Psoriasis: Menter A

Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, Gottlieb A, Koo JY, Lebwohl M, Lim HW, Van Voorhees AS, Beutner KR, Bhushan R, Anonymous00035. · Baylor University Medical Center, Dallas, Texas, USA. · J Am Acad Dermatol. · Pubmed #19217694 No free full text.

Abstract: Psoriasis is a common, chronic, inflammatory, multi-system disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this third of 6 sections of the guidelines of care for psoriasis, we discuss the use of topical medications for the treatment of psoriasis. The majority of patients with psoriasis have limited disease (<5% body surface area involvement) and can be treated with topical agents, which generally provide a high efficacy-to-safety ratio. Topical agents may also be used adjunctively for patients with more extensive psoriasis undergoing therapy with either ultraviolet light, systemic or biologic medications. However, the use of topical agents as monotherapy in the setting of extensive disease or in the setting of limited, but recalcitrant, disease is not routinely recommended. Treatment should be tailored to meet individual patients' needs. We will discuss the efficacy and safety of as well as offer recommendations for the use of topical corticosteroids, vitamin D analogues, tazarotene, tacrolimus, pimecrolimus, emollients, salicylic acid, anthralin, coal tar, as well as combination therapy.

Gottlieb A, Korman NJ, Gordon KB, Feldman SR, Lebwohl M, Koo JY, Van Voorhees AS, Elmets CA, Leonardi CL, Beutner KR, Bhushan R, Menter A. · Department of Dermatology, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA. · J Am Acad Dermatol. · Pubmed #18423261 No free full text.

Abstract: Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this second of 5 sections of the guidelines of care for psoriasis, we give an overview of psoriatic arthritis including its cardinal clinical features, pathogenesis, prognosis, classification, assessment tools used to evaluate psoriatic arthritis, and the approach to treatment. Although patients with mild to moderate psoriatic arthritis may be treated with nonsteroidal anti-inflammatory drugs and/or intra-articular steroid injections, the use of disease-modifying antirheumatic drugs, particularly methotrexate, along with the biologic agents, are considered the standard of care in patients with more significant psoriatic arthritis. We will discuss the use of disease-modifying antirheumatic drugs and the biologic therapies in the treatment of patients with moderate to severe psoriatic arthritis.

Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, Lebwohl M, Koo JY, Elmets CA, Korman NJ, Beutner KR, Bhushan R. · Baylor University Medical Center, Dallas, Texas, USA. · J Am Acad Dermatol. · Pubmed #18423260 No free full text.

Abstract: Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this first of 5 sections of the guidelines of care for psoriasis, we discuss the classification of psoriasis; associated comorbidities including autoimmune diseases, cardiovascular risk, psychiatric/psychologic issues, and cancer risk; along with assessment tools for skin disease and quality-of-life issues. Finally, we will discuss the safety and efficacy of the biologic treatments used to treat patients with psoriasis.

Gordon KB, Feldman SR, Koo JY, Menter A, Rolstad T, Krueger G. · No affiliation provided · Arch Dermatol. · Pubmed #15655149 No free full text.

This publication has no abstract.

Farley E, Masrour S, McKey J, Menter A. · Baylor University Medical Center, Dallas, Texas, USA. · J Am Acad Dermatol. · Pubmed #19467374 No free full text.

Abstract: BACKGROUND: Palmoplantar psoriasis is associated with significant quality-of-life issues. Its epidemiology and phenotypical expression remain ill defined. OBJECTIVE: We reviewed the literature and our clinical experience and developed a new quality-of-life assessment tool. METHODS: We conducted a retrospective review of 150 patients with palmoplantar psoriasis. RESULTS: In all, 78 (52%) patients displayed predominantly hyperkeratotic palmoplantar lesions, 24 (16%) pustular, 18 (12%) combination, and 30 (20%) had an indeterminate phenotype. In 27 (18%) patients, lesions were confined to the palms and soles. A new quality-of-life index was constructed to characterize disease severity. In all, 27 (18%) had mild, 72 (48%) moderate, and 51 (34%) severe disease involvement. Palmoplantar disease severity appeared independent from the degree of body surface area involvement. LIMITATIONS: This was a retrospective review. The quality-of-life index remains to be statistically verified in prospective clinical studies. CONCLUSION: Defining morphologic subtypes together with the use of a specific quality-of-life assessment tool in patients with palmoplantar psoriasis will improve our understanding and treatment of this recalcitrant form of psoriasis.

Perlmutter A, Mittal A, Menter A. · Baylor Research Institute, 3900 Junius Street, Suite 145, Dallas, TX 75246, USA. · Br J Dermatol. · Pubmed #19016693 No free full text.

Abstract: Tumour necrosis factor (TNF)-alpha inhibitors, long used in rheumatology and gastroenterology, have made a significant impact on the therapy of psoriasis and psoriatic arthritis. TNF-alpha is an important cytokine in normal physiological processes such as the immune response to granulomatous infection. Inhibition of this process by TNF-alpha inhibitors has been reported to increase the susceptibility of patients to granulomatous infections such as Mycobacterium tuberculosis. Despite the numerous reported cases in the literature and appropriate warnings on the labels for the three currently approved TNF-alpha inhibitors, current guidelines do not address case-specific issues across the full spectrum of tuberculosis. The probability of developing active tuberculosis has been reported to be as much as seven times higher when recommendations are not followed. We report three cases of tuberculosis induced by TNF-alpha inhibitors despite a rigorous screening policy in our tertiary care psoriasis centre, and suggest tuberculosis-specific guidelines for clinicians using these agents based on a review of the literature.

Feldman SR, Horn EJ, Balkrishnan R, Basra MK, Finlay AY, McCoy D, Menter A, van de Kerkhof PC, Anonymous00051. · Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. · J Am Acad Dermatol. · Pubmed #18835062 No free full text.

Abstract: Topical therapy has an important role in psoriasis treatment. It is efficacious and has a favorable safety profile as demonstrated in clinical trials. However, poor treatment outcomes from topical therapy regimens likely result from poor adherence and ineffective use of the medication. The International Psoriasis Council Topical Therapy Working Group has developed a new model to describe the complex interactions among patient, disease, and treatment characteristics, adherence behavior, and treatment outcomes. Recommendations are provided that may assist the health care provider in encouraging adherent behavior in their patients. By understanding and manipulating the factors that affect treatment adherence, improvement in adherence is possible and hence better control and outcomes in the topical treatment of psoriasis are likely.

Warren RB, Chalmers RJ, Griffiths CE, Menter A. · Department of Dermatological Sciences, Salford Royal Hospital, University of Manchester, Manchester, UK. · Clin Exp Dermatol. · Pubmed #18801095 No free full text.

Abstract: Methotrexate's traditional role as a first line agent for moderate to severe psoriasis is being challenged by the rapid and growing use of biological therapies. A recent study comparing adalimumab with methotrexate showed significantly superior efficacy of adalimumab over methotrexate over 16 weeks. Although it is inexpensive, the future use of methotrexate may be compromised by its unpredictable response and toxicity, and by the introduction of newer, more effective biological therapies. However, recent advances in the screening of liver fibrosis by monitoring serum levels of the aminoterminal peptide fragment of type III procollagen have reduced the need for liver biopsy. Furthermore, the potential for personalized methotrexate use by application of modern pharmacogenetics and pharmacokinetics may ensure its place as a first-line agent for the treatment of psoriasis for the foreseeable future.

Gottlieb AB, Dann F, Menter A. · Tufts Medical Center, Boston, MA 02111-1533, USA. · J Drugs Dermatol. · Pubmed #18561588 No free full text.

Abstract: Psoriasis is a chronic immune-inflammatory-mediated disease that can predispose patients to other inflammatory conditions. For example, individuals with psoriasis are at increased risk for insulin resistance, obesity, dyslipidemia, and hypertension--components that characterize the metabolic syndrome. The metabolic syndrome is an important driver of adverse cardiovascular outcomes. Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and other factors that are overproduced in patients with psoriasis likely contribute to the increased risk for development of metabolic syndrome. This article reviews the association of psoriasis with metabolic syndrome, as well as the impact of biologic agents that are currently used to treat psoriasis (ie, TNF antagonists) on risk factors for metabolic syndrome.

Brimhall AK, King LN, Licciardone JC, Jacobe H, Menter A. · University of California, Davis, CA, USA. · Br J Dermatol. · Pubmed #18547300 No free full text.

Abstract: BACKGROUND: The relatively recent introduction of biological agents to treat psoriasis presents clinicians with the need to objectively compare and contrast these agents to allow more effective treatment of their patients. OBJECTIVES: To evaluate and compare the efficacy and safety of biological agents in the treatment of plaque psoriasis. METHODS: (i) DATA SOURCES: Four parallel systematic reviews conducted through July 2006, including peer-reviewed data and U.S. Food and Drug Administration (FDA) reports. (ii) STUDY SELECTION: Randomized, controlled, double-blind, monotherapy trials of alefacept (n = 3), efalizumab (n = 5), etanercept (n = 4) and infliximab (n = 4); 16 studies comprising 7931 patients met inclusion criteria. (iii) DATA EXTRACTION: Efficacy was measured by Psoriasis Area and Severity Index (PASI) 75 achievement after 10-14 weeks of treatment, using intention-to-treat analysis. Safety was evaluated by the incidence of one or more adverse event(s) (AEs) and serious adverse event(s) (SAEs) during 10-30 weeks of treatment. RESULTS: Pooled relative risk (RR) and number needed to treat (NNT) of PASI 75 achievement compared with placebo was computed using Mantel-Haenszel methods and the random effects model. All biological agents for psoriasis were efficacious (P < 0.001); however, there was a graded response for achievement of PASI 75: infliximab (RR = 17.40, NNT = 2), etanercept (RR = 11.73, NNT = 3), efalizumab (RR = 7.34, NNT = 4) and alefacept (RR = 3.70, NNT = 8). The risk of one or more AEs was evaluated by RR and number needed to harm (NNH). This was increased in the alefacept (RR = 1.09, P = 0.03, NNH = 15), efalizumab (RR = 1.15, P < 0.001, NNH = 9) and infliximab (RR = 1.18, P < 0.001, NNH = 9) groups compared with placebo. SAEs were increased in a sensitivity analysis of four efalizumab trials (n = 2443, RR = 1.92, P = 0.03, NNH = 60). CONCLUSIONS: The decreasing rank order for pooled efficacy was infliximab, etanercept, efalizumab and alefacept when compared with placebo. Pooling safety data revealed a previously unreported increased risk of AEs for alefacept, efalizumab and infliximab.

Kourosh AS, Miner A, Menter A. · The University of Texas Southwestern Medical School, Dallas, TX, USA. · Skin Therapy Lett. · Pubmed #18357363 links to  free full text

Abstract: Psoriasis is associated with comorbidities that include metabolic syndrome and increased cardiovascular risk. These conditions share etiologic features and health consequences that directly correlate with the severity of psoriatic disease. This disease, in both its skin and joint manifestations, may represent a relevant healthcare issue as an indicator of a broader, underlying disorder of systemic inflammation, and warrants more comprehensive study and multidisciplinary collaboration on its pathophysiology, epidemiology, and treatment in relation to its comorbid conditions.

Menter A, Griffiths CE. · Baylor Research Institute and Southwestern Medical School, Dallas, Texas 75246, USA. · Lancet. · Pubmed #17658398 No free full text.

Abstract: Management of psoriasis begins with identification of the extent of cutaneous disease. However, a holistic, contractual approach to treatment is encouraged, with particular reference to psychosocial disability and quality-of-life issues. The presence of psoriasis on palms, soles, body folds, genitals, face, or nails, and concomitant joint disease, are also important when considering treatment options. An evidence-based approach is essential in delineating differences between the many available treatments. However, archaic approaches, especially combinational ones, are routinely used by some clinicians, with inadequate prospective or comparative evidence. Treatments currently available are: topical agents used predominantly for mild disease and for recalcitrant lesions in more severe disease; phototherapy for moderate disease; and systemic agents including photochemotherapy, oral agents, and newer injectable biological agents, which have revolutionised the management of severe psoriasis. Other innovative treatments are undergoing clinical studies, with the aim of maintaining safe, long-term control of the condition.

Sterry W, Strober BE, Menter A, Anonymous00299. · Department of Dermatology and Allergy, Charité University Medicine and Humboldt University/Free University, Berlin, Germany. · Br J Dermatol. · Pubmed #17627791 No free full text.

Abstract: Experts on psoriasis convened with authorities from other medical specialties to discuss the recently described association between psoriasis, obesity and subsequent cardiovascular comorbidity. Similar to other diseases of increased systemic inflammation, psoriasis has been linked to a heightened risk of myocardial infarction, especially in the more severely affected, younger patients. However, unlike in other inflammatory diseases - such as rheumatoid arthritis - more severely affected patients with psoriasis are much more likely to be obese. Importantly, the pathophysiology of both psoriasis and obesity shows many shared cytokines that are known to contribute to features of the metabolic syndrome, such as hypertension, dyslipidaemia and insulin resistance. The strong association between psoriasis and obesity potentially makes psoriasis an important healthcare issue that requires an update in its standard of care. This meeting reviewed the evidence-based literature and addressed how, moving forward, dermatologists and other specialists may redefine the magnitude of health risk associated with more severe psoriasis and its comorbidities, while clarifying both the epidemiology and pathophysiology of the association with obesity.

Menter A, Leonardi CL, Sterry W, Bos JD, Papp KA. · Baylor University Medical Center, Dallas, Texas, USA. · J Am Acad Dermatol. · Pubmed #16488340 No free full text.

This publication has no abstract.

Carey W, Glazer S, Gottlieb AB, Lebwohl M, Leonardi C, Menter A, Papp K, Rundle AC, Toth D. · Royal Victoria Hospital, Montreal, Quebec, Canada. · J Am Acad Dermatol. · Pubmed #16488339 No free full text.

Abstract: Psoriasis is a chronic disease, the severity of which varies among patients and changes unpredictably over time in individual patients. Psoriasis can be exacerbated during treatment by infection, endocrine factors, hypocalcemia, medications, psychologic stress, skin trauma, or other factors. Patients who discontinue treatments may experience a return of disease--relapse--or worsening of disease--rebound. The National Psoriasis Foundation (NPF) proposed standardized definitions of relapse and rebound. Efalizumab, a recombinant humanized immunoglobulin G-1 monoclonal antibody, is approved for the management of psoriasis. During efalizumab clinical trials, a small percentage of patients experienced protocol-defined adverse events related to psoriasis. After publication of the NPF definition of rebound, post hoc exploratory analyses of the efalizumab clinical trial data were performed. The efalizumab clinical trial investigators discussed their observations, the analyses, and their individual approaches to the treatment of patients receiving or discontinuing efalizumab therapy, the conclusions of which are described herein.

Feldman SR, Koo JY, Menter A, Bagel J. · Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1071, USA. · J Am Acad Dermatol. · Pubmed #15965429 No free full text.

Abstract: 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.

Cather JC, Menter A. · Baylor University Medical Center, Dallas, TX, USA. · Semin Cutan Med Surg. · Pubmed #15900797 No free full text.

Abstract: Psoriasis patients deserve long-term control of their disease with optimal safety. Traditional agents (methotrexate, cyclosporine, retinoids, and photochemotherapy [PUVS]), although providing excellent short-term control, may produce acute or chronic toxicities, thus limiting their usage. Dermatologists are well versed in combination and rotational therapies for psoriasis, using these and other agents. With the advent of biologic therapies (three currently approved, and others pending), the potential for safer long-term psoriasis control is being realized. A review of the literature, plus our personal experience in using combinations of traditional agents and biologics, is presented.

Cather JC, Menter A. · Baylor University Medical Center, 5310 Harvest Hill Rd., Ste. 260, Dallas, TX75230, USA. · Expert Opin Biol Ther. · Pubmed #15833076 No free full text.

Abstract: Efalizumab is a humanised monoclonal antibody targeting the CD11a subunit of lymphocyte function-associated antigen-1, specifically developed for psoriasis. Indicated for patients with moderate-to-severe plaque psoriasis, efalizumab is FDA-approved in the US for patients aged > or = 18, as well as being approved in several other European countries. Clinical studies have proven the efficacy of efalizumab for a majority of patients, improving quality of life with continuous maintenance therapy by means of weekly subcutaneous self-injections. Controlled trials have demonstrated the safety and tolerability of efalizumab. Clinical trials have established that approximately 30% of patients can achieve a PASI-75 response within 12 weeks of initiating treatment, with further clinical benefit noted with continued therapy up to 24 and even 36 months of therapy. Efalizumab may thus potentially offer patients a safe option for long-term safe control in managing their disease.

Winterfield LS, Menter A, Gordon K, Gottlieb A. · Department of Dermatology, University of Texas Southwestern Medical School, Dallas, Texas 75230, USA. · Ann Rheum Dis. · Pubmed #15708946 links to  free full text

Abstract: Quality of life studies in patients with cutaneous psoriasis attest to its significant impact on day to day activities and personal social interactions. Up to 40% of patients with psoriasis may develop psoriatic arthritis, usually within 5-10 years after onset of the cutaneous disease, heightening quality of life issues. These data have prompted an increased awareness and interest in more aggressive management of psoriasis; coupled with a better understanding of immunopathogenesis, this has led to the development of new agents targeting specific cells and molecules involved in the development and maintenance of psoriatic plaques. Although non-biological therapies, including methotrexate and ciclosporin, show significant efficacy their side effect profiles have precluded their long term use for moderate to severe psoriasis. This review concentrates on new biological agents, focusing on the three agents approved for psoriasis within the past 18 months (alefacept, efalizumab, and etanercept). Phase II and III trial data on other agents in development (adalimumab and infliximab) are also presented. Surveys show many patients want to be treated more aggressively. It is hoped that the introduction of new agents that are more targeted and that hold the promise of fewer side effects will cause patients and their physicians to reconsider systemic treatment and, as a consequence, stimulate other patients to reconsider treatment for psoriasis. Close cooperation between dermatologists and rheumatologists, particularly in the area of psoriatic joint disease, will enhance these considerations.

Menter A. · Baylor University Medical Center, Texas Dermatology Associates, 5310 Harvest Hill Road, Suite 260, Dallas, TX 75230, USA. · J Cutan Med Surg. · Pubmed #15668752 No free full text.

Abstract: Patients with psoriasis may experience impaired psychosocial mental status regardless of their objectively defined disease severity. The objective clinical measures of disease that are commonly used to evaluate a patient's psoriasis fail to take into account the effect of psoriasis on patients' quality of life (QOL). As a result, a significant number of patients are dissatisfied with conventional treatments and are searching for new options. A high unmet need for effective and safe long-term therapies that can also improve patients' QOL exists in psoriasis. Alefacept, a selective biologic agent specifically designed for the treatment of psoriasis, provides improvement in both the physical (as measured by the Psoriasis Area and Severity Index) and mental (as measured by the Dermatology Life Quality Index) aspects of the disease. Additionally, alefacept is extremely well tolerated, with no negative effect on QOL, and the improvement in QOL are maintained off-treatment, which is consistent with its remittive effects on the disease. Alefacept helps fulfill the needs of psoriasis patients by providing efficacy, safety, off-treatment remissions, and improvement in QOL.

Riddle C, Young M, Menter A. · Department of Internal Medicine, Baylor University Medical Center, 3500 Gaston Avenue, Dallas, TX 75246, USA. · Dermatol Clin. · Pubmed #15450344 No free full text.

Abstract: Exciting new therapies are becoming available that allow dermatologists and patients safe and effective alternatives to traditional psoriasis therapy. Because these new biologic drugs are parenterally administered, practical aspects of their integration into clinical practice must be addressed. This article offers guidelines for incorporating subcutaneous,intramuscular, and intravenous injectables into dermatology offices. Several tiers of psoriasis care are outlined to encourage individual physicians to choose the optimum level of service compatible with their individual practices.

Winterfield L, Menter A. · Department of Dermatology, University of Texas Southwestern Medical School, Dallas, TX, USA. · Dermatol Clin. · Pubmed #15450339 No free full text.

Abstract: The pathogenesis of psoriasis, a chronic immune-mediated inflammatory skin disease,involves increased concentrations and activity of several proinflammatory cytokines,including tumor necrosis factor alpha (TNF-alpha). Infliximab is a chimeric human-murine TNF-alpha antibody that selectively blocks the activity of TNF-alpha. In controlled clinical trials, infliximab treatment has produced rapid and sustained improvements in psoriasis lesions and psoriatic joint involvement, with a favorable short-term safety and tolerability profile.Treatment with infliximab may be associated with an increased risk of infection or infusion reaction: however, the side-effect profile of infliximab in patients with psoriasis remains to be fully characterized, and assessment of infliximab in this population is currently ongoing in phase 3 studies. Comprehensive evaluation in controlled trials may allow infliximab to take its place among the expanding group of biologic drugs for the treatment of moderate to severe psoriasis.

Winterfield LS, Menter A. · Department of Dermatology, University of Texas Southwestern Medical School, Dallas, Texas, USA. · Dermatol Ther. · Pubmed #15379776 No free full text.

Abstract: Infliximab is a chimeric monoclonal antibody that interferes with the actions of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Clinical trials of infliximab have demonstrated a rapid and substantial response in patents with psoriasis and psoriatic arthritis, substantiating the role of TNF-alpha in the immunopathogenesis of psoriatic disease. This review summarizes the current data regarding the use of infliximab in treating psoriasis and psoriatic arthritis, as well as the safety data available from patients with other immune-mediated inflammatory disorders. Practical issues such as patient selection, monitoring, cost, and potential combination therapies are also discussed.

Sterry W, Barker J, Boehncke WH, Bos JD, Chimenti S, Christophers E, De La Brassinne M, Ferrandiz C, Griffiths C, Katsambas A, Kragballe K, Lynde C, Menter A, Ortonne JP, Papp K, Prinz J, Rzany B, Ronnevig J, Saurat JH, Stahle M, Stengel FM, Van De Kerkhof P, Voorhees J. · Department of Dermatology and Allergy, University Hospital Charité, Berlin, Germany. · Br J Dermatol. · Pubmed #15265063 No free full text.

Abstract: Psoriasis is a chronic, immune-mediated disorder that usually requires long-term treatment for control. Approximately 25% of patients have moderate to severe disease and require phototherapy, systemic therapy or both. Despite the availability of numerous therapeutic options, the long-term management of psoriasis can be complicated by treatment-related limitations. With advances in molecular research and technology, several biological therapies are in various stages of development and approval for psoriasis. Biological therapies are designed to modulate key steps in the pathogenesis of psoriasis. Collectively, biologicals have been evaluated in thousands of patients with psoriasis and have demonstrated significant benefit with favourable safety and tolerability profiles. The limitations of current psoriasis therapies, the value of biological therapies for psoriasis, and guidance regarding the incorporation of biological therapies into clinical practice are discussed.

Lebwohl M, Menter A, Koo J, Feldman SR. · Department of Dermatology, Mount Sinai School of Medicine, Mt. Sinai Medical Center, 5 E. 98th Street, 12th Floor, New York, NY 10029-6574, USA. · J Am Acad Dermatol. · Pubmed #14988684 No free full text.

Abstract: 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.