Table 1.
Influence of ever‐positive alemtuzumab‐specific binding and neutralizing antibodies on clinical activity, lymphocyte depletion and adverse events
| Time | Always Ab negative | Ever BAb positive/NAb negative | Ever BAb positive/NAb positive | |||
|---|---|---|---|---|---|---|
| n | Outcome | n | Outcome | n | Outcome | |
| (a) Influence of ever‐positive anti‐neutralizing antibodies and lymphocyte depletion | ||||||
| Mean ± SD CD4 T cells × 10 9 /l | ||||||
| Baseline | 91 | 0·96 ± 0·35 | 68 | 0·97 ± 0·40 | 210 | 0·98 ± 0·35 |
| 1 month | 85 | 0·03 ± 0·11 | 65 | 0·03 ± 0·02 | 211 | 0·05 ± 0·04 |
| 3 month | 90 | 0·09 ± 0·11 | 65 | 0·09 ± 0·04 | 213 | 0·11 ± 0·06 |
| 6 month | 90 | 0·15 ± 0·12 | 68 | 0·16 ± 0·06 | 214 | 0·17 ± 0·09 |
| 9 month | 92 | 0·22 ± 0·10 | 67 | 0·22 ± 0·10 | 214 | 0·24 ± 0·11 |
| 12 month | 91 | 0·27 ± 0·19 | 65 | 0·29 ± 0·12 | 215 | 0·28 ± 0·12 |
| 13 month | 45 | 0·06 ± 0·12 | 18 | 0·06 ± 0·04 | 300 | 0·06 ± 0·04 |
| 15 month | 50 | 0·11 ± 0·22 | 16 | 0·10 ± 0·04 | 291 | 0·11 ± 0·08 |
| 18 month | 51 | 0·17 ± 0·14 | 18 | 0·16 ± 0·08 | 296 | 0·18 ± 0·09 |
| 21 month | 49 | 0·23 ± 0·15 | 18 | 0·23 ± 0·12 | 294 | 0·26 ± 0·12 |
| 24 month | 47 | 0·30 ± 0·22 | 18 | 0·28 ± 0·13 | 288 | 0·32 ± 0·17 |
| Mean ± SD CD8 T cells × 10 9 /l | ||||||
| Baseline | 91 | 0·48 ± 0·19 | 68 | 0·53 ± 0·27 | 210 | 0·50 ± 0·22 |
| 1 month | 85 | 0·05 ± 0·08 | 65 | 0·07 ± 0·09 | 211 | 0·08 ± 0·10 |
| 3 month | 90 | 0·12 ± 0·14 | 65 | 0·11 ± 0·08 | 213 | 0·13 ± 0·11 |
| 6 month | 90 | 0·16 ± 0·14 | 68 | 0·17 ± 0·13 | 214 | 0·16 ± 0·13 |
| 9 month | 92 | 0·23 ± 0·19 | 67 | 0·21 ± 0·14 | 214 | 0·22 ± 0·16 |
| 12 month | 91 | 0·26 ± 0·19 | 65 | 0·26 ± 0·18 | 215 | 0·24 ± 0·16 |
| 13 month | 45 | 0·07 ± 0·11 | 14 | 0·08 ± 0·07 | 300 | 0·06 ± 0·08 |
| 15 month | 50 | 0·11 ± 0·13 | 16 | 0·12 ± 0·09 | 291 | 0·11 ± 0·08 |
| 18 month | 51 | 0·16 ± 0·14 | 17 | 0·17 ± 0·13 | 296 | 0·16 ± 0·09 |
| 21 month | 49 | 0·19 ± 0·14 | 18 | 0·19 ± 0·10 | 294 | 0·20 ± 0·12 |
| 24 month | 47 | 0·23 ± 0·18 | 18 | 0·22 ± 0·12 | 288 | 0·24 ± 0·14 |
| Mean ± SD CD19 B cells × 10 9 /l | ||||||
| Baseline | 91 | 0·25 ± 0·14 | 68 | 0·27 ± 0·14 | 210 | 0·27 ± 0·12 |
| 1 month | 85 | 0·02 ± 0·02 | 65 | 0·03 ± 0·03 | 211 | 0·02 ± 0·01 |
| 3 month | 90 | 0·20 ± 0·13 | 65 | 0·21 ± 0·12 | 213 | 0·21 ± 0·12 |
| 6 month | 90 | 0·26 ± 0·14 | 68 | 0·28 ± 0·19 | 214 | 0·28 ± 0·17 |
| 9 month | 92 | 0·30 ± 0·17 | 67 | 0·30 ± 0·16 | 214 | 0·32 ± 0·18 |
| 12 month | 91 | 0·33 ± 0·28 | 65 | 0·33 ± 0·18 | 215 | 0·35 ± 0·18 |
| 13 month | 45 | 0·03 ± 0·03 | 14 | 0·06 ± 0·10 | 283 | 0·03 ± 0·05 |
| 15 month | 50 | 0·15 ± 0·11 | 16 | 0·19 ± 0·10 | 291 | 0·18 ± 0·11 |
| 18 month | 51 | 0·26 ± 0·18 | 17 | 0·25 ± 0·14 | 296 | 0·27 ± 0·16 |
| 21 month | 49 | 0·29 ± 0·20 | 18 | 0·28 ± 0·11 | 294 | 0·31 ± 0·17 |
| 24 month | 47 | 0·36 ± 0·22 | 18 | 0·31 ± 0·12 | 288 | 0·35 ± 0·18 |
| (b) Influence of ever‐positive anti‐neutralizing antibodies and clinical events | ||||||
| Number (annualized rates, 95% CI) of relapses | ||||||
| Overall | 49 | 13 (0·22, 0·13–0·37) | 22 | 2 (0·18, 0·03–0·97) | 305 | 67 (0·15, 0·12–0·19) |
| Cycle 1 | 92 | 15 (0·19, 0·12–0·31) | 68 | 10 (0·26, 0·12–0·52) | 216 | 31 (0·16, 0·11–0·22) |
| Cycle 2 | 51 | 7 (0·16, 0·08–0·34) | 18 | 0 | 300 | 32 (0·13, 0·09–0·18) |
| Mean ± SD overall T2‐hyperintense volume | ||||||
| Baseline | 48 | 7·47 ± 7·72 | 21 | 7·91 ± 7·28 | 302 | 7·40 ± 9·33 |
| 24 month | 48 | 6·61 ± 7·38 | 20 | 7·74 ± 7·31 | 298 | 6·56 ± 8·57 |
| (c) Influence of ever‐positive anti‐neutralizing antibodies and treatment‐related adverse events | ||||||
| Number (percentage) of people with MS with adverse event | ||||||
| Overall | 49 | 45 (91·8) | 22 | 19 (86·4) | 305 | 274 (89·8) |
| Cycle 1 | 92 | 77 (83·7) | 68 | 59 (86·8) | 216 | 187 (86·6) |
| Cycle 2 | 51 | 32 (62·7) | 18 | 9 (50) | 300 | 202 (67·3) |
| Number (percentage) of administration site reactions | ||||||
| Overall | 49 | 26 (53·1) | 22 | 13 (59·1) | 305 | 164 (53·8) |
| Cycle 1 | 92 | 36 (39·1) | 68 | 27(39·7) | 216 | 91 (42·1) |
| Cycle 2 | 51 | 12 (23·5) | 18 | 5 (27·8) | 300 | 92 (30·7) |
The presence of binding (BAb) and Binding and neutralizing antibodies (NAb) was assessed as being present or absent during each cycle of treatment of alemtuzumab. The results were extracted from tabulated data within the EMA dataset. They represent the mean and standard deviation, the number and annualized relapse rate and 95% confidence intervals. The mean and standard deviation of T2 lesions and the number of adverse events and (percentage).