Tocilizumab: new drug. Rheumatoid arthritis: another 'mab', no therapeutic advantage.
(1) First-line disease-modifying treatment for rheumatoid arthritis is based on "slow-acting" antirheumatic agents, generally methotrexate. Subsequent options include a TNF-alpha antagonist, followed by rituximab or possibly abatacept; (2) Tocilizumab, a monoclonal antibody, inhibits interleukin-6 receptors. It is licensed in the European Union for patients with rheumatoid arthritis in whom other drugs have failed; (3) Clinical evaluation includes 4 placebo-controlled trials of the methotrexate-tocilizumab combination, after failure of a slow-acting antirheumatic drug (3 trials) or failure of a slow-acting antirheumatic drug and a TNF-alpha antagonist (1 trial). An indirect comparison suggests that tocilizumab is no more effective than rituximab in patients with multiple treatment failure; (4) Tocilizumab, like TNF-alpha antagonists, is an immunosuppressant. It carries a risk of serious infections, haematological disorders (neutropenia, thrombocytopenia), gastrointestinal bleeding, hepatic disorders, and systemic and local reactions during the infusion; (5) the adverse effects of long-term tocilizumab therapy are unknown, particularly the risk of cancer; (6) Tocilizumab carries a risk of interactions with drugs that are metabolised by cytochrome P450 isoenzymes. Clinical consequences cannot be ruled out when co-administered drugs have a narrow therapeutic margin; (7) Tocilizumab is administered intravenously every 4 weeks, making it slightly more convenient that rituximab at the beginning of treatment; (8) In patients with rheumatoid arthritis and multiple treatment failure, it remains to be shown whether tocilizumab has a better risk-benefit balance than rituximab, a drug with which we have more experience. It is therefore better to continue to use rituximab, or possibly abatacept.
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005060:Europe; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D008727:Methotrexate; D000069283:Rituximab; D000093242:Interleukin-6 Inhibitors; C502936:tocilizumab