Does caffeine reduce methotrexate intolerance in patients with rheumatoid arthritis: a randomized controlled study

Background Intolerance to MTX is the most common cause of non-compliance that leads to poor disease control. Treatment is usually discontinued due to intolerance which interferes with compliance of the patient to long-term treatment. Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs). Our aim was to investigate the effect of caffeine intake on reducing symptoms of MTX intolerance in patients with RA. Methods Ninety patients were diagnosed as RA with MTX intolerance divided into 2 groups. Sixty patients were prescribed caffeine or dark chocolate. Control group included 30 patients who will continue MTX regimen without addition of any extra caffeine. Results Group A (caffeine group): There was no statistically significant difference between patients and controls at the start of the study. There was statistically significant decrease in methotrexate intolerance severity score (MISS) all over the study period (P = 0.001), and also MISS was statistically significantly lower in each follow-up time when compared with time 0 (P = 0.001). Group B (control group): There was statistically significant increase in MISS all over the study period (P = 0.017); also, MISS was statistically significantly higher in follow-up time 2 and time 3 when compared with time 0 (P = 0.033). We found that after 3 months, 80% of group A patients showed complete relief, 6.7% showed partial relief, 10% showed minimal relief, and 3.3% got worse. Conclusion Adding caffeine to management regimen can reduce the symptoms of MTX intolerance in RA patients. Caffeine relieved the symptoms of MTX intolerance in 80% of RA patients after 3 months of adding caffeine to management regimen.