Background: Satralizumab reduced relapse risk vs placebo in neuromyelitis optica spectrum disorder (NMOSD) patients and had a favourable safety profile in two phase 3 trials: SAkuraSky (satralizumab in combination with baseline immunosuppressants, NCT02028884) and SAkuraStar (satralizumab monotherapy, NCT02073279). Here, we present long-term safety data with satralizumab from the double-blind (DB) and open-label extension (OLE) periods of the SAkura studies. Objectives: To analyse the long-term safety of satralizumab in NMOSD patients from the SAkura studies. Methods: SAkuraSky and SAkuraStar are randomised studies comprising a DB period (satralizumab 120 mg every 4 weeks vs placebo) followed by an OLE (satralizumab only). The overall satralizumab treatment (OST) period comprised all patients who received ?1 dose of satralizumab in the DB and/or OLE periods (through to 18 Feb 2020). Safety was evaluated in the DB and OST periods and rates of adverse events (AEs) were reported as events per 100 patient-years (PY). Results: In the SAkuraSky DB period, 41 patients received satralizumab and 42 received placebo; 75 patients were included in the OST period. In the SAkuraStar DB period, 63 patients received satralizumab and 32 received placebo; 91 patients were included in the OST period. Median treatment exposure was 205 weeks (range 4311) in SAkuraSky and 157 weeks (range 5265) in SAkuraStar during the OST period. The safety profile of satralizumab was comparable between the DB and OST periods in both studies. Rates of AEs (SAkuraSky: 389.6 AE/100 PY [95% CI 365.9414.4]; SAkuraStar: 403.0 AE/100 PY [95% CI 379.4427.6]) and serious AEs (SAEs; SAkuraSky: 11.2 SAE/100 PY [95% CI 7.516.1]; SAkuraStar: 12.2 SAE/100 PY [95% CI 8.417.1]) in the OST periods were comparable with satralizumab and placebo in the DB periods. Rates of infection (SAkuraSky: 130.5 AE/100 PY [95% CI 117.0145.2]; SAkuraStar: 89.7 AE/100 PY [95% CI 78.8101.7]) or serious infection (SAkuraSky: 3.5 SAE/100 PY [95% CI 1.66.6]; SAkuraStar: 3.0 SAE/100 PY [95% CI 1.35.8]) with satralizumab in the OST period were not higher than with placebo in the DB period and did not increase over time in either study. Longer exposure to satralizumab in the OST period was not associated with more severe laboratory abnormalities vs the DB period. No deaths or anaphylactic reactions to satralizumab were reported in either study. Conclusions: The favourable safety profile of satralizumab was sustained with long-term treatment.