Natalizumab-related PML in multiple sclerosis patients in Italy. Report of the Italian Group for MS-PML Study (P4.034)

Objective: To identify safety instruments and prognostic indicators in italian MS patients treated with natalizumab. Background: there is no shared consensus in long-term natalizumab treatment monitoring for PML risk. Choice and timing of diagnostic tests and their correlation to PML clinical outcome is crucial. Design-methods: 20 Italian MS Centers shared data of 25/26 natalizumab-related PML cases. Demographic and MRI data, previous MS treatment(s), EDSS, Karnofsky score, JCV antibodies status, number of natalizumab infusions were recorded. Results: JCV serology was positive in 20/25 patients, not tested in 5/25 (Stratify test not available yet). PML occurred within the 24th month of treatment in 8/25 patients (32[percnt]), between 25th-36th month in 8/25, between 37th-48th month in 3/25 (12[percnt]), over 48 months in 6/25 (24[percnt]). PML was diagnosed due to clinical (18/25) or MRI suspect (7/25). MRI lesions were single (16/25, 64[percnt]), multiple (9/25, 36[percnt]), subcortical (16/25, 64[percnt]). Gadolinium enhancement was observed in 36[percnt] of lesions, without correlation to clinical worsening. A lower MRI lesion load was correlated to a better prognosis. Clinical symptoms at onset were cognitive-behavioural (10/18, 40[percnt]), motor (5/18, 20[percnt]), other (seizures, dystonia, myoclonic jerks: 6/18, 24[percnt]). Onset with motor symptoms was associated with a longer diagnostic delay than cognitive symptoms (mean: 25 vs 75 days). Karnofsky score and EDSS worsened steadily during PML course peaking at 6th month, then disability gradually decreased. A higher number of CSF virus copies was significantly correlated to the worse clinical course and death (2/25). Natalizumab infusions after PML was suspected represent a negative prognostic factor. Conclusions: any new clinical sign observed during natalizumab treatment must raise the suspect of PML. MRI has to be considered a safety exam and should be followed by lunbar puncture to enhance prompt diagnosis. Lower lesion load and number of CSF-JCV copies are correlated to better clinical outcome. Disclosure: Dr. Cordioli has received personal compensation for activities with Genzyme and Biogen Idec. Dr. De Rossi has received personal compensation for activities with Teva. Dr. Gerevini has nothing to disclose. Dr. Amato has received personal compensation for activities with Biogen Idec, Merck, Serono, Inc., Bayer, Novartis, Teva Neuroscience, Sanofi-Aventis, Genzyme, and Almirall as a speaker and/or advisor. Dr. Amato has received research support from Biogen I Dr. Bandini has nothing to disclose. Dr. Cavalla has nothing to disclose. Dr. Capobianco has received personal compensation for activities with Biogen Idec, Sanofi-Genzyme, Novartis, Merck Serono, and Teva as a consultant and/or speaker. Dr. Deotto has received personal compensation for activities with Bayer, Merck Serono, Teva, Novartis, Biogen Idec, and Almirall. Dr. De Riz has nothing to disclose. Dr. Ferrari has nothing to disclose. Dr. Fusco has nothing to disclose. Dr. Ghezzi has received personal compensation for activities with Merck Serono, Novartis, Biogen Idec, Teva, Bayer Schering, Sanofi-Genzyme, Serono, and Almirall as an advisory board member and/or speaker. Dr. Grimaldi has nothing to disclose. Dr. Lugaresi has received personal compensation for activities with Bayer Schering, Biogen Idec, Merck Serono, Genzyme, Sanofi-Aventis Pharmaceuticals, and Teva Neuroscience. Dr. Moiola has received personal compensation for activities with Biogen Idec, Sanofi-Aventis Pharmaceuticals, and Merck Serono as a speaker, Dr. Perrone has nothing to disclose. Dr. Prosperini has received personal compensation for activities with Bayer Schering, Biogen Idec, Genzyme, Novartis, and Teva Neuroscience. Dr. Rezzonico has received personal compensation for activities with IMS Health, McCann Complete Medical, Biogen Idec, Serono, Inc., Bayer Pharmaceuticals Corporation, Teva Neuroscience, Novartis, Aventis Pharmaceuticals Inc., and Baxter International. Dr. Rovaris has received personal compensation for activities with Almirall, Bayer Schering Pharma, Biogen Idec, Novartis, Teva Neuroscience. Dr. Salemi has received research support from Merck Serono, Biogen Idec, Teva Neuroscience, Novartis, Bayer, and Sanofi-Aventis. Dr. Salvetti has received personal compensation for activities with Sanofi-Aventis, Biogen Idec, Bayer Schering, and Merck Serono. Dr. Salvetti has received research support from Sanofi-Aventis, Biogen Idec, Bayer Schering, Merck Serono, and the Italian M Dr. Solaro has received personal compensation for activities with Biogen Idec, Merck Serono, Bayer Schering Pharma, Almirall, Teva Neuroscience, and Genzyme Corporation as an advisory board participant and/or speaker. Dr. Solaro has received research supp Dr. Tortorella has nothing to disclose. Dr. Capra has received personal compensation for activities with Biogen Idec, Sanofi-Aventis, and Novartis as a lecturer and/or consultant.