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Observational Study
. 2023 Apr 5;69(1):11-20.
doi: 10.5387/fms.2022-06. Epub 2023 Mar 30.

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study

Masayuki Miyata  1 , Yasuhiko Hirabayashi  2 , Yasuhiko Munakata  3 , Yukitomo Urata  4 , Koichi Saito  5 , Hiroshi Okuno  6 , Masaaki Yoshida  7 , Takao Kodera  8 , Ryu Watanabe  9 , Seiya Miyamoto  10 , Tomonori Ishii  11 , Shigeshi Nakazawa  12 , Hiromitsu Takemori  13 , Takanobu Ando  14 , Takashi Kanno  15 , Masataka Komagamine  16 , Ichiro Kato  6 , Yuichi Takahashi  17 , Atsushi Komatsuda  18 , Kojiro Endo  19 , Chihiro Murai  20 , Yuya Takakubo  21 , Takao Miura  22 , Yukio Sato  23 , Kazunobu Ichikawa  24 , Tsuneo Konta  25 , Noriyuki Chiba  26 , Tai Muryoi  27 , Hiroko Kobayashi  28 , Hiroshi Fujii  11 , Yukio Sekiguchi  29 , Akira Hatakeyama  6 , Ken Ogura  30 , Hirotake Sakuraba  31 , Tomoyuki Asano  32 , Hiroshi Kanazawa  13 , Eiji Suzuki  15 , Satoshi Takasaki  33 , Kenichi Asakura  34 , Yoko Suzuki  35 , Michiaki Takagi  21 , Takahiro Nakayama  36 , Hiroshi Watanabe  32 , Keiki Miura  37 , Yu Mori  38 ; Michinoku Tocilizumab Study Group
Affiliations
Observational Study

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study

Masayuki Miyata et al. Fukushima J Med Sci. .

Retraction in

  • RETRACTED ARTICLE.
    Editorial Committee. Editorial Committee. Fukushima J Med Sci. 2024 Jan 27;70(1):55. doi: 10.5387/fms.retraction. Epub 2024 Jan 25. Fukushima J Med Sci. 2024. PMID: 38267028 Free PMC article. No abstract available.

Abstract

Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients.

Methods: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups.

Results: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01).

Conclusions: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.

Keywords: discontinuation; long-standing; methotrexate; rheumatoid arthritis; tocilizumab.

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Conflict of interest statement

The authors of this work have nothing to disclose.

Figures

Fig. 1.
Fig. 1.
Patient selection and study flow chart TCZ, tocilizumab; MTX, methotrexate; DAS28-ESR, DAS28 score calculated using ESR
Fig. 2.
Fig. 2.
Changes in DAS28-ESR in the DISC and MAIN groups Mean values are shown. Bars indicate SD. Changes in the DAS28-ESR scores in the DISC and MAIN groups were assessed every 3 months up to 36 months. DAS28-ESR scores were significantly lower in the DISC group at 3 (P < .05), 6 (P < .01), and 9 months (P < .01) and consistently lower than the scores in the MAIN group. **P < .01; * P < .05
Fig. 3.
Fig. 3.
Changes in DAS28-ESR remission rates in the DISC and MAIN groups Changes in DAS28-ESR remission rates in the DISC and MAIN groups were assessed every 3 months up to 36 months. DAS28-ESR remission rates were significantly higher in the DISC group at 6 (P < .01) and 9 months (P < .01). DAS28-ESR remission rates were significantly higher in the DISC group than in the MAIN group at 18, 21, 24, and 30 months (P < .05). ** P < .01; * P < .05
Fig. 4.
Fig. 4.
Changes in Boolean remission rates in the DISC and MAIN groups Changes in Boolean remission rates in the DISC and MAIN groups were assessed every 3 months to 36 months. The Boolean remission rates were significantly higher in the DISC group at 6 (P < .01) and 33 months (P < .05). **P < .01; * P < .05
See this image and copyright information in PMC

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