Methotrexate subcutaneous injection for the initial treatment of rheumatoid arthritis can achieve earlier remission compared with oral administration.

In Japan, subcutaneous methotrexate (SC-MTX) administration was introduced in 2022; however, available data regarding its use as an initial treatment or its effectiveness when switching from oral MTX remain limited. The present study aimed to examine the introduction timing and effects of a SC-MTX injection in patients with rheumatoid arthritis (RA). The oral MTX administration group (n=202, O-MTX), initial SC-MTX group (n=59, SC-MTX) and SC-MTX-switched group (n=25, SWITCH) were compared for the disease activity score in the disease activity score in 28 joints with C-reactive protein (DAS28-CRP), health assessment questionnaire (HAQ), remission rate of MTX, combination rate of biological agents and JAK inhibitors, the discontinuation rate (DR) of glucocorticoids, alanine aminotransferase, low-density lipoprotein, estimated glomerular filtration rate, hemoglobin, white blood cell count, lymphocyte count, DR of medications. A survey on SC-MTX self-injection was also conducted. SC-MTX achieved greater improvements in both HAQ and DAS28-CRP than O-MTX, and the difference became evident by 12 weeks following treatment introduction. In SWITCH, the disease activity also decreased after switching. The proportions of remission cases on MTX monotherapy at 24 weeks in the O-MTX, SC-MTX and SWITCH groups were 31.3, 65.96 and 33.33%, respectively and the DR rates of glucocorticoids in these groups were 59.3, 85.7 and 50%, respectively. As regards safety, no differences were noted in renal function, liver function, or changes in blood cells. According to the questionnaire for the usability of the SC-MTX self-injection, patients were very satisfied. On the whole, the present study demonstrates that in the treatment of RA, the initial introduction of SC-MTX is considered very useful, particularly in patients with high disease activity.