Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial

Area of Science:

• Immunology
• Rheumatology
• Clinical Trials

Background:

• Tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, has not been previously evaluated in methotrexate (MTX)-naive patients exclusively with early rheumatoid arthritis (RA).
• The FUNCTION trial (NCT01007435) investigated TCZ efficacy in this specific patient population.

Purpose of the Study:

• To evaluate the efficacy of tocilizumab (TCZ) in patients with early, active rheumatoid arthritis (RA) who are naive to methotrexate (MTX).
• To assess TCZ's impact on disease remission, radiographic progression, and physical function compared to MTX monotherapy.

Main Methods:

• A double-blind, randomized controlled trial involving 1162 MTX-naive early RA patients.
• Patients were assigned to receive 4 mg/kg TCZ + MTX, 8 mg/kg TCZ + MTX, 8 mg/kg TCZ + placebo, or placebo + MTX.
• Primary outcome was remission (DAS28-ESR < 2.6) at 24 weeks; radiographic and functional outcomes were assessed through 52 weeks.

Main Results:

• Significantly higher remission rates at week 24 were observed in the 8 mg/kg TCZ + MTX (45%) and 8 mg/kg TCZ + placebo (39%) groups compared to placebo + MTX (15%).
• The 8 mg/kg TCZ + MTX group showed significantly reduced radiographic progression (0.08 vs 1.14) and improved physical function (-0.81 vs -0.64) at week 52.
• TCZ in combination with MTX or as monotherapy demonstrated efficacy comparable to MTX for key secondary endpoints. Adverse event profiles were similar across groups, with 20% withdrawal in the 8 mg/kg TCZ + MTX arm.

Conclusions:

• Tocilizumab (TCZ) is effective in combination with methotrexate (MTX) for treating patients with early rheumatoid arthritis (RA).
• Tocilizumab (TCZ) also demonstrated efficacy as monotherapy in patients with early RA.
• The study supports TCZ as a viable treatment option for early RA, impacting remission, radiographic progression, and physical function.