Compared with placebo, satralizumab reduces the risk of severe relapse in patients with neuromyelitis optica spectrum disorder (NMOSD), according to investigators. The drug also was associated with a lower likelihood of using acute relapse therapy.
These results were presented at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS–ACTRIMS) 2020, this year known as MSVirtual2020.
NMOSD is characterized by acute relapses that are unpredictable and lead to the accumulation of disability. “Patients with NMOSD often recover poorly from relapses, therefore, the primary goal for disease management is to reduce attack frequency,” said Ingo Kleiter, MD, medical director of Marianne-Strauß-Klinik in Berg, Germany. “In the two phase 3 trials SAkuraSky and SAkuraStar, the IL-6 receptor inhibitor satralizumab was found to significantly reduce the risk of relapses versus placebo.” Satralizumab is a humanized, monoclonal, recycling antibody that targets the interleukin-6 receptor.
Dr. Kleiter and colleagues examined pooled data from the two phase 3 trials of satralizumab to determine the treatment’s effect on relapse severity in patients with NMOSD. Participants in those trials received placebo or 120 mg of satralizumab at weeks 0, 2, 4, and every 4 weeks thereafter.
For their research, the investigators analyzed data from the pooled intention-to-treat population in the double-blind periods of both studies. To evaluate the severity of protocol-defined relapses, they compared patients’ Expanded Disability Status Scale (EDSS) scores at the time of relapse with their scores before the relapse (i.e., their scores at the last scheduled study visit). Using the visual Functional Systems Score (FSS), Dr. Kleiter and colleagues performed a similar analysis on optic neuritis relapses. They categorized a protocol-defined relapse as severe if it entailed a change of two or more points on the EDSS or visual FSS. The investigators conducted Kaplan-Meier analyses to evaluate the time to first severe protocol-defined relapse. They also compared the number of patients receiving acute therapy for any relapse between treatment groups.
Safety Profile Confirmed
Dr. Kleiter and colleagues included 178 patients in their analyses. A total of 27 of 104 patients (26%) who received satralizumab had a protocol-defined relapse, compared with 34 of 74 patients (46%) who received placebo. The number and proportion of severe protocol-defined relapses were lower in the satralizumab group (5 of 27 events [19%]), compared with the placebo group (12 of 34 events [35%]). In addition, the number and proportion of severe protocol-defined optic neuritis relapses were lower in patients receiving satralizumab (2 of 8 events [25%]), compared with those receiving placebo (5 of 13 events [39%]). Compared with placebo, satralizumab was associated with a 79% reduction in the risk of severe protocol-defined relapse (hazard ratio, 0.21).
A lower proportion of patients receiving satralizumab was prescribed acute relapse therapy (38%), compared with patients receiving placebo (58%). The odds ratio of receiving a prescription of acute relapse therapy was 0.46 among patients receiving satralizumab.
The activity of IL-6 may cause neurologic damage in patients with NMOSD through astrocytic damage, disruption of the blood–brain barrier, and T cell polarization. “It is proposed that through inhibiting IL-6 across these multiple mechanisms, satralizumab reduces the risk and severity of NMOSD attacks,” Dr. Kleiter said.
To date, the rates of infection and serious infection for patients treated with satralizumab in the combined double-blind and open-label extension periods have been consistent with those for patients treated with satralizumab in the double-blind portion. These rates have not increased over time. Satralizumab is administered as a subcutaneous injection every 4 weeks, and treatment can be self-administered at the discretion of the managing physician. “These data provide reassurance to physicians about the overall profile of satralizumab, with respect to efficacy and safety in the longer term,” said Dr. Kleiter.
Does Satralizumab Differ From Other New Agents?
The main strength of the study is that sufficient numbers of relapses were available for analysis in the active and control groups, said Achim Berthele, MD, associate professor of neurology at the Technical University of Munich. This allowed the researchers to examine whether satralizumab led to a better outcome after each relapse, which it did. “A weakness is how the severity of relapses was quantified,” said Dr. Berthele. “The EDSS as a measure is not linear, and its functional systems are not clinically equivalent. However, the whole NMOSD community is struggling with this problem.”
The study’s implications for neurologists’ clinical practice are unclear, however. “Although the results presented are encouraging, the data are still too small to say with certainty that satralizumab does indeed improve the outcome of relapses,” said Dr. Berthele. “It is also an open question whether satralizumab differs in this respect from the other new immunotherapeutic agents.”
Investigators must collect further data on the outcome of relapses that occur during treatment with modern immunomodulatory therapy, Dr. Berthele added. Future research could examine whether the new anti-inflammatory immunotherapeutic agents also are suitable drugs for relapse therapy. Another salient question is whether clinical vigilance or relapse therapy in NMOSD has improved in general. “This is what Kleiter and colleagues show as well: The number of severe relapses under placebo was much lower than expected,” said Dr. Berthele.
Chugai/Roche funded the study. Dr. Kleiter has received compensation for consulting, speaking, or serving on advisory boards for Alexion, Biogen, Celgene, Merck, and Roche. Dr. Berthele was not involved in any of the satralizumab trials, but is an investigator and coauthor of the PREVENT trial of eculizumab.
SOURCE: Kleiter I, et al. MSVirtual2020. Abstract FC01.03.
This article also appeared on MDedge.com , part of the Medscape Professional Network.