Background/Purpose:

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 (methotrexate).

Methods:

The study was designed as a phase III, randomized, double-blind, parallel-group (1:1), multicentre clinical trial. During the first part of the study all patients with active RA and previous inadequate response to MTX were treated with combined TCZ 8 mg/Kg i.v. every 4 weeks + oral MTX for 16 weeks and then all which showed a low activity (DAS28 ≤ 3.2) were randomized (1:1) to either TCZ + MTX or TCZ + placebo with a follow-up of 28 weeks. 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. 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:

The first part of the study included 263 RA patients with previous inadequate response to MTX (DAS28 5.6 ± 1.2). Of those, 165 patients showed low disease activity (LDA) at 16 weeks (DAS ≤ 3.2) and 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 monotherapy (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. Hypertransaminasemia was the most frequently adverse event reported in both groups (9.6% and 4.9%, respectively)

Conclusion:

Switching from TCZ + MTX to TCZ monotherapy in patients with LDA is not followed by any clinical change, either in the efficacy or the safety profiles. Therefore, the TCZ monotherapy could be an efficacious and safe alternative for those patients not suitable to receive MTX in combination.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/switch-from-tocilizumab-methotrexate-to-tocilizumab-monotherapy-maintenance-of-response-in-patients-with-rheumatoid-arthritis-at-low-disease-activity/