Many people with rheumatoid arthritis (RA) try methotrexate as an initial treatment option. Due to side effects and other reasons, you may want to stop taking the medication, but this may cause some issues you should be aware of.

Methotrexate is a disease-modifying antirheumatic drug (DMARD) that can slow down RA and prevent further joint damage. It calms the immune system to help prevent inflammation.

About two-thirds of people who use methotrexate say that it helps keep their RA from getting worse. Still, some people who use it have side effects such as fatigue, nausea, and diarrhea, which might make them want to stop taking the medication.

This article will discuss the issues with stopping methotrexate, methotrexate withdrawal, and how to safely work with your healthcare provider to make changes to your RA treatment plan.

Does Stopping Methotrexate Cause Withdrawal?

Some drugs and medications can lead to dependence. When you’ve been taking some drugs for a long time, your body begins to rely on them to function properly. When you stop using them, you go through withdrawal and experience physical or mental symptoms.

Researchers aren’t yet sure whether people can go through withdrawal from stopping methotrexate treatment. Clinical studies haven’t reported any major methotrexate withdrawal symptoms from people stopping this therapy.

However, stopping methotrexate treatment can increase the risk of RA flare-ups.

Some research shows that people who were taking higher doses of methotrexate were more likely to experience flare-ups after discontinuing the drug than people on lower doses.

Stopping Methotrexate and RA Flares

Flare-ups — periods during which symptoms worsen — are common when living with RA. Flare-ups can last for days, weeks, or months. They often lead to symptoms like joint stiffness, pain, and swelling, as well as fatigue and fever.

Stopping Methotrexate May Lead to RA Flares

Some studies have found that people with RA can experience disease flares when they stop using methotrexate. One small study compared people taking methotrexate with people taking a placebo (a “fake” treatment that mimics a real medication) for their RA. Within one month, all of the participants taking the placebo experienced a flare-up.

Reducing Methotrexate Dose May Lead to RA Flares

Other studies have analyzed whether taking methotrexate less often could lead to flare-ups.

Studies have found that anywhere from 8 percent to 48 percent of people have an RA flare when they go from taking methotrexate once every week to once every two weeks. This treatment plan may work best for people with early-stage RA who have gone into remission. It can also help when people are using methotrexate in combination with other DMARDs that are working to help control the disease.

It’s important to note that this research was conducted many years ago, before biologics became a common RA treatment option.

Taking Biologic DMARDs While Stopping Methotrexate May Reduce RA Flares

More recently, research has found that some people may be able to stop using methotrexate if they’re also taking biologics.

Studies have looked at people who had stable RA after taking tofacitinib (Xeljanz) or etanercept (Enbrel) along with methotrexate. Researchers found that when people stopped using methotrexate but continued taking the biologic drug, they didn’t have a higher risk of a flare-up.

How To Stop Taking Methotrexate

Methotrexate can help people with RA go into remission. People in remission have dramatically improved RA symptoms. For example, your doctor may consider you to be in remission if you have just a single swollen joint or if your blood tests show that you have low levels of inflammation.

If you’re in remission from RA, your doctor may give you the option of stopping methotrexate therapy or reducing your dose. Some guidelines recommend slowly tapering off methotrexate if your RA is well controlled. Before trying to switch to a lower dose, talk to your rheumatologist to see if it’s the right choice for you. Your doctor will consider factors like:

• Whether you experience side effects from using methotrexate
• How long you’ve been in remission
• Whether you’re concerned about experiencing a disease flare-up if you lower your dose

Your rheumatologist may be OK with you stopping methotrexate altogether. They may also suggest changing your dosage or taking the medication less frequently. This may help prevent flare-ups and help you stay in remission.

Treating Flare-Ups After Stopping Methotrexate

If you experience a flare-up after stopping or reducing methotrexate, your RA may become active again. In this case, your healthcare provider may suggest going back on your previous treatment plan.

In one study, 36 percent of people who took etanercept and methotrexate for at least six months and then stopped using methotrexate needed to go back to their original therapy. Out of this group, 75 percent were able to get back into remission, and 92 percent had low disease activity after restarting methotrexate.

Nonmedication strategies to help manage symptoms during flare-ups include:

• Lowering your stress levels
• Getting more sleep
• Relieving pain with hot water bottles, heated blankets, warm baths, or ice packs
• Getting very light exercise, if your doctor says it’s OK
• Taking over-the-counter or prescription medications to ease flare symptoms, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids

These strategies may not be enough to treat a flare-up that occurs after you stop taking methotrexate. You may feel better if you go back to your original medication. Work with your healthcare team to weigh the benefits and risks of your treatment options.

Talking To Your Doctor About Methotrexate

Make sure to talk to your doctor before you stop taking methotrexate or try to change your dose. If you don’t like methotrexate because of its side effects or if you want to try a different treatment, your doctor can help you change your treatment plan. They may also be able to suggest other ways to ease methotrexate side effects, such as:

• Taking methotrexate after a meal, when your stomach is full
• Receiving methotrexate therapy on Friday or Saturday, so you have the weekend to recover
• Taking a folic acid (folate) supplement
• Using other medications to treat side effects like nausea

You should keep taking methotrexate even if you’re feeling good, unless you and your doctor discuss otherwise. Having fewer RA symptoms means that your medication is working — if you stop taking it, your condition could worsen.

Find Your Team

On myRAteam, the social network for people with RA and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with rheumatoid arthritis.

Have you used methotrexate? If you stopped taking it, did your symptoms flare up? Share your experience in the comments below, or start a conversation by posting on your Activities page.