Background

NMOSD is a chronic, auto-immune disease characterized by acute relapses that lead to accumulating disability. Satralizumab, a humanized, monoclonal antibody that inhibits the interleukin-6 receptor, reduced relapse frequency and had a favourable safety profile in two randomized, phase 3 clinical trials: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).

Objectives

To assess the impact of satralizumab on infection risk in patients with NMOSD.

Methods

Infections and serious infections (those meeting serious adverse event [AE] criteria) in the double-blind (DB: satralizumab 120mg Q4W vs placebo) and open-label extension (OLE: satralizumab 120mg Q4W) periods of SAkuraSky and SAkuraStar were evaluated (data cut 7 Jun 2019). Exposure-adjusted rates (events per 100 patient-years [PY] of exposure) were assessed, as the total exposure time in the DB period was longer for satralizumab than placebo.

Results

Overall, 180 patients were included. In the DB period, infection rates [95% CI] were lower with satralizumab vs placebo in SAkuraStar (99.8 [82.4–119.8] vs 162.6 [125.8–206.9] events/100PY); there was no between-group difference in infection rates in SAkuraSky (satralizumab: 132.5 [108.2–160.5]; placebo: 149.6 [120.1–184.1] events/100PY). Serious infection rates were comparable between satralizumab and placebo in both studies (SAkuraSky: 2.6 [0.3–9.2] vs 5.0 [1.0–14.7] events/100PY, respectively; SAkuraStar: 5.2 [1.9–11.3] vs 9.9 [2.7–25.2] events/100PY, respectively). In both studies, the most common infections in both treatment groups were upper respiratory tract infections and urinary tract infections.

In the combined DB/OLE period (all patients receiving ≥1 dose of satralizumab; n=166; median [range] exposure: 184 [4–276] weeks in SAkuraSky; 122 [5–243] weeks in SAkuraStar), infection and serious infection rates were similar to the DB period (SAkuraSky: 134.5 [119.5–150.8] infections/100PY, 4.1 [1.9–7.8] serious infections/100PY; SAkuraStar: 90.6 [78.4–104.0] infections/100PY, 3.6 [1.6–7.2] serious infections/100PY). The rates of infections and serious infections did not increase over time. There were no cases of progressive multifocal leukoencephalopathy in either study.

Conclusions

There was no increased risk of infection or serious infection observed in patients treated with satralizumab vs placebo in the DB and OLE periods of the SAkura studies.