Table 3.
Change in HAM-D-17 Total Score from Baseline to Treatment Week 8 for Subjects Treated with EPA vs. Placebo (PLA) with High Inflammation on Individual Biomarkers and Pairs of Biomarkers at Baseline1
| High Inflammatory Status on | Change from Baseline to Treatment Week 8 | Standardized Treatment Effect Size at Treatment Week 8 | EPA vs. PLA at Treatment Week 8 | Significance of Treatment-by-Time Interaction | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EPA | PLA | |||||||||||||
| Individual Biomarkers: | LS-Mean | (seM) | [N] | LS-Mean | (seM) | [N] | ES2 | (95% CI) | t | df3 | P | F | df | P |
| hs-CRP | −12.44 | (1.54) | [15] | −7.99 | (1.86) | [8] | −0.78 | (−1.67 to +0.11) | −1.84 | 42.8 | 0.073 | 1.70 | 1, 90.6 | 0.195 |
| IL-6 | −9.78 | (1.44) | [15] | −7.84 | (1.40) | [12] | −0.37 | (−1.13 to +0.40) | −0.96 | 54.0 | 0.341 | 0.42 | 1, 104 | 0.518 |
| IL-1ra | −12.14 | (1.16) | [23] | −9.63 | (1.61) | [11] | −0.46 | (−1.18 to +0.27) | −1.26 | 72.1 | 0.213 | 0.31 | 1, 127 | 0.580 |
| Leptin | −8.99 | (1.29) | [19] | −5.61 | (1.46) | [13] | −0.62 | (−1.34 to +0.11) | −1.72 | 63.3 | 0.090 | 1.01 | 1, 101 | 0.318 |
| Adiponectin | −11.69 | (1.10) | [21] | −8.81 | (1.06) | [21] | −0.58 | (−1.20 to +0.04) | −1.88 | 94.9 | 0.063 | 1.69 | 1, 159 | 0.195 |
|
| ||||||||||||||
| 10 Pairs of Biomarkers: | ||||||||||||||
| hs-CRP + IL-6 | −12.00 | (1.68) | [10] | −4.44 | (2.30) | [4] | −1.47 | (−2.77 to −0.17) | −2.65 | 22.2 | 0.015 | 4.13 | 1, 51.9 | 0.047 |
| hs-CRP + IL-1ra | −12.74 | (1.60) | [13] | −7.05 | (3.66) | [2] | −0.99 | (−2.53 to +0.54) | −1.42 | 25.1 | 0.167 | 1.18 | 1, 54.2 | 0.281 |
| hs-CRP + Leptin | −10.56 | (1.91) | [12] | −6.30 | (2.52) | [5] | −0.67 | (−1.74 to +0.40) | −1.34 | 28.3 | 0.192 | 0.87 | 1, 64.6 | 0.354 |
| hs-CRP + Adip. | −12.12 | (1.70) | [9] | −3.56 | (2.33) | [4] | −1.72 | (−3.10 to −0.34) | −2.92 | 18.9 | 0.009 | 3.66 | 1, 47.5 | 0.062 |
| IL-6 + IL-1ra | −11.53 | (1.98) | [9] | −7.41 | (2.21) | [6] | −0.72 | (−1.79 to +0.35) | −1.35 | 23.7 | 0.189 | 0.68 | 1, 56.1 | 0.415 |
| IL-6 + Leptin | −10.15 | (1.63) | [12] | −3.15 | (1.96) | [6] | −1.30 | (−2.38 to −0.22) | −2.74 | 32.1 | 0.010 | 3.94 | 1, 65.3 | 0.051 |
| IL-6 + Adip. | −10.27 | (1.68) | [11] | −7.46 | (2.03) | [6] | −0.52 | (−1.53 to +0.49) | −1.06 | 27.7 | 0.300 | 0.28 | 1, 65.7 | 0.597 |
| IL-1ra + Leptin | −10.22 | (1.66) | [14] | −5.80 | (2.54) | [5] | −0.73 | (−1.78 to +0.32) | −1.43 | 32.1 | 0.162 | 0.60 | 1, 71.4 | 0.441 |
| IL-1ra + Adip. | −12.99 | (1.44) | [12] | −10.44 | (2.33) | [4] | −0.52 | (−1.67 to +0.63) | −0.92 | 28.1 | 0.367 | 0.00 | 1, 52.9 | 0.954 |
| Leptin + Adip. | −9.88 | (1.27) | [15] | −5.42 | (1.86) | [6] | −0.92 | (−1.92 to +0.07) | −1.99 | 38.2 | 0.054 | 1.22 | 1, 72.1 | 0.274 |
HAM-D-17 was administered at Baseline and at 2-week intervals during the 8-week study. Mixed Model Repeated Measures (MMRM) analyses were performed on change from Baseline to Week 8 for subsets of N=155 evaluable subjects with all 5 biomarkers present at baseline, testing the significance of effects of treatment, time, and treatment-by-time interaction, covarying for the Baseline HAM-D-17 score.
By Cohen’s d effect size = (difference between LS-Mean change) / pooled sd for each pair of treatments (sd per group computed from se of LS-Mean from MMRM). A negative effect size indicates that the EPA group improved more than the PLA group (had a larger negative LS-mean change).
Degrees of freedom were determined using the Satterthwaite approximation method.