Diepgen_subbed.qxp 21/5/09 5:02 pm Page 37
Alitretinoin in Chronic Hand Eczema – From Clinical Trials to Clinical Practice
always suitable for long-term use due to toxicity issues, and the Figure 1: Physical Symptoms of Severe Chronic
severity of CHE can actually worsen after cessation of these
Hand Eczema
aggressive treatments.
Alitretinoin – A New Treatment
Option for Severe Chronic Hand Eczema
As a result of the limitations of the long-term use of systemic
corticosteroids, immunosuppressants and phototherapy, until
recently there was no reliable treatment option for patients with
severe CHE refractory to topical corticosteroids. However, after
recently being introduced in Europe for the treatment of severe
CHE, the retinoid alitretinoin (Toctino
®
; Basilea Pharmaceutica
International Ltd, Basel, Switzerland) could address this unmet
medical need.
Retinoids are either naturally occurring or synthetic derivatives of
vitamin A (retinoic acid). Since the early 1980s they have been used
successfully to treat dermatological disorders, with proven efficacy in
psoriasis and acne. Alitretinoin (9-cis retinoic acid) is an endogenously
Figure 2: Physician's Global Assessment Responses at
occurring physiological vitamin A derivative that shows strong anti-
End of Treatment in the BACH Study
inflammatory and immunomodulatory activity.
8,9
*p<0.001
50
Clear
Clinical Efficacy of Alitretinoin in
45
48%
Almost clear
Chronic Hand Eczema
’
or
40
35
The efficacy of oral alitretinoin in the treatment of CHE was first
‘
clear ’
hands
30
*p=0.004
demonstrated in an open-label proof-of-concept study of 38 patients
25
28%
with refractory CHE.
8
This was subsequently confirmed in a
20
15 17%
double-blind, randomised, placebo-controlled, dose-ranging study in
‘
almost clear
10
P
atients with
312 patients with moderate or severe CHE.
10
These studies paved the 5
way for the largest clinical trial conducted in CHE to date, the Benefit
0
Placebo Alitretinoin 10mg Alitretinoin 30mg
of Alitretinoin in Chronic HE (BACH) study.
11
In this prospective, (n=205) (n=418) (n=409)
randomised, double-blind, placebo-controlled, parallel-group study,
*Change from baseline. Forty-eight per cent of patients treated with alitretinoin 30mg had
1,032 patients were randomised to receive alitretinoin 30mg (n=409),
‘clear’ or ‘almost clear’ skin at the end of treatment in the Benefit of Alitretinoin in Chronic
alitretinoin 10mg (n=418) or placebo (n=205) once daily for 12–24
Hand Eczema (BACH) study, as determined by the Physician’s Global Assessment (PGA) score.
weeks. Only patients with severe refractory CHE were included, and
Figure 3: Modified Total Lesion Symptom Score
the average disease duration of the study population was
Responses During the BACH Study
approximately nine years. Treatment-refractory was defined as
unresponsiveness to potent topical corticosteroids and no response
Baseline Week 4 Week 8 Week 12 Week 16 Week 20 Week 24
to the use of skin moisturisers or allergen/irritant avoidance. The
0
primary efficacy parameter was the Physician’s Global Assessment
(PGA), which was evaluated at baseline and at four-weekly intervals
-10
)
%
thereafter during treatment. The percentage of patients with a PGA
-20
score of ‘clear’ or ‘almost clear’ was defined as response (i.e. the
primary end-point).
-30
-40
Both doses of alitretinoin were significantly more efficacious than
placebo. A clear or almost clear hand, which reflected a 90%
-50
improvement of symptoms, was reached by 48% of patients in the
Median reduction in mTLSS (
-60
alitretinoin 30mg group. For the lower-dose group (10mg), the rate
Placebo
was 28% (see Figure 2), compared with 17% in the placebo group.
-70
Alitretinion 10mg
This was despite there being more patients rated as most difficult
Alitretinion 30mg
-80
to achieve a ‘clear’ PGA score in the 30mg (n=90) and 10mg (n=39)
groups compared with the placebo (n=6) group. Using the
Alitretinoin 30mg provided a 75% reduction in signs and symptoms during the course of the
Benefit of Alitretinoin in Chronic Hand Exzema (BACH) study, as determined by Modified Total
secondary end-point – the Modified Total Lesion Symptom Score Lesion Symptom Score (mTLSS).
(mTLSS), which is the sum of seven individual symptom scores
(erythema, vesiculation, hyperkeratosis, pruritus/pain, oedema, and 10mg groups was 75 and 56%, respectively, compared with 39%
desquamation, fissures) rated on a zero to three scale of severity – in the placebo group.
a reduction of 50% after just eight weeks could be demonstrated
for all patients treated with alitretinoin 30mg (see Figure 3). Patients who did not achieve a clear/almost clear response at the
Moreover, at week 24 reduction in median mTLSS score in the 30 end of the 24-week study duration entered an open-label extension
EUROPEAN DERMATOLOGY 37
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99