Table 2.
Efficacy through 9 years in alemtuzumab-treated patients with HAD according to different definitions (CARE-MS I and II pooled)
| Parameter | Alemtuzumab-treated patients | |||
|---|---|---|---|---|
| Primary HAD definition (N = 208)a | Alternative HAD definition 1 (N = 438)b | Alternative HAD definition 2 (N = 174)c | Alternative HAD definition 3 (N = 180)d | |
| Proportion of the overall pooled CARE-MS alemtuzumab-treated population satisfying each HAD definition (%) | 26 | 54 | 21 | 22 |
| Proportion of patients who received neither additional alemtuzumab nor another DMT in the extensions (%) | 50 | 50 | 41 | 40 |
| Proportion of patients who received additional alemtuzumab (%) | 48g | 48h | 55i | 55j |
| 3 total courses, % | 26g | 25h | 26i | 29j |
| 4 total courses, % | 14g | 15h | 18i | 16j |
| 5 total courses, % | 5g | 4h | 8i | 7j |
| 6 total courses, % | 2g | 2h | 1i | 2j |
| 7 total courses, % | 0.5g | 0.5h | 2i | 1j |
| 8 total courses, % | 0.5g | 0.2h | 0 | 0.6j |
| ARR over Y3–9 (95% CI) | 0.16 (0.13–0.19) | 0.18 (0.16–0.21) | 0.17 (0.14–0.21) | 0.17 (0.14–0.21) |
| Proportion of patients relapse-free over Y3–9 (%) (95% CI)e | 53 (45–61) | 51 (46–57) | 47 (39–56) | 47 (38–56) |
| Mean EDSS score change over Y0–9 (95% CI) | 0.17 (− 0.06 to 0.39) | 0.19 (0.04–0.34) | 0.28 (0.01–0.55) | 0.33 (0.03–0.63) |
| Proportion of patients with improved or stable EDSS over Y0–9f (%) | 72 (improved 25; stable 47) | 71 (improved 22; stable 50) | 70 (improved 22; stable 48) | 66 (improved 22; stable 44) |
| Proportion of patients free of 6-month CDW over Y0–9 (%) (95% CI) | 62 (54–69) | 64 (59–69) | 59 (51–66) | 56 (48–64) |
| Proportion of patients with 6-month CDI over Y0–9 (%) (95% CI) | 50 (41–59) | 46 (40–52) | 49 (40–59) | 51 (42–60) |
| Proportion of patients free of MRI disease activity in Y9 (%) (95% CI)e | 69 (61–77) | 69 (63–74) | 57 (48–66) | 69 (60–78) |
| Proportion of patients with NEDA in Y9 (%) (95% CI)e | 62 (54–70) | 61 (56–67) | 53 (44–63) | 59 (49–69) |
| Proportion of patients with cumulative NEDA over Y3–9 (%) (95% CI)e | 18 (11–25) | 20 (15–26) | 9 (3–15) | 10 (3–17) |
| Median BPF change over Y0–9 (%) (95% CI) | − 2.15 (− 2.65 to − 1.78) | − 1.77 (− 2.02 to − 1.55) | − 2.40 (− 2.80 to − 2.05) | − 1.80 (− 2.20 to − 1.35) |
Improved EDSS score: ≥ 1.0-point decrease from core study baseline; stable EDSS score: ≤ 0.5-point change in either direction from core study baseline
CDW: ≥ 1.0-point EDSS increase from core study baseline (or ≥ 1.5 points if baseline EDSS = 0) confirmed over 6 months
CDI: ≥ 1.0-point EDSS decrease from core study baseline confirmed over 6 months (assessed only in patients with baseline EDSS score ≥ 2.0)
Freedom from MRI disease activity: no new Gd-enhancing T1 lesions on current MRI and no new/enlarging T2 hyperintense lesions since last MRI
NEDA: absence of relapse, 6-month CDW, and MRI disease activity
ARR annualized relapse rate, BPF brain parenchymal fraction, CARE-MS Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis, CDI confirmed disability improvement, CDW confirmed disability worsening, CI confidence interval, DMT disease-modifying therapy, EDSS Expanded Disability Status Scale, Gd gadolinium, HAD highly active disease, MRI magnetic resonance imaging, NEDA no evidence of disease activity, Y year
aPrimary HAD definition: ≥ 2 relapses in the year prior to baseline and ≥ 1 Gd-enhancing lesion at baseline (number of evaluable patients ranged from 112 to 208)
bAlternative HAD definition 1: ≥ 2 relapses in year prior, independent of Gd-enhancing lesion count at baseline (number of evaluable patients ranged from 211 to 438)
cAlternative HAD definition 2: ≥ 1 relapse in year prior and ≥ 3 Gd-enhancing lesions at baseline (number of evaluable patients ranged from 98 to 174)
dAlternative HAD definition 3: ≥ 1 relapse and ≥ 1 Gd-enhancing lesion in the year prior to baseline while on therapy with another DMT (number of evaluable patients ranged from 79 to 180)
eCIs were calculated using the Wald method
fValues may not sum appropriately due to rounding
gN = 191
hN = 401
iN = 159
jN = 161