Background In a proportion of patients methotrexate (MTX) has to be withdrawn because of lack of efficacy or side effects. MTX results indirectly in increased adenosine release. Adenosine, acting at the A2 receptor, mediates the anti-inflammatory effects of MTX. Caffeine is a non selective adenosine receptor antagonist and reverses the anti-inflammatory effects of MTX in the rat adjuvant arthritis model.

Objectives To see if there was any correlation between withdrawal of MTX due to treatment failure and caffeine ingestion.

Methods Over a 10 month period 91 sequential patients in 2 centres who had ever been on MTX were interviewed. They were classified as either minimal or regular coffee drinkers dependant on whether they drank more or less than 7 cups of coffee per week. Concomitant theophyline medication and tea and cola ingestion were also documented. Doses used varied from 5 to 15 mg weekly (mean = 10.3 ± 2.75).

Results The proportion of people who have to discontinue MTX is higher in those who are regular coffee drinkers (P value = 0.02). In this group the reason for discontinuing was due to treatment failure in 80% of cases. 90% of those still on MTX and 74% of those who discontinued MTX were minimal coffee drinkers.

Conclusion Patients who are on MTX should decrease their caffeine intake as there is a statistically significant increase in treatment failure in those who drink coffee regularly. This may account for the reason that much higher doses of MTX are used in countries with a heavier caffeine consumption.