Vasileios Kyttaris, MD
Vasileios Kyttaris, MD, assistant professor of medicine at the Harvard Medical School and a board-certified rheumatologist at the Beth Israel Deaconess Medical Center Division of Rheumatology, Boston.
Rheumatoid arthritis affects about 3 to 4 percent of women and 1 to 2 percent of men. RA is an autoimmune disease. That means your body’s defense system—your immune system—attacks normal tissues instead of foreign invaders like germs. The method of attack is inflammation, which causes the swelling, pain, and gradual erosion of joint tissue.
The American College of Rheumatology issues new treatment guidelines based on new drugs and clinical studies every few years. In the latest guidelines, the disease-modifying antirheumatic drug (DMARD) methotrexate is still the gold standard, but new biologic and targeted synthetic DMARDs have become an important part of the treatment landscape.
Biologics are genetically engineered antibodies that block specific steps in the immune system path to inflammation. The first biologic approved for RA blocked a type of cytokine called tumor necrosis factor. Cytokines are proteins the immune system needs to cause inflammation. These biologics are called tumor necrosis factor (TNF) inhibitors. There are now several other classes of biologics that block different pathways.
Targeted synthetic DMARDs are the latest addition to the treatment arsenal. The most common one for RA is called a Janus kinase (JAK) inhibitor. JAK inhibitors, unlike TNF inhibitors, block multiple cytokines that immune cells need to increase inflammation. All these drugs have their own risks and benefits:
If you have been recently diagnosed with RA, the first step is for your health-care provider to determine your level of disease activity, which could be low, moderate, or high. The next step is to set a target or treatment goal you want to reach in six months. Although about one-third of patients may be able to reach symptom-free remission, in most cases, the target is low disease activity. There are three steps to treatment, depending on your disease activity:
Step 1. For low disease activity, you may start with a single conventional synthetic DMARD. Hydroxychloroquine may be the first choice, since it is well tolerated by most people. Hydroxychloroquine and sulfasalazine do not suppress your immune system, so they may be favored over methotrexate for mild disease, or when there is a history of an immune-sensitive cancer like melanoma. Less aggressive disease may be predicted in people who do not have RA antibodies on a blood test, a scenario called seronegative RA. Hydroxychloroquine or sulfasalazine may be a good choice for these people.
Step 2. If low disease activity is not maintained after six months, or your disease activity starts as moderate to high, methotrexate single treatment (monotherapy) is recommended. About 50 percent of people reach their target on methotrexate monotherapy. Methotrexate is recommended over biologic monotherapy because it is almost as effective, easy to take, and much less expensive. If your target is not reached, you may be switched from oral methotrexate to subcutaneous injections. If you still don’t reach your target, step three is the addition of other DMARDs.
Step 3. For patients who do not reach their goals on methotrexate alone, there are two options recommended. One is triple therapy, which is methotrexate, hydroxychloroquine, and sulfasalazine. The other is methotrexate plus a biologic (usually a TNF inhibitor) or targeted synthetic DMARD (a JAK inhibitor). TNF inhibitors generally have a better safety profile. Patients who still need more help to stay on target can switch to a different biologic or targeted synthentic DMARD. Choosing which is the best is hit or miss, since there is not enough research available yet to guide the choice.
Patients often ask why they can’t start with biologic monotherapy instead of methotrexate. The reason is that some studies find a biologic to be more effective and others don’t. The results are not consistent.
At one time, there was a fear that biologics increased the risk of white blood cell cancer, but that has not been supported by more recent research. However, biologics still increase your risk of some rare but serious infections, and they are still very expensive. So for the time being, they are not used as initial therapy.
For patients on multiple drugs who have sustained remission or low disease activity for at least six months, the doses of drugs can be lowered and some drugs may be gradually discontinued, but stopping therapy completely is not recommended, due to the risk of a flare.
For patients who are doing well on a TNF inhibitor, tapering off the drug has been associated with a 30 to 50 percent relapse rate. With other biologics, tapering down to monotherapy with methotrexate is possible. For people on triple therapy, sulfasalazine should be the first drug removed; the next drug would be hydroxychloroquine.
A Mediterranean-style diet reduces the risk of heart disease, which is more common in RA. Exercise and strength training are important for maintaining a heathy weight and to strengthen muscles that support joints. Obesity makes RA worse, and so does smoking. If you are on methotrexate, you should avoid alcohol because of an increased risk of liver damage.
The American College of Rheumatology has been changing the treatment guidelines for RA whenever new research or new drugs become available. This type of evidence-based research has been very successful. In 1950, the life expectancy of a person with RA was about 67 years. Today it is 80.
Living with RA is also much different. With proper treatment and care, most people with RA can now have a good quality of life, continue to work, and enjoy physical and social activities.
