Calcipotriene/betamethasone in the treatment of psoriasis: a review article

Plaque-type psoriasis is a chronic and immune-mediated skin disease affecting ～ 1 – 3% of the Caucasian population. Most cases are of mild or moderate severity and benefit from local treatment that represents the mainstay therapy. Topical corticosteroids and vitamin D₃ analogues remain the option of choice. Optimization of these treatments is made by the combination of calcipotriene and betamethasone dipropionate. This formulation combines the keratinocyte differentiation and antiproliferative action of the vitamin D₃ analogues with the anti-inflammatory effect of steroids enhancing effectiveness while reducing the side-effect profile of the single topical agent. In this article, we highlight the advantages of the association of calcipotriene and betamethasone in the treatment of localized plaque-type, scalp and nail psoriasis.     

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。     

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.     

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.     

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.     

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.     

Calcipotriol/betamethasone dipropionate: a review of its use in the treatment of psoriasis vulgaris of the trunk, limbs and scalp

Calcipotriol/betamethasone dipropionate (calcipotriol 50?μg/g and betamethasone 0.5?mg/g) is a fixed-dose combination of a vitamin D(3) analogue and a corticosteroid indicated for the once-daily, topical treatment of psoriasis vulgaris of the trunk, limbs and scalp in adults. Both the ointment (Daivobet?; Dovobet?) and gel (Xamiol?; Daivobet? Gel; Dovobet? Gel) formulations of calcipotriol/betamethasone dipropionate can be used to treat psoriasis vulgaris of the trunk and/or limbs, although the gel formulation was specifically developed for the treatment of scalp psoriasis. This article reviews the efficacy and tolerability of calcipotriol/betamethasone dipropionate in patients with psoriasis vulgaris, as well as summarizing its pharmacological properties. Calcipotriol/betamethasone dipropionate has low systemic absorption and displays local anti-inflammatory and immunoregulatory properties. It reduces the hyperproliferation of keratinocytes and helps normalize keratinocyte differentiation. In large, well designed clinical trials, calcipotriol/betamethasone dipropionate, either as the ointment or the gel formulation, applied once daily for 4-8 weeks, was more effective than placebo, calcipotriol and tacalcitol, as well as betamethasone dipropionate in most instances, for the topical, symptomatic treatment of psoriasis vulgaris of the trunk/limbs. Likewise, calcipotriol/betamethasone dipropionate gel applied once daily for 8 weeks was more effective than placebo or either component alone in the topical, symptomatic treatment of psoriasis vulgaris of the scalp. Long-term, once-daily, when required therapy with calcipotriol/betamethasone dipropionate for 52 weeks was more effective than calcipotriol alone for the treatment of scalp psoriasis, and was at least as effective as switching to calcipotriol for 48 weeks after 4 weeks of calcipotriol/betamethasone dipropionate or alternating between calcipotriol/betamethasone dipropionate and calcipotriol every 4 weeks for 52 weeks in the treatment of psoriasis vulgaris of the trunk/limbs. Calcipotriol/betamethasone dipropionate also improved health-related quality of life. Calcipotriol/betamethasone dipropionate was generally well tolerated, with most adverse drug reactions being lesional or perilesional effects of mild or moderate severity. Calcipotriol/betamethasone dipropionate was often associated with fewer lesional/perilesional adverse reactions than calcipotriol or tacalcitol and did not appear to be associated with a higher incidence of corticosteroid-related adverse events during long-term therapy. Pharmacoeconomic analyses predicted calcipotriol/betamethasone dipropionate to be more cost effective than other topical therapies. Thus, calcipotriol/betamethasone dipropionate is an important, effective, once-daily, topical therapy for the symptomatic treatment of psoriasis vulgaris of the trunk, limbs and scalp.     

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 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.     

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.     

Topical treatment of psoriasis

Importance of the field: The majority of patients with psoriasis can be safely and effectively treated with topical therapy alone, either under the supervision of a family physician or dermatologist. For those requiring systemic agents, topical therapies can provide additional benefit. Optimal use of topical therapy requires an awareness of the range and efficacy of all products.

Areas covered in this review: The review covers the efficacy and role of topical therapies including emollients, corticosteroids, vitamin D analogs, calcineurin inhibitors, dithranol, coal tar, retinoids, keratolyics and combination therapy. The report was prepared following a PubMed and Embase literature search up to April 2010.

What the reader will gain: The paper provides a broad review of the relevant topical therapeutic options available in routine clinical practice for the management of psoriasis and a recommendation for selection of treatment.

Take home message: Topical therapies used appropriately provide a safe and effective option for the management of psoriasis. An awareness of the available products and their efficacy is key to treatment selection and patient satisfaction.     

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.     

Combination topical therapy for the treatment of psoriasis

Dermatological research continues to move toward the goal of developing an effective psoriasis treatment that would rapidly clear lesions and provide long-term freedom from visible signs and symptoms. Currently, topical corticosteroids remain a pivotal treatment due to their effective anti-inflammatory properties; however, potential adverse effects associated with chronic application limit long-term continuous therapy. Vitamin D analogues provide another mechanism of action, reducing lesions through effects on both keratinocytes and on the cytokine environment. A topical combination of corticosteroid and vitamin D derivative appears to provide a balanced approach to psoriasis treatment. The development of clobetasol propionate foam 0.05% (clobetasol propionate foam/Olux) offers a convenient topical corticosteroid that can be used concomitantly, that is, immediately followed by application of calcipotriene ointment 0.005% (Dovonex). This regimen has been shown to offer an increased short-term efficacy compared with either agent alone. Continued application of calcipotriene ointment on weekdays supplemented by long-term clobetasol propionate foam pulse therapy on weekends appears to provide an enhanced maintenance of remission compared with calcipotriene monotherapy.     

Established treatments of psoriasis

Psoriasis is a complex disease with a spectrum of clinical manifestations. Psoriasis may express as a few coin-sized erythemato-squamous plaques up to widespread disease covering the entire body surface (erythrodermic psoriasis). Psoriasis may present as a few stable plaques or unstable disease, rapidly relapsing after treatment. Some patients may respond excellently to topical treatments whereas other patients may be difficult to manage, showing treatment resistance even to the systemic treatments. Therefore, a spectrum of treatments is available to individualize care of psoriasis. In this chapter the available treatments are presented. The vast majority of patients is treated with topical treatments, with vitamin D(3)analogs and topical corticosteroids as the first line treatments. Tazarotene is an alternative for vitamin D(3) treatment if this treatment fails. In some special cases, dithranol and tar treatment may be used. Phototherapy with UVB and photochemotherapy (PUVA) are indicated in patients not responding sufficiently to topical treatment. However, chronic exposure, in particular to photochemotherapy implies an increased risk for photo- carcinogenicity. Systemic treatments including methotrexate, cyclosporin, acitretin and fumarates are indicated in patients who cannot be managed with topical treatments or phototherapy, either for treatment resistance or cumulative toxicity. In this article the opportunities and limitations of the available treatments are presented.     

Recent developments in vitamin D analogs

Within the past decade it has been shown that psoriasis can be treated topically with analogs of vitamin-D3. Impaired differentiation and increased proliferation of keratinocytes are key features in psoriatic lesions together with a local activation of T lymphocytes. Evidence has accumulated showing that analogs of vitamin D3 increase differentiation and inhibit proliferation of keratinocytes. Therefore, analogs of vitamin D3 have been investigated in a number of trials showing improvement of psoriasis. It has been shown that vitamin D analogs are better than their vehicle and show the same potency as potent topical steroids. However, vitamin D analogs have been proven efficacious and without side effects also when used on long term basis. Vitamin D analogs can be used both as monotherapy and in combination topical steroids, UVB, PUVA, retinoids and cysclosporine. The vitamin D3 analog calcipotriol has been investigated in most detail and is available as an ointment, a creme and as a scalp solutation. From clinical studies involving thousands of patients, it can be concluded that calcipotriol is efficacious, safe, well tolerated and can be used on a long term basis. Other analogs are available, however, these analogs have not been studied in greater details yet.     

Use and abuse of topical corticosteroids in infections of the skin and related structures

Topical corticosteroids have improved the management of many inflammatory skin diseases, such as psoriasis and atopic dermatitis. However, these medications are associated with certain adverse effects that are potentially serious. The potent anti-inflammatory actions of these drugs increase susceptibility to bacterial and fungal infections, and therefore may preclude them from use when infection is the known cause of the disease. In addition, children may be more vulnerable than adults to systemic effects of topical corticosteroids because percutaneous absorption is proportionately greater. These are important considerations, and physicians need to weigh and compare the risks and benefits associated with these medications before initiating treatment. This involves an appreciation of which patient populations are at high risk, which skin conditions are incompatible with topical corticosteroid therapy, and which alternative nonsteroidal medications are effective in treating inflammatory skin diseases.     

Clobetasol propionate emollient formulation foam in the treatment of corticosteroid-responsive dermatoses

Background: Topical corticosteroids are the most common treatment modality for patients with psoriasis and atopic dermatitis; however, the efficacy of topical corticosteroids is often hampered by barriers to patient adherence, such as lack of efficacy, side effects and inconvenience. Recently published studies have investigated the safety and efficacy of a novel emollient foam (EF) formulation of clobetasol propionate (CP), a class I topical corticosteroid in psoriasis and atopic dermatitis. Objectives: To summarize recent literature on CP EF foam, and to evaluate recent Phase II and III clinical trials of CP EF foam in psoriasis and atopic dermatitis. Methods: The MEDLINE (1950 – January 2008) database was searched using the following terms: ‘clobetasol propionate foam’, ‘topical corticosteroids’, ‘topical glucocorticoids’, ‘psoriasis’ and ‘atopic dermatitis’. Results were evaluated for relevance and quality, and additional references were obtained from bibliographies of selected articles. Conclusion: CP EF foam appears to be safe and effective for corticosteroid-responsive dermatoses in adults and children ≥ 12 years of age. As compared to its hydroethanolic foam predecessor, CP EF presents a potential advance for patients who are less likely to tolerate alcohol-based foam. As alcohol-based foams can be irritating and cause stinging in non-hair-bearing areas, this new emollient formulation has the potential to widen the use of CP foam to more patients with atopic dermatitis and to more non-scalp body sites in patients with psoriasis.     

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.