Repeat courses of intravenous alefacept in patients with chronic plaque psoriasis provide consistent safety and efficacy

Background Psoriasis is a chronic, relapsing skin disease that may require multiple treatment courses. Alefacept targets the memory T cells implicated in psoriasis pathogenesis. This open-label study evaluated the safety and tolerability, efficacy, and pharmacodynamics of repeat courses of alefacept in men and women with chronic plaque psoriasis. This article reports the interim results of this ongoing study. Methods Patients ( n  = 174) who participated in previous phase II studies of alefacept were included in this retreatment study. Intravenous alefacept (7.5 mg) was administered once weekly for 12 weeks followed by 12 weeks of observation. Initial and subsequent retreatment courses were only given when, in the opinion of the investigators, disease had returned and necessitated treatment; CD4 + T-cell counts had to be at or above the lower limit of normal. Results Adverse events were similar regardless of the retreatment course. No opportunistic infections, rebound of disease, or flares were reported. Low titers of anti-alefacept antibodies occurred in a few patients without related safety issues. Sixty-six per cent of patients achieved a ≥ 50% reduction in the Psoriasis Area and Severity Index (PASI) at any time after the first dose of retreatment course 1. Patients who received two retreatment courses ( n  = 50) had consistent or improved responses after the second course; 64% and 68% of these patients achieved a ≥ 50% PASI improvement at any time after the first dose of retreatment courses 1 and 2, respectively. Alefacept selectively reduced memory T cells without cumulative effects. Conclusions Repeat courses of alefacept were well tolerated, and subsequent retreatment courses were at least as effective as the initial course of therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65825/1/j.1365-4362.2003.01793.x.pd

Dietary Recommendations for Adults With Psoriasis or Psoriatic Arthritis From the Medical Board of the National Psoriasis Foundation: A Systematic Review

Importance: Psoriasis is a chronic, inflammatory skin disease and has significant associated morbidity and effect on quality of life. It is important to determine whether dietary interventions help reduce disease severity in patients with psoriatic diseases. Objective: To make evidence-based dietary recommendations for adults with psoriasis and/or psoriatic arthritis from the Medical Board of the National Psoriasis Foundation. Evidence Review: We used literature from prior systematic reviews as well as additional primary literature from the MEDLINE database from January 1, 2014, to August 31, 2017, that evaluated the impact of diet on psoriasis. We included observational and interventional studies of patients with psoriasis or psoriatic arthritis. The quality of included studies was assessed using the Newcastle-Ottawa scale for observational studies and the Cochrane Risk of Bias Tool for interventional studies. We made evidence-based dietary recommendations, which were voted on by the National Psoriasis Foundation Medical Board. Findings: We identified 55 studies meeting the inclusion criteria for this review. These studies represent 77557 unique participants of which 4534 have psoriasis. Based on the literature, we strongly recommend dietary weight reduction with a hypocaloric diet in overweight and obese patients with psoriasis. We weakly recommend a gluten-free diet only in patients who test positive for serologic markers of gluten sensitivity. Based on low-quality data, select foods, nutrients, and dietary patterns may affect psoriasis. For patients with psoriatic arthritis, we weakly recommend vitamin D supplementation and dietary weight reduction with a hypocaloric diet in overweight and obese patients. Dietary interventions should always be used in conjunction with standard medical therapies for psoriasis and psoriatic arthritis. Conclusions and Relevance: Adults with psoriasis and/or psoriatic arthritis can supplement their standard medical therapies with dietary interventions to reduce disease severity. These dietary recommendations from the National Psoriasis Foundation Medical Board will help guide clinicians regarding the utility of dietary interventions in adults with psoriatic diseases

Combining Topical Psoriasis Treatment to Enhance Systemic and Phototherapy: A Review of the Literature

Psoriasis is a chronic inflammatory skin disease that affects millions of people in the United States as well as worldwide. While there is currently no cure for psoriasis, many treatment options are available. Topical therapies are the mainstay for the majority of patients who have limited or mild psoriasis. Among these medications, topical vitamin D analogs (eg, calcipotriene) and corticosteroids (eg, betamethasone), and these drugs in combination, are the most widely prescribed psoriasis drugs and are the cornerstone of topical therapies. For patients with more severe disease, phototherapy, conventional systemic agents, and biologics are often indicated. Currently, the goal of treatment is to control the clinical symptoms of the skin, reduce systemic disease potential, and improve the patient\u27s quality of life. Despite the availability of various therapeutic options for psoriasis, many patients go untreated, and even among those who are treated, many do not achieve complete resolution of the disease. The new consensus is to treat to a target of 1% or less of body surface area involvement. Innovative treatment strategies are needed to meet this goal and patients\u27 desire to achieve clear skin. Combination therapies are widely used by physicians, and adjunctive topical therapies used with other antipsoriatic regimens have been demonstrated to provide many clinical benefits. This article reviews the most recently published clinical evidence of adjunctive use of topical agents with biologics, conventional systemic agents, and phototherapy, to better establish the role of topical agents in combination therapy for the treatment of psoriasis

27611 Fixed-combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion for the treatment of plaque psoriasis in patients with 3-5% body surface area (BSA) and poor quality of life (QoL)

Use of TAZ with topical steroids, such as superpotent HP, is recommended for mild-to-moderate psoriasis as the combination may provide synergistic efficacy while increasing duration of treatment effect and remission. The objective of this analysis was to investigate HP 0.01%/TAZ 0.045% lotion in patients with relatively low affected BSA and poor QoL, as objective measures such as BSA may underestimate disease severity. Two phase 3, multicenter, double-blind studies enrolled 418 adults with 3-12% BSA and Investigator’s Global Assessment (IGA) score of 3 or 4 (‘moderate’ or ‘severe’) at baseline. Participants were randomized (2:1) to receive HP/TAZ or vehicle lotion once-daily for 8 weeks, with a 4-week posttreatment follow-up. Pooled, post hoc analyses were conducted in a subset of 65 participants with baseline BSA of 3-5% and Dermatology Life Quality Index (DLQI) score ≥11. At week 8, 50.3% of HP/TAZ-treated participants achieved treatment success (≥2-grade reduction from baseline in IGA and score of 0 or 1 [‘clear’ or ‘almost clear’]), vs 14.6% of vehicle-treated participants (P ˂.05). BSA was significantly reduced with HP/TAZ ( 39.2%) vs vehicle lotion (+15.9%; P ˂.05). The percentage of participants experiencing a clinically meaningful ≥4-point reduction in DLQI score was greater for HP/TAZ (85.3%) vs vehicle (55.6%). Numerical improvements with HP/TAZ lotion were maintained 4-weeks posttreatment for efficacy measures and DLQI, consistent with the overall population. Though analyses were limited by the small population, HP/TAZ lotion provided significantly greater efficacy vs vehicle in participants with low BSA and poor QoL, with clinically relevant improvements in QoL

Betamethasone dipropionate spray 0.05% alleviates troublesome symptoms of plaque psoriasis

Patients consider pruritus and scaling to be the most bothersome symptoms of psoriasis. Psoriatic plaques on the knees and elbows are widely considered difficult to treat because of the thicker stratum corneum, which reduces skin hydration and topical absorption. Betamethasone dipropionate (BD) spray 0.05% is a topical steroid with demonstrated efficacy in treating plaque psoriasis. Post hoc analyses of 2 phase 3 trials were done to assess the efficacy of BD spray in relieving the symptom of itching and improving the signs of erythema, scaling, and plaque elevation on plaques located on the knees and elbows vs its vehicle and an augmented BD (AugBD) lotion 0.05%. Betamethasone dipropionate spray reduced the incidence of pruritus, with approximately half of patients who reported itching at baseline showing complete itch relief by day 4. Betamethasone dipropionate spray also reduced the signs of psoriasis on knee and elbow plaques in more patients than AugBD lotion at day 4, though the differences were not statistically significant. Efficacy was similar between the 2 formulations on days 8 and 15. Betamethasone dipropionate spray rapidly relieved 2 of the most bothersome symptoms of psoriasis and improved psoriatic signs in hard-to-treat knee and elbow plaques

Serlopitant for psoriatic pruritus: A phase 2 randomized, double-blind, placebo-controlled clinical trial

Pruritus, a common symptom of psoriasis, negatively affects quality of life; however, treatment of lesional skin does not consistently alleviate psoriatic itch. To examine the effects of serlopitant, an oral, once-daily neurokinin 1 receptor antagonist, for treatment of psoriatic pruritus in a phase 2, randomized clinical trial (NCT03343639). Patients (n = 204) were randomized to receive serlopitant, 5 mg, or placebo daily for 8 weeks. Eligible adult patients had plaque psoriasis for ≥6 months, plaques covering ≤10% of body surface area, pruritus for ≥4 weeks, and Worst Itch Numeric Rating Scale (WI-NRS) score ≥7 at the initial screening. Participants (54.2% women) had a mean age of 47.5 years and 85.2% were white. Mean baseline WI-NRS scores were 8.3 for serlopitant and 8.1 for placebo. The WI-NRS 4-point response rate at 8 weeks (primary end point) was 33.3% for serlopitant vs 21.1% for placebo (P = .028); at 4 weeks the rates were 20.8% for serlopitant vs 11.5% for placebo (P = .039). Treatment-related adverse events were reported for 4.9% of serlopitant-treated and 4.0% of placebo-treated patients. This was a phase 2 study with a small study population. Patients with severe psoriasis were excluded. Serlopitant significantly reduced pruritus associated with mild to moderate psoriasis, supporting continued development of serlopitant for this patient population

Improvement in scalp and nails with apremilast in patients with moderate plaque psoriasis naive to systemic and biologic therapy: 52-week results of the UNVEIL study

Background/Objective: Patients with moderate plaque psoriasis (i.e., 5–10% psoriasis-involved Body Surface Area [BSA]) often receive no treatment or are undertreated with topical monotherapy. Plaque psoriasis that occurs in difficult-to-treat areas such as the scalp and nails might be disproportionately more distressing to patients because it is highly visible and can severely impact daily functioning. Apremilast is an oral, small-molecule phosphodiesterase 4 inhibitor that works intracellularly to regulate inflammatory pathways relevant to the pathogenesis of psoriasis. Apremilast has been shown to be effective and has demonstrated acceptable tolerability in Phase IV clinical studies in patients with moderate-to-severe psoriasis. Evaluating Apremilast in a Phase IV Trial of Efficacy and Safety in Patients With Moderate Plaque Psoriasis (UNVEIL; ClinicalTrials.gov: NCT02425826) is the first prospective, randomized, placebo (PBO)-controlled trial to demonstrate the clinical efficacy and safety of a systemic treatment (apremilast) in systemic- and biologic-naive patients with moderate plaque psoriasis. To further understand the efficacy of apremilast in patients with moderate plaque psoriasis, analyses were performed in the subset of patients with baseline scalp and/or nail involvement. Methods: UNVEIL is a Phase IV, multicenter, randomized, PBO-controlled, double-blind study. Men and women at least 18 years of age with chronic plaque psoriasis for six months before screening were included in the study. Subjects had moderate plaque psoriasis at screening and baseline as defined by BSA of 5 to 10 percent and static Physician’s Global Assessment (sPGA) of 3 (moderate) based on a scale ranging from 0 (clear) to 5 (very severe). Included subjects had no prior exposure to systemic or biologic treatments for psoriasis, psoriatic arthritis, or any other condition that could affect the assessment of psoriasis. Potential subjects with an inflammatory or dermatologic condition, including forms of psoriasis other than plaque psoriasis, were excluded. Persons using topical therapy within two weeks or phototherapy within four weeks of randomization were also excluded. Patients were randomized (2:1) to receive apremilast 30mg twice daily (APR) or PBO during Weeks 0 to 16; patients in the PBO group were switched to APR at Week 16. All patients continued taking APR through Week 52. A nonmedicated moisturizer was the only topical therapy permitted during the study. Patients with a baseline Scalp Physician Global Assessment (ScPGA) score of 1 or a Nail Psoriasis Severity Index (NAPSI) score of 1 in the target nail were included in subanalyses of scalp and nail involvement. ScPGA was assessed on a 6-point scale ranging from 0 (clear) to 5 (very severe). One thumbnail or fingernail with the worst nail psoriasis involvement at baseline was designated as the target nail. NAPSI score was calculated in the target nail as the sum of scores for the nail matrix and nail bed, with each score based on the number of quadrants with psoriasis features. Efficacy assessments in patients with scalp psoriasis at baseline included proportion of patients achieving ScPGA score of 0 (clear) or 1 (minimal), with a 2-point reduction from baseline score, at Week 16 and Week 52. Efficacy assessments in patients with nail psoriasis at baseline included change from baseline in NAPSI score at Week 16 and Week 52, proportion of patients achieving a 50-percent reduction from baseline in NAPSI score (NAPSI-50) at Week 16 and Week 52. Safety was evaluated based on adverse events (AEs), vital signs, clinical laboratory testing, and complete physical examinations. Efficacy and safety assessments were conducted for the intent-to-treat (ITT) population, which included all randomized patients; safety assessments included all patients who received one dose of study medication. The proportions of patients achieving ScPGA and NAPSI-50 responses were compared between the PBO and APR groups at Week 16 using a two-sided Cochran-Mantel-Haenszel test stratified by site. Changes from baseline in NAPSI score at Week 16 were compared between treatment groups using a two-way analysis of covariance (ANCOVA) model with treatment and site as factors and baseline value as a covariate. Efficacy parameters at Week 52 were evaluated descriptively. The last-observation-carried-forward (LOCF) methodology was used to impute missing values. Safety assessments were summarized using frequencies and percentages. Results: A total of 221 patients were randomized to study treatment. Of these, 167 patients (75.6%) had scalp psoriasis and 83 patients (37.6%) had nail psoriasis at baseline. Demographic and baseline disease characteristics of the cohorts with scalp psoriasis or nail psoriasis were generally comparable between treatment groups. Mean baseline NAPSI scores were comparable between treatment groups. Across treatment groups, most patients had mild or moderate scalp involvement (i.e., ScPGA score of 2 or 3). Regarding efficacy of APR in scalp psoriasis, at Week 16, more patients treated with APR than with PBO achieved an ScPGA score of 0 or 1 with a 2-point reduction from baseline (38.4% vs. 20.0%, P=0.0178). At Week 52, patients remaining on APR maintained ScPGA response, and those who switched to APR from PBO at Week 16 (PBO/APR) demonstrated an improvement in ScPGA response comparable to those who continued APR treatment (APR/APR). An ScPGA score of 0 or 1 with a 2-point reduction from baseline was achieved by 47.7 percent of patients randomized to APR who continued on APR (APR/APR), and 46.9 percent of patients randomized to PBO who switched to APR (PBO/APR). Regarding the efficacy of APR in nail psoriasis, at Week 16, the mean percentage change from baseline in NAPSI score was -10.5 percent in the PBO group and -28.9 percent in the APR group (P=0.12). At Week 52, continued improvement in NAPSI score was seen in patients who remained on APR treatment (mean percentage change from baseline, -51.9%). Patients who switched from PBO to APR at Week 16 demonstrated an improvement in NAPSI score (mean percentage change from baseline, -52.7%). At Week 16, NAPSI-50 response was achieved by 18.5 percent of patients in the PBO group and 26.8 percent of patients in the APR group (P=0.50). Although differences in NAPSI-50 response with APR compared with PBO are numerically greater, the number of patients with nail psoriasis at baseline was low and thus statistical significance was not demonstrated. At Week 52, the proportion of patients who achieved NAPSI-50 response increased in patients who remained on APR treatment and in patients who switched to APR from PBO at Week 16. The most common AEs reported with APR treatment from 0 to 52 weeks were diarrhea, nausea, headache, and nasopharyngitis. Most AEs were mild or moderate; discontinuations due to AEs occurred in 6.6 percent of patients over the 52-week study. The incidence of AEs, based on exposure-adjusted incidence rate (EAIR) per 100 patient-years, did not increase with longer exposure up to 52 weeks when compared with Weeks 0 to 16. No new safety or tolerability issues were observed up to 52 weeks. Conclusion: APR treatment improved scalp and nail psoriasis at Week 16 in systemic- and biologic-naive patients with moderate plaque psoriasis (BSA 5–10%); continued improvement was seen with APR treatment up to 52 weeks. The efficacy of APR on scalp and nail psoriasis was consistent with that previously reported in patients with moderate-to-severe plaque psoriasis in randomized Phase III trials. The safety and tolerability profile of APR was also consistent with previous studies. Funding/Disclosures: The authors acknowledge financial support for this study from Celgene Corporation. J. Mark Jackson provides research, honoraria, consulting, and/or other support to the Celgene Corporation. Ali Alikhan is a former speaker for Celgene Corporation. Mark Lebwohl is an investigator and/or consultant for the Celgene Corporation. Linda Stein Gold is an investigator and/or consultant for the Celgene Corporation. Joana Goncalves and Eugenia Levi are employees of the Celgene Corporation. Jerry Bagel is an advisory board member, speaker, consultant, and/or provides research support to the Celgene Corporation