Rituximab Effective for People With Refractory MG, Study Finds
People with myasthenia gravis (MG) who fail to respond to standard therapies or are dependent on steroid use can safely and effectively be treated with rituximab, an immune modulating medicine, a real-world study found.
Patients taking rituximab were also able to reduce their steroid dose.
The study, “Efficacy and safety of Rituximab in myasthenia gravis: A French multicentre real‐life study,” was published in the European Journal of Neurology.
MG is caused by the formation of autoantibodies against proteins at the neuromuscular junction, the site where nerves communicate with muscle cells. About 80% of MG patients have antibodies targeting acetylcholine receptors (ACh-R) at the neuromuscular junction, and around 10% have antibodies against the associated MuSK protein.
While several treatment options are available to MG patients, around 15% fail to improve or their disease progresses while on treatment (refractory disease).
Rituximab (brand names include Rituxan in the U.S. and Mabthera in Europe) is an antibody that works to lower the levels of B-cells, immune cells that produce the damaging antibodies in myasthenia gravis. It is approved to treat certain types of cancer, as well as autoimmune diseases like rheumatoid arthritis.
While clinical trials are underway testing rituximab in MG patients, researchers based at the University Hospital of Nantes in France designed a real-world study to assess the efficacy and safety rituximab in MG patients who failed to respond to other treatments.
They analyzed the medical records of 29 adults with MG who were refractory or steroid-dependent (unable to reduce steroid use), and had been prescribed rituximab. The MG Foundation of America Post-intervention Status (MGFA-PIS) was used to assess changes in clinical signs of MG after rituximab treatment, and the Myasthenic Muscle Score (MMS) was applied to measure muscle strength, with a lower score indicating more severe disease.
Patients’ average age was about 50, and they had an average disease duration of 8.8 years when rituximab treatment began. Of those selected, 20 had antibodies against the acetylcholine receptor, five had anti-MuSK antibodies, while four patients tested negative for both (seronegative).
Steroid treatment had been given to 21 patients, 15 were steroid dependent, and 16 were using non-steroid immunosuppressive therapy. All therapies, except for steroids, were stopped either immediately or within three months of beginning with rituximab.
Significant improvements in MGFA-PIS scores were reported after six months of rituximab use for 86.2% of patients. Specifically, scores improved in 90% of those with anti-ACh-R antibodies, 60% of those with anti-MuSK antibodies, and in all seronegative patients. Four patients were in remission.
Data covering 12 months of treatment was available for 21 patients. Among these, 20 scored significantly better, with eight people in remission. Six-month scores did not differ with 12-month scores.
The average MMS scores significantly improved, dropping from 68.9 before treatment to 83.1 at six months, and 85.0 at 12 months.
MG-related exacerbations or flares occurred in five patients, and one experienced a myasthenic crisis after taking rituximab. A contributing factor to an exacerbation was identified in three patients, and included two infections and one surgery. Four of these six continued using rituximab after an exacerbation.
Of the 21 patients using steroids before rituximab, their average daily dose significantly declined— from an average of 20 mg to 13 mg. Among 19 taking doses higher than 10 mg a day, seven were able to lower their dose by six months, and 11 by 12 months. Four patients stopped taking steroids at six months, and seven by 12 months.
Adverse events were reported in about 43% of participants, which included infections, infusion reactions, slow heartbeat, and low blood cell counts. Two died during the study, including one of an infection.
These findings show that rituximab is effective in MG patients, particularly in those with anti-ACh-R antibodies, and that patients could safely reduce their steroid dose the researchers wrote.
Long-term steroid use is known to carry worrisome side effects, such as increased risk of infection and other health issues, they added, and rituximab may be effective in helping to reduce their use.
“Our study demonstrates the efficacy and safety of rituximab in MG patients,” the researchers concluded. “Additional studies are still necessary to set the actual place of rituximab in pharmacopeia of MG treatment and to establish precise recommendations for infusion protocol.”