Targeting interleukin-6 for noninfectious uveitis

Figures & data

Figure 1 Signaling and activity of IL-6.

Notes: (A) Signaling of IL-6 occurs through its receptor and gp130 in a heterotrimeric complex. The targets of IL-6 biologics are also shown. (B) Biological activity of IL-6 in various human organ systems. Modified with permission of Elsevier from: A new era for the treatment of inflammatory autoimmune diseases by interleukin-6 blockade strategy, Tanaka et al; Semin Immunol. © 2014; 26(1).⁸ Permission conveyed through Copyright Clearance Centre, Inc.
Abbreviations: JAK, janus kinase; STAT3, signal transducer and activator of transcription 3; MAPK, mitogen activated protein kinase.

Table 1 Conditions in which IL-6 plays a role in pathogenesis

Uveitic diseases^Citation16^–^Citation18,Citation21,Citation35

Vogt–Koyanagi–Harada syndrome

Toxoplasma chorioretinitis

Fuchs heterochromic iridocyclitis

Behçet disease-associated uveitis

Sarcoidosis-associated uveitis

Idiopathic uveitis

Systemic inflammatory disorders^Citation2,Citation36^–^Citation39

Chronic rheumatoid arthritis

Juvenile idiopathic arthritis and Still disease

Castleman disease

Graves disease

Inflammatory bowel disease

Systemic sclerosis

Relapsing polychondritis

Ankylosing spondylitis

Infectious diseases^Citation40^–^Citation42

HIV

HTLV-1

Cerebral malaria

Neoplastic diseases^Citation43^–^Citation46

Breast cancer

Colon cancer

Prostate cancer

Multiple myeloma

Neurological diseases^Citation47,Citation48

Alzheimers disease

Multiple sclerosis

Note: Modified from Interleukin-6 blockade in ocular inflammatory diseases. Mesquida M, et al; Clin Exp Immunol. 2014;176(3).¹⁵ © 2014 John Wiley and Sons Inc.

Abbreviation: HTLV-1, human T-lymphotropic virus-1.

Table 2 Summary of anti-IL-6 or IL-6R biologics

Biologic name	Molecular target	Company	Studied dosing	Potential uses
Tocilizumab^Citation13,Citation15,Citation24,Citation26,Citation27	Membrane and soluble IL-6 receptor	Genentech	4 or 8 mg/kg IV q4wk for 6 doses or 162 mg SC qwk	RA, JIA, Castleman disease, Behçet disease, systemic sclerosis, uveitis
Sarilumab^Citation31	Membrane and soluble IL-6 receptor	Regeneron	150–200 mg SC q2wk	RA, uveitis
Sirukumab^Citation30	IL-6	Janssen	100 mg SC q2wk	RA
Olokizumab^Citation32	IL-6	UCB	60–240 mg SC q2–4wk	RA
Clazakizumab^Citation33	IL-6	Alder BioPharmaceuticals	80–320 mg IV on day 1, and week 8	RA
Siltuximab^Citation34	IL-6	Janssen	11 mg/kg IV q3wk	Castleman disease, multiple myeloma, prostate cancer

Note: Bold denotes FDA-approved uses.

Abbreviations: IV, intravenous; RA, rheumatoid arthritis; JIA, juvenile idiopathic arthritis; SC, subcutaneous; q4wk, every 4 weeks; q2–4wk, every 2 to 4 weeks; q3wk, every 3 weeks.

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