[P02.155] The Cellular Immune Response Against Epstein-Barr Virus in Multiple Sclerosis and Cross-Reactivity with Brain Antigens
J. William Lindsey, Landon M. Hatfield, Houston, TX
The cellular immune response against EBV is similar in PwMS and controls; with no evidence of cross-reactivity between EBV and brain antigens.
[S31.003] Evaluation of the Incidence of Anti-JCV Antibodies in a Cohort of Natalizumab-Treated MS Patients
Leonid Gorelik, Sarah Bixler, Michaela Lerner, Ewa Wilson, Anne Cheung, Ling Ling Chen, Melissa Berman, Mary Crossman, Ken Simon, Brian Schlain, Susan Goelz, Meena Subramanyam, Cambridge, MA
Classification of MS patients as sero-negative or sero-positive with respect to previous JC virus exposure is possible with a new assay. Thirteen out of 13 patients who developed PML all had evidence of prior infection with JCV, as measured by the presence of anti-JCV antibodies. This assay will help stratify patients into high and low risk groups and modify the risk for individual subjects; those with positive antibodies will have double the risk of getting PML (this is based on the observation that ~54% of subjects in the original natalizumab trial were sero-positive. The corollary to this is that subjects seronegative have a very low risk of getting the disease.
[P05.047] The Kinetics of CSF Lymphocyte Recovery after Cessation of Natalizumab in Patients with Multiple Sclerosis
Adil Javed, Chicago, IL, Howard Rossman, Farmington Hills, MI, Anthony Reder, Chicago, IL
After stopping natalizumab treatment CSF lymphocytes counts may recover within 3 months. This implies that immune surveillance is restored shortly after cessation of natalizumab therapy and coincides with observation that IRIS in the setting of natalizumab-associated PML also occurs at this time-point unless hastened by plasma exchange.
[S31.002] Effects of Natalizumab Treatment on the Presence of JC Virus DNA in Blood or Urine in Multiple Sclerosis Patients
Richard Rudick, Solon, OH, Paul O'Connor, Toronto, ON, Canada, Chris Polman, Amsterdam, The Netherlands, Andrew Goodman, Rochester, NY, Soma S. Ray, Stephanie Jurgensen, Cambridge, MA, Susan Goelz, Portland, OR, Fiona Forrestal, Maidenhead, Berkshire, United Kingdom, Leonid Gorelik, Alfred Sandrock, Cambridge, MA
Cross-sectional and longitudinal testing in a large cohort of MS patients demonstrates that there is no substantial change in the presence of JCV DNA in the plasma, whole blood or urine with natalizumab treatment. Less than 1% (4 out of 1397) patients had JCV DNA in their blood, which did not predict the occurrence of PML. In addition, in cases that developed PML plasma samples were negative prior to diagnosis. This study and other recent studies seriously calls into question the validity of the results of other smaller studies suggesting that natalizumab increases peripheral blood and urine JCV detection rates. From a practical perspective we cannot use plasma, peripheral blood or urine JCV DNA detection to predict PML risk in natalizumab-treated patients. Will this study end the debate? Please watch this space.
[P05.036] Long-Term Follow-Up of Immune Thrombocytopenia after Treatment of Multiple Sclerosis Patients with Alemtuzumab in CAMMS223
Edward Fox, Round Rock, TX, N. A. on Behalf of the CAMMS223 Study Group
Cutaneous symptoms of ITP went unrecognized in the 1st case until onset of a fatal cerebral haemorrhage. Five other cases were subsequently diagnosed with ITP with onset between 1.5 and 16 months after alemtuzumab. In one case ITP resolved without treatment. In 2 cases, remission was achieved with corticosteroid treatment alone and in the other 2 patients following treatment with rituximab cycle. On balance these results suggest that ITP is a manageable side effect of alemtuzumab provided it is detected and treated early.
[P04.213] Alemtuzumab Reduces Disease Progression in RRMS: Long-Term Results of the CAMMS223 Trial
Omar Khan, Detroit, MI, N. A. on Behalf of the CAMMS223 Study Group
At year 4: (1) 77% of alemtuzumab-treated patients were relapse–free compared to 49% of IFNB-1a-treated patients; (2) 91% of alemtuzumab-treated patients were disease progression free vs. 68% of IFNB-1a patients (p<0.001); (3) 71% of alemtuzumab patients were clinically disease-free v. 35% for IFNB-1a at year 4 (p<0.001). A treatment effect at year 4 in patients who only completed 2 annual cycles of alemtuzumab during the first 12 months supports the strategy of aggressive induction therapy in early MS. No wonder PwMS want this drug.