End point | Week 9 | Week 12 | Week 16 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Tabalumab | Tabalumab | Tabalumab | ||||||||||
Placebo (N=35) | 30 mg (N=35) | 80 mg (N=28) | p Value | Placebo (N=35) | 30 mg (N=35) | 80 mg (N=28) | p Value | Placebo (N=35) | 30 mg (N=35) | 80 mg (N=28) | p Value | |
ACR20*† | ||||||||||||
n/N (%) | 6/35 (17.1) | 14/35 (40.0) | 12/28 (42.9) | 0.012 | 9/35 (25.7) | 14/35 (40.0) | 13/28 (46.4) | 0.070 | 6/35 (17.1) | 9/35 (25.7) | 8/28 (28.6) | 0.198 |
ACR50*† | ||||||||||||
n/N (%) | 0/35 (0.0) | 9/35 (25.7) | 5/28 (17.9) | 0.001 | 1/35 (2.9) | 6/35 (17.1) | 3/28 (10.7) | 0.068 | 1/35 (2.9) | 4/35 (11.4) | 4/28 (14.3) | 0.101 |
ACR70*† | ||||||||||||
n/N (%) | 0/35 (0.0) | 3/35 (8.6) | 3/28 (10.7) | 0.065 | 0/35 (0.0) | 3/35 (8.6) | 2/28 (7.1) | 0.104 | 0/35 (0.0) | 1/35 (2.9) | 1/28 (3.6) | 0.411 |
DAS28-CRP<3.2* | ||||||||||||
n/N (%) | 1/35 (3.2) | 6/35 (18.8) | 7/28 (26.9) | 0.014 | 1/35 (3.3) | 5/35 (16.7) | 4/28 (16.7) | 0.066 | 0/35 (0.0) | 5/35 (14.3) | 6/28 (21.4) | 0.005‡ |
DAS28-CRP<2.6* | ||||||||||||
n/N (%) | 1/35 (3.2) | 3/35 (9.4) | 5/28 (19.2) | 0.110 | 0/35 (0.0) | 3/35 (10.0) | 3/28 (12.5) | 0.064 | 0/35 (0.0) | 3/35 (8.6) | 2/28 (7.1) | 0.104‡ |
DAS28-CRP§ | ||||||||||||
N | 31 | 32 | 25 | 30 | 30 | 23 | 34 | 35 | 26 | |||
Mean change | −0.50± | −1.42± | −1.59± | −0.76± | −1.50± | −1.40± | −0.61± | −0.91± | −1.29± | |||
SD | 1.06 | 1.22 | 1.25 | <0.001 | 0.91 | 1.10 | 1.16 | <0.001 | 1.04 | 1.14 | 0.93 | 0.016‡ |
CRP¶ | ||||||||||||
N | 31 | 32 | 26 | 0.038 | 30 | 30 | 24 | 35 | 35 | 27 | ||
Median % change | −8.07 | −32.98 | −23.69 | −29.78 | −15.97 | −22.55 | 0.996 | −29.15 | −5.72 | −20.19 | 0.650‡ | |
EULAR response(good+moderate)* | ||||||||||||
n/N (%) | 9/31 (29.0) | 22/32 (68.8) | 17/25 (68.0) | <0.001 | 15/30 (50.0) | 21/30 (70.0) | 15/23 (65.2) | 0.085 | 15/34 (44.1) | 13/35 (37.1) | 17/26 (65.4) | 0.398‡ |
Regional subanalysis | Week 9 (Observed)** | Week 12 (Observed)** | Week 16 (NRI) | |||||||||
ACR20 (US) | ||||||||||||
n/N (%) | 3/12 (25.0) | 6/16 (37.5) | 5/14 (35.7) | NC | 6/12 (50.0) | 4/16 (25.0) | 3/12 (25.0) | NC | 3/14 (21.4) | 5/18 (27.8) | 2/16 (12.5) | NC |
ACR20 (OUS) | ||||||||||||
n/N (%) | 3/19 (15.8) | 8/16 (50.0) | 7/12 (58.3) | NC | 3/19 (15.8) | 10/15 (66.7) | 10/12 (83.3) | NC | 3/21 (14.3) | 4/17 (23.5) | 6/12 (50.0) | NC |
ACR50 (US) | ||||||||||||
n/N (%) | 0/12 (0.0) | 4/16 (25.0) | 2/14 (14.3) | NC | 1/12 (8.3) | 2/16 (12.5) | 1/12 (8.3) | NC | 1/14 (7.1) | 1/18 (5.6) | 1/16 (6.3) | NC |
ACR50 (OUS) | ||||||||||||
n/N (%) | 0/19 (0.0) | 5/16 (31.3) | 3/12 (25.0) | NC | 0/19 (0.0) | 4/15 (26.7) | 2/12 (16.7) | NC | 0/21 (0.0) | 3/17 (17.6) | 3/12 (25.0) | NC |
OUS countries were Argentina (n=12), Austria (n=7), Belgium (n=1), Brazil (n=15), Canada (n=4), Germany (n=4), Poland (n=6) and Puerto Rico (n=1).
US patients (n=48).
Values are n/N (%) unless otherwise noted. For the NRI, patients who discontinued from the study prior to week 16 were imputed as non-responders.
*One-sided Fisher exact test of tabalumab (the two dose groups combined) versus placebo.
†Imputed by NRI.
‡Imputed by LOCF (last-observation-carried-forward).
§One-sided ANCOVA test of tabalumab (the two dose groups combined) versus placebo with treatment and baseline value in the model.
¶Two-sided ranked ANCOVA with treatment and the standardised rank baseline value in the model based on mean percentage change in tabalumab (the two dose groups combined) versus placebo.
**For regional subanalysis, data at weeks 9 and 12 are observed, whereas data at the 16-week primary end point are imputed by NRI.
ACR20, proportion of patients achieving a 20% improvement in American College of Rheumatology criteria (ACR); ACR50, proportion of patients achieving a 50% improvement in ACR criteria; ACR70, proportion of patients achieving a 70% improvement in ACR criteria; CRP, C-reactive protein; DAS28, Disease Activity Score based on 28-joint count; EULAR, European League Against Rheumatism index; n, the number of responders; N, the number of patients assessed at that time point; NC, not calculated; NRI, non-responder imputation; OUS, outside of the USA; US, USA.