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doi: 10.1046/j.1365-2133.2001.144s58003.xpmid: 11501511
Calcitriol 3 μg g−1 ointment (Silkis ointment®, Galderma Laboratories) is a new treatment for psoriasis. Calcitriol is the biologically active metabolite of vitamin D3. It induces keratinocyte differentiation, inhibits keratinocyte, T‐cell and fibroblast proliferation, and inhibits the production of some inflammatory mediators, all contributors to the pathogenesis of psoriasis. Preclinical studies have shown an effect of topical calcitriol on calcium homeostasis at doses higher than those in clinical use. No adverse local events were observed when calcitriol was applied to animal skin. Phase I clinical studies confirmed that calcitriol 3 μg g−1 ointment is well tolerated in humans. These studies have demonstrated that at the minimal effective concentration of 3 μg g−1, calcitriol ointment has no discernible photosensitizing or phototoxic potential and no skin irritant or allergic potential in healthy volunteers. Its low systemic absorption through human skin is unlikely to significantly affect calcium homeostasis. This paper summarizes the findings of the preclinical and early clinical studies that provided the foundation of the later Phase II and III clinical trials on efficacy and safety with topical calcitriol 3 μg g−1 ointment for the treatment of plaque psoriasis.
Langner, A.; Stapór, W.; Ambroziak, M.
doi: 10.1046/j.1365-2133.2001.144s58011.xpmid: 11501507
Although topical vitamin D3 derivatives have been used in the treatment of patients with psoriasis for the past 15 years, questions remain about the indications and limitations of application. Extensive personal experience gained during the development of calcitriol (1α25‐dihydroxyvitamin D3) is therefore reviewed. Three double‐blind, vehicle‐controlled trials have revealed that calcitriol 3 μg g−1 ointment (Silkis ointment®, Galderma Laboratories) has very good clinical efficacy. In a left–right comparison with vehicle ointment, complete clearance of psoriatic lesions was achieved in 48% of sites treated with calcitriol and a further 41% showed considerable or definite improvement. The clinical response to calcitriol in another study was as good as, or even better than, that achieved with betamethasone valerate 0·1% ointment. A preparation containing calcitriol 15 μg g−1 did not show any clinical superiority to the lower dose but was associated with a higher risk of hypercalciuria, particularly when applied to extensive skin lesions. These results suggest that calcitriol 3 μg g−1 ointment is an effective and safe treatment for chronic plaque psoriasis.
Gerritsen, M.J.P.; Van De Kerkhof, P.C.M.; Langner, A.
doi: 10.1046/j.1365-2133.2001.144s58017.xpmid: 11501508
To assess the topical and systemic safety and tolerance of twice‐daily application of 3 μg g−1 1α25‐dihydroxyvitamin D3 (calcitriol) ointment (Silkis ointment®, Galderma Laboratories) in the long‐term treatment of patients suffering from chronic plaque psoriasis, we performed an open‐design, multicentre study. Two hundred and fifty‐three patients (155 males, 98 females) treated all their psoriatic lesions, except for those on the head and scalp, for up to 78 weeks. No serious adverse events were reported; 37 patients (14·6%) had a transient skin irritation reaction on one or more occasions during the study that resulted in study withdrawal for seven of them. The baseline/endpoint analyses showed no clinically relevant changes in measures of calcium and phosphorus homeostasis and renal function. Slight hypercalcaemia was observed in five (2%) patients; in four of these patients, serum albumin‐adjusted total calcium levels normalized during treatment. In conclusion, twice‐daily calcitriol 3 μg g−1 ointment is safe and well tolerated in the long‐term treatment of chronic plaque psoriasis.
doi: 10.1046/j.1365-2133.2001.144s58021.xpmid: 11501509
The use of vitamin D analogues for the treatment of chronic plaque psoriasis is well documented. Of importance now is their comparability and compatibility with other established treatments for psoriasis. This paper reviews five studies with calcitriol 3 μg g−1 ointment (Silkis ointment®, Galderma Laboratories). Calcitriol applied twice daily was found to be as effective as short‐contact dithranol in terms of global improvement and PASI scores. However, patients favoured calcitriol over dithranol when both quality of life and treatment acceptability were assessed. Two studies provide evidence of the benefit of combining calcitriol with other antipsoriatic therapies. Combination with ultraviolet (UV) B phototherapy proved as effective as UVB alone over an 8‐week period; however, the combination had a radiation dose‐sparing effect, thus reducing the risk of adverse events. Likewise, calcitriol combined with betamethasone valerate (each applied separately, once daily) was as efficacious as twice‐daily betamethasone, thereby achieving a corticosteroid‐sparing effect. Finally, two studies confirm that calcitriol 3 μg g−1 ointment can be used safely in patients with psoriasis of the head and confirm the high level of clinical efficacy achieved with this compound.
doi: 10.1046/j.1365-2133.2001.144s58027.xpmid: 11501510
Monotherapy with vitamin D analogues has been shown to be effective in the treatment of psoriasis. Vitamin D analogues have also been used in combination with other topical therapies, systemic therapies and phototherapy. In many instances, the efficacy of these other treatments can be maximized and adverse effects minimized when combined with vitamin D analogues. The combination of a topical corticosteroid with a vitamin D analogue can work synergistically to improve efficacy and reduce the side‐effects from both treatments. However, caution must be used when mixing the two agents, as some topical corticosteroids will result in the degradation of the vitamin D analogue. Benefit from phototherapy is also increased when using vitamin D analogues, so that greater improvement occurs with fewer treatments. Effects on minimal erythema dose must be considered and the potential for ultraviolet blocking by vitamin D analogues may affect treatment. Some vitamin D analogues may also be susceptible to degradation by certain wavelengths of ultraviolet light. Combining vitamin D analogues with systemic agents exerts a dose‐sparing effect, thus reducing the possibility of side‐effects, but such combinations require further study. As long as treatments are used correctly, the benefits of combination therapy with vitamin D analogues usually outweigh the few drawbacks.
De Arruda, L.H.F.; De Moraes, A.P.F.
doi: 10.1046/j.1365-2133.2001.144s58033.xpmid: 11501512
Psoriasis is a chronic inflammatory skin disease in which the signs vary from one patient to another and over time. Traditionally, physicians have used various parameters to assess the severity of the disease: percentage of body surface area covered, erythema, plaque thickness, degree of scaling and systemic symptoms such as arthritis. However, these clinical assessments alone do not accurately reflect the overall effect of the disease on patients’ daily activities. Apart from the clinical severity of affected areas, psoriasis can also have a profound psychosocial impact on the patient’s quality of life. This concept is multidimensional, encompassing the physical, social and psychological wellbeing of the person and is based on the patient’s view of their condition.
doi: 10.1046/j.1365-2133.2001.144s58037.xpmid: 11501513
The aetiology of psoriasis is still unclear but our knowledge of the psoriatic process has grown substantially over the last two decades. The future will undoubtedly bring advances in our understanding of the pathogenesis of psoriasis and, as a consequence, new therapies. Defining the molecular genetics of psoriasis will enhance our understanding of the disease process and hopefully facilitate the development of a representative animal model. This in itself will be a key step in the development and testing of new therapies. Precise identification of the immunological events involved in psoriasis will allow specific T‐cell‐ and cytokine‐targeted, and perhaps less toxic, immunotherapies. Anti‐angiogenic agents that are in development for use in oncology may also be effective in psoriasis. The adaptation of current topical therapies such as retinoids and vitamin D analogues to produce more effective and better‐tolerated formulations will also play a significant role in our future first‐line management of patients. The increased recognition and better management of environmental trigger factors such as psychological distress will become an important factor in future psoriasis care. The development of physical therapies including photodynamic therapy and excimer lasers has the potential to expand the remit of psoriasis therapy. There is little doubt that the future for our patients with psoriasis is bright. However, this will only be achievable by a concerted research effort to understand all facets of this enigmatic disease ranging from the molecular to the environmental.
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