What is Dovonex? How does Dovovex help in the treatment of psoriasis? What research has been done on Dovonex?
DOVONEX CREAM calcipotriol is one form of topical treatment for Psoriasis.Dovonex, a synthetic topical form of vitamin D reduces the production of skin cells and thus slows down psoriasis. The skin grows usually every 28 days or so whereas in psoriasis, it grows every three to six days and forms plaques or lesions.
AS a user of Dovonex, I saw an improvement almost immediately in my psoriasis. Dovonex is generally used with mild psoriasis. A write up for Dovenex for psoriasis can be found hereat the Bristol Myers site. Psoriasis is often called an "immune-mediated" disorder where the immune system attacks itself. Close to five million people in the U.S. suffer from Psoriasis. Studies show there is a genetic component but as of yet don't know what triggers the outbreaks. Some say to avoid acidic food, alcohol, root vegetables and coffee but there is no firm research to back that up. Possible triggers for psoriasis are emotional stress, reactions to certain drugs such as lithium, ace inhibitors, and beta blockers. Changes in weather may be a trigger for psoriasis. Then there are skin trauma, and infection. .An indepth article can be found here
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J Cutan Med Surg. 2004 May 3 [Epub ahead of print] : Nail Psoriasis: Combined Therapy with Systemic Cyclosporin and Topical Calcipotriol.
Feliciani C, Zampetti A, Forleo P, Cerritelli L, Amerio P, Proietto G, Tulli A, Amerio P.
Department of Dermatology, Catholic University of the Sacred Heart, Rome, Italy.
BACKGROUND. Nail psoriasis is a common problem in psoriatic patients and often it is difficult to cure. Several treatments have been proposed in the last decade using new molecules like vitamin-D analog and/or immunosoppressive drugs both systemically and locally.OBJECTIVE. Our goal was to evaluate a combination of cyclosporin and topical calcipotriol cream versus cyclosporin alone in a matched group of patients treated with cyclosporin alone.METHOD. Fifty-four patients affected by severe psoriasis and nail involvement were selected and matched for severity of nail involvement, sex, age, and cyclosporin dosage. Group A included 21 patients treated with cyclosporin alone (3.5 mg/kg/day) for three months. Group B included 33 patients treated with the same cyclosporin dosage plus, for the same time, topical application of calcipotriol cream twice a day. Evaluation for clinical improvement was the personal feeling of the patient after three months, while clinical appearance of the lesions was evaluated by the same dermatologist using digital pictures and who was blind as to the treatment of the patient. A score ranging from + to +++ was used in order to evaluate the improvement, and data were statistically evaluated with the Wilcoxon test.RESULTS. Both cyclosporin alone and a combination of cyclosporin with topical calcipotriol twice a day were useful for treating nail psoriasis after three months of therapy although the combined therapy showed a better overall result in both mild and severe nail psoriasis. Improvement of the clinical appearance of the nail lesions was seen in about 79% of patients in group B ( p Dermatol Nurs. 2004 Feb;16(1):89-90, 93, 100. : Topical vitamin D analogs.
Kieffer MA.
Calcipotriene offers a safe and effective option in the treatment of plaque psoriasis. It helps regulate the abnormal growth and production of keratinocytes, as well as has a number of effects on inflammation seen with psoriasis. When used as monotherapy or in combination with corticosteroids, it may help reduce the adverse effects seen with chronic steroid use. Calcipotriene is currently only indicated for plaque psoriasis; however, it has shown promise for use in a wide range of dermatologic conditions
Exp Dermatol. 2004 Feb;13(2):106-12. : The effect of the combination of calcipotriol and betamethasone dipropionate versus both monotherapies on epidermal proliferation, keratinization and T-cell subsets in chronic plaque psoriasis.
Vissers WH, Berends M, Muys L, van Erp PE, de Jong EM, van de Kerkhof PC.
Department of Dermatology, University Medical Centre St Radboud, Nijmegen, The Netherlands.
w.vissers@derma.umcn.nl
Several reports have indicated that the combination of calcipotriol ointment and potent or ultrapotent corticosteroids are more effective and better tolerated, as compared to the monotherapies. The aim of the present study was to find out the effect of combination of calcipotriol ointment once daily and betamethasone dipropionate ointment once daily vs. the effect of twice-daily applications of each of the two treatments as monotherapy during a four-week treatment period. Seven patients with chronic plaque psoriasis were included for treatment with the three treatment schedules. Biopsies were taken before treatment and after four weeks of treatment, and markers for epidermal proliferation (Ki-67) and epidermal differentiation (keratin-10) were studied using a quantitative image analysis, and T-cell subsets in epidermis and dermis (CD4, CD8, CD25, CD45RO, CD45RA, CD94, CD161, and CD2) were studied using immunohistochemical scoring. The most impressive clinical result was reached with the combination. Calcipotriol proved to have a major effect on the proliferation marker Ki-67 and differentiation marker keratin-10, whereas the effect on T-cell subsets was more selective with major reductions of CD45RO(+) and CD8(+) T cells. In contrast, the effect of betamethasone dipropionate on the epidermis was restricted to a normalization of differentiation with a highly significant increase of keratin-10 positive epidermal surface without a significant effect on Ki-67 positive nuclei, and the effect on T-cell subsets was restricted to a reduction of natural killer T-cell receptors designated by CD94 and CD161 in the epidermis. The combination of the two treatments did not affect the proliferation marker Ki-67 and keratinization marker keratin-10, beyond the effect of calcipotriol monotherapy. However, the combination had a profound effect on, virtually, all T-cell subsets, beyond the effect of the monotherapies. It is concluded that the action spectra of calcipotriol and betamethasone on the psoriatic plaque are different and that the combination has effects on T-cell subsets, beyond the addition of the effects of monotherapies.
Am J Clin Dermatol. 2004;5(2):71-7. : Fixed-dose combination therapy for psoriasis.
Guenther LC.
The Guenther Dermatology Research Centre, London, Ontario, Canada.
Fixed-dose combination therapy offers stable products containing two or more medications with different mechanisms of action and safety profiles. It is also convenient for patients since only one product rather than two or more needs to be applied. Topical corticosteroids are often the mainstay of therapy in psoriasis. Diprosalic((R)) and Nerisalic((R)) contain a topical corticosteroid (betamethasone dipropionate and diflucortolone, respectively) and salicylic acid. A left/right study showed that both products have comparable efficacy. It has also been shown that betamethasone dipropionate + salicylic acid ointment has similar efficacy to clobetasol and calcipotriene (calcipotriol) ointments. Betamethasone dipropionate + salicylic acid lotion has similar efficacy to clobetasol lotion. Faster improvement of scaling, itching, and redness was noted with betamethasone dipropionate + salicylic acid lotion compared with betamethasone dipropionate alone. Dovobet((R)) (Daivobet((R))) ointment is a fixed-dose combination product containing betamethasone dipropionate and calcipotriene. Clinical studies have shown that it has greater efficacy and a faster speed of onset than the individual components or tacalcitol. Once daily and twice daily treatments have similar efficacy. Psoriasis Area and Severity Index reductions of approximately 40% after 1 week and 70% after 4 weeks of therapy were consistently noted in six large international studies involving >6000 patients. Betamethasone dipropionate + calcipotriene treatment is associated with approximately 75% less adverse cutaneous events as compared with tacalcitol, 50% less compared with calcipotriene, and a similar number as treatment with betamethasone dipropionate.
Int J Dermatol. 2003 Oct;42(10):834-8. : Calcipotriol versus coal tar: a prospective randomized study in stable plaque psoriasis.
Sharma V, Kaur I, Kumar B.
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
BACKGROUND: Topical therapies are the first line of treatment for patients with stable plaque psoriasis (SPP) affecting a limited body surface area. Very few trials comparing newer agents, such as 0.005% topical calcipotriol, with conventional modes of therapy, such as coal tar ointment, have been reported. METHODS: A prospective, right-left randomized, investigator-blinded study with a 12-week treatment period and an 8-week follow-up period was performed. Thirty-six patients with nearly bilaterally symmetrical SPP lesions on the limbs were instructed to apply 5% coal tar ointment overnight on one side once daily and 0.005% calcipotriol ointment on the other side twice a day. All patients were advised to expose both sides to the sun for 2 h every day. Psoriatic lesions and progress during treatment were evaluated using the severity (0-3) scale of erythema, scaling and induration (ESI score). Evaluation was carried out every 2 weeks during the treatment period and monthly during follow-up. At the end of 12 weeks, patients with > 75% reduction in the ESI score were considered to be markedly improved, those with 51-75% reduction to be moderately improved, those with 26-50% reduction to be minimally improved and those with < 25% to be non-responders. Self-assessment by the patients regarding the efficacy and acceptability of the two modalities was on a five-point scale. Serum calcium, serum phosphate, total and differential serum proteins, 24-h urinary calcium and phosphate were monitored both at baseline and after completion of therapy. RESULTS: Thirty of the 36 recruited patients completed the study. The difference in clinical response between the two sides was statistically significant at 4, 6 and 8 weeks, with the percentage reduction in ESI score with calcipotriol being 65.7 +/- 12.2% compared with 45.8 +/- 16.6% with coal tar at 8 weeks (P < 0.01, t = 6.4). However, the difference in clinical response at 10 and 12 weeks between the two sides was not significant, with a mean reduction of 71.9 +/- 13.3% in ESI score on the calcipotriol-treated side compared with 69.4 +/- 15.4% with coal tar ointment (P > 0.05). In the follow-up period of 8 weeks, recurrence of lesions was noted in 10% of patients treated with calcipotriol compared with 16.7% in those treated with coal tar after an average period of 6 +/- 1.2 and 5 +/- 1.3 weeks, respectively (P > 0.05). CONCLUSIONS: It was found that 0.005% calcipotriol ointment produced a faster initial response and had better cosmetic acceptability in patients, although after a long period of treatment, i.e. 12 weeks, 5% coal tar ointment had comparable efficacy. There was no statistically significant difference in the relapse rates between the two modalities.
Br J Dermatol. 2003 Aug;149(2):350-3. : Observer-blind, randomized, intrapatient comparison of a novel 1% coal tar preparation (Exorex) and calcipotriol cream in the treatment of plaque type psoriasis.
Tzaneva S, Honigsmann H, Tanew A.
Division of Special and Environmental Dermatology, Department of Dermatology, University of Vienna Medical School, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
BACKGROUND: In a recent pilot study a novel, patented fatty acid-based 1% coal tar preparation (Exorex) has been found to be similar in efficacy to calcipotriol in the treatment of psoriasis. OBJECTIVES: Our aim was to investigate the therapeutic efficacy, safety and cosmetic acceptability of the new 1% coal tar preparation in comparison with calcipotriol cream in a larger patient cohort. PATIENTS AND METHODS: Forty patients with chronic plaque type psoriasis were included in this randomized, observer-blind, intrapatient comparison trial. In each patient two comparable target plaques were treated twice daily with 1% coal tar preparation or calcipotriol cream. At the onset of therapy and at weeks 2, 4, 6 and 8, the response to treatment was determined by the psoriasis severity index (PSI) that assesses the degree of erythema, infiltration and scaling of the psoriatic lesions on a five-point scale. In addition, all treatment-related side-effects were recorded and cosmetic acceptability of both treatments was rated every second week by the patients. After complete or near complete clearing the patients were followed up until relapse or for a maximum period of 18 months. RESULTS: Thirty-eight patients completed the study. At termination of the trial the mean +/- SD baseline PSI score of 9.2 +/- 1.5 was reduced to 3.0 +/- 2.9 by 1% coal tar preparation and to 2.8 +/- 2.7 by calcipotriol. The mean PSI reduction between baseline and final assessment did not differ significantly between 1% coal tar preparation and calcipotriol (P = 0.77). The mean intraindividual difference in reduction of PSI score between 1% coal tar preparation and calcipotriol was 0.1 score points (95% confidence interval - 0.84 to + 0.63). No difference between either preparation was observed with regard to time until relapse. Itching was caused by 1% coal tar preparation in four patients and by calcipotriol in one patient. Unpleasant odour or staining of the 1% coal tar preparation was reported by six patients, whereas one patient complained about the smell of the calcipotriol cream. CONCLUSIONS: The novel 1% coal tar preparation was found to be comparably as effective as calcipotriol in treating psoriasis. Tolerability and cosmetic acceptability was better for calcipotriol. Taking into consideration that the coal tar preparation is considerably less expensive than calcipotriol this new product appears as a very useful topical medication for chronic plaque type psoriasis.
Br J Dermatol. 2003 Jul;149(1):146-50. : Combination TL01 ultraviolet B phototherapy and topical calcipotriol for psoriasis: a prospective randomized placebo-controlled clinical trial.
Woo WK, McKenna KE.
Department of Dermatology, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, U.K.
keithwoo@doctors.org.uk
BACKGROUND: Previous studies have demonstrated the ultraviolet (UV)-sparing effect of combining topical calcipotriol with broadband UVB in the treatment of psoriasis. OBJECTIVES: To determine if the combination of narrowband TL01 UVB phototherapy and topical calcipotriol produces the same UVB-sparing effect. METHODS: This was a randomized, placebo-controlled, blinded clinical trial. Fifty psoriasis patients were recruited, 25 of whom were randomized into the active group who received TL01 phototherapy together with twice-daily application of calcipotriol cream 50 microg g(-1). The control group received TL01 phototherapy and twice-daily application of a topical emollient as placebo. TL01 phototherapy was given three times per week starting at 70% minimal erythema dose with 20% increments as tolerated for up to approximately 20 sessions. Patients were assessed using the Psoriasis Area and Severity Index (PASI) and Psoriasis Disability Index (PDI). They were evaluated at treatment sessions 8, 14 and 20, and followed up at 5 and 10 weeks post-treatment. Statistical analysis was performed using a two-tailed t-test. RESULTS: There were no significant differences in demographic characteristics and baseline PASI and PDI scores between the two groups. The mean PASI score declined significantly (P < 0.01) for both groups after treatment. The difference in mean PASI score reduction from baseline between the two groups was only significant during the first eight sessions, with a net reduction of 3.6 (95% confidence interval 1.0-6.2, P = 0.008) in the active group relative to the control group. The mean PDI score declined significantly (P < 0.05) for both groups, but there was no statistical difference in mean PDI score reduction between the two groups (P = 0.8) at the end of treatment. The mean cumulative UVB dose for the active group was significantly lower (P < 0.02) at 16 204 mJ cm-2 compared with 21 082 mJ cm-2 for the control group. CONCLUSIONS: We conclude that combining TL01 phototherapy with topical calcipotriol cream has a UVB-sparing effect.
Eur J Dermatol. 2003 Jul-Aug;13(4):382-4. : Combination of calcipotriol and clobetasol propionate as a premixed ointment for the treatment of psoriasis.
Katoh N, Kishimoto S.
Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawara-machi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
nkatoh@koto.kpu-m.ac.jp
The treatment of psoriasis requires good compliance, efficacy and low toxicity because of its long-term course and wide distribution. The aim of the study was to compare the efficacy of a once daily application of calcipotriol alone or calcipotriol and a superpotent steroid in a premixed form in patients with psoriasis. The monotherapy group of 32 patients with stable plaque psoriasis received 0.005% calcipotriol alone once daily. The combination group of 29 patients was treated once per day with 0.004% calcipotriol/0.01% clobetasol propionate as a premixed ointment. Eruption score of truncal involvement was evaluated. The combination regimen was more efficacious than the monotherapy as evidenced by (1) more patients with at least 50% reduction in the eruption score after 2 weeks, (2) lower eruption score after 6 weeks and later, and (3) less adverse effects. The combined once-per-day application of 0.004% calcipotriol/0.01% clobetasol propionate as a premixed ointment is a promising regimen for psoriasis.
Eur J Dermatol. 2003 May-Jun;13(3):261-5. : Calcitriol ointment and clobetasol propionate cream: a new regimen for the treatment of plaque psoriasis.
Lahfa M, Mrowietz U, Koenig M, Simon JC.
Hopital Saint-Louis,1 avenue Claude Vellefaux, 25015 Paris, France.
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. Mini Rev Med Chem 2003 Jun;3(3):195-206 : Vitamin d receptor as a drug discovery target.
Pinette KV, Yee YK, Amegadzie BY, Nagpal S.
Gene Regulation, Bone and Inflammation Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN-46285, USA.
nagpal_sunil@lilly.com
1alpha, 25-dihydroxyvitamin D3 [1,25 (OH)(2)D(3)], the active metabolite of vitamin D3, is known for the maintenance of normal skeleton architecture and mineral homeostasis. Apart form these traditional calcemic actions, 1,25 (OH)(3)D(1) and its synthetic analogs are increasingly recognized for their potent anti-proliferative, prodifferentiative and immunomodulatory activities. The calcemic and non-calcemic actions of 1,25 (OH)(2)D(3) and its synthetic analogs are mediated through vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. Physiological and pharmacological actions of 1,25 (OH)(2)D(3) in various systems, along with the detection of VDR in target cells, have indicated potential applications of VDR ligands in inflammation, dermatological indications, osteoporosis, cancers and autoimmune diseases. VDR ligands have shown therapeutic potential in limited clinical trials as well as in animal models of these diseases. As a result, a VDR ligand, calcipotriol is in clinic for psoriasis and another, OCT, [2-oxa-1,25 (OH)(2)D(3)] is being developed as a topical agent for the same indication. Further, 1alpha,-hydroxyvitamin D3 (alphacalcidol), a prodrug of 1,25 (OH)(2)D(3) is in clinic and a synthetic VDR ligand, ED-71, is under consideration for approval in Japan for the treatment of osteoporosis. Interestingly, VDR ligands have shown not only preventive but also potent therapeutic anabolic activities in animal models of osteoporosis. However, the wide spread use of VDR ligands in above-mentioned indications is hampered by their major side effect, namely hypercalcemia. In view of this associated toxicity, synthetic VDR ligands with reduced calcemic potential have been synthesized with the ultimate aim of improving their therapeutic efficacy. This review presents recent advances in VDR biology, novel VDR ligands and therapeutic applications of VDR ligands.
Br J Dermatol. 2003 Apr;148(4):779-83. : Calcitriol vs. dithranol in combination with narrow-band ultraviolet B (311 nm) in psoriasis.
Hofmann UB, Eggert AA, Brocker EB, Goebeler M.
Department of Dermatology, University of Wurzburg, Josef-Schneider-Str. 2, D-97080 Wurzburg, Germany.
uta.hofmann@mail.uni-wuerzburg.de
BACKGROUND: Narrow-band ultraviolet (UV) B (311 nm) phototherapy is an effective treatment for psoriasis. In order to reduce cumulative UV doses and to enhance clearance of psoriasis plaques, combination therapies with topical agents such as dithranol and calcipotriol have been established. OBJECTIVES: To compare the clinical efficacy, in a half-side manner, of UVB (311 nm) in combination with either calcitriol or dithranol. METHODS: Ten patients with symmetrical stable plaque psoriasis were treated with narrow-band UVB (311 nm) five times a week. In addition, topical calcitriol was applied twice daily to one arm, whereas the other arm and the rest of the body were treated once daily with dithranol. The follow-up period was at least 4 weeks. Efficacy was assessed separately for both arms prior to treatment and once weekly thereafter by a modified Psoriasis Area and Severity Index (PASI) score. The cumulative irradiation dose and the number of treatment sessions required for clearance of psoriasis lesions were determined for each patient. Additionally, all patients completed a quality of life questionnaire. RESULTS: Both treatment modalities notably reduced the PASI score. A clinical comparison of UVB (311 nm) in combination with either calcitriol or dithranol revealed no significant therapeutic differences between the regimens. CONCLUSIONS: Combination of narrow-band UVB (311 nm) therapy with calcitriol is equally effective as the combination with dithranol for the treatment of psoriasis. However, patients preferred calcitriol rather than dithranol when both quality of life and treatment acceptability were assessed.
Br J Dermatol. 2003 Feb;148(2):318-25. : The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial.
de Jong EM, Mork NJ, Seijger MM, De La Brassine M, Lauharanta J, Jansen CT, Guilhou JJ, Guillot B, Ostrojic A, Souteyrand P, Vaillant L, Barnes L, Rogers S, Klaber MR, Van De Kerkhof PC.
Department of Dermatology, University Hospital Center St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
e.dejong@derma.wncn.nl
BACKGROUND: A multicentre, randomized, double-blind, vehicle-controlled, parallel-group study was carried out to study the effect of the addition of calcipotriol ointment to methotrexate (MTX) therapy in patients with psoriasis vulgaris. OBJECTIVES: To investigate whether the addition of calcipotriol to treatment with MTX has an MTX-sparing effect, and whether the combination of treatments is safe. Additionally, to compare the effect of calcipotriol or vehicle on the duration of the relapse-free interval after cessation of MTX. METHODS: Patients on maintenance therapy with MTX with controlled psoriasis were selected. The study was divided into three phases: (i) an MTX-free phase with double-blind treatment with either calcipotriol ointment or vehicle; (ii) an MTX titration phase with open MTX treatment and additional double-blind treatment with either calcipotriol or vehicle until target response; and (iii) follow-up phase: in a group of 97 patients, psoriasis was assessed using the modified psoriasis severity score, patients' assessment and safety parameters were monitored as well. RESULTS: The combined use of calcipotriol with MTX resulted in an MTX-sparing effect of 3.4 mg week-1 (phase (II) and 2.6 mg week-1 (phase I and II taken together), while still maintaining efficacy. Calcipotriol treatment increased the time to relapse of psoriasis following discontinuation of MTX: 113 days vs. 35 days. A decrease in aspartate aminotransferase and alanine aminotransferase was seen during the study of 8% (calcipotriol) and 12% (vehicle). CONCLUSIONS: The combination of calcipotriol and MTX was safe and well tolerated. The combination resulted in lower cumulative dosages of MTX compared with MTX and vehicle. Therefore the risk of side-effects is substantially decreased.
Am J Clin Dermatol. 2003;4(7):507-10. : The efficacy of calcipotriol + acitretin combination therapy for psoriasis: comparison with acitretin monotherapy.
Rim JH, Park JY, Choe YB, Youn JI.
Department of Dermatology, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
BACKGROUND: Although the use of an oral retinoid as monotherapy is an effective treatment for psoriasis, it is usually used in combination with other topical or systemic therapies including topical corticosteroids, UVB phototherapy, psoralens + UVA (PUVA) chemotherapy and cyclosporine mainly in an effort to reduce or avoid adverse effects. AIM: To compare the efficacy of the calcipotriol + acitretin combination treatment with acitretin alone over a long period in Korean patients with psoriasis. METHODS: A randomized, bilateral paired comparison was conducted involving 40 patients with psoriasis who received calcipotriol + acitretin combination therapy and 20 psoriasis patients who received acitretin alone. The initial dose of acitretin was 10 or 20 mg/day. The dose was adjusted at each visit (2, 4 and 6 weeks) in steps of 10mg according to patient responsiveness and adverse effects. The maximum dose was 40 mg/day. The treatment duration for all patients ranged from 4-52 weeks. After 12 weeks, the efficacy of therapy, according to Psoriasis Area and Severity Index scores, was assessed. At the end of the study (52 weeks), we selected patients who had achieved complete clearance and compared the duration of treatment and total dose of acitretin used in both groups. RESULTS: After 12 weeks, 16 patients (40%) achieved complete clearance in the calcipotriol + acitretin group and 3 patients (15%) in the acitretin monotherapy group (p < 0.05). After 52 weeks, 24 patients (60%) in the calcipotriol + acitretin group and 8 patients (40%) in the acitretin monotherapy group achieved complete clearance. The duration of treatment and total dose of retinoid required to achieve clearance were slightly lower in the calcipotriol + acitretin combination group, however, this was not statistically significant. With the exception of liver enzyme elevation (which affected more patients in the acitretin monotherapy group than in the combination group), adverse effects were not significantly different. DISCUSSION: Our results showed that calcipotriol might enhance the clinical outcome of systemic acitretin therapy. More large, well-controlled, long-term studies need to be conducted to determine whether there is indeed a beneficial effect of the addition of calcipotriol to acitretin treatment and whether this effect is maintained over long-term periods.
Am J Clin Dermatol. 2003;4(3):197-202. : Optimizing treatment with topical tazarotene.
Guenther LC.
Division of Dermatology, University of Western Ontario, London, Ontario, Canada.
Tazarotene is a receptor-selective retinoid, which is efficacious in the treatment of patients with psoriasis, acne vulgaris, and photoaging. It normalizes keratinocyte differentiation, reverses keratinocyte hyperproliferation, and has anti-inflammatory effects. Clinical studies have shown that tazarotene 0.1% gel has greater comedolytic activity than tretinoin (Retin-A 0.025% gel, Retin-A Micro 0.1%) and adapalene (Differin) 0.1% gel. Although it is efficacious as monotherapy, tazarotene is more commonly used as part of combination therapy with a topical antibacterial in patients with acne vulgaris, and with a mid- or high-potency topical corticosteroid or with phototherapy in patients with psoriasis. Combination therapy enhances efficacy and tolerability. Tazarotene 0.1% gel, used in combination with mometasone furoate 0.1% cream, was shown in psoriasis clinical trials to be more efficacious than calcipotriene (calcipotriol) ointment used twice daily, or mometasone furoate 0.1% cream used twice daily. Use of tazarotene in conjunction with broad band UVB, narrow band UVB or bath psoralens + UVA (PUVA) results in greater efficacy than with phototherapy alone. Tazarotene should not be administered during pregnancy or in women who are not practicing adequate contraception. Adverse events consist primarily of irritation, peeling, erythema, dryness, burning, and itching. They are most common during the first 1-2 weeks of therapy and can be minimized with use of the cream formulation, alternate day application, short contact therapy, mild cleansers, and combination therapy.
J Am Acad Dermatol. 2003 Jan;48(1):48-54. : Early onset of action and efficacy of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis.
Papp KA, Guenther L, Boyden B, Larsen FG, Harvima RJ, Guilhou JJ, Kaufmann R, Rogers S, van de Kerkhof PC, Hanssen LI, Tegner E, Burg G, Talbot D, Chu A.
Probity Medical Research, Waterloo, Ontario, Canada.
kapapp@probitymedical.com
BACKGROUND: Calcipotriene and betamethasone dipropionate are topical treatments for psoriasis vulgaris. Their mode of action is different. Improved risk/benefit may result with concomitant use of the two compounds together. A new vehicle has been created with the objective of obtaining optimal stability of both calcipotriene and betamethasone dipropionate in the combination product. OBJECTIVE: We compared the clinical efficacy of a fixed combination of calcipotriene and betamethasone dipropionate in a new vehicle to calcipotriene in the new vehicle, betamethasone in the new vehicle, and the new vehicle alone. METHODS: This was an international, multicenter, prospective, randomized, double-blind, parallel-group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. RESULTS: The mean percentage reduction in PASI from baseline to end of treatment was 73.2% in the combination group (n = 301), 48.8% in the calcipotriene group (n = 308), 63.1% in the betamethasone dipropionate group (n = 312) and 28.8% in the new vehicle group (n = 107), (P < .001). The mean percentage reduction in PASI during the first week was 48.1%, 28.4%, 41.4%, and 21.5%, respectively (P < .001). CONCLUSION: A combination product of calcipotriene 50 microg/g and betamethasone dipropionate 0.5 mg/g in the new vehicle shows superior efficacy with a more rapid onset of action than the new vehicle containing either constituent alone in the treatment of psoriasis vulgaris.
J Am Acad Dermatol 2003 Apr;48(4):564-8 : Tacrolimus ointment for the treatment of psoriasis on the face and intertriginous areas.
Freeman AK, Linowski GJ, Brady C, Lind L, Vanveldhuisen P, Singer G, Lebwohl M. Mount Sinai School of Medicine, Fujisawa Healthcare Incorporated, and the Emmes Corporation.
The safety and efficacy of 0.1% tacrolimus ointment for the treatment of psoriasis on the face, intertriginous areas, or both were evaluated in an open-label, clinical trial of 21 patients with psoriasis. Patients applied 0.1% tacrolimus ointment twice daily for 8 weeks. Efficacy was assessed through the investigator's evaluation of the individual signs and symptoms of psoriasis, and the physician's global evaluation of change in disease status. Assessments of cutaneous atrophy and other adverse events were made throughout the study to evaluate the safety of tacrolimus ointment. A total of 21 patients were enrolled in the study; 21 patients at least 18 years of age received study medication. Statistically significant improvement in the physician's assessment of the individual signs and symptoms was observed during the study. A total of 81% of patients (17 of 21) experienced complete clearance at day 57 (end of treatment). Only 2 patients reported adverse events, which were limited to itching and the feeling of warmth at the application site. None of the patients had atrophy, telangiectasia, or striae develop during the study. In summary, tacrolimus 0.1% ointment may be a safe and effective treatment option for patients with psoriasis on the face, intertriginous areas, or both.
Prescrire Int 2003 Apr;12(64):59-60
: Cutaneous ulceration with methotrexate.
(1) Low-dose methotrexate, as used to treat rheumatoid arthritis and psoriasis, can cause cutaneous and buccal ulceration. Ulceration of psoriatic plaques is a known adverse effect of methotrexate. Methotrexate can also trigger leg ulcers or make them worse. (2) Cutaneous ulceration has been reported with several other antimitotic and immunosuppressive drugs including hydroxycarbamide (hydroxyurea), tacrolimus, sirolimus, leflunomide, infliximab and etanercept.
Br J Dermatol 2003 Mar;148(3):444-451 : Beneficial effects of fumarate therapy in psoriasis vulgaris patients coincide with downregulation of type 1 cytokines.
Litjens NH, Nibbering PH, Barrois AJ, Zomerdijk TP, Van Den Oudenrijn AC, Noz KC, Rademaker M, Van De Meide PH, Van Dissel JT, Thio B.
Department of Infectious Diseases, C5-P, Leiden University Medical Center, 2300 RC Leiden, the Netherlands, Department of Dermatology, Leyenburg Hospital, The Hague, the Netherlands, U-CyTech, University of Utrecht, Utrecht, the Netherlands, Department of Dermatology and Venereology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
Background Fumarates have been shown to be effective in psoriasis vulgaris. Objectives To find out whether successful therapy is associated with modulation of cytokines. Methods We determined interferon (IFN)-gamma, interleukin (IL)-4 and IL-10 secretion capacities of peripheral blood mononuclear cells (PBMC) after phytohaemagglutinin stimulation, and IL-12p70 and IL-10 secretion capacities of PBMC after endotoxin stimulation in psoriasis vulgaris patients during treatment with fumarates. In a cohort study, 12 patients (five men, median age 50 years; seven women, median age 46 years) with psoriasis vulgaris were followed during 24 months of fumarate treatment. In addition, we followed 14 healthy controls (six men, median age 31 years; eight women, median age 29 years) without skin diseases during 12 months to investigate possible changes in the cytokine secretion capacity of PBMC as a result of seasonal changes. Disease activity in patients was determined by Psoriasis Area and Severity Index (PASI) score. Blood was collected for measurement by enzyme-linked immunosorbent assay of cytokine levels after stimulation of PBMC. Results Within 6 months of fumarate treatment, the mean +/- SD PASI score had decreased to 22 +/- 9% of its initial value. These beneficial effects coincided with lymphocytopenia and a significant (P < 0.05) downregulation of IFN-gamma expression by circulating blood cells, followed by a significant downregulation of IL-4 expression. Notably, production of the cytokine synthesis inhibitor IL-10 by PBMC was unchanged. Conclusions The beneficial effects of fumarates may be attributed to their downregulatory action on type 1 cytokines.
Am J Clin Dermatol 2003;4(2):131-9 : Effects of Alefacept on Health-Related Quality of Life in Patients with Psoriasis: Results from a Randomized, Placebo-Controlled Phase II Trial.
Ellis CN, Mordin MM, Adler EY.
Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
INTRODUCTION: Chronic plaque psoriasis has a profound impact on patient quality of life (QOL), including adverse psychosocial effects, impaired daily activities, anxiety, and depression. OBJECTIVE: To assess health-related QOL in a randomized phase II trial of alefacept (human LFA-3/IgG(1) fusion protein), a selective immunomodulator for psoriasis. Study design: Multicenter, randomized, placebo-controlled, double-blind trial. Methods: 229 patients with moderate to severe psoriasis were randomized to alefacept (0.025, 0.075, or 0.150 mg/kg) or placebo by 30-second intravenous bolus once weekly for 12 weeks and followed for 12 additional weeks. Patients completed a general (SF-36((R))1 Health Survey) and dermatology-specific (Dermatology Life Quality Index [DLQI] and Dermatology Quality Of Life Scales [DQOLS]) QOL surveys at each study visit. Results: Patients treated with alefacept had significantly greater improvements on dermatology-specific QOL scales compared with patients receiving placebo (p < 0.05). Patients who achieved a >/=50% or a >/=75% reduction in Psoriasis Area and Severity Index (PASI) reported similar improvement in QOL, which was significantly greater than that of other patients. Conclusions: The clinical effect of alefacept on psoriasis is associated with an improvement in patients' QOL. Among patients with moderate to severe psoriasis, an improvement in PASI of 50% or more is associated with better QOL scores.
DOVONEX CREAM calcipotriol is one form of topical treatment for Psoriasis.Dovonex, a synthetic topical form of vitamin D reduces the production of skin cells and thus slows down psoriasis. The skin grows usually every 28 days or so whereas in psoriasis, it grows every three to six days and forms plaques or lesions.
AS a user of Dovonex, I saw an improvement almost immediately in my psoriasis. Dovonex is generally used with mild psoriasis. A write up for Dovenex for psoriasis can be found hereat the Bristol Myers site. Psoriasis is often called an "immune-mediated" disorder where the immune system attacks itself. Close to five million people in the U.S. suffer from Psoriasis. Studies show there is a genetic component but as of yet don't know what triggers the outbreaks. Some say to avoid acidic food, alcohol, root vegetables and coffee but there is no firm research to back that up. Possible triggers for psoriasis are emotional stress, reactions to certain drugs such as lithium, ace inhibitors, and beta blockers. Changes in weather may be a trigger for psoriasis. Then there are skin trauma, and infection. .An indepth article can be found here
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J Cutan Med Surg. 2004 May 3 [Epub ahead of print] : Nail Psoriasis: Combined Therapy with Systemic Cyclosporin and Topical Calcipotriol.
Feliciani C, Zampetti A, Forleo P, Cerritelli L, Amerio P, Proietto G, Tulli A, Amerio P.
Department of Dermatology, Catholic University of the Sacred Heart, Rome, Italy.
BACKGROUND. Nail psoriasis is a common problem in psoriatic patients and often it is difficult to cure. Several treatments have been proposed in the last decade using new molecules like vitamin-D analog and/or immunosoppressive drugs both systemically and locally.OBJECTIVE. Our goal was to evaluate a combination of cyclosporin and topical calcipotriol cream versus cyclosporin alone in a matched group of patients treated with cyclosporin alone.METHOD. Fifty-four patients affected by severe psoriasis and nail involvement were selected and matched for severity of nail involvement, sex, age, and cyclosporin dosage. Group A included 21 patients treated with cyclosporin alone (3.5 mg/kg/day) for three months. Group B included 33 patients treated with the same cyclosporin dosage plus, for the same time, topical application of calcipotriol cream twice a day. Evaluation for clinical improvement was the personal feeling of the patient after three months, while clinical appearance of the lesions was evaluated by the same dermatologist using digital pictures and who was blind as to the treatment of the patient. A score ranging from + to +++ was used in order to evaluate the improvement, and data were statistically evaluated with the Wilcoxon test.RESULTS. Both cyclosporin alone and a combination of cyclosporin with topical calcipotriol twice a day were useful for treating nail psoriasis after three months of therapy although the combined therapy showed a better overall result in both mild and severe nail psoriasis. Improvement of the clinical appearance of the nail lesions was seen in about 79% of patients in group B ( p Dermatol Nurs. 2004 Feb;16(1):89-90, 93, 100. : Topical vitamin D analogs.
Kieffer MA.
Calcipotriene offers a safe and effective option in the treatment of plaque psoriasis. It helps regulate the abnormal growth and production of keratinocytes, as well as has a number of effects on inflammation seen with psoriasis. When used as monotherapy or in combination with corticosteroids, it may help reduce the adverse effects seen with chronic steroid use. Calcipotriene is currently only indicated for plaque psoriasis; however, it has shown promise for use in a wide range of dermatologic conditions
Exp Dermatol. 2004 Feb;13(2):106-12. : The effect of the combination of calcipotriol and betamethasone dipropionate versus both monotherapies on epidermal proliferation, keratinization and T-cell subsets in chronic plaque psoriasis.
Vissers WH, Berends M, Muys L, van Erp PE, de Jong EM, van de Kerkhof PC.
Department of Dermatology, University Medical Centre St Radboud, Nijmegen, The Netherlands.
w.vissers@derma.umcn.nl
Several reports have indicated that the combination of calcipotriol ointment and potent or ultrapotent corticosteroids are more effective and better tolerated, as compared to the monotherapies. The aim of the present study was to find out the effect of combination of calcipotriol ointment once daily and betamethasone dipropionate ointment once daily vs. the effect of twice-daily applications of each of the two treatments as monotherapy during a four-week treatment period. Seven patients with chronic plaque psoriasis were included for treatment with the three treatment schedules. Biopsies were taken before treatment and after four weeks of treatment, and markers for epidermal proliferation (Ki-67) and epidermal differentiation (keratin-10) were studied using a quantitative image analysis, and T-cell subsets in epidermis and dermis (CD4, CD8, CD25, CD45RO, CD45RA, CD94, CD161, and CD2) were studied using immunohistochemical scoring. The most impressive clinical result was reached with the combination. Calcipotriol proved to have a major effect on the proliferation marker Ki-67 and differentiation marker keratin-10, whereas the effect on T-cell subsets was more selective with major reductions of CD45RO(+) and CD8(+) T cells. In contrast, the effect of betamethasone dipropionate on the epidermis was restricted to a normalization of differentiation with a highly significant increase of keratin-10 positive epidermal surface without a significant effect on Ki-67 positive nuclei, and the effect on T-cell subsets was restricted to a reduction of natural killer T-cell receptors designated by CD94 and CD161 in the epidermis. The combination of the two treatments did not affect the proliferation marker Ki-67 and keratinization marker keratin-10, beyond the effect of calcipotriol monotherapy. However, the combination had a profound effect on, virtually, all T-cell subsets, beyond the effect of the monotherapies. It is concluded that the action spectra of calcipotriol and betamethasone on the psoriatic plaque are different and that the combination has effects on T-cell subsets, beyond the addition of the effects of monotherapies.
Am J Clin Dermatol. 2004;5(2):71-7. : Fixed-dose combination therapy for psoriasis.
Guenther LC.
The Guenther Dermatology Research Centre, London, Ontario, Canada.
Fixed-dose combination therapy offers stable products containing two or more medications with different mechanisms of action and safety profiles. It is also convenient for patients since only one product rather than two or more needs to be applied. Topical corticosteroids are often the mainstay of therapy in psoriasis. Diprosalic((R)) and Nerisalic((R)) contain a topical corticosteroid (betamethasone dipropionate and diflucortolone, respectively) and salicylic acid. A left/right study showed that both products have comparable efficacy. It has also been shown that betamethasone dipropionate + salicylic acid ointment has similar efficacy to clobetasol and calcipotriene (calcipotriol) ointments. Betamethasone dipropionate + salicylic acid lotion has similar efficacy to clobetasol lotion. Faster improvement of scaling, itching, and redness was noted with betamethasone dipropionate + salicylic acid lotion compared with betamethasone dipropionate alone. Dovobet((R)) (Daivobet((R))) ointment is a fixed-dose combination product containing betamethasone dipropionate and calcipotriene. Clinical studies have shown that it has greater efficacy and a faster speed of onset than the individual components or tacalcitol. Once daily and twice daily treatments have similar efficacy. Psoriasis Area and Severity Index reductions of approximately 40% after 1 week and 70% after 4 weeks of therapy were consistently noted in six large international studies involving >6000 patients. Betamethasone dipropionate + calcipotriene treatment is associated with approximately 75% less adverse cutaneous events as compared with tacalcitol, 50% less compared with calcipotriene, and a similar number as treatment with betamethasone dipropionate.
Int J Dermatol. 2003 Oct;42(10):834-8. : Calcipotriol versus coal tar: a prospective randomized study in stable plaque psoriasis.
Sharma V, Kaur I, Kumar B.
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
BACKGROUND: Topical therapies are the first line of treatment for patients with stable plaque psoriasis (SPP) affecting a limited body surface area. Very few trials comparing newer agents, such as 0.005% topical calcipotriol, with conventional modes of therapy, such as coal tar ointment, have been reported. METHODS: A prospective, right-left randomized, investigator-blinded study with a 12-week treatment period and an 8-week follow-up period was performed. Thirty-six patients with nearly bilaterally symmetrical SPP lesions on the limbs were instructed to apply 5% coal tar ointment overnight on one side once daily and 0.005% calcipotriol ointment on the other side twice a day. All patients were advised to expose both sides to the sun for 2 h every day. Psoriatic lesions and progress during treatment were evaluated using the severity (0-3) scale of erythema, scaling and induration (ESI score). Evaluation was carried out every 2 weeks during the treatment period and monthly during follow-up. At the end of 12 weeks, patients with > 75% reduction in the ESI score were considered to be markedly improved, those with 51-75% reduction to be moderately improved, those with 26-50% reduction to be minimally improved and those with < 25% to be non-responders. Self-assessment by the patients regarding the efficacy and acceptability of the two modalities was on a five-point scale. Serum calcium, serum phosphate, total and differential serum proteins, 24-h urinary calcium and phosphate were monitored both at baseline and after completion of therapy. RESULTS: Thirty of the 36 recruited patients completed the study. The difference in clinical response between the two sides was statistically significant at 4, 6 and 8 weeks, with the percentage reduction in ESI score with calcipotriol being 65.7 +/- 12.2% compared with 45.8 +/- 16.6% with coal tar at 8 weeks (P < 0.01, t = 6.4). However, the difference in clinical response at 10 and 12 weeks between the two sides was not significant, with a mean reduction of 71.9 +/- 13.3% in ESI score on the calcipotriol-treated side compared with 69.4 +/- 15.4% with coal tar ointment (P > 0.05). In the follow-up period of 8 weeks, recurrence of lesions was noted in 10% of patients treated with calcipotriol compared with 16.7% in those treated with coal tar after an average period of 6 +/- 1.2 and 5 +/- 1.3 weeks, respectively (P > 0.05). CONCLUSIONS: It was found that 0.005% calcipotriol ointment produced a faster initial response and had better cosmetic acceptability in patients, although after a long period of treatment, i.e. 12 weeks, 5% coal tar ointment had comparable efficacy. There was no statistically significant difference in the relapse rates between the two modalities.
Br J Dermatol. 2003 Aug;149(2):350-3. : Observer-blind, randomized, intrapatient comparison of a novel 1% coal tar preparation (Exorex) and calcipotriol cream in the treatment of plaque type psoriasis.
Tzaneva S, Honigsmann H, Tanew A.
Division of Special and Environmental Dermatology, Department of Dermatology, University of Vienna Medical School, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
BACKGROUND: In a recent pilot study a novel, patented fatty acid-based 1% coal tar preparation (Exorex) has been found to be similar in efficacy to calcipotriol in the treatment of psoriasis. OBJECTIVES: Our aim was to investigate the therapeutic efficacy, safety and cosmetic acceptability of the new 1% coal tar preparation in comparison with calcipotriol cream in a larger patient cohort. PATIENTS AND METHODS: Forty patients with chronic plaque type psoriasis were included in this randomized, observer-blind, intrapatient comparison trial. In each patient two comparable target plaques were treated twice daily with 1% coal tar preparation or calcipotriol cream. At the onset of therapy and at weeks 2, 4, 6 and 8, the response to treatment was determined by the psoriasis severity index (PSI) that assesses the degree of erythema, infiltration and scaling of the psoriatic lesions on a five-point scale. In addition, all treatment-related side-effects were recorded and cosmetic acceptability of both treatments was rated every second week by the patients. After complete or near complete clearing the patients were followed up until relapse or for a maximum period of 18 months. RESULTS: Thirty-eight patients completed the study. At termination of the trial the mean +/- SD baseline PSI score of 9.2 +/- 1.5 was reduced to 3.0 +/- 2.9 by 1% coal tar preparation and to 2.8 +/- 2.7 by calcipotriol. The mean PSI reduction between baseline and final assessment did not differ significantly between 1% coal tar preparation and calcipotriol (P = 0.77). The mean intraindividual difference in reduction of PSI score between 1% coal tar preparation and calcipotriol was 0.1 score points (95% confidence interval - 0.84 to + 0.63). No difference between either preparation was observed with regard to time until relapse. Itching was caused by 1% coal tar preparation in four patients and by calcipotriol in one patient. Unpleasant odour or staining of the 1% coal tar preparation was reported by six patients, whereas one patient complained about the smell of the calcipotriol cream. CONCLUSIONS: The novel 1% coal tar preparation was found to be comparably as effective as calcipotriol in treating psoriasis. Tolerability and cosmetic acceptability was better for calcipotriol. Taking into consideration that the coal tar preparation is considerably less expensive than calcipotriol this new product appears as a very useful topical medication for chronic plaque type psoriasis.
Br J Dermatol. 2003 Jul;149(1):146-50. : Combination TL01 ultraviolet B phototherapy and topical calcipotriol for psoriasis: a prospective randomized placebo-controlled clinical trial.
Woo WK, McKenna KE.
Department of Dermatology, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, U.K.
keithwoo@doctors.org.uk
BACKGROUND: Previous studies have demonstrated the ultraviolet (UV)-sparing effect of combining topical calcipotriol with broadband UVB in the treatment of psoriasis. OBJECTIVES: To determine if the combination of narrowband TL01 UVB phototherapy and topical calcipotriol produces the same UVB-sparing effect. METHODS: This was a randomized, placebo-controlled, blinded clinical trial. Fifty psoriasis patients were recruited, 25 of whom were randomized into the active group who received TL01 phototherapy together with twice-daily application of calcipotriol cream 50 microg g(-1). The control group received TL01 phototherapy and twice-daily application of a topical emollient as placebo. TL01 phototherapy was given three times per week starting at 70% minimal erythema dose with 20% increments as tolerated for up to approximately 20 sessions. Patients were assessed using the Psoriasis Area and Severity Index (PASI) and Psoriasis Disability Index (PDI). They were evaluated at treatment sessions 8, 14 and 20, and followed up at 5 and 10 weeks post-treatment. Statistical analysis was performed using a two-tailed t-test. RESULTS: There were no significant differences in demographic characteristics and baseline PASI and PDI scores between the two groups. The mean PASI score declined significantly (P < 0.01) for both groups after treatment. The difference in mean PASI score reduction from baseline between the two groups was only significant during the first eight sessions, with a net reduction of 3.6 (95% confidence interval 1.0-6.2, P = 0.008) in the active group relative to the control group. The mean PDI score declined significantly (P < 0.05) for both groups, but there was no statistical difference in mean PDI score reduction between the two groups (P = 0.8) at the end of treatment. The mean cumulative UVB dose for the active group was significantly lower (P < 0.02) at 16 204 mJ cm-2 compared with 21 082 mJ cm-2 for the control group. CONCLUSIONS: We conclude that combining TL01 phototherapy with topical calcipotriol cream has a UVB-sparing effect.
Eur J Dermatol. 2003 Jul-Aug;13(4):382-4. : Combination of calcipotriol and clobetasol propionate as a premixed ointment for the treatment of psoriasis.
Katoh N, Kishimoto S.
Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawara-machi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
nkatoh@koto.kpu-m.ac.jp
The treatment of psoriasis requires good compliance, efficacy and low toxicity because of its long-term course and wide distribution. The aim of the study was to compare the efficacy of a once daily application of calcipotriol alone or calcipotriol and a superpotent steroid in a premixed form in patients with psoriasis. The monotherapy group of 32 patients with stable plaque psoriasis received 0.005% calcipotriol alone once daily. The combination group of 29 patients was treated once per day with 0.004% calcipotriol/0.01% clobetasol propionate as a premixed ointment. Eruption score of truncal involvement was evaluated. The combination regimen was more efficacious than the monotherapy as evidenced by (1) more patients with at least 50% reduction in the eruption score after 2 weeks, (2) lower eruption score after 6 weeks and later, and (3) less adverse effects. The combined once-per-day application of 0.004% calcipotriol/0.01% clobetasol propionate as a premixed ointment is a promising regimen for psoriasis.
Eur J Dermatol. 2003 May-Jun;13(3):261-5. : Calcitriol ointment and clobetasol propionate cream: a new regimen for the treatment of plaque psoriasis.
Lahfa M, Mrowietz U, Koenig M, Simon JC.
Hopital Saint-Louis,1 avenue Claude Vellefaux, 25015 Paris, France.
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. Mini Rev Med Chem 2003 Jun;3(3):195-206 : Vitamin d receptor as a drug discovery target.
Pinette KV, Yee YK, Amegadzie BY, Nagpal S.
Gene Regulation, Bone and Inflammation Research, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN-46285, USA.
nagpal_sunil@lilly.com
1alpha, 25-dihydroxyvitamin D3 [1,25 (OH)(2)D(3)], the active metabolite of vitamin D3, is known for the maintenance of normal skeleton architecture and mineral homeostasis. Apart form these traditional calcemic actions, 1,25 (OH)(3)D(1) and its synthetic analogs are increasingly recognized for their potent anti-proliferative, prodifferentiative and immunomodulatory activities. The calcemic and non-calcemic actions of 1,25 (OH)(2)D(3) and its synthetic analogs are mediated through vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. Physiological and pharmacological actions of 1,25 (OH)(2)D(3) in various systems, along with the detection of VDR in target cells, have indicated potential applications of VDR ligands in inflammation, dermatological indications, osteoporosis, cancers and autoimmune diseases. VDR ligands have shown therapeutic potential in limited clinical trials as well as in animal models of these diseases. As a result, a VDR ligand, calcipotriol is in clinic for psoriasis and another, OCT, [2-oxa-1,25 (OH)(2)D(3)] is being developed as a topical agent for the same indication. Further, 1alpha,-hydroxyvitamin D3 (alphacalcidol), a prodrug of 1,25 (OH)(2)D(3) is in clinic and a synthetic VDR ligand, ED-71, is under consideration for approval in Japan for the treatment of osteoporosis. Interestingly, VDR ligands have shown not only preventive but also potent therapeutic anabolic activities in animal models of osteoporosis. However, the wide spread use of VDR ligands in above-mentioned indications is hampered by their major side effect, namely hypercalcemia. In view of this associated toxicity, synthetic VDR ligands with reduced calcemic potential have been synthesized with the ultimate aim of improving their therapeutic efficacy. This review presents recent advances in VDR biology, novel VDR ligands and therapeutic applications of VDR ligands.
Br J Dermatol. 2003 Apr;148(4):779-83. : Calcitriol vs. dithranol in combination with narrow-band ultraviolet B (311 nm) in psoriasis.
Hofmann UB, Eggert AA, Brocker EB, Goebeler M.
Department of Dermatology, University of Wurzburg, Josef-Schneider-Str. 2, D-97080 Wurzburg, Germany.
uta.hofmann@mail.uni-wuerzburg.de
BACKGROUND: Narrow-band ultraviolet (UV) B (311 nm) phototherapy is an effective treatment for psoriasis. In order to reduce cumulative UV doses and to enhance clearance of psoriasis plaques, combination therapies with topical agents such as dithranol and calcipotriol have been established. OBJECTIVES: To compare the clinical efficacy, in a half-side manner, of UVB (311 nm) in combination with either calcitriol or dithranol. METHODS: Ten patients with symmetrical stable plaque psoriasis were treated with narrow-band UVB (311 nm) five times a week. In addition, topical calcitriol was applied twice daily to one arm, whereas the other arm and the rest of the body were treated once daily with dithranol. The follow-up period was at least 4 weeks. Efficacy was assessed separately for both arms prior to treatment and once weekly thereafter by a modified Psoriasis Area and Severity Index (PASI) score. The cumulative irradiation dose and the number of treatment sessions required for clearance of psoriasis lesions were determined for each patient. Additionally, all patients completed a quality of life questionnaire. RESULTS: Both treatment modalities notably reduced the PASI score. A clinical comparison of UVB (311 nm) in combination with either calcitriol or dithranol revealed no significant therapeutic differences between the regimens. CONCLUSIONS: Combination of narrow-band UVB (311 nm) therapy with calcitriol is equally effective as the combination with dithranol for the treatment of psoriasis. However, patients preferred calcitriol rather than dithranol when both quality of life and treatment acceptability were assessed.
Br J Dermatol. 2003 Feb;148(2):318-25. : The combination of calcipotriol and methotrexate compared with methotrexate and vehicle in psoriasis: results of a multicentre placebo-controlled randomized trial.
de Jong EM, Mork NJ, Seijger MM, De La Brassine M, Lauharanta J, Jansen CT, Guilhou JJ, Guillot B, Ostrojic A, Souteyrand P, Vaillant L, Barnes L, Rogers S, Klaber MR, Van De Kerkhof PC.
Department of Dermatology, University Hospital Center St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
e.dejong@derma.wncn.nl
BACKGROUND: A multicentre, randomized, double-blind, vehicle-controlled, parallel-group study was carried out to study the effect of the addition of calcipotriol ointment to methotrexate (MTX) therapy in patients with psoriasis vulgaris. OBJECTIVES: To investigate whether the addition of calcipotriol to treatment with MTX has an MTX-sparing effect, and whether the combination of treatments is safe. Additionally, to compare the effect of calcipotriol or vehicle on the duration of the relapse-free interval after cessation of MTX. METHODS: Patients on maintenance therapy with MTX with controlled psoriasis were selected. The study was divided into three phases: (i) an MTX-free phase with double-blind treatment with either calcipotriol ointment or vehicle; (ii) an MTX titration phase with open MTX treatment and additional double-blind treatment with either calcipotriol or vehicle until target response; and (iii) follow-up phase: in a group of 97 patients, psoriasis was assessed using the modified psoriasis severity score, patients' assessment and safety parameters were monitored as well. RESULTS: The combined use of calcipotriol with MTX resulted in an MTX-sparing effect of 3.4 mg week-1 (phase (II) and 2.6 mg week-1 (phase I and II taken together), while still maintaining efficacy. Calcipotriol treatment increased the time to relapse of psoriasis following discontinuation of MTX: 113 days vs. 35 days. A decrease in aspartate aminotransferase and alanine aminotransferase was seen during the study of 8% (calcipotriol) and 12% (vehicle). CONCLUSIONS: The combination of calcipotriol and MTX was safe and well tolerated. The combination resulted in lower cumulative dosages of MTX compared with MTX and vehicle. Therefore the risk of side-effects is substantially decreased.
Am J Clin Dermatol. 2003;4(7):507-10. : The efficacy of calcipotriol + acitretin combination therapy for psoriasis: comparison with acitretin monotherapy.
Rim JH, Park JY, Choe YB, Youn JI.
Department of Dermatology, Seoul National University College of Medicine and Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea
BACKGROUND: Although the use of an oral retinoid as monotherapy is an effective treatment for psoriasis, it is usually used in combination with other topical or systemic therapies including topical corticosteroids, UVB phototherapy, psoralens + UVA (PUVA) chemotherapy and cyclosporine mainly in an effort to reduce or avoid adverse effects. AIM: To compare the efficacy of the calcipotriol + acitretin combination treatment with acitretin alone over a long period in Korean patients with psoriasis. METHODS: A randomized, bilateral paired comparison was conducted involving 40 patients with psoriasis who received calcipotriol + acitretin combination therapy and 20 psoriasis patients who received acitretin alone. The initial dose of acitretin was 10 or 20 mg/day. The dose was adjusted at each visit (2, 4 and 6 weeks) in steps of 10mg according to patient responsiveness and adverse effects. The maximum dose was 40 mg/day. The treatment duration for all patients ranged from 4-52 weeks. After 12 weeks, the efficacy of therapy, according to Psoriasis Area and Severity Index scores, was assessed. At the end of the study (52 weeks), we selected patients who had achieved complete clearance and compared the duration of treatment and total dose of acitretin used in both groups. RESULTS: After 12 weeks, 16 patients (40%) achieved complete clearance in the calcipotriol + acitretin group and 3 patients (15%) in the acitretin monotherapy group (p < 0.05). After 52 weeks, 24 patients (60%) in the calcipotriol + acitretin group and 8 patients (40%) in the acitretin monotherapy group achieved complete clearance. The duration of treatment and total dose of retinoid required to achieve clearance were slightly lower in the calcipotriol + acitretin combination group, however, this was not statistically significant. With the exception of liver enzyme elevation (which affected more patients in the acitretin monotherapy group than in the combination group), adverse effects were not significantly different. DISCUSSION: Our results showed that calcipotriol might enhance the clinical outcome of systemic acitretin therapy. More large, well-controlled, long-term studies need to be conducted to determine whether there is indeed a beneficial effect of the addition of calcipotriol to acitretin treatment and whether this effect is maintained over long-term periods.
Am J Clin Dermatol. 2003;4(3):197-202. : Optimizing treatment with topical tazarotene.
Guenther LC.
Division of Dermatology, University of Western Ontario, London, Ontario, Canada.
Tazarotene is a receptor-selective retinoid, which is efficacious in the treatment of patients with psoriasis, acne vulgaris, and photoaging. It normalizes keratinocyte differentiation, reverses keratinocyte hyperproliferation, and has anti-inflammatory effects. Clinical studies have shown that tazarotene 0.1% gel has greater comedolytic activity than tretinoin (Retin-A 0.025% gel, Retin-A Micro 0.1%) and adapalene (Differin) 0.1% gel. Although it is efficacious as monotherapy, tazarotene is more commonly used as part of combination therapy with a topical antibacterial in patients with acne vulgaris, and with a mid- or high-potency topical corticosteroid or with phototherapy in patients with psoriasis. Combination therapy enhances efficacy and tolerability. Tazarotene 0.1% gel, used in combination with mometasone furoate 0.1% cream, was shown in psoriasis clinical trials to be more efficacious than calcipotriene (calcipotriol) ointment used twice daily, or mometasone furoate 0.1% cream used twice daily. Use of tazarotene in conjunction with broad band UVB, narrow band UVB or bath psoralens + UVA (PUVA) results in greater efficacy than with phototherapy alone. Tazarotene should not be administered during pregnancy or in women who are not practicing adequate contraception. Adverse events consist primarily of irritation, peeling, erythema, dryness, burning, and itching. They are most common during the first 1-2 weeks of therapy and can be minimized with use of the cream formulation, alternate day application, short contact therapy, mild cleansers, and combination therapy.
J Am Acad Dermatol. 2003 Jan;48(1):48-54. : Early onset of action and efficacy of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis.
Papp KA, Guenther L, Boyden B, Larsen FG, Harvima RJ, Guilhou JJ, Kaufmann R, Rogers S, van de Kerkhof PC, Hanssen LI, Tegner E, Burg G, Talbot D, Chu A.
Probity Medical Research, Waterloo, Ontario, Canada.
kapapp@probitymedical.com
BACKGROUND: Calcipotriene and betamethasone dipropionate are topical treatments for psoriasis vulgaris. Their mode of action is different. Improved risk/benefit may result with concomitant use of the two compounds together. A new vehicle has been created with the objective of obtaining optimal stability of both calcipotriene and betamethasone dipropionate in the combination product. OBJECTIVE: We compared the clinical efficacy of a fixed combination of calcipotriene and betamethasone dipropionate in a new vehicle to calcipotriene in the new vehicle, betamethasone in the new vehicle, and the new vehicle alone. METHODS: This was an international, multicenter, prospective, randomized, double-blind, parallel-group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. RESULTS: The mean percentage reduction in PASI from baseline to end of treatment was 73.2% in the combination group (n = 301), 48.8% in the calcipotriene group (n = 308), 63.1% in the betamethasone dipropionate group (n = 312) and 28.8% in the new vehicle group (n = 107), (P < .001). The mean percentage reduction in PASI during the first week was 48.1%, 28.4%, 41.4%, and 21.5%, respectively (P < .001). CONCLUSION: A combination product of calcipotriene 50 microg/g and betamethasone dipropionate 0.5 mg/g in the new vehicle shows superior efficacy with a more rapid onset of action than the new vehicle containing either constituent alone in the treatment of psoriasis vulgaris.
J Am Acad Dermatol 2003 Apr;48(4):564-8 : Tacrolimus ointment for the treatment of psoriasis on the face and intertriginous areas.
Freeman AK, Linowski GJ, Brady C, Lind L, Vanveldhuisen P, Singer G, Lebwohl M. Mount Sinai School of Medicine, Fujisawa Healthcare Incorporated, and the Emmes Corporation.
The safety and efficacy of 0.1% tacrolimus ointment for the treatment of psoriasis on the face, intertriginous areas, or both were evaluated in an open-label, clinical trial of 21 patients with psoriasis. Patients applied 0.1% tacrolimus ointment twice daily for 8 weeks. Efficacy was assessed through the investigator's evaluation of the individual signs and symptoms of psoriasis, and the physician's global evaluation of change in disease status. Assessments of cutaneous atrophy and other adverse events were made throughout the study to evaluate the safety of tacrolimus ointment. A total of 21 patients were enrolled in the study; 21 patients at least 18 years of age received study medication. Statistically significant improvement in the physician's assessment of the individual signs and symptoms was observed during the study. A total of 81% of patients (17 of 21) experienced complete clearance at day 57 (end of treatment). Only 2 patients reported adverse events, which were limited to itching and the feeling of warmth at the application site. None of the patients had atrophy, telangiectasia, or striae develop during the study. In summary, tacrolimus 0.1% ointment may be a safe and effective treatment option for patients with psoriasis on the face, intertriginous areas, or both.
Prescrire Int 2003 Apr;12(64):59-60
: Cutaneous ulceration with methotrexate.
(1) Low-dose methotrexate, as used to treat rheumatoid arthritis and psoriasis, can cause cutaneous and buccal ulceration. Ulceration of psoriatic plaques is a known adverse effect of methotrexate. Methotrexate can also trigger leg ulcers or make them worse. (2) Cutaneous ulceration has been reported with several other antimitotic and immunosuppressive drugs including hydroxycarbamide (hydroxyurea), tacrolimus, sirolimus, leflunomide, infliximab and etanercept.
Br J Dermatol 2003 Mar;148(3):444-451 : Beneficial effects of fumarate therapy in psoriasis vulgaris patients coincide with downregulation of type 1 cytokines.
Litjens NH, Nibbering PH, Barrois AJ, Zomerdijk TP, Van Den Oudenrijn AC, Noz KC, Rademaker M, Van De Meide PH, Van Dissel JT, Thio B.
Department of Infectious Diseases, C5-P, Leiden University Medical Center, 2300 RC Leiden, the Netherlands, Department of Dermatology, Leyenburg Hospital, The Hague, the Netherlands, U-CyTech, University of Utrecht, Utrecht, the Netherlands, Department of Dermatology and Venereology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
Background Fumarates have been shown to be effective in psoriasis vulgaris. Objectives To find out whether successful therapy is associated with modulation of cytokines. Methods We determined interferon (IFN)-gamma, interleukin (IL)-4 and IL-10 secretion capacities of peripheral blood mononuclear cells (PBMC) after phytohaemagglutinin stimulation, and IL-12p70 and IL-10 secretion capacities of PBMC after endotoxin stimulation in psoriasis vulgaris patients during treatment with fumarates. In a cohort study, 12 patients (five men, median age 50 years; seven women, median age 46 years) with psoriasis vulgaris were followed during 24 months of fumarate treatment. In addition, we followed 14 healthy controls (six men, median age 31 years; eight women, median age 29 years) without skin diseases during 12 months to investigate possible changes in the cytokine secretion capacity of PBMC as a result of seasonal changes. Disease activity in patients was determined by Psoriasis Area and Severity Index (PASI) score. Blood was collected for measurement by enzyme-linked immunosorbent assay of cytokine levels after stimulation of PBMC. Results Within 6 months of fumarate treatment, the mean +/- SD PASI score had decreased to 22 +/- 9% of its initial value. These beneficial effects coincided with lymphocytopenia and a significant (P < 0.05) downregulation of IFN-gamma expression by circulating blood cells, followed by a significant downregulation of IL-4 expression. Notably, production of the cytokine synthesis inhibitor IL-10 by PBMC was unchanged. Conclusions The beneficial effects of fumarates may be attributed to their downregulatory action on type 1 cytokines.
Am J Clin Dermatol 2003;4(2):131-9 : Effects of Alefacept on Health-Related Quality of Life in Patients with Psoriasis: Results from a Randomized, Placebo-Controlled Phase II Trial.
Ellis CN, Mordin MM, Adler EY.
Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
INTRODUCTION: Chronic plaque psoriasis has a profound impact on patient quality of life (QOL), including adverse psychosocial effects, impaired daily activities, anxiety, and depression. OBJECTIVE: To assess health-related QOL in a randomized phase II trial of alefacept (human LFA-3/IgG(1) fusion protein), a selective immunomodulator for psoriasis. Study design: Multicenter, randomized, placebo-controlled, double-blind trial. Methods: 229 patients with moderate to severe psoriasis were randomized to alefacept (0.025, 0.075, or 0.150 mg/kg) or placebo by 30-second intravenous bolus once weekly for 12 weeks and followed for 12 additional weeks. Patients completed a general (SF-36((R))1 Health Survey) and dermatology-specific (Dermatology Life Quality Index [DLQI] and Dermatology Quality Of Life Scales [DQOLS]) QOL surveys at each study visit. Results: Patients treated with alefacept had significantly greater improvements on dermatology-specific QOL scales compared with patients receiving placebo (p < 0.05). Patients who achieved a >/=50% or a >/=75% reduction in Psoriasis Area and Severity Index (PASI) reported similar improvement in QOL, which was significantly greater than that of other patients. Conclusions: The clinical effect of alefacept on psoriasis is associated with an improvement in patients' QOL. Among patients with moderate to severe psoriasis, an improvement in PASI of 50% or more is associated with better QOL scores.