Evaluation of Nearly 10,000 Natalizumab Infusions at an Academic MS Center Reveals Lack of Clinically Relevant Infusion-related Safety Events

Background: Natalizumab is an approved treatment for relapsing-remitting multiple sclerosis (RRMS) since 2006. Though infusion reactions are usually mild, occur typically within the first six months of treatment and clinically relevant infusion reactions are extraordinarily rare, there is a mandatory one-hour post-infusion monitoring after each dose, independent of treatment duration. This has posed concerns of unnecessarily increasing SARS-CoV2 exposure risks for patients and staff. Objectives: To determine the frequency, severity, and timing of infusion reactions encountered in patients with RRMS during natalizumab infusion and one-hour post-infusion monitoring. Methods: Retrospective cohort study of all patients receiving natalizumab at the University of Washington MS Center's infusion suite. The medical records of patients were reviewed from July 2012 (establishment of the infusion suite) until September 2020, with extracted data being demographics (age, sex), natalizumab treatment (start date, number of infusions), occurrence and nature of the adverse event (type and severity, treatment, time of occurrence in reference to natalizumab treatment), and presence of anti-natalizumab antibody in serum. Adverse events were characterized based on severity (mild to severe). Descriptive statistics are provided. Results: Total of 333 patients with RRMS underwent 9,682 infusions of natalizumab. The mean age was 41 years (standard deviation of 12 years) and 87 (26%) were male. The number of infusions per patient ranged from one to 174, with the mean being 27. Thirtythree infusion-related adverse events were recorded in 26 patients (0.34% of total infusions and 7.8% of patients). The majority occurred during the infusion (77%) and within the first 6-months of treatment (92%). All were categorized as mild in severity. Most common adverse events were itching, gastrointestinal symptoms, headache, and flushing. Symptoms were either self-limited or easily managed with standard clinical protocols, and no patient required emergency care nor hospitalization. Anti-natalizumab antibody was assessed and absent in four cases. Natalizumab was continued in all patients. Conclusions: Infusion-related adverse events are rare, generally mild, and occur during the initial few natalizumab infusions. In this systematic review of almost 10,000 natalizumab infusions, all infusion-related adverse events were mild, and no clinically relevant safety concerns were associated with natalizumab infusions. This highlights a potential opportunity to improve and streamline the infusion and post-infusion monitoring process. Anticipated benefits may include reducing SARS-CoV2 exposure risks for patients and staff, reducing patients' treatment burden, increasing efficiency, as well as improving access to care without neglecting patient safety.