Paul S. Yamauchi

Effects of etanercept on C-reactive protein levels in psoriasis and psoriatic arthritis.

Background  C‐reactive protein (CRP), an inflammation biomarker, indicates cardiovascular risk and is elevated in psoriasis. The effect of etanercept on CRP in psoriasis has not been previously examined.

Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis

Background  The tumour necrosis factor‐α antagonist etanercept and the interleukin (IL)‐12/23p40 antagonist ustekinumab have been shown to be effective psoriasis therapies. The IL‐12/23p40 antagonist briakinumab was shown to be effective psoriasis treatment in a phase II study.

Topical photodynamic therapy in clinical dermatology

The growing incidence of cutaneous malignancies each year necessitates the development of new and more effective methods for both the diagnosis and the treatment of cancerous lesions, while assuring better cosmetic results and improving patient satisfaction. With that in mind, the use of topical photodynamic therapy (PDT) has been explored in the treatment as well as the diagnosis of various cutaneous malignancies. Using the intrinsic cellular haem biosynthetic pathway and principles of photoillumination, topical PDT carries the goal of selectively targeting abnormal cells, while preserving the normal surrounding structures. This paper will discuss the various applications and data on the use of topical PDT in dermatology.

Psoriasis: immunopathogenesis and evolving immunomodulators and systemic therapies; U.S. experiences

Background  Psoriasis is a chronic inflammatory skin disorder that is presently without a permanent cure. Up to 40% of patients with psoriasis also develop psoriatic arthritis. The mainstay armamentarium to treat psoriasis systemically includes methotrexate, ciclosporin and oral retinoids, all with significant potential for toxicity and the need for close laboratory supervision. The although the exact mechanism of psoriasis is still unclear, the involvement of T‐cell‐mediated cytokine expression in the aetiology of psoriasis is becoming clearer. The goal of modern treatment is to target such immune responses that lead to the formation of psoriatic plaques and psoriatic arthritis using selective immunomodulating pharmacotherapy. The advantages of these biological agents are less toxic systemic side‐effect profiles that will improve the quality of life in psoriatic patients.

Etanercept for severe psoriasis and psoriatic arthritis: observations on combination therapy: ETANERCEPT FOR PSORIASIS and PSORIATIC ARTHRITIS

Background The antitumour necrosis factor (TNF) activity of etanercept has been utilized to generate an important and novel treatment for rheumatoid arthritis. TNF has also been implicated in the pathogenesis of psoriasis.

Botulinum toxins types A and B for brow furrows: preliminary experiences with type B toxin dosing

BACKGROUND : Facial lines resulting from hyperactivity can be misleading manifestations of negative emotions, fatigue and stress. They may also contribute to a perception of facial aging. A well established treatment is botulinum toxin type A (BTX-A). Recently, botulinum toxin type B (BTX-B) has become available for the treatment of cervical dystonia. There has been little comparison on the efficacy of the two different types of botulinum toxins, nor is there information on appropriate dosing of BTX-B for facial muscles. OBJECTIVES : The purpose of this pilot study was to observe the effects of BTX-B in comparison to BTX-A, on patients with brow furrows assessing initial efficacy and duration of effect. METHODS : Patients were injected with BTX-B in two different dose conversions against BTX-A to the corrugator-procerus complex. Some patients received a conversion of 50 units of BTX-B (total of 1000 units) to one unit of BTX-A while others received a conversion of 100 units of BTX-B (total of 2000 units) to one unit of BTX-A. The patients treated with BTX-A received a total of 20 units. These patients were clinically assessed prior to treatment and 3 days, 1 week, 4 weeks, 12 weeks and 16 weeks after treatment. RESULTS : Both types of botulinum toxin were effective at improving glabellar frown lines. The onset of actions occurred slightly sooner (2-3 days) with BTX-B than with BTX-A (3-7 days). Duration of effect with BTX-A was at least 16 weeks. With 1000 units of BTX-B, dose duration was 6-8 weeks and with 2000 units of BTX-B, duration was 10-12 weeks. SUMMARY : Both types of botulinum toxin are effective at correcting deep glabellar furrows. At least with the doses used, BTX-B has a quicker onset of action and BTX-A has longer benefit for glabellar wrinkles. These data strongly suggest that further dose ranging studies of BTX-B are necessary and indicated in controlled double blind studies in a larger patient population.

OBSERVE-5: Observational postmarketing safety surveillance registry of etanercept for the treatment of psoriasis final 5-year results

BACKGROUND OBSERVE-5 was a 5-year Food and Drug Administration-mandated surveillance registry of patients with psoriasis. OBJECTIVE We sought to assess long-term etanercept safety and effectiveness. METHODS Patients with moderate to severe psoriasis enrolled; a single baseline dose of etanercept was required. Key outcome measures included serious adverse events, serious infectious events, events of medical interest, psoriasis-affected body surface area, physician global assessment score, and Dermatology Life Quality Index score. Safety outcomes were assessed relative to data from the MarketScan database. RESULTS For 2510 patients, 5-year cumulative incidence was 22.2% (95% confidence interval [CI] 20.3%-24.2%) for serious adverse events; 6.5% (95% CI 5.4%-7.7%) for serious infectious events; 3.2% (95% CI 2.3%-4.1%) for malignancies excluding nonmelanoma skin cancer; 3.6% (95% CI 2.7%-4.5%) for nonmelanoma skin cancer; 2.8% (95% CI 2.0%-3.6%) for coronary artery disease; 0.7% (95% CI 0.3%-1.2%) for psoriasis worsening; 0.2% (95% CI 0.0%-0.4%) for central nervous system demyelinating disorder; 0.1% (95% CI 0.0%-0.3%) for lymphoma and for tuberculosis; and 0.1% (95% CI 0.0%-0.2%) for opportunistic infection and for lupus; 55 fatal events were reported. Rates of malignancies, lymphomas, nonmelanoma skin cancer, and hospitalization-associated infections were not higher than expected relative to administrative claims data. The percentage of patients rated as clear/almost clear was 12% at baseline, which increased to 51% at month 6 and remained relatively stable throughout 5 years. LIMITATIONS No internal comparator group was included; rare events may not have been detected. CONCLUSION No new safety signals were observed with long-term, real-world etanercept use.

Botulinum toxin type A gives adjunctive benefit to periorbital laser resurfacing

OBJECTIVE: Periorbital aging and lines are a result of intrinsic skin aging, ultraviolet damage, and repetitive action of periorbital muscles. Rejuvenation of this area should therefore be optimized by combining treatments that approach the different causative factors. METHODS: This was a single-center, prospective, randomized, placebo-controlled study comparing the efficacy and safety of combining Botox injections (18 units per area) with ablative laser resurfacing versus laser resurfacing alone without Botox in the treatment of periorbital rhytids. RESULTS: We have concluded a bilateral study comparing the effects of Botox® versus saline placebo injections to the periorbital areas before and following erbium: YAG laser resurfacing of the areas in 33 patients. The results demonstrated that the Botox-treated side with laser resurfacing improved significantly more than the contralateral area treated with saline and laser in diminishing periorbital rhytids as well as textural, pigmentation, and other features of periorbital skin aging. CONCLUSION: This study illustrates the benefits of a combined approach to treating periorbital skin aging.

Retinoid therapy for psoriasis

This article focuses on the treatment of psoriasis with acitretin, the only systemic retinoid approved for psoriasis, and also briefly discusses its predecessor, etretinate, which was replaced by acitretin in 1997 and is no longer available. The use of topical tazarotene is also discussed in detail. Combination therapy of retinoids, both topical and systemic,with phototherapy and other therapeutic agents is described. In addition, new retinoid analogues that are undergoing clinical investigation are mentioned. Finally, potential toxicities and adverse effects associated with retinoids are discussed.

Combining Biologic Therapies With Other Systemic Treatments in Psoriasis: Evidence-Based, Best-Practice Recommendations From the Medical Board of the National Psoriasis Foundation

IMPORTANCE While monotherapy with biologic agents is effective for many patients with psoriasis, some patients require combination therapy. Evidence-based recommendations on combination therapy provide guidance for treating appropriately selected patients with psoriasis. OBJECTIVE To make evidence-based, best-practice recommendations regarding combining biologics with other systemic treatments, including phototherapy, oral medications, or other biologics, for psoriasis treatment. EVIDENCE REVIEW We searched the MEDLINE database for studies from January 1, 1946, to June 18, 2013, that evaluated therapies combining biologics with phototherapy, oral medications, or other biologic agents. The Medical Board of the National Psoriasis Foundation arrived at best-practice recommendations through group discussion and voting. FINDINGS Few trials evaluated the efficacy and safety of combination therapies in moderate to severe psoriasis. Combining biologics, such as etanercept or adalimumab, with phototherapy likely results in greater reduction in disease severity than either alone. Etanercept and methotrexate combination is more effective than monotherapy with either medication. A combination of infliximab with methotrexate results in greater efficacy than infliximab alone. With concomitant use of acitretin, the dosing of etanercept can be reduced to maintain similar levels of efficacy. Short-term cyclosporine use has been combined with etanercept or adalimumab to control psoriasis flares. Based on the expert opinion of the Medical Board of the National Psoriasis Foundation, the preferred order for combining a second modality with biologics is biologic and methotrexate combination, biologic and acitretin combination, and then biologic and phototherapy combination. In the psoriasis literature, there are overall insufficient data on combining biologics with acitretin, cyclosporine, or a second biologic. CONCLUSIONS AND RELEVANCE Among appropriately selected patients with psoriasis, carefully chosen combinations may result in greater efficacy, while minimizing toxicity.