Newly published in Neurology and Therapy, a 6-month interim analysis of an ongoing post-marketing surveillance (PMS) study on satralizumab (Enspryng; Genentech), an anti-interleukin-6 receptor antibody approved for neuromyelitis optica spectrum disorder (NMOSD), demonstrated safety and efficacy in the routine clinical practice among Japanese patients with the disease. These findings are consistent with those observed in prior studies and investigators noted that they will continue to analyze data gathered from this study over a 6-year period.1
Among 570 Japanese patients with NMOSD, 523 of them were women (91.75%) and the mean age was 52.4 years (SD, 14.1). At baseline, researchers reported that the mean expanded disability status scale (EDSS) among the included cohort was 4.19 (SD, 2.19). In addition, at baseline, 490 patients used glucocorticoids (85.96%) and 277 patients used immunosuppressants concomitantly (48.59%). Notably, 85 (14.91%) of 570 satralizumab-treated patients discontinued satralizumab treatment after 6 months.
"The results (safety and efficacy) are within the range of my expectations, but most surprising was that so many patients have already been given satralizumab for patients with NMO in Japan. The drug was approved in Japan just 4 years ago, and there are only 6500 patients in Japan," senior author Takashi Yamamura, MD, PhD, director of the Multiple Sclerosis Center at National Center of Neurology and Psychiatry in Japan told NeurologyLive®. "How rapidly the practice with satralizumab will spread in Japan was not anticipated before approval of the drug. The entry of more than 500 patients may indirectly reflect the fact that satralizumab is a user-friendly drug allowing self-injection monthly. It may also indicates that occurrence of unexpected events was not common, which pushed the doctors to use satralizumab for these patients."
In an analysis of the ongoing PMS study, which is expected to complete in February 2027, investigators assess the efficacy and safety of satralizumab among Japanese patients with NMOSD using data collected between August 2020 and July 2021. Conducted by senior author Takashi Yamamura, MD, PhD, director of the Multiple Sclerosis Center at National Center of Neurology and Psychiatry in Japan, and colleagues, the primary outcomes assessed were the proportion of patients with adverse drug reactions (ADRs); incidence of adverse reactions; and concomitant oral glucocorticoids for maintenance therapy. The secondary outcomes were time to relapse and relapse rate when being on continuous treatment with satralizumab.
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Top Clinical Takeaways
- The interim analysis of satralizumab in Japanese patients with NMOSD confirms its safety and efficacy, consistent with prior clinical trials results.
- Despite its limitations, including potential reporting bias and lack of a control group, the study provides valuable real-world data, particularly for Japanese patients.
- A significant reduction in glucocorticoid use and a high relapse-free rate were observed, though serious infections, including one fatal case, were reported.
Further results showed that the mean glucocorticoid dose reduced from 12.28 mg/day (SD, 10.17) at the index date to 8.11 mg/day (SD, 7.30) at 6 months. Moreover, investigators reported that the Kaplan-Meier cumulative relapse-free rate was 94.59% at 6 months (95% CI, 92.25-96.23). In the overall reported ADRs, 76.22 events/100 person-years (66.07-87.48) were observed in 118 (20.70%) patients, while infections were noted in 28 patients (4.91%).
Additional safety findings showed serious infections in 18 treated patients (3.15%), leading to an event rate of 9.05 events/100 person-years (5.80-13.47). Among the 24 reported serious infections, respiratory tract infections (n = 7, 29.17%) and urinary tract infections (n = 6, 25.00%) accounted for the most commonly observed. Authors only reported one fatal ADR suspected of relation to satralizumab in a patient, which was septic shock.
"I am not sure how many of the patients will stay on satralizumab treatment, in 2027 although it is hoped that many will continue. My guess is that a small proportion of the patients may switch to another drug becasue of limited efficacy, side effects, or development of neutralized antibodies to satralizumab," Yamamura added.
In comparison with previous phase 3 trials assessing satralizumab, the patient population in this study was older (mean 52.4 years vs. 45.3 years and 40.8 years in SAkuraStar [NCT02073279] and SAkuraSky [NCT02028884], respectively) and the findings were from an entirely Japanese population.2 In the prior clinical trials, SAkuraStar had no Japanese patients,3 and SAkuraSky was comprised of more than 70% non-Japanese patients.4 Thus, authors noted that these data add value to current evidence, showing that the clinical trial data translates well to a real-world setting in Japan.
All told, limitations of the study include potential reporting bias and lack of a control group since this is an ongoing observational study. Also, investigators noted that assessment of risk factors for infections and other ADRs were adjusted for other variables in the analysis. Authors highlighted that they did not use EDSS and MRI as effectiveness indicators, another limitation of the study. Therefore, researchers underscored that the relapse data collected in this study were not clearly defined in contrast to a clinical trial and may lead to an overestimation relapse incidence. Overall, investigators noted that these PMS study findings may result in underestimation of the effectiveness with the treatment.
"I am sure that under satralizumab treatment glucocorticoid dosage can be reduced. However, I know some patients in whom satralizumab monotherapy was of limited efficacy and use of glucocorticoid is needed. So, It is too much to say that steroid-free treatment is possible with satralizumab, but it can be said that glucocorticoid reduction will be the reality in many patients," Yamamura said.
REFERENCES
1. Yamamura T, Isobe N, Kawachi I, et al. Safety and Effectiveness of Satralizumab in Japanese Patients with Neuromyelitis Optica Spectrum Disorder: A 6-month Interim Analysis of Post-marketing Surveillance. Neurol Ther. Published online July 16, 2024. doi:10.1007/s40120-024-00640-7
2. Yamamura T, Weinshenker B, Yeaman MR, et al. Long-term safety of satralizumab in neuromyelitis optica spectrum disorder (NMOSD) from SAkuraSky and SAkuraStar. Mult Scler Relat Disord. 2022;66:104025. doi:10.1016/j.msard.2022.104025
3. Traboulsee A, Greenberg BM, Bennett JL, et al. Safety and efficacy of satralizumab monotherapy in neuromyelitis optica spectrum disorder: a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2020;19(5):402-412. doi:10.1016/S1474-4422(20)30078-8
4. Yamamura T, Kleiter I, Fujihara K, et al. Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder. N Engl J Med. 2019;381(22):2114-2124. doi:10.1056/NEJMoa1901747
