Methotrexate is the most commonly prescribed drug to treat RA, yet it only helps about half of those who try it. Find out how it works and how to manage its side effects.

For people who have more than mild symptoms of rheumatoid arthritis, or RA, methotrexate (Rheumatrex, Trexall) is one of the most commonly prescribed drugs. It's a leader in a class of drugs known as DMARDs – for disease-modifying anti-rheumatic drug – and it works to slow the progression of joint damage from the disease.

Methotrexate works by reducing the function of the cells that are causing inflammation in the joint tissues, explains Arthur Weinstein, MD, a professor of medicine at Georgetown University and chief of rheumatology and associate chairman of the department of medicine at MedStar Washington Hospital Center in Washington, D.C. Less inflammation in the joints should mean less joint pain and less joint swelling. You should also feel less fatigue and less morning stiffness.

People with swollen and painful joints whose RA has not improved with simple therapies will most likely be prescribed methotrexate for RA management. But it may take weeks to months until the full benefits of methotrexate are noticeable, says Barbara Young, PharmD, MHA, editor of consumer medication information for the American Society of Health-System Pharmacists in Bethesda, Md. While you’re waiting for the effects to start, you may be given other medications, such as corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), to help with RA management.

The goal is to feel more and more improvement over a few months, reaching a level of stabilization after four to six months. But methotrexate doesn’t work for everyone. "Although no pain, no joint swelling, and very little morning stiffness is hoped for, less than half of RA patients achieve this," says Dr. Weinstein.

According to a research review, published in the journal BMC Medicine, that analyzed predictors for methotrexate success, men respond better than women, non-smokers respond better than smokers, and people who take methotrexate as their first DMARD do better than people who have already tried another drug in this category. The review also found that those who take methotrexate in an early and mild stage of RA do better than those who start the drug after they have had RA for a long time. The researchers point out that if doctors can identify who is unlikely to respond to methotrexate, those patients can be spared exposure to a potentially toxic drug.

If you do not have a significant improvement in joint inflammation and well-being after about three months of RA treatment, your doctor will probably consider adding another RA drug to your treatment, especially a biologic drug such as etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade). "The reason that RA is treated in this way is because early complete or near complete control of joint inflammation leads to reduced joint damage over the years," Weinstein says.

Dealing With Methotrexate Side Effects

 

Because methotrexate affects rapidly dividing cells that line the mouth and stomach, Weinstein says that painful mouth ulcers, nausea, and diarrhea are very common in people who take this RA drug.

Call your doctor right away if you have diarrhea, mouth sores, dehydration, bleeding, shortness of breath or cough, any signs of an infection, or a rash.

Methotrexate can lower your white blood count, which can make you more likely to get an infection. It can also cause your hair to thin and make you bruise more easily or get the chills. Some people get headaches and fatigue for a day or two after taking methotrexate, which is usually taken by mouth once a week.

Because methotrexate can lead to spontaneous abortions, women taking this RA drug should take precautions to prevent pregnancy. Women should also use a contraceptive if their sexual partner is taking methotrexate. "Reliable contraception must be used for three months after men stop taking methotrexate and for women until after they have had their menstrual cycle return," Young says. "Women must notify their physician immediately if they think that they may be pregnant while they (or their partner) are taking methotrexate."

To prevent mouth pain, ulcers, and nausea, Weinstein suggests taking a low dose of folic acid, a B vitamin, once a day. In addition, your doctor will want to do blood work, including a chemistry profile, every month to monitor your white blood count. After a few months of monitoring, you should be able to reduce the frequency of blood tests to once every two to four months. People with RA and kidney disease may be especially susceptible to the side effects of methotrexate and instead may need to take a different medication for RA treatment.

Long-Term Issues: Possible Liver Problems

 

Liver damage from methotrexate is very rare, Weinstein says. However, mild liver inflammation is not uncommon. Blood tests can check for liver problems. If your liver test is abnormal, your doctor may lower your dose of this RA drug or stop it temporarily. Later on, your doctor might start you on methotrexate again at a lower dose.

Alcohol increases the risk for liver inflammation when taking methotrexate and should be avoided. "The combination of excessive alcohol and methotrexate may lead to liver damage," Weinstein says.