Less-Toxic Drug for Lupus

Oct. 27, 2003 -- For many women, a lupus diagnosis means a lifetime of painful flare-ups and drugs with terrible side effects.

But after 30 years with no new treatments, some doctors have welcomed a drug called CellCept, which they are predicting will yield a much-improved quality of life for lupus patients, and possibly open the door to primary care physicians assuming a greater role in lupus treatment.

A new study released at the American College of Rheumatology annual meeting on Friday finds that CellCept is just as effective as the current lupus drug, Cyclophosphamide (known as Cy), but CellCept has far fewer side effects than Cy.

Side effects from Cy include a high risk of infection, severe nausea, and infertility.

"It's the silent women's health disease that no one is talking about," says Sandra Raymond, president of the Lupus Foundation of America. Systemic lupus erethematosus (SLE) is an auto-immune disorder in which the immune system attacks healthy tissues, including skin, kidneys and the brain.

Of the 1.5 million Americans battling lupus, most are young women, aged 20-40.

Rheumatologist Erin Arnold from the Illinois Bone and Joint Institute said the use of Cy was "dictated by the side effects of therapy. Because of the risk … patients are either reluctant to comply or are simply unable."

Dr. John Hardin, a rheumatologist from the Albert Einstein College of Medicine said Cy was a difficult drug to administer and very toxic.

"It is not just patient compliance [that's a problem]; it is the difficulty overall of managing a drug that suppresses the immune system to such a degree that the treatment can be as bad as the disease," Hardin said.

What Is CellCept?

Like Cy, CellCept suppresses the immune system to counteract the immune system's attack on healthy tissue. CellCept has been used for years to prevent rejection in organ transplants, but only in the last 1-2 years did doctors begin using it to treat lupus.

The study released this week was the first multicenter, U.S. study that performed a head-to-head comparison of CellCept versus Cy. A total of 130 lupus patients with advanced lupus nephritis (lupus of the kidneys) took either Cy or CellCept for six months.

There were 14 complete remissions with CellCept versus 4 complete remissions with Cy. CellCept also induced more partial remissions, 21 compared to 14 for Cy. These results suggest CellCept is at least as effective in treating lupus nephritis, and may even edge out Cy. Cellcept also had fewer complications and fewer side effects.

"This is an outstanding and well-conducted multicenter study," said Dr. Frank Arnett, Chairman of the Deptartment of Internal Medicine at the University of Texas-Houston Medical School. Arnold said the drug was a "wonderful thing to be able to offer patients."

Some Cautions

Other specialists are more guardedly optimistic. Dr. Larry Moreland, rheumatology specialist at the University of Alabama, Birmingham, said: "It was not a double blind study and it was of short duration. The numbers of patients treated was small. The less … infection seen with CellCept is of note, but there was not a [significantly] better efficacy with CellCept."

Dr. Daniel Wallace, rheumatology expert at Cedars-Sinai/UCLA School of Medicine, agrees. "[CellCept] is safer than standard chemotherapy, but … a combination of chemotherapy with CellCept maintenance may be the ultimate way to go. The long-term effects and potential long-term efficacy of using the drug in lupus is still not known."

"CellCept will not be for everyone," Raymond acknowledges. One 28-year-old woman in the study had to be taken off the drug when she had an adverse reaction.

The Future of Lupus Treatment

One possible twist that widespread CellCept use could trigger: primary care physicians taking over management of lupus. As of now, drug management of lupus is often a difficult venture, requiring specialist supervision. If CellCept proves both safer and more effective, the burden of lupus treatment could shift somewhat from rheumatologists to primary care physicians.

"I have a few patients on CellCept related to transplants, but I have no Lupus patients — they are usually seen by specialists since they are so sick. However, if this drug works, primary care doctors may start seeing more of them again," said Dr. Lyle Berkowitz of the Northwestern Memorial Physicians Group.

M.D. Neil Brooks agrees, but adds, "If there are therapies that are less hazardous and are easier to handle then primary care might adopt them, although I believe this would be a very slow process."

Lupus May Lead the Way

More research is needed, both on CellCept and on other possible lupus treatments, primary care physicians and specialists concur. Raymond agrees, "This is only one step. We need more public interest. We need more public and private money dedicated to fighting this disease."

Getting the fire started under lupus research has proved difficult. Lupus is a relatively rare disorder, and the complex nature of it (any organ can be affected) makes it tough to untangle. But Raymond believes that money devoted to lupus research could yield many other benefits.

"Lupus is the prototypic autoimmune disorder. Other immune disorders follow lupus research because what is learned here often applies to them. And when you lump all the autoimmune disorders together, you are talking upwards of 20 million people."