Rituximab Effectively Treats Refractory Juvenile MG Patients, Small Study Suggests

Rituximab, an approved treatment for certain cancers and autoimmune conditions, appears to also be effective and well tolerated in people with juvenile myasthenia gravis (JMG) who fail to respond to available therapies, a small study suggests.

But before more definitive recommendations can be made, its investigators advise that rituximab be studied more rigorously in a larger group of juvenile patients.

The study, “Rituximab as Adjunct Maintenance Therapy for Refractory Juvenile Myasthenia Gravis,” was published in the journal Pediatric Neurology. 

Myasthenia gravis (MG) occurs when the immune system mistakenly attacks the neuromuscular junction, or the connection between neurons and muscle cells. Its juvenile form, JMG, usually begins before age 18 and requires life-long management.

Treatment for JMG often includes the acetylcholine esterase inhibitor known as Mestinon (pyridostigmine; generics available), given along with immunomodulatory medications. For patients whose disease is related to a tumor in the thymus gland, the removal of the thymus (thymectomy) is another treatment option. 

Still, not all patients achieve remission with standard treatment approaches.

Rituximab (marketed under the brand names Rituxan and Truxima, among others) is a monoclonal antibody that targets B-cells, immune cells that produce antibodies and participate in autoimmune conditions. It is approved for certain lymphomas, leukemias, and autoimmune diseases, such as rheumatoid arthritis.

While rituximab has been well-studied as a potential treatment for adults with MG, its use in juvenile patients is limited. 

“Currently, no standardized protocol exists for determining initiation of rituximab therapy in JMG,” the investigators said.

Researchers at the University of Florida College of Medicine conducted a retrospective study to investigate the efficacy and tolerability of rituximab given to children with JMG who failed to respond to current therapies.

A search of medical records identified five JMG patients with ongoing symptoms, despite Mestinon and at least one immunomodulatory medication, and who were treated with rituximab.

The team focused on the number of hospital admissions and immunomodulatory or immunosuppressive medications needed with rituximab’s use, as well as changes in the Myasthenia Gravis Foundation of America (MGFA) severity class. 

Elevated antibodies targeting acetylcholine receptors (AChR) at the neuromuscular junction, the most common antibodies causing MG, were found in four of these patients. The other had antibodies against the muscle-specific kinase (MuSK) protein.

All patients with AChR antibodies had drooping upper eyelids and variable muscle weakness, with three reporting double vision. The MuSK-positive child had facial and eye weakness, and difficulty swallowing.

Patients were diagnosed at an average age of 11.6, and had an average disease duration of 15.1 months at the time they began treatment with rituximab. On average, these patients were taking 2.8 immunomodulatory medications and had been hospitalized 2.8 times.

These patients were given two 750 mg/m² initial doses of rituximab spaced two to three weeks apart, followed by at least one 375 mg/m² maintenance dose every 12 weeks. Each dose was followed by intravenous immunoglobulin (IVIg) treatment, which is a pool of antibodies from healthy donors.

After being followed for a mean of 11.6 months (range 4–24 months), the average number of immunomodulatory medications dropped to 1.6, and there were no hospitalizations. 

Patients reported an easing of disease symptoms, including double vision, difficultly swallowing, and muscle weakness, with four patients also showing improvement in MGFA class, meaning their disease became less severe.

Drooping upper eyelids persisted, however. According to the researchers, “this has been previously documented in JMG patients with stable disease.”

All had lower levels of AChR or MuSK antibodies, with antibodies becoming undetectable in three of the five cases. Two patients using prednisone, an immunosuppressive medication with some side effects, were able to lower their dose or stop the medication. 

Rituximab’s benefits were most prominent in the patient with MuSK antibodies, a girl. She had previously failed to respond to five immunomodulatory therapies, and had been hospitalized on eight prior occasions. Over two years after being treated with rituximab, she had no hospitalizations, even after developing influenza.

The therapy was well tolerated, with no significant adverse events recorded for any of the participants.

“Rituximab has the potential to fill a significant therapeutic gap for refractory JMG, but should be studied more rigorously in a larger cohort before more definitive recommendations can be made,” the investigators concluded.