Abatacept in Rheumatoid Arthritis: A New Branch on the “Biologics” Tree

In the last 2 decades, rheumatology has become a field with high yield potential for drug developers, and the complex diseases that rheumatologists treat have come under intense scrutiny. Targeting tumor necrosis factor (TNF) and its receptor by monoclonal antibodies has become a highly successful treatment for rheumatoid arthritis (RA) and a growing list of other diseases. Ongoing research is increasing both our knowledge of (patho)immunology and our treatment options. Once the dust has settled, science historians will doubtless find many research opportunities in the almost yearly change of paradigms of autoimmune disease.

In this issue, the third and pivotal phase III trial of abatacept in RA by Kremer and colleagues (1) marks the coming of age of a new therapeutic pathway, based on the inhibition of full T-cell activation. Strong points of the trial include state-of-the-art trial procedures, large sample size, and meticulous attention to handling missing data. On the basis of this and other trials, the U.S. Food and Drug Administration (FDA) recently approved abatacept, saying that it reduces signs and symptoms, slows joint damage, and improves physical function in active RA, which has responded inadequately to disease-modifying drugs, such as methotrexate or TNF antagonists (2, 3). The last 2 words are important: Abatacept is the first drug to receive a label referring to TNF antagonists. Because of safety concerns expressed at the FDA advisory board meeting (mainly about severe infections and cancer), the company producing the drug has implemented an extensive pharmacovigilance program (4).

I will not discuss the safety concerns or the mysteries of pricing, wherein the price of each new biological agent is almost exactly the same as that of its competitors. Both topics merit an editorial. Instead, I will argue that the study questions answered in the “registration” trials that are necessary …