Table 2.
Change in Plasma VEGF Concentrations (pg/ml) at 52 Weeks from Baseline by Treatment Assignment and Injection Status
| Observed Data | Treatment Group
Comparisons: Differences in Mean Log Change Adjusted CI and Adjusted P-value b |
|||||
|---|---|---|---|---|---|---|
| Aflibercept | Bevacizumab | Ranibizumab | Aflibercept vs Bevacizumab | Aflibercept vs Ranibizumab | Bevacizumab vs Ranibizumab | |
| VEGF concentration available at both baseline and 52-week visits, N a | 132 | 115 | 130 | |||
| Days between last injection and 52-week plasma collection, Median (Q1, Q3) | 34 (28, 68) | 35 (28, 90) | 35 (28, 101) | |||
| Within 1 month prior to 52-week plasma collection | ||||||
| No injections, N (%) | 76 (58%) | 70 (61%) | 82 (63%) | |||
| Baseline | ||||||
| Mean ± SD | 27.49 ± 13.54 | 29.97 ± 16.50 | 33.66 ± 28.22 | |||
| Median (Q1, Q3) | 24.95 (19.90, 32.60) | 27.65 (20.10, 34.80) | 26.70 (20.80, 36.80) | |||
| 52 weeks | ||||||
| Mean ± SD | 28.60 ± 17.78 | 32.44 ± 43.78 | 37.22 ± 69.32 | |||
| Median (Q1, Q3) | 24.30 (19.35, 31.70) | 23.50 (16.10, 33.60) | 26.45 (20.20, 32.30) | |||
| Change at 52 weeks | ||||||
| Mean ± SD | +1.11 ± 13.40 | +2.47 ± 42.55 | +3.55 ± 68.15 | |||
| Median (Q1, Q3) | +0.35 (−6.40, +8.60) | −1.00 (−6.50, +5.40) | +0.55 (−4.80, +3.90) | |||
| Mean ± SD (ln) c | +0.03 ± 0.44 | −0.07 ± 0.52 | −0.04 ± 0.55 | +0.07 (−0.10, +0.24) P=0.78 |
+0.00 (−0.14, +0.15) P=0.95 |
−0.06 (−0.23, +0.10) P=0.78 |
| Median (Q1, Q3) (ln) c | +0.02 (−0.27, +0.33) | −0.05 (−0.28, +0.23) | +0.03 (−0.16, +0.17) | |||
| Received injections, N (%) | 56 (42%) | 45 (39%) | 48 (37%) | |||
| Baseline | ||||||
| Mean ± SD | 28.94 ± 13.38 | 34.36 ± 31.67 | 33.14 ± 22.41 | |||
| Median (Q1, Q3) | 25.15 (19.45, 34.60) | 26.40 (18.60, 38.50) | 27.10 (19.35, 34.20) | |||
| 52 weeks | ||||||
| Mean ± SD | 23.43 ± 15.08 | 18.68 ± 10.79 | 30.93 ± 19.78 | |||
| Median (Q1, Q3) | 18.85 (12.90, 30.50) | 15.00 (11.40, 22.50) | 26.55 (18.35, 33.95) | |||
| Change at 52 weeks | ||||||
| Mean ± SD | −5.52 ± 14.14 | −15.68 ± 31.22 | −2.21 ± 21.14 | |||
| Median (Q1, Q3) | −6.90 (−12.95, +0.20) | −8.80 (−22.80, −2.70) | −0.90 (−6.50, +3.35) | |||
| Mean ± SD (ln) c | −0.28 ± 0.50 | −0.51 ± 0.63 | −0.03 ± 0.48 | +0.20 (+0.02, +0.38) P=0.03 |
−0.29 (−0.49, −0.09) P=0.003 |
−0.49 (−0.72, −0.26) P<0.001 |
| Median (Q1, Q3) (ln) c | −0.28 (−0.61, +0.02) | −0.42 (−0.89, −0.12) | −0.03 (−0.26, +0.12) | |||
| Within 2 month prior to 52-week plasma collection | ||||||
| No injections, N (%) | 43 (33%) | 42 (37%) | 50 (38%) | |||
| Baseline | ||||||
| Mean ± SD | 28.57 ± 15.53 | 29.45 ± 17.84 | 30.25 ± 16.00 | |||
| Median (Q1, Q3) | 23.20 (19.90, 34.10) | 25.35 (18.00, 32.40) | 26.35 (20.60, 37.80) | |||
| 52 weeks | ||||||
| Mean ± SD | 31.78 ± 21.14 | 28.03 ± 18.95 | 43.53 ± 88.27 | |||
| Median (Q1, Q3) | 26.30 (21.70, 35.10) | 23.50 (16.90, 32.90) | 26.50 (19.00, 30.40) | |||
| Change at 52 weeks | ||||||
| Mean ± SD | +3.21 ± 14.05 | −1.42 ± 21.61 | +13.27 ± 79.91 | |||
| Median (Q1, Q3) | +4.40 (−5.20, 10.20) | +0.65 (−4.90, +5.40) | +1.20 (−3.20, +3.80) | |||
| Mean ± SD (ln) c | +0.09 ± 0.42 | −0.06 ± 0.48 | +0.05 ± 0.54 | +0.15 (−0.09, +0.39) P=0.43 |
+0.03 (−0.16, +0.22) P=0.79 |
−0.12 (−0.33, +0.10) P=0.44 |
| Median (Q1, Q3) (ln) c | +0.15 (−0.18, +0.38) | +0.02 (−0.19, +0.21) | +0.05 (−0.13, +0.17) | |||
| Received injections, N (%) | 89 (67%) | 73 (63%) | 80 (62%) | |||
| Baseline | ||||||
| Mean ± SD | 27.88 ± 12.39 | 32.98 ± 26.37 | 35.48 ± 30.76 | |||
| Median (Q1, Q3) | 25.10 (19.80, 33.90) | 27.60 (19.20, 38.50) | 27.15 (19.95, 34.65) | |||
| 52 weeks | ||||||
| Mean ± SD | 23.81 ± 13.68 | 26.49 ± 42.13 | 29.50 ± 16.29 | |||
| Median (Q1, Q3) | 20.70 (14.60, 29.60) | 18.10 (12.60, 26.30) | 26.35 (19.90, 34.10) | |||
| Change at 52 weeks | ||||||
| Mean ± SD | −4.07 ± 13.50 | −6.48 ± 46.70 | −5.98 ± 30.58 | |||
| Median (Q1, Q3) | −4.60 (−10.60, +0.90) | −6.50 (−13.70, 0.00) | −0.65 (−7.70, +3.70) | |||
| Mean ± SD (ln) c | −0.20 ± 0.50 | −0.35 ± 0.65 | −0.09 ± 0.51 | +0.11 (−0.04, +0.25) P=0.15 |
−0.19 (−0.35, −0.03) P=0.02 |
−0.30 (−0.48, −0.12) P<0.001 |
| Median (Q1, Q3) (ln) c | −0.22 (−0.47, +0.05) | −0.29 (−0.68, 0.00) | −0.02 (−0.31, +0.13) | |||
All VEGF concentration values below 7.8 pg/ml were truncated at 7.8 pg/ml. The analyses include only participants whose samples had acceptable quality and a CV less than 20% at both baseline and 52 weeks.
The change in ln(VEGF) concentration was the difference between baseline level and follow-up level (both on natural logarithm scale), and was truncated at 3 standard deviations from the mean at [−1.97, +1.66] pg/ml.
The pairwise treatment group comparisons of the change in ln(VEGF) concentration were performed using ANCOVA, with the adjustment for baseline VEGF concentration (on natural log scale). Reported P-values have been adjusted for multiple treatment-group comparisons to account for an overall type I error rate of 0.05, and corresponding [1-(ɑ÷i)]×100% confidence intervals are reported, where i is the rank (1, 2, 3) of the Hochberg-adjusted P-value from among the descending ordered raw pairwise P-values.