpredictable way. To evaluate the variability, improvement of the standardization of study designs, entry criteria, and outcome measures is necessary in psoriasis trials.
The direct cost of care for psoriasis and psoriatic arthritis in the United States.
Javitz HS, Ward MM, Farber E, Nail L, Vallow SG.
Center for Health Sciences, SRI International, Menlo Park, the Department of Health Management and Policy, University of Iowa, Psoriasis Research Center, Palo Alto, Stanford University, Palo Alto, and SmithKline Beecham, Collegeville.
J Am Acad Dermatol 2002 Jun;46(6):850-60 Abstract quote
BACKGROUND: Relatively little information is available in the literature concerning the cost of psoriasis in the United States, and much of that information is out of date.
OBJECTIVE: The present analyses estimate the direct cost of medical care for psoriasis (including psoriatic arthritis) from a societal perspective among adults in the United States. Method and Data: The costs of hospitalizations, outpatient and physician office visits, prescription and over-the-counter (OTC) medications, and medical procedures were estimated from the literature, analysis of publicly available health databases (Health and Nutrition Examination Survey, National Hospital Discharge Survey, Medicare Public Use Files, National Ambulatory Medical Care Survey, and the National Hospital Ambulatory Medical Care Survey), and analysis of privately available health databases (United Health Care/Diversified Pharmaceutical Services, the Medstat Group diagnosis-related group guide, and the National Disease and Therapeutic Index). Costs were expressed as of 1997 by using Medicare and health maintenance organization reimbursement rates and wholesale drug costs. Costs of OTC medications were derived by adjusting a previous estimate in the literature for inflation in over-the-counter drugs and population increases.
RESULTS: The cost of illness for the approximately 1.4 million individuals with clinically significant disease is substantial-approximately $30.5 million for hospitalizations, $86.6 million for outpatient physician visits, $27.4 million for photochemotherapy, $147.9 million for dermatologic prescription drugs, and $357.2 million for OTC drugs, for a total direct cost of $649.6 million.
CONCLUSION: Cost estimates from this study are substantially less than those found in previous studies ($1.09 billion and $4.32 billion after adjustment of estimates in the literature for medical inflation and population increases). This appears to be principally a result of decreases in hospitalization rates since 1979 and the valuation methodology per unit of medical services (with prior studies using "list" prices and the current study using reimbursement rates).
TREATMENT CHARACTERIZATION GENERAL J Invest Dermatol 1992;98:602
Estimated that 23% of patients have disease that topical therapy is impractical or ineffective
J Am Acad Dermatol. 2005 Jul;53(1):101-7. Abstract quote
Psoriasis has a tremendous effect on health-related quality of life. Phototherapy and systemic treatments are used for patients with more debilitating (physically and emotionally) forms of the disease. These treatments can be extremely effective but can also have potentially significant adverse effects. The decision to undertake systemic treatment of psoriasis is a complex one that requires both experience and judgment. With the recent advent of new biologic systemic drugs for moderate to severe psoriasis, the need to clarify patient candidates for systemic therapy has become very important.
Here, we present a diagnostic algorithm and a formal measure, the Koo-Menter Psoriasis Instrument (KMPI), to aid in identifying patients that would benefit from systemic therapy. In addition, the KMPI can be used to document and justify treatment decisions for health care payers.
While the decision to undertake systemic treatment and the choice of specific treatment plan must ultimately be made mutually by the patient and physician, these tools are designed to provide information that will be valuable in these determinations.
Combination therapy to treat moderate to severe psoriasis.
Lebwohl M, Menter A, Koo J, Feldman SR.
J Am Acad Dermatol. 2004 Mar;50(3):416-30. Abstract quote
In patients with moderate-to-severe psoriasis, remission can be difficult to achieve and sustain. Both acutely acting and long-term maintenance agents are needed. Speed and efficiency of available monotherapies tend to be inversely proportional to safety. Combination, rotational, and sequential approaches are often more effective and safer than single-agent therapy. Combining agents with complementary adverse effect profiles is preferable.
Apparent synergistic enhancement is seen with most paired combinations of the four major therapies: acitretin, phototherapy (ultraviolet B/psoralen plus ultraviolet A), cyclosporine, and methotrexate. Of those, only cyclosporine in combination with psoralen plus ultraviolet A is contraindicated because of increased cancer risk. Combinations of each of those major therapies with topical agents (retinoids, steroids, vitamin D derivatives, and others) have been used with varying efficacy and safety. The immunomodulators, hydroxyurea and thioguanine, have also shown some success in combination therapy. The new biologic agents with their novel modes of action and adverse effect profiles may prove to be important adjuncts in combination/rotational/sequential approaches. In some cases, monotherapy (with either systemic agents or phototherapy) adequately controls moderate to severe disease. A regimen using a single agent has the advantages of lower cost and greater adherence by the patient.
For any number of reasons, however, including loss of efficacy, adverse effects, or cumulative or acute toxicity-and especially the inability to clear resistant lesions-a single modality will not be adequate. Using two or more therapies is thus the rule rather than the exception for most patients with moderate-to-severe psoriasis, but picking a combination that serves to balance safety and efficacy needs careful consideration, especially since no evidence-based treatment guidelines exist.
Treatment of psoriasis. Part 1. Topical therapy and phototherapy
Mark Lebwohl, MD
Suad Ali, MD
New York, New York
J Am Acad Dermatol 2001;45:487-98 Abstract quote
New developments in the topical therapy and phototherapy of psoriasis have greatly improved our ability to safely and effectively treat this debilitating disease.
Topical corticosteroids remain the most commonly prescribed agents for psoriasis, but they are frequently prescribed with other agents. Investigations of corticosteroids claiming an improved benefit/risk ratio have yielded promising results, but more work is needed. Use of anthralin and tar has declined with the availability of the noncorticosteroids calcipotriene and tazarotene. Other experimental topical therapies are in various stages of development.
Broadband ultraviolet B (UVB) remains the most commonly used phototherapy light source, but many patients are being treated with a new form of ultraviolet light, narrowband UVB. Although PUVA remains one of the most effective psoriasis treatments, its use is declining because of its association with cutaneous malignancies. New radiation sources such as lasers have been added to our armamentarium of available therapies and even newer light source-based treatments are being examined.
Treatment of psoriasis. Part 2. Systemic therapies
Mark Lebwohl, MD
Suad Ali, MD
New York, New York
J Am Acad Dermatol 2001;45:649-61 Abstract quote
The array of systemic medications used in the treatment of psoriasis is rapidly expanding. In the United States, methotrexate, retinoids, and cyclosporine are the only systemic drugs approved by the Food and Drug Administration for the treatment of psoriasis. Monitoring and dosage recommendations for these medications are reviewed.
Other drugs that are currently available include tacrolimus, mycophenolate mofetil, hydroxyurea, 6-thioguanine, and sulfasalazine. Experience with these drugs is summarized, and dosage and monitoring recommendations in published literature are presented.
Combinations of different treatments are addressed and investigational therapies that are in development are reviewed.
Biologic therapy for psoriasis: the new therapeutic frontier.
Singri P, West DP, Gordon KB.
Department of Dermatology, Feinberg School of Medicine, 675 N St Clair St, Suite 19-150, Chicago, IL 60611.
Arch Dermatol 2002 May;138(5):657-63 Abstract quote
OBJECTIVES: (1) To develop a clinically useful model with which dermatologists can understand the potential uses of biologic therapy for psoriasis and understand the potential differences among these novel drugs, (2) to discuss the process by which recombinant DNA technology is used to develop rationally designed protein medications along with the potential benefits and difficulties of therapy with biologic agents, and (3) to provide a short review of the medications under development for psoriasis.
DATA SOURCES: The pertinent literature was reviewed with particular emphasis on published, randomized, and placebo-controlled trials. Phase 1 and early phase 2 trials were also included in our review when more stringent studies were not available. Studies presented as peer-reviewed abstracts at major conferences were also reviewed.
CONCLUSIONS: With the development of recombinant DNA techniques, it has become possible to develop new biologic therapies that can be designed to specifically alter physiological responses. These new drugs are in use in many different medical fields and will soon be available for the treatment of dermatological diseases, primarily psoriasis. Dermatologists should be familiar with the potential benefits and risks of these therapies to make rational decisions concerning their use in the treatment of their patients with psoriasis.
Consensus conference: Acitretin in combination with UVB or PUVA in the treatment of psoriasis
Mark Lebwohl, MD
Lynn Drake, MD
Alan Menter, MD
John Koo, MD
Alice B. Gottlieb, MD, PhD
Michael Zanolli, MD
Melodie Young, MSN, RN
Patricia McClelland, RN
New York, New York; Oklahoma City, Oklahoma; Dallas, Texas; San Francisco, California; New Brunswick, New Jersey; and Nashville, Tennessee
J Am Acad Dermatol 2001;45:544-53 Abstract quote
Although adjunctive treatment with retinoids in concert with either psoralen-ultraviolet A (PUVA) or ultraviolet B (UVB) phototherapy has been a treatment option for chronic, moderate to severe plaque psoriasis for nearly two decades, acitretin-UV therapy is an underutilized therapeutic modality. According to a recent member survey by the National Psoriasis Foundation, many psoriasis patients are frustrated with available treatment options, which they perceive as ineffective, inconvenient, and/or excessively conservative.
Treatment of psoriasis with acitretin in concert with UVB or PUVA is emerging as a viable clinical strategy. Compared with either acitretin or UV light monotherapy alone, the combination regimen enhances efficacy and limits treatment frequency, duration, and cumulative doses. These effects translate into care that is more effective, better tolerated, more convenient, less costly, and, perhaps, safer during long-term treatment than phototherapy alone. Drawing from an extensive literature search and the expertise of its participants, this consensus conference advances clinical recommendations as well as “clinical pearls” for health providers who treat patients with chronic, moderate to severe plaque psoriasis and suggests avenues for future research.
- Adalimumab therapy for moderate to severe psoriasis: A randomized, controlled phase III trial.
- Menter A, Tyring SK, Gordon K, Kimball AB, Leonardi CL, Langley RG, Strober BE, Kaul M, Gu Y, Okun M, Papp K.
Division of Dermatology, Baylor Research Institute, University of Texas Southwestern Medical School, 3900 Junius St, 125, Dallas, TX 75246-1613, USA.
- J Am Acad Dermatol. 2008 Jan;58(1):106-15. Abstract quote
BACKGROUND: Adalimumab is a fully human monoclonal antibody that binds tumor necrosis factor, a key proinflammatory cytokine involved in the pathogenesis of psoriasis.
OBJECTIVE: We sought to evaluate clinical efficacy and safety of adalimumab for moderate to severe psoriasis and investigate continuous versus interrupted therapy.
METHODS: We conducted a 52-week, multicenter study of 1212 patients randomized to receive adalimumab (40 mg) or placebo every other week for the first 15 weeks. At least 75% improvement in the Psoriasis Area and Severity Index (PASI) score was the criterion for advancement through this multiphase study.
RESULTS: At week 16, 71% (578 of 814) of adalimumab- and 7% (26 of 398) of placebo-treated patients achieved greater than or equal to 75% improvement in the PASI score. During weeks 33 to 52, the percentage of patients rerandomized to placebo who lost adequate response (defined as <50% improvement in the PASI response relative to baseline and at least a 6-point increase in PASI score from week 33) was 28% compared with 5% of patients treated continuously with adalimumab.
LIMITATIONS: Lack of an active comparator and evaluation of maintenance of response beyond week 52 are limitations.
CONCLUSION: Adalimumab is efficacious and well-tolerated in the treatment of chronic plaque psoriasis.
TRIAL REGISTRATION: Clinical trials.gov. NCT00237887.
- Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study.
- Gordon KB,
- Langley RG,
- Leonardi C,
- Toth D,
- Menter MA,
- Kang S,
- Heffernan M,
- Miller B,
- Hamlin R,
- Lim L,
- Zhong J,
- Hoffman R,
- Okun MM.
Division of Dermatology, Evanston Northwestern Healthcare and Northwestern University Feinberg School of Medicine, Skokie, IL 60077, USA.
- J Am Acad Dermatol. 2006 Oct;55(4):598-606. Epub 2006 Aug 10 Abstract quote
BACKGROUND: Tumor necrosis factor is pivotal in the pathogenesis of psoriasis. Adalimumab is a fully human monoclonal immunoglobulin G1 antibody that neutralizes tumor necrosis factor.
OBJECTIVES: We sought to assess the efficacy and safety of adalimumab in patients with moderate to severe plaque psoriasis.
METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, 147 patients received adalimumab (40 mg every other week or 40 mg/wk) or placebo. After 12 weeks of blinded therapy, patients taking adalimumab could continue their assigned dosages in a 48-week extension trial; patients taking placebo were switched to adalimumab (40 mg every other week).
RESULTS: At week 12, 53% of patients taking adalimumab every other week, 80% of patients taking adalimumab weekly, and 4% of patients taking placebo achieved 75% improvement in Psoriasis Area and Severity Index score (P < .001). Responses were sustained for 60 weeks. No new safety signals were noted compared with the existing adalimumab clinical safety database.
LIMITATIONS: The study was insufficiently powered to detect rare adverse events associated with adalimumab.
CONCLUSIONS: Adalimumab significantly improved psoriasis and was well tolerated for 60 weeks.
J Am Acad Dermatol. 2005 Jul;53(1):73-5. Abstract quote
BACKGROUND: The efficacy and safety of one and two courses of alefacept have been demonstrated in phase 2 and 3 clinical trials, with a course of alefacept defined as 12 weeks of once-weekly treatment followed by 12 weeks of observation.
METHODS: This randomized, single-center study compared the safety and efficacy of a standard 12-week versus extended 16-week alefacept dosing period in 20 patients with chronic plaque psoriasis.
RESULTS: Both dose groups showed marked improvement in mean Psoriasis Area and Severity Index (PASI) score from baseline through week 24 (between-group difference: not significant). In each group, 60% of patients achieved PASI 50 (> or =50% reduction from baseline PASI score) at any time between weeks 12 and 24. For patients who received 16 weeks of alefacept, the mean percentage change from week-12 PASI score was higher and continued to increase through week 24 compared with that for patients who received 12 weeks of alefacept (P < .05). Adverse events were similar between the two groups and comparable with those observed in phase 2 and 3 clinical studies of alefacept.
CONCLUSIONS: This was an open-label, single-center study of 20 patients. Further study is warranted to assess the effect of alefacept when administered for more than 12 weeks. Extended dosing with alefacept appeared to have a similar safety profile to 12-week dosing and may offer further benefit to some patients for disease improvement.
A randomized trial of etanercept as monotherapy for psoriasis.
Gottlieb AB, Matheson RT, Lowe N, Krueger GG, Kang S, Goffe BS, Gaspari AA, Ling M, Weinstein GD, Nayak A, Gordon KB, Zitnik R.
Clinical Research Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, 08901-0019, USA.
Arch Dermatol. 2003 Dec;139(12):1627-32; discussion 1632. Abstract quote
OBJECTIVE: To determine safety and efficacy of monotherapy with etanercept.
DESIGN: Randomized, double-blind, placebo-controlled, multicenter study.
SETTING: Outpatient, ambulatory; private practice and university dermatology research centers.
PATIENTS: Patients aged at least 18 years, with plaque psoriasis involving 10% or more of body surface area; 148 were screened and 112 were randomly assigned to treatment groups and received study drug.
INTERVENTIONS: Patients received placebo or etanercept, 25 mg, subcutaneously twice a week for 24 weeks. Other psoriasis therapies were limited during the study.
MAIN OUTCOME MEASURES: Safety measurements included tracking of adverse events and laboratory values. Efficacy was evaluated using the Psoriasis Area and Severity Index (PASI); the primary end point was a 75% improvement in PASI. Other efficacy measurements included patient and physician global assessments and quality-of-life measures.
RESULTS: After 12 weeks of treatment, 17 (30%) of the 57 etanercept-treated patients and 1 (2%) of the 55 placebo-treated patients had achieved PASI 75%, and after 24 weeks, 32 (56%) of etanercept-treated patients and 3 (5%) of placebo-treated patients had reached this level (P<.001 for both time points). By 24 weeks, psoriasis was clear or minimal by physician's global assessment in more than 50% of patients who received etanercept. Treatment failure (PASI response <50) occurred in 23% of patients at week 24. All other measures confirmed the efficacy of etanercept. Adverse events were similar among etanercept and placebo groups.
CONCLUSION: Etanercept monotherapy provided significant benefit to patients with psoriasis and had a favorable safety profile.
CD4+ T-cell-directed antibody responses are maintained in patients with psoriasis receiving alefacept: Results of a randomized study.
Gottlieb AB, Casale TB, Frankel E, Goffe B, Lowe N, Ochs HD, Roberts JL, Washenik K, Vaishnaw AK, Gordon KB.
J Am Acad Dermatol. 2003 Nov;49(5):816-25. Abstract quote
BACKGROUND: Alefacept, human LFA-3/IgG(1) fusion protein, selectively reduces memory-effector (CD45RO(+)) T cells, a source of the pathogenic mediators of psoriasis.
OBJECTIVE: To evaluate the effect of alefacept on immune function, T-cell-dependent humoral responses to a neoantigen (PhiX174) and recall antigen (tetanus toxoid) were assessed.
METHODS: Patients with psoriasis were randomized to the control group or to receive alefacept (7.5 mg intravenously weekly for 12 weeks). The alefacept group received PhiX174 immunizations at weeks 6, 12, 20, and 26 and tetanus toxoid at week 21; control subjects received PhiX174 at weeks 6 and 12 and tetanus at week 10.
RESULTS: Mean anti-PhiX174 titers were comparable in both groups. There was no difference in the percentage of responders (anti-PhiX174 IgG >/=30% of the total anti-PhiX174) between the alefacept group and the control group (86% and 82%, respectively; P =.73). The percentage of patients with anti-tetanus toxoid titer increases >/=2 times baseline also was similar (alefacept, 89%; control 91%).
CONCLUSION: A single 12-week course of alefacept did not impair primary or secondary antibody responses to a neoantigen or memory responses to a recall antigen. The selective immunomodulatory effect of alefacept against a potentially pathogenic T-cell subset is associated with maintenance of a significant aspect of immune function (antibody response) to fight infection and respond to vaccinations.
An International, Randomized, Double-blind, Placebo-Controlled Phase 3 Trial of Intramuscular Alefacept in Patients With Chronic Plaque Psoriasis.
Lebwohl M, Christophers E, Langley R, Ortonne JP, Roberts J, Griffiths CE.
Mount Sinai School of Medicine, New York, NY.
Arch Dermatol. 2003 Jun;139(6):719-27. Abstract quote
BACKGROUND: Alefacept, human lymphocyte function-associated antigen 3/immunoglobulin 1 fusion protein, binds to CD2 molecules on the surface of activated T cells, selectively targeting memory-effector (CD45RO+) T cells, which comprise more than 75% of T cells in psoriatic plaques.
OBJECTIVE: To examine the efficacy and tolerability of intramuscular alefacept.
DESIGN: International, randomized, double-blind, placebo-controlled, parallel-group trial.Patients A total of 507 patients with chronic plaque psoriasis.Intervention Placebo, 10 mg of alefacept, or 15 mg of alefacept administered once weekly for 12 weeks followed by 12 weeks of observation.
Main Outcome Measure Psoriasis Area Severity Index (PASI).
RESULTS: Alefacept treatment was associated with dose-related significant improvements in PASI from baseline. Throughout the study, a greater percentage of patients in the 15-mg group than in the placebo group achieved a significant reduction in PASI. Of patients in the 15-mg group who achieved at least 75% PASI reduction 2 weeks after the last dose, 71% maintained at least 50% improvement in PASI throughout the 12-week follow-up. There were no opportunistic infections and no cases of disease rebound.
Conclusion Intramuscular administration of alefacept was a well-tolerated and effective therapy for chronic plaque psoriasis and thus represents a convenient alternative to intravenous dosing.
A randomized, double-blind, placebo-controlled phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis.
Krueger GG, Papp KA, Stough DB, Loven KH, Gulliver WP, Ellis CN; Alefacept Clinical Study Group.
University of Utah Health Sciences Center, Salt Lake City, USA.
J Am Acad Dermatol 2002 Dec;47(6):821-33 Abstract quote
BACKGROUND: In previous phase II studies, alefacept significantly improved psoriasis and was well tolerated. The clinical response to alefacept was durable.
OBJECTIVE: Our purpose was to further evaluate efficacy and tolerability of alefacept in a phase III study of patients (n = 553) with chronic plaque psoriasis.
METHODS: Two 12-week courses of once-weekly intravenous alefacept 7.5 mg or placebo were given in a randomized double-blind study; patients were followed up for 12 weeks after each course.
RESULTS: During treatment and follow-up of course 1, a 75% or greater reduction in the Psoriasis Area Severity Index (PASI) was achieved by 28% of alefacept-treated and 8% of placebo-treated patients (P <.001). Patients who received a single course of alefacept and achieved a 75% or greater reduction from baseline PASI during or after treatment, without the use of phototherapy or systemic therapies, maintained a 50% or greater reduction in PASI for a median duration of more than 7 months. Among patients who received 2 courses of alefacept, 40% and 71% of patients achieved a 75% or greater and 50% or greater reduction in PASI, respectively, during the study period. Alefacept was well tolerated over both courses. In course 1, the incidence of transient chills was higher in the alefacept group compared with the placebo group; more than 90% of cases occurred within 24 hours after the first few doses.
CONCLUSION: Alefacept significantly improved psoriasis and produced durable clinical improvements among patients who responded. A second course of alefacept increased efficacy and was equally well tolerated.
ANTI-CD4 Anti-CD4 IgG4 monoclonal antibody for moderate to severe disease
J Am Acad Dermatol 2000;43:595-604
Multicenter double blinded, multiple dose, placebo controlled study-28 patients
Severity of disease decreased by 11% in placebo group, 4% in low dose group, and 17% in high dose group at 15 days
Clinical and histologic response to single-dose treatment of moderate to severe psoriasis with an anti-CD80 monoclonal antibody.
Gottlieb AB, Lebwohl M, Totoritis MC, Abdulghani AA, Shuey SR, Romano P, Chaudhari U, Allen RS, Lizambri RG.
University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick; Mt Sinai School of Medicine, New York; and IDEC Pharmaceuticals Corporation, San Diego
J Am Acad Dermatol 2002 Nov;47(5):692-700 Abstract quote
Pathologic T-cell activation is implicated in psoriasis progression. CD80, a costimulatory molecule involved in T-cell activation, likely plays a key role. IDEC-114, an IgG(1) anti-CD80 antibody, was evaluated for safety, pharmacokinetics, and preliminary clinical activity in this open-label, single-dose, dose-escalating study in patients with moderate to severe chronic plaque psoriasis.
Twenty-four patients received IDEC-114 (0.05 mg/kg, 0.25 mg/kg, 1 mg/kg, 5 mg/kg, 10 mg/kg, or 15 mg/kg). Psoriasis Area and Severity Index, Physician's Global Psoriasis Assessment, and Psoriasis Severity Scale scores improved in the highest-dose groups.
Average plaque thickness and plaque CD3(+) and CD8(+) T-cell counts decreased in the 10 mg/kg dose group. Adverse events were primarily mild, transient, constitutional symptoms; the most common related events were mild asthenia (29% of patients), chills (25%), and headache (21%). The serum half-life of IDEC-114 was approximately 13 days.
A single dose of IDEC-114 appears to be safe and well tolerated and has promising clinical activity in psoriasis.
- A randomized, double-blind, vehicle-controlled, bilateral comparison trial of bexarotene gel 1% versus vehicle gel in combination with narrowband UVB phototherapy for moderate to severe psoriasis vulgaris.
Magliocco MA, Pandya K, Dombrovskiy V, Christiansen L, Wong Y, Gottlieb AB.
Psoriasis Center of Excellence, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901-0019, USA.
J Am Acad Dermatol. 2006 Jan;54(1):115-8. Epub 2005 Nov 28. Abstract quote
We report results of a randomized, vehicle-controlled, bilateral comparison pilot study of bexarotene gel 1% with narrowband UVB (NBUVB) phototherapy for moderate to severe psoriasis.
In all, 9 patients applied drug or vehicle gel to comparable target lesions up to twice daily for 10 weeks. NBUVB was initiated 2 weeks after topical therapy began. Limitations include small sample size and interim analysis.
Based on analysis of target lesion scores, bexarotene gel 1%/NBUVB was significantly more effective than placebo/NBUVB.
Systemic treatment of psoriatic patients with bexarotene decreases epidermal proliferation and parameters for inflammation, and improves differentiation in lesional skin.
Smit JV, de Jong EM, van Hooijdonk CA, Otero ME, Boezeman JB, van de Kerkhof PC.
Department of Dermatology, University Medical Center, Nijmegen, The Netherlands.
J Am Acad Dermatol. 2004 Aug;51(2):257-64. Abstract quote
BACKGROUND: Bexarotene, a novel synthetic retinoid X receptor (RXR)-selective retinoid, has been reported to have antiproliferative and apoptotic stimulating effects in cutaneous T-cell lymphoma. In benign, hyperproliferative, and retinoid sensitive disorders, such as psoriasis, bexarotene has not been evaluated so far and no information on these parameters is available.
OBJECTIVE: In the present study, immunohistochemical parameters for proliferation, differentiation, inflammation, and apoptosis were investigated in a group of bexarotene-treated psoriatic patients.
METHODS: Twenty-nine patients with plaque-type psoriasis were treated for 12 weeks with oral bexarotene in four dose-defined treatment panels. Treatment was initiated in the following consecutive order: 1.0 mg/kg/day, 2.0 mg/kg/day, 0.5 mg/kg/day, and 3.0 mg/kg/day. Biopsies for immunohistochemical analysis were taken at the baseline and after 12 weeks of treatment.
RESULTS: Significant reductions in Ki-67, keratin 16, transglutaminase, dermal CD4, epidermal CD8, and inflammation scores were seen after bexarotene treatment in combination with a significant increase in keratin 10. No induction of keratin 13 and 19 and no alterations in apoptosis associated p53 expression were observed. Apart from a weak significant dose-response effect for Ki-67, no other significant dose-response effects were seen.
CONCLUSION: We have demonstrated efficacy of oral bexarotene in psoriasis in doses up to 3.0 mg/kg/day during 12 weeks of treatment for proliferation, differentiation, and inflammation parameters. Studies investigating higher doses of bexarotene in a larger number of patients are necessary to reveal potentially dose-related immunohistochemical effects of this new rexinoid and to elucidate the role of RXR-signaling in retinoid-associated keratin expression.
A phase II multicenter clinical trial of systemic bexarotene in psoriasis.
Smit JV, Franssen ME, de Jong EM, Lambert J, Roseeuw DI, De Weert J, Yocum RC, Stevens VJ, van De Kerkhof PC.
Department of Dermatology at the University Medical Center, Nijmegen, The Netherlands.
J Am Acad Dermatol. 2004 Aug;51(2):249-56. Abstract quote
BACKGROUND: Bexarotene, a novel and unique synthetic P, RXR-selective retinoid, is available as a treatment for cutaneous T-cell lymphoma. In psoriasis, a common retinoid-sensitive disease, no data are available on bexarotene treatment.
OBJECTIVE: In this phase II study we investigated the safety, tolerability, and effectiveness of bexarotene in psoriasis at doses of 0.5 to 3.0 mg/kg/day.
METHODS: Fifty patients with moderate to severe plaque-type psoriasis were treated with bexarotene in 4 sequential dose-defined panels of 12-13 patients at doses of 1.0, 2.0, 0.5, and 3.0 mg/kg/day for 12-24 weeks. Patients were monitored for safety and clinical efficacy.
RESULTS: No serious adverse events related to the drug occurred. Bexarotene was well tolerated in most patients. Most frequently observed adverse events related to bexarotene were hypertriglyceridaemia (56%) and a decrease in free T4 serum levels (54%). Significant improvement of psoriasis after bexarotene at all doses was confirmed by a modified psoriasis area and severity index (mPASI), plaque elevation (PEL), and physician's global assessment (PGA). Overall response rates (> or =50% improvement) for mPASI, PEL, and PGA were 22%, 52%, and 36%, respectively. No significant dose-response effect was established for these parameters.
CONCLUSION: The present study indicates an anti-psoriatic effect of bexarotene. Further studies are necessary to assess the optimal dose and the potential for bexarotene as a new therapy for psoriasis.
Repeated exposure to blue light does not improve psoriasis.
Maari C, Viau G, Bissonnette R.
Division of Dermatology, University of Montreal Hospital Centre, Quebec, Canada.
J Am Acad Dermatol. 2003 Jul;49(1):55-8. Abstract quote
BACKGROUND: Increased endogenous levels of protoporphyrin IX (PpIX) have been reported in the skin of patients with psoriasis. Activation of PpIX with blue light after exogenous topical application of its precursor, aminolevulinic acid, can improve psoriasis. Light activation of endogenous PpIX for the treatment of psoriasis has never been studied.
OBJECTIVE: The purpose of this study was to determine the efficacy of multiple exposures to blue light in patients with plaque psoriasis.
METHODS: A total of 17 patients with plaque psoriasis presenting increased endogenous level of PpIX were enrolled. Of the 2 identified plaques on each patient, 1 was exposed to 10 J/cm(2) of blue light from a fluorescent panel 3 times per week for 4 consecutive weeks. Plaque severity was assessed in a blinded fashion. PpIX levels were measured with in vivo fluorescence spectroscopy weekly.
RESULTS: A single exposure to blue light induced almost complete photobleaching of PpIX. There was no significant difference between the mean psoriasis severity score of the plaques before and after 12 exposures to blue light.
CONCLUSION: Repeated exposure to blue light did not improve psoriasis.
Early onset of action and efficacy of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis.
Papp KA, Guenther L, Boyden B, Larsen FG, Harvima RJ, Guilhou JJ, Kaufmann R, Rogers S, van de Kerkhof PC, Hanssen LI, Tegner E, Burg G, Talbot D, Chu A.
Probity Medical Research, Waterloo, Ontario, Canada.
J Am Acad Dermatol 2003 Jan;48(1):48-54 Abstract quote
BACKGROUND: Calcipotriene and betamethasone dipropionate are topical treatments for psoriasis vulgaris. Their mode of action is different. Improved risk/benefit may result with concomitant use of the two compounds together. A new vehicle has been created with the objective of obtaining optimal stability of both calcipotriene and betamethasone dipropionate in the combination product.
OBJECTIVE: We compared the clinical efficacy of a fixed combination of calcipotriene and betamethasone dipropionate in a new vehicle to calcipotriene in the new vehicle, betamethasone in the new vehicle, and the new vehicle alone.
METHODS: This was an international, multicenter, prospective, randomized, double-blind, parallel-group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment.
RESULTS: The mean percentage reduction in PASI from baseline to end of treatment was 73.2% in the combination group (n = 301), 48.8% in the calcipotriene group (n = 308), 63.1% in the betamethasone dipropionate group (n = 312) and 28.8% in the new vehicle group (n = 107), (P < .001). The mean percentage reduction in PASI during the first week was 48.1%, 28.4%, 41.4%, and 21.5%, respectively (P < .001).
CONCLUSION: A combination product of calcipotriene 50 microg/g and betamethasone dipropionate 0.5 mg/g in the new vehicle shows superior efficacy with a more rapid onset of action than the new vehicle containing either constituent alone in the treatment of psoriasis vulgaris.
Combination regimens with topical calcipotriene
Arch Dermatol 2000;136:1536-1543
Meta-analysis of 11 randomized trials involving 756 patients with chronic plaque psoriasis
Looked at treatment combinations with:
Insufficient evidence to support any large effects of combination treatment
Cost-effectiveness comparison of therapy for psoriasis with a methotrexate-based regimen versus a rotation regimen of modified cyclosporine and methotrexate.
Ellis CN, Reiter KL, Bandekar RR, Fendrick AM.
Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
J Am Acad Dermatol 2002 Feb;46(2):242-50 Abstract quote
BACKGROUND: Because health care resources are limited, therapeutic regimens should be assessed for their relative costs and effectiveness.
OBJECTIVE: We assessed cost-effectiveness for treating psoriasis using two strategies: one consisted principally of methotrexate and the other was principally a rotational schedule of modified cyclosporine (Neoral) with methotrexate.
METHODS: We performed a cost-effectiveness analysis using a computerized decision analytic model of simulated patients with moderate to severe psoriasis. Patients were randomly assigned to receive treatment with one of the two strategies. Direct costs included acquisition of medications, laboratory and physician fees, and costs of treating side effects. Because of uncertainty regarding rates of clearing of psoriasis, the relative efficacy of methotrexate and cyclosporine was varied over a wide range in a sensitivity analysis.
RESULTS: In the base case over a 10-year treatment period, the methotrexate strategy cost $33,000 and provided approximately 2 years clear of psoriasis compared with $38,000 and approximately 4 years clear of psoriasis for the rotational strategy. When the relative effectiveness of cyclosporine to methotrexate in clearing psoriasis varied from approximately 1 to 20, the rotational strategy cost from $4100 to $2700 per incremental clear year.
CONCLUSION: In selecting therapies for psoriasis patients, both costs and effectiveness should be considered. In this simulation, patients could obtain additional periods clear of psoriasis at an incremental cost by using cyclosporine in rotation with methotrexate. If even a small utility gain accompanies the complete clearing of psoriasis, such a strategy may be a worthwhile investment of resources comparable to other healthcare interventions.
A multicenter dose-escalation trial with denileukin diftitox (ONTAK, DAB389IL-2) in patients with severe psoriasis
Ann Martin, MD
Elsa Gutierrez, MD
Jennie Muglia, MD
Charles J. McDonald, MD
Cynthia Guzzo, MD
Alice Gottlieb, MD, PhD
Amy Pappert, MD
W. Thomas Garland, MD
Jerry Bagel, MD
Patricia Bacha, PhD
St Louis, Missouri; Providence, Rhode Island; Philadelphia, Pennsylvania; New Brunswick, Lawrenceville, and East Windsor, New Jersey; and San Diego, California
J Am Acad Dermatol 2001;45:871-81 Abstract quote
Background: Denileukin diftitox, a fusion protein targeting both malignant and normal activated lymphocytes, has been shown previously to have antipsoriatic activity. However, the ideal dosing regimen for treating psoriasis was not established.
Objective: We examined the safety and efficacy of denileukin diftitox in patients with severe plaque-type psoriasis.
Methods: This was a cohort dose-escalation trial. Patients were administered denileukin diftitox on 3 consecutive days every other week. Patients were evaluated for toxicity, improvement in psoriasis, immunogenicity, and serum levels.
Results: Thirty-five patients were treated at 3 dose levels. Eight patients had a 50% decrease or more in Psoriasis Area and Severity Index score from baseline (0/10 at 0.5 µg/kg per day, 1/10 at 1.5 µg/kg per day, and 7/15 at 5 µg/kg per day). Adverse events primarily consisted of constitutional events and skin reactions.
Conclusions: The potential antipsoriatic activity of denileukin diftitox demonstrated in this study was comparable to that observed in other psoriasis studies with this agent. However, this dosing regimen was better tolerated than the dosing regimen used in the last study with denileukin diftitox in psoriasis patients.
EFALIZUMAB (ANTI CD11a)
- Extended efalizumab therapy improves chronic plaque psoriasis: results from a randomized phase III trial.
Leonardi CL, Papp KA, Gordon KB, Menter A, Feldman SR, Caro I, Walicke PA, Compton PG, Gottlieb AB; Efalizumab Study Group.
Saint Louis University School of Medicine, St. Louis, Missouri, USA.
J Am Acad Dermatol. 2005 Mar;52(3 Pt 1):425-33. Abstract quote
BACKGROUND: Efalizumab inhibits multiple T-cell-mediated processes.
OBJECTIVE: To evaluate 12- and 24-week efalizumab therapy for psoriasis.
METHODS: In this phase III, randomized, double-blind trial, 498 patients received subcutaneous 1 or 2 mg/kg/wk efalizumab or placebo for 12 weeks. Efalizumab-treated patients who achieved <75% Psoriasis Area and Severity Index improvement (PASI-75) were re-randomized to a second 12-week course of treatment. Results At week 12, 39% and 27% of efalizumab-treated patients (1 and 2 mg/kg, respectively) achieved PASI-75 (vs 2% placebo; P < .001, both dose groups). At week 24, an additional 20% of efalizumab-treated patients achieved PASI-75 (vs placebo 7%, P = .018). Efalizumab was well tolerated.
CONCLUSION: Twelve-week efalizumab treatment resulted in significant improvement; extension of therapy to 24 weeks resulted in additional improvement in patients who initially had not achieved PASI-75. There were no significant changes in safety profile during weeks 13-24.
- Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis.
Menter A, Gordon K, Carey W, Hamilton T, Glazer S, Caro I, Li N, Gulliver W.
Author Affiliations: Baylor University Medical Center, Dallas, Tex.
Arch Dermatol. 2005 Jan;141(1):31-8. Abstract quote
OBJECTIVE: To assess the efficacy and safety of a 24-week course of efalizumab.
DESIGN: Phase 3, randomized, double-blind, parallel-group, placebo-controlled 12-week study followed by a 12-week open-label study.
SETTING: Outpatient dermatology clinics.Patients A total of 556 patients with moderate to severe chronic plaque psoriasis who were seeing an outpatient dermatologist were included in the study.Intervention For weeks 1 to 12, the 556 patients were randomized to receive 1 mg/kg of efalizumab weekly or placebo subcutaneously. For weeks 13 to 24, 516 of these patients received 1 mg/kg of efalizumab weekly.
MAIN OUTCOME MEASURES: Proportion of patients with a 75% or greater improvement in Psoriasis Area and Severity Index (PASI-75), a 50% or greater improvement in PASI (PASI-50), static Physician's Global Assessment (sPGA) rating of minimal or clear, and improvements in Dermatology Life Quality Index (DLQI), itching scale, and Psoriasis Symptom Assessment (PSA) frequency and severity scores at weeks 12 and 24. Safety was evaluated by reviewing adverse events, laboratory parameters, vital signs, and anti-efalizumab antibodies.
RESULTS: At week 12, 26.6% of efalizumab-treated patients achieved PASI-75 and 58.5% achieved PASI-50. After 24 weeks of continuous efalizumab therapy, PASI responses increased: 43.8% of patients achieved PASI-75 and 66.6% achieved PASI-50. The percentage of patients who achieved an sPGA rating of minimal or clear increased from 25.7% to 35.9%. The mean percentage of improvement in all patient-reported outcomes (DLQI, itching scale, and PSA frequency and severity scores) at week 12 was maintained at week 24 (DLQI, 49.2%; itching scale, 42.2%; PSA frequency, 47.6%; PSA severity, 47.3%). There was a decline in overall reported adverse events from weeks 1 to 12 (80.4%) to weeks 13 to 24 (63.2%) without evidence of cumulative toxic effects.
Conclusion Extending efalizumab treatment from 12 to 24 weeks leads to improved efficacy and maintenance of quality of life with no evidence of cumulative toxic effects noted in patients with moderate to severe chronic plaque psoriasis.
Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial.
Gordon KB, Papp KA, Hamilton TK, Walicke PA, Dummer W, Li N, Bresnahan BW, Menter A; Efalizumab Study Group.
Loyola University Medical Center, Maywood, Ill 60153, USA.
JAMA. 2003 Dec 17;290(23):3073-80 Abstract quote.
CONTEXT: Because T-cell interactions are involved in the pathophysiology of psoriasis, therapy with a T-cell modulator may have beneficial effects on psoriasis severity and health-related quality of life (HRQL).
OBJECTIVE: To assess the efficacy and safety of efalizumab, a T-cell modulator, in patients with plaque psoriasis.
DESIGN, SETTING, AND PATIENTS: Phase 3 randomized, double-blind, parallel-group, placebo-controlled trial involving 556 adult patients with stable, moderate to severe plaque psoriasis and conducted at 30 study centers in the United States and Canada between January and July 2002.
INTERVENTIONS: Patients were randomly assigned in a 2:1 ratio to receive 12 weekly doses of subcutaneous efalizumab, 1 mg/kg (n = 369), or placebo equivalent (n = 187).
MAIN OUTCOME MEASURES: At least 75% improvement on the Psoriasis Area and Severity Index (PASI-75); improvement on the overall Dermatology Life Quality Index (DLQI), Itching Visual Analog Scale (VAS), and Psoriasis Symptom Assessment (PSA) at week 12 vs baseline.
RESULTS: Efalizumab-treated patients experienced significantly greater improvement on all end points than placebo-treated patients. Twenty-seven percent of efalizumab-treated patients achieved PASI-75 vs 4% of the placebo group ( P<.001). Efalizumab-treated patients exhibited significantly greater mean percentage improvement than placebo-treated patients on the overall DLQI (47% vs 14%; P<.001), Itching VAS (38% vs -0.2%; P<.001), and PSA frequency and severity subscales (48% vs 18% and 47% vs 17%, respectively; P<.001 for both) at the first assessment point. Efalizumab was safe and well tolerated, with primarily mild to moderate adverse events.
CONCLUSION: In this 12-week study, efalizumab resulted in significant improvements in clinical end points, including physician-assessed and dermatology-specific patient-reported HRQL measures, in patients with moderate to severe plaque psoriasis.
The treatment of moderate to severe psoriasis with a new anti-CD11a monoclonal antibody
Kim Papp, MD
Robert Bissonnette, MD, etal.
Waterloo, Markham, Mississauga, and Toronto, Ontario; Montreal, Sherbrooke, Quebec; Vancouver, British Columbia; and St Johns, Newfoundland, Canada; New York, New York; Charlottesville, Virginia; and South San Francisco and Berkeley, California
J Am Acad Dermatol 2001;45:665-74. Abstract quote
Background: Anti-CD11a (hu1124) is a humanized monoclonal antibody directed against the CD11a subunit of LFA-1. This study investigated whether treatment with anti-CD11a antibody provides clinical benefit to patients with moderate to severe plaque psoriasis.
Methods: This was a double-blind, placebo-controlled, phase II, multicenter study. In total, 145 patients with minimum Psoriasis Area and Severity Index scores of 12 and affected body surface area of 10% or more were sequentially enrolled into low-dose (0.1 mg/kg, n = 22) or high-dose (0.3 mg/kg, n = 75) groups. Within groups, patients were randomized to treatment or placebo (n = 48) in a 2:1 ratio. Drug was administered intravenously at weekly intervals for 8 weeks.
Results: The percentage of subjects achieving more than 50% improvement in physician's global assessment at day 56 (1 week after final dose) was 15% and 48% for placebo and 0.3 mg/kg of drug, respectively (P = .002). A physician's global assessment of excellent (>75% improvement) was greater in the 0.3 mg/kg group versus placebo (25% vs 2%, P = .0003). Average Psoriasis Area and Severity Index scores at day 56 were 13.9 ± 7.5 (placebo) and 10.9 ± 8.4 (0.3 mg/kg) (P < .0001). Epidermal thickness was reduced in the 0.3 mg/kg group compared with the placebo group (37% vs 19%, P = .004). Treatment was well tolerated; mild to moderate flu-like complaints were the most common adverse events. White blood cell counts and lymphocyte counts transiently increased. Depletion of circulating lymphocytes did not occur.
Conclusions: Anti-CD11a antibody administered intravenously in 8 weekly doses of 0.3 mg/kg was well tolerated and induced clinical and histologic improvements in psoriasis.
Psoriasis as a Model for T-Cell-Mediated Disease: Immunobiologic and Clinical Effects of Treatment With Multiple Doses of Efalizumab, an Anti-CD11a Antibody.
Gottlieb AB, Krueger JG, Wittkowski K, Dedrick R, Walicke PA, Garovoy M.
University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Clinical Research Center, 1 Robert Wood Johnson Place, Room CN19, New Brunswick, NJ 08903-0019.
Arch Dermatol 2002 May;138(5):591-600 Abstract quote
BACKGROUND: Leukocyte function-associated antigen 1 (LFA-1), consisting of CD11a and CD18 subunits, plays an important role in T-cell activation and leukocyte extravasation.
OBJECTIVE: To test whether blocking CD11a decreases immunobiologic and clinical activity in psoriatic plaques.
DESIGN: Open-label, multicenter, dose escalation study.
PATIENTS: Thirty-nine patients with moderate-to-severe psoriasis.
INTERVENTION: Intravenous infusions of efalizumab, a humanized anti-CD11a monoclonal antibody, for 7 weeks at doses of 0.1 mg/kg every other week or 0.1 mg/kg weekly (category 1), 0.3 mg/kg weekly (category 2), and 0.3 increasing to 0.6 or 1.0 mg/kg weekly (category 3). Skin biopsies were performed on days 0, 28, and 56.
MAIN OUTCOME MEASURES: Serum efalizumab levels, levels of total and unoccupied T-cell CD11a, T cell counts, epidermal thickness, cutaneous intercellular adhesion molecule 1 (ICAM-1) and keratin 16 (K16) expression, Psoriasis Area and Severity Index (PASI) scores. RESULTS: Dose-response relationships were observed for pharmacokinetics and pharmacodynamic measures. Category 1 failed to maintain detectable serum efalizumab or T cell CD11a down-modulation between doses. Category 2 achieved both. Category 3 achieved both and additionally maintained sustained T-cell CD11a saturation between doses. A dose-response relationship was also observed clinically and histologically. The mean decrease in the PASI score was 47% in category 3, 45% in category 2, and 10% in category 1 (P<.001). Epidermal and dermal T-cell counts, epidermal thickness, and ICAM-1 and K16 expression decreased in categories 2 and 3 but not in category 1. Circulating lymphocyte counts increased in categories 2 and 3.
CONCLUSIONS: At doses of 0.3 mg/kg or more per week, intravenous efalizumab produced significant clinical and histologic improvement in psoriasis, which correlated with sustained serum efalizumab levels and T-cell CD11a saturation and down-modulation.
- Etanercept therapy for patients with psoriatic arthritis and concurrent hepatitis C virus infection: report of 3 cases.
Magliocco MA, Gottlieb AB.
Clinical Research Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901-0019, USA.
J Am Acad Dermatol. 2004 Oct;51(4):580-4. Abstract quote
Psoriasis and psoriatic arthritis are exacerbated by interferon alfa and other treatments for hepatitis C virus infection. Immunosuppressants and hepatotoxic drugs are relatively contraindicated in hepatitis C. Data in the literature suggest that etanercept is a safe option in the treatment of patients with rheumatoid arthritis and concurrent hepatitis C.
We present three cases in which we have successfully used etanercept to treat psoriatic arthritis/psoriasis in patients with hepatitis C without worsening their hepatitis or interfering with their hepatitis treatment.
With close monitoring of viral load and hepatic enzymes, etanercept may be a safe option for treating psoriatic arthritis/psoriasis in patients who also have hepatitis C.
INFLIXIMAB (TUMOR NECROSIS FACTOR ANTIBODY)
- J Am Acad Dermatol. 2007 Jan;56(1):31.e1-15. Abstract quote
BACKGROUND: Previous studies of infliximab in psoriasis have demonstrated rapid improvement with induction therapy and sustained response with regularly administered maintenance therapy.
OBJECTIVE: The efficacy and safety of continuous (every-8-week) and intermittent (as-needed) maintenance regimens were compared.
METHODS: Patients with moderate-to-severe psoriasis (n = 835) were randomized to induction therapy (weeks 0, 2, and 6) with infliximab 3 mg/kg or 5 mg/kg or placebo. Infliximab-treated patients were randomized again at week 14 to continuous or intermittent maintenance regimens at their induction dose.
RESULTS: At week 10, 75.5% and 70.3% of patients in the infliximab 5 mg/kg and 3 mg/kg groups, respectively, achieved PASI 75; 45.2% and 37.1% achieved PASI 90 (vs 1.9% [PASI 75] and 0.5% [PASI 90] for placebo; P < .001). Through week 50, PASI responses were better maintained with continuous compared with intermittent therapy within each dose, and with 5 mg/kg compared with 3 mg/kg continuous therapy.
LIMITATIONS: Longer term (>1 year) maintenance therapy and further study of infliximab serum concentrations over this period, in both PASI 75 responders and non-responders, would be preferable.
CONCLUSIONS: Through week 50, response was best maintained with continuous infliximab therapy. Infliximab was generally well-tolerated in most patients.
- Infliximab induction therapy for patients with severe plaque-type psoriasis: a randomized, double-blind, placebo-controlled trial.
Gottlieb AB, Evans R, Li S, Dooley LT, Guzzo CA, Baker D, Bala M, Marano CW, Menter A.
University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
J Am Acad Dermatol. 2004 Oct;51(4):534-42. Abstract quote
BACKGROUND: Tumor necrosis factor-alpha is a key mediator in the pathogenesis of psoriasis. Infliximab is a monoclonal antibody that specifically binds to tumor necrosis factor-alpha, blocking its biologic activity.
OBJECTIVE: The purpose of this study was to access the efficacy and safety of infliximab induction therapy for patients with severe plaque psoriasis.
METHODS: In this multicenter, double-blind, placebo-controlled trial, 249 patients with severe plaque psoriasis were randomly assigned to receive intravenous infusions of either 3 or 5 mg/kg of infliximab or placebo given at weeks 0, 2, and 6. The primary end point was the proportion of patients who achieved at least 75% improvement in Psoriasis Area and Severity Index score from baseline at week 10. At week 26, patients whose Physician Global Assessment indicated moderate or severe disease were eligible for a single intravenous infusion of their assigned treatment to assess the safety of retreatment after a 20-week, treatment-free interval.
RESULTS: At week 10, 72% of patients treated with infliximab (3 mg/kg) and 88% of patients treated with infliximab (5 mg/kg) achieved a 75% or greater improvement from baseline in Psoriasis Area and Severity Index score compared with 6% of patients treated with placebo (P <.001). Improvement was observed in both infliximab groups as early as 2 weeks. Overall, 63%, 78%, and 79% of patients in the placebo, 3-, and 5-mg/kg groups, respectively, reported one or more adverse events.
CONCLUSIONS: Infliximab treatment resulted in a rapid and significant improvement in the signs and symptoms of psoriasis. Infliximab was generally well tolerated.
Potential of tumor necrosis factor inhibitors in psoriasis and psoriatic arthritis.
Krueger G, Callis K.
University of Utah School of Medicine, Department of Dermatology, Salt Lake City. Dr Krueger is a consultant for Amgen Inc, Centocor Inc, and Serono Inc. Dr Callis has been a consultant for Amgen Inc and Centocor Inc.
Arch Dermatol. 2004 Feb;140(2):218-25. Abstract quote
Objectives To summarize the role of tumor necrosis factor (TNF) in the pathogenesis of psoriasis and psoriatic arthritis (PsA) and to present the latest data on the efficacy of TNF inhibitors in these diseases.
Data Sources PubMed was used with the following indexing terms: TNF, TNF inhibitor, psoriasis, psoriatic arthritis, etanercept, infliximab, and/or T cell. Abstract booklets and manufacturer's package inserts were also used. When possible, only sources published after the year 2000 were incorporated.
Study Selection Sources that described a role for TNF in the pathogenesis of psoriasis and PsA were selected based on relevance. Clinical trials that examined the efficacy of the TNF inhibitors etanercept and infliximab in psoriasis and PsA were selected.
Data Extraction Data were extracted if they represented safety information, the American College of Rheumatology criteria for improvement, the Health Assessment Questionnaire, or the PsA response criteria. These data were abstracted independently by the authors.
Data Synthesis Aberrant regulation of TNF is involved in the development of psoriasis and PsA. Therefore, recent intervention strategies for psoriasis and PsA have incorporated biologic agents that specifically target TNF. Etanercept and infliximab are effective at reducing disease activity and are generally well tolerated in the treatment of psoriasis and PsA.
Conclusion Tumor necrosis factor plays a major role in the pathogenesis of psoriasis and PsA, and TNF antagonists provide clinicians with a worthy alternative to traditional therapies, which are associated with toxic effects and poor compliance.
Infliximab monotherapy provides rapid and sustained benefit for plaque-type psoriasis.
Gottlieb AB, Chaudhari U, Mulcahy LD, Li S, Dooley LT, Baker DG.
Clinical Research Center, University of Medicine and Dentistry of New Jersey-The Robert Wood Johnson Medical School, and Centocor Incorporated.
J Am Acad Dermatol. 2003 Jun;48(6):829-35 Abstract quote
BACKGROUND: Effective, rapid-acting, safe therapies are needed for the long-term treatment of psoriasis.
OBJECTIVE: We sought to evaluate infliximab monotherapy in maintaining clinical benefit in psoriasis.
METHODS: A total of 33 patients received 3 doses of 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6 (double-blind phase). During the open-label phase (weeks 10-26), responding patients were evaluated for relapse (loss of at least half of the improvement in the Psoriasis Area Severity Index score at week 10) and retreated with open-label infliximab (5 or 10 mg/kg) as needed. Placebo nonresponders were treated with an induction regimen of infliximab (5 or 10 mg/kg) and followed up through week 26.
RESULTS: In all, 29 patients received either 5 or 10 mg/kg of infliximab in the open-label extension. At week 26, psoriasis area severity index response was maintained in 40% and 73% of patients receiving 5 and 10 mg/kg of infliximab, respectively.
CONCLUSION: Infliximab produced a rapid, effective, and sustainable (through week 26) effect in patients with moderate to severe psoriasis.
Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-alpha monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris.
Gottlieb AB, Masud S, Ramamurthi R, Abdulghani A, Romano P, Chaudhari U, Dooley LT, Fasanmade AA, Wagner CL.
Clinical Research Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, and Centocor Inc.
J Am Acad Dermatol 2003 Jan;48(1):68-75 Abstract quote
OBJECTIVE: Infliximab monotherapy provided a rapid and high degree of clinical benefit in patients with moderate to severe psoriasis in a previously conducted trial. Herein we describe the pharmacodynamic and pharmacokinetic results observed in this clinical trial.
METHODS: Patients with psoriasis received 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6. Immunohistochemical analysis of lesional (weeks 0, 2, 10) and nonlesional (week 0) biopsies was conducted. Median infliximab half-life and peak serum concentrations over time were calculated.
RESULTS: Infliximab immunotherapy resulted in rapid and dramatic decreases in epidermal inflammation and normalization of keratinocyte differentiation in psoriatic plaques; these changes preceded maximal clinical response. Infliximab concentrations were maintained above the detection limit (0.1 mg/mL) in the majority of patients through week 14.
CONCLUSION: The clinical and immunohistologic data demonstrate a pivotal role for tumor necrosis factor-alpha in the pathogenesis of psoriasis and support further development of drugs targeting tumor necrosis factor-alpha.
The Effectiveness of Tumor Necrosis Factor alpha Antibody (Infliximab) in Treating Recalcitrant Psoriasis: A Report of 2 Cases.
O'Quinn RP, Miller JL.
3900 The Vanderbilt Clinic, Nashville, TN 37232.
Arch Dermatol 2002 May;138(5):644-8 Abstract quote
BACKGROUND: Psoriasis is being recognized as an autoimmune disease in which immunocyte-derived cytokines are thought to drive the development of the altered keratinocyte phenotype. Although the role of tumor necrosis factor alpha (TNF-alpha) in psoriasis is not completely understood, it may underlie many of the key steps that lead to induction and maintenance of the disease. Infliximab is an immunoglobulin monoclonal antibody that binds and inactivates TNF-alpha and has been successfully used in the management of TNF-alpha-mediated diseases, such as Crohn disease and rheumatoid arthritis.
OBSERVATIONS: Two patients with recalcitrant psoriasis that was unresponsive to multiple skin-directed and systemic therapies were treated with a single infusion of infliximab. The treatments resulted in rapid and complete clearing of psoriatic erythroderma and resolution of symptoms of arthritis in one case and complete clearing of widespread psoriatic plaques and improvement of symptoms of arthritis and inflammatory bowel disease in the other. The single treatments with infliximab were well tolerated with no immediate or long-term adverse effects noted.
CONCLUSION: A single infusion of infliximab at 5 to 10 mg/kg resulted in the rapid and complete clearing of recalcitrant psoriatic plaques and erythroderma with a disease-free interval of 3 to 4 months in these 2 patients and improved the symptoms of psoriatic arthritis.
Treatment of psoriasis with the chimeric monoclonal antibody against tumor necrosis factor alpha, infliximab.
Schopf RE, Aust H, Knop J.
Department of Dermatology, Johannes Gutenberg University, Mainz.
J Am Acad Dermatol 2002 Jun;46(6):886-91 Abstract quote
BACKGROUND: Psoriatic skin lesions in patients with Crohn's disease or psoriatic arthritis have shown improvement during infliximab treatment.
OBJECTIVE: The purpose of our study was to systematically assess the effects of infliximab in patients with psoriatic skin lesions.
METHODS: Eight patients with severe psoriasis were enrolled in an open-label clinical trial. Patients received infliximab, 5 mg/kg, intravenously at weeks 0, 2, and 6. The Psoriasis Area and Severity Index (PASI) was used to monitor disease activity at weeks 0, 2, 4, 6, 8, 10, and 14. Week 10 was the end point of the treatment phase; week 14 was the follow-up end point. Pruritus was assessed on a scale of 0 to 3. Histologic sections were prepared from biopsy specimens of uninvolved skin and of psoriatic lesions at weeks 0, 1, and 10 to measure epidermal thickness with the use of a microscopic micrometer grid.
RESULTS: The PASI diminished from 21.8 +/- 4.2 (mean +/- SE) at week 0 to 3.4 +/- 2.0 at week 10, corresponding to 10.7% +/- 4.3% of the original values (100%); on follow-up at week 14, the PASI was 7.1 +/- 2.7 (or still 33.3% +/- 11.3% of the values at week 0). Pruritus decreased from 2.5 +/- 0.26 at week 0 to 0.43 +/- 0.2 at week 10 and to 0.83 +/- 11.3 at week 14. Likewise, epidermal thickness (acanthosis) tended to normalize from 0.41 +/- 0.06 mm at week 0 to 0.14 +/- 0.02 mm at week 10. No adverse effects other than fatigue during infusion on some occasions were reported.
CONCLUSION: Although psoriasis tends to recur beyond 2 months of the infusions, this open study provides evidence that infliximab is an effective treatment.
Clinical and Immunologic Assessment of Patients With Psoriasis in a Randomized, Double-blind, Placebo-Controlled Trial Using Recombinant Human Interleukin 10.
Kimball AB, Kawamura T, Tejura K, Boss C, Hancox AR, Vogel JC, Steinberg SM, Turner ML, Blauvelt A.
Dermatology Branch, National Cancer Institute, Building 10/Room 12N238, 10 Center Dr MSC 1908, Bethesda, MD 20892-1908
Arch Dermatol 2002 Oct;138(10):1341-6 Abstract quote
BACKGROUND: In several open-label studies, recombinant human interleukin 10 (rhIL-10), a type 2 anti-inflammatory cytokine, has been reported to improve psoriasis, a disease characterized by type 1 cytokine inflammation.
OBJECTIVE: To evaluate the safety, efficacy, and immunologic parameters in individuals with psoriasis treated with rhIL-10.
DESIGN AND INTERVENTION: Patients received rhIL-10 (20 micro g/kg) or placebo subcutaneously 3 times weekly for 12 weeks in a randomized, double-blind manner.
SETTING AND PATIENTS: National Institutes of Health Clinical Center in Bethesda. Twenty-eight patients with moderate-to-severe psoriasis as defined by a Psoriasis Area Severity Index (PASI) score of 10 or higher.
MAIN OUTCOME MEASURE: The primary clinical end point was the mean percentage change in the PASI score comparing baseline and week 12 scores. Intracellular cytokine production by peripheral blood mononuclear cells (PBMCs) was measured by flow cytometry.
RESULTS: There was no significant difference in the mean percentage change in the PASI score from baseline to week 12 between the rhIL-10-treated group and control patients (17% vs 13% improvement, respectively; P =.69), although a modest trend toward improvement in patients receiving rhIL-10 was documented at both the 6- and 8-week points. Interestingly, proinflammatory and type 1 cytokine production by PBMCs progressively declined in the rhIL-10-treated patients during the entire 12-week study period.
CONCLUSIONS: Treatment with rhIL-10 resulted in only temporary clinical improvement in psoriasis, despite sustained systemic decreases in proinflammatory and type 1 cytokine production. These data suggest that immunotherapy that decreases the ratio of systemic type 1 and type 2 cytokine production does not necessarily lead to improvement of type 1 cytokine-mediated disease.
308-nm Excimer Laser for the Treatment of Psoriasis: Induration-Based Dosimetry.
Taneja A, Trehan M, Taylor CR.
Gange Photomedicine Research Center, Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, Boston.
Arch Dermatol. 2003 Jun;139(6):759-64. Abstract quote
OBJECTIVE: To determine the response of stubborn psoriatic plaques to the 308-nm excimer laser.
DESIGN: Controlled study with a before-after design.
SETTING: A university-based clinical research center.Patients Adult subjects with recalcitrant plaque psoriasis that have not responded to other therapies for at least 2 months.Interventions Selected psoriatic plaques were treated with the 308-nm excimer laser. One lesion was left as a control. Each plaque was treated 2 times a week, with an initial dose based solely on the induration component of the modified Psoriasis Area and Severity Index score for that lesion. Subsequent treatments were twice a week with dosage increments up to 50%, based on the change in induration. Four final consolidation doses were given once the induration score was reduced to zero.
RESULTS: Eighteen subjects were treated. There were 4 dropouts because of various scheduling problems. In the remaining 14 subjects, 44 plaques received a mean of 10 treatments (range, 4-14). Treatments were quick and well tolerated. The mean cumulative dose was 8.8 J/cm2 (range, 2.2-22.8 J/cm2). Compared with controls, treated plaques showed significant improvement (P<.001). The only adverse event was a mild sunburn-like reaction in 2 subjects after 1 treatment.
CONCLUSIONS: Selective targeting of laser-generated 308-nm excimer radiation with this convenient subblistering dosage schedule based on induration allows for individualized treatment plans for each plaque. Clearing of stubborn psoriatic lesions occurs rapidly and safely.
High-dose 308-nm excimer laser for the treatment of psoriasis.
Trehan M, Taylor CR.
Gange Photomedicine Research Center, Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School
J Am Acad Dermatol 2002 May;46(5 Pt 1):732-7 Abstract quote
BACKGROUND: The excimer laser can deliver high-intensity ultraviolet B (UVB) energy at 308 nm, a wavelength similar to that used in narrow-band UVB phototherapy.
OBJECTIVE: The goal of this investigation was to evaluate the role of high-dose single treatments with the excimer 308-nm laser in stable plaque-type psoriasis.
METHODS: Eighteen volunteers were enrolled in the study. Two plaques were selected and half of each plaque was held as a control while the other half was treated with a single dose of either 8 or 16 times the minimal erythema dose.
RESULTS: Sixteen subjects completed the study. Two patients signed up but never actually participated because of scheduling problems. Eleven showed significant improvement within 1 month, and 5 still demonstrated persistent areas of clearing at 4 months.
CONCLUSION: As little as one high-dose excimer laser treatment can be effective for localized plaque-type psoriasis. Multiple treatments or other irradiation schedules with this innovative device may prove even more efficacious.
Efficacy of the 308-nm excimer laser for treatment of psoriasis: results of a multicenter study.
Feldman SR, Mellen BG, Housman TS, Fitzpatrick RE, Geronemus RG, Friedman PM, Vasily DB, Morison WL.
Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1071, USA.
J Am Acad Dermatol 2002 Jun;46(6):900-6 Abstract quote
OBJECTIVE: Our purpose was to demonstrate the efficacy of the 308-nm excimer laser for treatment of psoriasis.
METHODS: This study was a multicenter open trial from 5 dermatology practices (one university-based and 4 private practices). Up to 30 patients per center with stable mild to moderate plaque-type psoriasis constituted the study population. Patients received 308-nm ultraviolet B doses to affected areas. The initial dose was based on multiples of a predetermined minimal erythema dose. Subsequent doses were based on the response to treatment. Treatments were scheduled twice weekly for a total of 10 treatments. The main outcome measure was 75% clearing of the target plaque. Time to clearing was analyzed by Kaplan-Meier methods, accounting for truncated observations.
RESULTS: One hundred twenty-four patients were enrolled in the study, and 80 completed the entire protocol. The most common reason for exiting from the study was noncompliance. Of the patients who met the protocol requirements of 10 treatments or clearing, 72% (66/92) achieved at least 75% clearing in an average of 6.2 treatments. Eighty-four percent of patients (95% confidence interval [CI], 79%-87%) reached improvement of 75% or better after 10 or fewer treatments. Fifty percent of patients (95% CI, 35%-61%) reached improvement of 90% or better after 10 or fewer treatments. Common side effects included erythema, blisters, hyperpigmentation, and erosions, but they were well tolerated.
CONCLUSIONS: Monochromatic 308-nm excimer laser treatment appears to be effective and safe for psoriasis. It requires fewer patient visits than conventional phototherapy, and, unlike those treatments, the laser targets only the affected areas of the skin, sparing the surrounding uninvolved skin.
Medium-dose 308-nm excimer laser for the treatment of psoriasis.
Trehan M, Taylor CR.
Gange Photomedicine Research Center, Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School.
J Am Acad Dermatol 2002 Nov;47(5):701-8 Abstract quote
BACKGROUND: The excimer laser delivers targeted ultraviolet B 308-nm radiation.
OBJECTIVE: This investigation evaluated the efficacy of multiple, medium-dose excimer 308-nm laser treatments for psoriasis.
METHODS: Twenty volunteers with plaque psoriasis were enrolled. Six plaques received treatment 3 times per week for up to 8 weeks; another plaque served as a control. As in standard phototherapy, a flexible dose escalation scheme was implemented during the course of treatment. Modified Psoriasis Area and Severity Index scores were rendered throughout the study with follow-ups at 1, 2, 4, and 6 months.
RESULTS: Fifteen subjects completed the study without complications. The mean number of treatments to achieve >95% clearance was 10.6. The mean cumulative UV radiation dose was 6.1 J/cm(2), and the mean remission time was 3.5 months.
CONCLUSION: A thrice-weekly, medium-dose irradiation schedule with the 308-nm laser can effectively clear localized plaque-type psoriasis in fewer treatments with an overall lower cumulative dose, compared with standard phototherapy. This innovative UV device allows specific targeting of affected sites without needless exposure of unaffected skin.
Neovastat (AE-941), an inhibitor of angiogenesis: Randomized phase I/II clinical trial results in patients with plaque psoriasis.
Sauder DN, Dekoven J, Champagne P, Croteau D, Dupont E.
Department of Dermatology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21287, USA.
J Am Acad Dermatol 2002 Oct;47(4):535-41 Abstract quote
There is considerable evidence to support an immunopathogenic basis of psoriasis. However, changes such as altered angiogenesis have also been implicated in the pathogenesis of psoriasis. AE-941 (Neovastat; Aeterna Laboratories, Quebec City Quebec, Canada) is a naturally occurring product currently in clinical investigation that blocks two main mechanisms of angiogenesis activation, namely, vascular endothelial growth factor and matrix metalloproteinase.
We hypothesized that psoriasis could be modulated by inhibiting the neovascularization of psoriatic plaques. We conducted a randomized dose-comparison trial to evaluate the safety and potential therapeutic benefit of AE-941, administered orally to patients with psoriasis. Forty-nine patients with psoriasis were enrolled and assigned to receive AE-941 at 30, 60, 120, or 240 mL/d for 12 weeks. Patients were followed up for another 12-week period. Improvement in the Psoriasis Area and Severity Index (PASI) score was observed in 50%, 41.7%, and 30.8% of te patients receiving 240, 120, and 60 mL/d, respectively. No patients receiving a dosage 30 mL/d showed a PASI score improvement. A statistically significant improvement with increasing dose was observed for the PASI score, severity of itch, and the physician's global assessment. The most commonly reported nonserious drug-related adverse events affected the gastrointestinal system in 12 of 49 patients (primarily nausea, diarrhea, vomiting, flatulence, and constipation) and the skin and appendages in 4 of 49 patients (primarily acne and rash).
This randomized phase I/II study provides evidence that the antiangiogenic agent AE-941 offers a new therapeutic approach to the management of psoriasis.
- Pimecrolimus cream 1% in the treatment of intertriginous psoriasis: a double-blind, randomized study.
Gribetz C, Ling M, Lebwohl M, Pariser D, Draelos Z, Gottlieb AB, Zaias N, Chen DM, Parneix-Spake A, Hultsch T, Menter A.
Mt Sinai School of Medicine, Department of Dermatology, New York, New York, USA.
J Am Acad Dermatol. 2004 Nov;51(5):731-8. Abstract quote
BACKGROUND: Inverse psoriasis can be difficult to treat because of the high sensitivity of intertriginous areas to cutaneous side effects, such as irritation and striae. Pimecrolimus, a well-tolerated, nonatrophogenic, skin-selective inflammatory cytokine inhibitor, has been shown to be effective in the treatment of psoriasis when applied topically under occlusion.
OBJECTIVE: This study evaluated the efficacy and safety of pimecrolimus cream 1% versus vehicle twice a day in the treatment of inverse psoriasis. Methods This was a double-blind, randomized, vehicle-controlled study in 57 patients with moderate to severe inverse psoriasis. Patients were evaluated using Investigator's Global Assessment of overall severity, Target Area Score, and Patient Self-Assessment.
RESULTS: A significant between-group difference was observed early on, with 54% of the pimecrolimus group versus 21% of the vehicle group having an Investigator's Global Assessment score of 0 or 1 (clear or almost clear) at week 2 ( P = .0169). By week 8, 71% of the pimecrolimus group had an Investigator's Global Assessment score of 0 or 1. Change from baseline in Target Area Score was -2.4 (pimecrolimus group) compared with -0.7 (vehicle) at day 3 ( P < .0001). By week 8, 82% of patients using pimecrolimus scored their disease as well or completely controlled versus 41% of the vehicle group ( P = .0007). Adverse events were similar between groups.
CONCLUSION: Pimecrolimus cream 1% is an effective treatment for inverse psoriasis with a rapid onset of action, and is safe and well-tolerated.
Phototherapy utilization for psoriasis is declining in the United States.
Housman TS, Rohrback JM, Fleischer AB Jr, Feldman SR.
Bristol-Myers Squibb Center for Dermatology Research, and Department of Dermatology, Wake Forest University School of Medicine.
J Am Acad Dermatol 2002 Apr;46(4):557-9 Abstract quote
Phototherapy is an established treatment modality for psoriasis. The use of phototherapy for psoriasis appears to be in decline in nonfederal and non-university-based settings.
We used data from the National Ambulatory Medical Care Survey to estimate the number of visits for phototherapy and psoralen ultraviolet A-range (PUVA) light therapy from 1993 to 1998. There were 873,000 visits for UV light therapy in 1993-1994, 189,000 in 1995-1996, and 53,000 in 1997-1998 (P <.0001). There were 175,000 psoralen visits in 1993-1994, 61,000 in 1995-1996, and 25,000 in 1997-1998 (P =.0053). Similar decreases in phototherapy visits occurred in our university-based practice.
The decline in phototherapy represents decreased utilization of a safe and effective treatment for psoriasis.
The persistent risk of genital tumors among men treated with psoralen plus ultraviolet A (PUVA) for psoriasis.
Stern RS, Bagheri S, Nichols K; PUVA Follow Up Study.
Department of Dermatology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA..
J Am Acad Dermatol 2002 Jul;47(1):33-9 Abstract quote
BACKGROUND: In the general population, squamous cell carcinomas (SCCs) of the male genitalia are rare. Ten years ago, we documented a significant dose-dependent increase in the risk of malignant genital neoplasms among men treated with psoralen plus ultraviolet A (PUVA). Since that time, fewer cohort patients have used PUVA, and genital protection among PUVA users is likely to be frequent.
OBJECTIVE: Our aim was to determine the incidence and risk factors for genital neoplasms since 1989 and risk factors for these neoplasms among patients treated with PUVA.
METHODS: We conducted a prospective cohort study of 892 men first treated with PUVA in 1975-1976.
RESULTS: Twenty-four men (2.7%) had 51 genital neoplasms, including 10 patients with a first tumor after May 1, 1989 (the ending date for our 1990 report). Since May 1, 1989, the incidence of invasive penile and scrotal SCCs was elevated 52.6-fold (95% confidence interval, 19.3-114.6) compared with that expected for the general white population. Multivariate models revealed the highest genital tumor risk among men with high-dose exposure to both PUVA and topical tar/ultraviolet B, with an incidence rate ratio of 4.5 (95% confidence interval, 1.3-16.1) compared with the low-dose exposure group.
CONCLUSION: Although use of PUVA has decreased and genital shielding in our cohort has increased, the dose-dependent increase in the risk of genital tumors in men treated with PUVA has persisted. Particularly high risks occur among those with high-dose exposures to both PUVA and topical tar/ultraviolet B.
SALINE SPA WATER
Saline Spa Water or Combined Water and UV-B for Psoriasis vs Conventional UV-B Lessons
From the Salies de Béarn Randomized Study
Christine Léauté-Labrèze, MD; Florence Saillour, MD; Geneviève Chêne, MD; Colette Cazenave, MD; Marie-Laure Luxey-Bellocq, MD; Catherine Sanciaume, MD; Jean François Toussaint, MD; Alain Taïeb, MD
Arch Dermatol. 2001;137:1035-1039 Abstract quote
Objective To study the effects of UV-B therapy and saline spa water given alone or in combination for the treatment of psoriasis.
Design Randomized, controlled, comparative study with blinded observers.
Setting Salies de Béarn, saline spa water center located in the southwest of France.
Participants Seventy-one adult patients with psoriasis with a Psoriasis Area and Severity Index (PASI) score greater than 10. Intervention Patients were randomly assigned to 1 of 3 treatments: spa water alone (group A); UV-B 311-nm phototherapy alone (group B); and a combination of the 2 therapies (group C). The 3 groups were treated on a daily basis 5 days a week for a total of 21 days.
Main Outcome Measures Change in PASI score from baseline as determined by an investigator blinded to randomization; variation in quality of life, adverse effects, and long-term effects (1 year after treatment).
Results Four patients dropped out because of secondary effects. Efficacy was similar in groups B and C, with changes in PASI of -64% and -55%, respectively at 3 weeks. For group A, change in PASI was -29%, thus showing a minor therapeutic effect of saline spa water alone and poor efficacy compared with groups B and C (P<.001). More adverse effects were reported in groups A and C but did not reach significance. Combined saline spa water and UV-B therapy had no sparing effect on UV-B dosages. One year after treatment, no long-term benefit could be attributed specifically to a given regimen, but the patients had overall significantly better PASI scores than at baseline.
Conclusions Saline spa water alone had a minor therapeutic effect in psoriasis, and the beneficial effect of bathing to enhance phototherapy was not demonstrated.
Combination of calcipotriene (Dovonex) ointment and tazarotene (Tazorac) gel versus clobetasol ointment in the treatment of plaque psoriasis: A pilot study.
Bowman PH, Maloney JE, Koo JY.
Department of Dermatology, University of California at San Francisco.
J Am Acad Dermatol 2002 Jun;46(6):907-13 Abstract quote
BACKGROUND: Both calcipotriene and tazarotene have been shown to be effective in the treatment of psoriasis. No study has evaluated the effect of using both agents simultaneously.
OBJECTIVE: Our purpose was to evaluate the effectiveness of combination treatment of psoriasis with calcipotriene ointment and tazarotene gel by comparing them with clobetasol ointment, a class I topical corticosteroid. A secondary objective was to evaluate the clinical compatibility of applying both agents at the same time.
METHODS: This pilot study was a prospective, single-center, open-label, right/left comparison of 28 lesion pairs in 15 patients. It consisted of a 2-week treatment phase, followed by a 4-week post-treatment observation phase.
RESULTS: All 15 patients completed the treatment phase of the study. At the end of the active treatment phase (end of week 2), calcipotriene- and tazarotene-treated lesions showed nearly identical reductions in scaling (P =.93), plaque elevation (P =.76), and overall lesional severity scores (P =.29) compared with their matched clobetasol-treated counterparts. Erythema improved significantly more in clobetasol-treated lesions (P <.05) during the treatment period, but differences became statistically insignificant during the post-treatment period (;P =.20). No patients had significant irritation from the treatments. During the post-treatment phase (weeks 3-6), all lesions worsened; plaque elevation returned somewhat more rapidly in calcipotriene- and tazarotene-treated lesions (P <.01), whereas changes in scaling, erythema, and overall lesional severity were not significantly different between the two treatment groups (P >.05).
CONCLUSION: The nonsteroid combination of twice-daily calcipotriene ointment and once-daily tazarotene gel was not statistically different from twice-daily application of the class I corticosteroid clobetasol ointment in reducing psoriatic scaling, plaque elevation, and overall lesional severity over a 2-week period. There does not seem to be any chemical incompatibility between calcipotriene ointment and tazarotene gel that is clinically significant.
Topical tacrolimus ointment combined with 6% salicylic Acid gel for plaque psoriasis treatment.
Carroll CL, Clarke J, Camacho F, Balkrishnan R, Feldman SR.
Arch Dermatol. 2005 Jan;141(1):43-6. Abstract quote
BACKGROUND: While oral tacrolimus is effective for the treatment of psoriasis, tacrolimus ointment has shown only spotty efficacy in the treatment of plaque psoriasis. The efficacy of tacrolimus ointment for the treatment of facial and intertriginous psoriasis suggests that if tacrolimus penetration can be increased, the ointment could be used for effective treatment of plaque psoriasis.
OBJECTIVE: To assess whether tacrolimus ointment is an effective psoriasis treatment when used in a combination regimen with the penetration-enhancer salicylic acid.
METHODS: A total of 30 adult subjects with generally symmetrical plaque-type psoriasis were randomized to treatment with 6% salicylic acid gel plus vehicle or 6% salicylic acid gel plus 0.1% tacrolimus ointment in a 12-week left-right comparison study. The primary outcome was the difference between tacrolimus- and vehicle-treated target lesions in the change in the sum of erythema, scale, and thickness scores from baseline to end of treatment.
RESULTS: A total of 24 subjects completed the trial. Combination treatment with tacrolimus ointment or vehicle plus salicylic acid gel was well tolerated. There was greater improvement of the sum score in the tacrolimus plus salicylic acid-treated target plaques than in the vehicle plus salicylic acid-treated plaques at weeks 1, 2, and 8 (P<.05). The efficacy of this regimen was confirmed by investigator and subject global assessments of plaque severity.
CONCLUSIONS: The combination of 0.1% tacrolimus ointment and 6% salicylic acid gel is an effective treatment for psoriasis. Although the results reported herein are from a small exploratory study, the magnitude of the effect was sufficiently large as to be detectable with statistical significance (P<.05).
- Tacrolimus ointment is effective for facial and intertriginous psoriasis.
Lebwohl M, Freeman AK, Chapman MS, Feldman SR, Hartle JE, Henning A; Tacrolimus Ointment Study Group.
Mt. Sinai School of Medicine, New York, New York, USA.
J Am Acad Dermatol. 2004 Nov;51(5):723-30. Abstract quote
BACKGROUND: Intertriginous and facial involvement are manifestations of psoriasis that require a different approach than is used for typical plaque psoriasis on other skin areas. Topical corticosteroids are the primary treatment for psoriasis; however, the side effects of corticosteroids are magnified on intertriginous and facial skin. Topical tacrolimus offers the potential for anti-inflammatory effect without the atrophy or other local side effects associated with the use of topical corticosteroids.
OBJECTIVE: To determine the efficacy and tolerability of 0.1% tacrolimus ointment for the treatment of facial or intertriginous psoriasis.
METHODS: One hundred sixty-seven patients 16 years or older were evaluated in an 8-week, randomized, double-blind, vehicle-controlled, multi-center study. Upon entry into the study, patients were randomized 2:1 to apply the tacrolimus ointment 0.1% or vehicle twice daily to all psoriatic lesions of the face or intertriginous areas for 8 weeks. The physician's global assessment was used to assess improvement from baseline. The inverse psoriasis severity for patients was measured using a 6-point scale from clear to very severe.
RESULTS: As early as day 8, more patients ( P = .004) had cleared or achieved excellent improvement in the 0.1% tacrolimus ointment group compared to the vehicle group (24.8% vs 5.8%). At the end of the 8-week treatment period 65.2% of the tacrolimus ointment group and 31.5% of the vehicle were clear or almost clear ( P < .0001) based on a Static Severity Score. Adverse events were similar in the 0.1% tacrolimus ointment and vehicle groups.
Conclusion Tacrolimus ointment is an effective treatment for psoriasis of the face or intertriginous areas.
Tacrolimus ointment for the treatment of psoriasis on the face and intertriginous areas.
Freeman AK, Linowski GJ, Brady C, Lind L, Vanveldhuisen P, Singer G, Lebwohl M.
Mount Sinai School of Medicine, Fujisawa Healthcare Incorporated, and the Emmes Corporation.
J Am Acad Dermatol 2003 Apr;48(4):564-8 Abstract quote
The safety and efficacy of 0.1% tacrolimus ointment for the treatment of psoriasis on the face, intertriginous areas, or both were evaluated in an open-label, clinical trial of 21 patients with psoriasis. Patients applied 0.1% tacrolimus ointment twice daily for 8 weeks.
Efficacy was assessed through the investigator's evaluation of the individual signs and symptoms of psoriasis, and the physician's global evaluation of change in disease status. Assessments of cutaneous atrophy and other adverse events were made throughout the study to evaluate the safety of tacrolimus ointment. A total of 21 patients were enrolled in the study; 21 patients at least 18 years of age received study medication. Statistically significant improvement in the physician's assessment of the individual signs and symptoms was observed during the study. A total of 81% of patients (17 of 21) experienced complete clearance at day 57 (end of treatment). Only 2 patients reported adverse events, which were limited to itching and the feeling of warmth at the application site.
None of the patients had atrophy, telangiectasia, or striae develop during the study. In summary, tacrolimus 0.1% ointment may be a safe and effective treatment option for patients with psoriasis on the face, intertriginous areas, or both.
Tacrolimus (FK 506)--a new therapeutic agent for severe recalcitrant psoriasis.
Jegasothy BV, Ackerman CD, Todo S, Fung JJ, Abu-Elmagd K, Starzl TE.
Department of Dermatology, University of Pittsburgh Medical Center, PA 15213.
Arch Dermatol 1992 Jun;128(6):781-5 Abstract quote
BACKGROUND--Psoriasis, a disease of unknown etiology, is in some patients severe, extremely debilitating, and unresponsive to conventional therapies, including UV-B, oral psoralen with long-wave UV radiation in the A range (PUVA), oral retinoids, and methotrexate. We report the results from our study of seven patients with refractory psoriasis who were treated with the new immunosuppressive drug, tacrolimus (FK 506).
OBSERVATIONS--All seven patients showed a dramatic resolution of psoriasis that remained in remission as long as they received full-dose therapy. Serial skin biopsy specimens demonstrated a rapid disappearance of the inflammatory infiltrate and a slower resolution of the epidermal changes. Tacrolimus was well tolerated during the 5.5 to 14 months of observation. Side effects, including nephrotoxicity and hypertension, were controlled by appropriate modification of drug dosage.
CONCLUSIONS--Tacrolimus, a new immunosuppressive agent, is effective in treating patients with severe recalcitrant psoriasis. The mechanism of its action in psoriasis is unknown, but it may be related to its ability to modulate immune function. Further studies will establish criteria for patient selection and drug dosage, to maximize efficacy of this agent in psoriasis, while minimizing its toxicity.
Tazarotene cream in the treatment of psoriasis: Two multicenter, double-blind, randomized, vehicle-controlled studies of the safety and efficacy of tazarotene creams 0.05% and 0.1% applied once daily for 12 weeks.
Weinstein GD, Koo JY, Krueger GG, Lebwohl MG, Lowe NJ, Menter MA, Lew-Kaya DA, Sefton J, Gibson JR, Walker PS; Tazarotene Cream Clinical Study Group.
University of California, Irvine, USA.
J Am Acad Dermatol 2003 May;48(5):760-7 Abstract quote
BACKGROUND: Tazarotene in a gel formulation is widely used in the treatment of psoriasis.
OBJECTIVE: To determine the efficacy and safety of tazarotene 0.1% and 0.05% creams in the treatment of psoriasis.
METHODS: A total of 1303 patients participated in 2 clinical trials. Patients applied tazarotene creams 0.1% and 0.05% or vehicle once daily to all psoriatic lesions for 12 weeks followed by a 12-week posttreatment period.
RESULTS: Both creams were significantly more effective than vehicle on the basis of an overall assessment of psoriasis, a global response to treatment, and reduction in plaque elevation and scaling. Therapeutic effect was maintained during the posttreatment period. Common adverse events included signs and symptoms of skin irritation.
CONCLUSION: Tazarotene creams were associated with significant reductions in the severity of the clinical signs of psoriasis and were found to be safe with acceptable tolerability. Tazarotene cream 0.1% was generally more effective, although slightly less well tolerated, than the 0.05% cream.
Narrowband UV-B (TL-01) Phototherapy vs Oral 8-Methoxypsoralen Psoralen-UV-A for the Treatment of Chronic Plaque Psoriasis.
Markham T, Rogers S, Collins P.
City of Dublin Skin and Cancer Hospital, Hume St, Dublin 2, Ireland.
Arch Dermatol 2003 Mar;139(3):325-8 Abstract quote
OBJECTIVE: To compare the efficacy of narrowband UV-B (TL-01) phototherapy with oral 8-methoxypsoralen photochemotherapy (8-MOP psoralen-UV-A [PUVA]) in patients with chronic plaque psoriasis (CPP).
DESIGN: Open, randomized, controlled study.
SETTING: Phototherapy unit in a dermatology hospital.
PATIENTS: Fifty-four patients with CCP.
INTERVENTIONS: Patients received whole-body threshold erythemogenic dose of either 3-times weekly TL-01 or twice-weekly oral 8-MOP PUVA, based on minimal erythema or phototoxic doses. Patients were treated until completely clear.
OUTCOME MEASURES: Number of treatments to clear, number of days in treatment, number of days in remission, and adverse effects of both therapies were assessed. RESULTS: Forty-five patients completed the study. Those in the PUVA group required significantly fewer treatments to clear (P =.03). There was no significant difference in the number of days to clear or number of days in remission. A similar percentage of patients in the TL-01 and PUVA groups developed minimal perceptible erythema, showing that the regimens were equally erythemogenic. Asymptomatic, well-defined erythema occurred only in the PUVA group. Pruritus and polymorphic light eruption occurred equally in both groups, but only patients in the PUVA group developed nausea.
CONCLUSION: Narrowband UV-B phototherapy, used 3 times weekly, is as effective for the treatment of CPP as oral 8-MOP PUVA used twice weekly.
UV-B Phototherapy Clears Psoriasis Through Local Effects.
Dawe RS, Cameron H, Yule S, Man I, Ibbotson SH, Ferguson J.
Photobiology Unit, Department of Dermatology, Dundee University, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland.
Arch Dermatol 2002 Aug;138(8):1071-6 Abstract quote
OBJECTIVE: To determine if UV-B phototherapy clears psoriasis through systemic effects.
DESIGN: Randomized, within-subject comparison of change in psoriasis in 3 plaques in patients attending for whole-body UV-B therapy. Change in patients' psoriasis plaques covered during UV-B treatment was compared with plaques in an untreated control group.
SETTING: University hospital phototherapy unit.
PATIENTS: The study population comprised 17 patients with chronic plaque psoriasis treated with UV-B and 24 psoriasis control patients awaiting UV-B phototherapy.
INTERVENTIONS: Treatment with a standard 3-times weekly narrowband TL-01 UV-B regimen. Three similar plaques were randomly allocated to be covered every treatment, covered for 2 of 3 weekly treatments, and exposed to local UV-B every treatment. Similar plaques were selected in control patients (awaiting but not yet started UV-B therapy). Severity of psoriasis plaques was assessed using a scaling, erythema, and induration (SEI) scoring system.
MAIN OUTCOME MEASURES: Change in SEI score of the selected plaques over the complete treatment course for UV-B-treated patients and change over 3 weeks in SEI score of plaques covered during UV-B treatment compared with that of plaques in controls.
RESULTS: There was a significant (P<.001) difference in how much the SEI score changed in the 3 plaques in UV-B-treated patients. It fell by a mean of 7.6 for uncovered plaques compared with 3.2 for plaques covered during each UV-B exposure (95% confidence interval for difference, 3.0 to 5.8). In patients awaiting UV-B, SEI score of plaques fell by a mean of 0.4 over 3 weeks, compared with a mean fall of 1.4 for covered plaques in UV-B-treated patients (95% confidence interval for difference in means, 0.1 to 2.0).
CONCLUSIONS: If UV-B therapy has any systemic effect capable of improving psoriasis, this effect is small and unlikely to be of clinical importance. It is insufficient to alter interpretation of findings of within-subject comparative phototherapy studies. UV-B phototherapy works for chronic plaque psoriasis through local effects.
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