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THE LEADER IN NEWS AND MEETING COVERAGE

Skin & Allergy News
VO L . 3 8 , N O. 1 1 www.skinandallerg ynews.com T he Leading Inde pendent Ne wspaper for Medical, Surgical, and Aesthetic Der matology

N OV E M B E R 2 0 0 7

INSIDE
S TEVE G LADFELTER /S TANFORD U NIVERSITY M EDICAL C ENTER

Two-Thirds Reach PASI-75 With New Biologic Agent
Ustekinumab combines efficacy and safety.
BY ROBERT FINN

MELTUMP
The treatment of tumors of unknown malignant potential causes uncertainty.
PAGE 22

San Francisco Bureau

For most patients, p16 genetic mutation testing will add no new information to their known melanoma risk, said Dr. Susan Swetter.

M

p16 Genetic Testing Has Limited Impact
B Y B E T S Y B AT E S

Liposuction Alternative?
Despite warnings Lipodissolve mesotherapy gaining popularity.
PAGE 25

Los Angeles Bureau

M O N T E R E Y , C A L I F . — Recommend 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 Society of Dermatology and Dermatologic Surgery. While it is true that a p16 genetic mutation confers a profoundly elevated risk of melanoma—up to 80% by age 80—few melanoma patients actually carry the mutation, said Dr. Swetter of the Veterans Affairs 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 general 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 going to be abnormal.” She noted that physicians and patients alike have been receiving mailings from laboratories suggesting that melanoma patients should “alleviate their anxiety” by undergoing the p16 test.

However, in many cases, the test will add no new useful information to a person’s known risk for melanoma. She cited the case of a 64-yearold patient who desired a p16 genetic test because of a personal history of melanoma and atypical mole syndrome. The patient reported having no family history of melanoma or pancreatic cancer. Based on current proposed criteria for consideration of genetic testing for the p16 mutation, p16 testing would not be indicated in this patient, who is considered at low See p16 page 23

ore than two-thirds of patients with moderate to severe plaque psoriasis achieved at least a 75% reduction 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 Congress of Dermatology. “With any drug you want efficacy, safety, and convenience,” Dr. Kristian Reich of Georg-AugustUniversität, Göttingen, Germany, one of the trial’s principal investigators, said during a Web-based news conference. “We have an efficacy 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.” Ustek inumab—for merly known as CNTO 1275—is a fully human monoclonal antibody discovered by Centocor Inc. with a novel mechanism of action that targets the cytokines interleukin12 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 45mg doses of ustekinumab every 4 weeks; or two 90-mg doses of ustekinumab every 4 weeks. See Two-Thirds page 9

Dr. Dad
Physicians share how they balance the demands of patients and parenthood.
PAGE 61

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

CASE OF THE MONTH
n adult male inpatient receiving massive doses of corticosteroids to control cerebral edema that developed after 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 previous day’s dermatology consult. What’s your diagnosis? See Case of the Month, page 71.

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he Food and Drug Administration soon will begin to scrutinize the warning labels on tanning beds, under a new federal law signed by the president in late September. The Tanning Accountability and Notification Act was included in the Food and Drug Administration Amendments Act of 2007. Four members of Congress—Sen. Jack Reed (D-R.I.), Sen. Johnny Isakson (R-Ga.), Rep. Carolyn Maloney (D-N.Y.), and Rep. Ginny Brown-Waite (R-

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Fla.)—originally sponsored the TAN Act. Under the new federal law, the FDA is being directed to determine if the label is positioned correctly, whether it gives sufficient risk data, whether alternative warnings would better communicate risks, or if there is no warning that could communicate the risk of using tanning beds adequately. To reach those determinations, the law requires the FDA to conduct tests with consumers; the agency is to issue a report by September 2008. See TAN Act page 17

C OURTESY D R . D IRK E LSTON

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

News

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Biologics Compared For Plaque Psoriasis
BY BRUCE JANCIN

Diet Increases Effect of Low-Dose Cyclosporine in Psoriasis Patients
BY BRUCE JANCIN

Denver Bureau

Z U R I C H — Infliximab is the most effective biologic induction therapy for patients with moderate to severe plaque-type psoriasis, according to a meta-analysis of 17 randomized placebo-controlled clinical trials. Of patients receiving 10-12 weeks of infliximab (Remicade) induction therapy 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 efalizumab (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 weekly, 7.5 for efalizumab, and 3.4 with alefacept, according to Dr. Reich of Dermatologikum Hamburg (Germany). Infliximab also was associated with greater improvements in organ-specific quality of life as assessed by the Dermatology Life Quality Index (DLQI). At week 10, 47% of infliximab-treated subjects reported that psoriasis no longer had any effect on their health-related 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 contrast to the rather dazzling short-term results seen with infliximab as induction therapy for psoriasis in the carefully controlled setting of industryfunded 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, however, 74% of initial responders had abandoned 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 because of loss of efficacy. Particularly susceptible to drop out were patients with predominantly acral psoriasis and those treated on demand rather than in accord with the recommended treatment schedule of dosing every 6-8 weeks after the loading 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 maintenance 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 ScheringPlough Corp., which markets the biologic agent elsewhere. ■

Denver Bureau

Z U R I C H — Combining a supervised weight-loss diet with substandard-dose cyclosporine in obese patients with severe chronic plaque psoriasis makes for very effective therapy, Dr. Paolo Gisondi reported at the annual meeting of the European Society for Dermatological Research. The clinical implication of this finding? “A global approach to obese patients with severe 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 psoriasis 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 efficacy. Then they were randomized to either a dietitian-administered low-calorie diet designed 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 basis, 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 Severity 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 general population. The rationale for the dietary intervention hinged on prior reports that a calorie-restricted diet results in clinical improvement and reduces inflammatory markers in obese patients with other chronic inflammatory diseases, including asthma and rheumatoid arthritis, he explained. In accord with the prior studies involving other chronic inflammatory diseases, C-reactive protein levels in the obese psoriasis patients were elevated at baseline and dropped significantly in the dietary intervention group. Asked why he chose to prescribe suboptimal-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 cyclosporine would predictably result in a high PASI-75 with or without the dietary intervention. Plus, low-dose cyclosporine means fewer side effects and less expense. ■

Obese Psoriasis Patients Who Achieved a PASI-75
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

D A T A

W A T C H

Number of All-Cause Psoriasis Hospitalizations Up 83% Over a 12-Year Period
77,404

54,996 42,302
E LSEVIER G LOBAL M EDICAL N EWS

1993

2000

2004

Note: Based on data from the Nationwide Inpatient Sample. Source: Dr. Omar Dabbous

At week 12, the study end point, 67% of patients treated with 45 mg of ustekinumab and 76% of patients treated with 90 mg achieved at least a 75% reduction in psoriasis as measured by the Psoriasis Area and Severity Index (PASI-75), compared with just 4% of the patients treated with placebo. Additionally, 42% of patients in the lowdose group and 51% of patients in the highdose 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 either dose of ustekinumab experienced significant improvements in several quality of life measures, compared with patients receiving placebo. “These patients ... were some of the happiest patients that I’ve ever had the pleasure of treating with an experimental medication,” said Dr. Craig Leonardi of St. Louis University, and lead investigator of the study. “These results are wonderful. It validates the pathway as a target; 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-

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 experiencing at least one adverse event, and 1%-2% of patients in all three groups experiencing at least one serious adverse event. The drug was not associated with any significant effects on laboratory parameters. There was one death in the trial of a patient receiving the 90-mg dose of ustekinumab. The patient died of congestive cardiomyopathy. 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 disclosed during study enrollment. If approved by the FDA, Janssen-Cilag companies will market the drug outside the United States, while Centocor Inc. has exclusive marketing rights in the United States. Dr. Reich and Dr. Leonardi received grants from Centocor on a per-patient basis for conducting the trial. ■

E LSEVIER G LOBAL M EDICAL N EWS