Methotrexate and Lupus

Methotrexate is a disease-modifying anti-rheumatic drug (DMARD) that is used to reduce the swelling and pain associated with certain diseases like rheumatoid arthritis, psoriatic arthritis, vasculitis, juvenile arthritis and lupus.   More and more doctors are using methotrexate to treat lupus when antimalarials like hydroxychloroquine (Plaquenil) or nonsteroidal anti-inflammatory drugs aren’t controlling patient symptoms.  This can be scary for some lupus patients, primarily because 1) it is known as a “cancer drug” and 2) though it is generally safe at the doses given for SLE, it is still a powerful medication.  This blog will explore some important information about the drug, and hopefully allow you to make a comfortable decision with your doctor whether it is the right medication for you.


  • Originally designed to treat leukemia in the 1940’s, methotrexate was approved by the FDA to treat arthritis in the late 1980’s
  • It is thought of as one of the best medications available to treat rheumatoid arthritis
  • Brand names are: Rheumatrex, Trexall, Otrexup, Rasuvo
  • It works slow, but some people feel symptom relief after 3 to 6 weeks  
  • In certain cases, it can help prevent joint damage
  • Some doctors use it to control lupus flares
  • It should be taken with milk or food
  • It can be taken orally or as an injection under the skin
  • It can be taken with steroids or as steroid “bridge” therapy and may help lower the dose of steroid use altogether in some patients.
  • It has been used to treat pleuritis and skin lesions in lupus patients


Methotrexate works by suppressing the immune system (a network of cells, tissues, and organs that work together to protect the body from infection).  In diseases like rheumatoid arthritis and lupus, the immune system is overactive. Methotrexate steps in and interferes with the production of folic acid (a building block for cell growth) and lowers that overactive immune response, preventing swelling and damage.  Although it was designed in high doses to be used for chemotherapy purposes, in lower doses, it is considered safe and pretty well tolerated.


As with any drug that is prescribed, it is important to remember that your doctor believes that the benefits of the drug should outweigh the side-effects.  Thankfully, some of the side effects of methotrexate go away after taking the medication for a period of time.   

The most commonly reported side effects of Methotrexate include:

  • Nausea
  • Mouth sores
  • Vomiting
  • Poor appetite
  • Diarrhea
  • Rashes
  • Hair loss
  • Eye irritations

More serious side effects may include:

  • Unusual bleeding or bruising
  • Blood in the urine or stool
  • Jaundice
  • Extreme fatigue
  • The inability to eat or drink
  • Kidney toxicity or failure
  • Low Red Blood Cell count

If you experience any of these serious side effects after starting methotrexate, seek immediate medical attention.  


If you are planning to become pregnant, are pregnant, or are breastfeeding, you should not take methotrexate.  This medication can cause birth defects and complications during pregnancy.  If you are a women taking this medication, you should use an effective birth control method.  Make sure to tell your doctor about all medications you are currently taking, including any supplements.  Your rheumatologist knows the nuances of this drug and any possible interactions.  It is important to discuss concerns and questions with them, not your pharmacist.  This drug may interact with certain medications including some NSAID’s (Advil, Motrin) and celecoxib (Celebrex) and the antibiotic Bactrim.   It is recommended to avoid alcohol use, over sun exposure, maintain healthy eating habits and get plenty of rest with taking this medication.  And lastly, since methotrexate can suppress your immune system, try and take precautionary measures to stay healthy by avoiding public areas with raised germ exposure.  

    Things to be monitored when you are taking methotrexate:

  • Complete blood cell counts should be checked, as well as, liver function every few months. It is not uncommon for blood counts to dip while on methotrexate, it usually resolves itself when the dosage is decreased.  
  • Check with your doctor before getting vaccinated, certain live vaccines should be avoided.  
  • Any infections, chills, painful urination, red painful skin or sore throat should be addressed immediately with a healthcare professional.  


Methotrexate has been proven to be effective in not only relieving pain and inflammation for those with rheumatoid arthritis and other rheumatic diseases, it has also been proven to slow disease progression and joint damage.  Sometimes, when it is combined with another DMARD drug (like leflunomide) or a biologic (like Humira) in lower doses, it can be particularly helpful.  Because of it’s effectiveness, it is being used more and more as the first line of defense against RA, and other disease that affect the joints.  Immunosuppressants, like methotrexate, are currently one of the most beneficial and used group of drugs in treating moderate to severe lupus.    

Though it may be scary when your doctor suggests you start ANY new medication, being informed and having an open conversation with him or her is the best way to calm those nerves.  Methotrexate has come a long way, and has been proven helpful to many lupus and RA sufferers.  And though many people have side effects from steroids, fewer people experience side effects from immunosuppressants like methotrexate.  And that is good news for those who want to taper off prednisone!  And in the lupus world, we will take any good news we can get! Right?


The Lupus Encyclopedia, Donald R. Thomas, Jr. M.D. FACP, FACR, 2014 Johns Hopkins University Press: p. 544-545


Author: Kelli Roseta

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All resources provided by us are for informational purposes only and should be used as a guide or for supplemental information, not to replace the advice of a medical professional. The personal views expressed here do not necessarily encompass the views of the organization, but the information has been vetted as a relevant resource. We encourage you to be your strongest advocate and always contact your healthcare practitioner with any specific questions or concerns.


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