Long-term Efficacy of Satralizumab in Patients with Aquaporin-4-IgG-seropositive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD): Updated Analysis from the Open-label SAkuraMoon Study
Jacqueline Palace1, Anthony Traboulsee2, Albert Saiz3, Jérôme De Seze4, Ingo Kleiter5, Jeffrey L. Bennett6, Daniela Stokmaier7, Gaëlle Klingelschmitt7, Audrey Yeo Te-ying7, Ivana Vodopivec7, Takashi Yamamura8
1John Radcliffe Hospital, Oxford, United Kingdom, 2University of British Columbia, Vancouver, Canada, 3Service of Neurology, Hospital Clinic and August Pi i Sunyer Biomedical Research Institute, University of Barcelona, Barcelona, Spain, 4Hautepierre Hospital, Strasbourg, France, 5Ruhr University Bochum, Bochum, Germany, 6University of Colorado School of Medicine, Aurora, Colorado, USA, 7F. Hoffmann-La Roche Ltd, Basel, Switzerland, 8National Center of Neurology and Psychiatry, Tokyo, Japan
Objective:
To assess the long-term efficacy of satralizumab in patients with AQP4-IgG+ NMOSD.
Background:

Satralizumab significantly reduced the risk of protocol-defined relapse (PDR) in two pivotal Phase 3 trials in patients with NMOSD: SAkuraSky (NCT02028884; satralizumab + baseline immunosuppressants [IST]) and SAkuraStar (NCT02073279; satralizumab monotherapy).

Design/Methods:
Patients who completed the double-blind periods (DBPs) and open-label extensions (OLEs) of SAkuraSky and SAkuraStar were rolled-over into SAkuraMoon (NCT04660539) and continued receiving satralizumab 120mg Q4W ± IST. Efficacy analyses were based on the overall satralizumab treatment period; patients who received ≥1 dose of satralizumab during the SAkuraSky and SAkuraStar studies (data cut-off: 31 January 2023). PDRs were adjudicated by a Clinical Endpoint Committee in the DBPs and were determined by the investigator (iPDRs) in the OLEs and SAkuraMoon. Annualized iPDR rate (ARR), time to first iPDR, severe iPDR (≥2 point increase in EDSS score), and sustained EDSS worsening (EDSS increase of ≥2, ≥1, or ≥0.5 points for patients with baseline scores of 0, 1–5, or ≥5.5, respectively, confirmed ≥24 weeks post-initial-worsening) were analyzed.
Results:

Overall, 111 AQP4-IgG+ patients were included. The median (range) duration of satralizumab exposure was 5.9 (0.1–8.9) years. The overall adjusted ARR (95% CI) was 0.08 (0.06–0.10), where the ARR did not increase with additional years of exposure (Y1: 0.17 [0.10–0.28]; Y2: 0.10 [0.05–0.19]; Y3: 0.04 [0.01–0.14]; Y4: 0.08 [0.02–0.25]; Y5: 0.05 [0.01–0.17]). At Week 288 (5.5 years), 72% (95% CI: 62–80%) of satralizumab-treated patients were free from iPDR, 91% (83–95%) were free from severe iPDR, and 83% (74–90%) had no sustained EDSS worsening. Three patients discontinued SAkuraMoon (switch to commercial satralizumab, n=2; pregnancy, n=1).

Conclusions:

These results demonstrate the effective long-term management of NMOSD with satralizumab over 5.5 years of treatment. The ARR remained consistently low in satralizumab-treated patients, with high proportions of patients remaining free from relapse, severe relapse, and worsening disability.

10.1212/WNL.0000000000204402