The double blind phase III study used ACR20 (An improvement of 20% in rheumatoid arthritis signs and symptoms according to American College of Rheumatology criteria) at 24 weeks as a primary endpoint with additional endpoints measured according to a variety of scales (ACR50, ACR70, EULAR response, ACR-N AUC). Safety was assessed by adverse events and clinical laboratory results.
Of 127 patients enrolled, 125 patients received at least one dose of the study drugs (61 patients in the tocilizumab group vs. 64 patients in the methotrexate group). Baseline characteristics were similar between groups with a mean age of 50.8 years and mean disease duration of 8.7 years.
At 24 weeks, ACR20 response rate was statistically significantly higher in the tocilizumab group than in the methotrexate group (80.3% vs. 25.0%, p<0.001, LOCF). Patients in the tocilizumab group also showed significantly higher ACR50 and ACR 70 than patients treated by methotrexate (49.2% vs. 10.9%, p<0.001 and 29.5% vs. 6.3%, p<0.001, respectively). Consistent improvements were observed in the EULAR response criteria as well as ACR-N AUC.
Tocilizumab was very well-tolerated as shown by the percentage of patients who continued the therapy as planned: 7 pts and 31 pts were withdrawn in the tocilizumab and methotrexate groups, respectively.
With regards to adverse events within the study, the most common reported was nasopharyngitis in both groups (tocilizumab 18.0% and methotrexate 10.9%). Withdrawals due to adverse events (tocilizumab n=2, methotrexate n=3) as well as the occurrence of serious adverse events (tocilizumab n=4, methotrexate n=3) were similar between groups. Increases in lipids were noted in the tocilizumab group but became stable at around upper limit of normal. The frequency of liver function test abnormalities as adverse events was higher in the methotrexate group (ALT increase 10.9%) but most cases were grade 1. No tuberculosis was reported.
"In this double blind study tocilizumab in monotherapy for 24 weeks significantly improved signs and symptoms and was well tolerated in patients who had active rheumatoid arthritis despite receiving methotrexate", explained N. Nishimoto, study lead and professor at the Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Suita-City. "These data support the use of tocilizumab in the treatment of rheumatoid arthritis patients with inadequate response to methotrexate." he concluded.
Table of results:
DAS28 changes and EULAR response* at 24 weeks
¬ Treatment Baseline DAS28
(Mean) DAS28 changes
at 24 wks (Mean) Good
8 mg/kg††† 6.073††-3.295†† 65.5†† 96.6†† 43.1
8 mg/week††6.183†† -1.069†† 3.2†† 39.7†† 1.6
p-value Not Significant p<0.001 p<0.001 p<0.001 p<0.001
* LOCF, **DAS28<2.6
For further information on this study, or to request an interview with the study lead, please do not hesitate to contact the EULAR congress press office on:
Jim Baxter - Onsite tel: +44 (0) 7900 605652
Jo Spadaccino - Onsite tel: +44 (0) 7773 271930
Mia Gannedahl - Office tel: +44 (0) 20 7331 2325
Abstract number: OP0020
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
Published on PsychCentral.com. All rights reserved.