updateonthetnf-(blockingagents.docVIP

UPDATE ON THE TNF-( BLOCKING AGENTS INTRODUCTION The intent of this document is to summarize the efficacy data that resulted in the licensure of the three tumor necrosis factor (TNF) blocking agents and to provide a more comprehensive update on their safety. The three products, Etanercept (Enbrel), Infliximab (Remicade) and Adalimumab (Humira) are indicated for treatment of patients with RA. Clinical studies have shown the products to improve signs and symptoms, inhibit the progression of structural damage, and impact functional outcomes in patients with RA. The efficacy section will begin with a summary of Adalimumab, the newest of the TNF blocking therapies. While all these agents have demonstrated efficacy in patients with active RA despite treatment with other DMARDs (disease modifying anti-rheumatic drugs), they have also been associated with certain uncommon but serious adverse events. Most of these events have come to light through the post-marketing passive surveillance program. At the time of approval of the first two TNF blocking agents, the total numbers of patients treated and extent of exposure from controlled clinical trials and the open label extension studies were relatively limited. As will be summarized in the safety section of this document, the post market safety updates and data from controlled clinical trials in other settings have triggered several different FDA actions, including updates to the prescribing information in the package inserts, communications to health care providers (Dear Health Care Provider Letters) a safety update on August 17, 2001 to the AAC, as well as presentations at ACR and other national and international meetings and publications in journals. This safety update will summarize safety data from the randomized controlled trials contained in the Biologics License Application (BLA) of Adalimumab for RA, and provide an update on safety information for Remicade and Enbrel. One major focus of this safety update w