New vitamin D analogs in psoriasis

Psoriasis is a common inflammatory and hyperproleferative skin disease characterized by infiltrated plaques of the skin and may involve nails, scalp and intertreginous areas. Recent years of research has shown that psoriasis can be treated topically with analogs of vitamin-D(3). Impaired differentiation and increased proliferation of epidermal keratinocytes are key features in psoriatic lesions together with a local activation of T lymphocytes. Evidence has accumulated that analogs of vitamin D(3) increase differentiation and inhibit proliferation of keratinocytes. Topical treatment with analogs of vitamin D(3) have in a number of trials shown improvement of psoriasis. Vitamin D analogs show the same efficacy as potent topical corticosteroids and do not produce skin atrophy during long-term therapy. Vitamin D analogs can be used both as monotherapy and in combination with topical corticosteroids, UVB, PUVA, acitretin, methotrexate and cyclosporine. The vitamin D(3) analog calcipotriol has been investigated in most detail and is available as an ointment, a cream and as a scalp solution. From clinical studies involving several thousands of patients, it can be concluded that calcipotriol is efficacious, safe and well-tolerated even on a long term basis.     

Psoriasis

Psoriasis is an inflammatory disorder of the skin that involves complex interactions between the dermis and epidermis. There are several forms of psoriasis, the most common being plaque type psoriasis. Other forms include guttate, pustular and erythrodermic psoriasis. Both the skin and joints are affected in this disease. Psoriasis ranges in severity from a few small plaques to involvement of the entire cutaneous surface. Therapy of psoriasis depends on the location, type and severity of the disease. Treatments include a wide array of topical medications including tars, anthralin, topical corticosteroids, vitamin D(3) analogs, retinoids and over-the-counter preparations. Phototherapy with ultraviolet B and PUVA are used for more widespread involvement. Common systemic therapies include methotrexate, retinoids and cyclosporin. This article will review the pathogenesis and clinical features of psoriasis, as well as current and future therapies.     

Emerging drugs for moderate-to-severe psoriasis

Psoriasis is a chronic, incurable, disabling skin disease characterised by red, scaly plaques. Approximately 23% of psoriasis patients also have an accompanying arthritis that can become debilitating. Psoriasis has a stigmatising effect on its victims, who often feel socially isolated. Although the exact aetiology of psoriasis is still unknown, it is clearly an immune-mediated disease. Traditional therapies for psoriasis include topical drugs, such as corticosteroids, retinoids and vitamin D3 analogues; systemic drugs, such as methotrexate, ciclosporin and retinoids; and phototherapy. These mainstays of treatment are efficacious for the treatment of severe disease; however, most are associated with toxicities or are inconvenient. Recent advances in biotechnology have produced new pharmaceuticals that interfere with immune responses thought to be involved in the pathogenesis of psoriasis and other inflammatory diseases. The immunobiologicals, one new family of drugs, consist of monoclonal antibodies and fusion proteins. Many have demonstrated efficacy in treating psoriasis. Some appear to offer safety benefits over traditional therapies; further monitoring and surveillance of these agents is required to adequately establish safety profiles. This article discusses existing and emerging treatments for moderate-to-severe psoriasis.     

Emerging drugs for moderate-to-severe psoriasis

Psoriasis is a chronic, incurable, disabling skin disease characterised by red, scaly plaques. Approximately 23% of psoriasis patients also have an accompanying arthritis that can become debilitating. Psoriasis has a stigmatising effect on its victims, who often feel socially isolated. Although the exact aetiology of psoriasis is still unknown, it is clearly an immune-mediated disease. Traditional therapies for psoriasis include topical drugs, such as corticosteroids, retinoids and vitamin D3 analogues; systemic drugs, such as methotrexate, ciclosporin and retinoids; and phototherapy. These mainstays of treatment are efficacious for the treatment of severe disease; however, most are associated with toxicities or are inconvenient. Recent advances in biotechnology have produced new pharmaceuticals that interfere with immune responses thought to be involved in the pathogenesis of psoriasis and other inflammatory diseases. The immunobiologicals, one new family of drugs, consist of monoclonal antibodies and fusion proteins. Many have demonstrated efficacy in treating psoriasis. Some appear to offer safety benefits over traditional therapies; further monitoring and surveillance of these agents is required to adequately establish safety profiles. This article discusses existing and emerging treatments for moderate-to-severe psoriasis.     

Management of scalp psoriasis: guidelines for corticosteroid use in combination treatment

Scalp psoriasis is a frequent expression of the common skin disease psoriasis, and scaling and itching are the two major complaints. Topical treatments are the mainstay of the treatment of psoriasis of the scalp, with the vehicle as well as the active ingredient relevant to efficacy, tolerability and compliance. Vehicles can be shampoos, lotions, gels, foams, creams and more greasy ointments. Active ingredients are keratolytics, coal tar (liquor carbonis detergens), dithranol, corticosteroids and vitamin D3 analogues. Some effect has also been described from topical or systemic imidazole derivatives. Topical corticosteroids remain the mainstay in the treatment of scalp psoriasis. The effects are rapid, the formulations are patient friendly and the adverse effects seem limited, although no data are available to support safety during prolonged use (more than 4 weeks). Topical vitamin D3 analogues have been available for the treatment of psoriasis since 1992. In the lotion formulation in particular, vitamin D3 analogues are a patient friendly, tolerable and effective alternative to corticosteroids, although the effects are optimal after 8 weeks, in contrast to 2-3 weeks for topical corticosteroids. Facial irritation (often temporary) can also be a disadvantage of vitamin D3 analogues, although only a small proportion of patients stop treatment for this reason. All other treatment options for psoriasis, such as tazarotene, phototherapy and systemic treatment with methotrexate, acitretin and cyclosporin are often not indicated or not suitable for treatment of the scalp. In daily practice, to make a choice from the available therapeutic arsenal for psoriasis, each patient should be examined individually. Deteriorating factors have to be excluded. For scaling, keratolysis is the first step. Subsequently, active treatment can be chosen depending on the clinical picture. When the psoriatic lesions are mainly characterised by inflammation, anti-inflammatory drugs such as topical corticosteroids are indicated. When scaling is the more important clinical feature, vitamin D3 analogues are indicated. Generally, intermittently used topical corticosteroids alternating with vitamin D3 derivatives either combined or not with liquor carbonis detergens containing shampoo is the most suitable treatment for most patients. Because psoriasis capitis is a chronic disease, long term treatment should, in addition to medical advice, also provide patient support and motivation.     

Topical treatments for scalp psoriasis

Psoriasis is a common, chronic inflammatory skin disease that affects the scalp more commonly than any other site. Scalp psoriasis causes significant psychosocial disability as it is highly visible and can, on occasion, extend onto the face. Furthermore, current treatment regimens are messy, time consuming and, in some instances, ineffective, leading to a high level of non-compliance. The majority of current evidence for topical treatments for this condition comes from open-label, uncontrolled studies. From such studies, there are data to support the use of topical corticosteroids in a number of different formulations and topical vitamin D analogues. However, these studies have not addressed issues such as the need for keratolytics, which may be required to remove adherent scale before a topical corticosteroid or vitamin D analogue may prove efficacious. There is an urgent need for well designed, controlled trials to assess the efficacy of existing and new treatment regimens for scalp psoriasis. The aim of this review is to critically assess the relative effectiveness and tolerability of available topical therapies for this problematic condition and provide recommendations for selection of treatment.     

Emerging topical treatments for psoriasis

Introduction: Psoriasis is an immune-mediated chronic inflammatory skin disease which classically presents as erythematous, scaly plaques affecting extensor surfaces of the limbs, scalp and trunk. Approximately 80% of patients have a mild-to-moderate form routinely treated with topical medications, whereas phototherapy, systemic and biological therapies are typically reserved for treatment of moderate-to-severe psoriasis.

Areas covered: The major advances in psoriasis therapy in the past 15 years have been in new immunomodulatory and biological molecules, with a significant unmet need to have new, efficient and safe topical treatment options for the large percentage of patients for whom systemic therapy is not indicated. The available topical therapies (corticosteroids and vitamin D3 analogs) have remained relatively unchanged over the past several decades. This article reviews emerging topical drugs and formulations currently under evaluation in clinical trials.

Expert opinion: The time is right for a revolution in our topical therapy armamentarium. It has lagged significantly behind the systemic biological evolution of new drug development. Our large psoriasis population with mild-to-moderate psoriasis certainly deserves potent but safe and innovative topical agents with a new mode of action as well as with long-lasting clinical efficacy.     

Treatment of psoriasis and long-term maintenance using 308 nm excimer laser, clobetasol spray, and calcitriol ointment: a case series

Psoriasis is a chronic inflammatory skin disease that is characterized by thickened red plaques covered with silvery scales. Excimer laser therapy is a cutting-edge advancement in UVB phototherapy. In contrast to traditional phototherapy, the 308 nm excimer laser only targets psoriasis plaques, while it spares uninvolved skin. It allows for treatment with a supra-erythmogenic dose of UVB irradiation. Targeted UVB therapy is a possible treatment especially for many who have failed topical treatments, systemic therapy, and traditional phototherapy. For safe and effective psoriasis treatment, a combination of therapies may be used, including a combination of laser treatment with topical medications. We present two cases demonstrating effective treatment with excimer laser in conjunction with clobetasol spray and calcitriol ointment for 12 weeks. Long-term near-clearance of psoriasis was sustained after 6 months and one-year follow up periods without further therapy.     

Non-invasive evaluation of tacalcitol plus puva versus tacalcitol plus UVB-NB in the treatment of psoriasis: "right-left intra-individual pre/post comparison design"

Photochemotherapy with psoralen plus ultraviolet A(PUVA) and phototherapy with UVB narrow band (UVB-NB) are used in the treatment of psoriasis. Numerous studies have shown that the additional administration of either topical or systemic antipsoriatic agents may effectively increase the efficacy of these therapies. This study aimed to compare through objective data the efficacy of topical tacalcitol in combination with PUVA or UVB-NB versus PUVA and UVB-NB monotherapy in the treatment of mild to moderate chronic plaque psoriasis. Modified Psoriasis Area and Severity Index (PASI) score, transepidermal water loss (TEWL) and stratum corneum hydration were used to monitor the restoration of skin barrier in the psoriatic plaques of 40 patients during photochemotherapy. The study was a right-left, intra-individual, pre/post comparison trial. PUVAand UVB-NB treatments were given three times a week. On those plaques localized on the right side of the body tacalcitol ointment was applied once a day, in the evening. Corneometry, TEWL and modified PASI score were used to evaluate the response to the treatment at baseline, one month and two months. Thirty-six of the forty enrolled subjects completed the study. The comparison between combination treatments and the PUVA/UVB-NB monotherapy showed no significant differences with regard to modified PASI index. However, significant differences were recorded with regard to TEWL and corneometry. The combination of tacalcitol plus PUVA or tacalcitol plus UVB-NB restored epidermal barrier functions as well as skin hydration faster than PUVA or UVB-NB monotherapy (TEWL: p=0.0050 and corneometry: p=0.003). The combination of tacalcitol plus UVB-NB allowed a better restoration of skin barrier functions than tacalcitol plus PUVA (p=0.013). In conclusion, the combination of tacalcitol plus PUVA or plus UVB-NB improves the therapeutic result. In addition, the data from TEWL and skin hydration suggest a means in which tacalcitol plus UVB-NB induces a better normalization of skin biophysical parameters.     

The therapeutic effects of vitamin D3 and its analogues in psoriasis

Psoriasis is a common skin disease which is characterised by the proliferation and abnormal differentiation of keratinocytes, coupled with complex immune disturbances. The beneficial effects of vitamin D derivatives in this disease are due to their capacity to inhibit proliferation, their ability to induce normal differentiation and their immunomodulatory properties. Since the systemic administration of these compounds is limited by their effect on calcium metabolism, topical preparations have become available in most countries. Topical calcipotriol and/or tacalcitol are now considered as first-line treatment for mild-to-moderate psoriasis and can be taken in combination with other systemic therapies in more severe cases of the disease. Novel orally active vitamin D analogues, with minimal calcitropic effercts, are, however, required for more effective treatment.     

银屑病发病机理及药物治疗进展

回顾近年来对银屑病病因和发病机理研究的以及用软化剂、角质促进剂、地蒽酚、焦油、外用皮质激素、维生素D3同类药、维A酸类、甲氨蝶呤、环孢素、他克莫司和PUVA疗法抗银屑病治疗的进展。     

Clobetasol propionate foam in the treatment of psoriasis

Psoriasis is a common, chronic, distressing skin disorder that frequently affects the scalp, skin, nails and joints. Despite treatment, many patients suffer from unremitting disease and decreased quality of life. Scalp-type psoriasis is particularly difficult to treat. Although topical corticosteroids are the mainstay of therapy for moderate-to-severe disease, patients frequently object to the messiness and unfavourable cosmetic appearance of topical treatments. In this context, foam vehicles, which have the advantage of minimal residue and increased ease of application, have emerged as novel alternatives to traditional creams, ointments and solutions. Clobetasol propionate foam 0.05% (OLUX, Connetics Corporation), a high potency topical steroid, has been shown to alleviate symptoms of several dermatological conditions, including scalp and body psoriasis, improve disease severity and increase quality of life. Dose should be limited to 50 g/week, given the risk of adrenal suppression. Because patient preference is an important determinant of medication efficacy in clinical practice, clobetasol foam is a useful new formulation in the treatment of psoriasis and other skin conditions.     

银屑病局部治疗和遗传药理学的关系

银屑病是一种炎症过度增生性皮肤病,有强烈的遗传易感性,主要受到遗传、免疫和环境的影响。由于大部分患者病情处于轻中度,所以相比全身治疗,局部治疗具有费用低、用药方便且安全性高的特点,因此具有更大的临床意义。然而,目前涉及银屑病局部治疗的遗传药理学研究却很少。本文主要对近几年银屑病局部治疗反应和遗传因素的关系进行一个较为全面的综述,以期为银屑病患者的个体化医学提供理论指导。     

Emerging drugs for psoriasis

Background: Psoriasis is a relatively common, chronic and disabling skin disease, due to a disturbed proliferation and differentiation of keratinocytes, accompanied by vascular alterations and infiltration of inflammatory cells with a local T_H1-type cytokine immune response. There is no cure, but several treatment options are available. Objective: The treatment of psoriasis is far from being satisfactory, due to the impractical modalities of topical treatment and the suboptimal safety profile of the systemic treatments available. In the last few years, parallel to an improved understanding of the disease pathogenesis, there has been a boosting of research in new agents for the treatment of psoriasis. These new agents are the focus of this paper. Methods: After a short review of the treatment options already available (mainly based on the available systematic reviews), we focused on agents that are still in clinical development (Phase I – III) and have not yet entered the market. For the purpose of this study, we systematically searched the main registries of ongoing trials up to August 2008. Results/conclusion: The field is very dynamic, with both immunopharmacology of recombinant DNA techniques and more traditional small-molecule pharmacology actively delivering new agents. With the increasing number of new options, there is a need for research systems that enable to effectively collect long-term safety data on treated patients.     

Clobetasol propionate foam in the treatment of psoriasis

Psoriasis is a common, chronic, distressing skin disorder that frequently affects the scalp, skin, nails and joints. Despite treatment, many patients suffer from unremitting disease and decreased quality of life. Scalp-type psoriasis is particularly difficult to treat. Although topical corticosteroids are the mainstay of therapy for moderate-to-severe disease, patients frequently object to the messiness and unfavourable cosmetic appearance of topical treatments. In this context, foam vehicles, which have the advantage of minimal residue and increased ease of application, have emerged as novel alternatives to traditional creams, ointments and solutions. Clobetasol propionate foam 0.05% (OLUX^?, Connetics Corporation), a high potency topical steroid, has been shown to alleviate symptoms of several dermatological conditions, including scalp and body psoriasis, improve disease severity and increase quality of life. Dose should be limited to 50 g/week, given the risk of adrenal suppression. Because patient preference is an important determinant of medication efficacy in clinical practice, clobetasol foam is a useful new formulation in the treatment of psoriasis and other skin conditions.     

The two-compound formulation of calcipotriol and betamethasone dipropionate for treatment of moderately severe body and scalp psoriasis - an introduction

Psoriasis is a common chronic inflammatory skin disease and many patients require lifelong treatment. Characteristic scaly, itchy, unsightly psoriatic lesions affect many body areas and most patients commonly experience scalp involvement. The cosmetic embarrassment of visible body lesions, inaccessibility of scalp skin to application of therapies and proximity of sensitive facial skin add to the challenges of most patients managing their psoriasis long term. Psoriasis can severely impact patients' quality of life. This can impact significantly on the patient. In economic terms patients may incur increased out-of-pocket expenditure or extended time away from work as a direct consequence of psoriasis, particularly in severe cases; In many countries, specialist review of patients provides pressures on hard-pressed services and the costs of psoriasis care are substantial, particularly in patients with severe recalcitrant psoriasis which may require lengthy inpatient admission. Around 80% of patients with psoriasis have mild to moderately severe disease and the majority are treated with topical medicines by their physician in primary care. Despite the availability of a wide range of treatment options, regimens have been unsatisfactory, associated with patient dissatisfaction, poor compliance and often safety concerns with long-term use. Evidence-based clinical guidelines aim to improve healthcare of patients and while there are such guidelines for psoriasis, to date the challenges of (and recommendations for) managing scalp psoriasis are often limited or missing from these treatment guidelines. In the following in-journal supplement, a connected suite of five papers focus on the use of topical therapies for the treatment of the person afflicted with psoriasis. This work harnesses robust evidence from randomised clinical trials (RCTs) of topical therapies commonly used in psoriasis patients and translates this into recommendations for the most appropriate treatment of patients with body or scalp psoriasis, from an efficacy, safety and cost-effectiveness perspective. Based upon systematic review and harnessing 'state of the art' evidence assessment methodologies, the modelling work suggests that the use of a two-compound formulation (TCF) product of calcipotriol and betamethasone dipropionate is the most appropriate treatment option for both body and scalp psoriasis. This Editorial acknowledges the results of any modelling exercise have limitations; indeed such limitations are acknowledged in each modelling contribution in this issue. With these caveats in mind, this introductory paper considers the implications of this research and distillation of the evidence. This work should guide cost-effective treatment choices for body and scalp psoriasis, assist in recommendations for management of scalp psoriasis in future iterations of psoriasis clinical guidelines and help primary care physicians striving to attain best outcomes in the care of the person with psoriasis.     

Psoriasis: emerging therapeutic strategies

Psoriasis is a chronic inflammatory skin disorder that is characterized by thickened, scaly plaques, and is estimated to affect approximately 1-3% of the Caucasian population. Traditional treatments, although effective in patients with limited disease, have numerous shortcomings, including inconvenience and toxicity. These drawbacks mean that many patients experience cycles of disease clearance, in which normal quality of life alternates with active disease and poor quality of life. However, as this review discusses, recent advances have highlighted the key role of the immune system in the pathogenesis of psoriasis, and have provided new defined targets for therapeutic intervention, offering hope for safe and effective psoriasis treatment.     

Calcipotriene and betamethasone dipropionate for the topical treatment of plaque psoriasis

Introduction: Psoriasis affects an estimated 2% of the world's population, with higher rates in developed countries. 80% have mild-to-moderate disease and 50 to 80% have scalp involvement. Topical treatments are the mainstay of treatment.

Areas covered: Two-compound calcipotriene and betamethasone dipropionate (BD) is a common topical combination therapy consisting of a vitamin D analogue and a corticosteroid. It comes in ointment, gel/suspension, and foam formulations. Phase II and III clinical trials have consistently shown the two-compound formulation to be effective and safe, with no clinically significant skin atrophy, calcium level changes, or adrenal suppression were seen. Topical scalp solution was also safe and effective in treating scalp psoriasis in pediatric populations.

Expert commentary: Calcipotriene plus BD is more effective and safer than the individual ingredients in the same vehicle for treating body and scalp psoriasis. It should be considered a first line therapy for mild-to-moderate plaque psoriasis.     

Emerging oral drugs for psoriasis

Introduction: Psoriasis is a chronic, immune-mediated inflammatory disease that classically presents with well-demarcated, scaly, erythematous plaques on the extensor surfaces of the extremities, scalp, and trunk. Nails and joints are frequently affected as well. Whereas a significant number of patients maintain adequate control with topical therapy, up to 25% of patients will require phototherapy, oral systemic medication, or biologic therapy.

Areas covered: The majority of recent advances in therapeutic options for moderate-to-severe psoriasis have been in biologic therapies whereas development of new oral agents has lagged behind. Currently, oral agents are largely confined to methotrexate, acitretin, cyclosporine and most recently apremilast. This article reviews emerging oral treatments for moderate-to-severe psoriasis.

Expert opinion: Despite the recent FDA approval of apremilast, the development of new oral treatments for moderate-to-severe psoriasis has not kept pace with biologic therapies. There continues to be a need for safe and effective long-term oral therapies.     

The two-compound formulation of calcipotriol and betamethasone dipropionate for treatment of moderately severe body and scalp psoriasis – an introduction

Abstract

Psoriasis is a common chronic inflammatory skin disease and many patients require lifelong treatment. Characteristic scaly, itchy, unsightly psoriatic lesions affect many body areas and most patients commonly experience scalp involvement. The cosmetic embarrassment of visible body lesions, inaccessibility of scalp skin to application of therapies and proximity of sensitive facial skin add to the challenges of most patients managing their psoriasis long term. Psoriasis can severely impact patients’ quality of life.

This can impact significantly on the patient. In economic terms patients may incur increased out-of-pocket expenditure or extended time away from work as a direct consequence of psoriasis, particularly in severe cases; In many countries, specialist review of patients provides pressures on hard-pressed services and the costs of psoriasis care are substantial, particularly in patients with severe recalcitrant psoriasis which may require lengthy inpatient admission.

Around 80% of patients with psoriasis have mild to moderately severe disease and the majority are treated with topical medicines by their physician in primary care. Despite the availability of a wide range of treatment options, regimens have been unsatisfactory, associated with patient dissatisfaction, poor compliance and often safety concerns with long-term use. Evidence-based clinical guidelines aim to improve healthcare of patients and while there are such guidelines for psoriasis, to date the challenges of (and recommendations for) managing scalp psoriasis are often limited or missing from these treatment guidelines.

In the following in-journal supplement, a connected suite of five papers focus on the use of topical therapies for the treatment of the person afflicted with psoriasis. This work harnesses robust evidence from randomised clinical trials (RCTs) of topical therapies commonly used in psoriasis patients and translates this into recommendations for the most appropriate treatment of patients with body or scalp psoriasis, from an efficacy, safety and cost-effectiveness perspective. Based upon systematic review and harnessing ‘state of the art’ evidence assessment methodologies, the modelling work suggests that the use of a two-compound formulation (TCF) product of calcipotriol and betamethasone dipropionate is the most appropriate treatment option for both body and scalp psoriasis. This Editorial acknowledges the results of any modelling exercise have limitations; indeed such limitations are acknowledged in each modelling contribution in this issue. With these caveats in mind, this introductory paper considers the implications of this research and distillation of the evidence. This work should guide cost-effective treatment choices for body and scalp psoriasis, assist in recommendations for management of scalp psoriasis in future iterations of psoriasis clinical guidelines and help primary care physicians striving to attain best outcomes in the care of the person with psoriasis.