Patients were randomly assigned to one of four different treatment groups: TNFR:Fc twice weekly at a dose of 0.25 mg/m2 of body surface area, 2 mg/m2, 16 mg/m2 and a placebo group. The primary end point was the percentage change in swollen and tender joint count from baseline to three months.
The group receiving TNFR:Fc achieved a significantly greater reduction in the number of swollen and tender joints, when compared to the placebo group. There was a linear dose response, demonstrating that those who received higher doses of the drug had greater improvement in measures of disease activity. By contrast, the placebo group showed an initial improvement only through week 2, but no improvement thereafter. TNFR:Fc was found to be safe at all doses administered, with mild injection site reactions and mild upper respiratory infections, but no serious adverse events.
In summary, the trial demonstrates significant dose-related positive outcomes and an acceptable safety profile with the use of TNFR:Fc in patients with refractory RA.
Impact on Rheumatology
This article was crucial in triggering the biologic renaissance in rheumatology. Etanercept became the first targeted biologic therapy to be approved by the U.S. Food & Drug Administration (FDA) for RA in 1998 and, later, the first TNFα inhibitor to be approved for juvenile idiopathic arthritis and ankylosing spondylitis.
Since the approval of etanercept, it would be an understatement to say that the treatment of rheumatic diseases has been transformed. In the past two decades, multiple, alternative TNFα inhibitors have been subsequently approved for a wide range of autoimmune diseases. For patients, this renaissance has generated dramatic improvement in disease control, quality of life and decreased morbidity. The study was one of the first to demonstrate the feasibility of studying biologic medications for the treatment of rheumatic conditions, thereby catalyzing the expansion of our arsenal for the treatment of rheumatic diseases.
Chances in the Tournament
Although a drug derived from hamster ovaries may not sound intimidating, we expect etanercept to live up to its title as the first biologic approved for RA with victories in the first two rounds. Some may argue that combination therapy will triumph because two is better than one. But who wants to take multiple medications? Not us! A matchup with the TEAR trial in the third round could prove to be a close contest and etanercept will need to put on a clinic to send its opponent home. Either way, we are excited to see if this TNF could prove to be the alpha for the 2023 tournament.
