Folic Acid and RA

In the world of rheumatoid arthritis, the subject of folic acid is forever tied to methotrexate. A discussion of one is incomplete without the other. In searching the medical literature for articles related to ‘rheumatoid arthritis and folate (folic acid)’, I discovered that most of the titles of the articles include mention of methotrexate.

Are folic acid and folinic acid effective against methotrexate side effects in RA patients?

Yes, according to the Cochrane Review updated in 2013 that included six randomized controlled trials involving 624 RA patients taking MTX (≤ 25 mg/week), of whom 385 also took low-dose folic acid (≤ 7 mg/week). Studies using higher doses of folic acid were excluded because the high dose is no longer recommended or used in clinical practice.

For patients supplemented with either folic or folinic acid while receiving MTX therapy for RA, a 26% relative (9% absolute) risk reduction was seen for the incidence of gastrointestinal side effects such as nausea, vomiting, or abdominal pain. Folic and folinic acid also appear to be protective against abnormal serum transaminase (liver enzyme) elevation caused by MTX, with a 76.9% relative (16% absolute) risk reduction, as well as reducing patient withdrawal from MTX for any reason by 60.8% relative (15.2% absolute) risk reduction.

Importantly, there was no significant reduction in MTX efficacy, as measured by disease activity measures such as tender and swollen joint counts or physician's global assessment scores.

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Folic Acid Use in Rheumatoid Arthritis

RA Treatment: Triple Therapy

Rheumatologists will often begin their newly diagnosed patients on conventional DMARDs such as methotrexate (MTX), sulfasalazine (SSZ), hydroxychloroquine (HCQ), each alone or in any combination.  In fact, when combining the three drugs, it is commonly known as “triple therapy” and is often used as a step-up in treatment after trying MTX alone.

Triple therapy as a treatment approach to RA has received recent attention in the news due to a study published in the New England Journal of Medicine (NEJM) on June 11, 2013.  In this study, no significant difference in disease activity was demonstrated in patients who received triple therapy as compared to those who received treatment with etanercept + methotrexate. All the patients prior to enrolling in this study had experienced active disease despite methotrexate therapy alone (O’Dell, 2013).

In a similar study, the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) study, patients were randomly assigned to MTX monotherapy (alone), triple therapy, or MTX + etanercept with no significant difference in primary outcome (based on Disease Activity Severity DAS28 scores) between the latter two groups. However, x-rays did show more disease progression in the triple therapy group.

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What is the Role of Triple Therapy in RA?

Photosensitivity and Methotrexate: Protect Your Skin

On our first full free day during our trip, Rob and I took the train into old town Zurich.  During the short ride, I slathered sunscreen on my face, neck, and arms.  It was very important that I protect myself from the ultraviolet light.  I insisted that Rob use the sunscreen as well.  Our skin was armed and ready to go.

I don’t spend much time in the sun and typically get my vitamin D through daily supplements.  Other than excessive squinting and heat sensitivity I experience due to MS, I tend to avoid sun exposure because of potential photosensitivity.

What is photosensitivity?

Photosensitivity, also called sun sensitivity, is an inflammation of the skin caused by a combination of certain chemicals and exposure to the sunlight.  Some medications commonly taken for RA may contain light-activated chemicals.  Photosensitivity is a common side-effect of methotrexate, plaquenil, and NSAIDs such as celebrex or advil, according to Epocrates Online.  Photosensitivity may be a serious side-effect of anti-TNF drugs such as cimzia, enbrel, humira, remicade, and simponi, as well as sulfasalazine.  It is not considered a side-effect of actemra, arava, kineret, orencia, or rituxan.

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Photosensitivity and RA: Protect Yourself From Skin Damage

Don't Mix Methotrexate with Antibiotics

If you don’t know, it is very important to avoid taking antibiotics and methotrexate at the same time. There is an issue of toxicity of the methotrexate as antibiotics tend to prevent the complete break down of MTX. If MTX can’t be broken down appropriately, higher amounts may be found in the body.

I personally like to think of letting the methotrexate set aside (by not taking it) to allow the antibiotic soldiers to go in a do their duty (killing the infection). Fortunately this summer, the antibiotics I took for two weeks did just that. Unfortunately, the RA mischiefs decided that it would be a good time to act up a bit.

The pain started with an extra stiffness in my left hand. I thought that maybe I was typing too much or playing too many computer games where I hold my hand in a lose fist and typically use just one finger. But after a few days, it was my left foot which joined in the ‘party.’

Moving my toes became a practice in slow motion. When my boyfriend offered a foot rub which was so very sweet of him (and I wouldn’t ever want to turn down or discourage a foot rub), I couldn’t stand the pressure or even the gentle movement of toes. Ouch!! Stop!

Enter very unhappy Lisa face. Seriously, who turns down a foot rub?

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Antibiotics, Methotrexate, and RA Flare-Ups

Can't wait to get back on meds: Methotrexate and RA

I only have to wait until Saturday.  Two more days.  Saturday is the big day and it will arrive none too soon, I gotta tell ya.

"What happens Saturday?" you ask.

I will be off the antibiotics and can take methotrexate once again.  Whoohoo!

"Lisa, aren't you a little too excited about getting immuno-suppressed again?"

Nope.  Each day during this past week, I wake up and face just how much more my feet or hands hurt.  Little by little, it has been creeping up on me. 

Well, today.  I was so very tempted to dip into my emergency (MS relapse) supply of oral steroids which I took with me on vacation in June/July.  Just half a tablet would probably relieve some of this pain but somehow that seems an abuse of having it available.

"What's wrong with taking a little prednisone/decadron for your RA?"

Only once have I taken oral steroids for my RA, but that was before I was diagnosed with RA.  I took a medrol pack over a holiday season and when the taper ended, the pain came back full force.  It seemed to serve no real purpose than to prove something bigger was going on.

Last fall when I was getting monthly pulse steroids (1000mg prednisone by IV every four weeks), not only was my MS happier but my RA was thrilled.  I didn't really feel any substantial pain that I can recall.  It was very nice.

Well, the past three weeks have proven that the methotrexate really DOES help keep my RA under control.  That's the good news.

Now I just wonder how long it will take before my feet will stop feeling like they will break, my hips/knees will move smoothly again, and my knuckles will stop their slow swelling.  I hope that it works as quickly as it works well.

Besides the pain increasing, my brain is foggy.  I'm TIRED and have slept each afternoon for a couple of hours.  As a result, I haven't done my normal amount of writing/researching.  I'm slacking, I tell ya.

But the good news is that the inflammation/infection in my colon has been obliterated and I feel perfectly fine on that front.  Yay, antibiotics.

Hopefully everything will be back to normal soon.  I'm just very thankful that my RA is well controlled when I'm on all of my medications.  That's the best news!!

Folic Acid: Mouth Sores vs. Cancer Risk

Ouch. Last Wednesday or Thursday, I noticed that I must have burned the roof of my mouth. I didn't remember eating anything so hot that it could singe the skin, but the tenderness in one spot let me know that I must have.

Friday it still hadn't really healed over. In fact, it seemed to be worse. Saturday afternoon, I realized that I had another tender spot in my mouth and a slight metallic taste was developing. Sometime in the afternoon, I realized what was really going on.

I have developed some mouth sores. Ouch and yuck. Why are these showing up now?

Last month when I visited with my rheumatologist, she asked if I had ever developed mouth sores before. No, I haven't. Why did she ask this? I take methotrexate.

Methotrexate is used to treat different types of cancer, but it is also used to treat rheumatoid arthritis. Methotrexate is an antimetabolite and antifolate drug which inhibits unusal rapid cell growth.

One of the many possible side effects of methotrexate is mouth ulcers, or mouth sores. To help prevent this and other side effects, it is customary to take supplementary folic acid which comes in 400mcg (otc) or 1mg (prescription). I had been taking 1.2mg daily for the past three years.

Based on research published in the Journal of the American Medical Association last fall (and other research studies), my rheumatologist suggested that I stop taking folic acid. Why, do you ask?

High doses of folic acid have been associated with an increased risk of developing lung cancer. The risk remains small, but an increase is an increase. Since I had not experienced many of the nasty side effects of methotrexate, my doctor simply wanted me to stop the folic acid, which may or may not have been helping to alleviate those potential side effects.

Well, one month off of the daily supplementation and I am beginning to develop mouth problems. So on the way home from a busy day accompanying several students at solo festival, I stopped at the grocery store.

My shopping list was short: Folic Acid!!

I immediately took four tablets as soon as I got home and will do so daily until my mouth feels good again. Hopefully at that point I can decrease the amount I need to keep the sores away without increasing the risk of cancer, especially since cancer has run in my family.

Hopefully, it won't be too long before my mouth is in tip top shape once again. :)