Joint AAD-NPF Guidelines of care for the management and treatment of psoriasis with topical therapy and alternative medicine modalities for psoriasis severity measures.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults.

Characterization of insufficient responders to ustekinumab in patients with moderate-to-severe psoriasis in the US Corrona Psoriasis Registry.

OBJECTIVE: Biologic therapies have revolutionized the management of moderate-to-severe psoriasis; however, there are a limited number of US real-world studies characterizing patients based on response to these treatments. This study examined characteristics at enrollment and change in outcomes of US patients with moderate-to-severe psoriasis who achieved insufficient responses with ustekinumab. METHODS: This study included patients enrolled in the Corrona Psoriasis Registry from April 2015 to June 2018 who initiated ustekinumab at enrollment and who were stratified based on achievement of psoriasis body surface area improving to <3% or by 75% from enrollment to the 6-month follow-up visit (response vs insufficient response). Patient demographics and disease characteristics were described at enrollment, and changes in outcomes were assessed at 6-month follow-up for ustekinumab responders and insufficient responders. RESULTS: Of the 178 patients who initiated ustekinumab in the Corrona Psoriasis Registry and had ≥1 follow-up visit, 99 (55.6%) were classified as responders at the 6-month follow-up visit. Logistic regression modeling showed that increasing age was significantly associated with a decreased likelihood of achieving a response (OR, 0.981 [95%CI, 0.962-0.999]; p = .049). CONCLUSIONS: These findings may help dermatologists characterize patients with moderate-to-severe psoriasis who have inadequate responses to biologic treatments.

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis with phototherapy.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world's population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light-based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments.

Depressive symptoms, depression, and the effect of biologic therapy among patients in Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: Patients with psoriasis are at an increased risk for depression. However, the impact of treatment on this risk is unclear. OBJECTIVE: Evaluate the incidence and impact of treatment on depression among patients with moderate-to-severe psoriasis. METHODS: We defined a study population within the Psoriasis Longitudinal Assessment and Registry and measured the incidence of depressive symptoms (Hospital Anxiety and Depression Scale-Depression score ≥8) and adverse events (AEs) of depression within cohorts receiving biologics, conventional systemic therapies, or phototherapy. Patients were evaluated at approximately 6-month intervals. Multivariate modeling determined the impact of treatment on risk. RESULTS: The incidence rates of depressive symptoms were 3.01 per 100 patient-years (PYs) (95% confidence interval [CI], 2.73-3.32), 5.85 per 100 PYs (95% CI, 4.29-7.97), and 5.70 per 100 PYs (95% CI, 4.58-7.10) for biologics, phototherapy, and conventional therapy, respectively. Compared with conventional therapy, biologics reduced the risk for depressive symptoms (hazard ratio, 0.76; 95% CI, 0.59-0.98), whereas phototherapy did not (hazard ratio, 1.05; 95% CI, 0.71-1.54). The incidence rates for AEs of depression were 0.21 per 100 PYs (95% CI, 0.15-0.31) for biologics, 0.55 per 100 PYs (95% CI, 0.21-1.47) for phototherapy, and 0.14 per 100 PYs (95% CI, 0.03-0.55) for conventional therapy; the fact that there were too few events (37 AEs) precluded modeling. LIMITATIONS: Incomplete capture of depression and confounders in the patients on registry. CONCLUSION: Compared with conventional therapy, biologics appear to be associated with a lower incidence of depressive symptoms among patients with psoriasis.

Secukinumab improves patient-reported psoriasis symptoms of itching, pain, and scaling: results of two phase 3, randomized, placebo-controlled clinical trials.

BACKGROUND: Secukinumab is a human interleukin-17A antagonist indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The objective of this analysis was to measure the treatment response on psoriasis-related itching, pain, and scaling via the Psoriasis Symptom Diary (PSD)(©). METHODS: ERASURE (n = 738) and FIXTURE (n = 1306) were double-blind, multicenter phase 3 studies in adults randomized to secukinumab (300, 150 mg, n = 1144) or placebo (n = 574) (administered at Weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks) or a biologic active control (FIXTURE only). Patient-reported itching, pain, and scaling were assessed during the first 12 weeks of treatment using the PSD. The results reported here are limited to subjects in the secukinumab and placebo treatment groups who completed the PSD. The proportions of subjects achieving prespecified responses (improvement:reduction of at least 2.2 points for itching, 2.2 points for pain, or 2.3 points for scaling) were compared for secukinumab versus placebo. RESULTS: Overall, 39% of subjects completed the PSD at baseline and Week 12 (n = 453 secukinumab; 225 placebo). Subjects treated with secukinumab achieved significantly greater improvements in itching, pain, and scaling at Week 12 versus placebo (all P < 0.0001) and had significantly greater proportions of itching, pain, and scaling responders at Week 12 versus placebo (all P < 0.05). CONCLUSION: Secukinumab significantly improves patient-reported itching, pain, and scaling in adults with moderate to severe psoriasis compared with placebo.

Treatment of atopic dermatitis in pregnancy.

Atopic dermatitis (AD), also referred to as eczema, is one of the most frequently observed skin diseases in pregnant patients. The presentation and histopathology of this condition during pregnancy is identical to that of the non-pregnant individual. AD is a T-helper 2 dominant disease and may worsen during pregnancy, which favors this population of T-lymphocytes. AD management during pregnancy requires special precautions to avoid harming the fetus. Herein is an exploration of the different options available for the treatment of the pregnant patient with AD. The management of concomitant bacterial and viral infections is also discussed.

Management of psoriasis in pregnancy.

Psoriasis is an inflammatory skin disorder not uncommonly seen in pregnant patients. Several drugs have been approved for its treatment in non-pregnant patients, but special precautions are necessary when selecting a treatment plan during pregnancy to prevent harm to the fetus and child. This article reviews the treatment options for the treatment of psoriasis in the pregnant and lactating patient.

A Delphi Consensus Approach to Challenging Case Scenarios in Moderate-to-Severe Psoriasis: Part 2.

INTRODUCTION: Clinicians may be confronted with difficult-to-treat psoriasis cases for which there are scant data to rely upon for guidance. To assist in managing such patients, who are typically excluded from clinical trials, a consensus panel of 14 experts in the field of psoriasis was formed to conduct a Delphi method exercise. METHODS: The exercise consisted of both survey questionnaires and a live meeting to review and discuss current data (as of 2009, when the exercise was conducted) and arrive at a consensus for optimal treatment options. Seventy difficult treatment scenarios were identified, and the top 24 were selected for discussion at the live meeting. RESULTS: Five of the 24 discussed case scenarios are presented in this article: (1) moderate-to-severe psoriasis that has failed to respond to all currently approved therapies for psoriasis; (2) palmoplantar psoriasis that is unresponsive to topical therapy and phototherapy; (3) erythrodermic psoriasis; (4) pustular psoriasis; and (5) the preferred therapeutic choice to combine with low-dose methotrexate. A previous article (part 1) presented six other scenarios. CONCLUSION: The Delphi exercise resulted in guidelines for practicing physicians to utilize when confronted with patients with challenging cases of psoriasis.

PSOLAR: design, utility, and preliminary results of a prospective, international, disease-based registry of patients with psoriasis who are receiving, or are candidates for, conventional systemic treatments or biologic agents.

BACKGROUND: Long-term observational studies can better characterize the impact of systemic agents on psoriasis. OBJECTIVE: To describe the on-going Psoriasis Longitudinal Assessment and Registry (PSOLAR) study. METHODS: PSOLAR is a large, international, long-term, prospective, disease-based registry enrolling patients with psoriasis who are receiving, or are candidates for, treatment with systemic therapies. The registry fulfills postmarketing regulatory commitments and charges a global Steering Committee to manage epidemiological research on psoriasis and its therapies. Key demographics, disease characteristics, and medication history are collected at enrollment. Adverse events and efficacy data are collected longitudinally. RESULTS: The August 2011 annual database extract includes 9,495 patients enrolled at 266 global centers. At entry, mean percent of body surface area affected by psoriasis was 12.3% (peak, 29.5%). Approximately 80% of patients were overweight/obese, more than one-third had cardiovascular disease (38.8%) or psoriatic arthritis as captured by the treatment center (37.1%), and over half had received one or two biologic agents (58.8%) or phototherapy (54.8%). Mean duration of participation is 1.3 years, and annual withdrawal rates are less than 6.5%. Of 9,495 patients, 7,476 have been exposed to at least one biologic agent. Serious infections, malignancies, all-cause mortality, and major adverse cardiovascular events (ie, myocardial infarction, stroke, cardiovascular death) occurred at rates of 1.40, 0.61, 0.37, and 0.36 per 100 patient-years of follow-up, respectively. LIMITATIONS: PSOLAR may be subject to limitations common to observational studies (eg, participation bias and potential confounders). CONCLUSION: PSOLAR is a disease-based registry designed to assess therapeutic risk and benefit in the general psoriasis population.

Switching to adalimumab for psoriasis patients with a suboptimal response to etanercept, methotrexate, or phototherapy: efficacy and safety results from an open-label study.

BACKGROUND: Strategies for transitioning patients with psoriasis from suboptimal therapy have not been delineated. OBJECTIVE: We sought to determine the efficacy and safety of transitioning to adalimumab for the treatment of psoriasis in patients with suboptimal response to prior therapy with etanercept, methotrexate (MTX), or narrowband (NB)-ultraviolet (UV)B phototherapy. METHODS: In this 16-week, open-label, phase IIIb trial, patients with chronic plaque psoriasis discontinued suboptimal therapy between 11 and 17 days (etanercept) or between 4 and 10 days (MTX and NB-UVB) before initiating adalimumab (80 mg at week 0, then 40 mg every other week from week 1). The primary end point was the percentage of patients achieving a Physician Global Assessment of "clear" or "minimal" at week 16. RESULTS: At week 16, Physician Global Assessment of "clear" or "minimal" was achieved by 52% of all enrolled patients (79 of 152) and 49%, 61%, and 48% in the etanercept, MTX, and NB-UVB subgroups, respectively. Four patients (2.6%) experienced at least 125% worsening of Psoriasis Area and Severity Index score relative to screening value at any study visit. The adalimumab safety profile was consistent with results from other psoriasis clinical trials. LIMITATIONS: This study is limited by its relatively short 16-week duration, small patient enrollment, and open-label design. CONCLUSION: Patients who had a suboptimal response to etanercept, MTX, or NB-UVB phototherapy experienced a similar, approximately 50% likelihood of achieving a clinically relevant response to adalimumab. Immediate transition to adalimumab from prior suboptimal therapy, with no dosage tapering or overlap, had a low risk of psoriasis flare.

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.

The use of therapeutic interchange for biologic therapies.

Therapeutic interchange is the practice of switching or dispensing drugs that are chemically distinct but therapeutically similar in terms of their efficacy, safety, and tolerability profiles. The stated goal of therapeutic interchange is to achieve an improved or neutral outcome with the new agent while reducing overall treatment costs. Until recently, most interchange programs have been limited to switches within drug classes, such as angiotensin-converting enzyme (ACE) inhibitors, proton pump inhibitors (PPIs), HMG-CoA reductase inhibitors (statins), and selective serotonin reuptake inhibitors (SSRIs), and generally to drugs that use the same routes of administration. Therapeutic interchange now is being applied to some biologic agents, such as those used to treat psoriasis and rheumatoid arthritis (RA). In some cases, these agents differ in structure and mode of administration. Patients who require a biologic agent are often difficult to manage, and the comorbidities that are prevalent in these patients further complicate management and agent selection. Population-based outcomes among various agents may not appear notably different, but because there is no a priori means to determine the effects of a given biologic agent on any individual patient, therapeutic interchange is inadvisable once a patient receiving RA or psoriasis therapy has been stabilized. However, if a biologic agent has been designated as preferred on a formulary, it is reasonable to initiate treatment with that agent in a patient who is naive to biologic therapy if that agent is not contraindicated. Respectful, two-way communication between health care professionals and managed care organizations (MCOs) will help ensure that a patient receives the appropriate therapy at the right time.

Folate supplementation during methotrexate therapy for patients with psoriasis.

Methotrexate is a folate antagonist that is a well-established therapy for autoimmune and inflammatory conditions. In some patients, methotrexate is associated with significant side effects and toxicity. Folate supplementation is often used to ameliorate methotrexate-associated side effects and toxicities. We sought to demonstrate that folate supplementation during methotrexate therapy reduces both toxicity and side effects without compromising efficacy. A MEDLINE search of the search terms "methotrexate," "folic acid," "folinic acid," and "leucovorin" was performed and literature relevant to the use of folates as a supplement to methotrexate was reviewed. According to studies reviewed, the use of folate supplements in patients treated with methotrexate reduces the incidence of hepatotoxicity and gastrointestinal intolerance without impairing the efficacy of methotrexate. Both folic acid and folinic acid are equally effective; however, folic acid is more cost effective. It must be noted that there are relatively few studies that have addressed folate supplementation with the use of methotrexate for the treatment of psoriasis. After examining the available data from the literature and drawing from clinical experience, we advise folate supplementation for every patient who receives methotrexate.