Disease Modifying Therapies – Risk Management Poster Presentation

P0411 - Treatment-emergent adverse events occurring early in the treatment course of cladribine tablets in two phase 3 trials in multiple sclerosis (ID 377)

  • J. Oh
  • J. Oh
  • B. Walker
  • G. Giovannoni
  • D. Jack
  • F. Dangond
  • A. Nolting
  • J. Aldridge
  • L. Lebson
  • T. Leist
Presentation Number
Presentation Topic
Disease Modifying Therapies – Risk Management



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.


To identify TEAEs early in the course of treatment in patients enrolled in the Phase 3 CLARITY and ORACLE-MS clinical trials.


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.


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.


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.