TABLE 2.
Changes in clinical and magnetic resonance imaging parameters and event‐free rates over the duration of the CASTING study
| Parameter | Ocrelizumab (N = 680) | ||||
|---|---|---|---|---|---|
| Baseline | Week 24 | Week 48 | Week 72 | Week 96 | |
| EDSS score a (mITT), mean (SD), n | 2.09 (1.06) 680 | 2.08 (1.15) 679 | 2.11 (1.28) 665 | 2.07 (1.29) 650 | 2.09 (1.30) 640 |
| Change in EDSS b score from baseline (mITT), adjusted mean (95% CI), n | ‐ | −0.02 (−0.11, 0.07) 679 | 0.00 (−0.10, 0.10) 665 | −0.02 (−0.12, 0.08) 650 | 0.00 (−0.10, 0.10) 640 |
| Time to onset of clinical measure, KM event‐free rate estimate %, (95% CI) patients at risk, n | |||||
| First protocol‐defined event of disease activity (ITT) | ‐ | 91.45 (89.08, 93.32) 618 | 85.50 (82.61, 87.94) 575 | ‐ | 76.25 (72.81, 79.31) 394 |
| 24‐week CDP (ITT) | ‐ | 98.08 (96.71, 98.88) 661 | 95.25 (93.35, 96.62) 636 | ‐ | 88.39 (85.68, 90.62) 439 |
| 24‐week CDI (mITT), baseline EDSS score ≥ 2 | ‐ | 95.99 (93.54, 97.52) 385 | 89.96 (86.56, 92.53) 358 | ‐ | 83.53 (79.49, 86.85) 241 |
| First PDR (ITT) | ‐ | 94.70 (92.73, 96.15) 639 | 93.51 (91.38, 95.13) 625 | ‐ | 90.00 (87.47, 92.04) 457 |
| MRI measures, adjusted rate (95% CI), n | |||||
| Number of T1‐weighted CELs (ITT) c | ‐ | 0.004 (0.001, 0.014) 665 | 0.004 (0.001, 0.011) 658 | ‐ | NR d |
| Number of new and/or enlarging T2‐weighted hyperintense lesions (ITT) c | ‐ | 0.053 (0.038, 0.075) 671 | 0.009 (0.004, 0.017) 666 | ‐ | 0.011 (0.006, 0.020) 636 |
Abbreviations: CEL, contrast‐enhancing lesion; CDI, confirmed disability improvement; CI, confidence interval; CDP, confirmed disability progression; CRF, case report form; DMT, disease‐modifying therapy; EDSS, Expanded Disability Status Scale; ITT, intention‐to‐treat; KM, Kaplan–Meier; mITT, modified intention‐to‐treat; MMRM, mixed‐effect model of repeated measures; MRI, magnetic resonance imaging; MS, multiple sclerosis; NR, not recorded; PDR, protocol‐defined relapse; SD, standard deviation.
Baseline EDSS score defined as the average of the EDSS scores at the screening and baseline visits. If one of the EDSS scores from screening or baseline visits was missing, the other was used for baseline EDSS.
Estimates are from analysis based on MMRM using unstructured covariance matrix: change = visit + baseline EDSS score + duration since MS symptom onset (≤3 years, >3 and ≤5 years, >5 and ≤10 years, >10 years) + presence of T1 gadolinium‐enhanced lesions at screening (Yes/No) + number of previous DMTs (1, >1) + enrollment reasons (relapse only, MRI only, or both relapse and MRI).
The total number of T1 gadolinium‐enhanced or new and/or enlarging T2‐weighted hyperintense lesions for all patients divided by the total number of brain MRI scans, adjusted by duration since MS symptom onset (continuous variable), presence of T1 gadolinium‐enhanced lesions at screening (Yes/No), presence of relapses prior to screening as per CRF (Yes/No) and number of previous DMTs (= 1 vs. > 1). The total number of new and/or enlarging T2‐weighted hyperintense lesions adjusted rate for Weeks 24, 48, and 96 combined was 0.032 (95% CI 0.025, 0.042). The total number of T1 gadolinium‐enhanced lesions adjusted rate for Weeks 24, 48, and 96 combined was 0.004 (95% CI 0.002, 0.007).
Due to the very low number of T1‐weighted CELs at Week 96, the Poisson model did not converge.