Robert E. Kalb

Methotrexate and psoriasis: Consensus conference

To the Editor: We appreciate the comments of Dr Roenigk, Dr Auerbach, and Dr Maibach regarding our article, ‘‘Methotrexate andPsoriasis: 2009National Psoriasis Foundation Consensus Conference.’’ We would like to acknowledge the work of these physicians who pioneered the use of methotrexate and developed the initial guidelines for its use. Their work was acknowledged with praise in our methotrexate article. We would like to apologize for not having consulted them directly. We welcome this opportunity to respond to their comments. The last methotrexate guidelines were a consensus statement of a small group of recognized experts, including two of the authors of the current guidelines (G. W. and M. L.). It was neither approved by the American Academy of Dermatology (AAD) nor reviewed by the AAD Board before its publication. The more recent psoriasis expert work group of the AAD guidelines did not deal exclusively with methotrexate. The brief portion of these guidelines concerning methotrexate was written by one of the authors of our methotrexate article (M. L.), and many of the recommendations (Tables I-VI) were used with permission from our article. We disagree that the article is largely unchanged from the 1998 methotrexate guidelines. Besides the change in liver biopsy guidelines new information was presented regarding the use of methotrexate in psoriasis, the role of folic acid supplementation, the importance of hematologic toxicity and the fact that this toxicity may be more clinically relevant than hepatotoxicity, and the significance of hepatic risk factors in the development of liver toxicity. Importantly, most of the newer information presented was primarily in patients with psoriasis and psoriatic arthritis. It is admittedly difficult to put together a large group of experts without any conflicts of interest. The conflicts of interest must be declared, as they were in our article. As for conflicts of interest affecting content, our article, in fact, eased the biopsy criteria for patients receiving methotrexate, a drug that has been generic for many years. Therefore, our recommendations only have made it a drug that is easier to prescribe. None of the authors of our article or members of the National Psoriasis Foundation

Methotrexate and psoriasis: 2009 National Psoriasis Foundation Consensus Conference

BACKGROUND Methotrexate remains a valuable option for the treatment of psoriasis. This report will summarize studies regarding the use of methotrexate since the last guidelines were published in 1998. OBJECTIVE A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options. Our aim was to achieve a consensus on new updated guidelines for the use of methotrexate in the treatment of psoriasis. METHODS Reports in the literature were reviewed regarding methotrexate therapy. RESULTS A consensus was achieved on use of methotrexate in psoriasis including specific recommendations on dosing and monitoring. The consensus received unanimous approval from members of the Medical Board of the National Psoriasis Foundation. LIMITATIONS There are few evidence-based studies on the treatment of psoriasis with methotrexate. Many of the reviewed reports are for the treatment of rheumatoid arthritis. CONCLUSIONS Methotrexate is a safe and effective drug for the treatment of psoriasis. Appropriate patient selection and monitoring will significantly decrease the risks of side effects. In patients without risk factors for hepatic fibrosis, liver biopsies may not be indicated or the frequency of liver biopsies may be markedly reduced.

A multicenter trial of calcipotriene ointment and halobetasol ointment compared with either agent alone for the treatment of psoriasis

Calcipotriene, a vitamin D3 analogue, inhibits cell proliferation and induces cell differentiation in vitro. 1, 2 Many studies have shown that calcipotriene ointment (0.005%) is effective in the treatment of plaque psoriasis. 3, 4 The purpose of this three-axrn trial was to evaluate the efficacy and safety of calcipotriene ointment 0.005% applied in the morning and halobetasol propionate 0.05% ointment applied in the evening versus calcipotriene ointment applied twice daily versus halobetasol propionate ointment applied twice daily for moderate plaque psoriasis.

Risk of Serious Infection With Biologic and Systemic Treatment of Psoriasis Results From the Psoriasis Longitudinal Assessment and Registry (PSOLAR)

IMPORTANCE The efficacy of treatment for psoriasis must be balanced against potential adverse events. OBJECTIVE To determine the effect of treatment on the risk of serious infections in patients with psoriasis. DESIGN, SETTING, AND PARTICIPANTS A multicenter, longitudinal, disease-based registry (Psoriasis Longitudinal Assessment and Registry [PSOLAR]) at dermatology centers. Participants were adult patients with psoriasis who were receiving or were eligible to receive conventional systemic or biologic agents. The registry opened on June 20, 2007, and data included herein were collected through August 23, 2013. EXPOSURES Patients were prescribed psoriasis therapies as in standard clinical practice. Patients will be followed for up to 8 years. Data were collected and serious adverse events (including serious infections) were assessed at regular intervals. MAIN OUTCOMES AND MEASURES Cohort characteristics are described based on evaluation at entry into the registry. The cumulative incidence rates of serious infections are reported across treatment cohorts, including ustekinumab, infliximab, adalimumab, etanercept, and nonbiologics (with or without methotrexate). A multivariate analysis using a Cox proportional hazards regression model was used to identify predictors of the time to the first serious infection using the nonmethotrexate/nonbiologics cohort as the reference. RESULTS Data were analyzed from 11,466 patients with psoriasis (22,311 patient-years). Differences in patient characteristics were found between the biologics and nonmethotrexate/nonbiologics cohorts (eg, age, sex, body mass index, and disease characteristics), as well as among the individual biologic groups (eg, a higher prevalence of psoriatic arthritis in the infliximab cohort). The cumulative incidence rate of serious infections was 1.45 per 100 patient-years (n = 323) across treatment cohorts, and the rates were 0.83, 1.47, 1.97, and 2.49 per 100 patient-years in the ustekinumab, etanercept, adalimumab, and infliximab cohorts, respectively, and 1.05 and 1.28 per 100 patient-years in the nonmethotrexate/nonbiologics and methotrexate/nonbiologics cohorts, respectively. The most commonly reported types of serious infections across the registry were pneumonia and cellulitis. Increasing age, diabetes mellitus, smoking, significant infection history, infliximab exposure, and adalimumab exposure were each associated with an increased risk of serious infection. CONCLUSIONS AND RELEVANCE Results from PSOLAR suggest a higher risk of serious infections with adalimumab and infliximab compared with nonmethotrexate and nonbiologic therapies. No increased risk was observed with ustekinumab or etanercept. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00508547.

Consensus Guidelines for the Management of Plaque Psoriasis

The Canadian Guidelines for the Management of Plaque Psoriasis were reviewed by the entire National Psoriasis Foundation Medical Board and updated to include newly approved agents such as ustekinumab and to reflect practice patterns in the United States, where the excimer laser is approved for psoriasis treatment. Management of psoriasis in special populations is discussed. In the updated guidelines, we include sections on children, pregnant patients or pregnant partners of patients, nursing mothers, the elderly, patients with hepatitis B or C virus infections, human immunodeficiency virus-infected patients, and patients with malignant neoplasms, as well as sections on tumor necrosis factor blockers, elective surgery, and vaccinations.

Treatment of pustular psoriasis: From the medical board of the National Psoriasis Foundation

BACKGROUND A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options for pustular psoriasis. Meetings were held by teleconference. Consensus on treatment of pustular psoriasis was achieved. Pustular psoriasis has been classified into localized and generalized forms. There are a number of treatment modalities, but there is little evidence-based information to guide the management of this type of psoriasis. OBJECTIVES The purpose of this article was to present treatment recommendations to aid in the treatment of patients with pustular psoriasis. METHODS A literature review was conducted to examine treatment options for pustular psoriasis and assess the strength of the literature for each option. RESULTS Overall the quality of the literature about the treatment of pustular psoriasis is weak. Treatment should be governed by the extent of involvement and severity of disease. Acitretin, cyclosporine, methotrexate, and infliximab are considered to be first-line therapies for those with generalized pustular psoriasis. Adalimumab, etanercept, and psoralen plus ultraviolet A are second-line modalities in this setting. Pustular psoriasis in children, in pregnant women, and in localized forms alter which agents are first-line modalities as concerns such as teratogenicity need to be factored into the decisionmaking for the individual patient. LIMITATIONS There are few high-quality studies examining treatment options for pustular psoriasis. CONCLUSIONS Treatment of patients with pustular psoriasis depends on the severity of presentation and patients underlying risk factors. The data are extremely limited for this type of psoriasis and we encourage further exploration.

Treatment of severe scalp psoriasis: from the Medical Board of the National Psoriasis Foundation.

BACKGROUND The scalp is the most commonly affected part of the body in patients with psoriasis. Signs and symptoms of scalp psoriasis vary significantly for individual patients. OBJECTIVE A task force of the National Psoriasis Foundation was convened to evaluate treatment options. Our aim was to achieve a consensus for scalp psoriasis therapy. METHODS Reports in the medical literature were reviewed regarding scalp psoriasis therapy. LIMITATIONS There is a paucity of evidence-based and double-blind studies in the treatment of scalp psoriasis particularly for long-term therapy. Many of the studies in scalp psoriasis were designed to attain Food and Drug Administration approval for a medication and not to provide treatment guidance. CONCLUSIONS The recommended short-term or intermittent therapy for scalp psoriasis is topical corticosteroids. The primary alternatives are topical retinoids, vitamin D analogues, and salicylic acid. Combination therapy has many advantages. The choice of an appropriate vehicle is crucial to increase patient compliance. While scalp psoriasis can often be adequately treated with topical therapy, recalcitrant disease may require more aggressive approaches, including systemic agents.

Treatment of intertriginous psoriasis: From the Medical Board of the National Psoriasis Foundation

BACKGROUND Involvement of areas of the skin fold is common in patients with psoriasis although the exact incidence is unknown. This report summarizes studies regarding the therapy of intertriginous psoriasis. OBJECTIVE A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options. Our aim was to arrive at a consensus on therapy for intertriginous or inverse psoriasis. METHODS Reports in the literature were reviewed regarding psoriasis affecting the skin-fold areas and its therapy. LIMITATIONS There are few evidence-based studies on the treatment of intertriginous psoriasis. RESULTS The recommended short-term (2-4 weeks) therapy for inverse psoriasis is low- to mid-potency topical steroids. For long-term therapy, topical calcipotriene (calcipotriol) or one of the immunomodulating agents, pimecrolimus or tacrolimus, is favored. CONCLUSIONS Low- to mid-potency topical steroids are recommended as first-line, short-term treatment. It is recommended that their use should either be of limited duration (less than 2-4 weeks) or that the lowest effective strength be used intermittently for long-term care to minimize the potential for risks. Calcipotriene (calcipotriol), pimecrolimus, and tacrolimus, while not as highly efficacious as topical steroids, are associated with fewer long-term risks and are therefore recommended for long-term therapy when feasible.

Concurrent use of methotrexate and acitretin revisited.

Background: According to Food and Drug Administration (FDA)‐approved prescribing information, combination therapy with acitretin and methotrexate (MTX) is contraindicated. This is based on company data suggesting increased hepatotoxicity in patients who received concomitant methotrexate and etretinate, the prodrug of acitretin. Methods: We reviewed the clinical data of 18 patients with psoriasis who received methotrexate and acitretin concurrently. Patients received 25 mg of acitretin once daily or alternating days and 7.5–25 mg methotrexate weekly. Baseline metabolic panels, including lipids, and complete blood counts (CBC) were drawn prior to therapy and every 4–12 weeks while on therapy. Results: The average length of treatment was 9 months. Two patients discontinued treatment after refusal to abstain from alcohol. Seven patients discontinued treatment due to a lack of response. Two patients discontinued treatment after clearing. One patient discontinued treatment secondary to hair loss. Six patients are currently continuing therapy. Conclusions: In this series of patients, combination therapy with acitretin and methotrexate was well tolerated and often effective. There were no new or unusual adverse events noted, including significant hepatotoxicity. In patients who would benefit from the use of acitretin, the concomitant use of methotrexate is not an absolute contraindication.

The efficacy and safety of infliximab in patients with plaque psoriasis who had an inadequate response to etanercept: Results of a prospective, multicenter, open-label study

BACKGROUND In patients with psoriasis and inadequate response (IR) to tumor necrosis factor-α antagonist treatment, the incremental benefit of switching to another tumor necrosis factor-α antagonist is unknown. OBJECTIVE We sought to evaluate the clinical response to an etanercept-to-infliximab switch in patients with psoriasis and IR to etanercept. METHODS Adults with moderate-to-severe plaque psoriasis and IR to etanercept (≥ 4 months) were eligible for this open-label study (called PSUNRISE). Patients had a Physician Global Assessment (PGA) score of at least 2 (mild) on a 5-point scale with etanercept, with or without concomitant oral systemic methotrexate or cyclosporine at baseline and during the study. Patients received intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, 14, and 22. PGA was used to evaluate efficacy at week 10 (primary end point) and week 26 (durability). Safety was evaluated through the end of the study. RESULTS Of 215 patients, only 10 received concomitant immunomodulators. At week 10, 65.4% of patients (138 of 211; 95% confidence interval 58.6%-71.8%) achieved a PGA score of clear (0) or minimal (1) (primary end point). This response was durable through week 26, at which time 61.3% (122 of 199; 95% confidence interval 54.2%-68.1%) achieved a PGA score of clear (0) or minimal (1). There were no unexpected side effects or safety concerns. LIMITATIONS This was an open-label, 26-week study; an incremental change of 1 PGA point, even mild to minimal, was considered clinically significant, as most psoriasis practitioners seek to achieve minimal psoriasis or clear skin. CONCLUSION After switching to infliximab, a substantial proportion of patients with psoriasis and IR to etanercept experienced rapid and durable improvement.