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Vancouver,
B.C.— Vancouver, B.C.- The first non-steroid cream indicated
for the treatment of mild-to-moderate atopic dermatitis will launch
soon in Canada. Pimecrolimus 1% cream (Elidel®, Novartis) was
shown in Phase III trials to reduce and sometimes even eliminate
the need for topical steroids in adults and in children as young
as three months of age.
At Dermatology Update 2002, the rationale for a new therapy was
discussed by Richard Langley, MD, director of research, Victoria
General Hospital, Halifax, N.S., and assistant professor, division
of dermatology, Dalhousie University. Aside from the obvious clinical
benefit of removing the long-term toxic effect of corticosteroid
use, there is a scientific rationale. "We are now able to identify
pathogenesis, and we can target these through our therapies,"
Dr. Langley said.
Safety and efficacy of pimecrolimus 1% cream over a one-year treatment
period has been demonstrated in Phase II and III trials involving
more than 1,500 adults, children and infants. Safety and efficacy
was discussed by Thomas Luger, MD, director and chairman, department
of dermatology, University of Münster, who conducted the Phase
II dosing study for pimecrolimus cream.
Clinical trials
Two identical Phase III trials were conducted by Eichenfield et
al and results were pooled for a total of 403 patients, aged one
to 17, with mild-to-moderate atopic dermatitis. At the end of the
six-week study, 35 per cent of Elidel patients were clear or almost
clear versus 18 per cent of the vehicle group (p<0.05).
A subsequent Phase III trial by Papp et al looked at 186 infants,
three to 23 months of age, most of whom had moderate disease. By
Day 8, 17 per cent of patients treated with pimecrolimus were clear
or almost clear, and this increased to 54.5 per cent by Day 43.
(This compared with 9.5 per cent and 23.8 per cent, respectively,
in the vehicle control group.)
Inflammatory
cytokine inhibition
Here is an easy way to remember how pimecrolimus 1% cream works.
It was first described by Harvey Lui, MD, at Dermatology Update
2002, and reiterated by Dr. Langley during the Elidel symposium.
Imagine the T cell as royalty. She is the queen, and, like all queens,
she likes to have things presented to her. Along comes a Langerhans'
cell and presents her with an antigen.
When
the queen receives the antigen, some of her offspring may become
delinquent. They will be activated and secrete cytokines. Pimecrolimus
1% cream works by preventing the activated TH2 cells and mast cells
from secreting pro-inflammatory cytokines that cause atopic dermatitis.
Low systemic exposure
In the early development phase of pimecrolimus more than 400 ascomycin
derivatives were screened; pimecrolimus was chosen for its lipophilicity.
While it penetrates the skin, it does not pass through the skin
into the bloodstream in significant amounts. Inflammation in the
skin is selectively targeted while blood levels remain consistently
low, even in children who use it on up to 92 per cent of their body
surface area, or long term.
Itch relief
Pimecrolimus 1% cream was shown to significantly reduce itching
and eliminate sleep disturbances in adult patients within three
days. (Meurer and Brautigam, Poster, American Academy of Dermatology,
New Orleans, 2002).
Ho et al (JEADV 2001;15(suppl 2):110) evaluated 186 infants
aged three months to two years with mild-to-moderate atopic dermatitis
for a duration of 26 weeks. Up to 70 per cent of patients in the
pimecolimus group had no or mild itching by Day 8 compared to 36
per cent in the vehicle control group.
Flare
control
When applied at the first signs or symptoms of atopic dermatitis,
pimecrolimus 1% cream prevents flare progression. In a poster by
Kapp et al, presented at the European Academy of Dermatology and
Venereology in 2001, up to 70 per cent of patients aged three to
23 months treated with pimecrolimus cream had no flares at the end
of six months, compared to up to 33 per cent of the vehicle control
group. At the end of 12 months, up to 57 per cent of pimecrolimus
patients had no flares, compared to up to 28 per cent of the vehicle
control group.
Side effects
Common side effects are limited to application sites. Ten per cent
of children and 15 per cent of adults experienced a temporary feeling
of warmth or burning where pimecrolimus 1% cream was applied. Side
effects led to less than two per cent
discontinuation in clinical trials. No clinically significant systemic
adverse effects were seen in patients treated for up to one year.
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