Lipid-Specific IgM Bands Contribute To Stratify PML Risk in MS Patients Treated With Natalizumab (P2.245)

BACK GROUND AND OBJECTIVE: Lipid-specific IgM bands (LSMB) associate with a suboptimal response to interferon beta in MS. Consequently, many patients treated with natalizumab show these antibodies in CSF. Our aim was to explore if progressive multifocal leukoencephalopathy (PML) risk may change in patients showing and lacking these antibodies. DESIGN/METHODS: Multicenter study including 367 MS patients treated with Natalizumab in 23 European hospitals. All patients gave their inform consent before entering the study. Anti JC antibodies were measured in serum by a two-step enzyme-linked immunosorbent assay (ELISA). LSMB were measured by isoelectrofocusing and affinity blot in paired serum and CSF samples. Previous treatments with immunossuppresant drugs and treatment duration were recorded. Data were analysed using U Mann-Whitney and Fisher exact tests. RESULTS: Twenty three patients developed a PML during natalizumab treatment. Only one of them had LSMB. However, 228 of the 344 patients that did not develop PML (66.3%) showed these antibodies. We analysed the risk of PML and observed a protective effect of LSMB (OR=40.4, CI: 5.4-303.8, p<0.0001). As described previously, the absence of anti JC antibodies also showed a protective effect (OR=24.5, CI: 3.2-185.2, p<0.0001). To study the effect of the combination of the two variables, we further classified anti JC+ patients according to LSMB status. 61% showed LSMB and 39% (69 patients) lacked these antibodies (Anti JC+, LSMB-). Twenty-one patients of this group developed PML. When analysed PML risk, no differences were found between anti JC- patients and anti JC+, LSMB+ ones (p=1.0). By contrast, we found clear differences between these groups and anti JC+LSMB- patients, which concentrated 90% of PML cases (OR=58.2, CI: 13.2-25,4, p<0.0001). CONCLUSIONS: The presence of lipid specific IgM bands contribute to identify JC+ patients at lower risk of PML during natalizumab treatment. Study Supported by: Red Espanola de Esclerosis Multiple (REEM) and Grants from the Spanish Ministry of Economy and by Instituto de Salud CarlosIII. Disclosure: Dr. Villar has received personal compensation for activities with Bayer Schering, Merck Serono, Biogen Idec, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals Inc., and Novartis as a consultant or speaker. Dr. Villar has received research support from Teva Neuroscience, Merck Serono and Biogen Idec. Dr. Costa-Frossard has received personal compensation for activities with Bayer Schering Pharma, Merck & Co. Inc., Biogen Idec, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals Inc., and Novartis. Dr. Masterman has nothing to disclose. Dr. Fernandez has received personal compensation for activities with Bayer Schering, Biogen Idec, Merck Serono, Teva Neuroscience, Novartis, and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Fernandez has received research support from Bayer Schering, Biogen Idec, Merck Serono, Teva Neuroscience, Novartis, and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Montalban has received personal compensation for activities with Bayer Pharmaceuticals Corp., BIogen Idec, EMD Serono, and Genente. Dr. Casanova has received personal compensation for activities with Merck & Co. Inc., Biogen Idec, Novartis, Genzyme-Sanofi, Teva Neuroscience, and Bayer Pharmaceuticals Corporation. Dr. Casanova has received research support from Biogen Idec, Almirall, Merck & Co. Inc., Teva Neuroscience, and Genzyme-Sanofi. Dr. Izquierdo has received personal compensation for activities with Biogen Idec, Merck & Co. Inc., Bayer Pharmaceuticals Corp., Sanofi-Aventis Pharmaceuticals Inc., Teva Neuroscience, and Novartis. Dr. Coret Ferrer has nothing to disclose. Dr. Tumani has received personal compensation for activities with Bayer Pharmaceuticals Corp., Biogen Idec, Merck Serono, Teva Neuroscience, Roche Diagnositcs Inc., and Genzyme Virotech. Dr. Tumani has received personal compensation for activities with Bayer Pharmaceuticals Corp., Biogen Idec, Merck Serono, Teva Neuroscience, Roche Diagnostics Corp., and Genzyme Virotech. Dr. Saiz has received personal compensation for activities with Bayer Schering, Merck Serono, Biogen Idec, Sanofi-Aventis Pharmaceuticals Inc., Teva Neuroscience, and Novartis. Dr. Arroyo has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Merck & Co., Inc., Biogen Idec, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals Inc., and Novartis. Dr. Fink has received personal compensation for activities with Novartis. Dr. Leyva has nothing to disclose. Dr. Espejo has received personal compensation for activities with Merck Serono and Almirall. Dr. Alvarez-Lafuente has received personal compensation for activities with Merck & Co., Inc., and Biogen Idec. Dr. Olascoaga has nothing to disclose. Dr. Olaskoaga Urtaza has nothing to disclose. Dr. Oterino has nothing to disclose. Dr. Llufriu Duran has received personal compensation for activities with Novartis, Biogen Idec, and Teva Neuroscience as a consultant. Dr. Lauda has nothing to disclose. Dr. De Andres has nothing to disclose. Dr Garcia-Merino has received personal compensation for activities with Bayer Pharmaceutical Corp., Merck & Co., Biogen Idec, Teva Neuroscience, Roche Diagnostics Corp., and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Fernandez-Bolanos has nothing to disclose. Dr. Landete Pascual has nothing to disclose. Dr. Aguera Morales has nothing to disclose. Dr. Diaz Nicolas has nothing to disclose. Dr. Menendez has nothing to disclose. Dr. Navarro has nothing to disclose. Dr. Perez has nothing to disclose. Dr. Girona has received personal compensation for activities with Biogen Idec, Merck Serono, Bayer-Schering, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals Inc., and Almirall. Dr. Sanchez Lopez has nothing to disclose. Dr. Serrano Castro has nothing to disclose. Dr. Tunon has nothing to disclose. Dr. Alvarez-Cermeno has nothing to disclose.