Is Injectable Methotrexate Better Than Oral Methotrexate?

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Methotrexate is commonly prescribed to treat rheumatoid arthritis and other rheumatic conditions. Methotrexate is classified as a disease-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?


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?

Methotrexate injection is considered less convenient by many patients when compared to oral methotrexate. Getting an additional prescription for syringes, as well as sharps contained to dispose the syringe/needle, and sticking yourself with a needle each week can be a hassle—and some people are needle-phobic. Methotrexate injections can reduce upset stomach, a side effect of the oral formulation.  

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 of Arthritis & 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.

From the study data, researchers concluded that methotrexate injection, using a possible dosage of 15 mg/week for a period of at least 24 weeks (including a possible dosage increase), is superior to initiation of methotrexate by the oral route. At 24 weeks, the percentage of patients with an ​ACR20 response was significantly higher in the group receiving methotrexate injection (78 percent) than in the group receiving oral methotrexate (70 percent).

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

Additional Reading

By Carol Eustice
Carol Eustice is a writer covering arthritis and chronic illness, who herself has been diagnosed with both rheumatoid arthritis and osteoarthritis.