Dataset Information

Slowing of brain atrophy with teriflunomide and delayed conversion to clinically definite MS.

ABSTRACT:

Background

We explored the effect of teriflunomide on cortical gray matter (CGM) and whole brain (WB) atrophy in patients with clinically isolated syndrome (CIS) from the phase III TOPIC study and assessed the relationship between atrophy and risk of conversion to clinically definite MS (CDMS).

Methods

Patients (per McDonald 2005 criteria) were randomized 1:1:1 to placebo, teriflunomide 7 mg, or teriflunomide 14 mg for ⩽108 weeks (core study). In the extension, teriflunomide-treated patients maintained their original dose; placebo-treated patients were re-randomized 1:1 to teriflunomide 7 mg or 14 mg. Brain volume was assessed during years 1-2.

Results

Teriflunomide 14 mg significantly slowed annualized CGM and WB atrophy versus placebo during years 1-2 [percent reduction: month 12, 61.4% (CGM; p = 0.0359) and 28.6% (WB; p = 0.0286); month 24, 40.2% (CGM; p = 0.0416) and 43.0% (WB; p < 0.0001)]. For every 1% decrease in CGM or WB volume during years 1-2, risk of CDMS conversion increased by 14.5% (p = 0.0004) and 47.3% (p < 0.0001) during years 1-2, respectively, and 6.6% (p = 0.0570) and 35.9% (p = 0.0250) during years 1-5. In patients with the least (bottom quartile) versus most (top quartile) atrophy during years 1-2, risk of CDMS conversion was reduced by 58% (CGM; p = 0.0024) and 58% (WB; p = 0.0028) during years 1-2, and 42% (CGM; p = 0.0138) and 29% (WB; p = 0.1912) during years 1-5.

Conclusion

These findings support the clinical relevance of CGM and WB atrophy and early intervention with teriflunomide in CIS.

SUBMITTER: Zivadinov R

PROVIDER: S-EPMC7672760 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Slowing of brain atrophy with teriflunomide and delayed conversion to clinically definite MS.

Zivadinov Robert R Dwyer Michael G MG Carl Ellen E Poole Elizabeth M EM Cavalier Steve S Briassouli Paraskevi P Bergsland Niels N

Therapeutic advances in neurological disorders 20201111

<h4>Background</h4>We explored the effect of teriflunomide on cortical gray matter (CGM) and whole brain (WB) atrophy in patients with clinically isolated syndrome (CIS) from the phase III TOPIC study and assessed the relationship between atrophy and risk of conversion to clinically definite MS (CDMS).<h4>Methods</h4>Patients (per McDonald 2005 criteria) were randomized 1:1:1 to placebo, teriflunomide 7 mg, or teriflunomide 14 mg for ⩽108 weeks (core study). In the extension, teriflunomide-treat ...[more]

PMID: 33240397

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Project description:Understanding the predictors of progression from a first to a second demyelinating event (and formerly, a diagnosis of clinically definite multiple sclerosis) is important clinically. Previous studies have focused on predictors within a single domain, e.g. radiological, lacking prospective data across multiple domains. We tested a comprehensive set of personal, environmental, neurological, MRI and genetic characteristics, considered together, as predictors of progression from a first demyelinating event to clinically definite multiple sclerosis. Participants were aged 18-59 years and had a first demyelinating event during the study recruitment period (1 November 2003-31 December 2006) for the Ausimmune Study (n = 216) and had follow-up data to 2-3 years post-initial interview. Detailed baseline data were available on a broad range of demographic and environmental factors, MRI, and genetic and viral studies. Follow-up data included confirmation of clinically definite multiple sclerosis (or not) and changes in environmental exposures during the follow-up period. We used multivariable logistic regression and Cox proportional hazards regression modelling to test predictors of, and time to, conversion to clinically definite multiple sclerosis. On review, one participant had an undiagnosed event prior to study recruitment and was excluded (n = 215). Data on progression to clinically definite multiple sclerosis were available for 91.2% (n = 196); 77% were diagnosed as clinically definite multiple sclerosis at follow-up. Mean (standard deviation) duration of follow-up was 2.7 (0.7) years. The set of predictors retained in the best predictive model for progression from a first demyelinating event to clinically definite multiple sclerosis were as follows: younger age at first demyelinating event [adjusted odds ratio (aOR) = 0.92, 95% confidence interval (CI) = 0.87-0.97, per additional year of age); being a smoker at baseline (versus not) (aOR = 2.55, 95% CI 0.85-7.69); lower sun exposure at age 6-18 years (aOR = 0.86, 95% CI 0.74-1.00, per 100 kJ/m2 increment in ultraviolet radiation dose), presence (versus absence) of infratentorial lesions on baseline magnetic resonance imaging (aOR = 7.41, 95% CI 2.08-26.41); and single nucleotide polymorphisms in human leukocyte antigen (HLA)-B (rs2523393, aOR = 0.25, 95% CI 0.09-0.68, for any G versus A:A), TNFRSF1A (rs1800693, aOR = 5.82, 95% CI 2.10-16.12, for any C versus T:T), and a vitamin D-binding protein gene (rs7041, aOR = 3.76, 95% CI 1.41-9.99, for any A versus C:C). The final model explained 36% of the variance. Predictors of more rapid progression to clinically definite multiple sclerosis (Cox proportional hazards regression) were similar. Genetic and magnetic resonance imaging characteristics as well as demographic and environmental factors predicted progression, and more rapid progression, from a first demyelinating event to a second event and clinically definite multiple sclerosis.

Dataset Information

Slowing of brain atrophy with teriflunomide and delayed conversion to clinically definite MS.

Background

Methods

Results

Conclusion

Publications

Slowing of brain atrophy with teriflunomide and delayed conversion to clinically definite MS.

Similar Datasets

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