TY - JOUR
T1 - Treatment Effect on Brain Atrophy Correlates with Treatment Effect on Cognition in Multiple Sclerosis
AU - Sormani, Maria Pia
AU - Schiavetti, Irene
AU - Ponzano, Marta
AU - Colato, Elisa
AU - de Stefano, Nicola
N1 - Funding Information: M.P.S. reports personal fees from Merck, Biogen, Roche, Sanofi, Novartis, Immunic, and Alexion outside the submitted work. N.D.S. reports personal fees from Schering, Biogen, Merck, Novartis, Immunic, and grants from the Italian MS Society, outside the submitted work. I.S., M.P., and E.C. have nothing to declare. Publisher Copyright: © 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
PY - 2023/11
Y1 - 2023/11
N2 - Objective: The purpose of this study was to evaluate the extent to which treatment effect on magnetic resonance imaging (MRI)-derived measures of brain atrophy and focal lesions can mediate, at the trial level, the treatment effect on cognitive outcomes in multiple sclerosis (MS). Methods: We collected all published randomized clinical trials in MS lasting at least 2 years and including as end points: active MRI lesions (defined as new/enlarging T2 lesions), brain atrophy (defined as a change in brain volume between month 12 and month 24), and change in cognitive performance (assessed by the Paced Auditory Serial Addition Test [PASAT]). Relative reductions were used to quantify the treatment effect on MRI markers (lesions and atrophy), whereas the standardized mean difference (Hedges g) between baseline and follow-up cognitive assessment was used to quantify the treatment effects on cognition. A linear regression, weighted for trial size, was used to assess the relationship between the treatment effects on MRI markers and cognition. Results: Fourteen trials including more than 8,813 patients with MS were included in the meta-regression. Treatment effect on cognition was strongly associated with the treatment effect on brain atrophy (R 2 = 0.79, p < 0.001), but was not correlated with the treatment effect on active MRI lesions (R 2 = 0.16, p = 0.14). Interpretation: Results reported here suggest that brain atrophy, a well-established MRI marker in MS clinical trials, can be used as a main outcome for clinical trials with drugs targeting cognitive impairment and neurodegeneration. ANN NEUROL 2023;94:925–932.
AB - Objective: The purpose of this study was to evaluate the extent to which treatment effect on magnetic resonance imaging (MRI)-derived measures of brain atrophy and focal lesions can mediate, at the trial level, the treatment effect on cognitive outcomes in multiple sclerosis (MS). Methods: We collected all published randomized clinical trials in MS lasting at least 2 years and including as end points: active MRI lesions (defined as new/enlarging T2 lesions), brain atrophy (defined as a change in brain volume between month 12 and month 24), and change in cognitive performance (assessed by the Paced Auditory Serial Addition Test [PASAT]). Relative reductions were used to quantify the treatment effect on MRI markers (lesions and atrophy), whereas the standardized mean difference (Hedges g) between baseline and follow-up cognitive assessment was used to quantify the treatment effects on cognition. A linear regression, weighted for trial size, was used to assess the relationship between the treatment effects on MRI markers and cognition. Results: Fourteen trials including more than 8,813 patients with MS were included in the meta-regression. Treatment effect on cognition was strongly associated with the treatment effect on brain atrophy (R 2 = 0.79, p < 0.001), but was not correlated with the treatment effect on active MRI lesions (R 2 = 0.16, p = 0.14). Interpretation: Results reported here suggest that brain atrophy, a well-established MRI marker in MS clinical trials, can be used as a main outcome for clinical trials with drugs targeting cognitive impairment and neurodegeneration. ANN NEUROL 2023;94:925–932.
UR - http://www.scopus.com/inward/record.url?scp=85168144253&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ana.26751
DO - https://doi.org/10.1002/ana.26751
M3 - Article
C2 - 37496368
SN - 0364-5134
VL - 94
SP - 925
EP - 932
JO - Annals of neurology
JF - Annals of neurology
IS - 5
ER -