Lupus : Treatment - Part 2, New Therapies

by Food and Drug Administration (FDA)

(Page 4 of 4)

Some people who experience severe flares also may need immunosuppressive or chemotherapy drugs, which are given by mouth or infusion. Examples are Imuran (azathioprine), Cytoxan (cyclophosphamide), and Sandimmune and Neoral (both cyclosporines). These drugs suppress the immune system and help limit organ damage. But they also make it harder to fight off infection, and all raise the risk of anemia and cancer. Other side effects are nausea, vomiting, hair loss, osteoporosis, and ovarian failure.

"Our biggest challenge is the toxicity of the drugs — trying to control the pathological immune response without doing considerable harm," says Wofsy. "In some cases, the treatment is worse than the disease. We always have to ask: "Are we making the person susceptible to infection? Are we causing osteoporosis? What other harm are we doing?"

Progress has been made in preventing and treating some of the secondary problems related to lupus, Wofsy says. For example, people taking corticosteroids may also require other medications to help prevent bone loss.

"We do a much better job of controlling hypertension, preventing osteoporosis, and treating infections with antibiotics in patients with lupus than we used to do," Wofsy says. "But the advances with lupus have not yet come in the form of treatments that reverse the immunologic problems that are at the heart of the disease."

Developing New Therapies

The FDA hasn't approved any drugs specifically for lupus in nearly 40 years. Lupus experts say that the disease has not attracted enough of an investment from drug companies. It also can be difficult to develop data that prove a drug's safety and effectiveness because lupus is such a highly variable disease. And the FDA can approve a drug only after determining that the benefits outweigh the risks in a comparative study.

One concern in drug development is that a drug may prove beneficial for one organ but may turn out to damage another. There are also challenges with assessing effectiveness in a disease in which symptoms come and go in cycles. And because lupus develops gradually, a patient may develop a new symptom that could be due to the disease. Or it could be a side effect of medication.

According to the FDA, creative trial design is needed to overcome these challenges. The agency's recently released guidance discusses the need for clear clinical endpoints to show what's being measured in trials and what the outcome means for both short- and long-term results.

Promising approaches under investigation for lupus include hormone modification drugs, immunosuppressive drugs that are more selective, and new biologics. Researchers are especially looking for lupus treatments that can minimize the use of corticosteroids.

In people with lupus who have severe kidney disease, CellCept (mycophenolate mofetil), a drug approved for organ transplants, has helped some of them. Of the biologics under study for lupus treatment, some block B cells and other parts of the immune system to both increase effectiveness and lower side effects. Examples include Rituxan (rituximab), made by Genentech Inc. of South San Francisco, Calif., and Lymphostat-B (belimumab), made by Human Genome Sciences Inc. of Rockville, Md.

Researchers are also investigating stem cell transplantation. In this process, stem cells are selected from the person's blood or bone marrow through a procedure known as leukopheresis. The stem cells are stored outside of the body. The individual receives potent systemic drugs or biologicals in an attempt to destroy the immune system cells that are attacking normal tissue, and is then reinfused with his or her stored stem cells. The goal is to destroy the cells that may be responsible for initiating inflammation, and to stimulate new cells that will no longer be programmed to attack normal tissues.

According to the National Institutes of Health (NIH), participating in clinical trials for new treatments can give people a more active role in their health care, access to new treatments before they are widely available, and a sense of making an important contribution to medical research. The NIH recommends that people find out about the benefits and risks of any clinical trial they are considering, including information on why researchers believe that an experimental treatment holds promise. In order to achieve the most reliable results, clinical trials have inclusion and exclusion criteria to determine who can participate.

Wofsy calls this an exciting time for lupus research. "There are more active clinical trials for lupus than ever before, and there are a number of promising ideas," he says. "They won't all work, but there is reason to hope that we will find treatments for lupus that are safer and more effective."

About the Author

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FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.