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Prednisone vs. Methotrexate: Which is Worse?

Prednisone vs. Methotrexate: Which is Worse?

Prednisone vs. Methotrexate

Three times this week I’ve been asked a variation of this question and that includes methotrexate and prednisone.

Which do you think is safer to take: prednisone or methotrexate? Is it advisable to take them together?

Which is worse, methotrexate or prednisone?

Here’s a story from a Prednisone Warrior:

Do you have any videos or advice for people like me who are younger that will likely be on Prednisone for 2-5 years if not a lifetime and whose disease is so substantially debilitating without it that Prednisone is truly a life saving medication? And am I wrong for not wanting to add in methotrexate “just to get my steroids lower” when I am not experiencing any side effects?? I have done a lot of research into methotrexate and the liver/kidney/body damage it does seems far worse in my opinion than staying at a slightly higher dose of Prednisone as we taper slower?

Watch the video to find out my surprising answer:

Watch Prednisone vs. Methotrexate now!

Is Methotrexate a Worse Medication than Prednisone?

Many people think that methotrexate sounds like a worse medication than prednisone because it has a few side effects that sound awful.

But the doctors who take care of people with rheumatoid arthritis have a different opinion. This is what they say:

Methotrexate is conditionally recommended over other medications.

RA Treatment Guidelines

According to the doctor’s guidelines, methotrexate is the safest option for people with rheumatoid arthritis. Doctors consider Methotrexate a safer option for long-term conditions such as rheumatoid arthritis, due to its lower side-effect profile compared to prednisone.

They went on to compare prednisone to methotrexate and said:

The toxicity associated with glucocorticoids [prednisone] was judged to outweigh its benefits.
benefits vs risk while on prednisone

Prednisone Has MORE Side Effects than Methotrexate

The reason the doctors say that the side effects of prednisone outweighs the benefits is because prednisone causes more side effects than any other drug. I’ve counted at least 150 side effects to prednisone, many of which get worse over time. Here are some of the prednisone side effects I personally experienced:

Dr. Megan's prednisone side effects

Methotrexate is considered a safer option than prednisone for long-term treatments, such as rheumatoid arthritis, due to its lower side effect profile.

What is Methotrexate used for?

Methotrexate, on the other hand, is an immunosuppressant and disease-modifying antirheumatic drug (DMARD). It effectively inhibits the production of certain cells involved in the immune response, decreasing inflammation and slowing down the progression of conditions like rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Perhaps the reason people perceive methotrexate as worse than prednisone is because methotrexate can be used as a chemotherapy drug. But what’s not often realized is that prednisone can also be used in cancer chemotherapy regimens as well.

What are the side effects of Methotrexate?

Although Methotrexate generally has fewer immediate side effects compared to Prednisone, it can still cause nausea, fatigue, hair loss, liver toxicity, and an increased risk of infections. Regular blood tests are often necessary to monitor its effects on the body.

Balancing Benefits and Drawbacks of Prednisone vs. Methotrexate

While both Prednisone and Methotrexate have their pros and cons, it is important to remember that each individual’s experience may vary. Prednisone offers quick relief from inflammation, making it a suitable option for short-term use to manage acute flares. Methotrexate, on the other hand, provides long-term benefits in slowing disease progression but may take longer to show results. It is often used as a maintenance therapy alongside other medications. Individual factors such as the severity of the condition, lifestyle, and personal preferences should be considered when making a decision.

Combination of Methotrexate and Prednisone Better?

New research suggests that taking prednisone along with methotrexate can help ease the side effects of methotrexate! What an interesting twist.

Navigating the Long-Term Impact of Prednisone and Methotrexate

Since both Prednisone and Methotrexate can have adverse effects on the body, it is crucial to discuss potential risks with your healthcare provider. Long-term use of Prednisone can result in a range of complications such as osteoporosis, weight gain, and an increased risk of infections. However, tapering off the medication under medical supervision can help mitigate these risks. Methotrexate, although generally well-tolerated, may necessitate routine monitoring of liver function and regular blood tests to ensure its safe usage.

  1. Rheumatoid Arthritis Treatment Guidelines. https://www.arthritis.org/diseases/more-about/rheumatoid-arthritis-treatment-guidelines
  2. van der Leeuw MS, Tekstra J, van Laar JM, Welsing PMJ. Concomitant prednisone may alleviate methotrexate side-effects in rheumatoid arthritis patients. BMC Rheumatol. 2023;7(1):8. doi:10.1186/s41927-023-00331-0

Dr. Megan Milne, PharmD, BCACP

Dr. Megan Milne, PharmD, BCACP, is an award-winning clinical pharmacist board certified in the types of conditions people take prednisone for. Dr. Megan had to take prednisone herself for an autoimmune condition so understands what it feels like to suffer prednisone side effects and made it her mission to counteract them as the Prednisone Pharmacist.

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