A New Calcipotriol/Betamethasone Dipropionate Formulation (Daivobet&lt;sup&gt;TM&lt;/sup&gt;) Is an Effective Once-Daily Treatment for Psoriasis vulgaris

Kaufmann, Roland; Bibby, Adrian; Bissonnette, Robert; Cambazard, F.; Chu, A.C.; Decroix, J.; Douglas, W.S.; Lowson, David; Mascaró, J. M.; Murphy, G. M.; Stymne, B.

doi:10.1159/000066440

Cited by 154 publications

(196 citation statements)

References 13 publications

(15 reference statements)

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“…Given the crucial role of NF-B in inflammatory response, and the therapeutic and pharmacological potentials of vitamin D and vitamin D analogs in treatment of autoimmune and inflammatory diseases, such as multiple sclerosis (5), type I diabetes (26,27), inflammatory bowel disease (22), and psoriasis (16,18), understanding the relationship and interaction between vitamin D, VDR, and NF-B pathway has broad implications. The direct involvement of VDR in the regulation of NF-B activation suggests an intrinsic inhibitory role of VDR in inflammation process, and this inhibitory action may likely be enhanced in the presence of vitamin D ligands.…”

Section: Resultsmentioning

confidence: 99%

Increased NF-κB activity in fibroblasts lacking the vitamin D receptor

Sun

Kong

Duan³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

213

194

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1,25-Dihydroxyvitamin D [1,25(OH)2D3] is known to have anti-inflammatory activity; however, the molecular mechanism remains poorly defined. Here we show that the nuclear vitamin D receptor (VDR) is directly involved in the regulation of NF-κB activation, a pathway essential for inflammatory response. In mouse embryonic fibroblasts (MEFs) derived from VDR−/− mice, the basal level of κB inhibitor (IκB) α protein was markedly decreased compared with VDR+/− MEFs; however, degradation of IκBα and its phosphorylation in response to TNF-α treatment or Salmonella infection were not altered in VDR−/− cells, neither were the levels of IκB kinase-α and IκB kinase-β proteins. Consistent with IκBα reduction, p65 accumulation in the nucleus was markedly increased in unstimulated VDR−/− cells. In addition, the physical interaction between VDR and p65 was absent in VDR−/− MEFs, which may free p65 and increase its activity. Consequently, these alterations combined led to a marked increase in nuclear p65 DNA binding and NF-κB transcriptional activity; consistently, induction of IL-6 by TNF-α or IL-1β was much more robust in VDR−/− than in VDR+/− cells, indicating that VDR−/− cells are more susceptible to inflammatory stimulation. Therefore, cells lacking VDR appear to be more proinflammatory due to the intrinsic high NF-κB activity. The reduction of IκBα in VDR−/− MEFs may be partially explained by the lack of VDR-mediated stabilization of IκBα by 1,25(OH)2D3. This is supported by the observation that IκBα degradation induced by TNF-α was inhibited by 1,25(OH)2D3 in VDR+/− cells, but not in VDR−/− cells. Taken together, these data suggest that VDR plays an inhibitory role in the regulation of NF-κB activation.

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Section: Resultsmentioning

confidence: 99%

Increased NF-κB activity in fibroblasts lacking the vitamin D receptor

Sun

Kong

Duan³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

213

194

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“…Psoriatic patients with thick, plaques often require treatment with the highest potency corticosteroids and associated with multiple side effects with long term use. 11 Calcipotriol is generally considered to be as effective as corticosteroid (betamethasone), in some studies in plaque psoriasis. Topical calcipotriol (0.005%) is found more effective than the conventional topical corticosteroid (betamethasone 0.1%) in some studies.…”

Section: Originalmentioning

confidence: 99%

Comparative Efficacy of Topical Calcipotriol (0.005%) Versus Topical Corticosteroid (Betamethasone 0.1%) in Treating Plaque Type Psoriasis

Ahmed

Khandker

Nessa³

et al. 2015

Med. Today

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“…[10][11][12][13][14][15] The two-compound ointment appears to have an improved tolerability profile vs. either compound alone; this may be due to the vitamin D analogue and steroid components each neutralizing the side-effects of the other agent (e.g. atrophy and tachyphylaxis ⁄ rebound effect may be reduced by the presence of the vitamin D analogue, and irritation may be reduced by the presence of the steroid).…”

Section: Combination Therapy Provides Enhanced Efficacymentioning

confidence: 99%

What is new in topical therapy for psoriasis?

Reich

Bewley

2011

Acad Dermatol Venereol

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This article describes a recent development in topical therapies for psoriasis and is based on a presentation given by the authors at a satellite symposium convened during the 19th Congress of the European Academy of Dermatology and Venereology, 6-10 October 2010, in Gothenburg, Sweden. Topical therapies are the mainstay of treatment for psoriasis; however, for optimal outcomes to be achieved, medications need to be used as prescribed. Patients with psoriasis often report low treatment adherence rates; the reasons for this are multifactorial, but can include specific aspects of the treatments themselves. For example, physical properties, ease of use and the vehicle in which the active ingredients are dissolved can all play a role in an individual patient's adherence to treatment. Of the available topical therapies, corticosteroids and vitamin D analogues are the treatment of choice, with combined efficacy that is superior to monotherapy with either agent. To permit simultaneous once-daily dosing, an ointment was formulated that allowed calcipotriol and betamethasone dipropionate to be delivered together; this twocompound ointment had an improved efficacy and tolerability profile vs. either compound alone. To provide an alternative for patients who may dislike ointments, but still want to benefit from the high efficacy of combination therapy, a two-compound (calcipotriol ⁄ betamethasone dipropionate) gel has recently been developed; data from phase 2 and phase 3 studies show that it is more effective than the comparators it was tested against, with fewer adverse events, and a rapid onset of action. In a series of one-to-one interviews recently conducted with 150 patients with psoriasis, gel and cream formulations were preferred for ease of use and cosmetic acceptability compared with ointment. The availability of this new gel thus increases patient choice. Ultimately, treatment should always be tailored to match individual patients' needs.

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A New Calcipotriol/Betamethasone Dipropionate Formulation (Daivobet<sup>TM</sup>) Is an Effective Once-Daily Treatment for Psoriasis vulgaris

Cited by 154 publications

References 13 publications

Increased NF-κB activity in fibroblasts lacking the vitamin D receptor

Increased NF-κB activity in fibroblasts lacking the vitamin D receptor

Comparative Efficacy of Topical Calcipotriol (0.005%) Versus Topical Corticosteroid (Betamethasone 0.1%) in Treating Plaque Type Psoriasis

What is new in topical therapy for psoriasis?

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