NEW YORK -- The biologics "Brat Pack" may be hogging the spotlight in psoriasis therapy lately, but there's still room on stage for an experienced performer like phototherapy, insisted Dr. John Koo at the Ninth International Psoriasis Symposium.

The truth of the matter is, not one of the

They are, however, infinitely more convenient and far less messy. But that convenience comes at a price that many communities, and many countries, can't afford.

"I have no illusion that in the age of the biologics, Goeckerman therapy or PUVA is going to make a huge comeback. But for places where the biologics are not affordable, these are very good, cost-effective alternatives," said Dr. Koo of the University of California, San Francisco.

They may not be sexy, but PUVA and Goeckerman UVB regimens can clear psoriasis very effectively. With modern "ultra-Goeckerman" narrow-band UVB with crude black coal tar and salicylic or lactic acid, 56% of patients will have 75% improvement in Psoriasis Area and Severity Index (PASI 75) scores within 1 month, and 96% will reach PASI 75-level clearance after 2 months of treatment.

"It's pretty amazing. You can get rid of a lot of scaly plaques pretty quickly," Dr. Koo said, adding that 90% of patients will remain clear 8 months after cessation of UVB therapy. For many patients, PUVA is similarly effective, especially if combined with low-dose retinoids.

"I'm not sure that infliximab is any more effective than PUVA when done properly. And compared with the best narrow-band UVB treatment, you'd have to double the recommended dose of alefacept to obtain the same therapeutic result," he said. "So I think that PUVA and UVB still have a role. The biologics are very, very exciting, but our view of reality can get very warped. These other treatments shouldn't be forgotten."

Casting Shadows on PUVA

Even before the advent of the biologics, phototherapy had fallen on hard times in the United States. With the rise of managed care, many phototherapy centers had to close. PUVA, in particular, fell out of favor owing to the perception that it increases risk of malignant melanoma.

That concern is grossly exaggerated, Dr. Koo said. "There are now 23 published [studies] on this issue. Only one, the U.S. 16-center study, has shown an increased risk of malignant melanoma," he said. "We don't have any studies to corroborate that. But that one study received such media attention that it scared the hock out of lots of practitioners, many of whom dropped PUVA."

There are, however, some major problems with that 16-center trial, the biggest being the fact that there was no real control group (Cancer 73[11]: 2759-64, 1994). The elevated risk seen in PUVA-treated patients was based on comparisons with data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. But Dr. Koo, whose center was one of the 16 trial centers, stressed that the SEER database is a poor source of melanoma surveillance data.

"There's no mandatory nationwide reporting system for malignant melanoma in the United States," he said. "If the SEER data underestimate the baseline rates of malignant melanoma--and this is very likely--then you will automatically overestimate PUVA-associated cancers."

Dr. Koo noted that all of the available studies on this issue were done exclusively in white populations; there is precious little information on how phototherapy affects dark-skinned populations.

Dr. Jenny Murase, a researcher at the University of California, San Francisco, recently pooled data on PUVA and malignant melanoma from treatment centers in Japan, Korea, Thailand, Egypt, and Tunisia, and found only three treatment-associated skin cancers in an aggregate population representing more than 10,000 patients.

"Overall, you see a 0.07% increase in skin cancer over the background rates worldwide, and this is based on years of follow-up and thousands of patients," Dr. Koo said at the conference, which was sponsored by the Skin Disease Education Foundation. The SDEF and this newspaper are wholly owned subsidiaries of Elsevier.

"Dermatologists in the United States love to scare ourselves. But the perception that PUVA increases malignant melanoma is like a little mouse in front of a candle flame casting a huge shadow," Dr. Koo said. "For the sake of our patients, many of whom are grossly undertreated, we need to stop scaring ourselves. PUVA is still a very effective therapy giving long-term remissions. We have almost 30 years of data showing no serious internal systemic side effects."

Resurrecting Goeckerman

Dr. Koo remains an unabashed advocate for what he terms "anything goes" Goeckerman, with the addition of various combinations of anthralin, tazarotene, vitamin D analogues, oral retinoids, bath PUVA, and laser therapies to the basic core Goeckerman regimen of UVB with black coal tar. He refers to this approach as "turtle-stacking": leveraging the efficacy of several relatively slow-acting but safe modalities in a way that optimizes outcomes without increasing the risk of adverse effects.

At 3 months, anything-goes Goeckerman stacks up very well against the state-of-the-art biologics, at least in terms of therapeutic outcomes, he said.

The downside, of course, is inconvenience. "You do have to consider the impact on a patient of having to drop out of work or other daily activities for 6-8 weeks to do Goeckerman therapy But it doesn't have to be all day," said Dr. Koo.

"You can do the therapy in 4 hours, and some patients can shift their work schedules to accommodate the treatment."

Something Old, Something New

Can the new biologics be folded into phototherapy protocols? Although there are no clinical studies yet, many psoriasis experts see this as a natural, almost inevitable progression.

Combining biologics with phototherapy could improve on the efficacy of either alone, and might be able to reduce the dosage requirements of the biologics, producing a cost savings along the way, said Dr. Alan Mentor of Baylor University Medical Center, Dallas.

Dr. Koo said he has had excellent results using phototherapy and biologics in serial combination. First, clear the thick scaly plaques with phototherapy, and then transition the patient to a biologic such as alefacept. At Dr. Koo's treatment center, some patients are on etanercept, infliximab, or alefacept while concurrently undergoing phototherapy There does not appear to be a photosensitization problem with any of the biologics, he added.

Dollars and Sense

Does this approach make economic sense? There is no question that phototherapy, even when all sorts of nonbiologic adjunctive agents are added on, will be cheaper than the new biologics. Although he is as enthusiastic as anyone about the treatment potential of the biologics, Dr. Koo turned a critical eye to the bottom line.

"Comparing the cost of phototherapy versus biologics, if you get $1,000 from Medicare to manage psoriasis [and] you have a phototherapy center, you will keep practically all of that money If you get $1,000 for biologics, you'll probably end up keeping about $50, because most of the money will go to the cost of the drugs."