Zilbrysq safe, effective in real world for treating generalized MG: Study
Most patients on approved injection therapy able to reduce or stop steroids
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- In real-world use, Zilbrysq is safe and effective for people with generalized myasthenia gravis who have anti-AChR antibodies, a study found.
- The medication was shown to significantly reduce gMG symptoms and improve function and quality of life.
- Most patients on Zilbrysq were able to stop or reduce long-term steroid use.
The approved therapy Zilbrysq (zilucoplan) safely and effectively eases symptoms and improves function and quality of life for people with generalized myasthenia gravis (gMG) who are positive for antibodies against the acetylcholine receptor (AChR) protein.
These are the main findings of a real-world study from Italy, which also showed that most patients on Zilbrysq were able to reduce or stop treatment with corticosteroids — potent anti-inflammatory medications frequently used for gMG, but whose long-term use is linked to serious side effects.
Further, according to the researchers, the data suggest that individuals with gMG previously on long-term intravenous immunoglobulin (IVIG) might respond better to Zilbrysq. IVIG refers to a treatment in which healthy antibodies are administered to potentially neutralize or reduce the production of disease-causing antibodies.
In the study highlights, the research team wrote that Zilbrysq “is a new potential treatment option for a broad population of AChR-positive gMG … with rapid effect onset and sustained benefit across clinical measures.”
The study, “Early real-life experience on Zilucoplan for generalized myasthenia gravis: ZILU25 multicenter observational study,” was published in the Journal of the Neurological Sciences.
In gMG, the immune system mistakenly attacks proteins involved in the communication between nerve and muscle cells. This leads to the development of the disease’s hallmark symptoms of widespread muscle weakness and fatigue. Most cases are caused by self-reactive antibodies targeting the AChR.
Zilbrysq, self-administered through subcutaneous, or under-the-skin, injections, is approved to treat adults with gMG who test positive for anti-AChR antibodies. It works by suppressing the complement cascade, a part of the immune system that contributes to the immune attacks that drive MG.
Investigating Zilbrysq’s use over time in the real world
The therapy, approved in both the U.S. and the European Union in 2023, had shown benefits in clinical trials. Now, a team of researchers from across Italy conducted a retrospective study to assess the safety and effectiveness of Zilbrysq in a real-world clinical setting.
Their research involved a total of 54 individuals with gMG treated with Zilbrysq at 13 referral MG centers. The patients had a mean age of 57.5 years and a mean disease duration of 10.7 years. Slightly more than two-thirds (69%) were women.
More than half had early-onset MG — meaning symptoms started before the age of 40 — and 57% had undergone thymectomy, a surgical procedure commonly performed in people with gMG. The surgery removes the thymus gland, an organ of the immune system that produces certain immune cells.
Before starting Zilbrysq, nearly all patients (98%) were being treated with the corticosteroid prednisone and/or Mestinon (pyridostigmine). Participants were followed for a mean of 26 weeks, or half a year.
After 24 weeks, or nearly six months, of Zilbrysq treatment, patients had experienced a significant reduction in disease severity, the data showed. This was indicated by score reductions of 13.8 points on the MG-Activities of Daily Living (MG-ADL), 20.46 points in the Quantitative MG (QMG), and 22.84 points in the MG Composite (MGC) scales. MG-ADL evaluates disease impact on daily activities, while QMG and MGC are objective measures of muscle weakness and function; in all, higher scores indicate more severe disease.
Significant score reductions in MG-ADL were observed as early as the first week of treatment, and were sustained for six months. After 48 weeks, or nearly one year, 88.9% of those on the therapy had experienced a clinically meaningful reduction in MG-ADL scores, and more than half (55.6%) showed few or no symptoms.
Clinically relevant reductions in the QMG score were reported in 66.7% of patients after 24 weeks and 57.9% after 48 weeks.
Data from 16 evaluable patients showed that Zilbrysq also improved quality of life after 24 weeks, as reflected by a significant score reduction on the MG Quality of Life 15-item scale (MG-QoL15).
The daily prednisone dose was significantly reduced, by a mean of 8.3 mg, after 24 weeks. At the last follow-up, more than half of the participants were taking a prednisone dose below 10 mg, and 11% were able to discontinue corticosteroids altogether at their last follow-up.
Substantial symptom reductions seen for one-quarter of patients
The positive effects seen with treatment were independent of the presence of simultaneous conditions, disease duration, age at disease onset, sex, or Zilbrysq dose, the data showed. Further, the presence of thymus cancer or treatment resistance did not affect the treatment’s effects.
According to the MGFA Post-intervention Status, used to assess disease remission, 25.6% of the participants experienced a substantial reduction in MG symptoms after 24 weeks of treatment, while symptoms remained stable in 11.1%. For 5.6% of the patients, symptoms worsened.
Overall, most of the patients (87.3%) did not experience disease exacerbation or symptom worsening. During the year prior to starting Zilbrysq, 83.3% of patients needed rescue therapy to manage symptoms, and 52% were hospitalized. After starting Zilbrysq, 9.3% required rescue therapy, and one patient (1.9%) was hospitalized.
[Zilbrysq] was well-tolerated and effective in most patients with AChR-positive gMG. … A clinical meaningful effect was reported since the first week and was sustained after 24 weeks [or nearly six months].
Further analyses indicated that long-term IVIG was significantly associated with a better MG-ADL score response to Zilbrysq after 12 weeks, or about three months, of treatment.
“We hypothesized that a higher complement activation as well as a high disease activity in patients chronically treated with IVIg might determine a better response,” the researchers wrote, adding, however, that “further studies with a broader population and longer follow-up are needed to confirm these real-life preliminary data.”
The therapy was generally well tolerated, with most patients (70%) not experiencing adverse events. Altogether, 15% of the patients discontinued Zilbrysq due to adverse events, and 4% due to the lack of efficacy.
Zilbrysq “was well-tolerated and effective in most patients with AChR-positive gMG,” the researchers wrote. “A [clinically] meaningful effect was reported since the first week and was sustained after 24 weeks.”
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