There are some weapons in the battle against RA that I consider “dragon-
Illustration by Howard David Johnson
slayers.” Unfortunately, I was unable to tolerate the one I’ll be telling you about, but from everything I’ve learned over the years, it’s one of the best.
It’s a Disease Modifying Anti-Rheumatic Drug (DMARD) that’s considered the “gold standard” in rheumatoid arthritis treatment. At some point, most rheumatologists prescribe it to their patients who have moderate to severe RA. In many of them, this drug causes their disease symptoms to greatly improve—or even disappear entirely. RA is incurable, but this rheuma-dragon slayer can send it yelping off with its tail between its legs.
What is this miracle drug?
It’s methotrexate—MTX for short—a powerful chemotherapy drug developed in 1950 to treat a variety of different cancers, including acute lymphoblastic leukemia in children. It works by keeping the body’s cells from metabolizing folic acid, a substance that is integral to cell growth and reproduction. Without adequate folic acid, cells die—in particular, fast-multiplying cancer cells. With methotrexate, many people who suffer from cancer may have a much better chance of surviving.
Methotrexate was quickly discovered to have a beneficial effect against several autoimmune diseases, including psoriasis, psoriatic arthritis, lupus, Crohn’s disease and many form of vasculitis. It was first used to treat rheumatoid arthritis in 1951. Generally safe, well-tolerated and effective in lower doses, methotrexate was approved by the FDA for use in treating RA in 1988.
As it does in treating cancers, MTX inhibits cells from metabolizing some of the folic acid found in the foods we eat, so most rheumatologists have their RA patients take a folic acid supplement along with their methotrexate. Doing so helps to relieve some of this powerful drug’s more common side effects (which occur in a small percentage of patients) such as nausea, headaches, fatigue and hair loss.
While it doesn’t work for everyone, methotrexate has been effective enough that it’s become the first line of treatment for rheumatoid arthritis. When it does work, it reduces the number of swollen, painful and tender joints patients report and, often, slows or even stops the progress of the disease altogether.
Methotrexate can be hard on the liver, so patients taking it must undergo frequent blood tests, monitored by their rheumatologists. In addition, because of the potential danger of liver damage, those who take it are asked to avoid alcoholic beverages. Women who wish to have a baby must stop taking the drug before becoming pregnant; men who are taking the drug should continue using birth control for three months after they stop taking MTX. Otherwise, the drug may cause harm or death to the fetus.
Sometimes, methotrexate alone isn’t enough to affect RA, so it’s given along with one or two other DMARDs. Usually, it’s taken in tablet form: several tablets just once a week. For those who cannot tolerate the oral form because of nausea, methotrexate can also be given by self-injection.
For more information about this “dragon slaying” drug, visit www.healthline.com/health-slideshow/rheumatoid-arthritis-methotrexate .
RheumaBlog 
I think MTX is the next step for me if Sulfasalazine, Hydroxychloroquine and anti-inflammatories can’t keep my RA in control. The summer was good, but so was the weather…now the change is coming, so I’ll find out if its the meds, or the sun keeping me functioning.
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For me, it’s never the sun–it’s sunny at least 85 percent of the time here–but a changing barometer does often go along with a flare. As for the meds, I take Arava (leflunomide) in place of the MTX, Plaquenil (hydroxycloroquine) and Sulafasalazine. I still have flares, but they tend to be mild-moderate compared to how they used to be. I sometimes wonder how well my “cocktail” works, but I’m frankly afraid to fool with it! Perhaps adding a third medication to what you’re already taking will help?
Wishing you the best, JGC, as always. 😉
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Nicely done article, Wren.
So sorry that mtx didn’t work for you. Sometimes I wonder if another attempt would yield a different result. Docs have learned so much, and prescribe differently now than in the past. Starting low and gradually increasing the dose can be much easier to tolerate. However, if I had a bad reaction to a med in the past, I wouldn’t be very inclined to try it a second time.
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Hi, Socks! Thanks! As I was writing this post, it felt sort of haphazard, but upon proofing, etc., it seemed okay, so I went ahead and clicked “publish.” I do appreciate your input. 🙂
I can’t recall the exact MTX dose I started with, but it was standard, I believe. The drug didn’t cause nausea, but instead simply wiped me out for the next 48 hours. The third day I’d start to feel somewhat more together, but foggy-minded. I stuck with it for roughly six months, but in the end when the wipeout didn’t abate, I begged my doc to try something else. (It also had no appreciable affect on my rheuma.) He prescribed Arava instead, which I understand is a similar drug. The after-effect of the MTX lasted another three weeks or so, then abated, and I’ve never had any problem at all with Arava. It’s strange to me how each of us reacts differently to both the disease and the drugs used to treat it…
I did ask my rheumatologist about trying the injectable version of MTX, but he told me that since nausea wasn’t my complaint, there would probably be little change in my reaction to the drug.
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Hi Wren,
Nice, clear article. 🙂 Hurrah for methotrexate. Sorry it didn’t work for you though. 😦
I’m on MTX now (I take it in combination with hydroxychloroquine) and it does it for me. By the way – I’ve only got ‘mild’ RA but these days most rheumatologists consider it’s better to treat mild RA than to wait for it to become moderate to severe before treating – thank goodness!! I’ve been on it about six years now, starting low, as WarmSocks says, and building up. I started on 7mg (a ‘baby dose’ my rheumy called it), built up and was on 15mg for several years, and then it wasn’t working quite so well last year so they upped it to 17.5 (fairly high but not drastic!) and it’s working pretty well again. My only concern is that if I have to have another increase in a couple of years that’s probably as high as they want to take it and then there’s not a lot open to me as I can’t get biologics on the NHS!
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@Pollyanna Penguin, mtx for RA can go up to 25mg. Also, switching to injectable instead of pills is supposed to make more of the medicine available for use. You have a few increases available yet – hope you never need them.
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Hi, Penguin!
I’m glad that MTX has worked for you over the years. It does indeed seem to be real dragon-slayer! I can understand your concern, though, that the NHS won’t offer biologics to RA (and other autoimmune disease sufferers). I guess it’s a matter of cost? They are stunningly expensive.
My health care is provided via the Veteran’s Administration; the only biologic DMARD it provides is Humira, at least so far. It’s my hope that before long the pharmaceutical companies manufacturing these drugs will drop the prices so they can be more consistently provided (at a lower cost or co-pay) to those who need them to live better, less painful and disabled lives. My twingy fingers are crossed.
Wishing you the best, Penguin. I hope you’re feeling well. 😉
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Thanks for this, you put it together really well. Sorry to read that you cannot tolerate it. I have been taking MTX for over three years now, tapering it down to a very low dose, keeping fingers crossed it will stay that way. Some of the side effects can be reduced if you take it (i.e. the weekly dose as subcutaneous injection) after a decent evening meal before bedtime. The nausea side effect is entirely in the brain and not related to food, and sleeping through it without an empty stomach works well for me. I have also been advised to drink 2 to 3 litres of water in the 24 hrs after injection and that coffee helps to reduce any headaches. In fact, when I was first introduced to MTX in hospital, I was given a cup of coffee about one hour after injection and the next morning 3 glasses of pineapple juice. While I never experienced any beneficial effects from the pineapple juice, other patients swear by it.
My secret worry is that the day may come when my body cannot tolerate it any longer – as I have been warned this may happen. We shall see. Take care and stay on the bright side, always.
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Guten tag, Sabine!
Thanks for your kind words. I do, always, try to stay on the bright side–it makes life ever so much better.
And thank you for telling us how we might better be able to tolerate methotrexate–I’ve no doubt that a full stomach, coffee and even pineapple juice could be very helpful. In my case, the MTX didn’t cause nausea, but a terrible, weak fatigue that stayed with me for nearly three days after taking my weekly dose. I got where I dreaded taking it.
That is NOT to say that others shouldn’t. These drugs seem to work differently on each of us, and my reaction wasn’t typical. I hope that MTX continues to work for you, Sabine. And of course, I wish you the best. Someday I hope to visit Germany–and the Rhine Valley–again. 🙂
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I, too, have problems tolerating MTX, although I understand people who take the injections have fewer issues than those who take it orally. Even with the advances in newer medications, it’s great that we do have a “dragon slayer” (love that term!) that has such a long history of known effects and side effects. Thanks for the always well-written post. Hope you’re doing well.
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Hi, Carla!
Thank you! It’s hard for me to believe that MTX has been around for so long. It was never offered to me when I was first diagnosed by the U.S. Army doctor in Germany, but it’s possible that it wasn’t on the military’s formulary at the time. Or perhaps, as this doc wasn’t a rheumatologist, but an internist, he wasn’t aware of it.
Anyway, it’s a wonderful drug–and a miracle that it works so well for so many people.
It’s always good to hear from you. I hope your knee continues to heal, slowly but surely, and that your dragon isn’t biting too hard in the meantime. 😉
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On my journey to manage RA, MTX was my 3rd oral DMARD…I started with Plaquenil, Sulfasalazine, then MTX. Like you, Wren, MTX didn’t make me sick, per se, just drained for 3 days following and then by the time I began feeling well, it was time to dose again. Since I had not gotten any relief from the joint swelling, stiffness, and tenderness, I decided to take myself off the meds in January thinking I could manage. That was NOT a good idea. Tomorrow will be my first infusion of Remicade. In hindsight, tolerating the side effects of the oral DMARDs may have been a better option than what lies ahead. Hopefully, this “dragon-slayer” leaves ME intact.
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Hi, Pauline!
You’re the first person I’ve heard of, other than myself, who wasn’t bothered with nausea by MTX, but instead simply got flattened by it. Such a strange, unaccustomed feeling that was! I can’t blame you for stopping it, but I cringe imagining the pain you must have experienced when the MTX and the other DMARDs left your system. Wow.
I do hope that Remicade turns out to be your best weapon against the dragon. Take care of yourself–and do come back and let us know how it goes, okay? Sending warmth and hugs your way. 🙂
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Sorry MTX and you did not get along. Fortunately for me I have been able to tolerate MTX (pills). I have to be much more careful with sun exposure now and have to use a heavier than normal sunscreen. I wound up early on in the ER over this so now I watch the UV forecast if I am going to be outside and limit my time in the sun with breaks out of the sun.
Have you checked into Xeljanz as a possibility? It is made by Pfizer for RA patients who have not responded well to methotrexate.
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You know, Terry, I haven’t. (Hi!) Arava as MTX’s replacement seems to work well enough–at least, it did. Jury’s out at the moment. I’d be very surprised if Xeljanz was on the VA’s formulary already, being such a new drug.
I’m glad MTX works for you. Was it a really bad sunburn that sent you to the ER, early on? My doc also prescribed a super-sunscreen for me back when I first started DMARDs. At first it was for the MTX, but after I switched to Arava, he told me to keep using it since I was taking others that caused sun-sensitivity as well.
Nice to hear from you! Keep feeling good!
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Wren, glad the Arava works for you. I’m not so sure I would want to jump on board with a new drug that was just approved anyway.
I drink a lot of water and Gatorade/Powerade while out in the heat. Actually … I wasn’t sunburned at all. Just extreme fatigue and a bit dizzy, seems like I had a slightly elevated temperature. 2 bags of iv fluids, some tests and 4 hours later I was leaving. It took a while to get to feeling normal again though.
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Love the pic! I also could not tolerate oral MTX. The reaction you describe mirrored mine. However, four years later my rheumy suggested giving injectable MTX a try. I’m up to 20mg weekly and seem to tolerate it very well – although the first couple of weeks were full of nausea. You never know, maybe you should try injections. MTX is still the gold standard with Arava coming in as the second line DMARD.
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I’ll bring the injectable version up with my rheumatologist again when I see him next month, Andrew. Thanks for the suggestion… added to the others who’ve commented here, yours was the one that changed my mind about it. Well, that and the fact that my ol’ dragon has been biting a LOT harder lately, which makes me a bit nervous. It may be that one of my trio of meds isn’t working so well anymore. These drugs do seem to lose their oomph after a while.
Wishing you the best. I hope you’re feeling well. 🙂
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I took mtx injections for 5yrs but never really tolerated it well. Last year I finally gave up and switched to arava. I think the mtx worked well but feeling unwell 3 days a week was just not worth it. Occasionally, I consider trying it again but I just can’t face the thought of it. I am afraid that the health care reform may eliminate some of the meds we take. I guess we have to hope for the best.
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I hear you. Three days a week feeling ucky and dragging around was miserable. Yet it may, for me, be worth trying the injectable version anyway. Who knows?
I’m of the mind that the ACA will make all of the meds we take available to everyone who needs them–as opposed to those who haven’t the money for health insurance or astronomical co-pays. And you’re right: We must hope for the best.
I hope you’re feeling good and enjoying the days as summer slips slowly into fall, Mary. Sending a hug your way.
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Heh. It’s been a long day. I meant: as opposed to denying them to those who haven’t the money, etc…. 😉
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Good morning, as a follow on to my comment a couple days ago, as I mentioned, I was having my 1st Remicade infusion on Wed. I’m 2 days post, and so far, the fear of the process was worse than any side effect. My rheumatologist saw me just prior to beginning and was very reassuring. He reminded me that while the list of possible side effects is hideously long, the mere fact that we HAVE RA increases our risk of these very things far more than the drug does. While in the infusion room, I met some very interesting folks getting their infusions. Some of them with R disease more advanced than mine. It was a reminder of why I was there….to prevent myself from reaching that more advanced stage. I’m keeping my fingers crossed that this will be the answer for me. Oral meds and I have never really gotten along…so yet, another tool in the ‘dragon-slaying’ arsenal, with even more being developed. Hope abounds….. 🙂
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I’m glad the Remicade infusion went well, Pauline, and that you’ve not suffered any adverse effects (so far; fingers are crossed). When I was first diagnosed, MTX hadn’t been approved by the FDA yet, and there were few other DMARDs available. Since then, WOW. There are so many! And, as you said, there are more in development as medical science learns more and more about the disease and how our bodies work.
Here’s wishing you the best of luck with the new dragon-slayer. I hope you start feeling a difference very soon. 😀
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