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Efficacy and local safety of a calcipotriol/ betamethasone dipropionate ointment in elderly patients with psoriasis vulgaris

European Journal of Dermatology. Volume 15, Number 1, 37-9, January-February 2005, Therapy

Summary

Author(s) : Richard Parslew, Jette Traulsen , Royal Liverpool and Broadgreen University Hospitals Trust, Liverpool L69 3BX, England Fax: +44 (0)151 282 6899., LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark.

Summary : The proportion of elderly patients with psoriasis vulgaris is set to increase in the future due to an ageing population. This descriptive analysis assessed the efficacy and safety of a new ointment containing calcipotriol and betamethasone dipropionate (Daivobet ^®/Dovobet ^®) in a pooled analysis of patients aged 60 years and over. A total of 1534 patients, including 357 aged ≥ 60 years, with psoriasis vulgaris received the two-compound ointment once-daily in four randomised, double-blind, studies. After 4 weeks treatment the mean reduction in PASI was 67.8% in patients <\; 60 years compared with 72.6% in patients ≥ 60 years. “Controlled disease” (i.e. a global assessment of “absence of disease” or “very mild disease”), according to the investigators, was achieved by 52.1% of patients <\; 60 years and 58.2% of patients ≥ 60 years. Patients in both age groups reported a similar number of lesional/perilesional adverse drug reactions\; 6.4% in patients <\; 60 years vs 5.0% in patients ≥ 60 years. Thus, the new two-compound ointment is effective and well-tolerated in the treatment of psoriasis vulgaris, regardless of age group.

Keywords : betamethasone dipropionate, calcipotriol, geriatric, psoriasis therapy

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ARTICLE

Auteur(s) :, Richard Parslew^1,*, Jette Traulsen²

¹Royal Liverpool and Broadgreen University Hospitals Trust, Liverpool L69 3BX, England Fax: +44 (0)151 282 6899.
²LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark

accepté le 11 Octobre 2004

Population demographics in most industrialised countries are changing, with rapidly increasing proportions of elderly people. Statistical projections for the USA indicate that the elderly (> 60 years) will constitute up to a quarter of the population by 2025 [1]. This trend is even more pronounced in the European Union where 21% of the population are currently aged 60 and over, and this is predicted to rise to 34% by 2050 [2]. The elderly already represent a significant proportion of patients with psoriasis vulgaris due to the chronic course of the disease and a bimodal onset with a second peak at age > 55 years. Therefore the management of geriatric psoriasis will be of increasing importance in the coming years. Despite this, there are very few publications in the scientific literature on the management of psoriasis in the elderly.Topical psoriasis treatments are often prescribed for elderly patients as first line therapy due to the potential risk of adverse reactions and drug interactions caused by polypharmacy or altered pharmacokinetics with systemic therapy. However, the physician must also take into account whether the patient is able to apply the medication without assistance. Many older patients find topical preparations time-consuming and difficult to apply, and non-compliance with treatment can be a problem in this population [3]. In particular, the use of combination or sequential topical therapy in the elderly can be complicated by the inconvenience of additional time spent applying different products and the potential risk of adverse events due to incorrect use of multiple medications. Of the various adverse events associated with topical psoriasis treatment, elderly patients are especially at risk of developing steroid-related skin atrophy and purpura, and localised skin irritations associated with vitamin D₃ analogue treatment [4]. Reasons for this include structural changes in the skin that occur with age such as a reduction in epidermal and dermal thickness and a decreasing number of elastic fibres [4, 5]. In geriatric patients the need for a simple therapy that is effective, safe and administered once-daily is considered important.A two-compound product containing calcipotriol and betamethasone dipropionate in a new stable ointment vehicle (Daivobet^®/Dovobet^®) was recently developed for the treatment of psoriasis vulgaris. The efficacy and tolerability of this new ointment has been demonstrated in a clinical trial programme involving more than 7000 patients, including more than 2000 patients treated with Daivobet^®. As well as providing significant improvements in terms of Psoriasis Area and Severity Index (PASI) score, the new ointment also has a tolerability profile which is significantly better than calcipotriol and similar to that of betamethasone dipropionate [6-11]. In order to gain the most information from the clinical trial programme, data from four of the clinical trials in which the two-compound product was administered once daily were pooled and results were extracted for various patient subgroups.This descriptive analysis will examine the efficacy and tolerability of the two-compound ointment in patients aged 60 years and over, and compare the results obtained in this elderly sub-group with those for patients aged less than 60 years.

Methods

All four studies included in this pooled analysis were randomised, blinded, parallel group studies of at least 4 weeks’ duration [6, 9-11]. Patients had to be aged 18 years or more and have a clinical diagnosis of psoriasis vulgaris of the trunk or limbs involving at least 10% of one or more body regions to be eligible for inclusion. Exclusion criteria included guttate, erythrodermic or pustular psoriasis and other inflammatory skin diseases, systemic treatment within the previous 4 weeks or topical treatment within the previous 2 weeks. Women who were pregnant or breast-feeding were also excluded.

The studies were designed to investigate the clinical efficacy and tolerability of once-daily treatment with the new two-compound product containing calcipotriol (50 μg/g) and betamethasone dipropionate (0.5 mg/g) in a new ointment vehicle.

The primary efficacy outcome in each study was the percentage change in the PASI after up to 4 weeks of treatment. Three of the four studies included in the current analysis also assessed the change in PASI score after 1 week of treatment [9-11]. Two of the studies used an Investigator’s Global Assessment of Disease Severity which used a 6-point scale from “absence of disease” to “very severe disease” [10, 11]. Patients were considered to have controlled disease if they were assessed to have either “absence of disease” or “very mild disease”. The Patients’ Assessment of treatment response was assessed in all four studies on a 6-point scale from “worse” to “clearance” [6, 9-11]. Treatment success was defined as “marked improvement” or “clearance” of lesions by the end of up to 4 weeks’ treatment. For up to 4 weeks’ analyses, a last observation carried forward (LOCF) approach was used. Full details of the study methodologies have been published elsewhere [6, 9-11].

Results

A total of 1534 patients, including 357 aged ≥ 60 years, received the two-compound product once daily for up to 4 weeks across the four studies. The baseline characteristics of the patients who received the two-compound product are detailed in table 1( Table 1 ). The mean age at onset of psoriasis was 44.3 years in the ≥ 60 years group, indicating that this group includes patients with both early- and late-onset psoriasis (table 1). The mean PASI at baseline was 10.2 in patients < 60 years and 9.7 in patients ≥ 60 years. After up to 4 weeks of treatment the mean reduction in PASI was 67.8% in patients < 60 years of age, compared to 72.6% in patients ≥ 60 years (( figure 1 )). As shown in ( figure 1 ), more than half of the treatment response was seen after the first week of treatment, with a 39.0% reduction in PASI in patients < 60 years of age, and a 40.7% reduction in patients ≥ 60 years.

In the two studies in which it was assessed, 52.1% of patients aged < 60 years and 58.2% of patients aged ≥ 60 years had controlled disease according to the Investigator’s Global Assessment of Disease Severity (defined as “absence of disease” or “very mild disease”) after up to 4 weeks of treatment. A total of 59.0% of patients aged < 60 years judged themselves to have attained treatment success (defined as “marked improvement” or “clearance” of lesions) compared with 64.6% of patients aged ≥ 60 years (( figure 2 )).

A similar proportion of patients aged < 60 years and ≥ 60 years experienced lesional/perilesional adverse drug reactions during the studies (6.4% vs 5.0%). Specifically, there were no reports of purpura or telangiectasia during the first 4 weeks of treatment in either age group, and only one patient, who was < 60 years, experienced skin atrophy. The rate of infection was low in both groups with 88 (7.5%) and 16 (4.5%) of patients aged < 60 and ≥ 60 years experiencing infections.
Table 1 Baseline demographic characteristics of patients treated with the two-compound product [calcipotriol 50 μg/g plus betamethasone 0.5 mg/g (as dipropionate)] by age group

	Age < 60 years	Age ≥ 60 years
Number of patients	1177	357
Mean (SD) age (years)	42.2 (10.4)	68.1 (6.1)
Mean (SD) age at onset of psoriasis (years)	25.0 (12.7)	44.3 (18.8)
Male (%)	59.6%	65.8%
Mean (SD) baseline PASI	10.2 (5.8)	9.7 (5.7)
Mean (SD) duration of psoriasis (years)	17.2 (11.4)	23.8 (18.0)

Discussion

Topical therapy for psoriasis vulgaris can be problematic in elderly patients because of factors such as the presence of physical limitations that prevent the correct use of a product, as well as an increased risk of skin irritation. However, topical treatments may be preferred over systemic therapies in elderly patients due to the risk of adverse drug interactions associated with the use of multiple medications or altered drug metabolism that can occur with age [3, 4].

The results of this descriptive analysis demonstrate that once-daily treatment with the new two-compound ointment is effective and safe in patients aged ≥ 60 years. Indeed, results for elderly patients were comparable to those for patients aged < 60 years. The similar treatment responses observed in elderly and younger patients indicates that the elderly patients were able to use the ointment correctly. Once-daily dosing with a single ointment provides elderly patients with an effective, convenient, uncomplicated way of treating their psoriasis.

Previous studies conducted with the two-compound product have suggested that the betamethasone component of the ointment helps to counteract the skin irritating effects of calcipotriol [11]. This is of particular benefit in elderly patients who are more at risk of experiencing such effects due to age-related skin changes [4]. In the current analysis only 5% of patients aged ≥ 60 years experienced lesional/perilesional adverse drug reactions, and there were no reports of purpura, telangiectasia or skin atrophy during the first four weeks of treatment. In fact, few reports of skin atrophy were recorded for patients aged < 60 years.

The current study is hampered by certain limitations inherent to such an analysis. Although the studies included in the pooled analysis are all prospective, randomised, controlled trials of very similar design, the current analysis is retrospective in nature. In conclusion, the new two-compound product containing calcipotriol and betamethasone dipropionate provides effective treatment of psoriasis vulgaris in both elderly and younger patients.

Acknowledgements

Assistance with preparation of the manuscript: Rosalind Black

References

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2 Eurostat. Regional population ageing of the EU at different speeds up to 2025, in Statistics in Focus. In: Eurostat. 1999: 1-8.

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