Enspryng, Tocilizumab for NMOSD Found Safe, Effective in Meta-analysis
Enspryng (satralizumab) and tocilizumab — two interleukin-6 (IL-6) receptor inhibitors that prevent inflammation — are generally safe and effective for the treatment of neuromyelitis optica spectrum disorder (NMOSD), a recent meta-analysis reported.
Researchers determined these results by analyzing safety and efficacy outcomes across published observational reports and clinical trials for the two therapies.
“To the best of our knowledge, this is the first meta-analysis to evaluate the effectiveness and safety of Interleukin-6-receptor inhibitors in the treatment of NMOSD,” the researchers wrote.
NMOSD is an autoimmune disease that leads to inflammation and damage to the spinal cord and optic nerve. Patients with the rare disorder experience waves of disease activity, or relapses, followed by periods of remission.
A primary goal of NMOSD treatment is to reduce the severity of disease attacks and prevent relapses, usually with therapies that target the immune system.
Levels of IL-6, an inflammatory mediator, are increased in NMOSD patients, and those with more IL-6 are at a greater risk for disease relapses and increased symptom severity.
Tocilizumab and Enspryng are monoclonal antibody therapies that block the IL-6 receptor, thereby preventing IL-6 from binding and causing inflammation. Enspryng is an approved NMOSD therapy, while tocilizumab — sold as Actemra/RoActemra for treating some inflammatory and autoimmune disorders, such as rheumatoid arthritis — is used as an off-label treatment.
To detail the overall safety and effectiveness of the two therapies for NMOSD, researchers from Tribhuvan University, in Nepal, conducted an analysis of previously published data on IL-6 inhibitors in NMOSD.
Included in the analysis were data from nine studies — six retrospective observational studies and three randomized controlled trials — covering a total of 202 patients. Enspryng was used in two studies and tocilizumab was used in the remaining seven.
The researchers first performed a meta-analysis of clinical outcomes across the seven tocilizumab studies.
Among all 97 patients who received tocilizumab, 76% had not relapsed during the time of follow-up, which was, on average, 12–31.8 months after beginning treatment.
Annualized relapse ratio (AAR) — a measure of relapse frequency over the course of disease — was measured for five of the seven tocilizumab studies, with a higher ratio indicating a greater relapse rate.
AAR was reduced by an average of 2.6 among patients who received tocilizumab, indicating these individuals had fewer relapses with treatment.
Scores on the expanded disability status scale (EDSS), a method of quantifying disability due to disease, did not change with tocilizumab treatment.
Regarding safety, mild or moderate adverse events (side effects) were reported in 56% of people who were given tocilizumab. This was most pronounced among those in randomized trials — where 97% experienced adverse events compared with 48% of those in observational studies.
Commonly reported adverse events included upper respiratory infections, urinary tract infections, high cholesterol, reduced white blood cell count, fatigue, and anemia.
A total of 11% of patients experienced serious adverse events, including pneumonia or deep vein thrombosis, a type of blood clot. Two deaths were reported in patients who were given tocilizumab, but the deaths were determined to be unrelated to treatment.
The researchers then compared results from the tocilizumab studies with the two clinical trials, SAkura Sky (NCT02028884) and SAkura Star (NCT02073279), which examined the effect of Enspryng as an add-on or monotherapy, respectively.
In SAkura Sky, 80% of people given the therapy were relapse-free, compared with 70% in SAkura Star — both of which were significant improvements over the placebo groups. These results were comparable to those seen in the tocilizumab studies.
In both Enspryng trials, relapse rate and disability scores were significantly decreased with treatment, compared with the placebo, indicating a positive effect of the therapy.
Although not included in this analysis, Enspryng also has been evaluated for long-term efficacy. Those data showed that many patients were still relapse-free after nearly four years.
The overall occurrence of adverse events was 90% for the Sky trial and 92% for Star. Serious adverse events occurred in 17% of the Sky participants and 19% of those in Star. The most common of these were upper respiratory and urinary tract infections, and high cholesterol in the bloodstream.
While adverse events were more frequent with Enspryng than tocilizumab, the types of reported events were similar, according to the researchers.
The increased risk of high cholesterol with IL-6 inhibitors makes heart disease a concern, the team noted. However, no recent trials have found a significantly increased risk of heart problems among patients on these therapies.
Summarizing their overall findings, the researchers concluded: “Interleukin-6-receptor inhibitors therapy showed a promising result with good efficacy and acceptable adverse events profile for treatment of NMOSD.”
Of note, IL-6 is thought to increase secretion of AQP4 antibodies, which are observed in about 70% of NMOSD cases. Thus, although these therapies are promising, they are currently only used for patients who are positive for these AQP4 antibodies.
While IL-6 receptor inhibitors “have established themselves as an important class of monoclonal antibodies in the field of treatment of relapses of NMOSD, the road ahead is long, as the benefits are only applicable to a large subset of … patients leaving behind the important hurdle to find a drug that can impact the disease course” for those note in that subgroup, the researchers wrote.