Recent regulatory decisions by the Food and Drug Adminstration on the anti-tumor necrosis factor (anti-TNF-alpha) drugs etanercept and infliximab underscore the importance of this class in the armamentarium for rheumatologic diseases, as well as their clinical benefits in the management of rheumatoid arthritis (RA).

The FDA has approved etanercept (Enbrel) as a pre-filled syringe formulation for once weekly use, and granted Amgen, the manufacturer of etanercept, approval for a supplemental labeling change stating that the medication can induce a major clinical response in patients with RA.

In another regulatory decision, the FDA has approved the use of infliximab (Remicade) in combination with methotrexate as a first-line treatment for patients with RA.

The approval of the syringe dosing for etanercept followed a study showing that the pre-filled syringe, carrying a dose of 50 mg, was biologically equivalent to two 25-mg vials. The manufacturers have stated that the new product would be available to patients in the fourth quarter of 2004, and that the 25-mg formulation will remain available for both patients with juvenile rheumatoid arthritis (RA) and for those who prefer twice weekly injections.

"The pre-filled ... syringe is a welcome addition to the delivery system for etanercept with respect to patient convenience," reported Roy Fleischmann, MD, a clinical professor of medicine at the University of Texas Southwestern Medical Center in Dallas and a CiaoMed editorial board member. "This system allows the patient to take one injection a week rather than two and eliminates the need for mixing the solution prior to injection. It should receive enthusiastic patient support."

The label change allows the manufacturers to use language stating that the drug can produce "the highest level of improvement in disease activity" within a six-month period, with disease activity consisting of joint swelling and tenderness, pain, and level of disability. Enbrel is manufactured by Amgen; Amgen and Wyeth share marketing rights in North America.

The FDA also will allow the label to cite data showing that most patients taking etanercept had up to five years of no additional joint damage.

In response to clinical trials demonstrating the efficacy of infliximab in combination with methotrexate, the FDA has approved this two-drug regimen as a first-line therapy for patients with moderate to severe RA. With this approval, a lack of response to methotrexate alone is no longer required before patients can start the combination. In a press release, Centocor, the manufacturer of Remicade, stated that patients can now start the combination earlier in the course of RA, and that this treatment strategy "has been shown to reduce signs and symptoms, inhibit further joint destruction, and improve physical function."

" It has become increasingly clear that the optimum treatment for patients with RA, at any stage of disease, is the combination of an anti-TNF and methotrexate," said Dr. Fleischmann, who is co-medical director of Radiant Research, also in Dallas. "The combination of methotrexate and an anti-TNF is much more effective ... than either agent alone. There have also been studies which show that the earlier a patient is effectively treated, the less likely is the possibility of x-ray progression."

The approval of the infliximab-methotrexate combination as first-line therapy is a rational response to these findings, because the physician no longer has to delay treatment before using "the most effective combination for treatment of RA," he told CiaoMed. These results have also been with other anti-TNF-methotrexate combinations, he said. "The important remaining question to be answered is that, if the patient is treated initially with the combination ... how long the combination needs to be maintained and how much methotrexate is required to maintain the effect."

For more information:

On etanercept: http://www.amgen.com/news/viewPR.jsp?id=619937

On infliximab: http://www.centocor.com/cgi-bin/site/media/media_news.cgi?news_id=64