Just say no to drugs.
This phrase has been part of American culture since the 1980s, when first lady Nancy Reagan proposed it as an answer to the drug problem in the U.S. And although it may be good advice when it comes to the recreational use of mind-altering substances, it’s bad policy if you’re talking about rheumatoid arthritis.
Rheumatoid arthritis is an incurable, inflammatory, autoimmune disorder in which the body’s immune system mistakenly attacks its own healthy tissue for reasons that are poorly understood. RA is probably most closely associated with potentially disabling destruction and deformation of the joints, but it also attacks many of the body’s major organ systems, including the heart, lungs, blood vessels, eyes and skin.
“If you don’t treat the disease, the consequences are life-threatening,” according to Dr. Roger Kornu, a rheumatologist with the University of California, Irvine.
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Over the past two decades, advances in pharmaceutical research have led to the development of several powerful medications that have significantly changed the course of the disease. They include disease-modifying anti-rheumatic drugs and biologic response modifiers.
DMARDs work by blocking the overall inflammatory response of the immune system, and include drugs like methotrexate, sulfasalazine (Azulfidine), leflunomide (Arava) and hydroxychloroquine (Plaquenil).
Biologics are genetically engineered from human genes and work by blocking specific inflammatory proteins, called cytokines, such as tumor necrosis factor-alpha (TNF-a), interleukin-6 and interleukin-1, which are elevated in people with RA.
Biologics include the drugs adalimumab (Humira), certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), tocilizumab (Actemra), rituximab (Rituxan) and others. Most biologics are administered in the doctor’s office or hospital by intravenous infusion or as a subcutaneous or intramuscular injection.
According to Dr. Susan Goodman, a rheumatologist and professor of clinical medicine at the Weill Cornell College of Medicine in New York, the drug or drug combination that the rheumatologist selects when a person is first diagnosed with RA depends on many factors, including whether he or she already has joint or organ damage and, if so, how much.
In addition, DMARDs have a lower side effect profile and are less expensive than biologics, so they are often the first line of defense.
“I — and most rheumatologists — usually start with methotrexate, frequently in combination with hydroxychloroquine, and progress to a biologic if there is not an adequate response. Methotrexate is really the anchor drug in RA, because of its relative efficacy, safety and tolerability,” explains Goodman, who is also an attending rheumatologist at the Hospital for Special Surgery in New York.
“However, if the patient is a woman who wants to start a family within the next year, we wouldn’t start with methotrexate because it can cause severe fetal malformations,” she adds.
It also takes three months to clear out of the system so conception is safe. The DMARD leflunomide has similar concerns, Goodman says.
According to Goodman, although rheumatologists take individual considerations like pregnancy plans into account when choosing the initial medications for RA, they typically follow a formula called “treat to target,” or T2T.
This formula requires frequent assessment of disease activity by determining how many joints are tender and swollen, performing a global assessment of overall functioning and possibly performing lab tests to determine the blood levels of certain markers of inflammation, such as the erythrocyte sedimentation rate and C-reactive protein.
“The most important part of the T2T strategy is discussions with the patient, which are ongoing,” Goodman says. “If the patient has long-standing RA with many damaged joints, or if [he or she] has been very prone to infections, they may not want to expose themselves to the more potent immunosuppressing biologics and targeted therapies,” she explains.
“There are also toxicity considerations,” she says. “If the patient has viral hepatitis, I may ask them to treat that before beginning a biologic.” Goodman is also likely to avoid prescribing a biologic medication in patients with infections such as tuberculosis, or who have frequent exposure to TB.
People who have only recently been diagnosed with RA are often treated more aggressively in an attempt to achieve remission of the disease, Goodman adds, although true remission is elusive for most people with RA.
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If the patient is very sick, with overwhelming fatigue, multiple swollen joints, fever and such severe inflammation that they have trouble getting out of bed, Goodman often gives the patient a long-acting injection of a steroid medication called a glucocorticoid, along with the DMARD, so that the steroid gradually leaves the system as the DMARD begins to take effect.
Modern drug therapies and early, aggressive treatment “have completely changed the face of RA,” Goodman says.
Dr. Seth Leopold, a hip and knee surgeon in Seattle, agrees.
“With the advent of biologics, medical options [for people with RA] are so much better that they have almost eliminated the need for joint replacement surgery, compared with 20 years ago,” says Leopold, who is a professor in the Department of Orthopaedics and Sports Medicine at the University of Washington School of Medicine.
“It’s not even a contest. Rheumatologists have us beat by a mile,” he adds.
Despite these advances, Goodman indicates that about 30 percent of people with RA do not respond well to drug therapy. In these cases, “you keep trying different combinations of drugs, integrate surgery to clean out the inflamed synovium [lining of the joint] and look to medications like glucocorticoids as an ongoing therapy, instead of restricting it to flares,” she says.
Goodman indicates that certain factors can help predict who will respond to drug therapy and who won’t.
“Individuals with high levels of certain antibodies like rheumatoid factor, or X-ray evidence of joint damage at the time of diagnosis may not respond well,” she says. Patient characteristics like obesity or smoking also decrease the likelihood of a good response to medication.
“However, although these features raise concerns, none are reliably predictive, and the best approach is frequent re-assessment [of disease activity] to quantify the patient’s response,” she adds.
Biologic medications can have side effects, like new or recurring infections such as shingles or tuberculosis. In addition, some people develop antibodies to biologics, which can make them less effective over time, Goodman says.
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Current research is examining different combinations of drugs for the treatment of RA, according to Goodman, and there is also an effort to identify new drugs.
“But I am impressed with the increase in efficacy that can be achieved by simply optimizing the use of our existing drugs and by adjusting doses based on the patient’s disease activity level,” she says. “This can be as simple as switching the route of administration for methotrexate from oral to injections, or by combining known medications.”
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Doctors Are Encouraged by Advances in Drug Therapy for Rheumatoid Arthritis originally appeared on usnews.com
