Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from a randomized, placebo-controlled trial

BACKGROUND/PURPOSE:

Treatment with tocilizumab (TCZ) in combination with MTX or as monotherapy (Mono) in MTX-naive patients (pts) with early RA resulted in improved signs and symptoms and inhibition of joint damage at wk 52 of the 104-wk, double-blind, placebo-controlled trial FUNCTION.1 Results to wk 104 are presented.

METHODS:

Pts were randomized 1:1:1:1 to TCZ 8 mg/kg (TCZ8) + MTX, TCZ8 Mono, TCZ 4 mg/kg (TCZ4) + MTX, or MTX for 104 wks. Pts received IV TCZ q4w, with MTX escalated from 7.5 mg qw to 20 mg qw by wk 8. Inclusion criteria have been described.1 At wk 52, TCZ4 + MTX and MTX pts who had not achieved low disease activity (DAS28 ≤3.2) switched to blinded escape therapy with TCZ8 + MTX. Efficacy end points (DAS28, ACR responses, and van der Heijde–modified Total Sharp Score) were assessed in the intent-to-treat (ITT) population, and a subgroup analysis was performed for postescape data. Adverse events (AEs) were evaluated under the treatment group in which the AE occurred. Wk 104 analyses were exploratory; no statistical testing was performed.

RESULTS:

At wk 52, 95/290 (33%) TCZ4 + MTX pts and 142/289 (49%) MTX pts switched to TCZ8 + MTX escape therapy. Baseline characteristics of escape pts were consistent with those of the full ITT population.1 Clinical efficacy was maintained through wk 104 in the TCZ8 groups, with similar proportions at wks 52 and 104 achieving ACR20/50/70 responses and DAS28, ACR/EULAR Boolean/Index, and Clinical Disease Activity Index criteria remission. Inhibition/slowing of radiographic progression was also maintained. In TCZ4 + MTX and MTX pts who switched to escape with TCZ8 + MTX at wk 52, further improvement in efficacy from the point of escape was generally seen at wk 104. Despite the inhibition of structural joint damage after escape, joint damage was numerically greater than in pts who received TCZ8 Mono or TCZ8 + MTX throughout (Table). TCZ serum levels were similar with both Mono and combination TCZ treatment. AE rates were similar across groups, with serious AE and serious infection rates numerically higher in the TCZ groups (Table). There were 14 deaths (9 reported earlier1); 5 occurred in year 2. Underlying causes varied and included 4 due to infection (2 MTX; 2 TCZ4 + MTX), 3 due to malignancy (1 TCZ8 + MTX; 2 TCZ8 Mono), and 2 due to cardiovascular disease (1 TCZ4 + MTX; 1 TCZ8 Mono).

CONCLUSION:

Pts with early RA who received TCZ8 + MTX or TCZ8 Mono for the duration of the study had sustained improvement in disease activity and maintained joint damage inhibition over 104 wks. Efficacy improved further in pts receiving MTX or TCZ4 + MTX who switched to escape with TCZ8 + MTX at wk 52; the overall degree of joint damage (though generally minor) was greater than that in pts who received TCZ8 for the entire study, highlighting the importance of early initiation of optimal therapy. Safety was consistent with the known safety profile of TCZ.