IVIG agent safe, may be effective as maintenance therapy for gMG
Use of Gamunex-C helped reduce disease severity in patients in Phase 2 trial
A maintenance regimen using an intravenous immunoglobulin (IVIG) therapy may reduce disease severity and improve function in people with generalized myasthenia gravis, according to data from a Phase 2 clinical trial.
IVIG is commonly used to treat acute symptom worsening in people with myasthenia gravis (MG). The Phase 2 trial (NCT02473952) evaluated whether Gamunex-C — an IVIG therapy marketed by Grifols Therapeutics and approved in the U.S. for other medical conditions — was effective and safe compared with a placebo when given once every three weeks to generalized MG patients as a maintenance treatment.
While the researchers did report positive results with the IVIG therapy, the team noted that the study likely was too small to generate robust data.
“Further studies may be warranted to fully elucidate the efficacy of IVIG as maintenance therapy in MG while carefully monitoring all patients for MG exacerbations,” the team wrote.
The study, “Efficacy and safety of maintenance intravenous immunoglobulin in generalized myasthenia gravis patients with acetylcholine receptor antibodies: A multicenter, double-blind, placebo-controlled trial,” was published in the journal Muscle & Nerve.
More patients on IVIG therapy saw clinical improvements in trial
An autoimmune disease, MG is caused by self-reactive antibodies, or autoantibodies, that target proteins at the neuromuscular junction — the site where nerve and muscle cells communicate to coordinate voluntary movements. Most commonly, these autoantibodies target acetylcholine receptors, or AChRs. Generalized MG, or gMG for short, is a more severe form of the disease that may cause weakness in several muscle groups.
IVIG preparations contain immunoglobulins, or antibodies, collected from healthy donors. They are believed to temporarily modulate the immune system in a way that promotes the destruction of MG-causing autoantibodies, and also prevents their production. Such treatments are commonly used as a rescue therapy for MG exacerbations and crises, or periods in which symptoms acutely worsen.
However, “data supporting the efficacy of IVIG as maintenance therapy for MG are lacking,” the researchers wrote.
Now, a team of researchers from Europe and North America reported data from a Phase 2 trial conducted on both continents. The study evaluated the efficacy and safety of Gamunex-C in 62 people with gMG who were positive for anti-AChR antibodies and were on standard of care therapy.
The patients had a mean age of 51.2, and slightly more than half (53.2%) were women. All were randomly assigned to receive Gamunex-C (30 patients) or a placebo (32 patients). The IVIG therapy was given at a loading dose of 2 g/kg over two to four days, followed by a maintenance dose of 1 g/kg once every three weeks for 21 weeks, or about five months.
The trial data showed that Gamunex-C did not significantly reduce disease severity over the course of 24 weeks of treatment, or about six months, compared with the placebo. Disease severity was assessed by changes in the Quantitative MG (QMG) score, and showed a decrease of 5.1 points for those on treatment versus 3.1 points for those on the placebo. QMG is a measure of MG severity in which higher scores indicate greater disability and more severe symptoms.
Moreover, there was no significant difference in the proportion of patients showing clinical improvement, defined as a three-point reduction or more in the QMG score (70% vs. 59.4%), or the MG Composite (MGC) score, a composite measure of disease severity (60% vs. 53.1%).
However, the proportion of patients achieving clinical improvement based on QMG scores was higher at all evaluated time points among those who received Gamunex-C, reaching statistical significance after nine weeks (70% vs. 40.6%), or slightly longer than two months, and 21 weeks (80% vs. 43.8%), or about five months, of treatment.
Researchers note study was small and likely ‘underpowered’
A significant increase was also seen in the proportion of patients who had clinically meaningful improvements in their abilities to perform activities of daily living after six months (70% vs. 40.6%). Such improvements were defined by a minimum two-point decrease in the MG Activities of Daily Living (MG-ADL) scale.
Further, a higher proportion of patients in the IVIG group were classified as improved, according to the MG Foundation of America (MGFA) post-interventional status (71.4% vs. 54.2%).
[With IVIG therapy,] several efficacy parameters showed numerical results greater than those seen in the placebo group.
Gamunex-C was generally well tolerated, with a similar proportion of patients in both groups experiencing at least one treatment-emergent adverse event. Headache and the common cold were the most common. However, treatment-emergent adverse events potentially related to treatment were more common in the IVIG group (53.3% vs. 25%).
Serious adverse events included episodes of MG exacerbation, relapse, or symptom worsening in three participants given IVIG and one given the placebo. Two patients in each group dropped off the study, and one patient in the IVIG group died, according to the researchers.
Overall, the team noted that, with IVIG therapy, “several efficacy parameters showed numerical results greater than those seen in the placebo group.”
One limitation noted by the researchers was the study’s size.
“This was a small study and may have been underpowered to see significant differences,” the team wrote, noting that “additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.”
About the Author
