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Is Methotrexate Under Utilized?

Methotrexate (MTX) is an accepted first-line drug for patients diagnosed with RA. Oral MTX was what my rheumatologist started me on after my diagnosis. For various reasons, the main one being I hated the side effects and I refused to take it, I was soon switched to my first biologic. However, researchers are now asking if this well-known and affordable drug is being used to its full potential.

Exploring this research I learned three important things about methotrexate:

  • It can take up to six months for MTX to be 90% effective and the Treatment of Early Aggressive Rheumatoid Arthritis Trial (TEAR) recommends six months of treatment with MTX before adding a DMARD or switching to a biologic. In comparison, many biologics are fully effective after three months.
  • The European League Against Rheumatism (EULAR) guidelines recommended sufficient dosages are 25-30 mg. per week.
  • Injected MTX has higher bioavailability, has greater clinical efficacy and is better tolerated than oral methotrexate. This is pretty standard for drugs that have both an oral/pill form and an injected form. The injected medication doesn’t travel through the digestive track so it’s absorbed better by the body, doesn’t cause GI upsets, and the actual dose is more consistent. What’s really interesting is that regardless of the dosage taken, the actual effective dose of oral MTX tends to plateau at 15 mg. ( So even if a person takes more pills, their body isn’t necessary absorbing more. (I am currently back on MTX to supplement my biologic. However, I’m doing injections, not pills, and I’m having better results without any noticeable side effects.)

These factors are important when you consider the findings of a research study recently published in Arthritis Care & Research and discussed on The findings of this study are completely contrary to the three points I listed above. This study found that:

  • An amazing 87 percent of the patients were switched to a biologic as the next treatment step. For 41 percent of the patients who were switched, this change occurred at three months, well before the recommended six-month course of treatment for MTX.
  • The average oral dose of MTX was 15.3 mg per week. This is 50-60 percent lower than the EULAR recommended dose. Only about one-third of the patients were taking more than 15 mg.
  • Only 13 percent of the patients moved from oral MTX to injected MTX although the injected form is clearly more effective.

What this study indicates is that when it comes to MTX, doctors generally haven’t (1) been prescribing a high enough dose; (2) given the MTX treatment long enough to work; or (3) didn’t move to injected MTX from oral MTX as the next logical step in treatment.

What the studies don’t tell us (and what I’d be really interested to know) is why biologics were prescribed before an effective treatment course of MTX was tried. All drugs, including MTX, have side effects and that was certainly why I helped drive the change in my situation. I also know that most people would rather take a pill than give themselves an injection – however, the majority of biologics are given either by injection or infusion, so I’m not sure that’s it.

While I think it’s great to know that we have an important drug that might be better utilized, insurance companies other treatment policy makers also look at this kind of research. We just need to be aware that since MTX is much less expensive than the biologics, they could take this into consideration and potentially adjust their treatment recommendations for MTX before switching to DMARD or biologic treatment options.

All this being said, if you’re a patient on MTX, this is good information to have and discuss with your doctor if you are contemplating a change in treatment.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.


  • Dave
    2 years ago

    Carla, First of all, thanks for this post (and all the efforts that you and others put forth here at I am one who doesn’t have a high tolerance for the side effects of MTX. I was diagnosed 3+ years ago and was immediately started on oral MTX and Sulfasalizene. After a few months I was switched to injections. Later on a biologic was added as the MTX and Sulfasalizene just wasn’t getting the job done. I couldn’t tolerate the full 25 mg dosage at all. It put me on the couch for 2 days after the injection. My Rheumtologist gradually cut the dosage down until I reached a level that I could tolerate. (12mg) after being on it for 2 years I started developing mouth sores and some bad liver enzymes so we stopped it altogether and my symptoms ramped up pretty dramatically. In the mean-time my Dr. left town and I was off my biologic for a couple of months and thing went crazy. Long story short: I have a new Rheumatologist and she has me back on my meds which includes MTX injections and I am on a higher dose of Folic Acid and Leucovorin to counter-act the side effects of MTX. So far no issues. My blood work is back to normal and my symptoms have calmed down. I hope that I can continue the MTX along with the Orencia. For me, a biologic just doesn’t work as well by itself. As we all know, RA is a wild roller-coaster ride and I am thankful for the treatment options that we have available.

  • Kathleen Hlavin
    2 years ago

    No problems with this drug, UNTIL it made my nails begin detaching from their beds. Stopped taking it and all is good again.

  • annlogan
    1 year ago

    Omg, are you serious? I was on MTX and sulfasalizene combo for about 4 mos, starting at 25mg and going down to 6mg, it didnt matter how low the dose was, it knocked me off my feet, I could barely function. Losing my fingernails though would be something altogether unacceptable, Im sorry. 🙁 Are your hands back to normal?

    I’m currently back on Humira and have added in a new natural supplement (from a clinical trial I was on last year), and I feel really good, no major flare ups in a few mos. (fingers crossed). And fingernails still in place. 🙂

  • lees
    2 years ago

    I’m not sure where everyone is buying their mtx. I pay about $1.50 for each 2.5 mg pill. That is affordable.

  • 1vdcomi
    2 years ago

    Please don’t say MTX is affordable – it is very expensive. Now a tier 2 or 3 drug and sky high in price. I can hard afford.

  • Dave
    2 years ago

    I am retired and on my drug insurance plan the injection form of MTX (I use syringes, not the Auto-injector.) costs me $12 per month versus $80 for the pills. It’s crazy how much prices vary from plan to plan and in different areas.

  • Carla Kienast author
    2 years ago

    Your point is well taken. Even in the year since I originally posted this article, prices have changed. When I reviewed my drug plan options last year, the “swing vote” was MTX which was more than $400/month on one plan and about $30/month on another. That being said, MTX is certainly less expensive than the biologics on the market. My biologic is charged to insurance at almost $17K every six weeks as opposed to a few hundred dollars for MTX. Having RA is an expensive proposition regardless of how you look at it. Thanks for your comment.

  • Tich
    2 years ago

    Nice piece, Carla. I do think some rheumatologists are over-enthused with the array of biologic choices now and the various encouragements they get from big pharma. That said, I’m sure MTX has helped me when the bio wasn’t doing enough. When it comes to efficacy the question we have to ask ourselves is ‘am I running to prednisone too much ?’

  • Carla Kienast author
    2 years ago

    Thanks, Tich. I think the thing that came through for me on this is that (based on the data) some rheumatologists not effectively using the injected form of MTX. MTX helps me and, to your point, helps me stay away from prednisone, with which I have a love-hate relationship. Regardless, it’s nice to have an arsenal of weapons, rather than basically JUST MTX which is what we had just a few years ago.

  • Karen
    3 years ago

    I was on the injected MTX and lost weight, hair and was hungover for two days each week. I am allergic to Enbrel and arava. Humera did not work for long. I have been on orencia and plaquenil for over 3 yrs now.

    I am also allergic to sulfa based meds so that rules out sulfazine.

    Sometimes this stuff is a messy crap shoot.

  • Carla Kienast author
    3 years ago

    These are all great comments and, as clearly pointed out, MTX (like all drugs) has side effects — for some people quite serious ones. This is why this forum is so great — so we get to hear personal experiences. Thank you so much for commenting. The more information we have, the more empowered we become.

  • Larry Sawyer
    3 years ago

    Have tried MTX 4 times in my RA career. Last time on a minimum dose it gave me cancer like symptoms which it took Shaw Cancer Clinic a while to find. Put me down for 8 weeks and whiffed away 22 lbs. its a tricky one

  • LifenowwithRD
    3 years ago

    For me I was started on Plaquenil (which did nothing for 5-6 months of being on it alone) and the MTX injections were added(my request not to take pills due to my being GI sensitive). I started the injection at 0.7 (17.5mg) last August. After a few weeks of getting used to it (I got a severe headache, some nausea, and extreme fatigue), the side effects improved, as did my RA symptoms. After 4 months, the Plaquenil was dropped and the MTX dose increased to 1ml (25mg). It was horrible. To say injecting does not cause GI upset is very wrong in my case. I was not only nauseated for 2-3 days, I had a dull throbbing headache, and I could barely keep my eyes open and function. Thank God I work from home. I decreased it to 0.9ml, and then down to 0.8ml(20mg) I still have side effects, but can tolerate them if the drug works. It seems that it worked great until the dose got messed and it seems like the side effects caused a flare that I have now been in for 2 months. So, I have been on the MTX for almost 8 months, and now a biologic is being added, Enbrel. I’m not excited about this but my rheum tells me that he can almost guarantee remission if I start the Enbrel along with the MTX and eventually discontinue the MTX altogether. This will be a golden day if that ever happens. It makes me a different person. No energy, crabby, depressed and hopeless feeling. I pray that the Enbrel helps and I can feel “normal” again…whatever that is.

  • Lawrence 'rick' Phillips moderator
    3 years ago

    Well MTX is not underutilized around my house. I do think it pulls me through in times like this when I cannot use the biologic.

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