Subcutaneous administration of methotrexate at high doses makes a better performance in the treatment of rheumatoid arthritis compared with oral administration of methotrexate: A systematic review and meta-analysis

Objectives: This study was conducted to determine whether subcutaneous (SC) methotrexate (MTX) makes better performance on bioavailability, clinical efficiency, side effects occurrence, and treatment failure in the treatment of RA compared with oral MTX.

Methods: The databases PubMed, Web of Science, Embase, and Cochrane Library were systematically searched. Seven studies involving 1335 patients were eligible for data extraction and meta-analysis. The outcomes of meta-analysis were presented as mean difference (MD) or odd ration (OR) with 95% confidence interval (95% CI).

Results: Meta-analysis showed that SC MTX can significantly increase the AUC0-t (area under plasma concentration curve from administration to last observed concentration at time t) (MD = 506.84; 95% CI: 80.80-932.89), shorten the time to reach maximum observed concentration (Tmax) (MD = -0.13; 95% CI: -0.25 to -0.01) and the apparent terminal elimination half-life (t(1/2)) (MD = -0.39; 95% CI: -0.70 to -0.08), reduce the occurrence of nausea (OR = 0.53; 95% CI: 0.28-0.97) and diarrhea (OR = 0.43; 95% CI: 0.20-0.95), improve the American College of Rheumatology criteria for 20% improvement (ACR20) (OR = 1.68; 95% CI: 1.09-2.61) and ACR70 (OR = 1.52; 95% CI: 1.02-2.26), and relieve the pain (MD = -0.65; 95% CI: -0.93 to -0.37) compared with oral MTX. However, the differences in maximum plasma concentration (Cmax), the occurrence of headache, vomiting and dyspepsia, ACR50, treatment failure were not significant between the two groups.

Conclusion: SC route of MTX at high doses made better performance on improving the bioavailability and clinical efficacy, reducing the GI disorders, but it cannot decrease the treatment failure when compared with oral administration of MTX.