Patient-reported reasons for the discontinuation of commonly used treatments for moderate to severe psoriasis.

BACKGROUND: Despite widespread dissatisfaction and low treatment persistence in moderate to severe psoriasis, patients' reasons behind treatment discontinuation remain poorly understood. OBJECTIVES: We sought to characterize patient-reported reasons for discontinuing commonly used treatments for moderate to severe psoriasis in real-world clinical practice. METHODS: A total of 1095 patients with moderate to severe plaque psoriasis from 10 dermatology practices who received systemic treatments completed a structured interview. Eleven reasons for treatment discontinuation were assessed for all past treatments. RESULTS: A total of 2231 past treatments were reported. Median treatment duration varied by treatment, ranging from 6.0 to 20.5 months (P < .001). The frequency of each cited discontinuation reasons differed by treatment (all P < .01). Patients who received etanercept (odds ratio [OR] 5.19; 95% confidence interval [CI] 3.23-8.33) and adalimumab (OR 2.10; 95% CI 1.20-3.67) were more likely to cite a loss of efficacy than those who received methotrexate. Patients who received etanercept (OR 0.34; 95% CI 0.23-0.49), adalimumab (OR 0.48; 95% CI 0.30-0.75), and ultraviolet B phototherapy (OR 0.21; 95% CI 0.14-0.31) were less likely to cite side effects than those who received methotrexate, whereas those who received acitretin (OR 1.56; 95% CI 1.08-2.25) were more likely to do so. Patients who underwent ultraviolet B phototherapy were more likely to cite an inability to afford treatment (OR 7.03; 95% CI 3.14-15.72). LIMITATIONS: The study is limited by its reliance on patient recall. CONCLUSIONS: Different patterns of treatment discontinuation reasons are important to consider when developing public policy and evidence-based treatment approaches to improve successful long-term psoriasis control.

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 patient's underlying risk factors. The data are extremely limited for this type of psoriasis and we encourage further exploration.

Comparative effectiveness of commonly used systemic treatments or phototherapy for moderate to severe plaque psoriasis in the clinical practice setting.

OBJECTIVE: To compare the effectiveness of biologic systemic therapy, nonbiologic systemic therapy, and phototherapy for treatment of psoriasis. DESIGN: A cross-sectional design was used. SETTING: Ten outpatient dermatology sites across the United States participating in the Dermatology Clinical Effectiveness Research Network contributed to the study. PARTICIPANTS: A total of 713 patients with plaque psoriasis receiving systemic monotherapy (ie, methotrexate sodium, adalimumab, etanercept, or ustekinumab) or narrowband UV-B phototherapy. MAIN OUTCOME MEASURES: The primary outcome of the study was clear or almost clear skin on the Physician Global Assessment scale. Secondary outcomes were score on the Psoriasis Area and Severity Index, affected body surface area, and score on the Dermatology Life Quality Index. RESULTS: The proportion of patients with clear or almost clear ratings on the Physician Global Assessment scale differed among treatments: methotrexate (23.8%), adalimumab (47.7%), etanercept (34.2%), ustekinumab (36.1%), and narrowband UV-B (27.6%) (P < .001). In adjusted analyses, patients receiving adalimumab (relative response rate, 2.15; 95% CI, 1.60-2.90), etanercept (1.45; 1.06-1.97), and ustekinumab (1.57; 1.06-2.32) were more likely to have clear or almost clear skin vs patients receiving methotrexate. Patients receiving phototherapy showed no significant difference (1.35; 95% CI, 0.93-1.96) compared with those receiving methotrexate. No response difference was observed with respect to quality of life. Treatment doses were double the recommended doses in 36.1% of patients taking etanercept and 11.8% of those taking adalimumab;10.6% of patients undergoing phototherapy received the recommended treatment frequency. CONCLUSIONS: The effectiveness of psoriasis therapies in clinical practice may be lower than that reported in previous trials. Although relative differences in objective response rates among therapies may exist, absolute differences are small and may not be clinically significant. Dosing of common therapies varied from trial recommendations. These results provide novel benchmarks emphasizing the critical importance of studying effectiveness in real-world practice.

Dermatologist preferences for first-line therapy of moderate to severe psoriasis in healthy adult patients.

BACKGROUND: Despite increasing therapies for moderate to severe psoriasis, dermatologists' treatment preferences are unknown. OBJECTIVE: We sought to assess dermatologists' preferences for first-line treatments and their selection determinants. METHODS: We surveyed 1000 US dermatologists (500 National Psoriasis Foundation and 500 American Academy of Dermatology members who treat psoriasis) about their preferences for first-line treatment of moderate to severe psoriasis in healthy adults of childbearing age using standardized patient vignettes. RESULTS: The response rate was 39% (N = 387). Preferred therapies for male and female patients were: ultraviolet (UV) B (40% and 56%, respectively), etanercept (15% and 19%), methotrexate (16% and 4%), and adalimumab (12% and 10%). Of respondents, 66% administered phototherapy in their practice. After adjusting for all physician characteristics, those preferring first-line UVB for male or female patients were significantly more likely to have phototherapy in their practice (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.8-6.6 and OR 2.8, 95% CI 1.5-5.3, respectively) and to have used UVB in more than 10 patients in the last 3 months (OR 8.0, 95% CI 3.9-16.4; OR 9.6, 95% CI 4.3-21.6). Dermatologists in the Midwest were more likely than those in the Northeast to prefer adalimumab first line for male and female patients. LIMITATIONS: We surveyed only dermatologists with interest in treating psoriasis and elicited their treatment preferences for a single base case scenario. Treatment preferences may differ between survey respondents and nonrespondents. CONCLUSION: UVB is most commonly preferred as a first-line treatment for moderate to severe psoriasis in healthy adults, and preferences vary based on region, phototherapy availability, and prior treatment use.

Review of treatment options for psoriasis in pregnant or lactating women: from the Medical Board of the National Psoriasis Foundation.

BACKGROUND: Treating psoriasis in pregnant and lactating women presents a special challenge. For ethical reasons, prospective randomized control trials have not been conducted in this patient population although these patients do encounter new-onset psoriasis in addition to flares and may require treatment throughout their pregnancies. OBJECTIVE: Our aim was to arrive at consensus recommendations on treatment options for psoriasis in pregnant and lactating women. METHODS: The literature was reviewed regarding all psoriasis therapies in pregnant and lactating women. RESULTS: Topical therapies including emollients and low- to moderate-potency topical steroids are first-line therapy for patients with limited psoriasis who are pregnant or breast-feeding. The consensus was that second-line treatment for pregnant women is narrowband ultraviolet B phototherapy or broadband ultraviolet B, if narrowband ultraviolet B is not available. Lastly, tumor necrosis factor-α inhibitors including adalimumab, etanercept, and infliximab may be used with caution as may cyclosporine and systemic steroids (in second and third trimesters). Some specific strategies may be used to minimize risk and exposure. LIMITATIONS: There are few evidence-based studies on treating psoriasis in pregnant and lactating women. CONCLUSIONS: Because there will always be a question of ethical concerns placing pregnant and lactating women in prospective clinical trials, investigation of both conventional and biologic agents are unlikely to ever be performed. Some of these medications used to treat psoriasis are known abortifacients, mutagens, or teratogens and must be clearly avoided but others can be used with relative confidence in select patients with appropriate counseling of risks and benefits.

Psoriasis in the elderly: from the Medical Board of the National Psoriasis Foundation.

BACKGROUND: The continuous increase in the US population older than 65 years and the chronic course of psoriasis make management of psoriasis in the elderly an important health care problem. OBJECTIVE: We sought to develop a treatment algorithm for patients with psoriasis who are older than 65 years. METHODS: A systematic literature search for studies on elderly patients with psoriasis was performed using MEDLINE. RESULTS: We summarize the available published data on therapeutic modalities used in the elderly. We suggest a treatment algorithm including topical medications as first-line treatment for limited disease, with phototherapy, systemic retinoids, methotrexate, and biologics as the first-line systemic treatments for patients with more extensive disease. Cyclosporine should only rarely be used as a second-line systemic treatment for extensive disease in elderly patients with psoriasis. LIMITATIONS: Limited data are available regarding treatment modalities specifically for elderly patients with psoriasis. CONCLUSION: Appropriate treatment for elderly patients with limited psoriasis includes topical corticosteroids, topical vitamin D analogues, and topical tazarotene. For appropriately monitored elderly patients who have psoriasis with extensive disease, phototherapy, acitretin, methotrexate, alefacept, etanercept, adalimumab, infliximab, and ustekinumab are first-line therapies that can generally be safely used. There remains a need for further research on the management of psoriasis in elderly patients with psoriasis.

Obesity and psoriasis: from the Medical Board of the National Psoriasis Foundation.

An association between obesity and psoriasis has been reported. For a variety of reasons, obese persons with psoriasis are often more difficult to treat. We sought to review the literature on obesity and psoriasis and to discuss efficacy and safety data that could be utilized by clinicians who are making treatment decisions for obese persons with psoriasis. We performed a literature review using the terms "obesity and psoriasis" and "metabolic syndrome and psoriasis." Evidence from relevant literature was evaluated and categorized according to the criteria of Shekelle et al (published 1999). Numerous reports cite an association between obesity and psoriasis. When compared with non-obese patients with psoriasis, obese patients with psoriasis are more likely to experience certain adverse effects to medications and are less likely to respond favorably to systemic therapies. The amount of category I evidence for objectively determining the best treatment choices for obese patients with psoriasis was scarce and thus did not allow for the development of a treatment algorithm that could be generally applied for all psoriasis patients who are obese. Efficacy and safety concerns affected by obesity are important considerations for clinicians who are making decisions on proper treatment of psoriasis.

Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation.

BACKGROUND: Patients with psoriasis and HIV infection often present with more severe and treatment-refractory cutaneous disease. In addition, many of these patients have significant psoriatic arthritis. Many effective drugs for psoriasis and psoriatic arthritis are immunosuppressive. Therefore, therapy for the HIV-infected patient is more challenging, requiring both careful consideration of the potential risks and benefits of treatment and more fastidious monitoring for potential adverse events. 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 psoriasis in patients with HIV. METHODS: A MEDLINE search of the terms "psoriasis," "psoriatic arthritis," "human immunodeficiency virus (HIV)," and "HIV skin diseases" was performed and literature relevant to HIV-associated psoriasis and the treatment of HIV-associated psoriasis were reviewed. RESULTS: Based on a review of the literature, 29 reports were included as evidence in this review. Topical therapy is the first-line recommended treatment for mild to moderate disease. For moderate to severe disease, phototherapy and antiretrovirals are the recommended first-line therapeutic agents. Oral retinoids may be used as second-line treatment. For more refractory, severe disease, cautious use of cyclosporine, methotrexate, hydroxyurea, and tumor necrosis factor-alpha inhibitors may also be considered. LIMITATIONS: There are no randomized, placebo-controlled trials evaluating the therapeutic efficacy or safety of treatments for patients with HIV-associated psoriasis; consequently, the evidence supporting this review consists mainly of case reports or case series. CONCLUSIONS: HIV-associated psoriasis is often refractory to traditional treatments. Treatment is challenging and requires careful consideration and should be tailored to patients based on disease severity and the input from an infectious disease specialist. Close monitoring for potential adverse events is necessary.

Treatment of psoriasis in patients with hepatitis C: from the Medical Board of the National Psoriasis Foundation.

BACKGROUND: Treating psoriasis in patients with concomitant hepatitis C virus (HCV) infection presents a special challenge. Not only is psoriasis exacerbated by interferon therapy, the standard of care for HCV, but many psoriasis therapies are potentially hepatotoxic, immunosuppressive, or both, which has been generally thought to be a contraindication in chronic infections such as HCV. OBJECTIVE: Our aim was to arrive at a consensus on treating psoriasis in patients with concomitant HCV infection. METHODS: Reports in the literature were reviewed regarding common psoriasis therapies and liver toxicity. RESULTS: Topical therapies are first-line therapy for patients with limited psoriasis and HCV. Ultraviolet B phototherapy may be considered as a second-line treatment when needed. Ultraviolet B phototherapies in combination with topical therapies are first line for patients with moderate to severe psoriasis, and are considered safe in those patients with concomitant HCV infection. Other systemic therapies, such as acitretin, etanercept, and, possibly, other tumor necrosis factor inhibitors, are considered second line. Psoralen plus ultraviolet A should also be considered a second-line therapy. LIMITATIONS: There are few evidence-based studies on treating psoriasis with systemic therapy in patients with pre-existing liver disease. CONCLUSIONS: There are no large double-blind clinical trials addressing the treatment of psoriasis in patients with HCV infection and more studies are needed.

LGD-5552, an antiinflammatory glucocorticoid receptor ligand with reduced side effects, in vivo.

Treatment of inflammation is often accomplished through the use of glucocorticoids. However, their use is limited by side effects. We have examined the activity of a novel glucocorticoid receptor ligand that binds the receptor efficiently and strongly represses inflammatory gene expression. This compound has potent antiinflammatory activity in vivo and represses the transcription of the inflammatory cytokine monocyte chemoattractant protein-1 and induces the antiinflammatory cytokine IL-10. The compound demonstrates differential gene regulation, compared with commonly prescribed glucocorticoids, effectively inducing some genes and repressing others in a manner different from the glucocorticoid prednisolone. The separation between the antiinflammatory effects of LGD-5552 and the side effects commonly associated with glucocorticoid treatment suggest that this molecule differs significantly from prednisolone and other steroids and may provide a safer therapeutic window for inflammatory conditions now commonly treated with steroidal glucocorticoids.