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Cited by 50Rheumatoid Arthritis Research and TherapiesBiosimilars and Bioanalytical MethodsAutoimmune and Inflammatory Disorders Research

Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What Have We Learned?

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Avci, Ali Berkant, Feist, Eugen, Burmester, Gerd R.·2024·BioDrugs
DOI 10.1007/s40259-023-00634-1PMC PMC10789669
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Abstract

The use of different pathways in the treatment of rheumatoid arthritis has led to a significant decrease in the number of treatment-resistant patients. In this context, interleukin (IL)-6 inhibition has filled an important gap in rheumatoid arthritis treatment with its effectiveness and safety in both monotherapy and combinations. The process of IL-6 inhibition initiated with IL-6 receptor blockers has prompted questions regarding the potential impact and safety of different inhibitions of this pathway, such as the direct blockade of IL-6. Following the termination of the development of sirukumab because of mortality data in early studies, the investigation of olokizumab, which targets a different region of the IL-6 cytokine, has renewed the hope in this area and the safety concerns have been largely alleviated by the open-label extension data. In addition, the efficacy and safety of tocilizumab and sarilumab have led to a rapid investigation of biosimilars and new potent IL-6 receptor blockers. A comprehensive understanding of mechanisms of this pathway with further long-term clinical data and basic research may provide a decisive impact on selecting the appropriate mechanism as the first choice in personalized treatments.

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  • Tocilizumab binds the IL-6 binding site of both membrane and soluble IL-6R, blocking classic, trans-, and cluster signaling.

    “Tocilizumab, a humanized monoclonal antibody, is determined to bind to the IL-6 binding site of both membrane and soluble IL-6R, thus blocking classic, trans-, as well as cluster signaling [84, 85].”

    From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [84]

    The Introduction identifies tocilizumab as an IL-6R inhibitor and explains that membrane-bound and soluble IL-6R mediate classic and trans-signaling, respectively. It also says anti-IL-6Rα antibodies can neutralize trans-presentation, but does not specify tocilizumab’s binding site or state that it binds both receptor forms and blocks all three pathways. (LLM, conf=0.82)

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References 54 · Cited by 50

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Authors
Avci, A. B., Feist, E., & Burmester, G. R.
Affiliations
  • Otto-von-Guericke-Universität Magdeburg (DE)
  • Stiftung Charité (DE)
Corresponding author
Burmester, Gerd R.
ORCID
Venue
BioDrugs
Publisher
Springer Science and Business Media LLC
Published
2023-11-21
Volume
38
Issue
1
Pages
61-71
ISSN
  • 1172-7039 (ISSN-L)
  • 1173-8804
  • 1179-190X
DOI
10.1007/s40259-023-00634-1
PMC
PMC10789669
OpenAlex
W4388867365
Cited by
50
References
54
Citations by year
2026: 19 · 2025: 22 · 2024: 9
FWCI
2.19
Type
journal article
Language
en
Open access
Licence
Locations
  • BioDrugs (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by-nc)
  • Refubium (Universitätsbibliothek der Freien Universität Berlin) (submittedVersion, cc-by-nc)
  • Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver
Funders
Charité - Universitätsmedizin Berlin
Topics
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
  • Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Keywords
rheumatoid arthritis, IL-6 inhibition, IL-6 receptor inhibition, sirukumab, olokizumab, tocilizumab, sarilumab, biosimilars, treatment-resistant rheumatoid arthritis, drug safety, personalized treatment
MeSH terms
Interleukin-6 Inhibitors, Arthritis, Rheumatoid, Humans, Interleukin-6, Treatment Outcome, Antirheumatic Agents, Receptors, Interleukin-6, Biosimilar Pharmaceuticals, Antibodies, Monoclonal, Humanized

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