Is Methotrexate Under Utilized?
Methotrexate (MTX) is an accepted first-line drug for patients diagnosed with RA. Oral MTX was what my rheumatologist started me on after my diagnosis. For various reasons, the main one being I hated the side effects and I refused to take it, I was soon switched to my first biologic. However, researchers are now asking if this well-known and affordable drug is being used to its full potential.
Exploring this research I learned three important things about methotrexate:
- It can take up to six months for MTX to be 90% effective and the Treatment of Early Aggressive Rheumatoid Arthritis Trial (TEAR) recommends six months of treatment with MTX before adding a DMARD or switching to a biologic. In comparison, many biologics are fully effective after three months.
- The European League Against Rheumatism (EULAR) guidelines recommended sufficient dosages are 25-30 mg. per week.
- Injected MTX has higher bioavailability, has greater clinical efficacy and is better tolerated than oral methotrexate. This is pretty standard for drugs that have both an oral/pill form and an injected form. The injected medication doesn’t travel through the digestive track so it’s absorbed better by the body, doesn’t cause GI upsets, and the actual dose is more consistent. What’s really interesting is that regardless of the dosage taken, the actual effective dose of oral MTX tends to plateau at 15 mg. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833794/) So even if a person takes more pills, their body isn’t necessary absorbing more. (I am currently back on MTX to supplement my biologic. However, I’m doing injections, not pills, and I’m having better results without any noticeable side effects.)
These factors are important when you consider the findings of a research study recently published in Arthritis Care & Research and discussed on Rheumatologynetwork.com. The findings of this study are completely contrary to the three points I listed above. This study found that:
- An amazing 87 percent of the patients were switched to a biologic as the next treatment step. For 41 percent of the patients who were switched, this change occurred at three months, well before the recommended six-month course of treatment for MTX.
- The average oral dose of MTX was 15.3 mg per week. This is 50-60 percent lower than the EULAR recommended dose. Only about one-third of the patients were taking more than 15 mg.
- Only 13 percent of the patients moved from oral MTX to injected MTX although the injected form is clearly more effective.
What this study indicates is that when it comes to MTX, doctors generally haven’t (1) been prescribing a high enough dose; (2) given the MTX treatment long enough to work; or (3) didn’t move to injected MTX from oral MTX as the next logical step in treatment.
What the studies don’t tell us (and what I’d be really interested to know) is why biologics were prescribed before an effective treatment course of MTX was tried. All drugs, including MTX, have side effects and that was certainly why I helped drive the change in my situation. I also know that most people would rather take a pill than give themselves an injection – however, the majority of biologics are given either by injection or infusion, so I’m not sure that’s it.
While I think it’s great to know that we have an important drug that might be better utilized, insurance companies other treatment policy makers also look at this kind of research. We just need to be aware that since MTX is much less expensive than the biologics, they could take this into consideration and potentially adjust their treatment recommendations for MTX before switching to DMARD or biologic treatment options.
All this being said, if you’re a patient on MTX, this is good information to have and discuss with your doctor if you are contemplating a change in treatment.