2 approved treatments for NMOSD may work better than off-label one
Review says Ultomiris, Soliris more effective than rituximab for preventing relapses
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Ultomiris (ravulizumab-cwvz) and Soliris (eculizumab), two approved treatments for neuromyelitis optica spectrum disorder (NMOSD), may work better than rituximab — a drug not cleared for treating the autoimmune disease but often used off-label — for preventing NMOSD relapses, according to a new review.
Still, the study findings also suggested that rituximab (sold as Rituxan and MabThera, with biosimilars available) may be more effective at preventing relapses in NMOSD than two other approved therapies, namely Uplizna (inebilizumab) and Enspryng (satralizumab-mwge).
Overall, although the data “favored” Ultomiris and Soliris over rituximab, the differences seen “were not statistically significant,” according to the researchers. Further, the scientists emphasized that none of the findings were sufficient to draw definitive conclusions about the relative effectiveness of these treatments.
Head-to-head studies are needed to determine whether these two approved therapies are superior to rituximab, the team concluded.
However, because rituximab is much cheaper and more widely available than any of the approved therapies, the off-label treatment will likely remain a mainstay for NMOSD, especially in parts of the world where resources are limited, according to the researchers.
The study, “Comparative Evaluation of Rituximab Versus Approved Therapies in Aquaporin-4-IgG-Positive Neuromyelitis Optica Spectrum Disorder: A Systematic Review and Network Meta-analysis,” was published in the journal Neurology and Therapy.
In NMOSD, self-reactive antibodies drive an autoimmune attack that damages the optic (eye) nerves and the spinal cord, causing symptoms such as vision problems and muscle weakness.
Because disease relapses, or sudden periods of symptom worsening, can cause permanent disability among patients, NMOSD treatment mainly aims to prevent such episodes.
Rituximab has long been a mainstay treatment for NMOSD
For many years, rituximab, which works by killing antibody-producing immune B-cells, has been a mainstay of NMOSD treatment. And even with the approval in the last decade of several NMOSD therapies — including Soliris, Ultomiris, Enspryng, and Uplizna — it’s still often used as an off-label treatment.
Soliris and Ultomiris both block an immune protein called C5 that contributes to the inflammatory attacks that mark NMOSD. Uplizna targets a broader population of B-cells than rituximab, while Enspryng suppresses a proinflammatory signaling protein involved in NMOSD.
The new therapies carry much heftier price tags than rituximab, and are generally less accessible to clinicians and patients, especially in resource-limited parts of the world. Moreover, according to the researchers, “their relative effectiveness compared with rituximab remains uncertain.”
Now, a research team composed mainly of scientists in Europe sought to determine whether Soliris, Ultomiris, Enspryng, and Uplizna are substantially more or less effective in NMOSD than the off-label drug.
To find out, the scientists conducted a network meta-analysis. Essentially, this study type pools data from previous clinical trials testing each therapy, then uses statistical analyses to draw comparisons.
The researchers stressed that this type of analysis has many inherent limitations. For example, different clinical trials usually have different designs and study populations, and it’s never possible to fully account for these differences.
New clinical trials directly comparing the different therapies would provide more definitive answers, but conducting those kinds of studies is time-intensive and costly, so network meta-analysis can be a helpful proxy.
“Because NMOSD is a rare condition and conducting large clinical trials is expensive, network meta-analysis provides a valuable tool for comparing available therapies,” the researchers wrote.
1 assessment was time to first relapse after treatment start
The team specifically looked at how well each therapy prevented NMOSD relapses, as measured by the time to first relapse after starting treatment. The results indicated that the time to first relapse tended to be shorter with rituximab than with Ultomiris and Soliris, suggesting that the two approved therapies may be more potent.
Rituximab’s inferiority was seen both in analyses considering trial participants receiving only one therapy (monotherapy) and those including patients also on standard immunosuppressive treatments (combination therapy).
In contrast, time to first relapse tended to be longer with rituximab than Uplizna and Enspryng in the monotherapy analysis. There were no Uplizna data for the combination therapy analysis, but Enspryng appeared to be inferior to rituximab at preventing relapses in that analysis as well.
The likelihood of each therapy being the optimal treatment for NMOSD was highest for Ultomiris in both analyses, the researchers noted. That treatment was followed by Soliris, rituximab, Uplizna, and Enspryng.
Despite numerical trends favoring newer [therapies], rituximab is likely to remain a cornerstone of NMOSD treatment globally owing to its substantially lower cost and wider accessibility, particularly in resource-limited settings.
Importantly, according to the team, the differences between therapies failed to reach statistical significance, meaning that it’s possible that these findings may be due to random chance. Given the inherent limitations of network meta-analysis, the researchers said it’s not possible to draw any definitive conclusions without more data.
The team also noted that their analysis didn’t compare other clinical outcomes, including long-term relapse rates. Further, the scientists did not look at safety profiles, which are very important for people with NMOSD to consider when deciding between treatments.
Overall, the data suggest that at least the two NMOSD-approved therapies may offer advantages over rituximab. But the researchers said that, as a logistical reality, rituximab will likely continue to be a key tool for NMOSD treatment in much of the world.
“Despite numerical trends favoring newer [therapies], rituximab is likely to remain a cornerstone of NMOSD treatment globally owing to its substantially lower cost and wider accessibility, particularly in resource-limited settings,” the team wrote.
Ultomiris and Soliris are sold by AstraZeneca, Enspryng by Roche, and Uplizna by Amgen. None of the companies were directly involved in this study.
