Improved physical function, pain, and health related quality of life with certolizumab pegol in japanese rheumatoid arthritis patients without methotrexate co-administration: Results from the hikari study

Background Physical function, pain and health-related quality of life (HRQoL) are important outcomes in RA. The HIKARI study examined the efficacy and safety of certolizumab pegol (CZP) in Japanese patients (pts) with active RA in whom methotrexate (MTX) could not be administered.1 Objectives To assess the impact of CZP on physical function, pain and HRQoL in the HIKARI study. Methods In this 24-week (Wk), Phase III, double-blind, randomized, placebo-controlled study, pts were randomized to CZP 200 mg (following induction dosing of 400 mg at Wks 0, 2, and 4) or placebo (PBO) every 2 Wks. Concomitant DMARDs other than MTX were permitted. Pts not achieving ACR20 at Wks 12 and 14 withdrew at Wk 16 and were eligible to enter an open-label extension, as were pts completing the study. Primary efficacy endpoint was ACR20 at Wk 12. Physical function was assessed with HAQ-DI and pain with VAS at each visit. HRQoL was evaluated with SF36 at Wks 12 and 24. ACR responses were assessed using NRI, and HAQ-DI, pain (VAS) and SF36 using LOCF. Results A total of 230 pts were randomized. Demographic and baseline characteristics were similar between CZP and PBO groups: mean RA disease duration was 5.4 and 5.8 years, mean HAQ-DI 1.05 and 1.21, and mean DAS28(ESR) 6.09 and 6.30, respectively. ACR20 response rates at Wk 12 in CZP and PBO groups were 67.2% and 14.9% (p<0.001) and at Wk 24 were 63.8% and 11.4% (p<0.001); ACR50 and ACR70 response rates were also significantly higher in the CZP group than in the PBO group at Wk 12 (ACR50: 37.9% vs 6.1%; ACR70:19.0% vs 0%) and Wk 24 (ACR50: 46.6% vs 6.1%; ACR70: 25.9% vs 0.9%). As early as Wk 1 HAQ-DI was improved in the CZP group compared to PBO; HAQ-DI change from baseline at Wk 1 was -0.30 in CZP group vs -0.01 in PBO group (p<0.001). At Wk 24 HAQ-DI change from baseline was -0.48 in CZP group vs 0.12 in PBO group (p<0.001). Pain (VAS) was also significantly improved; change from baseline at Wk 1 was -18.9 in CZP group vs -2.2 in PBO group, and at Wk 24 was -27.5 in CZP group vs -1.2 in PBO group (p<0.001 at both timepoints). CZP showed significantly greater improvements in both the physical and the mental components of the SF36 than PBO at Wks 12 and 24. Changes in physical and mental component summary scores from baseline at Wk 24 were 9.27 in CZP group vs -1.46 in PBO group (p<0.001), and 5.24 in CZP group vs -0.94 in PBO group (p<0.001). Conclusions Treatment with CZP resulted in a rapid and sustained reduction in RA signs and symptoms, and improved physical function and HRQoL in Japanese RA patients who could not be treated with MTX.