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Natalizumab is one of the most effective therapies for relapsing-remitting Multiple Sclerosis. One complication is Progressive Multifocal Leucoencephalopathy (PML), a viral brain infection in patients already infected with JC virus. Monitoring of neurological symptoms, JC virus serology and regular brain imaging are required to ensure safe use of this therapy. Local audit data from 2015 indicated poor compliance with safety monitoring, with less than 25% of patients undergoing required investigations within the recommended time intervals. Subsequently a protocol was implemented to improve monitoring, with specialist nurses coordinating the requests for MRI scans and arranging JC virus serology, the frequency of which was determined according to the JC virus index. The records of all patients receiving Natalizumab at the centre were audited to assess the impact of this protocol (n=155). 99.2% of patients were appropriately tested for JC virus and 95.3% were imaged within the recommended interval. Additional work with the informatics and virology team ensured serology results became more easily accessible. The use of a standardised nurse-led operating procedure has resulted in marked improvement in the safety monitoring of Natalizumab.