ARTICLE
Auteur(s) :, Richard Parslew1,*, 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
1 National Projections Program. Projected resident population of
the United States as of July 1, 2025, Middle Series. US Census
Bureau, 2002.
2 Eurostat. Regional population ageing of the EU at different
speeds up to 2025, in Statistics in Focus. In: Eurostat. 1999:
1-8.
3 Ritter J, Lewis L, Mant T. In: Ritter J,
ed. A textbook of clinical pharmacology. London: Hodder Arnold,
1994: 731.
4 Yosipovitch G, Tang M. Practical management of
psoriasis in the elderly: epidemiology, clinical aspects, quality
of life, patient education and treatment options. Drugs Aging 2002;
19(11): 847-63.
5 Bonifati C, Carducci M, Mussi A,
D’Auria L. Recognition and treatment of psoriasis: special
considerations in elderly patients. Drugs Aging 1998; 12(3):
177-90.
6 Ortonne J, Kaufmann R, Lecha M,
Goodfield M. Efficacy of treatment with
calcipotriol/betamethasone dipropionate followed by calcipotriol
alone compared with tacalcitol for the treatment of psoriasis
vulgaris: a randomised, double-blind trial. Dermatology. 2004; In
press.
7 Papp K, Guenther L, Boyden B, Larsen F,
Harvima R, et al. Early onset of action and efficacy of a
combination of calcipotriene and betamethasone dipropionate in the
treatment of psoriasis. J Am Acad Dermatol 2003; 48(1): 48-54.
8 Douglas W, Poulin Y, Decroix J, Ortonne J,
Mrowietz U, et al. A new calcipotriol/betamethasone
formulation with rapid onset of action was superior to monotherapy
with betamethasone dipropionate or calcipotriol in psoriasis
vulgaris. Acta Derm Venereol 2002; 82(2): 131-5.
9 Guenther L, Cambazard F, Van de Kerkhof P,
Snellman E, Kragballe K, et al. Efficacy and safety
of a new combination of calcipotriol and betamethasone dipropionate
(once or twice daily) compared to calcipotriol (twice daily) in the
treatment of psoriasis vulgaris: a randomized, double-blind,
vehicle-controlled clinical trial. Br J Dermatol 2002; 147(2):
316-23.
10 Kragballe K, Noerrelund K, Lui H,
Ortonne J, Wozel G, et al. Efficacy of once daily
treatment regimens with calcipotriol/betamethasone dipropionate
ointment and calcipotriol ointment in psoriasis vulgaris. Br J
Dermatol 2004; 150(6): 1167-73.
11 Kaufmann R, Bibby A, Bissonnette R,
Cambazard F, Chu A, et al. A new
calcipotriol/betamethasone dipropionate formulation (Daivobet) is
an effective once-daily treatment for psoriasis vulgaris.
Dermatology 2002; 205(4): 389-93.
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