Off-label therapy rapidly eases gMG symptoms, cuts corticosteroid use
Study: About a third of patients achieved remission with low rituximab dose
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- Low-dose rituximab rapidly eased generalized myasthenia gravis symptoms.
- It reduced corticosteroid use in gMG patients with AChR-related gMG.
- Most patients improved within three months, with some achieving remission.
Early treatment with a single low dose of rituximab rapidly eases symptoms and reduces use of corticosteroids in people with generalized myasthenia gravis (gMG) and antibodies against the acetylcholine receptor (AChR) protein, a small real-world study shows.
Most of the 17 patients in the study improved within three months after treatment, and six achieved complete disease remission (no symptoms) without the need for any other treatment, according to the data.
The study, “Early use of low dose rituximab in anti acetylcholine receptor generalized myasthenia gravis in South Wales – A retrospective study,” was published in the Journal of the Neurological Sciences.
Early rituximab treatment may improve long-term outcomes in gMG
Myasthenia gravis (MG) is a chronic autoimmune disease that affects the neuromuscular junction, the place where nerves communicate with muscles. It causes muscle weakness that worsens with activity and improves with rest. In most cases, MG is caused by self-reactive antibodies against AChR, a key protein needed for nerve-muscle communication.
The most severe form of the disease is gMG, which is marked by symptoms that affect many muscles throughout the body. Many MG patients progress from ocular MG, where only eye-related muscles are affected, to gMG.
Standard MG treatments include corticosteroids and other immunosuppressive medications, but these can take time to work and may cause side effects with long-term use. Rituximab (sold as Rituxan and MabThera, with biosimilars available) works by killing B-cells, the type of immune cell responsible for antibody production, including MG-driving antibodies.
Although not specifically approved for MG, rituximab, administered directly into the bloodstream, is sometimes used off-label in this patient population. Previous studies suggest that starting rituximab earlier after the onset of gMG may improve long-term outcomes, possibly by limiting the development of long-lived antibody-producing B-cells.
Disease severity eased quickly after treatment
In this study, a team of researchers in the U.K. retrospectively analyzed data from 17 adults (70.6% men; median age, 71) with AChR-related gMG who received a single low-dose of rituximab (500 mg) within one year of developing the disease.
They had been living with symptoms of gMG for a median of five months, and most had moderate to severe disease, as assessed with the validated Myasthenia Gravis Foundation of America (MGFA) classification.
None of the participants were eligible for surgical removal of the thymus, a part of the immune system that is thought to play a role in gMG.
They also had not previously received immunosuppressive treatment, aside from the corticosteroid prednisolone, intravenous immunoglobulin (which delivers healthy antibodies to help suppress the autoimmune attack) or plasmapheresis, a blood-filtering procedure that removes self-reactive antibodies.
After rituximab treatment, patients were followed for a minimum of three months and a maximum of 20 months (more than 1.5 years); most were followed for seven to 12 months.
Disease severity eased quickly after treatment, according to changes in MGFA class. Three months after treatment, 14 participants (82.4%) had reached MGFA class Ia, meaning they had no generalized symptoms. At six months, 12 patients remained in class Ia and one was in class IIa, indicating mild generalized weakness. This reflected a “minimal manifestation status in the responders,” the team wrote.
[The study] provides real-world evidence that early treatment of low-dose rituximab in individuals with [AChR-related gMG] is well tolerated even in the older population and can result in quick and sustained [corticosteroid] free disease remission.
Corticosteroid use also declined over time. Median prednisolone dose fell from 40 mg before rituximab to 20 mg at three months, 9.5 mg at six months, 5 mg at 12 months, and 0 mg between 12 and 20 months.
Daily functioning, as assessed with the validated MG Activities of Daily Living (MG-ADL) scale, also improved. MG-ADL scores were down by three points after both three and six months, reflecting fewer impacts of the disease on daily activities.
Three patients who initially responded to rituximab needed an additional dose six months later for recurrence of symptoms on prednisolone weaning.
Two people needed rescue therapy after rituximab and were considered non-responders. One required IVIG within a month and could not be safely weaned off it for more than six months. The other had persistent symptoms affecting muscles used for speech and swallowing, and later achieved disease control after starting Vyvgart (efgartigimod), a gMG-approved therapy.
At the time of the latest data collection, six participants (about one-third of the group) were in complete remission (no symptoms) and off all MG treatments.
Adverse events included shingles reactivation, mild infusion reactions, and one death 10 days after infusion from a presumed blood clot in the lungs. The fatal event occurred in a patient with pre-existing blood clot risk factors and was not considered related to rituximab.
Among the study’s limitations, the team noted its small size, retrospective design, and lack of a control group. Despite this, the study “provides real-world evidence that early treatment of low-dose rituximab in individuals with [AChR-related gMG] is well tolerated even in the older population and can result in quick and sustained [corticosteroid] free disease remission,” the researchers wrote.
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