FUNCTION Trial: Sustained Results for RA with Tocilizumab Maintained Through 2 Years

Dava Stewart

Alone or combined with methotrexate, benefits continued through week 104.

Researchers have confirmed that the clinical benefits of intravenous tocilizumab (TCZ) alone or in combination with methotrexate in patients with rheumatoid arthritis (RA) continue through week 104 of treatment. Professor Gerd Burmester (pictured) of Charité-Universitätsmedizin Berlin, Germany, led a team of researchers to investigate the safety and efficacy of TCZ treatment in patients with early RA beyond week 52.

Disease-modifying antirheumatic drugs (DMARDs) are recommended as an early, intensive treatment for patients with RA. “Tocilizumab, an interleukin-6 receptor-alpha inhibitor, has demonstrated safety and efficacy in combination with DMARDs in patients with RA and inadequate response to DMARDs and monotherapy in patients with RA,” explain the researchers. TCZ in combination with MTX and as monotherapy was tested in patients with early RA and who were MTX-naive in a phase III trial called FUNCTION, which lasted 52 weeks.

“This analysis investigated whether previously reported clinical benefits and safety profiles of TCZ were maintained through 104 weeks of double-blind treatment,” say the authors.

There were 1162 patients randomly assigned; 1157 were in the intent-to-treat population and 1153 in the safety population A total of 809 completed week 104. Remission rates were maintained from week 52 through week 104. Some patients who had not responded to treatment by week 52 had done so by week 104.

Patients were divided into four groups: 8 mg/kg TCZ+MTX; 8 mg/kg TCZ+placebo; 4 mg/kg TCZ+MTX; placebo+MTX. There were serious adverse events in each group, with the most being in the 8 mg/kg TCZ+MTX group. The majority of adverse events were mild to moderate, with infection being the most common.

The two groups receiving 8 mg/kg TCZ, with or without MTX showed the best results, leading the authors to note, “Maintenance of response with 8 mg/kg TCZ monotherapy suggests that early TCZ therapy is a viable option for patients intolerant of MTX”. Additionally, the findings show that longer treatment may be necessary for some patients.

Those patients who given “escape therapy”, that is who were moved from one of the 4 mg/kg treatment groups to one of the 8 mg/kg treatment groups response rates were lower and “the overall degree of joint damage was greater” according to the researchers, who go on to say these results highlight the need to begin treatment early.

One limitation of this study is the complexity of the multiple comparisons. The authors suggest that “data for the 4 mg/kg TCZ+MTX and placebo+MTX groups should be interpreted with caution given the large number of patient switching to escape therapy”.

FUNCTION was the first study of TCZ in patients with early RA, and the current study reflects that participants “sustained improvement in disease activity and maintained inhibition of joint damage during their second year of treatment,” say the researchers, noting that a post hoc analysis shows that some patients may need longer treatment for efficacy to be observed.

The full study can be found in Annals of the Rheumatic Diseases, published online ahead of print on April 7.

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