Table 3 Mediation analysis of the effects of clinical responses on changes in FACIT-Fatigue scores through week 24
Clinical response | Effect | Guselkumab 100 mg Q4W vs placebo Estimate (95% CI) | Guselkumab 100 mg Q8W vs placebo Estimate (95% CI) | |
|---|---|---|---|---|
ACR20 | DISCOVER-1 | NDE | 2.60 (0.58, 4.46)* | 0.36 (−1.72, 2.40) |
NIE | 1.20 (0.27, 2.31)* | 2.75 (1.38, 4.32)* | ||
Total effect | 3.79 (1.94, 5.44)* | 3.12 (1.05, 5.15)* | ||
% Indirect (mediated) effect | 31.5% | 88.3% | ||
% Direct effect | 68.5% | 11.7% | ||
DISCOVER-2 | NDE | 2.49 (0.96, 4.14)* | 1.44 (−0.11, 2.97) | |
NIE | 1.09 (0.42, 1.95)* | 2.53 (1.62, 3.64)* | ||
Total effect | 3.58 (2.10, 5.05)* | 3.97 (2.41, 5.53)* | ||
% Indirect (mediated) effect | 30.3% | 63.7% | ||
% Direct effect | 69.7% | 36.3% | ||
MDA | DISCOVER-1 | NDE | 2.84 (0.97, 4.71)* | 2.34 (0.24, 4.45)* |
NIE | 0.78 (0.16, 1.40)* | 0.74 (0.09, 1.39)* | ||
Total effect | 3.62 (1.76, 5.49)* | 3.08 (0.99, 5.18)* | ||
% Indirect (mediated) effect | 21.6% | 24.0% | ||
% Direct effect | 78.4% | 76.0% | ||
DISCOVER-2 | NDE | 3.13 (1.63, 4.63)* | 2.67 (1.09, 4.26)* | |
NIE | 0.28 (0.07, 0.50)* | 1.06 (0.49, 1.64)* | ||
Total effect | 3.41 (1.96, 4.86)* | 3.74 (2.13, 5.34)* | ||
% Indirect (mediated) effect | 8.3% | 28.5% | ||
% Direct effect | 91.7% | 71.5% | ||
Change in CRP | DISCOVER-1 | NDE | 3.19 (1.37, 5.02)* | 2.51 (0.52, 4.50)* |
NIE | 0.42 (−0.03, 0.86) | 0.56 (−0.10, 1.22) | ||
Total effect | 3.61 (1.74, 5.47)* | 3.06 (0.95, 5.17)* | ||
% Indirect (mediated) effect | 11.6% | 18.2% | ||
% Direct effect | 88.4% | 81.8% | ||
DISCOVER-2 | NDE | 2.88 (1.36, 4.41)* | 3.20 (1.62, 4.79)* | |
NIE | 0.49 (−0.07, 1.05) | 0.60 (0.05, 1.14)* | ||
Total effect | 3.37 (1.93, 4.81)* | 3.80 (2.24, 5.36)* | ||
% Indirect (mediated) effect | 14.5% | 15.7% | ||
% Direct effect | 85.5% | 84.3% |