As inhibitors of pro-inflammatory cytokines take center stage in treating rheumatoid arthritis, they continue to raise safety questions, a fact perhaps not surprising given the broad importance of the pathways they work in. These biologics for RA have the potential to act on other body systems, such as the immune and nervous systems.

In addition, very little is known about the potential interactions of these treatments, which so far hasn't been an issue since the two approved products, Enbrel etanercept from Immunex Corp. and Remicade infliximab from the Centocor division of Johnson & Johnson, both target TNF.

But if the FDA goes along with last Thursday's recommendation of its Arthritis Advisory Committee to approve Amgen Inc.'s Kineret anakinra IL-1 receptor antagonist, the question of how these biologics interact is bound to come up.

Surprisingly, however, even after probing the issue in its Kineret deliberations, the panel on Friday passed up another opportunity to examine the issue more deeply.

Thursday's meeting demonstrated clearly the challenges the agency faces in staying ahead of the changing therapeutic picture for RA. With two biologics on the market, FDA has given AMGN more hoops to jump through in its quest for approval of Kineret.

And while Kineret met its prespecified efficacy goals, AMGN's answers to some of the agency's requests gave the committee pause, making it appear that some members might like to see FDA raise its approval bar for biologic agents that are not first to market.

Combination therapy

On Thursday, Roger Perlmutter, AMGN's executive vice president of R&D, described Kineret's activity in terms of its place in the cytokine lexicon. The recombinant interleukin-1 receptor antagonist binds and occupies IL-1 receptors but blocks their activation by preventing assembly of the receptor complex.