Contributions
Abstract: P912
Type: Poster
Abstract Category: Clinical aspects of MS - 8 Clinical assessment tools
Background: Cladribine has been shown to exert long-lasting effects by preferentially targeting lymphocytes and the autoimmune processes involved in the pathophysiology of MS. Treatment guidelines have been proposed to manage the risk of developing severe sustained lymphopenia following cladribine treatment. They include possible modifications of the nominal dosing regimen, based on absolute lymphocyte counts (ALC) monitoring prior to the 2nd year treatment.
Objectives: To investigate the impact of these treatment rules on the occurrence of severe lymphopenia and on the probability of developing relapses, in subjects with RRMS presenting Grade 2 to 4 lymphopenia at the end of Year 1.
Methods: Modelling and simulation was used to analyse the data. In particular, previously developed models of relapse rate and ALC were used jointly in a clinical trial simulation analysis to obtain projections for these two responses in case of 2nd year treatment postponement or cancellation. To this purpose, a virtual population representative of patients, treated with a cumulative dose of 3.5 mg/kg cladribine tablets was generated, based on the Phase 3 CLARITY trial. A pre-set series of alternative rules allowing postponement of cladribine tablets treatment in Year 2 for up to 9 months, to permit ALC recovery to Grade 0 or 1 before retreating, were investigated.
Results: Results showed that 92% of virtual patients would recover to Grade 1 or better by the end of the first calendar year. A further 5% of patients recovered in the first month of postponement; ≤1% would not recover to Grade 0 or 1 within 6 months. By allowing patients to recover to Grade 0 or 1 before starting the Year 2 of cladribine treatment, less severe lymphopenia was observed at any time during Year 2. The probability of experiencing relapses was not affected by delaying the Year 2 dose up to 6 months. This suggests that the efficacy of cladribine could be sustained if its administration needs to be deferred to allow resolution of lymphopenia.
Conclusions: Modelling & simulation data support the risk minimization measure of proposed treatment guidelines to manage severe lymphopenia, while preserving cladribine tablets efficacy.
Disclosure: This study was sponsored by Merck KGaA, Darmstadt, Germany.
NT and AM are employee of Merck Serono S.A., Lausanne, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
FD is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Darmstadt, Germany.
CH is an employee of Merck KGaA, Darmstadt, Germany.
Abstract: P912
Type: Poster
Abstract Category: Clinical aspects of MS - 8 Clinical assessment tools
Background: Cladribine has been shown to exert long-lasting effects by preferentially targeting lymphocytes and the autoimmune processes involved in the pathophysiology of MS. Treatment guidelines have been proposed to manage the risk of developing severe sustained lymphopenia following cladribine treatment. They include possible modifications of the nominal dosing regimen, based on absolute lymphocyte counts (ALC) monitoring prior to the 2nd year treatment.
Objectives: To investigate the impact of these treatment rules on the occurrence of severe lymphopenia and on the probability of developing relapses, in subjects with RRMS presenting Grade 2 to 4 lymphopenia at the end of Year 1.
Methods: Modelling and simulation was used to analyse the data. In particular, previously developed models of relapse rate and ALC were used jointly in a clinical trial simulation analysis to obtain projections for these two responses in case of 2nd year treatment postponement or cancellation. To this purpose, a virtual population representative of patients, treated with a cumulative dose of 3.5 mg/kg cladribine tablets was generated, based on the Phase 3 CLARITY trial. A pre-set series of alternative rules allowing postponement of cladribine tablets treatment in Year 2 for up to 9 months, to permit ALC recovery to Grade 0 or 1 before retreating, were investigated.
Results: Results showed that 92% of virtual patients would recover to Grade 1 or better by the end of the first calendar year. A further 5% of patients recovered in the first month of postponement; ≤1% would not recover to Grade 0 or 1 within 6 months. By allowing patients to recover to Grade 0 or 1 before starting the Year 2 of cladribine treatment, less severe lymphopenia was observed at any time during Year 2. The probability of experiencing relapses was not affected by delaying the Year 2 dose up to 6 months. This suggests that the efficacy of cladribine could be sustained if its administration needs to be deferred to allow resolution of lymphopenia.
Conclusions: Modelling & simulation data support the risk minimization measure of proposed treatment guidelines to manage severe lymphopenia, while preserving cladribine tablets efficacy.
Disclosure: This study was sponsored by Merck KGaA, Darmstadt, Germany.
NT and AM are employee of Merck Serono S.A., Lausanne, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
FD is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Darmstadt, Germany.
CH is an employee of Merck KGaA, Darmstadt, Germany.