| |
Victoria,
B.C.-- In the eyes of patients who suffer from moderate-to-severe
plaque psoriasis, traditional treatments have been largely disappointing.
Of 1,108 patients surveyed last year by the Psoriasis Society of
Canada, 71% said they were dissatisfied with current treatments.
Emerging biologic agents are giving patients and dermatologists
new hope in meeting the challenge of this severely debilitating
disease. Efalizumab is a monoclonoal antibody that acts on the T
cell, the primary target in psoriasis therapy. One of the major
attributes of this biologic agent is that it does not possess some
of the safety concerns of traditional photo and systemic therapies,
allowing the dermatologist to provide continuous treatment for this
chronic disease.
To date, 2,762 patients have been assessed with efalizumab in randomized,
controlled trials and the data showing efficacy and safety extend
to two years. The treatment is approved in the United States, Switzerland,
and Australia and has recently received a positive opinion in Europe
by the Evaluation of Medicinal Products (EMEA). Efalizumab is currently
under review by Health Canada and is therefore not approved or available
in Canada.
Unmet needs
In his introduction, Dr. Neil Shear discussed the unmet needs of
psoriasis patients and the changing treatment paradigm. “For
some of the people I see who have really bad psoriasis, most of
them don’t go beyond topical therapy. Phototherapy is very
time consuming, and with systemic therapy there are mainly concerns
with safety,” Dr. Shear said. Moreover, traditional treatments
are cyclical, not continuous. “What we want to look at is,
can we not only get rapid improvement but also a good maintenance
of response, not worry about long-term toxicity, and truly improve
people’s quality of life—not intermittently—but improve
their life.”
Efalizumab:
Short-Term Results
Dr. Kim Papp described specifically how efalizumab works. He stated,
“Within one or two doses, complete saturation is achieved on
the T cell antigen binding sites known as CD11a.” This inhibits
T-cell activation in the lymph nodes. Blocking the CD11a also ensures
that T cells cannot move efficiently into the dermis and epidermis,
and that T cell reactivation is inhibited as well.(1)
In Phase III trials the primary endpoint was a 75% improvement in
the Psoriasis Area and Severity Index (PASI) after three months
of efalizumab treatment, 1 mg/kg, injected subcutaneously once a
week. This was preceded by a washout period and one conditioning
dose of 0.7 mg/kg. After only two weeks of treatment, a significant
difference from placebo was measured, and at three months 30% of
patients with moderate-to-severe plaque psoriasis had achieved PASI
75. Sixty percent (60%) had achieved PASI 50 at three months.(2,3)
“At Week 6 there was a clinically meaningful difference in
response from placebo. This improvement continues,” said Dr.
Papp, who has treated approximately 200 patients with efalizumab
in clinical trials during the past six years.
The most common adverse events were headache, infection (mostly
of the upper respiratory tract), chills, nausea, and generalized
pain. These occurred only with the first two doses and then dissipated.
Adverse events can be minimized with a conditioning dose, he said.
A multinational, prospective, placebo-controlled study conducted
by Serono compared safety and efficacy of efalizumab in moderate-to-severe
psoriasis patients who were candidates for systemic therapy with
a subgroup of “high-need” patients who were not controlled
by, intolerant to, or contraindicated for at least two systemic
therapies (mostly methotrexate, PUVA and UVB). The study design
was the same as in Phase III trials and included a placebo group.
At three months, responses in the two treatment groups were comparable
with respect to PASI 75 (31%) and PASI 50 (54%), as well as adverse
events.
Efalizumab:
Longer-Term Results
Dr. Charles Lynde presented the longer-term data, stating that more
than 900 patients have been treated with efalizumab for at least
six months. At six months, PASI 75 response was found to be 44%,
and PASI 50 was 67%4. Quality of life improvements achieved at three
months were maintained through six months.
Approximately 200 patients have been treated for two years in an
ongoing, open-label, three-year trial. PASI 75 was shown to increase
slightly beyond the six-month mark and was maintained in 55% of
patients at two years5. There was no increase in the overall incidence
of adverse events over time.
Quality of
Life
Dr. Wayne Carey reported on the impact of efalizumab on quality
of life using three patient-reported outcome measures: Dermatology
Life Quality Index (DLQI), Psoriasis Symptom Assessment (PSA), and
Itch Visual Analog Scale (VAS). Using these measures, mean improvements
from baseline ranged from 45% to 46% at three months.6,7,8,9 “We
see a statistical difference from placebo after one month of therapy,”
Dr. Carey said.
After completion of efalizumab therapy, 75% of patients said they
were satisfied or very satisfied. Eighty percent (80%) said it was
more convenient than previous therapies they had tried. “It
was a very simple therapy for patients, which they learned to administer
very quickly,” he said. Ninety percent (90%) of patients who
self-injected found the process easy or very easy.
Safety
Serious infections requiring hospitalization occurred at a similar
rate in treated patients (0.4%) versus patients on placebo (0.1%),
Dr. Lynde reported. Less than 1% discontinued treatment due to infection.
There was no increase in malignancy compared to the placebo group
or to external cohorts, and no cumulative or end-organ toxicity
was observed.
Reversible thrombocytopenia (platelet counts at or below 52,000)
was observed in 0.3% of patients. “It is unclear whether this
is truly related as a drug effect, and, although not mandated by
present FDA approval, I think it would be prudent to do baseline
counts and repeat them on a monthly basis for the first three months,
and then every three months after,” Dr. Lynde said.
Serious worsening of psoriasis occured in 0.7% of patients. Efalizumab
is best used as a continuous therapy. It has a reversible effect
on T cells, therefore, recurrence of disease is expected upon discontinuation
(within 64 to 70 days). Rebound has been reported upon discontinuation
of treatment and can be managed by retreatment with efalizumab or
other psoriasis therapies. There have been no reports of demyelinating
disorders, congestive heart diseaase or lupus, which have been reported
with some other biological therapies.
“The overall safety profile is excellent,” Dr. Lynde concluded.
This report appears through an unrestricted educational grant from
Serono Canada Inc.
|
|
