Image shows the word Methotrexate written on a clipboard with pills and a stethoscope

Methotrexate has long been considered the gold standard treatment for rheumatic disease. It’s often the first disease-modifying anti-rheumatic drug (DMARD) prescribed to treat conditions like rheumatoid arthritis (RA), lupus, and psoriatic arthritis (PsA), amongst others.

“Methotrexate has been around for a very long time,” explains Nilanjana Bose, MD, a rheumatologist at Lonestar Rheumatology in Houston, Texas. “It’s a very important drug to have on board. It’s cheap, it’s effective, and it works very well.” 

Though a new barrier is making it difficult for some to fill their methotrexate prescriptions: The reversal of Roe v Wade. Because methotrexate can be used to treat an incomplete miscarriage or an ectopic pregnancy, abortion restrictions are making it increasingly challenging to access this important drug in certain states. This is happening despite the recent warning from the Biden administration that stated pharmacies risk violating federal civil rights law if they refuse to fill prescriptions for pills that can induce abortion like methotrexate. 

While this is hopefully a temporary problem, it may be a good opportunity for you to consider whether you’d benefit from switching up your treatment regimen.  

Access restrictions or not, it’s normal to have to change your treatment strategy at one point or another. “While methotrexate is an excellent medication, a large number of people will need to either change medications or add on medications to their methotrexate,” explains Sandeep Krishna Agarwal, MD, PhD, Associate Professor of Rheumatology at Baylor College of Medicine in Houston. 

The good news? New treatments, including more targeted options like biologics and Janus kinase (JAK) inhibitors, mean there are more options than ever to choose from.  

These signs may indicate it’s time to talk to your doctor about re-evaluating your treatment strategy.  

1. You’re experiencing new or worsening symptoms

“One of the most common reasons people switch from methotrexate to other medications is an inadequate response to methotrexate,” says Agarwal.  

In fact, a recent study notes that up to 50 percent of people who take methotrexate for RA don’t respond well to this treatment. 

Though it’s also possible to attain remission, then relapse again. So if you’re experiencing new or worsening symptoms, or an increase in flares, it may be time to re-evaluate your treatment plan. 

2. You’re having trouble following your prescribed treatment

In order for any medication to work as well as it should, it must be taken exactly as prescribed.  

Though if you have trouble sticking with it, you’re not alone. A recent study found that around 37 percent of people living with psoriatic arthritis (PsA) aren’t taking methotrexate as directed. 

“Sometimes patients are not compliant, meaning they’re not taking it in the correct way, so they don’t have good results,” notes Bose. While that’s not the fault of the drug, she adds, it may be a sign you should find another medication that’s easier for you to take as prescribed.  

Methotrexate can be administered orally or by injection, ranging from once a week to a few times weekly. Meanwhile, newer treatment options, like biologics and JAK inhibitors, offer new routes of administration and dosing schedules, and can be given as a: 

  • Once-a-day pill 
  • Auto-injector pen you can do yourself at home every few weeks 
  • Infusion in a clinic setting every month or two 

Exact dosing schedules vary from medication to medication. If you prefer taking medication more or less often, or through different routes of administration, talk to your doctor.  

3. You’re dealing with treatment side effects

Another common reason for switching off methotrexate is due to side effects, notes Agarwal. Common side effects of methotrexate include: 

  • Fatigue  
  • Headaches 
  • Mouth sores 
  • Nausea 
  • Vomiting 

For some, lowering the dose or taking a folic acid supplement can help — but if you’re still experiencing bothersome side effects, you may benefit from a treatment change.  

4. You’ve developed an infection

Methotrexate works by suppressing the underlying overactive immune system activity. As a result, taking this medication can increase your risk of infection.  

Your doctor may recommend pausing treatment if you develop an infection to help your body fight it off. Be sure to call your doctor if you develop signs of infection, such as: 

  • Chills 
  • Fever 
  • Cough 
  • Sore throat  

Staying up to date on vaccines can help prevent infection. Though if you’re due for certain vaccinations, your doctor may recommend shifting the timing of your next methotrexate dosage to improve the vaccine’s efficacy.  

That said, infection and vaccination considerations are similar across many disease-modifying drugs, and may not be the sole reason make a treatment switch. Together, you and your doctor can develop a plan for how to handle infections and vaccinations, and whether or not switching to a new drug should be a part of that equation. 

5. You’re thinking of starting a family

According to the U.S. Food and Drug Administration, methotrexate is not considered safe for use in pregnancy. Taking methotrexate while pregnant poses severe health risks to the developing baby, as it has been linked to fetal abnormalities and pregnancy loss. As a result, use of this medication is often not recommended for use in women of childbearing age. 

If you do take methotrexate and wish to become pregnant, talk to your doctor first. Some health care providers recommend stopping treatment up to three months before trying to conceive to ensure the medication is completely cleared from the body. Some may also recommend stopping paternal use of methotrexate before trying to conceive as well — though some research suggests it may not pose the same risks.  

Methotrexate also isn’t recommended while nursing, as the drug could pass from the breastmilk to the baby.  

This is why it’s essential to talk to your doctor about any life changes you’re experiencing that may impact treatment, including family planning. “Starting a family is a very important decision, and we always encourage patients to keep us in the loop,” says Bose. 

Work with your doctor to develop a plan for switching from methotrexate to another drug that’s safe for use in pregnancy and while breastfeeding.  

6. Your insurance coverage has changed

“There could be cost or financial considerations, like an insurance change where the drug is not covered, or is covered sub-optimally,” explains Bose.  

While the cost of methotrexate can vary, its generally one of the more affordable treatment options with low out-of-pocket costs.  

Though if you’d rather not make a treatment switch strictly for financial reasons, consider other options to help keep out-of-pocket costs down, like GoodRX or SingleCare. Read more tips on how to “recession-proof your health care.”  

Work with Your Doctor 

The treatment option that works best for one person may not be the right fit for the next. So it’s important to work closely with you doctor to develop the right treatment strategy for you 

While your doctor plays a primary role in helping you determine which medication — or combination of treatments — will help you, your participation in treatment decisions is equally important. “You have to be involved in the treatment decision so you can take an active role in the management of the disease,” says Bose.  

“Fortunately, we have many options beyond methotrexate that can be used,” adds Agarwal. “That really enables rheumatologists and patients to work together to find the right individualized treatment regimen that can help.” 

If you would like to share your concerns or story about accessing medications as a result of abortion bans, please email Zoe Rothblatt, Associate Director of Community Outreach.

Want to Get More Involved with Patient Advocacy?

The 50-State Network is the grassroots advocacy arm of CreakyJoints and the Global Healthy Living Foundation, comprised of patients with chronic illness who are trained as health care activists to proactively connect with local, state, and federal health policy stakeholders to share their perspectives and influence change. If you want to effect change and make health care more affordable and accessible to patients with chronic illness, learn more here. 

The American College of Obstetricians and Gynecologists. Immune Modulating Therapies in Pregnancy and Lactation. 

American College of Rheumatology. Treatments. 

Eck, LK, et al. “Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy.” Obstetrics & Gynecology. April 2017. doi: 

Generali, E et al. “Non-Adherence and Discontinuation Rate for Oral and Parenteral Methotrexate: A Retrospective-Cohort Study in 8,952 Patients with Psoriatic Arthritis.” Journal of Translational Autoimmunity. 2021. doi: 

Interview with Nilanjana Bose, MD, a rheumatologist at Lonestar Rheumatology in Houston, Texas.  

Interview with Sandeep Krishna Agarwal, MD, PhD, Associate Professor of Rheumatology at Baylor College of Medicine in Houston. 

U.S. Food and Drug Administration. Why You Need to Take Your Medications as Prescribed or Instructed.  

Yu, M.B., et al. Predicting methotrexate resistance in rheumatoid arthritis patients. Inflammopharmacol. doi: 


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