EFFICACY AND SAFETY OF OLOKIZUMAB IN THE MANAGEMENT OF RHEUMATOID ARTHRITIS- A SYSTEMATIC REVIEW AND META-ANALYSIS

Authors

  • Saad Khalid Dow University of Health Sciences, Karachi-Pakistan
  • Laiba Imran Dow University of Health Sciences, Karachi-Pakistan
  • Muhammad Uzair Dow University of Health Sciences, Karachi-Pakistan
  • Javeria Tirmizi Dow University of Health Sciences, Karachi-Pakistan
  • Ayesha Khan Dow University of Health Sciences, Karachi-Pakistan
  • Suman Tashkil Dow University of Health Sciences, Karachi-Pakistan
  • Anas Adil Dow University of Health Sciences, Karachi-Pakistan

DOI:

https://doi.org/10.55519/JAMC-01-12456

Keywords:

Rheumatoid arthritis, olokizumab, methotrexate, monoclonal antibody, meta-analysis

Abstract

Background: Olokizumab (OKZ) is a monoclonal antibody against the interleukin receptor-6 that has shown promise in recent phase II and III trials in patients of rheumatoid arthritis (RA). This meta-analysis aims to evaluate the efficacy and safety of Olokizumab in managing rheumatoid arthritis. Methods: We searched different databases until March 2023 for randomized controlled trials inspecting the effects of OKZ on various outcomes in RA patients inadequately controlled with anti-TNF or methotrexate. Data were analyzed via Review Manager-v 5.4.1. Relative risks (RR) with 95% confidence intervals were calculated. Results: We evaluated five trials with 2761 patients under four treatment groups: 60mg OKZ administered 2-weekly, 64mg 2-weekly, 64mg 4-weekly, and 120mg 2-weekly. Clinical response as measured by ACR 20, 50, and 70 showed statistically significant improvement with the use of OKZ. A 50% disease improvement was seen across all 4 treatment groups (OKZ 64 mg q2w: RR= 2.96, p<0.0001, OKZ 64mg q4w: RR= 3.06, p=0.0002, OKZ 60 mg q2w: RR=5.06, p=0.007, and OKZ 120mg q2w: RR= 3.63, p=0.04). Moreover, 20% and 70% improvements were also noted with OKZ in doses 64mg 2-weekly and 4-weekly. Disease remission, as indicated by DAS28 <2.6 was also significantly higher than placebo across all groups. Safety data showed comparable mortality rates in treatment and placebo groups (OKZ 64mg q2w: p=0.48, OKZ 64 mg q4w: p=0.93). Conclusion: In conclusion, Olokizumab has shown significant improvement in disease activity compared to placebo with a favourable safety profile. However, further larger and longer-term studies are required to confirm these findings.

Author Biographies

Saad Khalid, Dow University of Health Sciences, Karachi-Pakistan

 

Laiba Imran, Dow University of Health Sciences, Karachi-Pakistan

 

Muhammad Uzair, Dow University of Health Sciences, Karachi-Pakistan

 

Javeria Tirmizi, Dow University of Health Sciences, Karachi-Pakistan

 

Ayesha Khan, Dow University of Health Sciences, Karachi-Pakistan

 

Suman Tashkil, Dow University of Health Sciences, Karachi-Pakistan

 

Anas Adil, Dow University of Health Sciences, Karachi-Pakistan

 

References

Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res 2018;6(1):15.

Sparks JA. Rheumatoid Arthritis. Ann Internal Med 2019;170(1):ITC1.

Fraenkel L, Bathon JM, England BR, St Clair EW, Arayssi T, Carandang K, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2021;73(7):1108–23.

Smolen JS, Landewé RB, Bijlsma JW, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis 2020;79(6):685–99.

McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 2007;7(6):429–42.

Kretsos K, Golor G, Jullion A, Hickling M, McCabe S, Shaw S, et al. Safety and pharmacokinetics of olokizumab, an anti‐IL‐6 monoclonal antibody, administered to healthy male volunteers: A randomized phase I study. Clin Pharmacol Drug Dev 2014;3(5):388–95.

Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL, et al. Olokizumab versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med 2022;387(8):715–26.

Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E, et al. Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis 2022;81(12):1661–8.

Mahmoud AM. Olokizumab's effectiveness and safety in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials. J Clin Densitom 2023;26(1):61–82.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg 2021;88:105906.

Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.

Genovese MC, Fleischmann R, Furst D, Janssen N, Carter J, Dasgupta B, et al. Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised Phase IIb study. Ann Rheum Dis 2014;73(9):1607–15.

Takeuchi T, Tanaka Y, Yamanaka H, Amano K, Nagamine R, Park W, et al. Efficacy and safety of olokizumab in Asian patients with moderate-to-severe rheumatoid arthritis, previously exposed to anti-TNF therapy: results from a randomized phase II trial. Mod Rheumatol 2016;26(1):15–23.

Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG, et al. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis 2022;81(4):469–79.

Yoshizaki K, Nishimoto N, Mihara M, Kishimoto T. Therapy of rheumatoid arthritis by blocking IL-6 signal transduction with a humanized anti-IL-6 receptor antibody. Springer Semin Immunopathol 1998;20(1-2):247–59.

Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology (Oxford) 2010;49(1):15–24.

Genentech Inc. Actemra (tocilizumab): US prescribing information. [Internet]. 2013. [cited 2023 Sep 7]. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/ label/2013/125276s092lbl.pdf

European Medicines Agency. Tocilizumab (RoActemra): summary of product characteristics. [Internet]. 2013. [cited 2023 Sep 7]. Available from: http://www.ema.europa.eu/docs/enGB/documentlibrary/EPAR-ProductInformation/human/000955/WC500054890.pdf

Mihara M, Kasutani K, Okazaki M, Nakamura A, Kawai S, Sugimoto M, et al. Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family. Int Immunopharmacol 2005;5(12):1731–40.

Sato K, Tsuchiya M, Saldanha J, Koishihara Y, Ohsugi Y, Kishimoto T, et al. Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth. Cancer Res 1993;53(4):851–6.

Shaw S, Bourne T, Meier C, Carrington B, Gelinas R, Henry A, et al. Discovery and characterization of olokizumab: a humanized antibody targeting interleukin-6 and neutralizing gp130-signaling. MAbs 2014;6(3):773–81.

Huizinga TW, Conaghan PG, Martin-Mola E, Schett G, Amital H, Xavier RM, et al. Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study. Ann Rheum Dis 2013;74(1):35–43.

Downloads

Published

2024-02-05

Issue

Vol. 36 No. 1 (2024): JOURNAL OF AYUB MEDICAL COLLEGE ABBOTTABAD

Section

REVIEW ARTICLE

License

Copyright (c) 2024 Saad Khalid, Laiba Imran, Muhammad Uzair, Javeria Tirmizi, Ayesha Khan, Suman Tashkil, Anas Adil

Creative Commons License

This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Journal of Ayub Medical College, Abbottabad is an OPEN ACCESS JOURNAL which means that all content is FREELY available without charge to all users whether registered with the journal or not. The work published by J Ayub Med Coll Abbottabad is licensed and distributed under the creative commons License  CC BY ND Attribution-NoDerivs. Material printed in this journal is OPEN to access, and are FREE for use in academic and research work with proper citation. J Ayub Med Coll Abbottabad accepts only original material for publication with the understanding that except for abstracts, no part of the data has been published or will be submitted for publication elsewhere before appearing in J Ayub Med Coll Abbottabad. The Editorial Board of J Ayub Med Coll Abbottabad makes every effort to ensure the accuracy and authenticity of material printed in J Ayub Med Coll Abbottabad. However, conclusions and statements expressed are views of the authors and do not reflect the opinion/policy of J Ayub Med Coll Abbottabad or the Editorial Board.

USERS are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author. This is in accordance with the BOAI definition of open access.

AUTHORS retain the rights of free downloading/unlimited e-print of full text and sharing/disseminating the article without any restriction, by any means including twitter, scholarly collaboration networks such as ResearchGate, Academia.eu, and social media sites such as Twitter, LinkedIn, Google Scholar and any other professional or academic networking site.

Most read articles by the same author(s)