Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis

Smolen, Josef S.; Feist, Eugen; Fatenejad, Saeed; Grishin, Sergey; Korneva, Elena; Nasonov, E.; Samsonov, Mikhail; Fleischmann, Roy

doi:10.1056/nejmoa2201302

Cited by 38 publications

(34 citation statements)

References 31 publications

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“…OKZ was generally safe and well tolerated with few subjects discontinuing treatment. However, a dose-dependent increase of SAEs was observed with more SAE in the q2w regimen; this had not been observed in other studies with OKZ in RA 14 21…”

Section: Discussionmentioning

confidence: 51%

“…With respect to the potential antigenic sites of IL-6,22 sirukumab and clazakizumab target site 1; interfering with the binding of IL-6 to the cognate IL-6R (IL-6Rα) in the trimolecular IL-6–IL-6R–gp130 complex. Of note, olokizumab binds to site 3 and inhibits the interaction of IL-6 and the IL-6–IL6-R dimer with the signal-transducing β-receptor subunit gp130 of the receptor complex 12–14 21. As a result, OKZ blocks the final hexamer formation on the molecular level, while the other anti-IL-6 inhibitors prevent dimer formation.…”

Section: Discussionmentioning

confidence: 99%

“…However, a dose-dependent increase of SAEs was observed with more SAE in the q2w regimen; this had not been observed in other studies with OKZ in RA. 14 21 …”

Section: Discussionmentioning

confidence: 99%

“…OKZ was previously shown to be generally safe and effective in reducing signs and symptoms of active RA in patients with an incomplete response to TNFi in two relatively small and short-term phase II randomised controlled trials (RCTs) 12 13. Two phase III study of OKZ in MTX-IR was previously reported with positive results 14 15. In the present global phase III study, we evaluated the efficacy and safety of OKZ 64 mg every 2 weeks (q2w) and every 4 weeks (q4w) in patients with active RA and inadequate response to TNFi.…”

Section: Introductionmentioning

confidence: 99%

“… 12 13 Two phase III study of OKZ in MTX-IR was previously reported with positive results. 14 15 In the present global phase III study, we evaluated the efficacy and safety of OKZ 64 mg every 2 weeks (q2w) and every 4 weeks (q4w) in patients with active RA and inadequate response to TNFi.…”

Section: Introductionmentioning

confidence: 99%

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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

Feist¹,

Fatenejad

Grishin

et al. 2022

Ann Rheum Dis

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ObjectivesTo assess the efficacy and safety of olokizumab (OKZ), a monoclonal antibody against the interleukin-6 (IL-6) cytokine, versus placebo (PBO) in patients with prior inadequate response to tumour necrosis factor inhibitors (TNFi-IRs).MethodsIn this 24-week multicentre, placebo-controlled, double-blind study, the patients were randomised in a 2:2:1 ratio to receive subcutaneously administered OKZ 64 mg once every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or PBO plus methotrexate. At week 16, the patients on PBO were randomised to receive either OKZ regime. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. Disease Activity Score 28-joint count C-reactive protein (DAS28 (CRP))<3.2 at week 12 was the major secondary efficacy endpoint. Safety and immunogenicity were assessed.ResultsIn 368 patients randomised, ACR20 response rates were 60.9% in OKZ q2w, 59.6% in OKZ q4w and 40.6% in PBO (p<0.01 for both comparisons). Achievement of DAS28 (CRP) <3.2 was significantly different, favouring the OKZ arms. Improvements in efficacy and patient-reported outcomes were maintained throughout 24 weeks and were noted after week 16 in patients who switched from PBO.Dose-related treatment-emergent serious adverse events were 7% in OKZ q2w, 3.2% in OKZ q4w and none in the PBO group.ConclusionsDirect inhibition of IL-6 with OKZ resulted in significant improvements in the signs and symptoms of rheumatoid arthritis compared with PBO in TNF-IR patients with a similar safety profile as observed for monoclonal antibodies to the IL-6 receptor.Trial registration numberNCT02760433.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

“…However, a dose-dependent increase of SAEs was observed with more SAE in the q2w regimen; this had not been observed in other studies with OKZ in RA. 14 21 …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Feist¹,

Fatenejad

Grishin

et al. 2022

Ann Rheum Dis

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Signaling pathways in macrophages: molecular mechanisms and therapeutic targets

Li,

Wang,

Wen

et al. 2023

MedComm

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Macrophages play diverse roles in development, homeostasis, and immunity. Accordingly, the dysfunction of macrophages is involved in the occurrence and progression of various diseases, such as coronavirus disease 2019 and atherosclerosis. The protective or pathogenic effect that macrophages exert in different conditions largely depends on their functional plasticity, which is regulated via signal transduction such as Janus kinase–signal transducer and activator of transcription, Wnt and Notch pathways, stimulated by environmental cues. Over the past few decades, the molecular mechanisms of signaling pathways in macrophages have been gradually elucidated, providing more alternative therapeutic targets for diseases treatment. Here, we provide an overview of the basic physiology of macrophages and expound the regulatory pathways within them. We also address the crucial role macrophages play in the pathogenesis of diseases, including autoimmune, neurodegenerative, metabolic, infectious diseases, and cancer, with a focus on advances in macrophage‐targeted strategies exploring modulation of components and regulators of signaling pathways. Last, we discuss the challenges and possible solutions of macrophage‐targeted therapy in clinical applications. We hope that this comprehensive review will provide directions for further research on therapeutic strategies targeting macrophage signaling pathways, which are promising to improve the efficacy of disease treatment.

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Comparison of the efficacy and safety of tocilizumab, sarilumab, and olokizumab in patients with active rheumatoid arthritis: a network meta-analysis of randomized controlled trials

Lee

Song

2023

Z Rheumatol

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Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis

Cited by 38 publications

References 31 publications

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

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

Signaling pathways in macrophages: molecular mechanisms and therapeutic targets

Comparison of the efficacy and safety of tocilizumab, sarilumab, and olokizumab in patients with active rheumatoid arthritis: a network meta-analysis of randomized controlled trials

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