Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H.
BACKGROUND
To assess the long-term effect of the lymphocyte-depleting humanized monoclonal antibody Campath 1H on MR markers of disease activity and progression in secondary progressive MS patients.


METHODS
Twenty-five patients participated in a crossover treatment trial with monthly run-in MR scans for 3 months, followed (after a single pulse of Campath 1H) by monthly MR scans from months 1 to 6 and again from months 12 to 18. MR analysis was performed to provide measurements of the number and volume of gadolinium (Gd)-enhancing lesions as well as the hypointense lesion volume on a T1-weighted sequence. In addition, serial measurements of T2 brain lesion volume, brain volume, and spinal cord cross-sectional area were made over the duration of the study. The relationship between clinical and MR measures of disease evolution was also assessed.


RESULTS
Treatment was associated with a reduction in the number and volume of Gd-enhancing lesions (p < 0.01). Despite this, a decrease in brain volume was seen in 13 patients during the 18 months post-treatment. The mean pretreatment Gd-enhancing lesion volume was predictive of subsequent reduction in brain volume (r = 0.77, p = 0.002). Reduction in brain volume also correlated with the change in T1 hypointense lesion volume after treatment (r = 0.53, p < 0.01). A reduction in spinal cord area was also seen throughout the study duration, and this correlated with an increase in disability (r = 0.65, p = 0.01).


CONCLUSIONS
Campath 1H treatment was associated with a sustained and marked reduction in the volume of Gd enhancement, indicating suppression of active inflammation. Nevertheless, many patients developed increasing brain and spinal cord atrophy, T1 hypointensity, and disability. This study highlights the potential role for novel MR techniques in monitoring the effect of treatment on the pathologic process in MS.
Paolillo
A
A
Institute of Neurology, National Hospital, Queens Square, London.
Coles
A J
AJ
Molyneux
P D
PD
Gawne-Cain
M
M
MacManus
D
D
Barker
G J
GJ
Compston
D A
DA
Miller
D H
DH
D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000473:pathology*; D013116:Spinal Cord / Q000473:pathology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab