TABLE 9.
Changes in blood cell subsets during treatment
| Treatment groupa | Group differenceb | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| PLACEBO (n=10) | RAPA (n=7) | |||||||||
| Pre | Post | P value | Difference (95%CI) | Pre | Post | P value | Difference (95%CI) | P value | Difference (95%CI) | |
| PANEL 1 | ||||||||||
| B cells (CD20+) | 2.72 ± 1.58 | 2.24 ± 1.64 | 0.002 | −0.48 [−0.73, −0.23] | 3.2 ± 1.42 | 2.43 ± 1.54 | 0.13 | −0.77 [−1.83, 0.29] | 0.54 | −0.29 [−1.36, 0.77] |
| T cells (CD3+) | 16.3 ± 7.55 | 11.24 ± 4.45 | 0.02 | −5.06 [−9.14, −0.98] | 15.2 ± 7.7 | 8.33 ± 3.82 | 0.032 | −6.87 [−12.91, −0.83] | 0.56 | −1.81 [−8.48, 4.86] |
| monocyte (CD11b+) | 6.07 ± 2.92 | 4.35 ± 1.62 | 0.08 | −1.72 [−3.68, 0.24] | 10.59 ± 7.52 | 7.04 ± 2.54 | 0.14 | −3.54 [−8.7, 1.62] | 0.45 | −1.82 [−7.08, 3.43] |
| P1 subset (see Supplemental Figure 2) | 75.11 ± 9.77 | 75.06 ± 10.27 | 0.99 | −0.05 [−7.03, 6.93] | 76.47 ± 9 | 76.2 ± 8.25 | 0.93 | −0.27 [−7.14, 6.6] | 0.96 | −0.22 [−9.12, 8.68] |
| P2 subset (see Supplemental Figure 2) | 16.04 ± 9.35 | 14.79 ± 7.44 | 0.62 | −1.25 [−6.83, 4.33] | 17.97 ± 7.88 | 14.5 ± 6.91 | 0.21 | −3.47 [−9.49, 2.55] | 0.53 | −2.22 [−9.67, 5.23] |
| P3 subset (see Supplemental Figure 2) | 6 ± 2.09 | 7.1 ± 3.47 | 0.43 | 1.1 [−1.9, 4.1] | 3.13 ± 1.94 | 6.31 ± 2.33 | 0.005 | 3.19 [1.37, 5] | 0.19 | 2.09 [−1.18, 5.35] |
| PANEL 2 | ||||||||||
| TH cells (CD4+ CD3+) | 72.1 ± 15.26 | 71.5 ± 14.62 | 0.71 | −0.6 [−4.19, 2.99] | 76.49 ± 10.77 | 74.11 ± 8.61 | 0.21 | −2.37 [−6.5, 1.76] | 0.46 | −1.77 [−6.74, 3.2] |
| TC cells (CD8+ CD3+) | 19.91 ± 5.28 | 20.6 ± 6.82 | 0.59 | 0.69 [−2.09, 3.47] | 19.74 ± 9.53 | 21.27 ± 8.02 | 0.33 | 1.53 [−2, 5.06] | 0.67 | 0.84 [−3.25, 4.93] |
| dp: CD4+ CD8+ CD3+ | 5.65 ± 15.06 | 5.46 ± 13.36 | 0.77 | −0.19 [−1.61, 1.23] | 1.36 ± 1.42 | 1.84 ± 1.64 | 0.2 | 0.49 [−0.35, 1.32] | 0.36 | 0.68 [−0.86, 2.21] |
| dn: CD4−CD8− CD3+ | 2 ± 1.08 | 1.87 ± 0.89 | 0.79 | −0.13 [−1.21, 0.95] | 1.93 ± 0.87 | 2.46 ± 1.31 | 0.23 | 0.53 [−0.45, 1.5] | 0.31 | 0.66 [−0.67, 1.98] |
| TREGS Foxp3+ CD4+ | 9.93 ± 3.28 | 11.2 ± 1.85 | 0.28 | 1.27 [−1.23, 3.77] | 9.03 ± 2.24 | 12.59 ± 3.05 | 0.008 | 3.56 [1.35, 5.76] | 0.13 | 2.29 [−0.75, 5.33] |
| PANEL 3 | ||||||||||
| T cells (CD3+) | 11.45 ± 5.43 | 9.69 ± 5.32 | 0.22 | −1.76 [−4.77, 1.25] | 10.34 ± 5.72 | 5.93 ± 3.01 | 0.12 | −4.41 [−10.39, 1.56] | 0.36 | −2.65 [−8.89, 3.58] |
| CD4+ T cell subset | 70.44 ± 15.06 | 71.05 ± 15.57 | 0.73 | 0.61 [−3.3, 4.52] | 72.87 ± 13.67 | 74.3 ± 8.82 | 0.67 | 1.43 [−6.3, 9.16] | 0.82 | 0.82 [−7.26, 8.89] |
| Naïve CD4+ (CD45RA+RO−) | 32.85 ± 16.24 | 33.91 ± 19.19 | 0.65 | 1.06 [−4.01, 6.13] | 34.8 ± 20.61 | 36.29 ± 14.33 | 0.81 | 1.49 [−13.19, 16.17] | 0.95 | 0.43 [−14.45, 15.3] |
| Naïve CD4+ expressing PD1 | 0.85 ± 0.66 | 2.4 ± 4.65 | 0.33 | 1.55 [−1.87, 4.97] | 1.79 ± 2.08 | 1.39 ± 1.12 | 0.36 | −0.4 [−1.39, 0.59] | 0.24 | −1.95 [−5.42, 1.52] |
| Memory CD4+ (CD45RA−RO+) | 44.43 ± 16.01 | 37.67 ± 18.05 | 0.016 | −6.76 [−11.95, −1.57] | 50.2 ± 24.21 | 44.87 ± 18.48 | 0.32 | −5.33 [−17.38, 6.73] | 0.8 | 1.43 [−10.95, 13.81] |
| Memory CD4+ expressing PD1 | 21.49 ± 14.37 | 31.54 ± 9.04 | 0.047 | 10.05 [0.18, 19.92] | 22.36 ± 8.38 | 29.66 ± 8.19 | 0.11 | 7.3 [−2.38, 16.98] | 0.65 | −2.75 [−15.31, 9.81] |
| CD8+ T cell subset | 20.95 ± 5.24 | 19.72 ± 5.56 | 0.34 | −1.23 [−3.97, 1.51] | 22.57 ± 12.11 | 21.27 ± 8.31 | 0.62 | −1.3 [−7.39, 4.79] | 0.98 | −0.07 [−6.35, 6.21] |
| Naïve CD8+ T cells (CD45RA+RO−) | 43.72 ± 20.08 | 39.49 ± 21.43 | 0.06 | −4.23 [−8.63, 0.17] | 37 ± 15.43 | 36.4 ± 13.13 | 0.88 | −0.6 [−9.85, 8.65] | 0.41 | 3.63 [−5.96, 13.22] |
| Naïve CD8+ expressing CD28 | 12.95 ± 10.31 | 9.34 ± 11.58 | 0.41 | −3.61 [−13.15, 5.93] | 15.97 ± 13.62 | 18.21 ± 12.84 | 0.67 | 2.24 [−9.91, 14.4] | 0.39 | 5.85 [−8.2, 19.91] |
| Naïve CD8+ expressing PD1 | 8.34 ± 7.86 | 12.8 ± 7.69 | 0.07 | 4.46 [−0.51, 9.43] | 10.91 ± 12.18 | 17.1 ± 12.2 | 0.016 | 6.19 [1.64, 10.73] | 0.56 | 1.73 [−4.41, 7.86] |
| Memory CD8+ T cells (CD45RA−RO+) | 24.04 ± 10.34 | 23.39 ± 12.62 | 0.75 | −0.65 [−5.19, 3.89] | 28.86 ± 10.67 | 26.29 ± 9.2 | 0.55 | −2.57 [−12.44, 7.3] | 0.68 | −1.92 [−12.12, 8.27] |
| Memory CD8+ expressing CD28 | 71.71 ± 16.8 | 78.41 ± 11.32 | 0.29 | 6.7 [−6.92, 20.32] | 76.91 ± 12.45 | 83.17 ± 8.19 | 0.31 | 6.26 [−7.45, 19.96] | 0.96 | −0.44 [−18, 17.11] |
| Memory CD8+ expressing PD1 | 42.61 ± 20.21 | 53.67 ± 18.1 | 0.07 | 11.06 [−0.9, 23.02] | 46.54 ± 19.99 | 53.5 ± 17.24 | 0.38 | 6.96 [−10.99, 24.91] | 0.66 | −4.1 [−23.85, 15.65] |
| Transitional CD8+ (CD45RA+RO+) | 31.08 ± 14.36 | 36.6 ± 16.37 | 0.11 | 5.52 [−1.62, 12.66] | 32.99 ± 11.87 | 36.5 ± 12.57 | 0.56 | 3.51 [−10.28, 17.3] | 0.76 | −2.01 [−16.46, 12.44] |
| Transitional CD8+ expressing CD28 | 49.61 ± 25.99 | 59.74 ± 16.99 | 0.1 | 10.13 [−2.53, 22.79] | 64.83 ± 15.97 | 71.79 ± 15.99 | 0.36 | 6.96 [−10.13, 24.05] | 0.73 | −3.17 [−22.56, 16.21] |
| Transitional CD8+ expressing PD1 | 23.55 ± 24.93 | 40.51 ± 17.2 | 0.01 | 16.96 [5.07, 28.85] | 35.06 ± 13.47 | 45.93 ± 15.04 | 0.1 | 10.87 [−2.98, 24.73] | 0.44 | −6.09 [−22.67, 10.49] |
| Ratio of CD4+/CD8+ | 3.59 ± 1.45 | 3.93 ± 1.7 | 0.27 | 0.34 [−0.31, 0.99] | 5.38 ± 5.72 | 4.47 ± 3.29 | 0.4 | −0.92 [−3.4, 1.57] | 0.27 | −1.25 [−3.75, 1.24] |
a
. Changes in PBMC populations were assessed by flow cytometry for the subjects in the Phase 2 study. The differences between pre-treatment values and those seen at 6 weeks of treatment are shown for both the RAPA and placebo groups. “Differences” due to treatment were assessed by paired t-tests to identify any statistically significant changes in either group and the p-values are shown. The direction of the change is indicated in the “Difference column” where a positive number indicates a higher mean value after treatment and a negative value reflects a decrease in that cell population. The 95% confidence interval is shown in brackets.
b
. To determine whether there was a difference in the RAPA vs. the placebo group, the mean “difference” values were compared using a Welch’s t-test. The resulting p-values are shown; the mean differences and 95% confidence interval are shown.