Is Methotrexate for RA Chemotherapy?

Dr. Irwin Lim has a new post up titled In My Hands, Methotrexate is NOT Chemotherapy.  Interesting, especially in light of all the bloggers who claim that they’re on chemo for their RA.

Methotrexate has gotten a bad rap.

Expectation effect means that people will respond to a treatment the way they expect to respond.  We’re all familiar with the term placebo effect.  The placebo effect occurs when people perceive that they feel better because they expect a treatment to work (ie improvement on sugar pills instead of a real medicine).  In contrast, a nocebo effect occurs when people perceive that they feel worse because they expect a treatment to have negative side effects (ie get worse/experience negative side effects while on sugar pills instead of real medicine).  Placebo and nocebo are both examples of people responding to treatment in a way that they expect to respond.

That’s a problem for methotrexate, because mtx has a lot of bad press.  If you visit any of the RA support pages, there’s quite a bit of discussion about how to deal with all the horrible side effects of this medication.  Anyone reading the popular RA sites is likely to go away convinced that methotrexate will make them incapacitated with nausea and vomiting.  In reality, 90% of people do not experience this side effect.

It’s important to recognize that the people spending time on those support sites are in the minority.  The vast majority of people feel fine and don’t frequent those sites because they’re too busy living their lives.

Is mtx chemo?  Methotrexate can be used for chemotherapy, and that contributes to its bad reputation.  When we hear the word “chemo” we tend to think:  nausea, vomiting, hair loss, really really sick.   That can happen in chemotherapy.  We need to be clear, though, that chemotherapy is defined as chemical (drug) treatment targeted at killing fast-growing tumor/cancer cells.  The fact that mtx can be used as a drug to kill cancer cells doesn’t mean that it is always used that way.

That’s the case with RA.  In treating RA, patients usually start out with 7.5mg once a week.  In contrast, if I were being treated for acute lymphoblastic leukemia, I’d get 5.5 mg daily, and then 25 mg twice a week once I was in remission (dose is based on body surface area).  If I were treated for lymphoma, the dose could be as high as 153 mg daily.  Even though I’m on the maximum RA mtx dose of 25 mg weekly, I’m still taking much less than I’d need on chemo.

Even though methotrexate can be used as a chemotherapy drug, when treating rheumatoid arthritis there are no cancer cells being killed.  Low-dose RA treatment doesn’t qualify as chemotherapy.

Read more about mtx, mtx dosing and body surface area.


20 thoughts on “Is Methotrexate for RA Chemotherapy?

  1. This is good information, but I sort think it should have went further? Having two kids with cancer and a similar type of disease as RA (psoriatic arthritis) I have steered from this treatment. It may not kill cancer cells (obviously, although it may. People have cancer cells roaming about in their bodies and don’t know it…so maybe metho will kill some cells unbeknownst to the person). But like so many drugs there could still be a price to pay down the road. If a drug reduces swelling it may affect organs after prolonged use.

    I have a website I love….Cochrane Collaborative. It is researchers and doctors…not people seeking relief and feeling pretty miserable so, indeed, their posts can border on manic at times (when your child is sent home to die as mine was…and another child is still struggling with cancer I can only imagine what some of my posts look like:) They show you truth in clinical trials and beg and plead for transparency in medicine. It is a vital sign that is missing at this point (although, the Open Notes project is just so exciting). They show you the long term affect of drugs…not just chemo drugs, or the immune system invaders. Just this week we find out blood pressure lowering drugs may be doing more harm than good.

    But the radical (often wrongly, discounted) Dr. Mercola does recommend metho as one of the effective treatments. Which is surprising because he recommends drugs as a last resort (a good philosophy). And he, obviously, recommends a lot of natural stuff (that hasn’t worked for me, but I am too scared to stop because sometimes it takes a long term effort to get real lasting results).

    The bottomline is that no one treatment helps every patient with a disease. My friend with MS had her mercury filled fillings removed and was out of her wheelchair in five days. Then she drank only water for 90 days to starve the mercury out of her fat cells (under a doctor’s guidance). She is well today and taking care of her five children. The picture of health. The vast majority of people would not go this radical route….but it worked. She takes no meds. I just haven’t been able to figure out how to slow down an overactive immune system naturally…but find the conversation fascinating.

    • My 25 yo daughter, an aspiring model, has Anklyosing Spondilitus. She started having psoriasis at age of 12. She has been on Methyltrexate for almost a year and continues with Remicade for 6 months. One vertebrae had started to fuse. But, 😀 we just uncovered that AS can be caused/triggered by a bacteria in the Colon called Klebasillia. It colonizes quickly in a high starch diet. She has been doing the London low starch diet, eating fruits, veggies, salmon, meat and nuts. It’s been only a week, and it has reduced her flare ups, pain, and increased her energy. She actually did 20 minutes of elyptical last Saturday. We ordered Sinclaires, Low Starch Diet. It helped her IBS and AS. She has also been taking Boswillia (reduces inflammation and fights Cancer) supplements. She seems to be doing great. I think both could be beneficial for all.

      • If you choose to use these medications or not, it may be beneficial to research the low starch diet. Also known as the Londons Low Starch Diet. Also the book the IBS Low Starch Diet by Sinclaire. You will have to order from th UK.

        What I do know is my daughters back started to fuse, she was in terrible pain, and very exhausted. Since she started the low starch diet only a week into it, she has less pain, and has more energy. The culprit appears to be the Klebesellia bactetia in the colon which colonizes when undigested starch enters it. In a nut shell, the body knows there us an Intruder, but since that bacteria is familiar to the body, the immune system attacks the body instead of the real intruder, the over abundance of Klebesellia. Thus, caused inflammation and her vertebrae to start to fuse. I rather her stop methyltrexate and Rmicade all together to be honest. And allow her body to start to heal naturally so her Anklyosing sponilitus will go into remission.

  2. As someone who has taken Methotrexate for over 25 years, I have done fairly well on it. Since my docs have said mine is severely active, there is a lot for a drug to corral. When I was in rehab for 8 weeks with a broken hip, they stopped my Methotrexate for 3 weeks – boy did I feel the effects about a week or two after. A terrible flare up and it took 3 or 4 weeks before I could begin to feel the effects when I was back on it.

    Like all meds, it depends on body chemistry, course of disease and as you pointed out so well, expectation. The body/mind connection is very real and has a lot to do with outcomes. I will admit that I have certain things I want to be more comfortable and that can be how I see it as working or not working. It is not the whole story and I need to refocus my attention on what is happening all through my body. I was recently on a drug study that was showing signs of working, unfortunately those positives were not enough to offset the very difficult and uncomfortable side effects. Although I had to stop, it gave them some valuable information – so it wasn’t a complete loss.

    • Nope. Your logon on your first comment was different than previously on this blog, so WP flagged it for moderation. I’ve been a bit busy and didn’t get it approved immediately, but intend to write a nice response to your thoughtful comments. That won’t happen today, though. In any event, I approved your comment and now (if WP works right) your future comments will show up immediately.

  3. I think it is an important point that the RA community discusses the side effects of MTX ad nauseum, often scaring new patients from treating what can be a progressive and debilitating disease. At the same time, I think discounting the anecdotal evidence (bloggers, forum users stories) is not a wise move – especially since so many patients have difficult or unfulfilling relationships with their rheumatologists.
    I take methotrexate (15mg weekly). I had nausea for the first few weeks and the first week every time I’ve upped the dosage. The nurse (not my doctor) gave me a few pointers (split the dosage -even over 2 days if necessary, full tummy, lots of water) and I wear seabands (maybe placebo, but hell, I’ll take it) and now I only feel it if I forget to eat. I’m losing hair at an alarming rate but that probably means I should take more folic acid. My point is, the side effects have not been prohibitive and the benefits outweigh them.
    So my two points are: 1) Don’t discount the side effects. I don’t buy 10%, regardless of citation (which is missing) and 2) Doctors should talk about the potential side effects, the various means of dealing with them, the fact that they’re often short-term, and the true, long lasting benefits of the drug (controlling the disease not just the pain!). An open dialogue would go along way. Many docs just don’t take the time or don’t have the knowledge to help with this.

    • I plan to do a separate post dealing with side effects. This was aimed more at the distinction between cancer treatment and RA treatment – chemo vs DMARD. Side effects of DMARDS are different than side effects of chemo. I can add a citation, but reality is that people rarely click on links when I do include them, so I tend to let that slide sometimes.

      I believe that people read all the horror anecdotes and talk themselves into having worse side effects than they otherwise would. As for doctors taking the time to explain possible side effects, that’s probably a whole separate post.

      • Here’s one citation (From
        Adverse Reactions in Double-Blind Rheumatoid Arthritis Studies

        The approximate incidences of methotrexate attributed (ie, placebo rate subtracted) adverse reactions in 12 to 18 week double-blind studies of patients (n=128) with rheumatoid arthritis treated with low-dose oral (7.5 to 15 mg/week) pulse methotrexate, are listed below. Virtually all of these patients were on concomitant nonsteroidal anti-inflammatory drugs and some were also taking low dosages of corticosteroids. Hepatic histology was not examined in these short-term studies. (See PRECAUTIONS.) Incidence greater than 10%: Elevated liver function tests 15%, nausea/vomiting 10%.
        Incidence 3% to 10%: Stomatitis, thrombocytopenia, (platelet count less than 100,000/mm³).

        Incidence 1% to 3%: Rash/pruritus/dermatitis, diarrhea, alopecia, leucopenia (WBC less than 3000/mm³), pancytopenia, dizziness.

        Two other controlled trials of patients (n=680) with Rheumatoid Arthritis on 7.5 mg – 15 mg/wk oral doses showed an incidence of interstitial pneumonitis of 1%. (See PRECAUTIONS.)

        Other less common reactions included decreased hematocrit, headache, upper respiratory infection, anorexia, arthralgias, chest pain, coughing, dysuria, eye discomfort, epistaxis, fever, infection, sweating, tinnitus, and vaginal discharge.

        Adverse Reactions in Psoriasis

        There are no recent placebo-controlled trials in patients with psoriasis. There are two literature reports (Roenigk, 1969 and Nyfors, 1978) describing large series (n=204, 248) of psoriasis patients treated with methotrexate. Dosages ranged up to 25 mg per week and treatment was administered for up to four years. With the exception of alopecia, photosensitivity, and “burning of skin lesions” (each 3% to 10%), the adverse reaction rates in these reports were very similar to those in the rheumatoid arthritis studies. Rarely, painful plaque erosions may appear.

        • Thanks for the study link – I guess I kinda have to buy it now 🙂
          And yes, I do believe that reading all the horror stories has an impact on how people feel. I also feel that it isn’t helpful for people to think they’re on chemo or describe their treatment as being on chemo… I guess I assumed it is a results of feeling like the disease/treatment isn’t be taking seriously. Which is another, bigger problem.
          Thanks for the post – lots of food for thought.

  4. I was one of the people who was unable to tolerate MTX. It didn’t make me particularly nauseated, but the “general malaise” catagory went up 500 percent. Along with that I was incredibly fatigued. I stayed on it for six months, but in the end, I asked to try something else.

    That said, I never considered MTX as chemotherapy, though I knew from the start that the drug is used in much, much larger doses to treat several forms of cancer. All the “chemotherapy” label gave it, for me, was a deep respect for it as a serious drug taken for serious disease, and one not to fool around with.

    Thanks for your post, Socks. You’ve been missed.

    • Canning apples and teaching swimming lessons is keeping me extraordinarily busy.

      Sorry that mtx didn’t help you. I really wish they’d put people on a bioligic first and then see if backing off to less dramatic meds would work. It will be interesting to see in 15-20 years what the standard of care is. Hopefully a lot better than what we have now.

  5. Socks, Good post! When I started taking MTX I was very hesitant – I am the puking queen! Everything makes me throw up – it’s a joke in my family and I was concerned that the primary side effect was nausea – figures! But I was in so much pain. I was pleasantly surprised. I had no side effects at all except some morning after hang over feeling until I hit 20mg then at my doctor’s suggestion I split the dose between two days. I still get that hang over feeling – now I get to feel like that two days – whoo hoo – but the nausea is gone. I did get some good hints – taking the med before bed and pros and cons and I think a good discussion of how many people get what kind of side effects and how bad they really are or are not from RAWarrior’s site. MTX wasn’t enough and I have since added Humira – miracle! I actually am starting to feel really good! I might be able to reduce the MTX at some point in the future. As far as MTX being chemotherapy, I think that knowing it is a chemo drug does impress the severity of the disease on people and I think that is one reason why people refer to it that way. It helps people to understand that you are not just dealing with a little OA. Although having a Mom with severe OA that has crippled her, I have a lot of difficulty discounting the effects of this disease. For some people, OA isn’t just a bad knee either. And while I am recieving effective treatment, the doctors have little or nothing for OA. It’s depressing.

  6. Great post, WS. It’s helpful for readers to be reminded of the placebo effect, the placebo response, the expectation effect and, importantly, the NOCEBO effect. Physicians may be the most common deliverer of the latter because medical training is generally negative. Patient communities may help each other to filter the potential for the less desirable effect, especially via social media such as your informative blog. Thanks again. apj

    • Dr. Jonas’ point about physicians being the most common deliverer of the NOCEBO effect is well taken. I had a rheumatologist who used the word chemo all the time when discussing mtx. In fact, he didn’t start calling it mtx until something like 8 or 10 months after I first started seeing him. And when I expressed concern about the effects of long term use of mtx, he actually told me he didn’t blame me for being concerned, which didn’t provide me with any comfort. Looking back, he totally added to my anxiety about the drug, whether he meant to or not.

      As a physician, my rheumatologist certainly had the obligation to NOT ignore the potential side effects of mtx, but on the flip side, he did a poor job of explaining to me how the benefits of the drug might outweigh the risk. Again, I don’t think he intended to add to my concerns but, respectfully, I have to say that I get frustrated when doctors express so much dismay about patients’ reluctance to take the medication, when they often do very little reflection on how they themselves (or their colleagues) may add to the problem.

      I thank Dr. Jonas for recognizing that there is work to be done all around.

  7. Saw rheumatologist today and was given rx for methotrexate and folic acid for what he said is either ra or lupus related. He explained that by taking this now(begining) that meds may prevent me from being disabled by disease. Any comments ?

    • I’m sorry to hear about your diagnosis 😦 Methotrexate is one of the most commonly prescribed Disease Modifying Anti-Rheumatic Drugs (DMARDs). DMARDs slow down damage done by RA/SLE. Twenty-five years ago, such a diagnosis would mean you’d likely be disabled and in a wheelchair within 5-10 years. The goal of DMARDs is to postpone – maybe even prevent – that from happening. The standard of care is early, aggressive treatment.

      BEFORE YOU TAKE YOUR FIRST DOSE, MAKE SURE ALL YOUR VACCINES ARE UP-TO-DATE! It is not recommended that people get any shots other than your annual flu shot while taking methotrexate. When I was given a mtx prescription, I got my tetanus booster the next day, and waited (however long the doctor recommended – don’t remember now how many days it was) before beginning the mtx. If you’re considering any overseas travel, check which vaccines would be needed to go there, too, and get everything done at once would be my suggestion, but I am not a doctor, so this is just one-patient-to-another, not medical advice.

      Most people tolerate mtx very well, although I will confess that I felt sick for the first couple weeks I took it. That quickly went away, though, so if you feel a little nauseated the first time you take it, don’t think that means you’ll always feel that way. 90% of people do just fine. Your pharmacist can give you tips on taking it. I was told to take it on an empty stomach, so I would eat supper and not do any snacking that evening. I took the pills immediately before climbing into bed so that if there were any unpleasant side effects, I’d sleep through them. It worked well. A beginning dose is probably around 10 mg once a week. If, after a few months, stronger medicine is needed, that dose can be gradually increased until the desired effect is achieved. Mtx comes in both pill and injectible form; if you give yourself a shot instead of taking pills, you don’t have to be concerned about taking it on an empty stomach.

      The folic acid prescription is because (short answer) extra FA is needed when you’re on mtx. After about a year, my rheumy increased me to 2 pills a day instead of one – it just depends on how you’re doing. I felt fine, but she saw something in the size of my red blood cells that made her think I’d do better with 2, and that made everything go back to normal.

      You were probably also given a lab slip with a standing order for lab work. Doctors differ in how often they say you need blood drawn, but it would typically be every 4-8 weeks. That’s to check and make sure that your liver and kidneys are handling the medicine okay. Potential problems will show up in you bloodwork before you would start experiencing any symptoms. If any of the values are alarmingly out of the normal range (small variations are okay), your doctor might have you stop taking the medicine until things look ideal again. After that, it’s safe to start taking the medicine again.

      Methotrexate can suppress your immune system, so you will want to be extra careful to avoid germs. Do things like washing your hands a little more frequently, scowling at people who sneeze in your face, and consider carrying little bottles of hand sanitizer in the pockets of all your coats.

      Best of luck. Come back in a few weeks and let me know how you’re feeling.

      • Oh, and if you didn’t get a slip for lab work, it probably means that you’ll be back to follow up with the doctor before those labs need to be drawn. Not anything to worry about 🙂

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