Safety of Intra-articular Methotrexate Injection With and Without Electroporation for Inflammatory Small Joints in Patients With Rheumatoid Arthritis.

The general disease activity of patients with rheumatoid arthritis (RA) is well controlled by disease-modifying antirheumatic drugs, but local inflammation often remains in a few small joints. Electroporation, making small pores in cell membranes, has proven useful for drug delivery. The safety of a combination therapy of methotrexate (MTX) and electroporation for local joint inflammation in RA was investigated in a prospective, randomized, double-blind, placebo-controlled, exploratory study (UMIN000016606). The patients were randomly allocated to groups receiving a combination of MTX and electroporation (True-EP) and MTX alone (False-EP) groups. The MTX solution was injected into finger joints under ultrasound guidance. The True-EP group underwent electroporation with MTX, and the False-EP group was given MTX but only pinched using the electrode. The ultrasound grade, disease activity, and safety were evaluated from baseline to 26 weeks. Five patients (3 True-EP and 2 False-EP) with a mean age of 57.4 years and disease duration of 10.2 years were enrolled. The grey-scale grade was unchanged in 3 cases (2 True-EP and 1 False-EP) and increased in 2 cases (1 True-EP and 1 False-EP). Disease activity was alleviated in 3 cases (2 True-EP and 1 False-EP). No patients experienced burned skin or electroshock. The combination therapy of electroporation and MTX was safe for RA patients.