Ultomiris found safe, effective in complex NMOSD cases: Study
Therapy showed 'relapse prevention and versatility' in managing disease
The infusion therapy Ultomiris (ravulizumab-cwvz) safely and effectively reduces the risk of a relapse in complex cases of neuromyelitis optica spectrum disorder (NMOSD) and may be combined with rituximab for short periods, a case series study shows.
For four NMOSD patients at a hospital in Fujiyoshida, Japan, Ultomiris prevented a relapse and allowed for a safe transition to the immunosuppressive therapy rituximab, with a period of overlap between the two treatments.
The cases were distinct, but all were complicated by factors like switching from other medications and fighting an active infection. The clinical team generally favored the safety profile of Ultomiris over other approved NMOSD therapies in these situations.
Ultomiris “offers effective relapse prevention and versatility in NMOSD management, even in challenging clinical contexts,” the study’s author, Ryota Amano, MD, PhD, wrote. The study, “Ravulizumab is Effective and Safe for Neuromyelitis Optica Spectrum Disorder Patients in Various Clinical Settings: A Single-Center Case Series with Concomitant Use of Rituximab,” was published in Cureus.
An autoimmune disorder, NMOSD is caused by self-reactive antibodies that target cells in the eye nerves and spinal cord, with resulting nerve inflammation leading to vision problems, numbness, and muscle weakness. Patients often see relapses, periods when symptoms worsen or new ones appear, that can result in cumulative damage and severe disability.
When deciding on a treatment strategy, clinicians and patients may need to strike a balance between managing the symptoms, preventing relapses, and a possible higher risk of infection, as most NMOSD therapies suppress the immune system. Depending on the priorities in a given case, different medications may be appropriate. For example, Ultomiris may carry a lower risk of some infections relative to Enspryng (satralizumab-mwge) due to the drugs’ separate mechanisms of action. Rituximab, which targets immune B-cells, may further increase a vulnerability to infection.
All the medications are approved for NMOSD in Japan. While rituximab (sold as Rituxan and MabThera, with biosimilars available) isn’t approved for it in the U.S., it’s sometimes used off-label.
Treating four ‘complex’ NMOSD cases
Amano documented the management of medication, including Ultomiris and rituximab, in four complex clinical cases. After starting Ultomiris, all the patients remained relapse-free, but still had symptoms. Three to six months into the treatment, they began the transition to rituximab, which was expected to better control their symptoms. During this transition, each patient spent six months on both Ultomiris and rituximab, then moved to rituximab alone.
By overlapping the therapies, the clinicians hoped to combine the relapse-suppressing effects of Ultomiris with the symptom control of rituximab. After six months, when rituximab was expected to reach full efficacy, Ultomiris coud be discontinued.
The patients followed a similar course of medications, but the reasoning was different for each.
The first patient, a man, began Ultomiris after nine relapses, when the “the top priority was to reliably prevent further relapses,” Amano wrote.
Because of persistent neurological symptoms, including walking difficulties and sensory impairment, he was also started on rituximab for better symptom control. His symptoms lessened and no relapses were reported during the year of rituximab treatment, including the six months when Ultomiris was simultaneously administered.
Patients two and three, both women, were initially on Enspryng, but continued having symptoms. Both saw a mild easing of symptoms after switching to Ultomiris, but the transition to rituximab had a greater effect, ultimately
Amano said clinicians may consider transitioning directly from Enspryng to rituximab in this type of situation, but the “transition to [Ultomiris] was expected to carry a lower risk of infection and relapse, making it a safer option.”
For the fourth patient, concerns about immunosuppression also factored into decisions about his treatment, as he tested positive for COVID-19 shortly after his NMOSD diagnosis. The clinical team was concerned about the more aggressive immunosuppressive effects of Enspryng and rituximab while the patient was fighting an infection.
About five months after starting Ultomiris, and in the absence of relapses, he began transitioning to rituximab to treat residual symptoms, including numbness. These eased slightly during the overlap period.
Follow-up monitoring for patients one and two showed no signs of a relapse after six and four months on rituximab alone. A follow-up wasn’t available for patients three and four.
Together, the cases show how Ultomiris can be used flexibly and safely in complex cases, Amano said. While rituximab tended to result in better symptom control, Ultomiris may have helped reduce a relapse risk during challenging moments.
Further research will help clarify the role of Ultomiris and its potential interactions with rituximab, including during longer overlap periods, Amano said. “When introducing [rituximab] with the aim of addressing residual symptoms, further investigation is warranted to identify the patient populations for whom this approach is most appropriate,” Amano wrote.
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