DENVER — The use of the monoclonal antibody satralizumab (Enspryng) for the long-term treatment of anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) provides sustained freedom from relapse with no new safety concerns over 5 years, new research shows.
"In long-term observations, we are seeing a nice, sustained suppression of relapses early, as well as late, in treatment," said study investigator Anthony Traboulsee, MD, University of British Columbia, Vancouver, Canada, in presenting the findings at the Consortium of Multiple Sclerosis Centers (CMSC) 2023 Annual Meeting.
"It remains very tolerable with no participants discontinuing because of side effects," he further told Medscape Medical News. "And importantly, [there are] no signs of a delayed risk of infections for both monotherapy and combination therapy."
Satralizumab, a monoclonal recycling antibody, targets the interleukin (IL)-6 receptor, which is elevated in the serum and cerebrospinal fluid of patients in NMOSD.
The drug was approved by the US Food and Drug Administration in 2020 for the treatment of AQP4 antibody-positive NMOSD after favorable results from two key trials: SAkuraSky and SAkuraStar.
The FDA approval marked satralizumab as the third therapy for NMOSD, following eculizumab (Soliris) and inebilizumab (Uplizna).
Satralizumab is administered in subcutaneous injections every 4 weeks after a run-in period of injections at weeks 0, 2, and 4.
Longest Trial To-Date
To evaluate the drug's long-term efficacy in the treatment of AQP4-IgG-positive NMOSD, patients from the two previous phase 3 trials were entered into the single arm, open-label SAkuraMoon study and continued treatment with the satralizumab 120 mg injections once monthly, with or without immunosuppressive therapy.
The study included 106 patients (mean age 44 years, 89.6% women), all of whom had received one or more doses of satralizumab by the data cutoff of January 2022.
With a median duration of satralizumab exposure of 5 years, the overall adjusted annualized rate of investigator protocol-defined relapse (ARR) was 0.09.
Longitudinal assessment further showed no significant increase in the relapse rate over the course of the study, with an ARR rate of 0.16 at year 1; 0.10 at year 2; 0.05 at year 3; and 0.07 at year 4.
At week 240 (4.6 years), 72% of satralizumab-treated patients were relapse-free, with 91% free from severe relapse.
In addition, 85% of patients had no sustained disability, as measured by Expanded Disability Status Scale (EDSS) worsening, over the study period.
Asked if there are potential subgroups of patients who may be more susceptible to the worsening of disability, Traboulsee responded "not that we can tell as of yet."
"I would like to explore this further as this is a relatively new observation, and, as far as I know, this is the longest follow up for an NMO treatment trial cohort," he said.
Favorable Safety Profile
The safety profile was also favorable, consistent with results in the earlier trials. The longer exposure to satralizumab was not associated with a higher risk of severe (grade 3 or higher) laboratory changes vs the double-blind studies.
"Rates of adverse events and serious adverse events with overall satralizumab treatment were comparable with the double-blind periods," said Traboulsee.
"With satralizumab combined with immunosuppressant therapy, we're not seeing an increased rate of infections, because it's not an immune suppressant — it doesn't suppress lymphocytes or lower immunoglobulin," he added.
While the use of combination therapy has been an important clinical concern, Traboulsee noted that "this does not appear to be the case with satralizumab when combined with daily prednisone or daily azathioprine."
"There is no increased risk of infections compared to placebo, and interestingly appears lower than patients on prednisone or azathioprine alone," he said.
While the median follow-up was 5 years, some in the clinical trial population have been on treatment for up to 7.9 years.
"Based on the current safety and efficacy data, they could stay on this therapy indefinitely, in my opinion," Traboulsee said.
In addition to its long-term safety and efficacy, satralizumab "is easy for patients to take and does not require access to an infusion center. It's easy for physicians to monitor safety, especially since no additional vaccinations or precautions are required beyond what is done in routine care."
"What I conclude from that clinically is that this is a highly effective and safe therapy by itself or in combination with another agent," Traboulsee said.
He noted that the lack of a bump in infections is "really encouraging and very important with a chronic disease that affects elderly patients. So far, so good," he added.
"A Good First-line Therapy"
Commenting on the study for Medscape Medical News, Shailee Shah, MD, an assistant professor in the Neuroimmunology Division at Vanderbilt University Medical Center, Nashville, Tennessee, agreed that that the findings bode well for satralizumab's long-term benefits.
"These are promising results and suggest that satralizumab is very effective in the long-term, and even when patients relapse, those relapses are less severe than they would likely be if the patient were off therapy," she said.
She noted that, while the ability to self-administer injections with satralizumab is convenient, preferences vary.
"This is patient-dependent," Shah said. "For some patients an injectable medication is ideal but for others an infusion medication [such as eculizumab] is preferred."
Overall, however, Shah described satralizumab as "a good first-line therapy for patients with NMOSD in addition to eculizumab/ravulizumab and inebilizumab."
"It is reasonable to consider this medication in isolation or with concomitant immunosuppressive therapy," she said.
Traboulsee's disclosures include relationships with Novartis, Roche, Sanofi (Genzyme), Ingo Kleiter, Alexion, Almirall, Bayer, Biogen, Celgene, Genentech, Hexal, Horizon, Merck, and Sanofi. Shah reports that she has served on advisory boards for Horizon, Alexion, and Genentech.
Consortium of Multiple Sclerosis Centers (CMSC) 2023 Annual Meeting: Abstract DMT05. Presented June 3, 2023.
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Cite this: Long-Term Freedom From NMOSD Relapse With Satralizumab - Medscape - Jun 05, 2023.