Contributions
Abstract: P1247
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Background: Natalizumab (NTZ) is a highly effective therapy for multiple sclerosis, but it is associated with a high risk to develop Progressive Multifocal leukoencephalopathy (PML). Infusion of NTZ every 5-8 weeks (extended interval dosing, EID) is an approach that has been explored with the aim of reducing PML risk while maintaining efficacy.
Goals: To evaluate, in the Italian PML cohort, the presence of PML when reducing the NTZ frequency and to describe the cases of PML emerged during EID.
Methods: Clinical and imaging data of all the Italian patients who develop NTZ-PML from 2009 were retrospectively collected from 35 Italian sites. The clinical course was described and the longitudinal EDSS were recorded. The data were centrally reviewed and full-blown IRIS was identified in each patient. We defined EID when NTZ infusions were performed every 5 weeks or more.
Results: Up to April 2018, 56 cases of NTZ-PML occurred in Italy, five of which in EID (8.92%). Here, we present the data of four out of five of these patients. These patients developed PML after 74, 50, 47 and 38 infusions, of which the last 22, 9, 26 and 22 respectively were administered in EID regimen. All the four patients had a high JCv index prior to PML onset (3; 3,18; 2.3; 3.13). No one of them had a previous history of immune suppressant use. For all of them, PML was suspected on radiological findings (occipital; frontal; parietal; temporo-parietal lesion). Two patients were asymptomatic at PML onset, while two were symptomatic (respectively motor impairment of the right hand; anomia). All of them but one, who had 37 JCV copies/ml, had undetectable CSF viral load. Three patients showed enhancement suggestive of immune reconstitution. In two cases, this enhancement was coupled with clinical worsening, thus meeting the shared criteria for full blown IRIS. Three patients had a positive outcome: the increase of EDSS from NTZ beginning and the last follow up (one year after PML onset) is of 0.5 EDSS points. The fourth patients has been only recently diagnosed (mid April), and the follow up is ongoing.
Conclusions: Patients in EID regimen may develop PML. Despite this, PML in these patients seems to be milder with a favorable clinical outcome as the first three patients ended with reduced impairment at last follow up. Contrarily to PML patients receiving NTZ in standard dose described in literature, in EID-PML patients the IRIS did not severely impacted on patients disability.
Disclosure: Dr. Scarpazza, Dr. Tabiadon, Dr. Turrini and Dr. Mancinelli have nothing to disclose. Dr. De Rossi received speaker honoraria from Biogen and Teva and travel grants from Biogen, Teva and Merk Serono. Dr. Gerevini received speaker honoraria from Biogen-Idec. Dr. Capra received consulting fees from Novartis, Biogen-Idec and lecture fees and/or travel grants from Novartis, Biogen-Idec, Genzyme and Sanofi-Aventis.
Abstract: P1247
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Background: Natalizumab (NTZ) is a highly effective therapy for multiple sclerosis, but it is associated with a high risk to develop Progressive Multifocal leukoencephalopathy (PML). Infusion of NTZ every 5-8 weeks (extended interval dosing, EID) is an approach that has been explored with the aim of reducing PML risk while maintaining efficacy.
Goals: To evaluate, in the Italian PML cohort, the presence of PML when reducing the NTZ frequency and to describe the cases of PML emerged during EID.
Methods: Clinical and imaging data of all the Italian patients who develop NTZ-PML from 2009 were retrospectively collected from 35 Italian sites. The clinical course was described and the longitudinal EDSS were recorded. The data were centrally reviewed and full-blown IRIS was identified in each patient. We defined EID when NTZ infusions were performed every 5 weeks or more.
Results: Up to April 2018, 56 cases of NTZ-PML occurred in Italy, five of which in EID (8.92%). Here, we present the data of four out of five of these patients. These patients developed PML after 74, 50, 47 and 38 infusions, of which the last 22, 9, 26 and 22 respectively were administered in EID regimen. All the four patients had a high JCv index prior to PML onset (3; 3,18; 2.3; 3.13). No one of them had a previous history of immune suppressant use. For all of them, PML was suspected on radiological findings (occipital; frontal; parietal; temporo-parietal lesion). Two patients were asymptomatic at PML onset, while two were symptomatic (respectively motor impairment of the right hand; anomia). All of them but one, who had 37 JCV copies/ml, had undetectable CSF viral load. Three patients showed enhancement suggestive of immune reconstitution. In two cases, this enhancement was coupled with clinical worsening, thus meeting the shared criteria for full blown IRIS. Three patients had a positive outcome: the increase of EDSS from NTZ beginning and the last follow up (one year after PML onset) is of 0.5 EDSS points. The fourth patients has been only recently diagnosed (mid April), and the follow up is ongoing.
Conclusions: Patients in EID regimen may develop PML. Despite this, PML in these patients seems to be milder with a favorable clinical outcome as the first three patients ended with reduced impairment at last follow up. Contrarily to PML patients receiving NTZ in standard dose described in literature, in EID-PML patients the IRIS did not severely impacted on patients disability.
Disclosure: Dr. Scarpazza, Dr. Tabiadon, Dr. Turrini and Dr. Mancinelli have nothing to disclose. Dr. De Rossi received speaker honoraria from Biogen and Teva and travel grants from Biogen, Teva and Merk Serono. Dr. Gerevini received speaker honoraria from Biogen-Idec. Dr. Capra received consulting fees from Novartis, Biogen-Idec and lecture fees and/or travel grants from Novartis, Biogen-Idec, Genzyme and Sanofi-Aventis.