Table 2.
CLARITY efficacy: clinical and imaging endpoints and relapses during the 96-week study (ITT population) [65]
| Endpoint | Placebo [n = 437] | Cladribine tablets 3.5 mg/kg [n = 433] | Cladribine tablets 5.25 mg/kg [n = 433] |
|---|---|---|---|
| Relapse rate (primary endpoint) | |||
| ARR (95% CI) | 0.33 (0.29–0.38) | 0.14 (0.12–0.17) | 0.15 (0.12–0.17) |
| Relative reduction in ARR for cladribine vs. placebo, %a | 57.6 | 54.5 | |
| p valueb | < 0.001 | < 0.001 | |
| Relapse-free rate | |||
| Patients without relapse [n (%)] | 266 (60.9) | 345 (79.7) | 360 (78.9) |
| OR for cladribine vs. placebo (95% CI)c | 2.53 (1.87–3.42) | 2.43 (1.81–3.27) | |
| p valued | < 0.001 | < 0.001 | |
| Relapse at 96 weeks | |||
| Number of relapses [n (%)] | |||
| 0 | 266 (60.9) | 345 (79.7) | 360 (78.9) |
| 1 | 109 (24.9) | 69 (15.9) | 77 (16.9) |
| 2 | 44 (10.1) | 13 (3.0) | 13 (2.9) |
| 3 | 15 (3.4) | 5 (1.2) | 5 (1.1) |
| ≥ 4 | 3 (0.7) | 1 (0.2) | 1 (0.2) |
| p valuee | < 0.001 | < 0.001 | |
| Need for rescue therapy | |||
| Patients receiving rescue therapy [n (%)] | 27 (6.2) | 11 (2.5) | 9 (2.0) |
| OR for cladribine vs. placebo (95% CI)c | 0.40 (0.19–0.81) | 0.31 (0.14–0.66) | |
| p valued | 0.01 | 0.003 | |
| Time to first relapse | |||
| 15th percentile of time to event, monthsf | 4.6 | 13.4 | 13.3 |
| HR for cladribine vs. placebo (95% CI)g | 0.44 (0.34–0.58) | 0.46 (0.36–0.60) | |
| p valueg | < 0.001 | < 0.001 | |
| Time to 3-month CDP | |||
| 10th percentile of time to event, monthsf | 10.8 | 13.6 | 13.6 |
| HR for cladribine vs. placebo (95% CI)g | 0.67 (0.48–0.93) | 0.69 (0.49–0.96) | |
| p valueg | 0.02 | 0.03 | |
| Patients without a 3-month CDP | |||
| Patients with no change [n (%)] | 347 (79.4) | 371 (85.7) | 387 (84.9) |
| OR for cladribine vs. placebo (95% CI)c | 1.55 (1.09–2.22) | 1.46 (1.03–2.07) | |
| p valued | 0.02 | 0.03 | |
| Lesion activity on brain MRI | |||
| Gd + T1-weighted lesions | |||
| Mean number | 0.91 | 0.12 | 0.11 |
| Relative reduction, % | 85.7 | 87.9 | |
| Active T2-weighted lesions | |||
| Mean number | 1.43 | 0.38 | 0.33 |
| Relative reduction, % | 73.4 | 76.9 | |
| Combined unique lesions | |||
| Mean number | 1.72 | 0.43 | 0.38 |
| Relative reduction, % | 74.4 | 77.9 | |
| p valueh | < 0.001 | < 0.001 |
ARR annualized relapse rate, CDP confirmed disability progression, CI confidence interval, Gd + gadolinium-enhancing, HR hazard ratio, ITT intent-to-treat, MRI magnetic resonance imaging, OR odds ratio
aThe relative reduction in the ARR was calculated as the ratio of the difference in the ARR between the placebo group and the cladribine group to the ARR rate in the placebo group
bThe p value was based on a Wald Chi-square test from an analysis of the number of relapses with the use of a Poisson regression model with fixed effects for treatment and region and the log of time in the study as an offset variable
cORs and associated 95% CIs were estimated with the use of a logistic regression model with fixed effects for study group and region
dThe p value was based on a Wald Chi-square test from an endpoint analysis with the use of a logistic-regression model with fixed effects for study group and region
eThe p value was based on a Cochran–Mantel–Haenszel test with adjustment for the baseline number of relapses
fThe 10th and 15th percentile values were estimated from the Kaplan–Meier survival curve
gThe HR, 95% CI, and p values were based on a Cox proportional hazards model with fixed effects for study group and region
hThe p value is for all comparisons with placebo for imaging measurements and was based on a non-parametric analysis of covariance model on ranked data with fixed effects for study group and region and number of GD+ T1-weighted lesions at baseline as a covariate