Background Tocilizumab (TCZ) represents an efficacious alternative for patients with rheumatoid arthritis (RA) with an inadequate clinical response to biological or non-biological disease-modifying anrirheumatic drugs (DMARDs). Previous data support the use of TCZ in monotherapy but there are limited data on its efficacy compared to TCZ + MTX.
Objectives The main objective was to assess the maintenance of response after switching to TCZ alone in patients with TCZ 8 mg/kg i.v. every 4 weeks + oral MTX who showed at week 16 a low activity (DAS28 ≤3.2). Secondary endpoints included clinical response after 28 weeks, improvement of general status and quality of life. Safety assessment was also assessed and included adverse events, serious adverse events, and change in laboratory parameters.
Methods Phase III, randomized, double-blind, parallel-group (1:1), multicenter study in patients with active RA treated with TCZ + MTX with previous inadequate response to MTX. All those patients who achieved at week 16 a DAS28 ≤3.2 were randomized (1:1) to either TCZ + MTX or TCZ + placebo with a follow-up of 28 weeks. Sample size was calculated in 79 patients per group in order to detect a minimum disease activity score (DAS28) clinically relevant difference of 0.5 (standard deviation 1.1) with 80% power and two-sided 5% alpha level. Statistical analysis was performed with SAS v9.2, and included analysis of covariance for the primary endpoint (with week 16 DAS28 as a covariate), and descriptive parameters for secondary endpoints, with an intention to treat approach. Safety cumulative incidences were estimated using Kaplan-Meier methods. (ClinicalTrials.gov Identifier: NCT01399697.)
Results Total of 263 RA patients with previous inadequate response to MTX (DAS28 5.6±1.2) were treated with TCZ + MTX. All patients achieving a DAS ≤3.2 at 16 weeks (n=165) were randomized to TCZ + MTX (n=83) or TCZ + placebo (n=82). DAS28 from week 16 to week 28 did not change significantly in both groups (from 1.77 to 1.87 with TCZ + MTX, and from 1.96 to 1.98 with TCZ + placebo, ANOVA, p=0.89). Remission rates (DAS28<2.6) at week 28 were similar in both groups TCZ + MTX and TCZ alone (82.3% and 75.9% respectively, p=0.33), and similar to those at week 16 in both groups (84.0% and 72.0% respectively). No statistically significant differences were observed in any of the secondary variables. The incidence of adverse events after week 16 was similar in both groups.
Conclusions Switching from TCZ + MTX to TCZ alone in patients with low disease activity is not followed by any clinical change, either in the efficacy or the safety profiles. Therefore, the monotherapy could be an efficacious and safe alternative for those patients not suitable for a combination therapy.
Disclosure of Interest None declared