Ultomiris lifts quality of life, easing fatigue and brain fog in small study

One year of treatment with Ultomiris (ravulizumab-cwvz) was associated with reduced fatigue and improved quality of life for three older adults with generalized myasthenia gravis (gMG), according to a small study in Italy.

While all three patients experienced less muscle weakness and fewer daily struggles, changes in cognitive performance — including task-switching and cognitive fatigue — varied from person to person.

Though these findings suggest that treatment with Ultomiris was associated with reductions in nonmotor symptoms such as fatigue, as well as muscle issues, researchers noted that larger studies with a control group are needed to confirm a direct treatment effect.

The study, “Multidomain Fatigue, Cognitive, and Quality of Life Observations in Generalized Myasthenia Gravis Under Ravulizumab: A Case Series,” was published in the journal Neurology and Therapy.

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Nonmotor symptoms often overlooked in gMG

gMG is an autoimmune disease where the body’s defense system mistakenly attacks the communication links between nerves and muscles, resulting in symptoms such as muscle fatigue and weakness. Clinical care and treatment decisions have traditionally focused on these physical symptoms.

However, many people living with gMG also experience nonmotor challenges, such as overwhelming fatigue, mental slowing, trouble staying focused, and a subjective sense of “cognitive fog.”

“These experiences are frequently described in clinical practice but remain poorly defined,” the researchers wrote. They explained that these mental difficulties likely stem from a mix of interacting factors, including daily fatigue, the extra mental effort needed to cope with fluctuating muscle weakness, poor sleep, medication side effects, and emotional stress.

Ultomiris, marketed by Alexion (a division of AstraZeneca Rare Disease), is approved in the U.S. for adults with gMG who test positive for anti-acetylcholine receptor (AChR) antibodies — the most common self-targeted proteins driving the condition. The therapy works by blocking a key part of the immune system’s complement pathway, stopping it from attacking nerve-muscle connections.

While Ultomiris is known to help control muscle weakness, few studies have measured its impact on everyday fatigue, cognitive fatigue, and overall quality of life.

To learn more, a research team analyzed medical data from three older adults (average age 73) with AChR-positive gMG who received Ultomiris at a single medical center in Italy. The patients completed clinical tests before starting treatment and again after roughly one year.

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Measuring real-world improvements in fatigue and daily life

All three patients experienced meaningful improvements in their ability to handle everyday tasks, measured by the Myasthenia Gravis Activities of Daily Living scale. Baseline scores ranged from 9 to 10 points out of 24. After one year of treatment, scores dropped to 7 in all three patients — exceeding the two-point drop that doctors consider a meaningful clinical improvement.

Muscle weakness also eased across the board. Scores on the Quantitative Myasthenia Gravis scale decreased from a range of 10 to 17 at baseline to 8 to 15 after treatment, indicating less severe disease.

Fatigue levels dropped significantly as well. On the Neuro-QoL Fatigue test, scores improved by 13 to 17 points — above the 5-point drop considered clinically meaningful. Similarly, scores on the Modified Fatigue Impact Scale, which assesses how fatigue affects physical, mental, and social functioning, decreased across all three patients (by 3, 9, and 20 points). However, fatigue’s impact on cognitive function showed mixed results: cognitive fatigue scores dropped noticeably in two patients but rose slightly in the third.

Overall quality of life, measured by the Myasthenia Gravis Quality of Life Scale, improved in all three patients. Scores dropped by 10 to 13 points,  surpassing the 3- to 4-point improvement threshold.

Cognitive performance was tested using the Trail Making Test, which measures visual focus, speed, and mental agility. Part A tests visual attention and processing speed, while Part B measures how easily a person can switch between different mental tasks.

All three patients completed Part A faster after treatment, showing better mental processing speed. Results on Part B were more variable: one patient made major strides in task-switching ability, another showed smaller gains, and the third patient — who could not finish the task within the time limit before treatment — successfully completed it after one year on Ultomiris.

Overall, the researchers concluded that case series like this highlight the need to measure fatigue and quality of life alongside muscle strength when evaluating Ultomiris. However, because the study was very small and lacked a control group for comparison, the researchers cautioned that these results should be viewed as preliminary until confirmed by larger trials.