Long-term Efficacy of Satralizumab in Adults with Aquaporin-4-IgG-seropositive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD): Results from SAkuraMoon (S5.001)
Bibliographic record
Abstract
Objective: To evaluate the long-term efficacy of satralizumab in patients with AQP4-IgG+ NMOSD. Background: Satralizumab reduced the risk of protocol-defined relapse (PDR) and severe PDR vs placebo in the double-blind periods (DBP) of two phase 3 trials in patients with NMOSD: SAkuraSky (NCT02028884; satralizumab + baseline immunosuppressants [IST]) and SAkuraStar (NCT02073279; satralizumab monotherapy). Design/Methods: Patients who completed the DBPs and open-label extensions (OLEs) of SAkuraSky and SAkuraStar were rolled-over into a single-arm, open-label study (SAkuraMoon [NCT04660539]) and continued receiving satralizumab 120mg Q4W +/− IST; we evaluated all AQP4-IgG+ adults (≥18 years) who received ≥1 dose of satralizumab during these studies (data cut-off: 31 January 2022). PDRs in the DBPs were adjudicated by a Clinical Endpoint Committee; however, PDRs in the OLEs and SAkuraMoon were determined by the investigator (iPDRs). We evaluated the annualized iPDR rate (ARR), time to first iPDR, severe iPDR (≥2 point increase in the Expanded Disability Status Scale [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). Results: Overall, 106 AQP4-IgG+ adults were included. The median (range) duration of satralizumab exposure was 5.0 (0.1–7.9) years. The overall adjusted ARR (95% CI) was 0.09 (0.06–0.12). When assessed longitudinally, the ARR did not increase with additional years of exposure (Y1: 0.16 [0.09–0.27]; Y2: 0.10 [0.05–0.20]; Y3: 0.05 [0.01–0.15]; Y4: 0.07 [0.02–0.26]). At Week 240 (4.6 years), 72% (95% CI: 62–80%) of satralizumab-treated patients were free from iPDR, 91% (84–96%) were free from severe iPDR, and 85% (75–91%) had no sustained EDSS worsening. Conclusions: These results demonstrate that the efficacy of satralizumab observed in the DBPs is sustained with long-term treatment. High proportions of patients remained free from relapse, severe relapse, or worsening disability, with a consistently low ARR over 4.6 years of satralizumab exposure. Disclosure: Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Traboulsee has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. The institution of Dr. Traboulsee has received research support from Roche. The institution of Dr. Traboulsee has received research support from Genzyme. Ingo Kleiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Ingo Kleiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Ingo Kleiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Ingo Kleiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Ingo Kleiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Ingo Kleiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Hexal. Ingo Kleiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Ingo Kleiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Almirall. Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck Serono, Medimmune, Argenx, Janssen, Mitsubushi, UCB, Roche, Novartis, Amplo, Alexion, Chugai, Sanofi. Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx, Sanofi. Dr. Palace has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Roche, UCB, Alexion, Chugai. Dr. Palace has stock in Astra Zenica. The institution of Dr. Palace has received research support from Roche, AMPLO, Alexion, UCB,.Meddimune, . Dr. Palace has received intellectual property interests from a discovery or technology relating to health care. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck Boipharma. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Japan Tobacco. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Mitsubishi-Tanabe. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chugai. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Fujihara has received research support from Ministry of Health, Welfare and Labor of Japan. Dr. Fujihara has received personal compensation in the range of $10,000-$49,999 for serving as a speaker, chair, etc with Novartis. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving as a speaker, chair, etc with Biogen. Dr. Fujihara has received personal compensation in the range of $10,000-$49,999 for serving as a speaker, chair, etc with Mitsubishi-Tanabe. Dr. Fujihara has received personal compensation in the range of $10,000-$49,999 for serving as a apeaker, chair, etc with Chugai. Dr. Fujihara has received personal compensation in the range of $10,000-$49,999 for serving as a speaker, chair, etc with Alexion. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a chair, speaker with Asahi Kasei Medical. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a speaker with Eisai. Dr. Fujihara has received personal compensation in the range of $500-$4,999 for serving as a speaker, chair with Teijin. Dr. Fujihara has received personal compensation in the range of $5,000-$9,999 for serving as a speaker with Roche. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janseen. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for novartis. Albert Saiz has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Vodopivec has received personal compensation for serving as an employee of Roche. An immediate family member of Dr. Vodopivec has received personal compensation for serving as an employee of Novartis. Dr. Vodopivec has stock in Roche. Gaelle Klingelschmitt, 17039 has received personal compensation for serving as an employee of F.Hoffmann-La Roche LTD. Carole Marcillat has received personal compensation for serving as an employee of Hoffmann La Roche. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Horizon Therapeutics. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Reistone Bio. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Antigenomycs. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chugai. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MedEdicus. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ImCyse. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Clene Nanomedicine. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Podoll. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Patterson. The institution of Dr. Bennett has received research support from Novartis. The institution of Dr. Bennett has received research support from Alexion. Dr. Bennett has received intellectual property interests from a discovery or technology relating to health care. Dr. Bennett has received publishing royalties from a publication relating to health care.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".