Do you combine methotrexate and leflunomide for the treatment of RA?

Absolutely! What a coincidence, as I was just communicating by email with a patient with horrible hard-to-control psoriatic arthritis (PsA) who failed numerous combos and biologics. (I know this question is RA, but also think of LEF with PsA).

It was not until I added leflunomide (LEF) to her regimen (started with just 10 mg to her 20 mg of MTX + Taltz) that she felt amazing for the first time after many years of treating her. Her email said, "I am exercising again."

Make sure to monitor cytopenias, and transaminases more closely at first and caution the patient to look out for alopecia, rash, and peripheral neuropathy symptoms.

I wish I had thought of adding LEF earlier (but with this being the biologic era, I typically grab a biologic or...

I agree with my colleagues Drs. @Dr. First Last and @Dr. First Last. This combination can be used safely and with good efficacy in RA and PSA patients, particularly those that have failed multiple agents or cannot utilize biologic therapy due to cost, other health issues, etc. There are a few studies demonstrating efficacy as well as similar rates of adverse events to either drug as monotherapy including the SMILE study. There is slightly more toxicity with leflunomide if the loading dose of 100 mg PO daily x 3 days is given.

@Dr. First Last... great question!

1. I completely understand why many rheumatologists would prefer not to use a loading dose (dealing with increased side effects).

2. However, I always questioned the validity of these results. Why would there be a higher response (ACR 20, by the way, not ACR 50 nor ACR 70) in the non-loading group? Made no theoretical sense at all unless there was worse adherence or something else going on in the loading group (possible in those who had nuisance side effects). The study was underpowered, with much fewer participants than they had set out to study. I don't give a hoot about ACR 20; I want to see ACR 50 and 70 and remissions. I was hoping someone would do a larger study, meeting the statistical predetermined...