Life after Raptiva

| Amy Stork

[This story originally appeared in the Summer 2009 print edition of Psoriasis Advance.Editor]

Three years ago, Earlene Fogle could barely walk. She had to delay her career as a radiology technician, and she was crying herself to sleep at night.

The 47-year-old Dallas resident suffers from palmar-plantar pustular psoriasis—a rare form of the disease that causes painful blisters on the hands and feet, followed by cracking and peeling. She sometimes had to wrap her raw hands in gauze to go to work. The itching on her feet could be excruciating. After years of failed treatments, Fogle finally found relief on the biologic drug Raptiva (efalizumab), made by California-based Genentech.

Two months after starting the injections, Fogle was happily strolling the beach with her husband and running her two children here, there and everywhere. After another six months, her skin was completely clear.

"I can't tell you how wonderful it is to walk without dreading it," she said "Looking back, I don't think I realized how bad it was. I didn't realize the mental depression I was probably in because of the pain and anxiety—until I got better."

Then in June, Genentech withdrew Raptiva from the market after the drug was linked to the deaths of at least three patients from a rare but often fatal brain disease, progressive multifocal leukoencephalopathy (PML). Doctors estimate that 80 percent of the public harbors the virus that causes PML, but the disease occurs almost exclusively in people with severely weakened immune systems.

For Earlene Fogle and many others who had found peace and health on Raptiva, the announcement felt like a punch in the stomach.

"It was not an easy decision," said Dr. Ivor Caro, Genentech senior medical director. "While we accept that many patients around the world have benefited from Raptiva, the benefits versus the risks changed."

A short history

Raptiva was approved for treating moderate to severe psoriasis in 2003. Genentech estimates that since then, 46,000 patients have been treated with the drug. About 2,000 were taking it at the time of the recall.

"The development of PML, we felt, was directly related to Raptiva, and we were not able to in any way mitigate the risk or identify those most likely to be at risk," said Caro. All of the patients who developed PML had been on Raptiva for some time, and none were taking any other immunosuppressant drugs.

For some patients, the fact that other biologic drugs still on the market have similar links to PML led to speculation that Genentech's decision was partly financial. Was the risk just not worth it for a drug taken by so few people?

"I think in development on the clinical side that really does not play a part," said Genentech's Caro. "It was really about patient safety."

Caro and other doctors said that while there are many treatment options for psoriasis, drugs that have similar risks may be a last resort for patients with other diseases—and that is a consideration when balancing risk and benefit.

Her 'miracle drug'

In April, Genentech sent letters to patients and doctors explaining that Raptiva would not be available after June 8, giving patients time to transition to a new treatment plan.

Like many dermatologists, Terriann DiLalo's doctor advised her to taper off Raptiva while starting a new treatment combining the drug methotrexate and the biologic drug Humira (adalimumab). Despite the overlap, DiLalo's psoriasis worsened drastically.

"The flare began between the fourth and fifth week of being off Raptiva," said the 53 year-old New Jersey woman. "I went from 90 percent clear to 80 percent covered. It felt like bugs crawling over me."

Such flares have been common in patients transitioning off Raptiva, said Dr. David Fiorentino, assistant professor of dermatology at Stanford University School of Medicine. He uses a number of agents such as cyclosporine, methotrexate, or ultraviolet (UV) light therapy to help to mitigate these flares.

For some patients, Fiorentino was forced to prescribe short courses of prednisone, a steroid medication that, although effective in the short term, can have many side effects with chronic use.

For long-term management of patients off Raptiva, "we're also using a lot of combination therapy, like methotrexate and UVB [ultraviolet light B], for example," he said.

Although there are many treatment options, Fiorentino said there may not be one single treatment that will work as well as Raptiva did for certain people, particularly those who hadn't responded well to other biologics.

DiLalo was one of those patients. Biologics she tried didn't help her psoriasis. Until Raptiva came along, "it would come and go, but it affected my life. My wedding dress was high-necked with long sleeves. My prom dress too.

"Raptiva was my miracle drug. Those two years were the first time [I was clear] since I was 11 years old."

Questions about biologics

Patients and doctors say the Raptiva story may continue to play out in the way the psoriasis community sees biologic drugs in general.

"There are days I wish I never started [Raptiva]," said Phil Aaronson, a 37-year-old who works in the computer industry in the San Francisco Bay Area. "When you're on effective medication, you hit a certain normal where you don't wake up and go to bed thinking about psoriasis. When it's taken away from you, it's the biggest, scariest wake-up call."

"In the backs of all of our minds, it provides a sense of uncertainty of the safety of biologic therapy," said Dr. Kristina Callis Duffin, who specializes in the treatment of psoriasis as an assistant professor at the University of Utah Department of Dermatology. "People are going to say, 'What is the long-term risk of a drug that is immunosuppressive?' "

"It's not an insignificant issue," said David Fiorentino. "Patients and doctors tend to group these agents, and when we see a wart on one, it becomes a wart on all even if they have a completely different mechanism of action."

He said dermatologists need to let patients know that Raptiva worked in a different way from other biologic treatments.

Added Bruce Bebo, National Psoriasis Foundation research director: "Because of Raptiva's distinct mechanism of action, this experience with the drug doesn't really provide insights into the risks of PML for the other biologics."

Making the switch

Meanwhile, patients are adjusting to a post-Raptiva world. Knowing that many people experience flares when they switch from Raptiva, Earlene Fogle obtained a three-month supply just before it disappeared. She also extended the time between injections, from once a week to about every two weeks. So far, she says she's had "only a little peeling."

She's hoping the U.S. Food and Drug Administration decides to approve the drug Stelara (ustekinumab)—which has done well in clinical trials but is still awaiting FDA OK—before her Raptiva runs out. If Stelara doesn't become available, Fogle plans to switch to the biologic drug Remicade (infliximab) along with the drug cyclosporine "if a bad flare happens." She is, she says, both anxious and hopeful. [Stelara was approved in 2009.Ed.]

Phil Aaronson is now taking the biologic drug Enbrel (etanercept). Terri DiLalo's painful flare didn't prevent her from going with her husband on a 30th-anniversary cruise, during which she slowly began to get better. Now, she says, she's about "80 percent clear." She has a message for others whose psoriasis gets worse during the switch from Raptiva: "The awful Raptiva flare does eventually go away!"

And physician David Fiorentino has a hopeful message for former Raptiva patients. "There are other agents in the pipeline that will provide us with treatment options. Nothing is forever—some method will work for you."

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