The Autoimmune Epidemic: Bodies Gone Haywire in a World Out of Balance--and the Cutting-Edge Science that Promises Hope (No Series) (29 page)

In lupus trials, the Rituxan story is less rosy: in 2006 the FDA issued a warning following two deaths from viral infections of lupus patients who were using Rituxan “off label”—meaning that they had been prescribed the drug even though it has not yet been approved for lupus. Doctors and analysts are unsure about cause and effect and may never know the truth; lupus patients have compromised immune systems, and it’s impossible to say whether Rituxan alone was responsible for these infections. Two clinical trials using Rituxan to treat lupus patients are now under way. So far, Rituxan has an overall record that is better than many other newer drugs, but how promising the drug turns out to be will only be truly known after it has been in use in patients with autoimmune disease for the next five to ten years.

Meanwhile, as drug companies see a worldwide trend in which rates of lupus are doubling and tripling, there is a horse race just breaking out of the starting gate to see who can be the first one to gain approval to make and market the first new lupus drug in many decades. At this writing, there are currently three other drugs in late-stage lupus trials in addition to Rituxan. These include Orencia, a rheumatoid arthritis drug new to the market that researchers hope will help lupus patients; LymphoStat-B, which has had some success in reducing lupus disease activity; and CellCept, a drug in use for organ-transplant recipients, now being tested in lupus patients with severe kidney disease—but which also carries an increased risk of lymphoma because of the way it suppresses the entire immune system.

“I FELT LIKE A TICKING TIME BOMB”

For many patients, that horse race is regrettably late out of the gate. Joy England, a thirty-two-year-old mom from Georgetown, Texas, began her struggle to find out what was happening to her in 1999, when she was twenty-four years old. Sore joints and a flulike fatigue that never abated led her to seek out the help of her family practitioner. England’s doctor took her ailments seriously from the get-go—four people on England’s mother’s side had rheumatoid arthritis, and her mother had diabetes. Her doctor ran an antinuclear antibodies test, or ANA. England’s ANA factors were moderately high, but her doctor reassured her that healthy people sometimes have comparable ANA counts and nothing comes of it at all. They could only wait and see whether this might turn into something more worrisome for Joy.

A committed athlete who, up until her illness, had been running on nearby park trails six days a week and working nine hours a day at a job she loved, traveling as a representative for a teachers’ association, England felt she was getting weaker by the day. “I woke up with joint pain and fatigue and I went to bed with it being worse than when I woke up,” she says. She went on the Internet and found out that a high ANA count could be indicative of lupus, rheumatoid arthritis, and scleroderma, as well as a number of other autoimmune diseases—but that testing for specific antibodies unique to each of those diseases is still imperfect, and many patients aren’t diagnosed until long after their symptoms become more severe. England had recently become engaged to a firefighter who worked twenty-four-hour shifts. When he was working and she was alone for long stretches of time, she says, “I would lie on the couch in my apartment and ask myself how could this be happening to me—a twenty-four-year-old runner with a great job, so in love for the first time in my life and planning my wedding?”

Six months later, England’s doctor sent her to a rheumatologist. The rheumatologist ran another ANA panel but could not find a pattern that bespoke any particular autoimmune disease, be it lupus, scleroderma, or rheumatoid arthritis. He was hesitant to start any medications, well aware of the significant health risks and side effects associated with most drugs used to treat autoimmunity. That, in conjunction with the fact that they did not yet know what disease it was they were going to need to treat, made it imprudent to commence with sledgehammer medications. Still, he told Joy that her high ANA titer was worrisome and would likely turn out to be indicative of an autoimmune disease down the road. Meanwhile he prescribed Advil four times a day and told her that they would keep a keen eye on the situation.

For the next year Joy lived, she says, in diagnostic purgatory—waiting, on one hand, to discover what might be wrong with her as her symptoms steadily worsened, and on the other hand planning for the “wedding moment I’d wanted and waited for.” At one point, she jokes, she was carrying a color-coded binder full of the details for her wedding and a second binder with all the information she was gathering on autoimmune diseases.

Around the time Joy and her fiancé decided to move into his house together, along with her schnauzer, Buster, and David’s Dalmatian, Lucky. Many nights, she would listen to the fire scanner David had had installed in the house, enabling Joy to hear what was happening, live, when David was in the midst of fighting a fire. While David was fighting actual fires, Joy was fighting what she likened to her own fire, only this one was happening from within. She would often lie on the sofa with Buster and Lucky next to her for company, sleepless from the constant pain in her hot, swollen, inflamed joints, unable to even shift her weight—her distress exacerbated by the sheer anxiety of not knowing what was happening to her body. “I would watch a television show and see people my age running through a field and it would suddenly hit me that I might never be able to run again.”

Joy was taking more and more sick days, unable to manage the joint aches and weakness, though she had to force herself to go into work as often as she could because she needed the health insurance. She was retested for autoantibodies but results remained inconclusive. She had been struggling to manage symptoms without any diagnosis for a year and a half and she was steadily deteriorating. The Advil wasn’t helping. Because her symptoms were intensifying, her rheumatologist started her on a nonsteroidal anti-inflammatory medicine, Relafen, used often in treating arthritis. It didn’t do much for Joy. Whatever autoimmune disease it was, it was continuing to progress. “I felt like a ticking time bomb, and we had no way of doing anything to defuse it,” England says. “My doctor and I knew that eventually I would fall into one of these autoimmune-disease categories, but meanwhile there was nothing we could do to keep my body from attacking itself. We could only watch and wait for the other shoe to drop.”

After Joy and David’s wedding, Joy—who was advised not to use birth-control pills because of the link between estrogen and autoimmune disease in women—found herself unexpectedly pregnant. She was frightened, but during the pregnancy she found, surprisingly, that her symptoms improved—as can sometimes happen in autoimmune disease. But after her daughter Emily was born, Joy’s health started going downhill fast.

Over the next several months, Joy’s joint pain and swelling became so intense that it was hard for her to get out of bed and lift her newborn daughter from her crib. Her white blood cell count fell very low. Then she developed a rash across her back that looked like a raging case of teen acne. She put some acne cream on it but it didn’t go away. She went to her dermatologist, who decided to biopsy the eruptions. The biopsy revealed that Joy did, indeed, have systemic lupus. At that point Joy England was finally given the lupus label. Her rheumatologist put her back on Relafen and began treating her with Plaquenil, a medication used for the treatment of malaria that is also useful in treating lupus and rheumatoid arthritis, although how Plaquenil helps with inflammation in autoimmune disease is still not well understood.

But it wasn’t enough. By then, Joy England had gone largely untreated for lupus for four years. She continued to have severe flares every other month and was frequently put on prednisone for a month at a time. She would feel better for a short time, only to flare again. Her rheumatologist worried about the ramifications of having her on a roller coaster of prednisone and decided to try Imuran, a chemotherapy medication that suppresses the immune system in general, which he and Joy had been hoping to avoid since it carries with it a heightened risk of lymphoma and leukemia. She stayed on Imuran for fifteen months. At that point she seemed stable enough that her doctor began to wean her off it, but suddenly she had another severe flare—her joints swelled and she developed pleurisy, an inflammation of the lining of the lungs. She began having severe migraines. And so she began another course of prednisone.

Joy and her rheumatologist often discuss new drugs coming down the pike that might be helpful in lupus—a disease for which no new drug has been approved for forty years—but clinical trials are only now in the works, and the potential health risks and side effects of the new drugs are far from known. “My doctor told me that if I were an older patient he might try me on a new drug that’s being tested in clinical trials in lupus patients, like Rituxan,” Joy says. “But I’m a young mom, and the jury on these drugs isn’t yet in and it isn’t going to be in for years. None of us want to take the chance that I might be that one patient who develops a rare, fatal viral infection.”

Joy says she’s perplexed as to why researchers haven’t done more sooner to help lupus patients. “I always worry about the long-term damage that being in this constant state of inflammation is doing—damage that can’t be reversed and could have been prevented. To have a drug that would target just the autoimmune process that is causing lupus without knocking out my entire immune system would make all the difference for me.” It is very difficult, she says, “having a young child and being on an immunosuppressant drug. My daughter is in day care, and if she gets sick for a few days then I usually get it and I get sick for weeks—which brings on a flare and then I need more immune-suppressing drugs. It’s a vicious cycle.” Joy and David always talked about a big family when they first fell in love, but they know it would be extremely risky given how Joy’s disease flared after the birth of their daughter. As her husband David says, “I’d rather have Joy here than two children and no wife—and we have one child who needs her mom.”

“It makes me angry,” Joy says. “Motherhood is something I truly love, and I want my daughter to have a brother or sister. If I knew there were drugs available that could safely help me to be stable then I would feel I could go off them, get pregnant, have a baby, and then go right back on. But that’s not the case, and it’s probably not going to be the case for a long time.” To do what she can to aid the lupus cause, England raises money for the Alliance for Lupus Research and finds corporate sponsors to support the Austin lupus walk. Meanwhile, she has never gone for a run since the summer eight years ago when her illness began. She is limited as a mom—she can’t run after her daughter, she can’t be in the sun with her at the swimming pool or on the soccer field because sunshine can provoke a flare. And when she does flare, she is often in bed, unable to be the mom she once imagined she would be.

One can only wonder: What if Joy England’s condition had developed at some future time when doctors would not only be able to better detect complex diagnostic biomarker patterns that foretell disease earlier on, but when drugs finally arrive on the market that will help to block only the cells and autoantibodies involved in autoimmunity without targeting the entire immune system? How many Joy Englands might then be able to go on and live their lives as the mothers, wives, athletes, and career women they always dreamed of being—without being broken down by years of pain and suffering?

THE ROAD TO REGENERATION

These diseases will not be felled by a single magic bullet. It will take exploring numerous avenues and eclectic approaches. For those with rheumatoid diseases such as lupus and rheumatoid arthritis, one set of drugs might prove most useful, while for those with neurological autoimmune diseases, other approaches may prevail. One such vanguard venture in the works for those with neurological autoimmune diseases is now under way at Johns Hopkins Hospital, under the direction of Dr. Ahmet Hoke, associate professor and director of the Division of Neuromuscular Diseases of the Department of Neurology and Neuroscience. In his lab on the fifth floor of the pathology building of Johns Hopkins Hospital, Hoke—who is also my own neurologist—recently discovered that a unique growth factor produced naturally by our nerve cells has a surprising ability to regenerate nerves in the body after they’ve been damaged by diseases such as multiple sclerosis, transverse myelitis, Guillain-Barré syndrome, and chronic inflammatory demyelinating polyneuropathy.

Once nerves have been impaired, regeneration is difficult. This is especially true in humans, versus lab mice, given the long distance between our spinal cords and the extremities where nerve damage so often occurs. To regenerate nerves in our arms and legs, axons have to shoot out from the spinal cord and travel as much as three feet in a human to get to a foot or a toe that no longer moves. While investigating one growth factor, called pleiotrophin, that has been around for a while—though no one has known its exact effect—Hoke uncovered something surprising. Pleiotrophin has a particularly robust ability to increase the growth of motor neurons and appears to aid in regenerating axons over long distances, which then allows damaged muscle to move again. In experiments in lab mice, even very low doses of pleiotrophin, or PTN, significantly enhanced the regeneration of myelinated axons, leading Hoke to hope that PTN may lead to novel treatment options for neurological autoimmune disease.

This is significant because most available therapies for those who have peripheral neuropathy, or damaged nerves in the peripheral limbs of their bodies, are designed to control painful symptoms, not to treat the underlying nerve degeneration. Others are protective therapies—such as Rituxan, which researchers hope will prevent autoimmune-disease relapses—but protective therapies do not help nerves to regenerate. “Pleiotrophin looks to be a unique growth factor that can cover long distances quickly,” says Hoke. “Uncovering its potential may lead to the development of growth factor–like drugs that will improve the intrinsic ability of neurons to regenerate and speed the growth of damaged axons in the body—without the side effects that come with drugs that tamp down T-cell and B-cell interactions.”