New molecular entity: Tocilizumab (Actemra) was approved in January 2010, for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor antagonist therapies.
This January, FDA approved tocilizumab intravenous infusion for marketing in the United States. Tocilizumab is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies (ie, infliximab). Rheumatoid arthritis, a chronic disease mainly characterized by inflammation of the lining or synovium of the joints, is estimated to affect 1.3 million Americans.
Efficacy. The efficacy of tocilizumab has been assessed in 5 multicenter, randomized, double-blind, placebo- or active-controlled trials. Each trial enrolled adult patients with rheumatoid arthritis having at least 8 tender and 6 swollen joints at baseline. Administered every 4 weeks, tocilizumab has been studied as monotherapy, in combination with methotrexate in patients not responding adequately to disease modifying anti-rheumatic drugs (DMARD), or in combination with methotrexate in patients not responding to one or more TNF antagonist therapies. In each of these trials, the proportion of patients achieving the American College of Rheumatology (ACR) 20, 50, and 70 end points at 24 weeks while taking tocilizumab 8 mg/kg was greater than control patients receiving either placebo or methotrexate. Typically, patients receiving tocilizumab 4 mg/kg had a poorer response in clinical trials than those receiving 8 mg/kg.
Safety. Common side effects of tocilizumab (occurring in greater than 5% of treated patients) include upper respiratory tract infections (common cold, sinus infections), headache, and hypertension. Other serious side effects of tocilizumab include perforation of the gastrointestinal tract, changes in blood test results (elevated liver function tests [AST or ALT], elevated serum lipids [total or low-density lipoprotein cholesterol or triglycerides], reduced neutrophil and platelet counts), increased risk of hepatitis B infection in those already carrying the virus, increased risk of nervous system problems (development of multiple sclerosis), malignancies, and serious allergic reactions. Patients treated with tocilizumab are also at an increased risk for developing serious infections that may lead to hospitalization or death, including tuberculosis, bacterial, invasive fungal, viral, or other opportunistic infections. If a serious infection develops, tocilizumab therapy should be stopped until the infection is controlled.