Your Guide to Rheumatoid Arthritis Medication: A Look at Methotrexate and Other Options

Rheumatoid arthritis (RA) is an autoimmune disease that causes painful swelling in the joints. This can make it challenging to carry out daily tasks, especially if it’s left untreated or ignored. 

Estimates show that more than 1 million adults in the U.S. are living with RA. There are several treatment options to ease RA symptoms. And prevention of permanent joint damage and disability is absolutely a realistic goal this day in age.

What’s the first-choice treatment for rheumatoid arthritis? 

For most people, methotrexate is the first-choice treatment for rheumatoid arthritis, according to the American College of Rheumatology. That’s because it’s affordable, effective for many, and safe. 

Methotrexate is a disease-modifying antirheumatic drug (DMARD) that’s only taken once a week. It’s available in oral and injectable forms. Most people prefer to start with pills, but injections are also a great option — especially for those who experience stomach upset with methotrexate pills. 

Of note, people taking methotrexate also need to take daily folic acid (a vitamin). Folic acid helps prevent potential side effects of methotrexate. It doesn’t treat RA itself.

Non-medication therapies, like diet and exercise, are also first-choice treatments for RA. Medications work best when combined with other self-care measures (more on these below).

Promotion disclosure

Methotrexate

Avg retail price

$30.86(Save 63.19%)

GoodRx discount

$11.36

Compare all prices

Which other medications can treat rheumatoid arthritis?

There are many treatment options for RA. But everyone responds to treatments differently, so there’s no one-size-fits-all approach. The best treatment is the one that works best for you. It can take time to find that treatment, but rest assured: You have options. 

DMARDs

DMARDs like methotrexate are typically prescribed first for RA because they’re cheap, safe, and effective for many. They all take about 6 to 8 weeks to take effect, with full effect around 3 to 6 months. If your symptoms have not significantly improved at 3 months, changes should be made to the dose of your DMARD (if possible), or other medications should be added. 

Other than methotrexate, other examples of DMARDs include:

• Leflunomide (Arava): This is a good option for people who experience side effects with methotrexate.

• Sulfasalazine (Azulfidine): This is a great option for those who are pregnant or trying to become pregnant.

• Hydroxychloroquine (Plaquenil): This is a great option for people with mild RA because it’s the least strong of all the options. It’s also safe for people who are pregnant or trying to become pregnant.

Methotrexate or leflunomide, sulfasalazine, and hydroxychloroquine may be used in combination. This is called “triple therapy” because it involves three medications. But when a DMARD alone isn’t controlling RA symptoms, experts recommend adding a biologic or JAK inhibitor, not triple therapy. That’s because this approach works faster and better than triple therapy. Triple therapy may still be a good option for people who can’t take or don’t have access to biologics or JAK inhibitors.

Biologics

When swollen and painful joints don’t get better with a DMARD alone, biologics are the next best step. Several different biologics are available to treat RA. They each block a specific molecule, which is like turning off a different “faucet” (piece of the immune system) in an effort to stop the flood of inflammation. 

Biologics are injected or infused into the vein, and they take about 3 to 6 months to take effect. They may be used in combination with DMARDs and/or NSAIDs, but not JAK inhibitors. Typically, two biologics may not be used at the same time, though future studies may change this.

There’s no best biologic for RA, since everyone responds differently. And there are a few different kinds, depending on which part of the immune system they turn off. 

These biologics block a molecule called TNF-alpha:

• Humira (injection)

• Enbrel (injection)

• Cimzia (injection)

• Simponi (injection) and Simponi Aria (infusion)

• Remicade (infusion)

This biologic blocks T-cells:

• Orencia 

The biologic blocks B-cells:

• Rituxan 

These biologics block a molecule called IL-6:

• Acemtra 

• Kevzara 

Of note, biosimilars for many of these medications are also available. These are like generic versions of biologics, and they may be less expensive. Pharmaceutical companies expect to develop more of them in the future.

JAK inhibitors

Janus kinase (JAK) inhibitors are similar to biologics because they turn off a molecule called “JAK” to stop the flood of inflammation. They come in pills and take about 6 to 8 weeks to kick in. Also like biologics, they may be used in combination with DMARDs and/or NSAIDs and steroids. But they may not be combined with biologics. JAK inhibitors have not been shown to be better than biologics.

Examples include:

• Xeljanz

• Rinvoq

• Olumiant

JAK inhibitors are not the safest choice for people with a history of blood clots, cancer, or certain types of heart disease. 

What are the best medications for rheumatoid arthritis pain?

All of the above medications help control the inflammation that causes RA, which ultimately leads to pain control. But there are additional medications that can help treat pain more quickly, while RA medications take time to work.

NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to quickly control joint pain and swelling. 

Many NSAIDs are available over the counter (OTC). But higher, prescription-strength doses are often needed to treat RA. Common examples of NSAIDs are:

• Ibuprofen (Advil, Motrin) 

• Naproxen (Aleve)

• Celecoxib (Celebrex)

• Meloxicam (Mobic)

NSAIDs may not be a safe option for certain people. For example, people with chronic kidney disease or a history of stomach bleeding should avoid these medications. Talk with your healthcare team about whether NSAIDs are a safe choice for you.

Steroids

Steroids (like prednisone and Medrol) are very strong anti-inflammatories that control RA pain and swelling quickly. The catch? They come with a lot of short- and long-term side effects.  That’s why the American College of Rheumatology recommends avoiding their use if possible. 

But sometimes RA symptoms are so severe that steroids are necessary. In these cases, the recommendation is to use the lowest dose that controls symptoms for the shortest amount of time. That’s because the risk of side effects increases with higher doses and longer periods of steroid use. 

Are there non-medication treatments for rheumatoid arthritis pain?

Yes. Lifestyle changes — such as diet and exercise — may also help lessen RA pain. But it's important to note that these aren’t substitutes for RA medications. They may help you feel your best when used along with RA medications. Examples include:

• Doing exercise, like yoga

• Quitting smoking

• Eating a Mediterranean diet, which has some anti-inflammatory effects

• Limiting stress

• Getting enough sleep

Some supplements (like turmeric) may also help improve joint pain slightly. But supplements are not substitutes for RA medications.

Why trust our experts?

Written by:

Samantha C. Shapiro, MD

Samantha Shapiro, MD, is a board-certified rheumatologist and internist with expertise in autoimmune and inflammatory conditions. She founded the division of rheumatology at Dell Medical School at The University of Texas at Austin.

Edited by:

Katie E. Golden, MD

Katie E. Golden, MD, is a board-certified emergency medicine physician and a medical editor at GoodRx.

Our editorial standards

Meet our experts