Patient-reported outcomes of adalimumab, phototherapy, and placebo in the Vascular Inflammation in Psoriasis Trial: A randomized controlled study.

BACKGROUND: There are limited data about the impact of narrowband ultraviolet B phototherapy on patient-reported measures of health-related quality of life. OBJECTIVE: To evaluate the impact of adalimumab and phototherapy on health-related quality of life. METHODS: We examined patient-reported outcomes from a multicenter, randomized, placebo-controlled trial (ClinicalTrials.gov no. NCT01553058). The Dermatology Life Quality Index and EQ-5D-3L were evaluated every 4 weeks. RESULTS: We enrolled 97 patients: 30.9% were female, mean age was 43.5 years (standard deviation, 14.0), and median Psoriasis Area and Severity Index score was 16.7 (interquartile range, 13.9-21.6). At week 12, patients being treated with adalimumab (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.02-8.17) and phototherapy (OR, 8.83; 95% CI, 2.47-31.57) were more likely to achieve the minimal clinically important difference in the Dermatology Life Quality Index compared with those receiving placebo. There were higher odds of achieving the minimal clinically important difference for the EQ-5D-3L Index score when comparing phototherapy versus placebo (OR, 9.78; 95% CI, 2.99-31.95) and phototherapy versus adalimumab (OR, 4.07; 95% CI, 1.42-11.70). LIMITATIONS: Small sample size, secondary analysis, generalizability. CONCLUSION: Phototherapy and adalimumab both improve skin-related quality of life and overall health-related quality of life compared with placebo in patients with psoriasis; however, patients treated with phototherapy achieved more improvement in overall health-related quality of life compared with patients treated with adalimumab.

Comparative effectiveness of less commonly used systemic monotherapies and common combination therapies for moderate to severe psoriasis in the clinical setting.

BACKGROUND: The effectiveness of psoriasis therapies in real-world settings remains relatively unknown. OBJECTIVE: We sought to compare the effectiveness of less commonly used systemic therapies and commonly used combination therapies for psoriasis. METHODS: This was a multicenter cross-sectional study of 203 patients with plaque psoriasis receiving less common systemic monotherapy (acitretin, cyclosporine, or infliximab) or common combination therapies (adalimumab, etanercept, or infliximab and methotrexate) compared with 168 patients receiving methotrexate evaluated at 1 of 10 US outpatient dermatology sites participating in the Dermatology Clinical Effectiveness Research Network. RESULTS: In adjusted analyses, patients on acitretin (relative response rate 2.01; 95% confidence interval [CI] 1.18-3.41), infliximab (relative response rate 1.93; 95% CI 1.26-2.98), adalimumab and methotrexate (relative response rate 3.04; 95% CI 2.12-4.36), etanercept and methotrexate (relative response rate 2.22; 95% CI 1.25-3.94), and infliximab and methotrexate (relative response rate 1.72; 95% CI 1.10-2.70) were more likely to have clear or almost clear skin compared with patients on methotrexate. There were no differences among treatments when response rate was defined by health-related quality of life. LIMITATIONS: Single time point assessment may result in overestimation of effectiveness. CONCLUSIONS: The efficacy of therapies in clinical trials may overestimate their effectiveness as used in clinical practice. Although physician-reported relative response rates were different among therapies, absolute differences were small and did not correspond to differences in patient-reported outcomes.

Safety observations in 12095 patients with psoriasis enrolled in an international registry (PSOLAR): experience with infliximab and other systemic and biologic therapies.

BACKGROUND: Long-term data are essential to assess the safety of biologic agents for the treatment of psoriasis. OBJECTIVE: To evaluate the incidence of adverse events of interest (AEIs), including all-cause mortality, major adverse cardiovascular events (MACE), malignancy (excluding nonmelanoma skin cancer), and serious infections (SI), in patients treated for psoriasis in clinical practice settings. METHODS: PSOLAR is a large, ongoing, observational study of patients receiving, or eligible to receive, biologic or systemic therapy for psoriasis. Cumulative incidence rates of AEIs per 100 patient-years (PY) are reported across treatment cohorts: (1) infliximab, (2) ustekinumab, (3) other biologics (eg, adalimumab and etanercept), and (4) non-biologic agents. Significant predictors of each AEI were identified using Cox proportional hazards regression methodology. RESULTS: PSOLAR is now fully enrolled at 12095 patients followed for 31818PY. The cumulative rate was 0.46/100PY for death, 0.36/100PY for MACE, 0.68/100PY for malignancy, and 1.50/100PY for SI. Increasing age was a significant predictor of all AEIs. A history of cardiovascular disease, malignancy, and significant infection was associated with a higher risk of developing MACE, malignancy, and SI, respectively. Exposure to infliximab (Hazard Ratio [HR]=3.101, P<0.001) and exposure to other biologics (HR=1.736, P<0.001) were significant predictors of SI. Use of immunomodulators (HR=1.954, P=0.005) was a significant predictor of MACE. Compared with non-biologic therapy, the use of biologic agents was not a significant predictor of death, MACE, or malignancy. CONCLUSIONS: Based on PSOLAR data through 2013, no new safety concerns were observed with infliximab for all-cause mortality, MACE, or malignancy; the data suggest that infliximab was associated with serious infections.

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.

Effect of infliximab on health-related quality of life and disease activity by body region in patients with moderate-to-severe psoriasis and inadequate response to etanercept: results from the PSUNRISE trial.

BACKGROUND: Treatment with tumor necrosis factor (TNF)-α antagonists is effective in patients with moderate-to-severe plaque psoriasis, including those with impaired health-related quality of life (HRQoL). METHODS: PSUNRISE is a multicenter, open-label, prospective study evaluating the efficacy and safety of switching from etanercept to infliximab in psoriasis patients with an inadequate response to etanercept. Patients received intravenous infusions of infliximab 5 mg/ kg at weeks 0, 2, 6, 14, and 22. HRQoL was assessed using the Dermatology Life Quality Index (DLQI), the 36-item Short-Form Health Survey (SF-36), and the EuroQoL (EQ-5D) index and EQ-5D visual analog scale (VAS; 0-100 cm) among patients receiving at least one infliximab infusion. Subgroup analyses (t- test) were performed to compare mean DLQI improvement between patients who achieved and did not achieve clinical response (Physician's Global Assessment [PGA] 0/1 and at least a 75% improvement in the Psoriasis Area and Severity Index [PASI 75]) at weeks 10 and 26. RESULTS: A total of 215 patients received at least one infliximab infusion. A DLQI score of 0 or 1 (no negative effect on HRQoL) was achieved by 3.7%, 44.2%, and 41.4% of patients at weeks 0, 10 and 26, respectively. Mean changes in SF-36 Physical Component Summary scores were 1.8 (week 10) and 2.4 (week 26); corresponding changes in Mental Component Summary scores were 4.5 and 5.0. The mean change in EQ-5D index score was 0.08 at week 10 and 0.09 at week 26; respective mean changes in EQ-5D VAS score were 7.73 and 9.49. Mean improvements in DLQI were significantly higher for patients achieving versus those not achieving PGA 0/1 (P=0.0193 [week 10] and P=0.0010 [week 26]) and PASI 75 response (P<0.0001 [week 10]; P=0.0012 [week 26]). CONCLUSION: Psoriasis patients with prior inadequate response to etanercept demonstrated sustained improvements in HRQoL after switching to infliximab, and HRQoL improvements were associated with clinical responses.

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.

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.

Association of Apremilast With Vascular Inflammation and Cardiometabolic Function in Patients With Psoriasis: The VIP-A Phase 4, Open-label, Nonrandomized Clinical Trial.

Importance: Psoriasis is an inflammatory condition associated with metabolic and cardiovascular disease. Apremilast, a phosphodiesterase 4 inhibitor, is commonly used for psoriasis and can cause weight loss. Objective: To determine the association between apremilast and aortic vascular inflammation as assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), cardiometabolic markers (primary outcomes at week 16), and abdominal fat composition. Design, Setting, and Participants: A single-arm, open-label, interventional, nonrandomized clinical trial in which the imaging and laboratory outcomes were measured by an investigator who was blinded to time was conducted between April 11, 2017, and August 17, 2021, at 7 dermatology sites in the United States. A total of 101 patients with moderate to severe psoriasis were screened, 70 enrolled, 60 completed week 16, and 39 completed week 52. Intervention: Apremilast, 30 mg, twice daily. Main Outcomes and Measures: Aortic vascular inflammation (measured by FDG-PET/CT), 68 cardiometabolic biomarkers, and abdominal fat composition (measured by CT) at week 16 and week 52 compared with baseline. Results: The mean (SD) age of the 70 patients was 47.5 (14.6) years, 54 were male (77.1%), 4 were Black (5.7%), and 58 were White (82.9%). There was no change in aortic vascular inflammation at week 16 (target to background ratio, -0.02; 95% CI, -0.08 to 0.05; P = .61) or week 52 (target to background ratio, -0.07; 95% CI, -0.15 to 0.01; P = .09) compared with baseline. At week 16, potentially beneficial decreases in interleukin 1b, valine, leucine, isoleucine, fetuin A, and branched-chain amino acids were observed. At week 52 compared with baseline, potentially beneficial decreases in ferritin, ß-hydroxybutyrate, acetone, and ketone bodies, with an increase in apolipoprotein A-1, were observed, but there was a reduction in cholesterol efflux. There was an approximately 5% to 6% reduction in subcutaneous and visceral adiposity at week 16 that was maintained at week 52. Conclusions and Relevance: The findings of this nonrandomized clinical trial suggest that apremilast has a neutral association with aortic vascular inflammation, variable but generally beneficial associations with a subset of cardiometabolic biomarkers, and associations with reductions in visceral and subcutaneous fat, indicating that the drug may have an overall benefit for patients with cardiometabolic disease and psoriasis. Trial Registration: ClinicalTrials.gov Identifier: NCT03082729.

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.

Nodular lymphangitis: Report of a case with presentation of a diagnostic paradigm.

A 54-year-old man with asthma, mitral valve prolapse, and a back injury developed erythematous nodules that progressed along the lymphatic drainage of his right arm. Skin biopsy revealed granulomatous inflammation with microabscess formation. Culture confirmed Mycobacterium marinum infection. The patient was treated with clarithromycin, ethambutol, rifampin, and topical silver sulfadiazine. Oral doxycycline hyclate was later added because of slow healing. Mycobacterium marinum is one of a group of infectious agents that can cause nodular lymphangitis. Sporotrichoid lesions most commonly develop after cutaneous inoculation with Sporothrix schenckii, Leishmania species, Nocardia species, and Mycobacterium marinum. A thorough clinical history and physical examination can narrow the differential diagnosis by eliciting information about the etiologic setting, incubation time, clinical appearance of the lesions, and presence or absence of systemic involvement for each of the causative organisms. Skin biopsy and microbiological tissue cultures are essential for diagnostic confirmation. The differential diagnosis and a suggested diagnostic paradigm will be reviewed.

Optimizing the Treatment of Moderate-to-Severe Psoriasis in Older Adults.

Psoriasis is a lifelong disease and its prevalence in older adults continues to increase as the population ages. Therefore, it is important for physicians to understand the management of the disease in this population. While the management of psoriasis in older adults is similar to the management of patients below the age of 65 years, there are special considerations when treating older patients. Older patients may have more comorbidities, more immunosuppression, and are often taking additional medications that can interact with those being used to treat psoriasis. Safer and more effective treatment options for psoriasis have been introduced in recent years, particularly injectable biological agents. Unfortunately, older patients with psoriasis are oftentimes underrepresented in the clinical trials for these new medications. Subsequent studies have focused on the safety and efficacy of these medications in older adults. The results of these studies demonstrate that biologic agents are well tolerated in older patients and are more effective in treating psoriasis than conventional systemic therapies. In addition, new small-molecule agents such as apremilast also offer an effective and safe treatment option for older patients with psoriasis. The results of these studies can help guide physicians with incorporating these newer medications into the treatment regimen of older psoriasis patients. Despite the proven safety and efficacy of biologic agents, their frequency of use in elderly patients is still almost half of that in non-elderly patients.

Biosimilars for the treatment of patients with psoriasis: A consensus statement from the Biosimilar Working Group of the International Psoriasis Council.

BACKGROUND: As biosimilars have become available in various parts of the world, the International Psoriasis Council has reviewed aspects of their use. OBJECTIVE: To provide consensus statements from the Biosimilar Working Group about the use of biosimilars in patients with psoriasis. METHODS: A semiqualitative structured process was employed to approve the consensus statements on biosimilars using the nominal group technique. The final statements were validated by a survey of the paricipants. The approval of the consensus statements was predefined as >80% positive opinions. RESULTS: A consensus was reached in 36/38 statements regarding regulatory considerations, extrapolation of indication, interchangeability, substitution at the pharmacy level, pharmacovigilance, traceability, naming, biosimilar policy, education, and cost of biosimilars. Example statements include "Switching a stable patient from a reference product to a biosimilar product is appropriate if the patient and physician agree to do so" and "Patients and patients' organisations should be involved in all decision making and policy development about the use of biosimilars." CONCLUSION: The International Psoriasis Council Biosimilar Working Group provides consensus statements for the use of biosimilars in the treatment of patients with psoriasis. We suggest that these statements provide global guidance to clinicians, healthcare organizations, pharmaceutical companies, regulators, and patients regarding the development and use of biosimilars in patients with psoriasis.

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.

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.

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.

Management of moderate to severe plaque psoriasis (part 2): clinical update on T-cell modulators and investigational agents.

This second part of a 2-part review on the use of biologics for treatment of patients with psoriasis is focused on currently approved therapies that work through modulation of T cells: alefacept, a leukocyte function-associated antigen 3-immunoglobulin G fusion molecule; and efalizumab, an anti-CD11 humanized antibody. Efficacy and safety data from pivotal clinical trials are summarized and new data are presented for these biological agents, and considerations for optimal therapeutic selection are discussed. Clinical data from investigational agents currently in development are also reviewed. One of these new agents is ustekinumab, a humanized antibody that targets interleukins 12 and 23 and inhibits the differentiation of Th17 cells, a recently identified subset of CD4+ T-helper cells.