Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, a severe form of arthritis in children, and COVID19. It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.
Tocilizumab was approved for medical use in the United States in January 2010.
Medical uses
In the United States, tocilizumab is indicated for the treatment of rheumatoid arthritis, giant cell arteritis, systemic sclerosis-associated interstitial lung disease, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, cytokine release syndrome, and COVID19.
In the European Union, tocilizumab is indicated for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, juvenile idiopathic polyarthritis, giant cell arteritis, cytokine release syndrome, and COVID19.
Rheumatoid arthritis
Tocilizumab is used for the treatment of moderate to severe rheumatoid arthritis, applied in combination with methotrexate, if other drugs like disease-modifying antirheumatic drugs (DMARDs) and TNF alpha blockers have proven to be ineffective or were not tolerated. It can be used as a monotherapy for patients who do not tolerate methotrexate. The drug slows down the progression of the disease and can improve physical function of patients.
Systemic juvenile idiopathic arthritis
The treatment of systemic juvenile idiopathic arthritis (SJIA) is similar to rheumatoid arthritis treatment: tocilizumab is combined with methotrexate unless the latter is not tolerated. General safety and effectiveness is established for children of two years and older. In 2011, the US Food and Drug Administration (FDA) approved tocilizumab for the treatment of active systemic juvenile idiopathic arthritis.
Castleman's disease
In Japan, tocilizumab is also approved for the treatment of Castleman's disease, a rare benign tumor of B cells.
Giant cell arteritis
In May 2017, the FDA approved tocilizumab for giant cell (temporal) arteritis.
Cytokine release syndrome
On 30 August 2017, the FDA approved tocilizumab for cytokine release syndrome, a side effect of CAR-T cell therapies.
COVID-19
In June 2021, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for tocilizumab for the treatment of COVID19 in hospitalized people aged two years of age and older who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). The FDA approved tocilizumab for those indications in December 2022.
Adverse effects
The most common adverse effects observed in clinical trials were upper respiratory tract infections (more than 10% of patients), nasopharyngitis (common cold), headache, and high blood pressure (at least 5%). The enzyme alanine transaminase was also elevated in at least 5% of patients, but in most cases without symptoms. Elevated total cholesterol levels were common. Among the less common side effects were dizziness, various infections, as well as reactions of the skin and mucosae like mild rashes, gastritis and mouth ulcer. Rare but severe reactions were gastrointestinal perforations (0.26% in six months) and anaphylaxis (0.2%).
Interactions
There are no certain interactions with other drugs. The blood plasma levels of simvastatin were reduced by 57% after a single dose of tocilizumab, but it is not known whether this is clinically relevant. A possible mechanism is that the elevated IL-6 levels of patients with rheumatoid arthritis suppress the biosynthesis of various cytochrome P450 enzymes, notably CYP1A2, CYP2C9, CYP2C19 and CYP3A4. Tocilizumab lowers IL-6 and thus normalises cytochrome levels, increasing the metabolization of simvastatin (and possibly other cytochrome metabolised drugs).