Table 2.
Efficacy endpoints for patients with moderate-to-severe RA randomised to MSB11456 or EU-approved tocilizumab—main estimand analyses
| Parameter | MSB11456 (N=302) | EU-approved tocilizumab (N=302) | Difference MSB11456—EU-approved tocilizumab (N=604) |
| LS mean (SE) change from baseline to week 24 in DAS28-ESR | −3.53 (0.11) | −3.54 (0.11) | |
| LS mean difference (90% CI) (95% CI)* | 0.01 (−0.16 to 0.18) (−0.19 to 0.22) | ||
| ACR20 response rate at week 24, n (%) | 244 (80.8) | 256 (84.8) | |
| Difference (95% CI)† | −3.94 (−9.97 to 2.11) | ||
| LS mean (SE) change from baseline to week 12 in DAS28-ESR | −3.13 (0.10) | −3.12 (0.10) | |
| LS mean difference (95% CI) | −0.01 (−0.21 to 0.19) | ||
| LS mean (SE) change from baseline to week 24 in DAS28-CRP | −2.78 (0.07) | −2.83 (0.07) | |
| LS mean difference (95% CI) | 0.05 (−0.12 to 0.22) | ||
| ACR50 response rate at week 24, n (%) | 183 (60.6) | 188 (62.3) | |
| Difference (95% CI) | −1.59 (−9.29 to 6.15) | ||
| ACR70 response rate at week 24, n (%) | 118 (39.1) | 116 (38.4) | |
| Difference (95% CI) | 0.73 (−7.01 to 8.45) |
*Change from baseline to week 24 in DAS28-ESR was analysed using analysis of covariance with treatment group and previous exposure to biological treatment for RA (yes/no) as fixed effects and baseline DAS28-ESR as a covariate. For the FDA: MSB11456 was considered equivalent to EU-approved tocilizumab if the 90% CI was included in the equivalence interval of (−0.6 to 0.5). For the EMA: MSB11456 was considered equivalent to EU-approved tocilizumab if the 95% CI was included in the equivalence interval of (−0.6 to 0.6).
†The stratified difference in ACR20 response rate at week 24 was analysed using a 95% stratified Newcombe CI adjusting for the stratification factor previous exposure to biological treatment for RA; the equivalence margin was (−15%, 15%).
ACR20/50/70, 20%/50%/70% improvement in American College of Rheumatology core set measures; DAS28-CRP, Disease Activity Score-28 C reactive protein; EMA, European Medicines Agency; ESR, erythrocyte sedimentation rate; EU, European Union; FDA, Food and Drug Administration; LS, least squares; RA, rheumatoid arthritis.