Author Of 2 Presentations
P0284 - Age-related efficacy of cladribine tablets in patients with relapsing-remitting MS in the CLARITY Extension study (ID 867)
Abstract
Background
In the CLARITY study, treatment with cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years [yr]) demonstrated significance over placebo on clinical and MRI efficacy outcomes in patients (pts) with relapsing-remitting multiple sclerosis. Pts who completed CLARITY were eligible to participate in CLARITY Extension (EXT).
Objectives
This post hoc analysis explored efficacy outcomes at the end of the core part of CLARITY EXT (Week 96) in pts who were ≤30yr vs >30yr at CLARITY enrollment.
Methods
Analyses were performed by age and treatment (CC7.0 [cladribine-cladribine]: cladribine tablets 3.5 mg/kg in CLARITY and CLARITY EXT; CP3.5 [cladribine-placebo]: cladribine tablets 3.5 mg/kg in CLARITY and placebo in CLARITY EXT). Endpoints included relapse, 3- and 6-month (mo) confirmed disability progression (CDP, based on Expanded Disability Status Scale), MRI activity, and no evidence of disease activity (NEDA; no relapse, 3- or 6-mo CDP, and MRI activity) at Week 96 of CLARITY EXT.
Results
Data from 284 pts were included: ≤30yr: CC7.0 N=49, CP3.5 N=23; >30yr: CC7.0 N=137, CP3.5 N=75. Annualized relapse rate (95% confidence interval [CI]) was similar between age groups for pts receiving CC7.0 (≤30yr, 0.08 [0.04; 0.15]; >30yr, 0.08 [0.05; 0.12]) and numerically higher in younger pts receiving CP3.5 (≤30yr, 0.27 [0.16; 0.47]; >30yr, 0.06 [0.03; 0.11]). The probabilities (Kaplan-Meier estimates) of being free of 3-mo CDP for CC7.0 were 0.98 for ≤30yr and 0.86 for >30yr; and for CP3.5 were 0.79 for ≤30yr and 0.88 for >30yr. The probabilities of being free of 6-mo CDP were similar to those of 3-mo CDP. Mean (95% CI) cumulative numbers of T1 gadolinium-enhancing lesions were similar between age groups for pts receiving CC7.0 (≤30yr, 0.02 [0.01; 0.08]; >30yr, 0.02 [0.01; 0.06]) or CP3.5 (≤30yr, 0.54 [0.16; 1.79]; >30yr, 0.27 [0.10; 0.73]). Mean (95% CI) numbers of active T2 lesions were similar between age groups for pts receiving CC7.0 (≤30yr, 1.36 [0.75; 2.45]; >30yr, 1.12 [0.78; 1.61]) and numerically lower in older pts receiving CP3.5 (≤30yr, 2.95 [1.22; 7.10]; >30yr, 1.40 [0.88; 2.22]). The proportion of pts achieving NEDA based on 3-mo CDP was numerically higher in younger pts receiving CC7.0 (≤30yr, 36.7%; >30yr, 28.5%) and older pts receiving CP3.5 (≤30yr, 21.7%; >30yr, 30.7%). NEDA results based on 6-mo CDP were similar to those based on 3-mo CDP.
Conclusions
Cladribine tablets result in similar clinical and MRI outcomes at Week 96 of CLARITY EXT in both older (>30yr) and younger (≤30yr) pts, providing further evidence of efficacy across age groups.
P0411 - Treatment-emergent adverse events occurring early in the treatment course of cladribine tablets in two phase 3 trials in multiple sclerosis (ID 377)
Abstract
Background
Tolerability and adherence to disease-modifying drugs (DMDs) can be influenced by treatment-emergent adverse events (TEAEs) that start shortly after therapy initiation. One potential advantage of cladribine tablets is its short treatment course which may limit TEAEs; patients who receive the approved 3.5 mg/kg dosage only receive doses for two 4 to 5-day periods per treatment year.
Objectives
To identify TEAEs early in the course of treatment in patients enrolled in the Phase 3 CLARITY and ORACLE-MS clinical trials.
Methods
This was a post hoc analysis of safety populations in CLARITY and ORACLE-MS studies. Patients received cladribine tablets 3.5 mg/kg (cumulative dose over 2 years; N=636) or placebo (N=641). The incidence of early adverse events, TEAEs, serious TEAEs, drug-related TEAEs, and TEAEs leading to discontinuation were summarized based on incidence within 2, 6, and 12 weeks (Wk) after commencement of therapy.
Results
The incidence of TEAEs occurring within the first 2–12Wk of treatment across both trials in both treatment groups was generally low, and the majority of events were mild (placebo: 53.8–68.4%; cladribine tablets: 54.4–68.0%). The most common TEAEs by time epoch after initiating placebo and cladribine tablets 3.5 mg/kg treatment, respectively, were: nausea: 3.3% vs. 4.9% (2Wk), 3.7% vs. 6.4% (6Wk), and 4.5% vs. 8.0% (12Wk); fatigue: 2.0% vs. 1.4% (2Wk), 3.1% vs. 2.5% (6Wk), and 4.4% vs. 3.1% (12Wk); headache: 8.3% vs. 9.0% (2Wk), 11.9% vs. 14.8% (6Wk), and 15.1% vs. 18.4% (12Wk); lymphopenia: 0.0% vs. 2.5% (6Wk) and 0.5% vs. 6.8% (12Wk); leukopenia: 0.0% vs. 1.3% (12Wk). Other endpoints will be shown in the final presentation.
Conclusions
Incidence of TEAEs experienced during the first 12 weeks of treatment with cladribine tablets 3.5 mg/kg in Phase 3 clinical trials was low and mostly mild. Nausea, headache, and lymphopenia were seen more frequently in cladribine tablets-treated patients versus those in the placebo group. These findings suggest that cladribine tablets are generally well tolerated, which may facilitate treatment adherence.