Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2018 Sep;77(9):1268-1275.
doi: 10.1136/annrheumdis-2018-213416. Epub 2018 May 31.

Tocilizumab discontinuation after attaining remission in patients with rheumatoid arthritis who were treated with tocilizumab alone or in combination with methotrexate: results from a prospective randomised controlled study (the second year of the SURPRISE study)

Yuko Kaneko  1 , Masaru Kato  2 , Yoshiya Tanaka  3 , Masayuki Inoo  4 , Hitomi Kobayashi-Haraoka  5 , Koichi Amano  6 , Masayuki Miyata  7 , Yohko Murakawa  8 , Hidekara Yasuoka  1 , Shintaro Hirata  3   9 , Eiichi Tanaka  10 , Nobuyuki Miyasaka  11 , Hisashi Yamanaka  10 , Kazuhiko Yamamoto  12 , Tsutomu Takeuchi  1 ; SURPRISE study group
Collaborators, Affiliations
Randomized Controlled Trial

Tocilizumab discontinuation after attaining remission in patients with rheumatoid arthritis who were treated with tocilizumab alone or in combination with methotrexate: results from a prospective randomised controlled study (the second year of the SURPRISE study)

Yuko Kaneko et al. Ann Rheum Dis. 2018 Sep.

Abstract

Objective: To evaluate the sustained remission and low disease activity after discontinuation of tocilizumab in patients with rheumatoid arthritis who were treated with tocilizumab alone or in combination with methotrexate.

Methods: The SURPRISE study was a 2-year, open-label randomised controlled study. Among patients who had been randomised to additional tocilizumab (ADD-ON) or switch to tocilizumab (SWITCH) in the first year, those who achieved remission based on the disease activity score for 28 joints (DAS28-ESR<2.6) discontinued tocilizumab at week 52 and were observed for the following 52 weeks. The endpoint of the second year included tocilizumab-free remission and low disease-activity rates, functional outcome, radiological outcomes assessed with the modified total Sharp score (mTSS) and safety. The efficacy of reinstituted tocilizumab/methotrexate was also evaluated.

Results: A total of 105 patients who achieved remission at week 52 discontinued tocilizumab; 51 in ADD-ON continued methotrexate and 54 in SWITCH received no disease-modifying antirheumatic drugs. Sustained DAS28 low disease-activity rates were significantly higher in ADD-ON than in SWITCH (55%vs27%, p=0.005). Sustained remission rates at week 104 were 24% for ADD-ON and 14% for SWITCH (p=0.29). Radiological progression was comparable between both groups (mTSS; 0.37vs0.64, p=0.36). The restart of tocilizumab induced remission in all except two patients after 36 weeks, irrespective of concomitant methotrexate.

Conclusion: Sustained low disease activity after tocilizumab discontinuation could be maintained with continued methotrexate in more than half of the patients. Retreatment with tocilizumab led to remission in more than 90% of patients.

Trial registration number: NCT01120366; Results.

Keywords: dmards (biologic); methotrexate; rheumatoid arthritis.

PubMed Disclaimer

Conflict of interest statement

Competing interests: YK has received grants or speaking fees from from AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Hisamitsu, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi and UCB. MK has received research grants or lecture fees from GlaxoSmithKline K.K. and Actelion Pharmaceuticals. YT has received grants or speaking fees from Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, AbbVie, MSD, Eli Lilly, YL Biologics, Daiichi-Sankyo, Sanofi, Janssen, Pfizer, Kyowa-Kirin, Eisai and Ono. HK-H has received speaking fees from Chugai, Astellas and Bristol-Myers Squibb. KA has received research grants from Chugai Pharmaceutical Co. and speaking fees from Daiichi-Sankyo, Eli Lilly, Pfizer Japan and Tanabe-Mitsubishi. MM is an employee of the Japanese Red Cross Society. YM has received grants, instructor fees or speaking fees from Chugai, Ono, Daiichi-Sankyo, Teijin, Eisai, Nippon Kayaku, Tanabe-Mitsubishi, Kissei, Janssen, Eisai, Astellas, Ayumi, Takeda, UCB, Sanofi and Eli- Lilly. HY has received grants or speaking fees from Bristol-Myers Squibb, Takeda, Japan Blood Products Organization, Eizai, Daiichi-Sankyo, Novartis, Chugai and Actelion. SH has received grants, lecture fees or speaking fees from AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi and UCB. ET received speaking fees from AbbVie, Ayumi Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, Eisai Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical and UCB Pharma. HY has received research grants, consultant fees or speaking fees from MSD, Astellas, AbbVie, Bristol-Myers Squibb, Kaken, UCB, Ono, Ayumi, Eisai, Daiichi-Sankyo, Takeda, Tanabe-Mitsubishi, Chugai, Teijin, Torii, Nipponshinyaku, Pfizer, YL Biologics and Nipponkayaku. KY has received grants or speaking fees from Astellas Pharmaceutical, Chugai Pharmaceutical, Eizai Pharmaceutical, Immunofuture Inc, Mitsubishi Tanabe Pharma Corporation, Santen Pharmaceutical, Pfizer Japan Inc, AbbVie GK, Bristol–Myers KK, Diaichi Sankyo, Eli Lilly, Sanofi, Janssen and UCB. TT has received research grants or speaking fees from Astellas Pharma Inc, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd, Daiichi Sankyo Co, Ltd, Takeda Pharmaceutical Co, Ltd, Teijin Pharma Ltd, AbbVie GK, Asahikasei Pharma Corp, Mitsubishi Tanabe Pharma, Astra Zeneca KK, Eli Lilly Japan KK, Novartis Pharma KK, AbbVie GK, Nipponkayaku Co, Ltd, Janssen, Pharmaceutical KK, Taiho Pharmaceutical Co, Ltd and Pfizer Japan Inc. MI and NM have nothing to declare.

Figures

Figure 1
Figure 1
Study flow chart. DAS28, disease activity score for 28 joints; DMARD, disease-modifying antirheumatic drug; MTX, methotrexate.
Figure 2
Figure 2
Tocilizumab-free rates. The restart of tocilizumab and/or methotrexate was deemed as a failure of tocilizumab-free remission if the drugs were restarted when the patients were still in remission or with low disease activity. (A) Overall tocilizumab-free rates, (B) tocilizumab-free remission rates, (C) tocilizumab-free low disease-activity rates. *P<0.05.
Figure 3
Figure 3
Structural outcome. (A) Cumulative probability plot of change from week 52 to week 104 in mTSS. (B) Mean change in mTSS and the percentage of patients with change in mTSS ≤0, ≤0.5, ≥3 or ≥3. mTSS, van der Heijde-modified total Sharp score.
Figure 4
Figure 4
Percentage of patients who achieved DAS28 remission after treatment was restarted (A) in the ADD-ON and SWITCH from the restart through 36 weeks, and (B) in the ADD-ON and the three SWITCH groups (re-treatment with methotrexate (MTX), tocilizumab (TCZ) or tocilizumab plus methotrexate) at week 36. DAS28, disease activity score for 28 joints. *P<0.05.
See this image and copyright information in PMC

References

    1. Smolen JS, Landewé R, Johannes Bijlsma J, et al. . EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017. - PubMed
    1. Smolen JS, Aletaha D, Bijlsma JW, et al. . Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010;69:69–317. 10.1136/ard.2009.123919 - DOI - PMC - PubMed
    1. Takeuchi T. Treatment of rheumatoid arthritis with biological agents—as a typical and common immune-mediated inflammatory disease. Proc Jpn Acad Ser B Phys Biol Sci 2017;93:600–8. 10.2183/pjab.93.038 - DOI - PMC - PubMed
    1. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. . Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 2005;52:3381–90. 10.1002/art.21405 - DOI - PubMed
    1. Tanaka Y, Takeuchi T, Mimori T, et al. . Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study. Ann Rheum Dis 2010;69:1286–91. 10.1136/ard.2009.121491 - DOI - PMC - PubMed

Publication types

Associated data