Calcipotriol/betamethasone (Dovobet) ointment for the treatment of adult patients with psoriasis vulgaris

06 Mar 2009 Calcipotriol/betamethasone (Dovobet) ointment for the treatment of adult patients with psoriasis vulgaris

Introduction: This report is a systematic review of Dovobet™ ointment in the treatment of adult patients with psoriasis vulgaris.

Drug

Dovobet™ (Betamethasone dipropionate/Calcipotriol) is a combination of the vitamin D analogue calcipotriol and the corticosteroid betamethasone dipropionate. Calcipotriol (Cal) is a non-steroidal antipsoriatic agent, derived from naturally occurring vitamin D. It is recommended to be applied once daily for duration of 4 weeks.

Disease

Psoriasis is a chronic immune-mediated, hyperproliferative disease of the skin and estimated to affect 2% of the population (Christophers 2001). Spontaneous remission is rare. There is currently no universally accepted definition of disease severity. The psoriasis area and severity index (PASI) is used in clinical trials for assessing disease severity. It is a composite score of disease extent, lesion erythema, scaling and induration and ranges from 0-72 . In general, a PASI score of 5-12 is considered moderate disease and a score over 12 is considered severe.

Current standards of treatment

Traditionally, psoriasis is managed using a step-wise approach, beginning with topical therapy [corticosteroids, calcipotriol, tazarotene, tar, anthralin and keratolytics] and progressing to phototherapy [broadband (290 – 320 nm) ultraviolet light B (UVB), narrowband (311 nm) UVB and psoralen plus ultraviolet light A (PUVA)] and then systemic therapy [retinoids (acitretin, tazarotene), mycophenolate mofetil, methotrexate and cyclosporine] (Lebwohl 2001, Ashcroft 2000).

Research questions

1. Does Dovobet™ ointment (Bet 0.5mg/g and Cal 50mcg/g) once a day provide a therapeutic advantage compared to either one of the individual components used at the same dose in published double blind randomized controlled trials (RCTs) of at least 4 weeks duration in adult patients with psoriasis?
2. Does Dovobet™ ointment (Bet 0.5mg/g and Cal 50mcg/g) once a day provide a therapeutic advantage compared to both the individual components used at the same dose, either at the same time or at different times on the same day, in published double blind randomized controlled trials (RCTs) of at least 4 weeks duration in adult patients with psoriasis?

Assessment principles

Included trials are full reports of published double-blind randomized controlled trials of adults with psoriasis vulgaris comparing Dovobet™ ointment (BDP 0.5mg/g and C 50mcg/g) to either one of the individual components used at the same dose or both the individual components used at the same dose, either at the same time or at different times on the same day. Therapeutic advantage will be assessed according to the following hierarchy of health outcomes – all-cause mortality; non-fatal serious adverse events; Quality of life (QOL) using validated measures including Dermatological Quality of Life Index (DQLI); Clinicians Global assessment and Patients Global Assessment; reduction in disease severity [includes percentage of patients achieving PASI 90, PASI 75, PASI 50, < PASI 50 response); time to achieving PASI 75 response; maintaining reduction in disease severity (i.e. duration of PASI 75 response); proportion of patients relapsing to baseline PASI score during continued treatment or following discontinuation of treatment; withdrawal due to adverse events and total adverse events.

Search strategy and findings: MEDLINE database (1966-Dec. 2008), EMBASE (1980- Dec. 2008), and the Cochrane database of systematic reviews and CENTRAL (issue 4, 2008). Key search words included Dovobet, calcipotriol, betamethasone, randomized controlled trials and randomized clinical trials. Three double blind RCTs met the inclusion criteria.

Results and Overall summary

Three double blind randomized controlled trials (Guenther 2002, Kaufman 2002 and Kragballe 2006) ranging from 4 to 52 weeks duration compared Dovobet™ ointment to calcipotriol used at the same dose in 3067 patients. One of these trials (4 weeks duration) also compared Dovobet to betamethasone alone. The trials did not report on serious adverse events, or quality of life. All trials report mean percentage change in PASI score. This is problematic in that the mean change in PASI does not indicate how many patients had a clinically relevant improvement (Katz 2005). None of the trials report how many patients achieve reductions in disease severity (PASI 90, 75 or 50% response), or time to achieving that response, nor did they report data on maintenance of a response. Also of interest is the number of patients relapsing to baseline PASI score during continued treatment or worsening following discontinuation of treatment. Dovobet™ ointment once daily leads to 2% fewer patients withdrawing (95%CI 0% to 4%, p=0.03) due to adverse events and 11% fewer patients having at least one adverse event (95%CI 6% to 16%, p=0.00001) than calcipotriol ointment once daily.

There were no trials identified that compared Dovobet™ ointment to both the individual components used at the same dose, either at the same time or at different times on the same day.

Conclusions

1. There is insufficient evidence that Dovobet™ ointment (Bet 0.5mg/g and Cal 50mcg/g) once a day provides a therapeutic advantage compared to either one of the individual components used at the same dose (either once or twice daily) in published double blind randomized controlled trials (RCTs) of at least 4 weeks duration in adult patients with psoriasis. Dovobet™ ointment once daily leads to 2% fewer patients withdrawing (95%CI 0% to 4%, p=0.03) due to adverse events than calcipotriol ointment once daily. Dovobet™ ointment once daily leads to 11% fewer patients having at least one adverse event (95%CI 6% to 16%, p=0.00001) than calcipotriol ointment once daily.
2. There is no evidence to suggest that Dovobet™ ointment (Bet 0.5mg/g and Cal 50mcg/g) applied topically once a day provides a therapeutic advantage compared to both the individual components used at the same dose (either once or twice daily, either at the same time or at different times on the same day in published double blind randomized controlled trials (RCTs) of at least 4 weeks duration in adult patients with psoriasis.

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