Rheumatoid Arthritis Progress: 50 Years of Advances
There may not be a cure for arthritis yet, but in the last 50 years or so, rheumatoid arthritis progress has advanced tremendously toward achieving this goal. Today, people with arthritis are better able to have their condition diagnosed and properly treated than ever before. Doctors are able to address arthritis and its symptoms in ways that were barely imaginable in 1958. That was the year the first scientific journal about rheumatology was published. Rheumatology is devoted to the diagnosis and treatment of disorders of the joints and soft tissues, and the new journal, Arthritis & Rheumatism, represented an important step toward the wide distribution of evidence-based information about these disorders. It also gave assistance and lent credibility to family physicians and to physicians entering the young and growing field of rheumatology. To a large extent, this event marked the beginnings of modern rheumatology.
Rheumatoid Arthritis Progress
Only if we look back, can we appreciate the full scope of the changes in the field of rheumatology since its beginning. In the early years of the 20th century, rheumatology did not exist as a separate discipline, and there were no rheumatologists. In fact, before the 1950’s, only a few forms of arthritis had been identified. These included osteoarthritis (OA), which affected older people; rheumatoid arthritis (RA), an inflammatory arthritis that seemed to strike mostly women and occasionally children, causing painful, swollen joints; gout, a very painful type of arthritis often associated with severe swelling of the big toe; and ankylosing spondylitis, which affects the spine.
Big changes in the field of rheumatology were already brewing in the 1940’s. In the early 1940’s, most doctors would have told people with RA that there was little that could be done to help them. “Go to bed” might have been the recommendation. By 1949, however, physicians were excited about a new treatment for RA that some thought might be a cure. In that year, researchers from the Mayo Clinic published a report on several people whose RA had been treated with high doses of cortisone, a natural steroid hormone found in the body, and who had seen their symptoms improve dramatically. (Cortisone is also referred to as a glucocorticoid or corticosteroid.) A nationwide “whistle-stop” train tour was organized to spread the good news. Within a few years, however, physicians learned that high doses of cortisone, while quieting RA symptoms, also had terrible side effects. In addition, when people stopped taking the drug, their RA symptoms returned and were now coupled with the symptoms of cortisone withdrawal and the long-lasting side effects of high-dose steroids.
Since that time, however, rheumatologists have learned a great deal about arthritis and its treatment. A series of discoveries and innovations has helped doctors diagnose and treat arthritis more successfully, while also helping people with arthritis better manage their condition.
Rheumatoid Arthritis Diagnosis and New Research
Rheumatologists are known for their excellent ability to diagnose. Diagnosis involves determining whether a person has arthritis and then determining which of the over 100 types of arthritis the person has. In earlier years, a rheumatologist had only a few tools to make a diagnosis: a thorough examination, an in-depth medical history, and observation over time. Since then, many new diagnostic tests, including blood tests and imaging tests, have been developed. While these newer tests help to confirm the diagnosis, the need for a complete examination and an in-depth history has not changed. Even today, they remain the cornerstones of an accurate diagnosis.
Besides routine blood tests, doctors can order tests to measure levels of inflammation in the blood. This helps them rule in or rule out different kinds of arthritis. They can also order blood tests for autoantibodies. Antibodies are developed by our bodies to fight viruses and bacteria that are foreign and possibly harmful. However, in conditions such as lupus and RA, a person’s antibodies may fight his or her own cells as if they were foreign enemies. In these cases the antibodies are called autoantibodies. For example, many people with RA have high levels of the rheumatoid factor (RF) autoantibody or the anti–cyclic citrullinated peptide (anti-CCP) autoantibody. People with lupus almost always have the antinuclear antibody (ANA), and the anti-Ro and anti-La antibodies are also associated with lupus. There are also autoantibodies associated with scleroderma, mixed connective tissue disease, Sjögren syndrome, and a few other rheumatic conditions. The presence of these autoantibodies gives the rheumatologist additional clues as to which type of arthritis the person has.
In recent years, researchers have been developing genetic tests. Researchers have now identified several genes that can predispose people to certain rheumatic conditions. The first gene connected with a rheumatic condition was the HLA-B27 gene, which is associated with ankylosing spondylitis. Since the 1980’s, more genes have been identified. The HLA-DR4 gene, for example, is now known to be associated with RA. Recent studies of DNA in people with lupus indicate that lupus may be associated with the IRF5 and FCGR3B genes, and scleroderma has been associated with the HLA-DR11 gene. Having any of these genes does not mean a person will definitely develop the associated type of arthritis. It does mean an increased risk, although the increase may only be modest. Perhaps more to the point in a discussion of diagnosing arthritis, the presence of a particular gene may help a rheumatologist confirm a specific diagnosis that the medical history and physical examination point to. At the moment, genetic tests are not widely used to diagnose arthritis. However, continuing research points the way toward a wider use of genetic diagnosis in the future. Also, a knowledge of genetics has helped researchers design effective treatments and offers promise for further treatments down the road.
While there are not yet any blood tests or genetic tests for OA, the most common type of arthritis, researchers are working to develop them. In the meantime, doctors use imaging tests, most often x-rays, to help diagnose OA. X-rays are also used in the diagnosis of other types of arthritis, along with newer tests such as magnetic resonance imaging (MRI) and ultrasound. With the newer tests, a rheumatologist can look into a joint for changes in the cartilage, bone, ligaments, and joint lining that may give clues to the type and severity of the arthritis.
Rheumatoid Arthritis Medicines: Then and Now
In the late 1950’s and early 1960’s, physicians had only a few medicines to offer people with arthritis. Aspirin was common and was often given in high doses (12 or more 325-milligram pills a day) to reduce pain and inflammation. Two nonsteroidal anti-inflammatory drugs (NSAIDs), phenylbutazone (Butazolidin) and indomethacin (Indocin), were also available. Unfortunately, high-dose aspirin, Butazolidin, and Indocin had many potential gastrointestinal side effects, such as irritation and bleeding. (Butazolidin has since been taken off the market.) In addition there was cortisone, which I mentioned earlier, but doctors were wary of using it because of the serious side effects it was by then known to have. These side effects included loss of bone density, weight gain, sleeplessness, high blood pressure, high blood glucose levels, and a reduced ability to fight infection. In children, cortisone even stunted bone growth. Gold injections had become known as a promising anti-inflammatory treatment for RA. Though gold injections could cause kidney problems, doctors had learned to order periodic tests of kidney function to make sure the kidneys weren’t being affected. Hydroxychloroquine (Plaquenil), originally a treatment for malaria, had been shown to help reduce joint inflammation in people with inflammatory arthritis. And doctors were successfully treating gout, which causes uric acid crystals to be deposited in the joints, with medicine that helped to regulate the buildup of uric acid.
While all of these medicines could be effective, many were plagued by side effects or did not work well for everyone. The 1970’s, however, brought additional help. Drug companies began work to produce new arthritis medicines that could meet the needs of the increasing numbers of people with arthritis. They soon came up with new and safer NSAIDs. By the mid-1990’s, approximately 21 NSAIDs were available by prescription and as over-the-counter drugs, including ibuprofen (Advil, Motrin) and naproxen (Aleve). As many of them were very similar, they were dubbed the “me too” drugs. These new NSAIDs were able to help people with almost all types of arthritis. Their major potential side effects, as with aspirin and the other early NSAIDs, were gastrointestinal. People with arthritis and their doctors still needed to be vigilant about stomach irritation and bleeding.
Also in the 1970’s, cortisone was reengineered so it could be used as a joint injection. This new cortisone stayed in the joint, reducing inflammation right where it was needed, without the side effects of oral cortisone. In the beginning, people had to use crutches for one and even up to six weeks after getting a cortisone injection. These injections have now become commonplace, and they have had a major positive effect on joint health. People are able to get their joint injection, rest their joint for a few hours, and go back to their regular activities with their swelling reduced and their pain controlled.
Other drugs first used for inflammatory arthritis in the 1960’s and 1970’s were azathioprine (Imuran) and cyclophosphamide (Cytoxin). As with Plaquenil, doctors noticed their ability to help people with arthritis when they used them for another purpose. Then, in the 1980’s, rheumatologists began noticing something interesting about their patients who had both RA and cancer. Those being treated with methotrexate for cancer were experiencing an improvement in their RA. This led to studies into whether methotrexate could help people with RA, with a focus on greatly reducing the dose. The drug worked. It slowed the disease process of RA, and the lower dose helped people avoid the side effects often associated with high-dose methotrexate, meaning they could take the medicine for extended periods of time. Eventually, methotrexate in combination with NSAIDs became the most common drug treatment for people with RA and other types of inflammatory arthritis, and it is now the tried-and-true treatment for many. New drugs today try to measure up to methotrexate’s record of effectiveness and safety.
Another change rooted in the 1980’s was a rethinking of how to use the available RA drugs. By 1988, when the Food and Drug Administration approved methotrexate for treating RA, it had become clear that much of the joint damage caused by inflammation in RA begins a lot earlier than doctors had thought. Originally, NSAIDs had been the first line of treatment for RA, and doctors only prescribed other drugs when NSAIDs proved unable to control its symptoms. But the other drugs, now collectively known as disease-modifying antirheumatic drugs (DMARDs), are more effective against inflammation. With the new knowledge in hand, it made sense to begin using DMARDs, among them methotrexate, sulfasalazine, and hydroxychloroquine, soon after diagnosis in the hope that they would reduce or prevent joint damage. And by the year 2000, as researchers learned more, doctors had increasingly begun to use DMARDs not only early but also in combinations (rather than one after another) to help people for whom a single DMARD was not effective enough. Corticosteroids were sometimes added to the mix, too, in the lowest possible dose for the shortest possible time to cut the risk of side effects.
Meanwhile, in the 1990’s new drugs called COX-2 inhibitors had come on the market. COX-2 inhibitors are a special class of NSAIDs. When they first appeared, doctors hoped that they would be as effective in treating pain and inflammation as the traditional NSAIDs but safer for the gastrointestinal system. When the COX-2s celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra) became available, drug companies began to advertise directly to consumers via TV and magazines. As thousands of people with many types of arthritis learned of and tried these drugs, researchers found that people taking Vioxx had a higher rate of heart attack. Vioxx was taken off the market, as was Bextra, because of these concerns (and in the case of Bextra, other safety concerns as well). Though having an arthritis drug taken off the market had happened before, never had such a move affected so many people.
Also in the 1990’s, joint injections of hyaluronic acid (available under the brand names Synvisc, Orthovisc, and others) were introduced. Unlike cortisone, hyaluronic acid is not meant to reduce inflammation. But in people with OA, these injections can help cushion the ends of the bones in a painful joint.
But the biggest drug breakthrough of the 1990’s may well have been the biologics. While the COX-2 inhibitors had been grabbing the headlines, scientists had been advancing their understanding of inflammation. This improved understanding led to drugs called biologics that could thwart the inflammatory process in RA and other types of inflammatory arthritis. The biologics now available are abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan), and tocilizumab (Actemra). They are given either in combination with methotrexate (or a similar drug) or, more recently, as a first-line treatment. Some are self-injected by the person with arthritis, and others are given intravenously (into a vein), usually in an infusion center at a doctor’s office or at a hospital outpatient center.
Additional studies are underway to learn even more about inflammation and other processes involved in arthritis. New information will allow scientists and the pharmaceutical companies to develop additional therapies for all types of arthritis. Although many of the newest drugs have targeted inflammatory arthritis, there is also ongoing research into possible ways to slow the disease process of OA. Another area where researchers have made progress is in the development of drugs to treat fibromyalgia. In 2007, a drug called pregabalin (Lyrica) became the first drug specifically approved to ease the pain of people with fibromyalgia. In 2008 a second drug, duloxetine (Cymbalta), was approved, and a third drug, milnacipran (Savella) was approved in 2009.
Modern Day Rheumatoid Arthritis Surgery
The use of surgery to treat arthritis is another area that has made tremendous progress. The 1960’s saw the advent of the modern joint replacement. Since then, joint replacements have become an increasingly important part of the care of people with many different types of arthritis.
A surgeon and bioengineer called Sir John Charnley developed the modern joint replacement in England. The first joint to be replaced was the hip. After removing damaged areas of bone, Dr. Charnley replaced them with a stainless steel stem topped by a stainless steel ball in the thighbone and a cup made out of stainless steel in the hip socket. Though other materials are available today (including plastics and ceramics), the principle is the same, and joint replacements continue to help millions throughout the world. Knee, elbow, shoulder, finger, wrist, ankle, and toe replacement joints are now available to help people who have had permanent joint damage due to arthritis or injuries. And new technology continues to improve the durability of replacement joints. Though it is best to prevent joint replacement with early diagnosis and effective treatment, replacement joints have helped many return to their jobs and to an active way of life (although some people do encounter problems related to the surgery). The challenge continues to be deciding when to give up on the old joint and embrace the joint replacement.
Exercise Recommendations for Arthritis Management: What’s Changed?
Remember in the 1940’s, when doctor recommendations to people with arthritis was, “Go to bed”? Seldom would anyone hear that today. There has been a huge change in the understanding of exercise’s role in arthritis management. Doctors and physical therapists now recommend range-of-motion, strengthening, and endurance exercise. They know that exercise helps to keep bones, joints, muscles, and ligaments strong and the body in overall good condition. Exercise also helps people avoid depression, maintain a healthy weight, and toughen the body. A toughened body can more easily cope with any flare-ups or other problems that occur with arthritis. Keeping the body and joints in good condition also helps people recover more quickly after surgery.
Today there are countless opportunities for people with arthritis to exercise. Videos, group exercise programs, physical therapists, and health clubs now exist to help people with arthritis get moving. Furthermore, researchers have studied exercise, and health professionals now know which exercises are the most helpful, which ones to avoid, and how people should prepare for exercise. For these reasons, rheumatologists regularly recommend that their patients get involved in an appropriate exercise program.
Self-help for Arthritis Sufferers
In the 1950’s, little was available in the area of self-help for people with arthritis. For the most part, they were on their own. Again, thanks to acceptance and promotion by rheumatologists, many courses, pamphlets, newsletters, magazines, books, and Internet sites are now available to help people manage their condition. Over the years, rheumatologists have donated their time to help many organizations develop quality programs and resources. Courses such as Stanford’s Arthritis Self-Management Program (ASMP) have taught people many helpful techniques for dealing with arthritis in their day-to-day lives. The ASMP has even been studied for effectiveness and has received endorsements from the Arthritis Foundation and the Centers for Disease Control and Prevention. Rheumatologists have urged their patients to attend courses such as these, join support groups, or even try some of the many self-help products now available.
Summing Up the Progress Rheumatoid Arthritis Diagnosis and Treatment Has Made
Rheumatology has come a long way, and its future looks bright. As researchers learn more about genes that are associated with the various rheumatic disorders and about the processes involved in these disorders, their findings might well lead to new medicines and therapies that will give additional choices to physicians and their patients. Perhaps even stem-cell research will address rheumatic conditions at some point. For the 46 million people in this country alone who live with one or more types of arthritis, advances in knowledge and treatment can’t come quickly enough.
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