Skip to main content
Erschienen in: Zeitschrift für Rheumatologie 1/2024

02.06.2023 | Originalien

Comparison of the efficacy and safety of olokizumab at different dosages in patients with active rheumatoid arthritis: a network meta-analysis of randomized controlled trials

verfasst von: Young Ho Lee, MD PhD, Gwan Gyu Song

Erschienen in: Zeitschrift für Rheumatologie | Sonderheft 1/2024

Einloggen, um Zugang zu erhalten

Abstract

Objective

This study aimed to assess the relative efficacy and safety of olokizumab at different dosages in patients with active rheumatoid arthritis (RA).

Methods

We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of olokizumab administered intravenously to RA patients at 64 mg/kg every 2 or 4 weeks (Q2 or Q4W).

Results

Five RCTs comprising 2609 patients met the inclusion criteria. Both olokizumab Q2 and Q4W treatments achieved a significant American College of Rheumatology 20% response (ACR20) compared with the placebo (odds ratio [OR] 3.21, 95% credible interval [CrI] 2.53–4.09; OR 3.05, 95% CrI 2.43–3.86). However, olokizumab Q2W was associated with the most favorable surface using the cumulative ranking curve (SUCRA) for the ACR20 response rate. The ranking probability based on the SUCRA indicated that olokizumab Q2W had the highest probability of being considered the best treatment option for achieving the ACR20 response rate, followed by olokizumab Q4W, adalimumab, and placebo. The ACR50 and 70 response rates showed a similar distribution pattern to the ACR20 response rate, except that olokizumab Q4W had a higher-ranking probability than olokizumab Q2W for ACR50. The SUCRA rating likelihood of adverse events (AEs) and withdrawal due to AEs showed that a placebo was likely to be the best intervention.

Conclusion

Both olokizumab Q2 and Q4W were efficacious and well-tolerated treatments for active RA.
Literatur
3.
Zurück zum Zitat Fonseca JE, Santos MJ, Canhao H, Choy E (2009) Interleukin‑6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev 8(7):538–542CrossRefPubMed Fonseca JE, Santos MJ, Canhao H, Choy E (2009) Interleukin‑6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev 8(7):538–542CrossRefPubMed
4.
Zurück zum Zitat Nurnberg W, Haas N, Schadendorf D, Czarnetzki BM (1995) Interleukin‑6 expression in the skin of patients with lupus erythematosus. Exp Dermatol 4(1):52–57CrossRefPubMed Nurnberg W, Haas N, Schadendorf D, Czarnetzki BM (1995) Interleukin‑6 expression in the skin of patients with lupus erythematosus. Exp Dermatol 4(1):52–57CrossRefPubMed
5.
Zurück zum Zitat Srirangan S, Choy EH (2010) The role of interleukin 6 in the pathophysiology of rheumatoid arthritis. Ther Adv Musculoskelet Dis 2(5):247–256CrossRefPubMedPubMedCentral Srirangan S, Choy EH (2010) The role of interleukin 6 in the pathophysiology of rheumatoid arthritis. Ther Adv Musculoskelet Dis 2(5):247–256CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A et al (2008) IL‑6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 67(11):1516–1523CrossRefPubMed Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A et al (2008) IL‑6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 67(11):1516–1523CrossRefPubMed
7.
Zurück zum Zitat Xu Z, Bouman-Thio E, Comisar C, Frederick B, Van Hartingsveldt B, Marini JC et al (2011) Pharmacokinetics, pharmacodynamics and safety of a human anti-IL‑6 monoclonal antibody (sirukumab) in healthy subjects in a first-in-human study. Br J Clin Pharmacol 72(2):270–281CrossRefPubMedPubMedCentral Xu Z, Bouman-Thio E, Comisar C, Frederick B, Van Hartingsveldt B, Marini JC et al (2011) Pharmacokinetics, pharmacodynamics and safety of a human anti-IL‑6 monoclonal antibody (sirukumab) in healthy subjects in a first-in-human study. Br J Clin Pharmacol 72(2):270–281CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Shaw S, Bourne T, Meier C, Carrington B, Gelinas R, Henry A et al (2014) Discovery and characterization of olokizumab: a humanized antibody targeting interleukin‑6 and neutralizing gp130-signaling. Mabs: Taylor Francis p:773–781CrossRef Shaw S, Bourne T, Meier C, Carrington B, Gelinas R, Henry A et al (2014) Discovery and characterization of olokizumab: a humanized antibody targeting interleukin‑6 and neutralizing gp130-signaling. Mabs: Taylor Francis p:773–781CrossRef
9.
Zurück zum Zitat Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG et al (2022) 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 81(4):469–479CrossRefPubMed Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG et al (2022) 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 81(4):469–479CrossRefPubMed
10.
Zurück zum Zitat Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL et al (2022) Olokizumab versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med 387(8):715–726CrossRefPubMed Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL et al (2022) Olokizumab versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med 387(8):715–726CrossRefPubMed
11.
Zurück zum Zitat Genovese MC, Fleischmann R, Furst D, Janssen N, Carter J, Dasgupta B et al (2014) 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 73(9):1607–1615CrossRefPubMed Genovese MC, Fleischmann R, Furst D, Janssen N, Carter J, Dasgupta B et al (2014) 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 73(9):1607–1615CrossRefPubMed
12.
Zurück zum Zitat Takeuchi T, Tanaka Y, Yamanaka H, Amano K, Nagamine R, Park W et al (2016) 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 26(1):15–23CrossRefPubMed Takeuchi T, Tanaka Y, Yamanaka H, Amano K, Nagamine R, Park W et al (2016) 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 26(1):15–23CrossRefPubMed
13.
Zurück zum Zitat Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E et al (2022) 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. https://doi.org/10.1136/ard-2022-222630CrossRefPubMed Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E et al (2022) 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. https://​doi.​org/​10.​1136/​ard-2022-222630CrossRefPubMed
14.
Zurück zum Zitat Catalá-López F, Tobías A, Cameron C, Moher D, Hutton B (2014) Network meta-analysis for comparing treatment effects of multiple interventions: an introduction. Rheumatol Int 34(11):1489–1496CrossRefPubMed Catalá-López F, Tobías A, Cameron C, Moher D, Hutton B (2014) Network meta-analysis for comparing treatment effects of multiple interventions: an introduction. Rheumatol Int 34(11):1489–1496CrossRefPubMed
15.
Zurück zum Zitat Song GG, Lee YH (2016) Comparison of disease activity score 28 using C‑reactive protein and disease activity score 28 using erythrocyte sedimentation rate in assessing activity and treatment response in rheumatoid arthritis: a meta-analysis. J Rheum Dis 23(4):241–249CrossRef Song GG, Lee YH (2016) Comparison of disease activity score 28 using C‑reactive protein and disease activity score 28 using erythrocyte sedimentation rate in assessing activity and treatment response in rheumatoid arthritis: a meta-analysis. J Rheum Dis 23(4):241–249CrossRef
16.
Zurück zum Zitat Caldwell DM, Ades A, Higgins J (2005) Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ 331(7521):897CrossRefPubMedPubMedCentral Caldwell DM, Ades A, Higgins J (2005) Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ 331(7521):897CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Hochberg MC, Chang RW, Dwosh I, Lindsey S, Pincus T, Wolfe F (1992) The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum 35(5):498–502CrossRefPubMed Hochberg MC, Chang RW, Dwosh I, Lindsey S, Pincus T, Wolfe F (1992) The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum 35(5):498–502CrossRefPubMed
18.
Zurück zum Zitat Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C et al (2008) Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations. Arthritis Care Res 59(10):1371–1377CrossRef Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C et al (2008) Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations. Arthritis Care Res 59(10):1371–1377CrossRef
19.
Zurück zum Zitat Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269CrossRefPubMed Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269CrossRefPubMed
20.
Zurück zum Zitat Brown S, Hutton B, Clifford T, Coyle D, Grima D, Wells G et al (2014) A Microsoft-Excel-based tool for running and critically appraising network meta-analyses—an overview and application of NetMetaXL. Syst Rev 3(1):110CrossRefPubMedPubMedCentral Brown S, Hutton B, Clifford T, Coyle D, Grima D, Wells G et al (2014) A Microsoft-Excel-based tool for running and critically appraising network meta-analyses—an overview and application of NetMetaXL. Syst Rev 3(1):110CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Salanti G, Ades A, Ioannidis JP (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 64(2):163–171CrossRefPubMed Salanti G, Ades A, Ioannidis JP (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 64(2):163–171CrossRefPubMed
22.
Zurück zum Zitat Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades A (2013) Evidence synthesis for decision making 4 inconsistency in networks of evidence based on randomized controlled trials. Med Decis Making 33(5):641–656CrossRefPubMedPubMedCentral Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades A (2013) Evidence synthesis for decision making 4 inconsistency in networks of evidence based on randomized controlled trials. Med Decis Making 33(5):641–656CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Higgins J, Jackson D, Barrett J, Lu G, Ades A, White I (2012) Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Res Synth Methods 3(2):98–110CrossRefPubMedPubMedCentral Higgins J, Jackson D, Barrett J, Lu G, Ades A, White I (2012) Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies. Res Synth Methods 3(2):98–110CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Valkenhoef G, Lu G, Brock B, Hillege H, Ades A, Welton NJ (2012) Automating network meta-analysis. Res Syn Meth 3(4):285–299CrossRef Valkenhoef G, Lu G, Brock B, Hillege H, Ades A, Welton NJ (2012) Automating network meta-analysis. Res Syn Meth 3(4):285–299CrossRef
25.
Zurück zum Zitat Lee YH, Bae SC, Song GG (2011) The efficacy and safety of rituximab for the treatment of active rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials. Rheumatol Int 31(11):1493–1499CrossRefPubMed Lee YH, Bae SC, Song GG (2011) The efficacy and safety of rituximab for the treatment of active rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials. Rheumatol Int 31(11):1493–1499CrossRefPubMed
26.
Zurück zum Zitat Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2012) Associations between interleukin-10 polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis. Mol Biol Rep 39(1):81–87CrossRefPubMed Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2012) Associations between interleukin-10 polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis. Mol Biol Rep 39(1):81–87CrossRefPubMed
27.
Zurück zum Zitat Song GG, Bae SC, Lee YH (2014) Association of the MTHFR C677T and A1298C polymorphisms with methotrexate toxicity in rheumatoid arthritis: a meta-analysis. Clin Rheumatol 33(12):1715–1724CrossRefPubMed Song GG, Bae SC, Lee YH (2014) Association of the MTHFR C677T and A1298C polymorphisms with methotrexate toxicity in rheumatoid arthritis: a meta-analysis. Clin Rheumatol 33(12):1715–1724CrossRefPubMed
Metadaten
Titel
Comparison of the efficacy and safety of olokizumab at different dosages in patients with active rheumatoid arthritis: a network meta-analysis of randomized controlled trials
verfasst von
Young Ho Lee, MD PhD
Gwan Gyu Song
Publikationsdatum
02.06.2023
Verlag
Springer Medizin
Erschienen in
Zeitschrift für Rheumatologie / Ausgabe Sonderheft 1/2024
Print ISSN: 0340-1855
Elektronische ISSN: 1435-1250
DOI
https://doi.org/10.1007/s00393-023-01367-w

Weitere Artikel der Sonderheft 1/2024

Zeitschrift für Rheumatologie 1/2024 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.