Effect of natalizumab on conversion of gadolinium enhancing lesions to T1 hypointense lesions in relapsing multiple sclerosis.
BACKGROUND
Natalizumab, a humanized monoclonal anti-adhesion molecule antibody, reduces the frequency of new gadolinium (Gd) enhancing lesions and relapses in multiple sclerosis (MS). Its effect on evolution of new Gd enhancing lesions to T1 hypointense lesions is unknown.


METHODS
213 patients were randomized to receive 3 mg/kg or 6 mg/kg natalizumab or placebo monthly for 6 months and then followed for a further 6 months. A subset of patients who had one or more new gadolinium enhancing lesions from Month 0 to Month 6 and available electronic data were analysed. Each new Gd enhancing lesion that developed during treatment (months 1-6) was investigated for conversion to a new T1 hypointense lesion at month 12. Lesions were classified as large or small if their cross-sectional area was greater or less than 20 mm2. Because of the similarity of both doses of natalizumab on the frequency of new Gd enhancing lesions, the two natalizumab arms were combined in all analyses.


RESULTS
Compared with the placebo group, the natalizumab group exhibited significant decreases in: (i) the proportion of patients with new Gd enhancing lesions that evolved to T1-hypointense lesions (10/38 [26 %] versus 27/40 [68 %]; p<0.01); (ii) the proportion of patients who developed large T1 hypointense lesions (2/38 [5 %] versus 16/40 [40 %]; p<0.01); (iii) the proportion of new Gd enhancing lesions that became T1 hypointense (11/75 [15 %] versus 118/466 [25 %]; p=0.045); (iv) the mean proportion per patient of new Gd enhancing lesions that converted to T1-hypointense lesions (0.15 versus 0.28; p=0.005), and (v) the odds ratio (OR) of converting from Gd enhancing to T1-hypointense lesions (OR=0.48; 95% CI=0.24, 0.94, p=0.031).


CONCLUSIONS
Natalizumab significantly suppresses the evolution of new Gd enhancing to T1-hypointense lesions. This may reflect several mechanisms including reduced cell migration across the blood brain barrier, reduced T cell activation within lesions, an inhibitory effect on subsequent axonal damage within the new central nervous system lesion, and a reduced likelihood of recurrent lesion inflammation.
Dalton
Catherine M
CM
Institute of Neurology, London, UK.
Miszkiel
Katherine A
KA
Barker
Gareth J
GJ
MacManus
David G
DG
Pepple
Tracy I
TI
Panzara
Michael
M
Yang
Minhua
M
Hulme
Allison
A
O'Connor
Paul
P
Miller
David H
DH
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D004311:Double-Blind Method; D017352:Echo-Planar Imaging / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D005682:Gadolinium; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D000069442:Natalizumab; D016017:Odds Ratio; D018709:Statistics, Nonparametric
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D005682:Gadolinium