Remission: A Goal of RA Treatment

Many people think rheumatoid arthritis remission is the goal of treatment. But what exactly do we mean when we talk about remission? Many of us are familiar with the term, which, generally speaking, means that symptoms of a disease have subsided. But we may be unsure how it applies to RA. Does remission mean that the RA has gone away, never to return? Or can RA that is simply improving be considered “in remission”? As it turns out, researchers and doctors who study and treat RA haven’t reached a consensus on a clear definition of remission either. When applied to RA, remission in rheumatoid arthritis can have several different meanings.

The good news is that we are talking about remission at all. Decades ago, remission was not much discussed because it happened so rarely. While symptoms subsided in a lucky few with RA, for most people RA was very unlikely to improve significantly. Advances in treatment have changed that, and now remission, however it’s defined, represents a realistic goal of RA treatment.

The Many Definitions of Rheumatoid Arthritis Remission

Doctors and researchers have many different definitions of remission. The definitions they use, however, may not agree with yours. “For the average person, remission means that the disease is gone,” says Eric Ruderman, MD, Professor of Medicine at the Northwestern University Feinberg School of Medicine in Chicago. “While that is what we are hoping for eventually in RA, at present we are talking more about managing symptoms on some type of medication.”

For most doctors and researchers, remission means there has been a significant reduction in the signs and symptoms of RA, but it doesn’t necessarily mean that the RA is gone. To determine how much these signs and symptoms have improved — and whether this improvement qualifies as remission — a doctor has to consider several factors in the course of a careful evaluation. These factors include the following:

  • Results of a physical examination. A doctor will examine the joints of a person with RA for tenderness, swelling, and loss of mobility. In addition, doctors may make a “global” assessment of the activity of a person’s RA after taking many factors into consideration.
  • Self-reported symptoms. These are the symptoms, including morning stiffness and pain, that you report to the doctor. Sometimes, doctors ask people with RA to rate their pain or general health on a scale from 1 to 10.
  • Blood tests. Several blood tests can give doctors a sense of how active a person’s RA is. These include the erythrocyte sedimentation rate (ESR) test, which measures general levels of inflammation in the body; the C-reactive protein (CRP) test, which also measures general levels of inflammation; and the rheumatoid factor (RF) test, which measures levels of an antibody present in high levels in many people with RA.
  • Imaging tests. X-rays and magnetic resonance imaging (MRI) tests can help doctors determine how much damage RA has caused to cartilage, bone, and other structures of the joint.
  • Questionnaires. There are several questionnaires that, when filled out by a person with RA, can help both doctors and researchers get a picture of how arthritis is affecting that person’s quality of life. Commonly used questionnaires include the Health Assessment Questionnaire (HAQ) and the Short-Form Health Survey (SF-36).

Doctors use some or all of this information to determine whether a person’s RA has gone into remission. Some organizations have proposed specific definitions of remission that can help doctors use the information they collect. For example, the American College of Rheumatology (ACR) has two ways of defining remission. The first method for deciding whether or not a person is in remission uses some of the standard diagnostic tests for RA. According to the ACR’s criteria, a person is in remission if he has one or fewer tender joints, one or fewer swollen joints, has 1 milligram per deciliter of C-reactive protein in his blood, and has a patient global assessment score of 1 or less on a scale of 1 to 10. The second method for deciding whether or not someone is in remission uses a version of the Disease Activity Score.

Many studies of treatments for RA use something called the Disease Activity Score (DAS) to measure improvements in disease activity and determine whether a person’s RA is in remission. The DAS takes into account the number of tender and swollen joints, the results of an ESR (or CRP) test, and the person with RA’s assessment of his or her own general health. Using this information, a number from 1 to 10 is given that represents the DAS. RA is often considered to be in remission if the DAS is below a certain number (often 2.4 or 2.6). The ACR uses a simplified version of the DAS to determine whether or not a person is in remission, and says a score of 3 is the upper limit.

What is your definition of remission? For you, being free of pain, stiffness, and generally feeling better may be the essential criteria. Because your definition may differ from that of your doctors, it is very important that you talk with your health-care team to make sure you are all on the same page. A recent survey of people with RA found that almost two-thirds do not recall talking with their doctors about remission.

Advances in Rheumatoid Arthritis

The reason we are able to discuss the possibility of remission in RA is that in recent years there have been remarkable advances in RA treatment. These advances have greatly increased the likelihood of symptom relief and reduced disease activity.

The major advance is the advent and increased use of disease-modifying antirheumatic drugs (DMARDs). DMARDs are drugs that interrupt the inflammatory process of RA and can slow or halt the progress of the condition. They differ from drugs that just reduce pain and inflammation, which include nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (brand names Advil, Motrin IB) and corticosteroids such as prednisone. The most commonly used DMARD is methotrexate (Rheumatrex, Trexall). Doctors began to use methotrexate to treat RA in the 1980’s, and it remains the “gold standard” of treatment. Since then, powerful DMARDs known as biologics have become available. These drugs, which include etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira), work by blocking particular immune-system substances that contribute to the inflammation of RA. Studies have shown that in people who respond to the biologics, these drugs can slow the progression of joint damage, increase the functioning of joints, and improve quality of life.

The advent of more powerful drugs for RA has coincided with a second key treatment advance: the recognition of the importance of early and aggressive treatment. In the old days, people with RA were most often “stepped up” from less to more powerful drugs as their condition got worse. But studies from the early 1990’s introduced the concept of a “window of opportunity,” a period of time when treatment for RA can be most effective. This window occurs early in the course of RA. Treating RA with DMARDs within this window may be able to stop the inflammation and prevent joint damage down the line. Treatment that is begun after joint damage has occurred can still be effective, but the damage already caused will remain.

Many studies have helped bolster the case for early treatment. For example, an analysis of over 1,400 people enrolled in 14 different studies found that those who had RA for less than one year had a better response to treatment than those who had more long-standing RA.

Some research suggests that delays in starting DMARD therapy may lessen the chance of reaching remission. Results from the Finnish RA Combination Therapy Trial, which looked at nonbiologic DMARD therapy in 195 people who had recently been diagnosed with RA, showed that starting a DMARD more than four months after RA symptoms began was the only factor that reduced the chance of remission. However, this was only true among people taking only one nonbiologic DMARD. People who took three nonbiologic DMARDs were not affected by the delay. Of the participants who took a combination of DMARDs, 40% had achieved remission two years into the study. After five years, 28% maintained remission.

As this study suggests, an important factor affecting the likelihood of remission may be the aggressiveness of the treatment. A study from the Netherlands known as the BEST study found that starting therapy with two medicines got better results than starting with just one. Moreover, these “combination” strategies were more effective when given early in the course of RA. However, many people with RA find that they are able to control their condition with one DMARD.

The Importance of Personalizing Treatment for Rheumatoid Arthritis

The results of current research suggest that rates of remission may be increasing. But that doesn’t mean that finding the right treatment has become much easier. There is still no standard guide to help you and your doctors choose the medicine or combination of medicines that will work best for you. RA affects each person differently, and different people’s responses to treatment can also vary a great deal.

Because of this uncertainty, people with RA often have to try several different medicines until they find one or more that work well for them. “Since we don’t have good ways yet to predict how someone will respond to a specific medication, management is restricted to prescribing medications and monitoring the response until a good regimen is found,” says E. William St. Clair, MD, Professor of Medicine and Immunology and Chief of Rheumatology and Immunology at Duke University Medical Center in Durham, North Carolina. “This can get very frustrating for the person with RA if the initial treatments do not work very well or cause unmanageable side effects.”

In addition, it often takes one to three months before people are able to feel the benefits of an RA medicine. This delay can add to the frustration, especially if people have to try several different medicines before finding the combination of medicines that works best.

What Happens After Your Rheumatoid Arthritis Symptoms Improve?

Say that you have found a combination of medicines that works well for you and that your RA symptoms have improved dramatically. Perhaps your doctor has even told you that your RA is in remission. What should you do now? That is very much an open question, largely because the newer biologic treatments have not been around long enough for there to be good long-term data on them. Some studies suggest that early and aggressive treatment of RA may allow some people to come off their medicines without a return of symptoms. However, most of these studies have followed people only for two years or fewer, making it impossible to determine whether the RA will stay away forever or eventually return.

The BEST study mentioned above provides some insight into the possibility of stopping RA medicines. It enrolled 508 people who had RA for less than two years. They were randomly split into four groups, and each group was given one of the following four treatments:

  1. Methotrexate alone
  2. Methotrexate with a second nonbiologic DMARD added later if necessary
  3. High doses of the corticosteroid prednisone plus methotrexate and another nonbiologic DMARD
  4. Infliximab (Remicade) and methotrexate

The researchers found that people who took multiple drugs at the beginning of the study (groups 3 and 4) experienced more immediate functional improvement and less joint damage. After two years, people in groups 3 and 4 still had less joint damage, but all four groups had similar improvements in functional ability. In addition, 56% of people who were first prescribed infliximab and methotrexate were able to stop the infliximab and begin reducing their dose of the methotrexate after two years.

It is not clear, however, how these research results should influence treatment. “We really don’t know what happens next,” said Joan Bathon, MD, Professor of Medicine and Director of the Arthritis Center at Johns Hopkins University School of Medicine in Baltimore. “Our mantra in the past has been that RA is a chronic disease that doesn’t magically go away, and we should never entirely take away medication. What we don’t yet understand is how to predict who will do well without drugs and how to best withdraw them.”

The doctors interviewed for this article said that the current strategy for treatment is to find a successful combination of medicines and then stay with it for a year or so. After that, doctor and patient can negotiate a plan to slowly taper one of the medicines and see how well the RA remains controlled. After successfully stopping one medicine, similar methods may be used to lower the doses of or even completely stop other drugs. “I start with the medication that is most toxic and/or expensive and discontinue that one first,” says Dr. Bathon. “Prednisone or another steroid [first], then the biologic where the long-term toxicity is not as well worked out. If I can get the patient down to only using methotrexate, I am happy with that.”

Stopping all medicines, however, may have some downsides that you should discuss at length with your doctor. A study from 1996 looked at the effects of stopping nonbiologic DMARDs for one year. The researchers split 285 people who were taking a DMARD and whose RA was well controlled into two groups: one that continued DMARD treatment and another that received a placebo instead of the DMARD. Compared with the continued-treatment group, people in the placebo group were twice as likely to have an RA flare. Again, it is important to note that this study was conducted before the advent of biologic drugs, so it is difficult to know how well its results apply today.

If your doctor has lowered the dose of or taken you off a medicine, he or she will want to examine you closely during office visits to determine how your RA is doing. In between visits, you should get in touch with your doctor if you are experiencing joint pain and tenderness that doesn’t respond to usual treatments such as rest or an increase in pain relievers. Increased fatigue and changes to your general feeling of well-being are other possible indicators that your RA is worsening. Identifying symptoms that are returning can be very important, and your doctor should restart you on medicines before more damage can occur.

“Listening to your body and following its suggestions is important,” says Daniel Furst, MD, Carl M. Pearson Professor of Rheumatology at the David Geffen School of Medicine at UCLA. “If it is saying you need to take it easy for while, do that. If it says you can push yourself a little further, go ahead.”

The experts stress that not everyone will be able to stop their medicines, but most should be able to reduce the dose and number of drugs they take. Under even the best of circumstances, flares may occur and should not be taken as a sign of failure. “Most patients with established disease will develop symptom flares down the road,” says Dr. St. Clair. “Even if they are able to stop medicines for a year or two, the joint pain and swelling will often reappear later and warrant reintensification of therapy. Whereas remission on medication is an outcome that we see often, long-standing remission off medications is really an uncommon event.”

What’s Next on the Horizon for Rheumatoid Arthritis Medicines?

There is some interesting science on the horizon that may help make it easier to decide when to start and stop taking RA medicines. “We are getting better and better at personalizing the medication for a specific person instead of averages across a group,” says Dr. Furst. “We are also beginning to see some early studies that may identify genes which predict a response. That is very exciting.”

Although medicines currently used to treat RA may not be cures, they have greatly changed the quality of life for many people with RA. “Ten years ago you would come into my waiting room and see visible deformities, people using walkers and canes,” remembers Dr. Bathon. “Now you can walk into any rheumatology department waiting room and you can’t really tell it from a general medicine clinic.”

Kurt Ullman has been a medical writer for over 25 years. He is based in Indiana.

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