Methotrexate is commonly prescribed to treatrheumatoid arthritisand other rheumatic conditions. Methotrexate is classified as adisease-modifying anti-rheumatic drug(DMARD). The drug decreases pain and swelling associated with rheumatoid arthritis, slows progression of the disease, and helps prevent joint damage. When considering effectiveness and safety, is methotrexate injection better than oral methotrexate?

Hero Images/Getty Images

Doctor reviewing medical chart with senior man

Availability

Oral methotrexate is available in 2.5 mg tablets. The usual starting dose for adults with rheumatoid arthritis is 7.5 to 10 mg (3 to 4 pills) taken together once a week. If needed, the dose may be gradually increased to 20 to 25 mg a week. Your healthcare provider will determine the correct dose for you.

Methotrexate injection is given under the skin (subcutaneously). It comes as 25 mg per 1 milliliter. Again, your healthcare provider will prescribe the dose you should use. In children with juvenile rheumatoid arthritis, the dose is based on the child’s weight.

Which Form of Methotrexate Is Preferred?

What if there was a difference between methotrexate injection and oral methotrexate in terms of effectiveness and risk of side effects? According to results from the first clinical trial to systematically investigate the optimal administration of methotrexate in patients with active rheumatoid arthritis, published in the January 2008 issue ofArthritis & Rheumatism, methotrexate injection (also referred to as subcutaneous methotrexate) is significantly more effective than oral administration of methotrexate at the same dosage, with no increase in side effects.

There were 384 study participants in the 24-week study who were randomly assigned methotrexate injection or oral methotrexate. The study participants, said to have high disease activity at the start of the study, received 15 mg weekly methotrexate injection plus oral placebo or 15 mg weekly oral methotrexate and placebo injection.

Methotrexate Is Slow-Acting

With methotrexate use, improvement in rheumatoid arthritis symptoms or disease activity is usually detected in 3 to 6 weeks. It can take 12 weeks of treatment with methotrexate to achieve full benefit.

Side Effects

Some rheumatoid arthritis patients do not experience any side effects while taking methotrexate and others experience minor side effects that improve over time.

The most common side effect of methotrexate is nausea. Other side effects can include abnormal liver function tests, mouth sores, rash, diarrhea, hair loss, sun sensitivity, and abnormalities in blood counts. There is the potential for lung problems as well.

1 SourceVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Braun et al.Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of Methotrexate in patients With active Rheumatoid Arthritis.Arthritis & RheumatismVolume 58, Issue 1, Pages 73-81. December 28, 2007. doi:10.1002/art.23144Additional ReadingMethotrexate (Rheumatrex, Trexall, Otrexup, Rasuvo).American College of Rheumatology. Michael Cannon, MD. March 2015.

1 Source

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Braun et al.Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of Methotrexate in patients With active Rheumatoid Arthritis.Arthritis & RheumatismVolume 58, Issue 1, Pages 73-81. December 28, 2007. doi:10.1002/art.23144Additional ReadingMethotrexate (Rheumatrex, Trexall, Otrexup, Rasuvo).American College of Rheumatology. Michael Cannon, MD. March 2015.

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Braun et al.Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of Methotrexate in patients With active Rheumatoid Arthritis.Arthritis & RheumatismVolume 58, Issue 1, Pages 73-81. December 28, 2007. doi:10.1002/art.23144

Methotrexate (Rheumatrex, Trexall, Otrexup, Rasuvo).American College of Rheumatology. Michael Cannon, MD. March 2015.

Meet Our Medical Expert Board

Share Feedback

Was this page helpful?Thanks for your feedback!What is your feedback?OtherHelpfulReport an ErrorSubmit

Was this page helpful?

Thanks for your feedback!

What is your feedback?OtherHelpfulReport an ErrorSubmit

What is your feedback?