Table 2.
MRI and clinical outcomes.
| Outcome | Treatment received during the DBP | |||
|---|---|---|---|---|
| Placebo + evobrutinib 25 mg QD |
Evobrutinib 25 mg QD |
Evobrutinib 75 mg QD |
Evobrutinib 75 mg BID |
|
| Treatment received during the OLE Evobrutinib 75 mg QD➔BID | ||||
| Unadjusted ARR (95% CI) | ||||
| Weeks 0–48 a | 0.37 (0.21–0.59) | 0.52 (0.33–0.78) | 0.25 (0.12–0.44) | 0.11 (0.04–0.25) |
| OLE evobrutinib 75 mg QD
c
(week 48/OLE BL to 75 mg BID dose switch b ) |
0.30 (0.15–0.53) | 0.22 (0.09–0.43) | 0.13 (0.04–0.31) | 0.16 (0.07–0.34) |
| OLE evobrutinib 75 mg BID
c
(75 mg BID dose switch to week 192 b ) |
0.10 (0.04–0.22) | 0.11 (0.04–0.24) | 0.06 (0.02–0.15) | 0.11 (0.05–0.22) |
| Week 48/OLE BL–week 192 c | 0.18 (0.10–0.28) | 0.15 (0.08–0.26) | 0.09 (0.04–0.16) | 0.13 (0.07–0.22) |
| Change from baseline (week 0) to week 192 in EDSS score | ||||
| Number of patients | 31 | 27 | 36 | 36 |
| Mean (±SEM) | 0.06 (±0.14) | 0.00 (±0.15) | 0.01 (±0.07) | 0.04 (±0.08) |
| Median (min; max) | 0.0 (-1.5; 3.0) | 0.0 (-1.5; 2.5) | 0.0 (-1.0; 1.5) | 0.0 (-0.5; 2.0) |
| Number of new T1 Gd + lesions at week 12 | ||||
| Number of patients | 52 | 48 | 51 | 50 |
| Mean (±SEM) | 1.15 (±0.27) | 1.73 (±0.78) | 0.45 (±0.21) | 0.18 (±0.14) |
| Median (min; max) | 0 (0; 9) | 0 (0; 34) | 0 (0; 10) | 0 (0; 7) |
| Number of T1 Gd + lesions at week 192 | ||||
| Number of patients | 30 | 27 | 35 | 36 |
| Mean (±SEM) | 0.87 (±0.43) | 0.41 (±0.23) | 0.80 (±0.59) | 0.58 (±0.19) |
| Median (min; max) | 0 (0; 11) | 0 (0; 6) | 0 (0; 20) | 0 (0; 5) |
| Change from baseline (week 0) to week 192 in T2 lesion volume, cm 3 | ||||
| Number of patients | 30 | 27 | 35 | 36 |
| Mean (±SEM) | 1.58 (±0.75) | 1.31 (±0.65) | 0.98 (±0.39) | 1.64 (±0.48) |
| Median (min; max) | 0.23 (-3.43; 18.34) | 0.06 (-1.86; 14.66) | 0.01 (-0.63; 10.67) | 0.74 (-2.23; 13.58) |
| NfL Z-scores at week 144 | ||||
| Number of patients | 30 | 29 | 33 | 37 |
| Median (95% CI) | 0.11 (0.67–0.84) | 0.03 (0.38–0.65) | -0.03 (0.85–0.73) | -0.13 (0.40–0.93) |
mITT analysis set: placebo + evobrutinib 25 mg QD/75 mg QD–BID, n = 53 (98%); evobrutinib 25 mg QD/75 mg QD–BID, n = 50 (96%); evobrutinib 75 mg QD/75 mg QD–BID, n = 51 (96%); evobrutinib 75 mg BID/75 mg QD–BID, n = 53 (98%).
Evobrutinib-treated patients (n = 151), mean (±SD) duration of exposure to evobrutinib 75 mg QD dose before the switch to 75 mg BID: 50.6 (± 6.0) weeks.
SAF-OLE analysis set: placebo + evobrutinib 25 mg QD/75 mg QD–BID, n = 39 (72%); evobrutinib 25 mg QD/75 mg QD–BID, n = 39 (75%); evobrutinib 75 mg QD/75 mg QD–BID, n = 42 (79%); evobrutinib 75 mg BID/75 mg QD–BID, n = 44 (82%).
The unadjusted ARR was defined as the number of relapses among patients divided by the number of patient-years of follow-up. For patients who discontinued the trial early, all relapses and follow-up through the safety follow-up visit were included. Mean number of new T1 Gd+ lesions were estimated using negative binomial regression, with covariates for presence or absence of baseline T1 Gd+ lesions and treatment arm.
ARR: annualised relapse rate; BID: twice-daily; CI: confidence interval; EDSS: Expanded Disability Status Scale; Gd+: gadolinium-enhancing; OLE: open-label extension; NE: not estimable; NfL: neurofilament light chain; QD: once-daily; SD: standard deviation; SEM: standard error of the mean.