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Rheumatology International

, Volume 38, Issue 12, pp 2307–2313 | Cite as

Efficacy and safety of extending intravenous tocilizumab intervals from 4 to 6 weeks in rheumatoid arthritis patients with good response to 4-week intervals

  • Osamu SaikiEmail author
  • Hiroshi Uda
Pharmacovigilance
  • 203 Downloads

Abstract

A period of 4 weeks (w) has been recommended for rheumatoid arthritis (RA) patients as the interval between intravenous (IV) tocilizumab (TCZ, 8 mg/kg). In a previous paper, we showed the possibility that the interval between successive IV TCZ can be extended from 4 to 6 weeks in more than 60% of patients with low diseases activity (LDA) at 4-week intervals. Herein, we aimed to investigate the efficacy and safety of extending the interval from 4 to 6 weeks. A retrospective observational study was conducted by enrolling patients in whom the intervals of TCZ infusions could be extended from 4 to 6 weeks with an LDA for more than 2 years. We compared the efficacy and side effects of TCZ infusions at intervals of 4 and 6 weeks in a cohort of patients. We also examined serum lipid, platelet, IL-6, and trough TCZ levels. A total of 125 patients with an LDA at 4 weeks intervals were enrolled in this study, of which 78 patients maintained LDA at 6-week intervals of TCZ infusion. After extending the infusion intervals, the efficacy of the treatment was maintained, and the side effects decreased significantly. In addition, the levels of total cholesterol and triglyceride were returned to normal, and the serum trough levels of TCZ became undetectable at 6-week intervals. We proved that intervals between TCZ infusions can be extended from 4 to 6 weeks in more than 60% of RA patients along with a decrease in the side effects, thus suggesting the need to change the infusion intervals in suitable patients.

Keywords

Intravenous tocilizumab Rheumatoid arthritis Extension of intervals Efficacy Safety 

Notes

Acknowledgements

The authors would like to acknowledge Dr. Taro Kinoshita of Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University for his kind suggestion.

Author contributions

Osamu Saiki was responsible for the concept and design of the study, and wrote the draft. Osamu Saiki and Hiroshi Uda contributed to the acquisition, analysis, and interpretation of data. We have no external editing support to acknowledge.

Funding

No funding.

Compliance with ethical standards

Conflict of interest

Hiroshi Uda and Osamu Saiki declare that they have no conflict of interest.

References

  1. 1.
    McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365:2205–2219CrossRefGoogle Scholar
  2. 2.
    Furst DE, Emery P (2014) Rheumatoid arthritis pathophysiology: update on emerging cytokine and cytokine-associated cell targets. Rheumatology 53:1560–1569CrossRefGoogle Scholar
  3. 3.
    Narazaki M, Tanaka T, Kishimoto T (2017) The role and therapeutic targeting of IL-6 in rheumatoid arthritis. Expert Rev Clin Immunol 13:535–551CrossRefGoogle Scholar
  4. 4.
    Tanaka T, Narazaki M, Kishimoto T (2017) Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy 8:959–970CrossRefGoogle Scholar
  5. 5.
    Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T (2008) Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood 112:3959–3964CrossRefGoogle Scholar
  6. 6.
    Nishimoto N, Hashimoto J, Miyasaka N et al (2007) Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an X ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis 66:1162–1167CrossRefGoogle Scholar
  7. 7.
    Genovese MC, McKay JD, Nasonov EL et al (2008) Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum 58:2968–2980CrossRefGoogle Scholar
  8. 8.
    Nishimoto N, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Azuma J (2009) Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): evidence of safety and efficacy in a 5-year extension study. Ann Rheum Dis 68:1580–1584CrossRefGoogle Scholar
  9. 9.
    Gabay C, Emery P, van Vollenhoven R et al, ADACTA Study Investigators (2013) Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet 381:1541–1550CrossRefGoogle Scholar
  10. 10.
    Dougados M, Kissel K, Sheeran T et al (2013) Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis 72:43–50CrossRefGoogle Scholar
  11. 11.
    Jones G, Sebba A, Gu J et al (2010) Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 69:88–96CrossRefGoogle Scholar
  12. 12.
    Burmester GR, Rubbert-Roth A, Cantagrel A et al (2016) Efficacy and safety of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional DMARDs in patients with RA at week 97 (SUMMACTA). Ann Rheum Dis 75:68–74CrossRefGoogle Scholar
  13. 13.
    Singh JA, Beg S, Lopez-Olivo MA (2011) Tocilizumab for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol 38:10–20CrossRefGoogle Scholar
  14. 14.
    European Medical Agency (2018) Tocilizumab (RoActemura) 20 mg/ml concentrate solution for infusion/162 mg solution for injection in pre-filled syringe: summary of product characteristicsGoogle Scholar
  15. 15.
    Nishimoto N, Kishimoto T (2006) Interleukin 6: from bench to bedside. Nat Clin Pract Rheumatol 2:619–626CrossRefGoogle Scholar
  16. 16.
    Robertson J, Porter D, Sattar N et al (2017) Interleukin-6 blockade raises LDL via reduced catabolism rather than via increased synthesis: a cytokine-specific mechanism for cholesterol changes in rheumatoid arthritis. Ann Rheum Dis 76:1949–1952CrossRefGoogle Scholar
  17. 17.
    Saiki O, Uda H (2017) Successful extension of tocilizumab infusion intervals from 4 weeks to 6 or 5 weeks in 90% of RA patients with good response to 4-week intervals. Clin Exp Rheumatol 35:666–670PubMedGoogle Scholar
  18. 18.
    Aletaha D, Neogi T, Silman AJ et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581CrossRefGoogle Scholar
  19. 19.
    Fransen J, Creemers MC, Van Riel PL (2004) Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the ARA preliminary remission criteria. Rheumatology 43:1252–1255CrossRefGoogle Scholar
  20. 20.
    Nishizono I, Iida S, Suzuki N et al (1991) Rapid and sensitive chemiluminescent enzyme immunoassay for measuring tumor markers. Clin Chem 37:1639–1644PubMedGoogle Scholar
  21. 21.
    Ogata A, Tanimura K, Sugimoto T et al, Musashi Study Investigators (2014) Phase III study of the efficacy and safety of subcutaneous versus intravenous tocilizumab monotherapy in patients with rheumatoid arthritis. Arthritis Care Res 66:344–354CrossRefGoogle Scholar
  22. 22.
    Rohleder N, Aringer M, Boentert M (2012) Role of interleukin-6 in stress, sleep, and fatigue. Ann N Y Acad Sci 1261:88–96CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of RheumatologyHigashiosaka City Medical CenterHigashiosakaJapan

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