Long-term effects of cladribine tablets on mri activity outcomes in patients with relapsing-remitting multiple sclerosis: The clarity extension study

Giancarlo Comi, Stuart Cook, Kottil W Rammohan, Per Soelberg Sorensen, Patrick Vermersch, Abidemi K. Adeniji, Fernando Dangond, Gavin Giovannoni

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: The CLARITY and CLARITY Extension studies demonstrated that treatment of relapsing-remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This paper presents the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study. Methods: Patients who received a cumulative dose of either CT 3.5 or 5.25 mg/kg in CLARITY were rerandomized to either placebo or CT 3.5 mg/kg in CLARITY Extension. Patients from the arm that received placebo in CLARITY were assigned to CT 3.5 mg/kg. MRI assessments were carried out when patients entered CLARITY Extension and after Weeks 24, 48, 72 and 96, and in a supplemental follow-up period. Results: At CLARITY Extension baseline, patients who received placebo during CLARITY had more T1 gadolinium-enhanced (Gd+) lesions than patients who received CT during CLARITY. These patients, who were then exposed to cladribine 3.5 mg/kg during the extension, experienced a 90.4% relative reduction (median difference -0.33, 97.5% confidence interval -0.33-0.00; p < 0.001) in T1 Gd+ lesions at the end of the extension compared with the end of CLARITY. Overall, the majority of patients in each treatment group remained free from T1 Gd+ lesions throughout CLARITY Extension. However, a small proportion of patients who were treated with cladribine in CLARITY and received placebo in CLARITY Extension showed evidence of increased MRI activity, and this was associated with a prolonged treatment gap between CLARITY and CLARITY Extension. Conclusion: A 2-year treatment with CT 3.5 mg/kg has a durable effect on MRI outcomes in the majority of patients, an effect that was sustained in patients who were not retreated in the subsequent 2 years after initial treatment.

Original languageEnglish (US)
JournalTherapeutic Advances in Neurological Disorders
Volume11
DOIs
StatePublished - Jan 1 2018

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Cladribine
Relapsing-Remitting Multiple Sclerosis
Tablets
Placebos
Magnetic Resonance Imaging
Therapeutics
Gadolinium
varespladib methyl

Keywords

  • Cladribine
  • Extension study
  • Magnetic resonance imaging
  • Relapsing-remitting multiple sclerosis

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology

Cite this

Long-term effects of cladribine tablets on mri activity outcomes in patients with relapsing-remitting multiple sclerosis : The clarity extension study. / Comi, Giancarlo; Cook, Stuart; Rammohan, Kottil W; Sorensen, Per Soelberg; Vermersch, Patrick; Adeniji, Abidemi K.; Dangond, Fernando; Giovannoni, Gavin.

In: Therapeutic Advances in Neurological Disorders, Vol. 11, 01.01.2018.

Research output: Contribution to journalArticle

Comi, Giancarlo ; Cook, Stuart ; Rammohan, Kottil W ; Sorensen, Per Soelberg ; Vermersch, Patrick ; Adeniji, Abidemi K. ; Dangond, Fernando ; Giovannoni, Gavin. / Long-term effects of cladribine tablets on mri activity outcomes in patients with relapsing-remitting multiple sclerosis : The clarity extension study. In: Therapeutic Advances in Neurological Disorders. 2018 ; Vol. 11.
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abstract = "Background: The CLARITY and CLARITY Extension studies demonstrated that treatment of relapsing-remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This paper presents the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study. Methods: Patients who received a cumulative dose of either CT 3.5 or 5.25 mg/kg in CLARITY were rerandomized to either placebo or CT 3.5 mg/kg in CLARITY Extension. Patients from the arm that received placebo in CLARITY were assigned to CT 3.5 mg/kg. MRI assessments were carried out when patients entered CLARITY Extension and after Weeks 24, 48, 72 and 96, and in a supplemental follow-up period. Results: At CLARITY Extension baseline, patients who received placebo during CLARITY had more T1 gadolinium-enhanced (Gd+) lesions than patients who received CT during CLARITY. These patients, who were then exposed to cladribine 3.5 mg/kg during the extension, experienced a 90.4{\%} relative reduction (median difference -0.33, 97.5{\%} confidence interval -0.33-0.00; p < 0.001) in T1 Gd+ lesions at the end of the extension compared with the end of CLARITY. Overall, the majority of patients in each treatment group remained free from T1 Gd+ lesions throughout CLARITY Extension. However, a small proportion of patients who were treated with cladribine in CLARITY and received placebo in CLARITY Extension showed evidence of increased MRI activity, and this was associated with a prolonged treatment gap between CLARITY and CLARITY Extension. Conclusion: A 2-year treatment with CT 3.5 mg/kg has a durable effect on MRI outcomes in the majority of patients, an effect that was sustained in patients who were not retreated in the subsequent 2 years after initial treatment.",
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AU - Comi, Giancarlo

AU - Cook, Stuart

AU - Rammohan, Kottil W

AU - Sorensen, Per Soelberg

AU - Vermersch, Patrick

AU - Adeniji, Abidemi K.

AU - Dangond, Fernando

AU - Giovannoni, Gavin

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AB - Background: The CLARITY and CLARITY Extension studies demonstrated that treatment of relapsing-remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This paper presents the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study. Methods: Patients who received a cumulative dose of either CT 3.5 or 5.25 mg/kg in CLARITY were rerandomized to either placebo or CT 3.5 mg/kg in CLARITY Extension. Patients from the arm that received placebo in CLARITY were assigned to CT 3.5 mg/kg. MRI assessments were carried out when patients entered CLARITY Extension and after Weeks 24, 48, 72 and 96, and in a supplemental follow-up period. Results: At CLARITY Extension baseline, patients who received placebo during CLARITY had more T1 gadolinium-enhanced (Gd+) lesions than patients who received CT during CLARITY. These patients, who were then exposed to cladribine 3.5 mg/kg during the extension, experienced a 90.4% relative reduction (median difference -0.33, 97.5% confidence interval -0.33-0.00; p < 0.001) in T1 Gd+ lesions at the end of the extension compared with the end of CLARITY. Overall, the majority of patients in each treatment group remained free from T1 Gd+ lesions throughout CLARITY Extension. However, a small proportion of patients who were treated with cladribine in CLARITY and received placebo in CLARITY Extension showed evidence of increased MRI activity, and this was associated with a prolonged treatment gap between CLARITY and CLARITY Extension. Conclusion: A 2-year treatment with CT 3.5 mg/kg has a durable effect on MRI outcomes in the majority of patients, an effect that was sustained in patients who were not retreated in the subsequent 2 years after initial treatment.

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KW - Magnetic resonance imaging

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