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STEVE GLADFELTER/STANFORD UNIVERSITY MEDICAL CENTER

THE LEADER IN NEWS AND MEETING COVERAGE
THE LEADER
IN NEWS
AND
MEETING
COVERAGE

N OVEMBER

2007

FDA AGREES TO RELAX IPLEDGE RULES, PAGE 17

Skin & Allergy News

R ELAX I PLEDGE R ULES , PAGE 17 Skin & Aller gy News V O

VO L .

38, N O.

11

www.skinandallergynews.com The Leading Independent Newspaper for Medical, Surgical, and Aesthetic Dermatology

Newspaper for Medical, Surgical, and Aesthetic Dermatology For most patients, p16 genetic mutation testing will add

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

BY BETSY BATES

Los Angeles Bureau

C ALIF. — 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

M ONTEREY,

(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.

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 or pancreatic cancer. Based on current proposed criteria for con- sideration of genetic testing for the p16 mutation, p16 testing would not be indicated in this pa- tient, who is considered at low See p16 page 23

 

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  I I N N S S I I D D E E MELTUMP The treatment

MELTUMP

The treatment of tumors of unknown malignant potential causes uncertainty.

PAGE

22

Liposuction

Alternative?

Despite warnings Lipodissolve mesotherapy gaining popularity.

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25

Lipodissolve mesotherapy gaining popularity. PAGE 25 Dr. Dad Physicians share how they balance the demands of

Dr. Dad

Physicians share how they balance the demands of patients and parenthood.

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61

CC AA SS EE OO FF TT HH EE MM OO NN TT HH A
CC AA SS EE
OO FF
TT HH EE
MM OO NN TT HH
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
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.
COURTESY DR. DIRK ELSTON

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

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.” Ustekinumab—formerly 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

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-

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

E LSEVIER G LOBAL M EDICAL N EWS

E LSEVIER G LOBAL M EDICAL N EWS

November 2007

w w w. s k i n a n d a l l e r g y n ew s . c o m

Biologics Compared For Plaque Psoriasis

BY BRUCE JANCIN

Denver Bureau

Z URICH — 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

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.

DD AA TT AA WW AA TT CC HH Number of All-Cause Psoriasis Hospitalizations Up
DD
AA
TT
AA
WW
AA
TT
CC
HH
Number of All-Cause Psoriasis Hospitalizations
Up 83% Over a 12-Year Period
77,404
54,996
42,302
1993
2000
2004
Note: Based on data from the Nationwide Inpatient Sample.
Source: Dr. Omar Dabbous

News

9

Diet Increases Effect of Low-Dose Cyclosporine in Psoriasis Patients

BY BRUCE JANCIN

Denver Bureau

Z URICH — 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/m 2 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

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%

67% 21%
67% 21%
67% 21%
67% 21%
67% 21%

21%

67% 21%

Diet group

Control group

Note: Based on a randomized 24-week study of 60 patients. Source: Dr. Gisondi

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

some of the happiest patients that I’ve ever 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-

were

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.