Methotrexate for RA

Methotrexate is one of the Disease Modifying Anti-Rheumatic Drugs that can be prescribed to treat rheumatoid arthritis.  It is usually prescribed along with folic acid (to reduce the possibility of mouth sores).

Other DMARDs such as plaquenil and sulfasalazine take two months or more to begin working.  Methotrexate can show results in as little as three weeks – although six weeks, or up to six months can be needed to get the full benefit.

Methotrexate comes in both pills and an injectable form.  The pills are tiny – only one-quarter of an inch in diameter:

People sometimes read the side-effects list on this medicine and are concerned.  That list sounds pretty scary!  Not to worry.  The list of side-effects includes things that most people don’t experience.  When you’re given a prescription, it’s because your doctor believes that the chances the medicine will help you are greater than the chances that there will be serious side effects.  Here’s a great info sheet by one doctor.

Side effects tend to be dose-related.  That means the higher the dose, the greater the chances for adverse reactions.  RA patients are taking a much lower dose than cancer patients, so most of the potential side effects listed will not be a problem for people who are taking mtx for RA.

When I wrote previously about mtx side effects (here and here and here), I said it would be interesting to look back in a year to see if my perspective had changed.  It’s already changed.

Anemia, low white blood cell count, and low platelet count.

Yes, these lab results are all lower than they were before mtx.  It doesn’t seem to be a causing any problems, though.

Risk of infection.  Avoid people with infections, colds, or flu.

One article I read said that rates of infection among those taking mtx are similar to those seen in the general population.  The difference is that those in the general population have an immune system that can fight infection.  RA patients taking immunosuppressants have a harder time fighting infections, so are supposed to phone the doctor and get early treatment.

Nausea or vomiting.  Small frequent meals, frequent mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help.

I’m now taking double the dose that I was in the beginning and don’t have any trouble with nausea or dizziness.  This was only a problem for the first 3-4 weeks.  Taking mtx at bedtime so you sleep through the worst of the side effects can help.  Dehydration can make it worse, so make sure you’re drinking plenty of water.

Not hungry.

I still don’t see why this is considered a problem.


Thankfully, this hasn’t been an issue.

Mouth irritation.  Frequent mouth care with a soft toothbrush or cotton swabs and rinsing mouth may help.

Mouth sores that occur with mtx use are thought to be from a folic acid deficiency.  Taking prescription-strength folic acid helps.  I’ve heard from a few people whose doctor recommended increasing to 2 mg daily when they still got mouth sores on 1mg.


Headaches were quite severe the first couple weeks, but are no longer a problem.  I suspect that taking this at bedtime helps.

Hair loss.  Hair usually grows back when medicine is stopped.

I didn’t notice any problem with this.  Hair loss was significant a few years ago without methotrexate.  It seems to be back to normal now.

Liver damage can rarely occur.

This is one of the reasons that monthly lab work is done.  Problems are unlikely, but if they occur, should show in the lft’s before symptoms become a problem.  Reducing the dose (or discontinuing temporarily) helps.

Alcohol use is hard on the liver, so doctors usually recommend abstaining from alcohol if you’re taking mtx.

Lung damage can rarely occur.

It’s more common for RA to affect the lungs than it is for methotrexate to cause lung problems.  Doctors take x-rays and a good history before beginning mtx in an effort to identify those most likely to have lung complications.  There’s a study linked at the bottom if you’re interested in reading more.

Other forms of cancer can rarely occur later in life.

The risks are still pretty small.

More Reading:

Ten Things You Should Know About Mtx
Risk Factors for Methotrexate-Induced Lung Injury in Patients with Rheumatoid Arthritis: A Multicenter, Case-Control Study

Additional methotrexate information:
American College of Rheumatology
NIH/MedLine Plus



A friend has been feeling pretty crummy lately, was sick all through her dream vacation, went to the doctor immediately upon returning home, and was just told that she might have RA.  This is someone who I had never discussed my diagnosis with (usually I won’t tell), but when she said she might have systemic arthritis or lupus, I thought it was time to share a little of my story with her.

After exchanging a few emails, I realized that some of the information I was giving her has never been posted here.  Maybe others can benefit, too.  What should you do when your doctor tells you that you might have rheumatoid arthritis?  If all you’ve ever heard about is osteoarthritis, it can be pretty confusing to think you’re being told you have an old person’s disease when you aren’t old! 

Here, then, is some Q&A for my friend (and everyone else who wants to listen in – or even add their $.02 in the comments section):

Q:  Do you have RA?
A:  Yes.  My first rheumatologist called it “rhupus” because I have some symptoms of RA and some symptoms of SLE.  My current rheumy has diagnosed RA and not said anything about lupus.  Maybe this will sound odd, but it doesn’t really matter to me any more what the diagnosis is.  When I first got sick, I was desperate for an answer: “What is wrong with me and when will I get better?”  It no longer matters what the exact label is.  Many of the autoimmune diseases are treated the same way.  I’m taking a more pragmatic approach now:  what do I have to do in order to function?

Q:  How long do flare-ups normally last?
A:  Every person is different.  My flares usually only last a couple days.  I started to say that my worst one ever was last November-January, but I realize now that it went away after I added a second DMARD.  Maybe I was getting worse instead of going through a flare.

Q:  Do they (flares) come very often?
A:  Not for me.  Once RA is controlled, flares should be rare.  You will probably want to keep a calendar so that you will notice if there’s a pattern.  Personally, I can guarantee a flare by pigging-out on cookies (or eating one piece of cake).  Some people discover that flares coincide with their cycle.  Others discover that there’s a dietary link (gluten and nightshades are common foods that people notice).  It will be much easier to find a pattern if you’re writing things down.

Q:  Have  you ever tried a prednisone taper to help with the pain and swelling?
A:  I had a prednisone injection and quick taper back when I had pneumonia and all this started.  I have not taken it long term. My rheumy suggested pred, but wanted to try an NSAID first.  Between rx-NSAID and a DMARD, I did well enough that he never added pred.  That might change given that I don’t think I can get through Christmas the way I’ve been feeling this past week.

Q:  How do you find a good rheumatologist?
A:  In general, if you get along well with your PCP, it is a good idea to ask that doctor for a recommendation on who is good (or who to avoid) when you need a specialist.  It’s nice if the doctor accepts your insurance.  Doctor D did a good series about how to choose a primary doctor, and I think his tips are equally applicable to any doctor you’ll be seeing long-term – such as a rheumatologist.

Q:  Do I really need a rheumatologist?  Can my PCP treat me?
A:  Yes.  No.

Normally, I think that people should find a family practice (or med/peds) doctor that they like and stick with a doctor who will treat the whole person/family.  A zillion different specialists are not usually necessary, so I asked my PCP to treat my RA.  In retrospect, that wasn’t one of my best choices.  Having tried both ways, I think it’s best to see a rheumatologist for autoimmune diseases.  That’s nothing against PCPs; they are trained to diagnose just about anything (lots of doctors only know about their little corner of the world).  Family practice and med/peds docs, in my opinion, are a lot more useful than physicians with specialized training who forget that they’re treating a person instead of one of a bunch of isolated parts.  I like my PCP a lot, but he just wasn’t familiar with what to look for with this particular disease; it probably wasn’t fair of me to ask him to do what he wasn’t trained to do.  A rheumatologist, not a PCP, should be treating RA.

Q:  Will prednisone/tramadol control my pain?
A:  Maybe.  This combination should help short-term while you’re waiting for long-term drugs to kick in.  Pain control is not the primary goal (even though you might think it is).  Your long-term goal is to control the disease and prevent joint damage.  Pain killers and anti-inflamatories won’t do that.

Controlling the disease and preventing joint damage will control the pain.  If you have RA, you need Disease Modifying Anti-Rheumatic Drugs.  My experience with DMARDs:

Plaquenil (hydroxychloroquine) – this is an anti-malarial.  People who took vacations to places noted for malaria came home and told their doctors how much better they felt while taking this drug.  Doctors eventually made the connection, did some studies, and discovered that it can slow/prevent disease progression in RA.  This drug is also used to treat lupus.  It takes two months to start working, so don’t expect any overnight miracles.  High doses can cause problems with eyes.  The dosage used to treat RA/SLE is not usually a problem, but it is still recommended that people have an annual eye exam.  My eye doctor bills my regular exam to my vision insurance, but there is an extra test that he does related to the plaquenil and that is billed to my medical insurance.  Can be hard on the stomach; take with food.  I take mine with breakfast and supper.

Azulfadine (sulfasalazine) – this, too, can be hard on the stomach; take with food.  This, too, takes a couple months to be effective.  It is not used to treat lupus.  The pills are brightly colored orange/yellow (one person I know calls it “prescription cheetos” because of the colored powder that comes off on your hands).  People who jump in with a full dose tend to get pretty sick.  I started with 500mg daily for one week, the second week increased to 500mg bid, the third week increased to 1g bid, and did not experience any stomach upset doing it this way (months later increase to 1g tid).  You will notice that sulfasalazine turns your urine bright yellow – expected, not to worry.  One possible side effect is kidney stones, so make sure you drink lots of water if you take this.  You’ll want to be drinking lots of water anyhow, as another side effect is constipation (why do doctors prescribe multiple drugs with this side effect and not consider a stool softener, too?).  If you take this, drink constantly.

Methotrexate – this is the “standard” DMARD.  Unlike the two mentioned above, this one is most effective if taken on an empty stomach.  Again, start with a low dose and increase if necessary.  This med can be hard on the liver, so no alcohol.  The side effects can be difficult in the beginning, but take hope that it will get better.  Really!  One way to make it easier is to take it at bedtime so you sleep through the worst of it.  For people who find this extremely hard on their stomach, an injectable form is available.  I take mine on Tuesday night at bedtime.

There are other DMARDs, too, but these are the most common (and the only ones with which I have any experience).  Notice that with DMARDs, it’s not “pick one.”  Combination therapy is typical.  If these don’t work to control a person’s RA, then there are stronger medicines available.  Insurance won’t cover those stronger ones (biologics) in the beginning, so you’ll probably start with one or two of these DMARDs and then move on from there if needed.

Hang in there!  It gets better!

Methotrexate Update

Tonight I’ll take my fourth dose of mtx.  My first two DMARDs both took a couple months before I noticed any difference.  I assumed this one would take a while, too.  I’ve heard people say it can take 3-6 months to kick in, but I’m feeling better already.  Placebo effect, or does it work this fast?

I have NO all-over morning stiffness now.  None!   Instead of easing myself out of bed and hobbling down the stairs, I hop out of bed like I did twenty years ago.  I can walk down the stairs like a normal person.

The swelling in my hands has gone down.  My rings fit!  When I could no longer wear my wedding ring (size 5) and it appeared this was going to last a while, we bought a plain gold band (size 8).  Last spring when I started getting worse, even the large ring was too small.  Now, after three weeks on the mtx, I can wear my size 5 ring.  Can this be real?

My achilles tendons don’t hurt.  My wrists don’t hurt.  My knees don’t hurt.  My hips don’t hurt.

There is one weird thing though.  Although overall I feel better, my elbows hurt worse.  What’s up with that?

The horrible nausea I experienced with the first dose is no longer an issue.  Whew!  I haven’t lost any more weight, and although I wouldn’t mind losing a few more pounds, that was a hard way to do it.  The first week was awful, the second week was medium, and by the third week I had very little nausea.

The down side:  My thinking was pretty scrambled the morning after my last dose.  Most likely it was scrambled with the first two doses, too, but at the time I was too sick to notice that I wasn’t thinking straight.  I feel enough better that I’m more than willing to arrange my commitments so that I don’t have to do much thinking on Wednesday mornings.

One small snag:  My rheumy wrote the prescription for four weeks and no refills until she sees me again.  I understand the need, but my follow-up appointment wasn’t scheduled in four weeks, it was scheduled for one month. That’s not quite the same, and although the difference is subtle, it means I’m short.  Last appointment was 9/21; next appointment is 10/23.  Doses taken 9/22, 9/29, 10/6 and 10/13 mean that I don’t have a dose for 10/20.  I hate to bother the doctor between appointments, but I don’t think she intended for me to miss a week.

Overall, I’m relieved that the side-effects were short-lived.  I was pretty apprehensive about starting yet another med – this one in particular – but now I’m feeling pretty positive about the methotrexate.