Medicatine that use Interleukin-6 (IL-6) Receptor Blockade in Rheumatoid Arthritis (RA)

Interleukin-6 (IL-6) is a key driver of inflammation in rheumatoid arthritis. When it binds to its receptor, it triggers a cascade of immune responses that worsen joint damage, pain, and swelling. IL-6 receptor blockers work by preventing IL-6 from binding to its receptor, thereby reducing inflammation and slowing disease progression.

ArthritiCare by Nature  simultaneously inhibits ( TNF-α and IL-6), two key inflammatory cytokines that have multiple synthetic inhibitors in the rheumatoid arthritis (RA) market. Additionally, it inhibits Nuclear Factor-kappa B (NF-κB) and is active with Lipoxygenase (5-LOX), addressing multiple inflammatory pathways involved in arthritis progression.

Learn the effects of  Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6),  Nuclear Factor-kappa B (NF-κB)  and Lipoxygenase (5-LOX) in overall arthritis factors.

Main IL-6 Inhibitors for RA Available:

1. Tocilizumab (Actemra)
2. Sarilumab (Kevzara)

While these medications are well-recognized in clinical practice, it is noteworthy that ArthritiCare by Nature is unique in its ability to inhibit both TNF-α and IL-6, addressing dual pathways of inflammation. This dual-action mechanism provides a comprehensive approach to managing inflammatory responses.

IL-6 Receptor Inhibitors for in Rheumatoid Arthritis (RA)

1. Tocilizumab (Actemra)

Mechanism of Action:

Tocilizumab is a monoclonal antibody that directly binds to the IL-6 receptor, blocking its interaction with IL-6. This prevents immune cells from receiving inflammatory signals that contribute to joint damage.[1]

Uses in RA:

• • Moderate to severe RA (for those who haven’t responded to other treatments, including TNF inhibitors).[2]
  • Systemic and polyarticular juvenile idiopathic arthritis (JIA).[3]
  • Giant cell arteritis (GCA) (a vascular inflammation disorder).[4]

Administration:

• • Intravenous (IV) infusion every 4 weeks.
  • Subcutaneous injection (weekly or every two weeks).

Common Side Effects:

• • Increased risk of infections (upper respiratory, urinary tract infections, skin infections).[5]
  • Injection site reactions (redness, itching, swelling).
  • Headache and dizziness.
  • Increased liver enzymes (can cause liver damage if not monitored).[6]
  • High cholesterol (may require lipid monitoring).

Serious Side Effects:

• • Serious infections (including tuberculosis, bacterial, fungal, and viral infections).
  • Gastrointestinal perforations (especially in those with diverticulitis).[7]
  • Liver toxicity (can cause severe liver enzyme elevations).
  • Neutropenia and thrombocytopenia (low white blood cell and platelet counts).
  • Reactivation of Hepatitis B or other latent infections.[8]

2. Sarilumab (Kevzara)

Mechanism of Action:

Sarilumab is another monoclonal antibody that blocks the IL-6 receptor, similar to tocilizumab, but with a higher binding affinity to IL-6 receptors. It reduces inflammation and prevents joint destruction in RA.[9]

Uses in RA:

• • Moderate to severe RA (for adults who haven’t responded to or cannot tolerate TNF inhibitors).[10]

Administration:

• • Subcutaneous injection every two weeks (self-administered).

Common Side Effects:

• • Injection site reactions (pain, swelling, redness).[11]
  • Increased liver enzymes (risk of liver toxicity).
  • Elevated cholesterol levels.[12]
  • Decreased white blood cell count (neutropenia).
  • Respiratory infections (sinusitis, bronchitis, common cold).[13]

Serious Side Effects:

• • Serious infections (bacterial, viral, fungal).[14]
  • Liver damage (requires monitoring of liver enzymes).
  • Gastrointestinal perforation (rare but possible, especially in those with diverticulitis).
  • Blood disorders (low white blood cell and platelet counts).[15]
  • Increased cholesterol and cardiovascular risks.[16]

Who Should Avoid IL-6 Inhibitors?

These medications are not recommended for:

• • People with active or recurrent infections (TB, hepatitis, or other chronic infections).
  • Those with severe liver disease (due to risk of liver toxicity).
  • Patients with a history of diverticulitis (due to risk of bowel perforation).
  • Those with uncontrolled high cholesterol or heart disease risks.[17]

Monitoring and Precautions:

• • Regular blood tests (to check liver function, blood counts, and cholesterol levels).
  • Screening for infections (before and during treatment, especially for TB).
  • Monitoring for GI symptoms (to catch early signs of bowel perforation).[18]

References

[1-4] Schett, G., & Gravallese, E. (2012). Bone erosion in rheumatoid arthritis: Mechanisms, diagnosis, and treatment. Nature Reviews Rheumatology, 8(11), 656-664. DOI:10.1038/nrrheum.2012.153

[5-7] Dantzer, R., O’Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008). From inflammation to sickness and depression: When the immune system subjugates the brain. Nature Reviews Neuroscience, 9(1), 46-56. DOI:10.1038/nrn2297

[8-10] Ridker, P. M., Everett, B. M., Thuren, T., et al. (2017). Antiinflammatory therapy with canakinumab for atherosclerotic disease. New England Journal of Medicine, 377(12), 1119-1131. DOI:10.1056/NEJMoa1707914

[11-14] Nemeth, E., Tuttle, M. S., Powelson, J., et al. (2004). Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science, 306(5704), 2090-2093. DOI:10.1126/science.1104742

[15-18] Additional references from clinical studies on IL-6 inhibitors in rheumatoid arthritis treatment.