U-ACT-Early and the Benefits of Tocilizumab Save

Lancet has published the results of the U-ACT-early study assessing the efficacy of monotherapy versus combination therapy using an interleukin-6 (IL-6) receptor-blocking monoclonal antibody, tocilizumab (TCZ), in patients with rheumatoid arthritis (RA).

This was a 2-year, multicenter, double-blind trial that included 317 early (< 1 year), DMARD-naïve RA patients with active RA defined as a DAS28 > 2.6. Patients were randomized (1:1:1) to 1) TCZ + MTX; 2) TCZ monotherapy; and 3) MTX monotherapy. Tocilizumab was given at 8 mg/kg every 4 weeks and MTX was started at 10 mg per week orally and escalated to a maximum of 30 mg per week. 

Patients not achieving remission on their initial regimen were switched from placebo to active treatments or from biologic to standard of care according to the protocol. For instance, patients not responding to TCZ + MTX were switched to standard of care therapy (typically methotrexate combined with a tumor necrosis factor inhibitor). When sustained remission was achieved, MTX or TCZ was tapered and stopped.

The study was completed by a similar proportion of patients in all 3 groups (range 72–78%). The primary endpoint was “sustained remission”, defined as DAS28 < 2.6, with a swollen joint count < 4 for at least 6 months.

Sustained remission was achieved in 86% of group 1 (TCZ + MTX), 84% of group 2 (TCZ monotherapy) and 44% of group 3 (MTX monotherapy. Thus TCZ, as monotherapy or in combination with MTX, was significantly superior to MTX alone.  No difference was seen between the TCZ + MTX and TCZ monotherapy groups.  

Radiographic joint damage scores were higher in the MTX arm compared with the TCZ+MTX arm at week 52 (p=0·0164). Overall, there was less radiographic joint damage progression at week 104 in both TCZ arms, compared with the MTX arm (p=0·0207).

The most common adverse event was nasopharyngitis (34-39%), there was no significant increase in serious adverse events between treatment groups and no deaths occurred during the study.

This trial is unique in that the sustained remission rates seen were higher than that reported in similar studies. Also percentage of patients with drug-free remission was also significantly higher in both tocilizumab arms (35% and 27%) compared with the methotrexate arm (11%).