Psoriasis: Mrowietz U

Mrowietz U, Altmeyer P, Bieber T, Röcken M, Schopf RE, Sterry W. · Psoriasis Center, Department of Dermatology, Venereology and Allergy, University Clinic of Schleswig-Holstein, Campus Kiel, Kiel, Germany. · J Dtsch Dermatol Ges. · Pubmed #17659047 No free full text.

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Nast A, Kopp IB, Augustin M, Banditt KB, Boehncke WH, Follmann M, Friedrich M, Huber M, Kahl C, Klaus J, Koza J, Kreiselmaier I, Mohr J, Mrowietz U, Ockenfels HM, Orzechowski HD, Prinz J, Reich K, Rosenbach T, Rosumeck S, Schlaeger M, Schmid-Ott G, Sebastian M, Streit V, Weberschock T, Rzany B, Anonymous00272, Anonymous00273. · Division of Evidence Based Medicine (dEBM), Klinik für Dermatologie, Venerologie und Allergologie, Charité-Universitätsmedizin Berlin, Germany. · J Dtsch Dermatol Ges. · Pubmed #17615051 No free full text.

Abstract: Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1 to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, patient surveys have revealed lack of satisfaction with the efficacy of available treatments and a high rate of non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) initiated a project to develop evidence-based guidelines for the management of psoriasis. These resulting Guidelines focus on induction therapy in cases of mild, moderate, and severe plaquetype psoriasis in adults. The Guidelines include evidence-based evaluation of the efficacy of all currently available therapeutic options in Germany. In addition, they offer detailed information on how best to administer the various treatments and give information on contraindications, adverse drug reactions, and drug interactions as well as estimates of practicability and cost. The Guidelines were developed following the recommendations of the Arbeitsgemeinschaft wissenschaftlicher medizinischer Fachgesellschaften (AWMF). The therapeutic recommendations were developed by an expert group and finalized during interdisciplinary consensus conferences.

Nast A, Kopp I, Augustin M, Banditt KB, Boehncke WH, Follmann M, Friedrich M, Huber M, Kahl C, Klaus J, Koza J, Kreiselmaier I, Mohr J, Mrowietz U, Ockenfels HM, Orzechowski HD, Prinz J, Reich K, Rosenbach T, Rosumeck S, Schlaeger M, Schmid-Ott G, Sebastian M, Streit V, Weberschock T, Rzany B. · Division of Evidence Based Medicine, Klinik für Dermatologie, Venerologie, Allergologie, Charité-Universitätsmedizin Berlin, Schumannstrasse 20/21, Berlin, Germany. · Arch Dermatol Res. · Pubmed #17497162 links to  free full text

Abstract: Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1-S126, 2006; or http://www.psoriasis-leitlinie.de ).

Nast A, Kopp IB, Augustin M, Banditt KB, Boehncke WH, Follmann M, Friedrich M, Huber M, Kahl C, Klaus J, Koza J, Kreiselmaier I, Mohr J, Mrowietz U, Ockenfels HM, Orzechowski HD, Prinz J, Reich K, Rosenbach T, Rosumeck S, Schlaeger M, Schmid-Ott G, Sebastian M, Streit V, Weberschock T, Rzany B, Anonymous00487. · Division of Evidence Based Medicine (dEBM), Klinik für Dermatologie, Venerologie und Allergologie, Charité-Universitätsmedizin Berlin. · J Dtsch Dermatol Ges. · Pubmed #17187649 No free full text.

This publication has no abstract.

Mrowietz U, Barth J, Boehncke WH, Reich K, Rosenbach T, Streit V, Wozel G. · Universitäts-Hauklinik Kiel. · J Dtsch Dermatol Ges. · Pubmed #16734844 No free full text.

This publication has no abstract.

Domm S, Cinatl J, Mrowietz U. · Psoriasis-Center at the Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Schittenhelmstr. 7, 24105 Kiel, Germany. · Br J Dermatol. · Pubmed #18945310 No free full text.

Abstract: Biologics that antagonize the biological activity of tumour necrosis factor (TNF)-alpha, namely infliximab, etanercept and adalimumab, are increasingly used for treatment of immune-mediated inflammatory diseases, including psoriasis, worldwide. TNF-alpha antagonists are known to increase the risk of reactivation and infection, particularly of infections with intracellular bacteria such as Mycobacterium tuberculosis. More frequently these agents are given to patients with viral infections. Viral hepatitis and human immunodeficiency virus infections are often present in these patients, with a considerable geographical variation. Other concomitant viral infections such as herpes, cytomegalovirus and varicella zoster virus may occur much more frequently than tuberculosis or leprosy. General recommendations about the management related to possible problems associated with anti-TNF-alpha treatment and these viral infections are lacking. This short review will give an overview of the most recent data available on the effects of anti-TNF-alpha therapy on viral infections with a particular focus on patient management and screening recommendations.

Yazdi MR, Mrowietz U. · Psoriasis Center at the Department of Dermatology, University of Kiel, Kiel, Germany. · Clin Dermatol. · Pubmed #18755371 No free full text.

Abstract: Several clinical studies have shown that systemic therapy with fumaric acid esters (FAEs) in patients with moderate to severe psoriasis is effective and has a good long-term safety profile. For therapeutic use, tablets with a defined mixture of FAEs (dimethylfumarate [DMF] and three different salts of monoethylfumarate) are registered in Germany. There is evidence that DMF is the most essential component in this formulation with an antipsoriatic effect. Currently, there are few data on the pharmacokinetics of fumarates in human beings. DMF seems to act as a prodrug for its main metabolite: monomethylfumarate. This hypothesis was supported by the observation that only monomethylfumarate was detected in the plasma of human beings after the oral administration of FAEs. FAEs have been tested in different biological assays, and effects such as inhibition of the nuclear factor kappa B pathway or induction of apoptosis by DMF have been described. For these data, the role of DMF as a modulator of intracellular glutathione plays an important role.

Rott S, Mrowietz U. · Department of Dermatology, Venereology and Allergy University of Schleswig-Holstein, Campus Kiel, Kiel, Germany. · J Dtsch Dermatol Ges. · Pubmed #17659038 No free full text.

Abstract: Autoimmune diseases like Crohn's disease, rheumatoid arthritis (RA) and psoriasis are often difficult to treat due to complex underlying immunologic pathways. Tumor necrosis factor (TNFalpha) is an important proinflammatory cytokine that seems to play an important role in the pathogenesis of these diseases. After the approval of a variety of drugs which block the biological activity of TNFalpha, new therapeutic options were available and especially infliximab became widely used. TNFalpha, as a member of the proinflammatory cytokine family, is a major cytokine in different inflammatory dermatological diseases such as cutaneous vasculitis, lupus erythematosus, eczema or psoriasis. Therefore infliximab has been used in a variety of inflammatory dermatoses lately, sometimes with great success. Several case reports showing new indications for a successful use of TNFalpha-inhibitors in dermatology have been published and will be reviewed in the following article. Nevertheless, infliximab is not approved for these indications at the moment and has to be considered as off-label use.

Reich K, Mrowietz U. · Dermatologikum Hamburg, Germany. · J Dtsch Dermatol Ges. · Pubmed #17610606 No free full text.

Abstract: The introduction of biologics has not only broadened the therapeutic armamentarium for psoriasis but also stimulated discussion about the treatment of this common skin condition. The recently presented German S3 psoriasis guideline contains detailed information on the efficacy of the different products and describes important safety and practical aspects of psoriasis treatments. Patient surveys and recent studies in Germany indicate a relatively high mean severity of skin symptoms and low quality of life among affected patients. One possible explanation is that the conventional traditional and new treatment options are not being used consistently. In this paper, minimum treatment goals for psoriasis that should be achieved by an individually selected treatment regimen are presented. If, after a defined period of time, an at least 50 % reduction of the baseline Psoriasis Area and Severity Index (PASI) and a Dermatology Life Quality Index of ( not less-than 5 is not reached, patients should be switched to another therapy, after a balanced discussion. Whenever necessary, a continuous maintenance therapy should be instituted with special attention to these goals. Patients should carefully be monitored for the presence of psoriatic arthritis and comorbidities because these may need to be integrated in the planning of treatment goals on an interdisciplinary basis.

Mrowietz U, Elder JT, Barker J. · Department of Dermatology, University of Kiel, Schittenhelmstrasse 7, 24105 Kiel, Germany. · Arch Dermatol Res. · Pubmed #17021761 links to  free full text

Abstract: It is well established that several inflammatory-type conditions, such as arthritis, diabetes, cardiovascular disease, and irritable bowel disease exist comorbidly and at an increased incidence in patients with psoriasis. Psoriasis and other associated diseases are thought to share common inflammatory pathways. Conditions such as these, with similar pathogenic mechanisms involving cytokine dysregulation, are referred to as immune-mediated inflammatory diseases (IMIDs). Considerable evidence for the genetic basis of comorbidities in psoriasis exists. The WHO has reported that the occurrence of chronic diseases, including IMIDs, are a rising global burden. In addition, conditions linked with psoriasis have been associated with increasing rates of considerable morbidity and mortality. The presence of comorbid conditions in psoriasis patients has important implications for clinical management. QoL, direct health care expenditures and pharmacokinetics of concomitant therapies are impacted by the presence of comorbid conditions. For example, methotrexate is contraindicated in hepatic impairment, while patients on cyclosporin should be monitored for kidney function. In addition, some agents, such as beta blockers, lithium, synthetic antimalarial drugs, NSAIDs and tetracycline antibiotics, have been implicated in the initiation or exacerbation of psoriasis. Consequently, collaboration between physicians in different specialties is essential to ensuring that psoriasis treatment benefits the patient without exacerbating associated conditions.

Mrowietz U, Boehncke WH. · Department of Dermatology, University of Kiel, Schittenhelmstr. 7, 24105 Kiel, Germany. · Curr Pharm Des. · Pubmed #16918413 No free full text.

Abstract: Inflammatory responses in all tissue compartments require the emigration of leukocytes from the microvasculature through endothelial cells into the respective microenvironment. Adhesion to endothelial cells is the most crucial step in order to facilitate selective and effective capture of leukocytes. The sequence of adhesions events, e.g. rolling, tethering, and firm adhesion are tightly regulated by a variety of molecules expressed by endothelial cells and leukocytes either constitutively or after induction by mainly inflammatory mediators. In diseases with a prominent inflammatory response such as psoriasis, rheumatoid arthritis, or Crohn's disease, interference with leukocyte adhesion and/or emigration may be of substantial clinical effect. A number of therapeutic approaches by using monoclonal antibodies, designed molecules, and other modulators of adhesion molecule expression have been investigated in clinical trials. This review aims to give an overview about the current knowledge of targeting adhesion molecules as a therapeutic strategy to treat inflammatory diseases.

Gerdes S, Mrowietz U. · Psoriasis-Zentrum an der Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Schleswig-Holstein. Campus Kiel, Schittenhelmstrasse 7, 24105 , Kiel. · Hautarzt. · Pubmed #16841204 No free full text.

Abstract: In most cases mild to moderate forms of psoriasis can be treated with topical therapy. In addition, topical agents are also routinely combined with UV or systemic therapy to treat severe forms of psoriasis. A variety of standard products are available. The oldest topical treatment is anthralin. Since 1952 the development of topical corticosteroids has revolutionized not only dermatological treatment in general but the treatment of psoriasis in particular. Through the continuous development of these compounds, a better risk-benefit profile has been achieved. Corticosteroids are the most frequently employed topical agent for psoriasis treatment worldwide.

Griffiths CE, Katsambas A, Dijkmans BA, Finlay AY, Ho VC, Johnston A, Luger TA, Mrowietz U, Thestrup-Pedersen K. · Dermatology Centre, University of Manchester, Hope Hospital, Manchester, UK. · Br J Dermatol. · Pubmed #16774579 No free full text.

Abstract: Immune-mediated dermatoses, such as psoriasis and atopic dermatitis, affect a significant proportion of the population. Although most cases are not life threatening, these diseases can have a profound effect on the sufferer's quality of life and that of their family. Systemic therapy, such as ciclosporin, is often indicated for severe or recalcitrant disease. The efficacy of ciclosporin in the treatment of psoriasis and atopic dermatitis has been established and clinical data also demonstrate its efficacy in treating less common but equally challenging conditions such as pyoderma gangrenosum, lichen planus, autoimmune bullous disease, recalcitrant chronic idiopathic urticaria and chronic dermatitis of the hands and feet. The risk of potential adverse events associated with ciclosporin is greatly reduced if current treatment and monitoring guidelines are followed.

Rott S, Mrowietz U. · Department of Dermatology, University of Kiel, 24105 Kiel, Germany. · BMJ. · Pubmed #15790644 links to  free full text

This publication has no abstract.

Mrowietz U, Asadullah K. · Department of Dermatology, University Clinic of Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany. · Trends Mol Med. · Pubmed #15649822 No free full text.

Abstract: Fumaric acid esters (FAEs) have been used for the oral treatment of psoriasis since 1959 and have been registered for this indication in Germany since 1994. Dimethylfumarate (DMF) and its metabolite methylhydrogenfumarate (MHF) are the pharmacologically active compounds, with DMF being the main component of the marketed FAE-mixture. However, the mechanism of action of FAE is yet to be fully understood. It has been shown that DMF inhibits NFkappaB translocation, which leads to (i) the inhibition of pro-inflammatory cytokine production and adhesion molecule expression, (ii) the inhibition of dendritic cell differentiation and, at higher concentrations, (iii) the induction of apoptosis. Recent evidence also shows that these effects are mediated through the interference of the intracellular redox system by DMF. Here, the mode of action of FAE and its clinical use for psoriasis will be discussed.

Ormerod AD, Mrowietz U. · Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB15 8SG, UK. · Br J Dermatol. · Pubmed #15099356 No free full text.

This publication has no abstract.

Ghoreschi K, Mrowietz U, Röcken M. · Department of Dermatology, University of Tübingen, Liebermeisterstrasse 25, 72076 Tübingen, Germany. · J Mol Med. · Pubmed #12879154 No free full text.

Abstract: Psoriasis is an autoimmune disease affecting 2-4% of the Caucasian population. Inflammatory processes induce the migration of interferon (IFN) gamma producing Th1 lymphocytes into the skin. These play a key role in the pathogenesis of psoriasis. These Th1 lymphocytes are responsible for the pathological reactions in psoriatic skin leading to keratinocyte hyperproliferation, small vessel proliferation and neutrophilic infiltration. Antigen-presenting cells activate dermal CD4+ T lymphocytes, and various signals can support the polarization of Th1 responses. The main signal for Th1 development is interleukin (IL) 12. After binding to their receptors both IL-12 and IFN-gamma promote intracellular IFN-gamma production by activating signal transducer and activator of transcription (STAT) 4 or 1. STAT1 activation by IFN-gamma is followed by T-bet activation, a master transcription factor for Th1 lymphocytes. In experimental models of Th1-mediated autoimmune diseases immune deviation of polarized autoreactive Th1 into anti-inflammatory Th2 responses generally improves the disease. Therefore new therapeutic approaches based on immunomodulating molecules have been developed for psoriasis, a prototypical Th1-mediated autoimmune disorder. Recently IL-4, the most effective Th2-inducing cytokine, has been shown to be safe and efficient for treating psoriasis. Improvement was associated with the induction of a Th2 phenotype of skin infiltrating lymphocytes. This review summarizes the IL-4 inducing potential of various conventional and newer systemic therapies for psoriasis. Many of these were thought to be primarily immunosuppressive. A review of the literature reveals that most of them can induce IL-4 and Th2, and that Th2 induction may be an underestimated mode of action in the therapy of Th1-mediated autoimmune disease. Further studies are needed to determine the central role of IL-4 in the control of Th1-induced autoimmune disease, namely psoriasis.

Mrowietz U. · Department of Dermatology, University of Kiel, Germany. · Clin Exp Dermatol. · Pubmed #12464155 No free full text.

Abstract: Expression of a variety of surface epitopes is a characteristic feature of immune cells. Receptors and adhesion molecules are the most predominant ones. It is also characteristic that epitope expression is modulated during cellular activation. In inflammatory skin diseases these structures can be used to define not only the type of cell but also their activity status. The availability of monoclonal antibodies and fusion proteins enabled to target cellular surface epitopes in order to modulate the cellular function as a principle of treatment. In psoriasis receptor-targeted therapy has been developed and tested in a considerable number of clinical trials. However, these approaches revealed that not all the strategies are equally effective. In this review the development of receptor-targeted treatment for skin disorders, mainly psoriasis, is described. Clinical as well as experimental data obtained with the various compounds employed are discussed with regard to clinical efficacy, safety and tolerability.

Mrowietz U. · Department of Dermatology, University of Kiel, Schittenhelmstrasse 7, 24105 Kiel, Germany. · Clin Exp Dermatol. · Pubmed #11422190 No free full text.

Abstract: Severe cases of psoriasis and psoriasis arthritis require systemic treatment. Although a number of established drugs are in clinical use, there is a need for new compounds with an improved risk-benefit ratio with a major emphasis on long-term safety. Furthermore, patients with moderate psoriasis ask for systemic drugs to make therapy easier and to avoid excessive local treatments. This article aims to give a brief overview about new drugs or groups of compounds together with an evaluation of their present status in the treatment of psoriasis and their future role with particular respect to efficacy, tolerability, safety and usability.

Gottlieb AB, Griffiths CE, Ho VC, Lahfa M, Mrowietz U, Murrell DF, Ortonne JP, Todd G, Cherill R, Marks I, Emady-Azar S, Paul CF, Anonymous00036. · UMDNJ-Robert Wood Johnson Medica School, New Brunswick, NJ, USA. · Br J Dermatol. · Pubmed #15948985 No free full text.

Abstract: BACKGROUND: There is a need for safe and effective alternative treatments for patients with moderate to severe psoriasis. OBJECTIVES: Pimecrolimus is a calcineurin inhibitor that is being investigated in oral form for the treatment of psoriasis. PATIENTS AND METHODS: A double-blind, randomized, parallel-group, dose-finding study was performed. Healthy adult outpatients with moderate to severe chronic plaque-type psoriasis (n = 143) were randomized to receive oral placebo or pimecrolimus 10 mg, 20 mg or 30 mg twice daily (b.d.) for 12 weeks. Main outcome measures: The Psoriasis Area and Severity Index (PASI) was used to assess clinical severity of psoriasis. Results were analysed at weeks 7 (primary endpoint) and 13. Safety was assessed by monitoring all adverse events, laboratory investigations (blood chemistry, urinalysis, haematology) and physical examinations. RESULTS: The change from baseline in PASI at week 7 showed a dose-dependent effect. The differences between each of the two higher doses of pimecrolimus and placebo were statistically significant (P < 0.001; ANOVA). The mean percentage decreases from baseline in PASI in the placebo group and pimecrolimus 10 mg, 20 mg and 30 mg b.d. groups at week 7 were 3.1%, 22.2%, 51.3% and 54.0%, respectively. Most adverse events were of mild or moderate severity. The only adverse event to show a dose-response relationship was a transient feeling of warmth. No clinically relevant effects on laboratory parameters were observed, and no increase in skin infection with pimecrolimus was seen. CONCLUSIONS: Oral pimecrolimus produces a dose-dependent reduction in psoriasis severity, with doses of 20 mg and 30 mg b.d. being the most effective and well tolerated.

Reygagne P, Mrowietz U, Decroix J, de Waard-van der Spek FB, Acebes LO, Figueiredo A, Caputo R, Poncet M, Arsonnaud S. · Centre Sabouraud, Paris, France. · J Dermatolog Treat. · Pubmed #15897165 No free full text.

Abstract: BACKGROUND: Scalp involvement in psoriatic patients represents a common issue. Treatment of the hairy skin requires adequate pharmaceutical formulations; hence, a new specific shampoo formulation of clobetasol propionate 0.05% was developed by Galderma R&D, Inc. METHODS: For this multicenter, randomized, investigator-masked, parallel group study, 151 subjects with moderate to severe scalp psoriasis were randomized to 4 weeks of treatment with clobetasol propionate shampoo or calcipotriol solution. RESULTS: Clobetasol propionate demonstrated significantly superior efficacy to calcipotriol solution (total severity score: mean difference 0.51, 95% CI 0.05-0.97, p = 0.028; global severity score: mean difference 0.43, 95% CI 0.08-0.78, p = 0.016). Adverse events were more common in the calcipotriol group than in the clobetasol propionate shampoo group. Telangiectasia and skin atrophy did not differ significantly between treatments; however, a burning sensation was significantly more common in the calcipotriol solution group. CONCLUSIONS: Short contact therapy of scalp psoriasis with this new shampoo formulation of clobetasol propionate was significantly more effective and better tolerated than calcipotriol solution for the treatment of scalp psoriasis.

Schmid-Ott G, Malewski P, Kreiselmaier I, Mrowietz U. · Abteilung Psychosomatik und Psychotherapie, Medizinische Hochschule, Hannover. · Hautarzt. · Pubmed #15711815 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: The aim of this study was to determine the psychosocial consequences of psoriasis in a large sample in Germany.PATIENTS AND METHODS: A questionnaire including the Psoriasis Disability Index (PDI) circulated by the German Psoriasis Alliance was answered by 3753 members representing a return rate of 42.3%. Psoriasis was graded-at the time of the examination-with less than 3% of the body surface affected as "mild", between 3 and 10% as "moderate," and more than 10% as "severe."RESULTS: The general impact of the illness on everyday life was "mild" in about 27%, "problematic" in about 45%, and "severe" in about 25% of the respondents. About 50% of the participants in the study had, concerning the skin, "mild" (PDI=9), about 35% "moderate" (PDI=14), and about 15% "severe" psoriasis (PDI=19). The differences of the PDI values are significant (ANOVA: p<0.001).CONCLUSIONS: This investigation confirms the enormous burden caused by the skin disease in the form of impairment and stigmatization, depending on the somatic severity, even when the current affection is rather mild. In connection with psychosocial consequences, future study should also focus on the disease burden of psoriasis.

Mrowietz U, Wustlich S, Hoexter G, Graeber M, Bräutigam M, Luger T. · Department of Dermatology, University of Schleswig-Holstein, Campus Kiel, Germany. · Acta Derm Venereol. · Pubmed #14609102 No free full text.

Abstract: Pimecrolimus (Elidel, SDZ ASM 981), a new macrolactam ascomycin derivative, was highly effective in treating plaque-type psoriasis when applied under Finn-chamber occlusion. A two-centre, randomized, double-blind, vehicle- and positive-controlled within-patient study was therefore conducted in 23 adult psoriasis patients. Pimecrolimus 1% was applied, twice daily, in an experimental ointment formulation, along with the corresponding vehicle, 0.005% calcipotriol ointment and 0.05% clobetasol-17-propionate ointment to test sites without occlusion for 21 days. Erythema, induration and scaling (score: 0 [absent] to 4 [severe]) were evaluated. The total sign score was defined as the sum of the erythema, induration and scaling scores (range 0-12). Pimecrolimus 1% ointment was significantly (p = 0.03) more effective than the corresponding vehicle, with an improvement in total sign score of 51.4% compared with 36.7% for the corresponding vehicle. Improvements with calcipotriol and clobetasol-17-propionate were 71.5% and 88.3%, respectively. No local or systemic drug-related side effects were observed in the study. We conclude that pimecrolimus 1% in the experimental ointment formulation was significantly more effective than its corresponding vehicle, but less effective than calcipotriol and clobetasol ointment. This is the first study reporting a significant therapeutic effect of pimecrolimus in an ointment formulation applied without occlusion to psoriatic plaques.

Lahfa M, Mrowietz U, Koenig M, Simon JC. · Hôpital Saint-Louis,1 avenue Claude Vellefaux, 25015 Paris, France. · Eur J Dermatol. · Pubmed #12804986 links to  free full text

Abstract: For psoriasis therapy, topical derivatives of vitamin D3 represent a versatile option: they can be used either alone or in combination with other agents such as topical corticosteroids. In this two-phase parallel-group study, the naturally occurring vitamin D3 analogue, calcitriol, was compared with the vitamin D analogue calcipotriol in 125 patients with chronic plaque-type psoriasis. The proposed treatment regimen was an initial bitherapy for 2 or 4 weeks, with clobetasol propionate 0.05% cream, a super potent topical corticosteroid applied in the morning and either calcitriol 3 mug/g ointment or calcipotriol 50 mug/g ointment applied in the evening, followed by monotherapy with either calcitriol or calcipotriol applied twice daily until endpoint week 12. Efficacy evaluations (global assessment of improvement, PASI and body surface area (BSA) affected) showed no significant differences between the two regimen groups at the primary endpoints (week 2 and week 12) or at any interim points. At week 2 the investigator's global assessment showed clinical success (psoriasis markedly improved, almost clear or clear) for more than 50% of the patients in both groups and for 48 (79%) and 56 (88%) patients, respectively in the calcitriol and calcipotriol regimen group at week 12. Least-square means analysis of PASI indicated the calcitriol regimen to be equivalent to the calcipotriol regimen. There were no significant differences between the two groups with regards to cutaneous safety or to incidence of adverse events. The present study shows that for the treatment of mild to moderate plaque psoriasis calcitriol 3 mug/g ointment can provide a safe and effective alternative to calcipotriol 50 mug/g ointment while being administered within a regimen based on a bitherapy with corticosteroids followed by a vitamin D3 maintenance monotherapy.

Douglas WS, Poulin Y, Decroix J, Ortonne JP, Mrowietz U, Gulliver W, Krogstad AL, Larsen FG, Iglesias L, Buckley C, Bibby AJ. · Department of Dermatology, Monklands Hospital, Lanarkshire, Scotland, UK. · Acta Derm Venereol. · Pubmed #12125943 No free full text.

Abstract: In this study, we compared a new combination ointment containing both calcipotriol and betamethasone dipropionate with betamethasone dipropionate ointment (Diprosone) and calcipotriol ointment (Daivonex) in patients with psoriasis vulgaris; 1106 patients were randomized to twice daily double-blind treatment with combination, betamethasone dipropionate or calcipotriol for 4 weeks. Patients then received twice daily calcipotriol, unblinded, for a further 4 weeks. Mean percentage change in PASI at end of the double-blind phase was -74.4 (combination group), -61.3 (betamethasone group) and -55.3 (calcipotriol group). Mean difference (95% Cl) combination-betamethasone was -13.1 (-16.9 to -9.3, p < 0.001) and for combination-calcipotriol -19.0 (-22.8 to -15.2, p <0.001). The differences in PASI were also statistically significant after 1 week. In the double-blind phase, 8.1% of patients (combination) reported lesional/ perilesional adverse reactions compared to 4.7% (betamethasone) and 12.0% (calcipotriol). In the combination group, mean PASI at the end of the double-blind phase was 2.5, and at end of the unblinded phase 3.6, compared with 3.9 and 4.1 (betamethasone) and 4.4 and 3.7 (calcipotriol). Calcipotriol/betamethasone combination is more effective and has a more rapid onset of action than either active constituent used alone, and is well tolerated. It is safe to transfer patients from combination to calcipotriol, with maintenance of clinical effect.