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.

Diarrhea.

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.

Headache.

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
RheumInfo
RxList
UpToDate
MedicineNet

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8 thoughts on “Methotrexate for RA

  1. I starting laughing out loud when I read your comment:

    “Not hungry.
    I still don’t see why this is considered a problem.”

    And that laughter was a good thing, cause I’ve had a pretty crappy, sore foot kind of day.

    Thanks so much for the info and the chuckle!
    :) Laurie

  2. I hope you have not mis-interpreted my comments on potential pulmonary complications of RA and/or methotrexate as attempts to discourage RA patients from taking methotrexate. Quite the contrary. Methotrexate is and has been a cornerstone drug for treating RA, and I still take it despite my personal experiences. Lung complications from taking methotrexate (or any other DMARD or biological used for RA, other autoimmune diseases, or cancers) is rare, but not non-existent and I only hope to raise awareness that the possibility does exist. Early recognigntion is the best prevention. It should not deter patients from trying these drugs to control their underlying diseases, and in some cases where the underlying disease is the cause of the pulmonary complications (which IS more common) these drugs can sometimes help control the lung disease. There is no way to determine who will develop lung disease (particularly interstial lung disease or ILD and pulmonary fibrosis – the most life threatening ones), although many researchers have tried.

    I have researched this issue for almost a decade. My computer is full of documents regarding this issue, although not the best organized, as I go off on various tangents depending on what the particular sub-issue is of the day. When I have time I will try to dig some of these out for anyone who is interested. It can be a complicated issue, but again, I do not mean to deter anyone from using these drugs as they are our best defence. I only want RA’ers to be aware and alert, and for their doctors to be the same. Again, I still take methotrexate, but only did so after much research and review of that along with my medical findings and discussions with my doctors.

    The website I link is not mine, but I put it out there as a resource for any RA, or any other auto-immuner, or non-autoiimuner/IPF’er/ILD’er.

  3. @Chelsea-I don’t think I’ve misinterpreted, but that’s always a possibility. The information that my rheumatologist provided (from UpToDate) said that mtx-lung is rare. When I tried to find solid numbers, some studies said .8%-6%; other studies said 20%. That’s a huge difference! I figured that once I have a chance to do some solid research I’ll do a post specifically about lung involvement.

    @Laurie- :)

  4. Yes, there is still controversy over the percentage of RA’ers affected with mtx-induced lung disease and it depends on how the studies were done – many in different ways, with different definitions. Suffice it to say though, that lung abnormalities in RA, regardless of drug treatment are pretty common considering all abnormality types that have been related to RA (up to 50%), and still needing to be studied to determine what is benign and what is not (most will be benign), and how drug treatment relates to those abnormalities. The following are for anyone interested, otherwise don’t bother.

    2009 – [The evaluation of early pulmonary involvement with high resolution computerized tomography in asymptomatic and non-smoker patients with rheumatoid arthritis] Karazincir S, Akoğlu S, Güler H, Balci A, Babayiğit C, Eğilmez E. [Article in Turkish]
    http://www.ncbi.nlm.nih.gov/pubmed/19533433?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=52

    1/28/08 – Progressive preclinical interstitial lung disease in rheumatoid arthritis.
    Gochuico BR, Avila NA, Chow CK, Novero LJ, Wu HP, Ren P, MacDonald SD, Travis WD, Stylianou MP, Rosas IO.

    Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Dr, MSC 1590, Bethesda, MD 20892-1590, USA. gochuicb@mail.nih.gov
    http://archinte.ama-assn.org/cgi/content/full/168/2/159

    Drs. Saravanan, Kelly, Dawson, and among others in the U.K. have been researching rheumatoid related lung disease for many, many years – more research than has taken place here in the US from what I’ve found in my years searching out this information. Here are some of their papers that are available free online. If you read these papers, the references in them and the linked citing articles you will get a much clearer idea of the issue – and perhaps understand why I want to continue to help raise awareness of pulmonary problems and drug-related pulmonary problems in RA:

    9/26/06 – What kills patients with rheumatoid arthritis?
    C. Kelly and J. Hamilton
    http://rheumatology.oxfordjournals.org/cgi/content/full/46/2/183

    3/9/06 – Drug-related pulmonary problems in patients with rheumatoid arthritis
    V. Saravanan and C. Kelly
    http://rheumatology.oxfordjournals.org/cgi/content/full/45/7/787?ijkey=115b7b784a7f3c28a58836616109a45b25d8f26e&keytype2=tf_ipsecsha

    12/10/06 – Reply to comment on ‘Drug-related pulmonary problems in patients with rheumatoid arthritis’ by Yazici and Yazici and ‘Pulmonary adverse events with Leflunomide—myth or reality?’ by Balakrishnan and Dasgupta
    V. Saravanan and C. A. Kelly
    http://rheumatology.oxfordjournals.org/cgi/content/full/46/2/372-a

    8/15/03 – Reducing the risk of methotrexate pneumonitis in rheumatoid arthritis
    V. Saravanan1 and C. A. Kelly2
    http://rheumatology.oxfordjournals.org/cgi/content/full/43/2/143?ijkey=2294fd58c512bf6043a1997f175c37eee2840621&keytype2=tf_ipsecsha

    12/08 – Treatment strategies for a rheumatoid arthritis patient with interstitial lung disease.
    Kelly C, Saravanan V.
    http://www.ncbi.nlm.nih.gov/pubmed/19040342?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=54

    567 Articles related to “Progressive Preclinical Interstitial Lung Disease (ILD) in Rheumatoid Arthritis”:
    http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=18227362&ordinalpos=1&log$=relatedarticles&logdbfrom=pubmed

    367 Articles related to “Pulmonary Manifestations of Rheumatoid Arthritis”
    http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=18971804&ordinalpos=1&log$=relatedarticles&logdbfrom=pubmed

  5. WS – I am not trying to argue with you. I am not saying it isn’t pretty rare. I am just trying to point out that the possibility exists. and should be kept in mind by docs prescribing these drugs, and patients before they start them. The argument would be whether it is cost effective to screen, what to screen, and/or whether to do baseline testing and what baseline tests. If posting that information helps even one person reading out here, then I’m happy.

    Yes, the percentages of just how many RA’ers get MTX-induced lung disease of some sort is controversial based on the study and the definitions and methods used. The fact that it isn’t compeletely settled and that there is a large percentage gap argues for continued research on the subject, not only with methotrexate, but the biologicals and other drugs as well. RA-induced lung disease, not related to drug treatment needs to be studied further also.

    2009 – [The evaluation of early pulmonary involvement with high resolution

    computerized tomography in asymptomatic and non-smoker patients with

    rheumatoid arthritis] Karazincir S, Akoğlu S, Güler H, Balci A, Babayiğit C,

    Eğilmez E. [Article in Turkish]
    http://www.ncbi.nlm.nih.gov/pubmed/19533433?itool=EntrezSystem2.PEntrez.

    Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=52

    1/28/08 – Progressive preclinical interstitial lung disease in rheumatoid arthritis.
    Gochuico BR, Avila NA, Chow CK, Novero LJ, Wu HP, Ren P, MacDonald SD,

    Travis WD, Stylianou MP, Rosas IO.

    Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood

    Institute, National Institutes of Health, 10 Center Dr, MSC 1590, Bethesda, MD

    20892-1590, USA. gochuicb@mail.nih.gov
    http://archinte.ama-assn.org/cgi/content/full/168/2/159

    Drs. Saravanan, Kelly, Dawson, and among others in the U.K. have been

    researching rheumatoid related lung disease for many, many years – more

    research than has taken place here in the US from what I’ve found in my years

    searching out this information. Here are some of their papers that are available

    free online. If you read these papers, the references in them and the linked citing

    articles you will get a much clearer idea of the issue – and perhaps understand

    why I want to continue to help raise awareness of them:

    9/26/06 – What kills patients with rheumatoid arthritis?
    C. Kelly and J. Hamilton
    http://rheumatology.oxfordjournals.org/cgi/content/full/46/2/183

    3/9/06 – Drug-related pulmonary problems in patients with rheumatoid arthritis
    V. Saravanan and C. Kelly
    http://rheumatology.oxfordjournals.org/cgi/content/full/45/7/787?ijkey=115b7

    b784a7f3c28a58836616109a45b25d8f26e&keytype2=tf_ipsecsha

    12/10/06 – Reply to comment on ‘Drug-related pulmonary problems in patients

    with rheumatoid arthritis’ by Yazici and Yazici and ‘Pulmonary adverse events

    with Leflunomide—myth or reality?’ by Balakrishnan and Dasgupta
    V. Saravanan and C. A. Kelly
    http://rheumatology.oxfordjournals.org/cgi/content/full/46/2/372-a

    8/15/03 – Reducing the risk of methotrexate pneumonitis in rheumatoid arthritis
    V. Saravanan1 and C. A. Kelly2
    http://rheumatology.oxfordjournals.org/cgi/content/full/43/2/143?ijkey=2294

    fd58c512bf6043a1997f175c37eee2840621&keytype2=tf_ipsecsha

    12/08 – Treatment strategies for a rheumatoid arthritis patient with interstitial

    lung disease.
    Kelly C, Saravanan V.
    http://www.ncbi.nlm.nih.gov/pubmed/19040342?itool=EntrezSystem2.PEntrez.

    Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=54

    567 Articles related to “Progressive Preclinical Interstitial Lung Disease (ILD) in

    Rheumatoid Arthritis”:
    http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=link&linkname=p

    ubmed_pubmed&uid=18227362&ordinalpos=1&log$=relatedarticles&logdbfrom

    =pubmed

    367 Articles related to “Pulmonary Manifestations of Rheumatoid Arthritis”
    http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=link&linkname=p

    ubmed_pubmed&uid=18971804&ordinalpos=1&log$=relatedarticles&logdbfrom

    =pubmed

  6. Pingback: Methotrexate For Ra | Medicine Blog

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