Tocilizumab (Actemra)

IL-6 receptor inhibitor.

A humanized antihuman interleukin-6- receptor monoclonal antibody that blocks soluble and membrane bound receptors, improves systemic juvenile idiopathic arthritis.

It binds to both soluble and membrane bound, IL-6R blocks the downstream, signal transduction pathway implicated in CRS.

Indicated for adults patients with moderately to severely active rheumatoid arthritis who have had inadequate response to tumor necrosis factor antagonist therapies.

Not indicated for treatment of MTX naive patients.

It is associated with serious infections including TB, bacterial fungal, viral and other opportunistic infections.

May be associated with cytopenias, elevated, liver enzymes, and lipid dysregulation.

43% of patients on 8mg/kg+ MTX and 56% on 8mg/kg monotherapy achieved an ACR20 response after 2 infusions.

45% of patients on this agent plus MTX achieves ACR50 responses at 72 weeks.

Increased risk of bowel perforations.

Indicated with children 2 years of age and older with active Systemic Juvenile Idiopathic Arthritis.

In Systemic Juvenile Idiopathic Arthritis Tocilizumab compared to placebo at 12 weeks was significantly better then the placebo group with absence of fever and improvement of 30% or more on at least three of the six variables in the American College of Rheumatolgy, 85% versus 24% (De Benedetti F et al).

Associated with increased risk for developing serious infections.

Commonly causes dyslipidemia.

Dampens inflammation, increase hemoglobin, and improve inflammatory anemia in rheumatoid arthritis.

Reduces CRP and the iron metabolism marker hepcidin.

Gradually increases hemoglobin, improving anemia in patients with RA.

May be associated with gastrointestinal perforations, changes in liver function, decrease in peripheral neutrophil counts, elevation of lipase, thrombocytopenia, demyelinating disorders, and malignancies.

Gastrointestinal perforation rate was 0.26 events per 100 patient-years during a six-month phase 3 clinical trial.

The FDA has approved the use of subcutaneous Actemra (tocilizumab) for the treatment of adults with giant cell arteritis.

This is the first FDA-approved drug specifically for the treatment of this form of arteritis.

Subcutaneous Actemra was previously approved for the treatment of severely active rheumatoid arthritis and intravenous Actemra was approved for systemic juvenile idiopathic arthritis and polyarticular juvenile idiopathic arthritis.

Tocilizumab can be used to treat CAR T cell–induced severe or life-threatening cytokine release syndrome (CRS), which is a potentially life-threatening side effect of tisagenlecleucel, in patients aged 2 years or older.

Tocilizumab was shown to resolve CRS within 2 weeks after 1-2 doses in 69% of patients.

Tocilizumab reverses this process by binding and blocking the IL-6 receptor

Tocilizumab is the mainstay of treatment for severe cytokine release syndrome.

May benefit patients with steroid refractory adverse effects due to PD-1 blockade.

It is not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19.
Tocilizumab an anti-Interleukin-6 receptor antibody used in treating patients with Covid-19 pneumonia reduced the likelihood of progression to mechanical ventilation or death, but did not improve overall survival (Salama C).
Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, results in greater percentage of patients with a CRP protein level of less than 10 with reduced prednisone requirements at 24 weeks.

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