FDA A GREES
THE LEADER
Skin & Allergy News
VO L . 3 8 , N O. 1 1
For most patients, p16 genetic mutation testing will add no new
information to their known melanoma risk, said Dr. Susan Swetter.
p16 Genetic Testing
Has Limited Impact
B Y B E T S Y B AT E S
Los Angeles Bureau
M O N T E R E Y , C A L I F . — Rec-
ommend p16 mutation genetic
testing only in patients with
multiple primary melanomas or
a family history that includes
multiple cases of melanoma or
pancreatic cancer, advised Dr.
Susan Swetter at the annual
meeting of the California Soci-
ety of Dermatology and Der-
matologic Surgery.
While it is true that a p16 ge-
netic mutation confers a pro-
foundly elevated risk of mel-
anoma—up to 80% by age
80—few melanoma patients ac-
tually carry the mutation, said
Dr. Swetter of the Veterans Af-
fairs Palo Alto (Calif.) Health
Care System and director of the
Pigmented Lesion and Cutaneous
Melanoma Clinic at Stanford
(Calif.) University Medical Center.
“If you take unselected
melanoma patients in the gener-
al population, their rates of p16
positivity are very low: only
0.2%-2%,” she said, “and a reason
to perform a genetic test is if you
have a fair suspicion that it’s go-
ing to be abnormal.”
She noted that physicians and
patients alike have been receiving
mailings from laboratories sug-
gesting that melanoma patients
should “alleviate their anxiety”
by undergoing the p16 test.
TO R ELAX I PLEDGE R ULES , PAGE 17
www.skinandallerg ynews.com
T he Leading Inde pendent Ne wspaper for Medical, Surgical, and Aesthetic Der matology
INSIDE
S TEVE G LADFELTER /S TANFORD U NIVERSITY M EDICAL C ENTER
MELTUMP
The treatment of tumors of
unknown malignant
potential causes uncertainty.
PAGE 22
Liposuction
Alternative?
Despite warnings
Lipodissolve mesotherapy
gaining popularity.
PAGE 25
However, in many cases, the
test will add no new useful in-
formation to a person’s known
risk for melanoma.
She cited the case of a 64-year-
old patient who desired a p16 ge-
netic test because of a personal
history of melanoma and atypi-
cal mole syndrome.
The patient reported having
no family history of melanoma
Dr. Dad
Physicians share how they
or pancreatic cancer. Based on
current proposed criteria for con- balance the demands of
sideration of genetic testing for patients and parenthood.
the p16 mutation, p16 testing
would not be indicated in this pa-
tient, who is considered at low
PAGE 61
See p16 page 23
CASE OF THE MONTH
A n adult male inpatient re-
ceiving massive doses of
corticosteroids to control cere-
bral edema that developed af-
ter a motor vehicle accident
rapidly developed a fuzzy
white lesion in an area of scalp
abrasions. The man, who had
adult-onset diabetes, suffered
the head trauma, including the
C OURTESY D R . D IRK E LSTON
abrasions, after being thrown
through the window of his
ice-cream truck. The lesion
was not present at the previ-
ous day’s dermatology con-
sult. What’s your diagnosis?
See Case of the Month, page 71.
Two-Thirds Reach
PASI-75 With New
Biologic Agent
Ustekinumab combines efficacy and safety.
BY ROBERT FINN
San Francisco Bureau
M
ore than two-thirds of
patients with moderate
to severe plaque psoria-
sis achieved at least a 75% reduc-
tion in area and severity after just
two subcutaneous doses of
ustekinumab, according to phase
III study results presented at the
21st meeting of the World Con-
gress of Dermatology.
“With any drug you want effi-
cacy, safety, and convenience,” Dr.
Kristian Reich of Georg-August-
Universität, Göttingen, Germany,
one of the trial’s principal investi-
gators, said during a Web-based
news conference. “We have an ef-
ficacy that’s in the championship
TAN Act Persistence Pays:
FDA to Study UV Bed Risks
B Y A L I C I A A U LT
Associated Editor, Practice Trends
T he Food and Drug Adminis-
tration soon will begin to
scrutinize the warning labels on
tanning beds, under a new feder-
al law signed by the president in
late September.
The Tanning Accountability
and Notification Act was includ-
ed in the Food and Drug Admin-
istration Amendments Act of
2007. Four members of Con-
gress—Sen. Jack Reed (D-R.I.),
Sen. Johnny Isakson (R-Ga.), Rep.
Carolyn Maloney (D-N.Y.), and
Rep. Ginny Brown-Waite (R-
IN NEWS
AND
MEETING
COVERAGE
N OV E M B E R 2 0 0 7
league of antipsoriatic therapy.
We have a safety that we haven’t
seen so far, and [with] injections
every 3 months, we have a very
convenient healinglike therapy.”
Ustek inumab—for merly
known as CNTO 1275—is a ful-
ly human monoclonal antibody
discovered by Centocor Inc. with
a novel mechanism of action that
targets the cytokines interleukin-
12 and interleukin-23.
The phase III multicenter
study involved 1,230 patients
with chronic plaque psoriasis
who were randomized to one of
the following: placebo; two 45-
mg doses of ustekinumab every
4 weeks; or two 90-mg doses of
ustekinumab every 4 weeks.
See Two-Thirds page 9
Fla.)—originally sponsored the
TAN Act.
Under the new federal law, the
FDA is being directed to deter-
mine if the label is positioned
correctly, whether it gives suffi-
cient risk data, whether alterna-
tive warnings would better com-
municate risks, or if there is no
warning that could communi-
cate the risk of using tanning
beds adequately.
To reach those determinations,
the law requires the FDA to con-
duct tests with consumers; the
agency is to issue a report by
September 2008.
See TAN Act page 17
 N o v e m b e r 2 0 0 7 • w w w. s k i n a n d a l l e r g y n e w s . c o m
Biologics Compared
For Plaque Psoriasis
BY BRUCE JANCIN
Denver Bureau
Z U R I C H — Infliximab is the most ef-
fective biologic induction therapy for
patients with moderate to severe
plaque-type psoriasis, according to a
meta-analysis of 17 randomized place-
bo-controlled clinical trials.
Of patients receiving 10-12 weeks of
infliximab (Remicade) induction thera-
py at the approved dose of 5 mg/kg,
83% achieved at least a 75% reduction
in Psoriasis Area and Severity Index
scores (PASI-75).
This was superior to the PASI-75
rates of 50% for etanercept (Enbrel) at
50 mg twice weekly, 36% for etanercept
at 25 mg twice weekly, 29% for efal-
izumab (Raptiva) at 1-2 mg/kg per
week, and 18% for alefacept (Amevive)
at 15 mg intramuscularly per week or
a 7.5-mg IV bolus, Dr. Kristian Reich
reported at the annual meeting of the
European Society for Dermatological
Research.
Dr. Reich and his coinvestigators at
Oxford Outcomes Ltd., calculated that
the pooled odds of achieving PASI-75
on infliximab were 25-fold greater than
on placebo. This was significantly
greater than the odds ratio of 11.9 for
a PASI-75 score with etanercept at 50
mg twice weekly compared to placebo,
10.7 for etanercept at 25 mg twice week-
ly, 7.5 for efalizumab, and 3.4 with ale-
facept, according to Dr. Reich of Der-
matologikum Hamburg (Germany).
Infliximab also was associated with
greater improvements in organ-specif-
ic quality of life as assessed by the Der-
matology Life Quality Index (DLQI).
At week 10, 47% of infliximab-treated
subjects reported that psoriasis no
longer had any effect on their health-re-
lated quality of life as indicated by a
DLQI score of 0, down from a mean of
10.3 at baseline. This was the case for
only 1.3% of patients on placebo. Less
than 25% of patients on etanercept at
50 mg twice weekly indicated psoriasis
D A T A
Number of All-Cause Psoriasis Hospitalizations
Up 83% Over a 12-Year Period
54,996
42,302
1993
Note: Based on data from the Nationwide Inpatient Sample.
Source: Dr. Omar Dabbous
had no effect on their health-related
quality of life at week 12, he continued.
In a separate presentation, Dr.
Robert Gniadecki noted that in con-
trast to the rather dazzling short-term
results seen with infliximab as induc-
tion therapy for psoriasis in the care-
fully controlled setting of industry-
funded clinical trials, longer-term
outcomes in real-world clinical practice
are mixed.
He presented a retrospective study
involving 36 consecutive patients with
plaque psoriasis treated with infliximab
in his clinical practice. The PASI-75
rate after 3 months was 77%.
By 30 months of follow-up, howev-
er, 74% of initial responders had aban-
doned infliximab. The chief reason was
drug-related side effects, led by infusion
reactions, which caused seven patients
to discontinue therapy. Another seven
patients discontinued infliximab be-
cause of loss of efficacy.
Particularly susceptible to drop out
were patients with predominantly
acral psoriasis and those treated on de-
mand rather than in accord with the
recommended treatment schedule of
dosing every 6-8 weeks after the load-
ing doses, observed Dr. Gniadecki of
Bispebjerg Hospital at the University
of Copenhagen.
Patients with acral psoriasis had a
mean half-life on infliximab of only 2
months. Those treated on demand had
a treatment half-life of 5 months. In
contrast, the mean treatment half-life of
the rest of the patients was 24 months.
Diligent management of infusion
reactions and strict adherence to the
treatment schedule would increase
the success rate of infliximab mainte-
nance therapy in clinical practice, he
concluded.
Dr. Gniadecki and Dr. Reich have
both served as consultants to Centocor
Inc., which markets infliximab in the
United States, as well as to Schering-
Plough Corp., which markets the bio-
logic agent elsewhere.
W A T C H
77,404
2000 2004
Diet Increases Effect of Low-Dose
Cyclosporine in Psoriasis Patients
BY BRUCE JANCIN
Denver Bureau
Z U R I C H — Combining a supervised
weight-loss diet with substandard-dose cy-
closporine in obese patients with severe
chronic plaque psoriasis makes for very ef-
fective therapy, Dr. Paolo Gisondi reported
at the annual meeting of the European So-
ciety for Dermatological Research.
The clinical implication of this finding? “A
global approach to obese patients with se-
vere psoriasis should include body weight
reduction,” declared Dr. Gisondi of the
University of Verona (Italy).
He presented the results of a randomized
trial involving 60 patients with severe pso-
riasis and a body mass index of 30 kg/m2 or
more. All were placed on 2.5 mg/kg per day
of cyclosporine, even though doses of less
than 3 mg/kg are known to have poor effi-
cacy. Then they were randomized to either
a dietitian-administered low-calorie diet de-
signed to achieve at least a 5%-10% weight
loss or to usual care. To ensure that the two
groups received equal attention, physicians
met with control subjects on a monthly ba-
sis, whereas the dietitian met with patients
in the intervention arm.
The primary study end point was at least
a 75% reduction in Psoriasis Area and Sever-
ity Index score (PASI-75) at 24 weeks. By
then, patients in the diet arm had lost a
mean of 6.6 kg, whereas the controls’ weight
was unchanged. As patients lost weight,
physicians adjusted their cyclosporine
dosage to maintain it at 2.5 mg/kg.
A PASI-75 assessed by blinded evaluators
was achieved in 67% of the diet group,
compared with 21% of controls. A PASI-50
was achieved by 86% of the diet group and
42% of controls, Dr. Gisondi said.
Obesity is more prevalent in patients with
Patients’ Quality of Life Improves
Two-Thirds from page 1
At week 12, the study end point, 67% of
patients treated with 45 mg of ustekinum-
■ ab and 76% of patients treated with 90 mg
achieved at least a 75% reduction in psoria-
sis as measured by the Psoriasis Area and
Severity Index (PASI-75), compared with
just 4% of the patients treated with place-
bo. Additionally, 42% of patients in the low-
dose group and 51% of patients in the high-
dose group achieved PASI-90, or nearly
complete clearance of psoriasis, compared
with just 1% of patients receiving placebo.
As early as week 4, patients receiving ei-
ther dose of ustekinumab experienced sig-
nificant improvements in several quality of
life measures, compared with patients re-
ceiving placebo. “These patients ... were
some of the happiest patients that I’ve ever
E LSEVIER G LOBAL M EDICAL N EWS
had the pleasure of treating with an exper-
imental medication,” said Dr. Craig
Leonardi of St. Louis University, and lead in-
vestigator of the study. “These results are
wonderful. It validates the pathway as a tar-
get; it tells us that it’s an important option
for treating psoriasis patients, and that this
fully human antibody is going to be a high-
News 9
chronic plaque psoriasis than in the gener-
al population. The rationale for the dietary
intervention hinged on prior reports that a
calorie-restricted diet results in clinical im-
provement and reduces inflammatory
markers in obese patients with other chron-
ic inflammatory diseases, including asthma
and rheumatoid arthritis, he explained.
In accord with the prior studies involving
other chronic inflammatory diseases, C-re-
active protein levels in the obese psoriasis
patients were elevated at baseline and
dropped significantly in the dietary inter-
vention group.
Asked why he chose to prescribe subop-
timal-dose cyclosporine in the study, Dr.
Gisondi replied that it made it much easier
to determine whether a weight-loss diet had
a beneficial effect, because full-dose cy-
closporine would predictably result in a high
PASI-75 with or without the dietary inter-
vention. Plus, low-dose cyclosporine means
fewer side effects and less expense. ■
Obese Psoriasis Patients
Who Achieved a PASI-75
67%
E LSEVIER G LOBAL M EDICAL N EWS
21%
Diet group Control group
Note: Based on a randomized 24-week
study of 60 patients.
Source: Dr. Gisondi
ly effective and significant treatment choice
for dermatologists and for the patients
[who] have high needs.”
Side effects from ustekinumab were mild
and were comparable with placebo, with
about 50% of patients in all three groups ex-
periencing at least one adverse event, and
1%-2% of patients in all three groups expe-
riencing at least one serious adverse event.
The drug was not associated with any sig-
nificant effects on laboratory parameters.
There was one death in the trial of a pa-
tient receiving the 90-mg dose of ustek-
inumab. The patient died of congestive car-
diomyopathy. It is unknown whether this
was related to the drug, because it was
found that the patient recently had been
treated for heart problems that were not dis-
closed during study enrollment.
If approved by the FDA, Janssen-Cilag
companies will market the drug outside the
United States, while Centocor Inc. has ex-
clusive marketing rights in the United States.
Dr. Reich and Dr. Leonardi received
grants from Centocor on a per-patient ba-
sis for conducting the trial. ■