Background An urgent need exists in the United States to establish treatment goals in psoriasis. Objective We aim to establish defined treatment targets toward which clinicians and patients with ...psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice. Methods The National Psoriasis Foundation conducted a consensus-building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre-Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds. Results A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less. Limitations Although BSA is feasible in practice, it does not encompass health-related quality of life, costs, and risks of side effects. Conclusion With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit-risk assessments of therapeutic options individualized to the patient.
Summary Background Dupilumab (an anti-interleukin-4-receptor-α monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines implicated in numerous allergic ...diseases ranging from asthma to atopic dermatitis. Previous 16-week monotherapy studies showed that dupilumab substantially improved signs and symptoms of moderate-to-severe atopic dermatitis with acceptable safety, validating the crucial role of interleukin 4 and interleukin 13 in atopic dermatitis pathogenesis. We aimed to evaluate the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids versus placebo with topical corticosteroids in adults with moderate-to-severe atopic dermatitis. Methods In this 1-year, randomised, double-blinded, placebo-controlled, phase 3 study (LIBERTY AD CHRONOS), adults with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids were enrolled at 161 hospitals, clinics, and academic institutions in 14 countries in Europe, Asia-Pacific, and North America. Patients were randomly assigned (3:1:3) to subcutaneous dupilumab 300 mg once weekly (qw), dupilumab 300 mg every 2 weeks (q2w), or placebo via a central interactive voice/web response system, stratified by severity and global region. All three groups were given concomitant topical corticosteroids with or without topical calcineurin inhibitors where inadvisable for topical corticosteroids. Topical corticosteroids could be tapered, stopped, or restarted on the basis of disease activity. Coprimary endpoints were patients (%) achieving Investigator's Global Assessment (IGA) 0/1 and 2-point or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI-75) at week 16. Week 16 efficacy and week 52 safety analyses included all randomised patients; week 52 efficacy included patients who completed treatment by US regulatory submission cutoff. This study is registered with ClinicalTrials.gov , NCT02260986. Findings Between Oct 3, 2014, and July 31, 2015, 740 patients were enrolled: 319 were randomly assigned to dupilumab qw plus topical corticosteroids, 106 to dupilumab q2w plus topical corticosteroids, and 315 to placebo plus topical corticosteroids. 623 (270, 89, and 264, respectively) were evaluable for week 52 efficacy. At week 16, more patients who received dupilumab plus topical corticosteroids achieved the coprimary endpoints of IGA 0/1 (39% 125 patients who received dupilumab plus topical corticosteroids qw and 39% 41 patients who received dupilumab q2w plus topical corticosteroids vs 12% 39 patients who received placebo plus topical corticosteroids; p<0·0001) and EASI-75 (64% 204 and 69% 73 vs 23% 73; p<0·0001). Week 52 results were similar. Adverse events were reported in 261 (83%) patients who received dupilumab qw plus topical corticosteroids, 97 (88%) patients who received dupilumab q2w, and 266 (84%) patients who received placebo, and serious adverse events in nine (3%), four (4%), and 16 (5%) patients, respectively. No significant dupilumab-induced laboratory abnormalities were noted. Injection-site reactions and conjunctivitis were more common in patients treated with dupilumab plus topical corticosteroids-treated patients than in patients treated with placebo plus topical corticosteroids. Interpretation Dupilumab added to standard topical corticosteroid treatment for 1 year improved atopic dermatitis signs and symptoms, with acceptable safety. Funding Sanofi and Regeneron Pharmaceuticals Inc.
Background Onychomycosis is a common nail infection, often resulting in nail plate damage and deformity. Topical lacquer treatments have negligible efficacy. Oral treatments, although more ...efficacious, are limited by drug interactions and potential hepatotoxicity. Objective We investigated the safety and efficacy of efinaconazole 10% solution (efinaconazole), the first triazole antifungal developed for distal lateral subungual onychomycosis. Methods Two identical, multicenter, randomized, double-blind, vehicle-controlled studies were conducted in patients with toenail distal lateral subungual onychomycosis (20%-50% clinical involvement study 1: N = 870, study 2: N = 785). Patients were randomized (3:1) to efinaconazole or vehicle, once daily for 48 weeks, with 4-week posttreatment follow-up. Debridement was not performed. The primary end point was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture) at week 52. Results Mycologic cure rates were significantly greater with efinaconazole (study 1: 55.2%, study 2: 53.4%) compared with vehicle ( P < .001). The primary end point, complete cure, was also significantly greater for efinaconazole (study 1: 17.8% vs 3.3%, study 2: 15.2% vs 5.5%, P < .001). Treatment success (percent affected target toenail 0%-≤10%) for efinaconazole ranged from 21.3% to 44.8% in study 1 and from 17.9% to 40.2% in study 2, compared with 5.6% to 16.8% and 7.0% to 15.4%, respectively, with vehicle. Adverse events associated with efinaconazole were local site reactions (2%) and clinically similar to vehicle. Limitations A period of 52 weeks may be too brief to evaluate a clinical cure in onychomycosis. Conclusions Once daily topical efinaconazole appears to be a viable alternative to oral treatment options for onychomycosis.
Background Many medications, including tumor necrosis factor antagonists, have been anecdotally reported to be effective in treating cutaneous sarcoidosis, but controlled study is lacking. Objective ...We sought to determine if adalimumab is a safe and effective treatment for cutaneous sarcoidosis. Methods Adalimumab or placebo was administered to 10 and 6 patients, respectively, in double-blind, randomized fashion for 12 weeks, followed by open-label treatment for an additional 12 weeks, followed by 8 weeks of no treatment. Assessments were made of cutaneous lesions, quality-of-life issues, laboratory findings, pulmonary function, and radiographic findings. Results At the end of the 12-week, double-blind phase, there was improvement in a number of cutaneous findings in the adalimumab-treated patients (group 1) relative to placebo recipients (group 2), most notably in target lesion area ( P = .0203). At the end of the additional 12-week open-label phase, significant improvement relative to baseline was found for target lesion area ( P = .0063), target lesion volume ( P = .0225), and Dermatology Life Quality Index score ( P = .0034). No significant changes were seen in pulmonary function tests, radiographic findings, or laboratory studies. After 8 weeks off treatment, there was some loss of this improvement. Limitations Standardized, validated measures for cutaneous sarcoidosis are lacking. There may be observer bias in the open-label portion of this study. The small size of this study makes it difficult to generalize results. Conclusions Adalimumab, at the dose and duration of treatment used in this study, is likely to be an effective and relatively safe suppressive treatment for cutaneous sarcoidosis.
Background There are no systemic therapies approved in the United States to treat pediatric psoriasis. Objective We sought to evaluate long-term safety and efficacy of etanercept in children and ...adolescents with moderate to severe plaque psoriasis. Methods This 5-year, open-label extension study enrolled patients aged 4 to 17 years who had participated in a 48-week parent study. End points included occurrence of adverse events (AEs) and serious AEs including infections, and rates of 75% and 90% improvement in Psoriasis Area and Severity Index score and clear/almost clear on static physician global assessment. Results Of 182 patients enrolled, 181 received etanercept and 69 completed 264 weeks. Through week 264, 161 (89.0%) patients reported an AE, most commonly upper respiratory tract infection (37.6%), nasopharyngitis (26.0%), and headache (21.5%). Seven patients reported 8 serious AEs; only 1 (cellulitis) was considered treatment-related. No cases of opportunistic infections or malignancy were reported. Rates of 75% improvement in Psoriasis Area and Severity Index score (∼60%–70%) and 90% improvement in Psoriasis Area and Severity Index score (∼30%–40%) and static physician global assessment status clear/almost clear (∼40%–50%) were maintained through week 264. Limitations The number of patients remaining on study at week 264 was small. Conclusion Etanercept in pediatric patients was generally well tolerated and efficacy was maintained in those who remained in the study for up to 264 weeks.
Topical photodynamic therapy (PDT) is used to treat nonmelanoma skin cancers, such as actinic keratoses, Bowen's disease, and basal cell carcinoma (superficial and nodular). This article presents ...up-to-date, practical, evidence-based recommendations on the use of topical PDT using 5-aminolevulinic acid or methyl aminolevulinate for the treatment (and prevention) of nonmelanoma skin cancers. A systematic literature review was conducted (using MEDLINE), and recommendations were made on the basis of the quality of evidence for efficacy, safety/tolerability, cosmetic outcome, and patient satisfaction/preference. Topical PDT is highly effective in the treatment of actinic keratoses, Bowen's disease, superficial and thin nodular basal cell carcinomas, with cosmesis typically superior to that achieved with existing standard therapies. PDT may also be a means of preventing certain nonmelanoma skin cancers in immunosuppressed patients.
Background Difficult-to-treat palmoplantar psoriasis has a disproportionately negative impact on quality of life. Objective We evaluated the efficacy and safety of apremilast in palmoplantar ...psoriasis. Methods A post hoc analysis of data pooled from phase IIb (PSOR-005) and phase III (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis ESTEEM 1 and 2) clinical studies was conducted to determine the effect of apremilast 30 mg twice daily versus placebo at week 16 in a subset of patients with moderate to severe plaque psoriasis with active palmoplantar psoriasis (baseline Palmoplantar Psoriasis Physician Global Assessment PPPGA score ≥1). Results Significantly more patients taking apremilast with moderate to severe palmoplantar psoriasis (baseline PPPGA score ≥3) achieved PPPGA score 0 (clear) or 1 (almost clear) compared with placebo at week 16 (48% vs 27%; P = .021). At week 16, 46% of the apremilast group with baseline PPPGA score 1 or higher achieved a PPPGA score of 0 versus 25% of the placebo group ( P < .001); 59% of the apremilast group had a PPPGA score of 0 or 1 with 1-point or more improvement versus 39% receiving placebo ( P < .001). Limitations This post hoc analysis was limited to 16 weeks and did not assess palmoplantar pustules, lesion localization, or surface area involvement. Conclusion Apremilast may be a useful oral treatment option for patients with moderate to severe palmoplantar plaque psoriasis.
Background Biologics are widely used in the treatment of psoriasis and psoriatic arthritis. Objective Our aim was to arrive at a consensus on the kind of monitoring and the vaccinations that should ...be performed before and during biologic therapy. Methods Medical literature and data presented at meetings were reviewed and a consensus conference was held by members of the Medical Board of the National Psoriasis Foundation. Results Consensus was established on monitoring and vaccination practices that included discussion and recognition of variations in those practices. History, physical examination, chemistry screen with liver function tests, complete blood cell count, and platelet count and tuberculosis testing are widely obtained at baseline and with variable frequencies thereafter. Patients treated with efalizumab have platelet counts checked more often; liver function tests are repeated more frequently in patients treated with infliximab; patients taking tumor necrosis factor blockers undergo tuberculosis testing more often; and patients treated with alefacept have CD4 counts checked approximately every 2 weeks. Avoidance of live vaccines during biologic therapy and administration of essential vaccines before biologic therapy were discussed, although vaccination is performed only to a variable degree. There was no consistency in the measurement of antinuclear antibodies among the experts. Limitations There are few evidence-based studies on monitoring practices for patients with psoriasis taking biologic therapies. Conclusions In patients taking biologic therapies for psoriasis, monitoring of blood chemistries, blood counts, CD4 counts, antinuclear antibodies, tuberculin skin tests, history, and physical examination may be warranted depending on the particular therapy and the particular patient. Vaccination practices are also addressed.
Background
Drug survival is a marker for treatment sustainability in chronic diseases such as psoriasis.
Objective
The aim of these analyses was to assess survival of biologic treatments in the ...PSOriasis Longitudinal Assessment and Registry (PSOLAR).
Methods
PSOLAR is a large, prospective, international, disease‐based registry of patients with psoriasis receiving (or eligible for) systemic therapy in a real‐world setting. Drug survival is defined as the time from initiation to discontinuation (stop/switch) of biologic therapy on registry. The number of patients who discontinued each treatment and the duration of therapy were recorded. Using Kaplan–Meier survival curves and Cox‐regression analyses hazard ratios (HR) and 95% confidence intervals (CIs), time to discontinuation was compared across cohorts undergoing first‐, second‐ or third‐line treatment with ustekinumab, infliximab, adalimumab or etanercept.
Results
As of the 2013 data cut, 12 095 patients with psoriasis were enrolled in PSOLAR. Of the 4000 patients initiating any new biologic therapy, approximately 3500 started a first‐line, second‐line or third‐line biologic therapy during the registry. Lack of effectiveness was the most common reason for discontinuation across biologic therapies. Based on the multivariate analysis, significantly shorter times to discontinuation were observed for infliximab HR (95%CI) = 2.73 (1.48–5.04), P = 0.0014; adalimumab 4.16 (2.80–6.20), P < 0.0001; and etanercept 4.91 (3.28–7.35) P < 0.0001 compared with ustekinumab reference treatment) for first‐line biologic use; results were similar for treatment effects for second/third‐line therapies. Although limited in power, analyses in patients with concurrent psoriatic arthritis confirmed by a rheumatologist reflect observations in the overall psoriasis population.
Conclusion
Drug survival was superior for ustekinumab compared with infliximab, adalimumab and etanercept in patients with psoriasis.
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