The Mere Thought of MTX Makes Many Patients Nauseous

January 17, 2014
Rita Baron-Faust

Methotrexate, according to a new study, is a nauseating thought even before most patients take their regular dose. What are the implications for treatment, and what can you do to help?

Alasan MB, van den Bosch OF, Creemers MC, et al., Prevalence of methotrexate intolerance in rheumatoid arthritis and psoriatic arthritis.Arthritis Res Ther. (2013) Dec 18;15(6):R217. [Epub ahead of print]

The gastrointestinal side effects of methotrexate (MTX) are well-known, but a new study finds patients can also experience symptoms merely from anticipating taking the drug – dubbed “MTX Intolerance.” This can prompt them to quit or switch to medications that are more expensive or less effective.

The study involved 291 patients, most of whom had rheumatoid arthritis (RA), more than half of whom were women with a mean age of 59. They all completed a validated questionnaire called the Methotrexate Intolerance Severity Score (MISS).

The overall prevalence of MTX Intolerance among RA patients and those with psoriatic arthritis (PsA) was 11%, with a greater frequency (20.6%) among those on injected (parenteral) MTX than on oral medication (6.2%), likely due to an aversion to needles.

But surprisingly, intolerance persisted even after patients switched to an oral MTX dose.

Patients younger than 66 years of age were more likely to be intolerant than older patients. In contrast, prior studies in juvenile idiopathic arthritis (JIA) found a 50.5% prevalence of MTX intolerance.

Pre-treatment nausea was the most common problem among the 42.3% of patients (n=123) who reported at least one adverse effect. Every patient who was MTX Intolerant reported pre-treatment nausea.

Nausea is one of four domains on the MISS -- abdominal pain, vomiting, and behavioral symptoms (including restlessness) -- that occur prior to taking MTX (anticipatory) and when thinking about the drug (associative).

Even GI symptoms are often not evident clinically or are identified by physician assessment and detected only with the MISS, the researchers note.

They urge use of the MISS to monitor all MTX patients so that intolerance and physical symptoms can be spotted and treated early (e.g. by lowering the MTX dose) to ward off intolerance, avoid noncompliance, prevent discontinuation -- or switching to more costly biologics or less effective NSAIDs.