Use of an alternative method to evaluate erythema severity in a clinical trial: difference in vehicle response with evaluation of baseline and postdose photographs for effect of oxymetazoline cream 1·0% for persistent erythema of rosacea in a phase IV study.

BackgroundOnce-daily topical oxymetazoline cream 1·0% significantly reduced persistent facial erythema of rosacea in trials requiring live, static patient assessments.ObjectivesTo evaluate critically the methodology of clinical trials that require live, static patient assessments by determining whether assessment of erythema is different when reference to the baseline photograph is allowed.MethodsIn two identically designed, randomized, phase III trials, adults with persistent facial erythema of rosacea applied oxymetazoline or vehicle once daily. This phase IV study evaluated standardized digital facial photographs from the phase III trials to record ≥ 1-grade Clinician Erythema Assessment (CEA) improvement at 1, 3, 6, 9 and 12 h postdose.ResultsAmong 835 patients (oxymetazoline n = 415, vehicle n = 420), significantly greater proportions of patients treated with oxymetazoline vs. vehicle achieved ≥ 1-grade CEA improvement. For the comparison between phase IV study results and the original phase III analysis, when reference to baseline photographs was allowed while evaluating post-treatment photographs, the results for oxymetazoline were similar to results of the phase III trials (up to 85.7%), but a significantly lower proportion of vehicle recipients achieved ≥ 1-grade CEA improvement (up to 29.7% [phase 4] vs. 52.3% [phase 3]; P<0.001). In the phase IV study, up to 80·2% of patients treated with oxymetazoline achieved at least moderate erythema improvement vs. up to 22·9% of patients treated with vehicle. The association between patients' satisfaction with facial skin redness and percentage of erythema improvement was statistically significant.ConclusionsAssessment of study photographs, with comparison to baseline, confirmed significant erythema reduction with oxymetazoline on the first day of application. Compared with the phase III trial results, significantly fewer vehicle recipients attained ≥ 1-grade CEA improvement, suggesting a mitigated vehicle effect. This methodology may improve the accuracy of clinical trials evaluating erythema severity

Vehicles for atopic dermatitis therapies: more than just a placebo

A topical vehicle is a ‘carrier system’ for an active pharmaceutical (or cosmetic) substance, referred to hereafter as the drug, but a vehicle may also be used on its own as an emollient to ameliorate dry skin. It is well established that the vehicle plays an important role in determining the bioavailability of a given drug at its ultimate target within the skin. Yet in the treatment of atopic eczema/dermatitis (AD), wherein the structure and function of the skin's outer barrier play a pivotal role in the development and course of the condition, the interaction of the vehicle with this barrier carries a particular importance. It is now clear that the often-considered inert excipients of a vehicle bring about changes within the skin at the molecular level that promote barrier restoration and enhance innate immune defenses with therapeutic value to AD patients. Moreover, the vehicle control in randomized controlled trials (RCTs) increasingly displays significant efficacy. In light of this, we consider the implications of vehicle design in relation to AD pathophysiology and the role vehicles play as controls in RCTs of new drug treatments for this condition

Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1)

BackgroundApremilast works intracellularly to regulate inflammatory mediators.ObjectiveESTEEM 1 evaluated efficacy/safety of apremilast at 30 mg twice a day for moderate to severe plaque psoriasis.MethodsThis phase III, multicenter, double-blind, placebo-controlled study randomized adults (2:1) to apremilast or placebo. At week 16, the placebo group switched to apremilast through week 32, followed by a randomized treatment withdrawal phase to week 52. Binary end points were analyzed using χ2 test; continuous end points used analysis of covariance.ResultsIn all, 844 patients were randomized (n = 282, placebo; n = 562, apremilast). At week 16, significantly more patients taking apremilast achieved 75% or greater reduction from baseline Psoriasis Area and Severity Index score (PASI-75) (33.1%) versus placebo (5.3%, P < .0001; primary end point). Most (61.0%) patients rerandomized to apremilast at week 32 achieved PASI-75 at week 52 versus 11.7% rerandomized to placebo. Of patients rerandomized to apremilast at week 32, mean percentage change from baseline PASI score was −88% to −81% (weeks 32-52). During the placebo-controlled period, 55.7% and 69.3% of patients randomized to placebo and apremilast, respectively, had 1 or more adverse events. Most adverse events were mild/moderate in severity. No new significant adverse events emerged with continued apremilast exposure versus the placebo-controlled period.LimitationsData were limited to 52 weeks and may not generalize to nonplaque psoriasis.ConclusionsApremilast was effective in moderate to severe plaque psoriasis

Evaluation of the glycemic effect of methotrexate in psoriatic arthritis patients with metabolic syndrome. a pilot study

Methotrexate (MTX) is a systemic immunosuppressant drug used for the treatment of psoriasis and psoriatic arthritis. Previous studies demonstrated a potential association between psoriasis and diabetes mellitus, obesity, atherosclerosis, hypertension, eventuating into metabolic syndrome. This study aimed at exploring the glycemic effects of MTX in psoriatic arthritis (PsA) patients. In this prospective cross-sectional study, 27 patients with PsA were evaluated. The status of PsA and presence of accompanying metabolic syndrome was determined by standard criteria and indices. Blood indicators including HbA1c, erythrocyte sedimentation rate, fasting blood sugar, total cholesterol, high-density lipoprotein, triglycerides, and C-reactive protein were examined before and 12 weeks after MTX therapy. There were no significant changes between HbA1c levels before and after MTX therapy in both genders (men: P=0.131, women: P=0.803). In addition, HbA1c levels in PsA patients with metabolic syndrome were not different before and after treatment (P=0.250). Finally, HbA1c levels did not change in PsA patients without metabolic syndrome before and after therapy (P=0.506). MTX in PsA patients does not appear to have hyperglycaemic effects in the short-term and can be safely used in patients with metabolic syndrome and diabete

Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments

Evidence-Based Management of Hand Eczema

Hand eczema is a common skin disease with a wide variation in morphology and a complex etiology based on endogenous and exogenous factors.The diagnosis of hand eczema is based on patient history, exposure assessment, physical examination, and the results of patch testing. Management of hand eczema starts with education of the patient on the etiology of the disease, and the needed changes in behavior regarding skin care and preventive measures, and avoidance of relevant exposure factors. In many cases, medical treatment is needed for successful management of the disease; use of medication can only be successful with proper education and avoidance of relevant exposure

National Psoriasis Foundation COVID-19 Task Force guidance for management of psoriatic disease during the pandemic: Version 2—Advances in psoriatic disease management, COVID-19 vaccines, and COVID-19 treatments

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objective To update guidance regarding the management of psoriatic disease during the COVID-19 pandemic. Study Design The task force (TF) includes 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation staff. Clinical questions relevant to the psoriatic disease community were informed by inquiries received by the National Psoriasis Foundation. A Delphi process was conducted. Results The TF updated evidence for the original 22 statements and added 5 new recommendations. The average of the votes was within the category of agreement for all statements, 13 with high consensus and 14 with moderate consensus. Limitations The evidence behind many guidance statements is variable in quality and/or quantity. Conclusions These statements provide guidance for the treatment of patients with psoriatic disease on topics including how the disease and its treatments affect COVID-19 risk, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 (including novel vaccination), and what they should do if they develop COVID-19. The guidance is a living document that is continuously updated by the TF as data emerge

National Psoriasis Foundation COVID-19 Task Force Guidance for Management of Psoriatic Disease During the Pandemic: Version 1

Objective To provide guidance about management of psoriatic disease during the coronavirus disease 2019 (COVID-19) pandemic. Study design A task force (TF) of 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care was convened. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation (NPF) staff. Clinical questions relevant to the psoriatic disease community were informed by questions received by the NPF. A Delphi process was conducted. Results The TF approved 22 guidance statements. The average of the votes was within the category of agreement for all statements. All guidance statements proposed were recommended, 9 with high consensus and 13 with moderate consensus. Limitations The evidence behind many guidance statements is limited in quality. Conclusion These statements provide guidance for the management of patients with psoriatic disease on topics ranging from how the disease and its treatments impact COVID-19 risk and outcome, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 and what they should do if they develop COVID-19. The guidance is intended to be a living document that will be updated by the TF as data emerge

Cutaneous Adverse Events in the Randomized, Double-Blind, Active-Comparator DECIDE Study of Daclizumab High-Yield Process Versus Intramuscular Interferon Beta-1a in Relapsing-Remitting Multiple Sclerosis

INTRODUCTION: Cutaneous adverse events (AEs) have been observed in clinical studies of daclizumab high-yield process (HYP) in relapsing-remitting multiple sclerosis (RRMS). Here, we report cutaneous AEs observed in the randomized, double-blind, active-comparator DECIDE study (ClinicalTrials.gov identifier, NCT01064401). METHODS: DECIDE was a randomized, double-blind, active-controlled phase 3 study of daclizumab HYP 150 mg subcutaneous every 4 weeks versus interferon (IFN) beta-1a 30 mcg intramuscular (IM) once weekly in RRMS. Treatment-emergent AEs were classified and recorded by investigators. Investigators also assessed the severity of each AE, and whether it met the criteria for a serious AE. Cutaneous AEs were defined as AEs coded to the Medical Dictionary for Regulatory Activities System Organ Class of skin and subcutaneous tissue disorders. The incidence, severity, onset, resolution, and management of AEs were analyzed by treatment group. RESULTS: Cutaneous AEs were reported in 37% of daclizumab HYP-treated patients and 19% of IFN beta-1a-treated patients. The most common investigator-reported cutaneous AEs with daclizumab HYP were rash (7%) and eczema (4%). Most patients with cutaneous AEs remained on treatment (daclizumab HYP, 81%; IM IFN beta-1a, 90%) and had events that were mild or moderate (94% and 98%) and subsequently resolved (78% and 82%). Most patients with cutaneous AEs did not require treatment with corticosteroids or were treated with topical corticosteroids (daclizumab HYP, 73%; IM IFN beta-1a, 81%). Serious cutaneous AEs were reported in 14 (2%) daclizumab HYP patients and one (<1%) IM IFN beta-1a patient. CONCLUSION: There was an increased risk of cutaneous AEs with daclizumab HYP. While physicians should be aware of the potential for serious cutaneous AEs, the typical cutaneous AEs were mild-to-moderate in severity, manageable, and resolved over time. FUNDING: Biogen and AbbVie Biotherapeutics Inc. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01064401. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12325-016-0353-2) contains supplementary material, which is available to authorized users