Author Of 2 Presentations
P0721 - Infection rates with satralizumab in patients with neuromyelitis optica spectrum disorder (NMOSD): results from the phase 3 SAkura studies (ID 1362)
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).
To assess the impact of satralizumab on infection risk in patients with NMOSD.
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.
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.
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.
P0753 - Safety of satralizumab based on pooled data from phase 3 studies in patients with neuromyelitis optica spectrum disorder (ID 1375)
Interleukin-6 (IL-6) is implicated in the immunopathology of neuromyelitis optica spectrum disorder (NMOSD). Satralizumab, a humanized recycling monoclonal antibody that inhibits the IL-6 receptor, demonstrated a reduction in NMOSD relapse risk in two phase 3 studies: SAkuraSky (satralizumab in combination with baseline immunosuppressants; NCT02028884), and SAkuraStar (satralizumab monotherapy; NCT02073279).
To evaluate the safety of satralizumab vs placebo in a pooled population of NMOSD patients from the SAkura studies, including the latest data from the open-label extension (OLE) period of the studies.
SAkuraStar and SAkuraSky are randomized studies comprising a double-blind (DB) period (satralizumab 120mg Q4W vs placebo) followed by an OLE period (satralizumab only). The combined DB and extension period was defined as the overall satralizumab treatment (OST) period (cut-off: 7 Jun 2019). Safety was evaluated in the DB and OST periods and reported as adverse event (AE) rates per 100 patient-years (PY).
The pooled DB population included 178 patients (satralizumab, n=104; placebo, n=74), and 166 patients received satralizumab in the OST. Median duration of safety observation with satralizumab was 96.1 weeks in the DB period and 131.9 weeks in the OST period. Rates of AEs and serious AEs were comparable between satralizumab and placebo groups in the DB period (AEs: 478.49 vs 506.51 events/100PY, respectively; serious AEs: 14.97 vs 17.98 events/100PY, respectively), and were consistent in the OST period. In the DB period, four patients (3.8%) in the satralizumab group and five (6.8%) in the placebo group discontinued treatment due to AEs. Serious infection rates were comparable between the satralizumab and placebo groups in the DB period (4.13 vs 6.99 events/100PY) and remained stable in the OST (3.88 events/100PY). No opportunistic infections were observed in the satralizumab group. The injection-related reaction (IRR) rate was higher with satralizumab vs placebo in the DB period (17.03 vs 8.99 events/100PY); IRRs were mostly mild-to-moderate and did not lead to treatment discontinuation. Laboratory abnormalities were in line with those expected with IL-6 receptor antagonists in the DB and OST period. No deaths or anaphylactic reactions were reported.
In NMOSD patients, satralizumab was well tolerated and showed a favorable safety profile. Results from the OST period were consistent with the DB period.