Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis

Irena Kafedziska; Snezhana Mishevska-Perchinkova; Dubravka Antova; Mimoza Kotevska Nikolova; Anzhelika Stojanovska; Filip Guchev

doi:doi:10.11648/j.ajim.20200803.16

Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis

Irena Kafedziska, Snezhana Mishevska-Perchinkova, Dubravka Antova, Mimoza Kotevska Nikolova, Anzhelika Stojanovska, Filip Guchev

Published in American Journal of Internal Medicine (Volume 8, Issue 3)

Received: 2 May 2019 Accepted: 27 January 2020 Published: 28 May 2020

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Abstract

Introduction: Biologic DMARDs (Disease Modifying Anti Rheumatic Drugs) have shown to be effective in the treatment of rheumatoid arthritis (RA) resistant to the use of synthetic DMARDs. The primary goal of this study was to assess the long-term safety of the use of tocilizumab in patients with early rheumatoid arthritis, moderate to severe disease activity. The secondary goal was to assess the efficiency of tocilizumab in achieving and maintaining clinical remission of the disease. Methods: ML28133 is a long-term, extended study of 13 patients with rheumatoid arthritis treated with tocilizumab. Two patients were male (15.4%), 11 (84.61%) female. The average age of patients was 53.27+/-10.68. Patients received 8 mg/kg tocilizumab i.v. every four weeks, 104 weeks overall. Safety was assessed following side effects, blood tests, physical examination and vital signs. Efficiency was assessed by achieving and maintaining clinical remission according to DAS28 (Disease Activity Score 28), global assessment of disease activity, VAS score and HAQ-DI (Health Activity Score) questionnaire. Results: Incidence of side effects was 76.92%. Infections were of special interest and were most common (15.3%). Four patients had serious adverse events, three of which associated with tocilizumab, and therapy was stopped. In 11 (84.6%) of the 13 treated patients clinical remission was achieved at times. At the end of the study, 8 out of 9 patients were in remission. Conclusion: The results have shown significant therapeutic effect of tocilizumab even in the most severe forms of the disease, which gives hope for its use as a monotherapy.

Published in	American Journal of Internal Medicine (Volume 8, Issue 3)
DOI	10.11648/j.ajim.20200803.16
Page(s)	125-132
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2020. Published by Science Publishing Group

Keywords

Rheumatoid Arthritis, Tocilizumab, Safety, Adverse Effects, Efficiency

References

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[4]	Turesson C, et al. Increased incidence of cardiovascular disease in patients with rheumatoid arthritis: results from a community based studyAnn Rheum Dis 2004; 63: 952–955.
[5]	Actemra (tocilizumab) Full report of drug characteristics, March 2014 https://lekovi.zdravstvo.gov.mk/drugsregister/detailview/5556 пристапено на 14.02.2017.
[6]	Mab Thera Full report of drug characteristics, August 2013 https://lekovi.zdravstvo.gov.mk/drugsregister/detailview/52913 пристапено на 14.02.2007.
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[9]	Emery P, Keystone E et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patient with rheumatoid arthritis refractory to anti-TNF biologic: results from a 24-week multicentre randomized placebo controlled trial. Ann Rheum Dis 2008; 67: 1516-1523 doi: 10.1136/ard.2008.092932.
[10]	Dougados M et al. Tocilizumab (TCZ) plus methotrexate (MTX) does not have superior clinical efficacy to TCZ alone in RA patients with inadequate response to MTX: 24-week results of the ACT-RAY study. Arthritis Rheum 2011; 63 (10 Suppl): S1032-10 Sibilia J, et al. Ann Rheum Dis 2011; 70 (Suppl. 3): 466.
[11]	Yen J.-H. Treatment of early rheumatoid arthritis in developing countries. Biologics or disease-modifying anti-rheumatic drugs? Biomedecine & Pharmacotherapy Volume 60, Issue 10, December 2006, Pages 688-692.
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[13]	Jones G, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 2010; 69: 88–96.
[14]	Smolen JS, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomized Lancet 2008; 371: 987–997.
[15]	Fleischman RM, et al Tocilizumab Inhibits Structural Joint Damage and Improves Physical Function in Patients with Rheumatoid Arthritis and Inadequate Responses to Methotrexate: LITHE Study 2-year Results, J Rheumatol 2013; 40; 113-126.
[16]	Strand V, et al. Improvements in health-related quality of life after treatment with tocilizumab in patients with rheumatoid arthritis refractory to tumour necrosis factor inhibitors: results from the 24-week randomized controlled RADIATE study, Rheumatology 2012; 51: 1860-1869 doi: 10.1093/rheumatology/kes131.
[17]	Genovese MC, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic tocilizumab in combination with traditional disease-modifying antirheumatic drug Arthritis Rheum 2008; 58: 2968–2980.
[18]	Josef S Smolen et al.: EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Published by group.bmj.com, Ann Rheum Dis 2013; 0: 1–18. doi: 10.1136/annrheumdis-2013-204573.
[19]	Cem Gabay, et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. The Lancet Volume 381, Issue 9877, 4–10 May 2013, Pages 1541–1550.

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Irena Kafedziska, Snezhana Mishevska-Perchinkova, Dubravka Antova, Mimoza Kotevska Nikolova, Anzhelika Stojanovska, et al. (2020). Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis. American Journal of Internal Medicine, 8(3), 125-132. https://doi.org/10.11648/j.ajim.20200803.16

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Irena Kafedziska; Snezhana Mishevska-Perchinkova; Dubravka Antova; Mimoza Kotevska Nikolova; Anzhelika Stojanovska, et al. Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis. Am. J. Intern. Med. 2020, 8(3), 125-132. doi: 10.11648/j.ajim.20200803.16

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AMA Style

Irena Kafedziska, Snezhana Mishevska-Perchinkova, Dubravka Antova, Mimoza Kotevska Nikolova, Anzhelika Stojanovska, et al. Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis. Am J Intern Med. 2020;8(3):125-132. doi: 10.11648/j.ajim.20200803.16

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@article{10.11648/j.ajim.20200803.16,
  author = {Irena Kafedziska and Snezhana Mishevska-Perchinkova and Dubravka Antova and Mimoza Kotevska Nikolova and Anzhelika Stojanovska and Filip Guchev},
  title = {Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis},
  journal = {American Journal of Internal Medicine},
  volume = {8},
  number = {3},
  pages = {125-132},
  doi = {10.11648/j.ajim.20200803.16},
  url = {https://doi.org/10.11648/j.ajim.20200803.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20200803.16},
  abstract = {Introduction: Biologic DMARDs (Disease Modifying Anti Rheumatic Drugs) have shown to be effective in the treatment of rheumatoid arthritis (RA) resistant to the use of synthetic DMARDs. The primary goal of this study was to assess the long-term safety of the use of tocilizumab in patients with early rheumatoid arthritis, moderate to severe disease activity. The secondary goal was to assess the efficiency of tocilizumab in achieving and maintaining clinical remission of the disease. Methods: ML28133 is a long-term, extended study of 13 patients with rheumatoid arthritis treated with tocilizumab. Two patients were male (15.4%), 11 (84.61%) female. The average age of patients was 53.27+/-10.68. Patients received 8 mg/kg tocilizumab i.v. every four weeks, 104 weeks overall. Safety was assessed following side effects, blood tests, physical examination and vital signs. Efficiency was assessed by achieving and maintaining clinical remission according to DAS28 (Disease Activity Score 28), global assessment of disease activity, VAS score and HAQ-DI (Health Activity Score) questionnaire. Results: Incidence of side effects was 76.92%. Infections were of special interest and were most common (15.3%). Four patients had serious adverse events, three of which associated with tocilizumab, and therapy was stopped. In 11 (84.6%) of the 13 treated patients clinical remission was achieved at times. At the end of the study, 8 out of 9 patients were in remission. Conclusion: The results have shown significant therapeutic effect of tocilizumab even in the most severe forms of the disease, which gives hope for its use as a monotherapy.},
 year = {2020}
}

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TY - JOUR
T1 - Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis
AU - Irena Kafedziska
AU - Snezhana Mishevska-Perchinkova
AU - Dubravka Antova
AU - Mimoza Kotevska Nikolova
AU - Anzhelika Stojanovska
AU - Filip Guchev
Y1 - 2020/05/28
PY - 2020
N1 - https://doi.org/10.11648/j.ajim.20200803.16
DO - 10.11648/j.ajim.20200803.16
T2 - American Journal of Internal Medicine
JF - American Journal of Internal Medicine
JO - American Journal of Internal Medicine
SP - 125
EP - 132
PB - Science Publishing Group
SN - 2330-4324
UR - https://doi.org/10.11648/j.ajim.20200803.16
AB - Introduction: Biologic DMARDs (Disease Modifying Anti Rheumatic Drugs) have shown to be effective in the treatment of rheumatoid arthritis (RA) resistant to the use of synthetic DMARDs. The primary goal of this study was to assess the long-term safety of the use of tocilizumab in patients with early rheumatoid arthritis, moderate to severe disease activity. The secondary goal was to assess the efficiency of tocilizumab in achieving and maintaining clinical remission of the disease. Methods: ML28133 is a long-term, extended study of 13 patients with rheumatoid arthritis treated with tocilizumab. Two patients were male (15.4%), 11 (84.61%) female. The average age of patients was 53.27+/-10.68. Patients received 8 mg/kg tocilizumab i.v. every four weeks, 104 weeks overall. Safety was assessed following side effects, blood tests, physical examination and vital signs. Efficiency was assessed by achieving and maintaining clinical remission according to DAS28 (Disease Activity Score 28), global assessment of disease activity, VAS score and HAQ-DI (Health Activity Score) questionnaire. Results: Incidence of side effects was 76.92%. Infections were of special interest and were most common (15.3%). Four patients had serious adverse events, three of which associated with tocilizumab, and therapy was stopped. In 11 (84.6%) of the 13 treated patients clinical remission was achieved at times. At the end of the study, 8 out of 9 patients were in remission. Conclusion: The results have shown significant therapeutic effect of tocilizumab even in the most severe forms of the disease, which gives hope for its use as a monotherapy.
VL - 8
IS - 3
ER -

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Author Information

Irena Kafedziska

Public Health Institution University Clinic of Rheumatology, Medical Faculty, University “Ss. Cyril and Methodius”, Skopje, Republic of North Macedonia
Snezhana Mishevska-Perchinkova

Public Health Institution University Clinic of Rheumatology, Medical Faculty, University “Ss. Cyril and Methodius”, Skopje, Republic of North Macedonia
Dubravka Antova

Public Health Institution University Clinic of Rheumatology, Medical Faculty, University “Ss. Cyril and Methodius”, Skopje, Republic of North Macedonia
Mimoza Kotevska Nikolova

Public Health Institution University Clinic of Rheumatology, Medical Faculty, University “Ss. Cyril and Methodius”, Skopje, Republic of North Macedonia
Anzhelika Stojanovska

Public Health Institution University Clinic of Rheumatology, Medical Faculty, University “Ss. Cyril and Methodius”, Skopje, Republic of North Macedonia
Filip Guchev

Public Health Institution University Clinic of Rheumatology, Medical Faculty, University “Ss. Cyril and Methodius”, Skopje, Republic of North Macedonia

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APA Style

Irena Kafedziska, Snezhana Mishevska-Perchinkova, Dubravka Antova, Mimoza Kotevska Nikolova, Anzhelika Stojanovska, et al. (2020). Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis. American Journal of Internal Medicine, 8(3), 125-132. https://doi.org/10.11648/j.ajim.20200803.16

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Irena Kafedziska; Snezhana Mishevska-Perchinkova; Dubravka Antova; Mimoza Kotevska Nikolova; Anzhelika Stojanovska, et al. Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis. Am. J. Intern. Med. 2020, 8(3), 125-132. doi: 10.11648/j.ajim.20200803.16

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AMA Style

Irena Kafedziska, Snezhana Mishevska-Perchinkova, Dubravka Antova, Mimoza Kotevska Nikolova, Anzhelika Stojanovska, et al. Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis. Am J Intern Med. 2020;8(3):125-132. doi: 10.11648/j.ajim.20200803.16

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@article{10.11648/j.ajim.20200803.16,
  author = {Irena Kafedziska and Snezhana Mishevska-Perchinkova and Dubravka Antova and Mimoza Kotevska Nikolova and Anzhelika Stojanovska and Filip Guchev},
  title = {Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis},
  journal = {American Journal of Internal Medicine},
  volume = {8},
  number = {3},
  pages = {125-132},
  doi = {10.11648/j.ajim.20200803.16},
  url = {https://doi.org/10.11648/j.ajim.20200803.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20200803.16},
  abstract = {Introduction: Biologic DMARDs (Disease Modifying Anti Rheumatic Drugs) have shown to be effective in the treatment of rheumatoid arthritis (RA) resistant to the use of synthetic DMARDs. The primary goal of this study was to assess the long-term safety of the use of tocilizumab in patients with early rheumatoid arthritis, moderate to severe disease activity. The secondary goal was to assess the efficiency of tocilizumab in achieving and maintaining clinical remission of the disease. Methods: ML28133 is a long-term, extended study of 13 patients with rheumatoid arthritis treated with tocilizumab. Two patients were male (15.4%), 11 (84.61%) female. The average age of patients was 53.27+/-10.68. Patients received 8 mg/kg tocilizumab i.v. every four weeks, 104 weeks overall. Safety was assessed following side effects, blood tests, physical examination and vital signs. Efficiency was assessed by achieving and maintaining clinical remission according to DAS28 (Disease Activity Score 28), global assessment of disease activity, VAS score and HAQ-DI (Health Activity Score) questionnaire. Results: Incidence of side effects was 76.92%. Infections were of special interest and were most common (15.3%). Four patients had serious adverse events, three of which associated with tocilizumab, and therapy was stopped. In 11 (84.6%) of the 13 treated patients clinical remission was achieved at times. At the end of the study, 8 out of 9 patients were in remission. Conclusion: The results have shown significant therapeutic effect of tocilizumab even in the most severe forms of the disease, which gives hope for its use as a monotherapy.},
 year = {2020}
}

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