Key ACTEMRA/RoACTEMRA publication summaries
IL-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs (DMARDs): the tocilizumab in combination with traditional DMARD therapy study
Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA, Alecock E, Woodworth T, Gomez-Reino JJ.
Arthritis Rheum 2008; 58:2968–2980.
The TOWARD study was a 24-week, double-blind, 2:1-randomised, placebo-controlled Phase III study designed to evaluate the efficacy and safety of tocilizumab (TCZ) in combination with a range of DMARDs in patients with moderate to severe RA who had had an inadequate response to DMARDs (N=1,220).
Median disease duration in the TCZ + DMARD and placebo + DMARD arms was 7.0 and 6.8 years, respectively. Seventy-six percent of patients received concomitant methotrexate, 21% chloroquine/hydroxylchloroquine, 13% sulphasalazine, 12% leflunomide and 2% azathioprine; 23% of patients received a combination of two or more DMARDs.
Key study results are summarised below.
- At 24 weeks, the proportion of patients achieving an ACR20 response was significantly greater in the TCZ group than the control group (61% vs. 25%; p<0.0001). Secondary efficacy endpoints also showed superiority of TCZ + DMARD over placebo + DMARD.
- A separation in ACR20 and ACR50 responses in the TCZ and control groups was apparent as early as Week 2, and by Week 4 for the ACR70 response, indicating a rapid onset of action with TCZ.
- This was also demonstrated by normalisation of C-reactive protein levels with the first dose of TCZ and increased haemoglobin levels.
- By Week 24, DAS28 remission (<2.6) was achieved by 30% of patients in the TCZ group vs. 3% of patients receiving placebo.
- The overall incidence of adverse events (AEs) was higher in the TCZ group compared with the control group (73% vs. 61%, respectively), although AEs that led to withdrawal were infrequent (4% vs. 2%). The most common serious AEs were serious infections (2.7% vs. 1.9%).
The TOWARD study therefore showed that treatment with the combination of TCZ + DMARDs has a high likelihood of inducing a clinically important benefit, in terms of ACR50 and ACR70 response rates and DAS28 remission, and is well tolerated.