Methotrexate and Rheumatoid Arthritis: How It Works and What You Should Know

If you have RA, you’re probably very familiar with the pain and joint swelling it can cause. And you may even have experienced the joint deformity that can occur as the disease progresses, deformity that can take a significant toll on joint function and overall quality of life. RA usually attacks the joints of the hands and feet first, and that means even simple activities like typing a shoe, brushing your teeth, combing your hair or getting dressed can become painful, drawn-out activities. Leisure pursuits like gardening or even taking long walks may have lost their appeal as a result of the pain and inflammation they can trigger.

But although there is no cure for RA, there are medications that can slow the progression of joint destruction and deterioration, and one of the most popular and most effective of these drugs – methotrexate – also has one of the longest and most well-established safety profiles of any drug on the market.

Methotrexate and RA Treatment

RA is an autoimmune disease, which means it’s caused by an abnormal immune response. In a healthy immune system, special cells seek out and destroy harmful germs to prevent infection and disease. But in an autoimmune disease, those cells attack healthy tissue, destroying it in the process. In RA, immune cells attack the tissues inside the joints, tissues that help the joints function normally and protect the joint surfaces from painful and destructive friction. DMARDs work by targeting that abnormal immune response that causes joint tissue destruction. And among the DMARDs, methotrexate has been around the longest.

In fact, methotrexate was introduced in the 1940s as a cancer drug. It works by interfering with cancer cells’ ability to absorb and use folate, a form of vitamin B that’s necessary for cell survival. Studies in the 1980s found methotrexate was also very effective in reducing the inflammation and swelling associated with RA, and by the late 1980s, methotrexate received FDA approval for the treatment of patients with rheumatoid arthritis. Today, it’s usually a first-line treatment for people with the disease.

Dosing and Side Effects

Because of its effectiveness and established safety profile, most patients who have RA take methotrexate at some point, usually by mouth. The typical dosing starts at about 5 mg to 10 mg per week, and it can be increased to about 25 mg per week or even higher if needed. For patients in whom side effects become an issue, methotrexate can also be given as an injection under the skin.

So what are those side effects? The most common side effects are gastrointestinal symptoms like nausea and vomiting. Splitting the dose into two daily doses instead of a single dose may help, or you can ask your doctor about anti-nausea medications. Some people develop mouth sores, fatigue, headache, dizziness or shortness of breath, and it may also cause hair loss in a few patients. Taking folic acid may help reduce or even eliminate these side effects, but you should never take any supplement or medication without talking to your doctor first. Having the drug injected instead of taking it orally can also help.

Rarely, methotrexate can cause liver damage, so patients who take the medication on a regular basis will need to have routine blood tests to make sure their liver stays healthy. To reduce the risk of liver damage, patients taking methotrexate also should avoid drinking alcohol, and they should also talk to their doctors about the use of any other kind of medication, including over-the-counter pain relievers, just to be on the safe side. In a very few cases, the drug may also cause lung inflammation or a decrease in white blood cells or platelets, but routine blood testing can identify these issues as well. Methotrexate should not be taken during pregnancy.

Finally, methotrexate works by interfering with the abnormal immune system activity that causes joint tissue destruction. As a result, it can also lower your ability to fight off other infections. The relatively low dose used in RA means this risk is reduced, but it’s something you and your doctor will need to discuss so you understand how the drug works and what issues to watch out for.

Is Methotrexate Right for You?

Methotrexate can be very effective in helping patients reduce the joint damage associated with RA, which in turn can reduce pain and improve mobility, function and overall quality of life. Despite its long history of safety, many patients worry about the drug’s side effects. That’s probably because they’ve heard about the side effects methotrexate can cause in cancer patients. But these patients take very, very high doses of methotrexate – much higher than the doses used in RA treatment. Not surprisingly, the side effects of those doses tend to be more prevalent and more severe.

One of the benefits of methotrexate is that it can be combined with other drugs, including other DMARDs, to provide symptom relief when methotrexate alone isn’t enough. Methotrexate can also be combined with biologics, drugs designed to target specific aspects of the abnormal immune response that causes joint destruction. This enables patients to receive truly customized treatment based specifically on their needs.

To find out if methotrexate is a good choice for helping you manage your RA, talk to your doctor. And if you’re prescribed methotrexate, be sure to take it exactly as the doctor prescribes it for maximum benefits and the lowest risk of side effects.