Why Methotrexate is my current Go-To drug in Rheumatoid Arthritis

I wrote "In my hands, Methotrexate is NOT chemotherapy" after a twitter conversation with @fridawrites and @RheumEpi.

It was a message that I have wanted to spread for a long time. In fact, it's a key reason I started to blog. My 1st post describes this:

"I experienced a strange run of patients developing unpredictable, serious side effects to medications I commonly use to treat their pain and to prevent their joint destruction. In all cases, the patients attended hospital and there were aspects to their treatment that suggested a lack of understanding about their underlying disease states and the medications they were using. And this lack of understanding occurred on the part of the staff treating them, and to an extent, the patient’s family members. I had previously thought that I was good at communicating and educating my patients. I need to do better. I accept that I have a responsibility to educate the people around them, both medical and social."

This paragraph was really about Methotrexate (MTX). One of the patients died, after a prolonged ICU admission with breathing complications. The family blamed the drug, even though there were many other complicating issues, such as active disease, and other medications. This fire was fanned by some comments about Methotrexate being a very strong chemotherapy. All rheumatologists I know would not regard Methotrexate as chemotherapy at the doses we use.

That was a difficult experience.

The MTX post generated lots of comment. Lisa brought up some important questions:

"I've been on it (sub q 20mg) with one 'vacation' for two and a half years. I sometimes get nausea and fatigue. My biggest issue with it was it didn't help much, I didn't get my RA controlled until I started an anti TNF. I have to wonder though, if only one third of patients have a major clinical response, why is it still the gold standard that all new drugs are measured against? An ACR20 improvement isn't so great at all- If you lost all ten fingers and a drug only had to give you back two of those ten to be considered a success, it wouldn't seem all that fantastic."

So, why do I use Methotrexate as my 1st line treatment for Rheumatoid Arthritis (RA)?

1. Familiarity. MTX has been used for over 30 years in RA. We're comfortable with it. There are few surprises.
2. It works. When used at an early stage & at adequate doses, and those are important points, it is effective in RA. Remission rates have been reported around the 40% mark and this would be consistent with what I experience.
3. It's good in COMBO. There are numerous trials showing additional effect when Methotrexate is used in combination with other DMARDs, such as Hydroxychloroquine, Leflunomide, Sulphasalazine, and many of the biologic DMARDs including the TNF-inhibitors.
4. It's cheap (but not nasty).
5. It's convenient. At least, in oral formulation. My standard dose is 20mg once a week which translates to 2 tablets once a week only.
6. It's required as part of the qualification process for using biologic DMARDs in many countries, including Australia.

Due to the points above, most regulatory bodies mandate that only patients who do not respond adequately to or who cannot tolerate MTX, can access the very much more expensive biologic DMARDs.

Methotrexate does not work for all. Lisa's "biggest issue with it was it didn't help much".

This is true for many. Rheumatoid arthritis management must be flexible, with regular patient follow-up, and treatment change & escalation as required. There are now many options with lots more on the horizon.

Methotrexate isn't the perfect drug but it's the current 1st line treatment for the reasons above. I hope this discussion helps you understand why.

As always, I invite your thoughts. This discussion is important and I'm happy to facilitate it.