Tocilizumab (Actemra) is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets the interleukin-6 (IL-6) receptor manufactured by Genentech, Inc. It is indicated (approved for use) for the treatment of adult patients with moderately to severely active RA who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). It is also indicated for the treatment of types of juvenile idiopathic arthritis.
Tocilizumab (Actemra): overview and efficacy
Tocilizumab (Actemra) is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets the interleukin-6 (IL-6) receptor manufactured by Genentech, Inc. It is indicated (approved for use) for the treatment of adult patients with moderately to severely active RA who have had an inadequate response to one or more conventional disease-modifying anti-rheumatic drugs (DMARDs). It is also indicated for the treatment of types of juvenile idiopathic arthritis.1
How does Actemra work?
Tocilizumab (Actemra) is a human immunoglobulin G1 (IgG1) monoclonal antibody. Remember that our bodies naturally produce antibodies against bacteria, viruses, and other foreign organisms that invade and pose a threat to our health. Following the example of our bodies, drug makers have engineered different antibodies designed to target the mechanisms that cause a variety of diseases, including RA. Actemra binds to IL-6 receptors, preventing their activation by the cytokine IL-6, that plays an important pro-inflammatory role in the immune response in RA. IL-6 promotes inflammation by activating and expanding T-cells, promoting B-cells, and inducing acute-phase reactants.1
How is Actemra taken?
Actemra is given as an intravenous (IV) infusion alone or in combination with methotrexate and/or other DMARDs. The recommended starting dose is 4 mg per kg every 4 weeks followed by an increase to 8 mg per kg every 4 weeks based on clinical response. An IV infusion of Actemra typically takes about 1 hour.1
Are there people who should not take Actemra?
Actemra should not be given to patients who are known to be hypersensitive (allergic) to Actemra or its components.1
Patients who take Actemra are at increased risk for serious infections, including tuberculosis, invasive fungal infections, viral infections, bacterial infections, and other opportunistic infections (infection caused by a microorganism that does not normally cause infection in humans, typically due to an abnormally functioning immune system).Actemra should not be given to patients who have an active infection. If a serious infection develops while taking Actemra, the drug should be discontinued until the infection has been resolved.1
Actemra is a pregnancy category C drug. Studies of Actemra in animals did show adverse effects on the developing fetus. However, there are no well-controlled studies in humans. Therefore, Actemra should only be used in pregnant women if the potential benefits justify the risk to the fetus.1
It is unknown whether Actemra is excreted into human milk. Because of the potential for adverse effects to the nursing infant, a nursing woman should either discontinue the drug or stop nursing while taking Actemra.1
What evidence is there that Actemra works in RA?
The effectiveness of Actemra in RA was evaluated in five randomized controlled trials.
One study (Study 1) was conducted in patients with active moderate to severe RA who were either methotrexate-naive (67% of patients in the study had never received methotrexate) or who had not received methotrexate within 24 weeks and had not discontinued the drug due to side effects or lack of efficacy. Patients in this study were randomized to Actemra 8 mg per kg alone or methotrexate alone.1
Two studies (Studies 2 and 3) were conducted in patients with moderate to severe RA who had had an inadequate response to methotrexate. Patients were randomized to Actemra 4 mg or 8 mg per kg every 4 weeks or placebo, each given in combination with methotrexate.1
Another study (Study 4) was conducted in patients with RA who had had an inadequate response to one or more DMARDs. Patients were randomized to Actemra 8 mg per kg every four weeks or placebo, each given in combination with DMARDs.1
A fifth study (Study 5) was conducted in patients who had had an inadequate response to one or more anti-tumor necrosis factor (anti-TNF) treatments. Patients were randomized to Actemra 4 or 8 mg per kg or placebo, each given in combination with methotrexate.1
Disease activity and clinical response. In all five studies, Actemra 8 mg per kg resulted in higher rates of ACR20, 50 and 70 response compared with methotrexate or placebo at week 24.1
Clinical responses at weeks 24 and 52 in studies of Actemra in RA
|Study 1||Study 2||Study 4||Study 5|
|Actemra 8 mg/kg (N=286)||MTX (N=284)||Actemra 8 mg/kg (N=398)||Placebo + MTX (N=393)||Actemra 8 mg/kg (N=803)||Placebo + MTX (N=413)||Actemra 8 mg/kg (N=170)||Placebo + MTX (N=158)|
|Major clinical (wk 52)||—||7%||1%||—||—||—||—||—|
Radiographic response. In Study 2 damage to joints was evaluated radiographically using the Sharp-Genant score. X-rays were taken at baseline, 24 weeks, 52, weeks, and 104 weeks. At 52 weeks, Actemra 4 and 8 mg per kg both resulted in a greater slowing of the progression of structural damage to joints compared with placebo + methotrexate. Actemra 4 mg/kg resulted in somewhat less than a 75% improvement in progression versus the control and Actemra 8 mg/kg resulted in at least a 75% improvement versus the control.1
Radiographic change from baseline to week 52 in Study 21
|Actemra 4 mg/kg + MTX||Actemra 8 mg/kg + MTX||Placebo + MTX|
|Total Sharp-Genant Score||0.33||0.25||1.17|
|Joint space narrowing score||0.13||0.10||0.41|
Is there a generic form of Actemra?
There is no generic equivalent of Actemra.