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

  • Authors:
    • Yukie Saio
  • View Affiliations / Copyright

    Affiliations: Department of Rheumatology, Toho Hospital, Midori, Gunma 379‑2311, Japan
    Copyright: © Saio et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 52
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    Published online on: August 11, 2026
       https://doi.org/10.3892/mi.2026.336
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Abstract

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.
View Figures

Figure 1

Changes in the HAQ and DAS28-CRP
scores in the three groups. (A) Transition of HAQ. The remission
threshold for HAQ (0.5) is shown as a thin horizontal dotted line
at the 0.5 mark. (B) Transition of DAS28-CRP.
*P<0.05, significant differences between the SC-MTX
group and the SWITCH group. **P<0.0001, significant
differences between the SC-MTX group and the O-MTX group. HAQ,
health assessment questionnaire; DAS28-CRP, disease activity score
in 28 joints with C-reactive protein; MTX, methotrexate; O-MTX,
oral MTX administration; SC-MTX, MTX subcutaneous injection from
the initial induction; SWITCH, group switched from O-MTX to MTX
subcutaneous injection; W, weeks.

Figure 2

Changes in DAS28-CRP from baseline to
24 weeks in the three groups. The ratios within the groups are
displayed according to disease activity: Remission, low disease
activity, moderate disease activity and high disease activity. (A)
O-MTX group, (B) SC-MTX group, and (C) SWITCH group. DAS28-CRP,
disease activity score in 28 joints with C-reactive protein; MTX,
methotrexate; O-MTX, oral MTX administration; SC-MTX, MTX
subcutaneous injection from the initial induction; SWITCH, switched
group from O-MTX to MTX subcutaneous injection; W, weeks.

Figure 3

Changes in remission rates based on
DAS28-CRP in the three groups. *P<0.05,
**P<0.01 and ***P<0.001 for significant
differences between the SC-MTX group and the O-MTX group.
DAS28-CRP, disease activity score in 28 joints with C-reactive
protein; MTX, methotrexate; O-MTX, oral MTX administration; SC-MTX,
MTX subcutaneous injection from the initial induction; SWITCH,
switched group from O-MTX to MTX subcutaneous injection; W,
weeks.

Figure 4

Comparison of changes in HAQ and
DAS28-CRP scores based on anti-CCP positivity. (A and B) Transition
of HAQ. The remission threshold for HAQ (0.5) is presented as a
thin horizontal dotted line at the 0.5 mark. (C and D) Transition
of DAS28-CRP. *P<0.05 and **P<0.0001,
significant differences between two groups. HAQ, health assessment
questionnaire; DAS28-CRP, disease activity score in 28 joints with
C-reactive protein; CCP, cyclic citrullinated peptide; MTX,
methotrexate; O-MTX, oral MTX administration; SC-MTX, MTX
subcutaneous injection from the initial induction; W, weeks.

Figure 5

Changes in liver function, lipids, and
blood cells over a 24-week period in the 3 groups. (A) ALT in U/l,
(B) LDL in mg/dl, (C) eGFR in ml/min/1.73 m2, (D) Hb in
g/dl, (E) white blood cell count in cells/µl, and (F) lymphocyte
count in cells/µl. *P<0.05, significant differences
between the groups. ALT, alanine aminotransferase; Hb, hemoglobin;
LDL, low-density lipoprotein; eGFR, estimated glomerular filtration
rate; MTX, methotrexate; O-MTX, oral MTX administration; SC-MTX,
MTX subcutaneous injection from the initial induction; SWITCH,
switched group from O-MTX to MTX subcutaneous injection; W, weeks.
ALT, alanine aminotransferase; LDL, low-density lipoprotein; eGFR,
estimated glomerular filtration rate; Hb, hemoglobin; WBC, white
blood cell count.

Figure 6

Association between cumulative MTX
dose and change in eGFR. (A and B) The change in eGFR was
calculated by subtracting the eGFR value at 24 weeks from the eGFR
value at the start of MTX administration. (A) SC-MTX case, (B)
O-MTX case. The straight line in the figure represents the
regression line derived from the multiple regression analysis, and
the R value indicates the correlation coefficient from that
analysis. eGFR, estimated glomerular filtration rate; MTX,
methotrexate; O-MTX, oral MTX administration; SC-MTX, MTX
subcutaneous injection from the initial induction.

Figure 7

Results of patient satisfaction survey
with the pen-type SC-MTX. (A) Survey results for cases where
self-injection was changed from a syringe to a pen-type
autoinjector. (B) Survey results for cases where a pen-type
autoinjector was used from the beginning. In both cases, the
highest satisfaction level was scored 10 points, and the average
score for each case is shown with a bold line.
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Spandidos Publications style
Saio Y: Methotrexate subcutaneous injection for the initial treatment of rheumatoid arthritis can achieve earlier remission compared with oral administration. Med Int 6: 52, 2026.
APA
Saio, Y. (2026). Methotrexate subcutaneous injection for the initial treatment of rheumatoid arthritis can achieve earlier remission compared with oral administration. Medicine International, 6, 52. https://doi.org/10.3892/mi.2026.336
MLA
Saio, Y."Methotrexate subcutaneous injection for the initial treatment of rheumatoid arthritis can achieve earlier remission compared with oral administration". Medicine International 6.5 (2026): 52.
Chicago
Saio, Y."Methotrexate subcutaneous injection for the initial treatment of rheumatoid arthritis can achieve earlier remission compared with oral administration". Medicine International 6, no. 5 (2026): 52. https://doi.org/10.3892/mi.2026.336
Copy and paste a formatted citation
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Spandidos Publications style
Saio Y: Methotrexate subcutaneous injection for the initial treatment of rheumatoid arthritis can achieve earlier remission compared with oral administration. Med Int 6: 52, 2026.
APA
Saio, Y. (2026). Methotrexate subcutaneous injection for the initial treatment of rheumatoid arthritis can achieve earlier remission compared with oral administration. Medicine International, 6, 52. https://doi.org/10.3892/mi.2026.336
MLA
Saio, Y."Methotrexate subcutaneous injection for the initial treatment of rheumatoid arthritis can achieve earlier remission compared with oral administration". Medicine International 6.5 (2026): 52.
Chicago
Saio, Y."Methotrexate subcutaneous injection for the initial treatment of rheumatoid arthritis can achieve earlier remission compared with oral administration". Medicine International 6, no. 5 (2026): 52. https://doi.org/10.3892/mi.2026.336
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