Study Suggests Rituximab Effective for Refractory Juvenile Myasthenia Gravis

 

In many cases, autoimmune disorders like myasthenia gravis are treatable. However, there are some cases of refractory (treatment resistant) myasthenia gravis that presents an unmet patient need. However, researchers recently attempted to find effective treatments for patients with treatment-resistant juvenile myasthenia gravis (JMG). One such treatment they discovered? Rituximab, a monoclonal antibody treatment used for autoimmune disorders. Find the full study results in Pediatric Neurology.

Juvenile Myasthenia Gravis (JMG)

Stemming from the Greek and Latin words for “grave muscle weakness,” myasthenia gravis (MG) is a progressive autoimmune neuromuscular disorder causing muscle weakness and fatigue. The body’s immune system mistakenly attacks proteins that help muscles and nerves communicate. Symptoms generally get worse with heightened levels of activity. Around 20 out of 100,000 people globally have MG.

Juvenile myasthenia gravis (JMG) is a rarer form of the disorder. Oftentimes, its ability to “mimic” other disorders causes diagnostic difficulty. Generally, JMG begins in adolescence, particularly in female patients. Patients with JMG may experience periods of “flares” and periods of remission throughout their life. Symptoms include:

  • Weakness and fatigue in voluntarily controlled, skeletal muscle groups (arms and legs, eyes, mouth, throat)
  • Drooping eyelids
  • Clumsiness
  • Chest wall weakness and breathing difficulties
  • Neck or limb weakness
  • Shortness of breath
  • Slurred speech
  • Double vision
  • Difficulty chewing and swallowing
  • Changes in gait and movement

According to the Children’s Hospital of Philadelphia (CHOP), some children with JMG struggle as they are:

mistakenly thought to be lazy, uncoordinated, or even unmotivated.

Learn more about refractory JMG here.

Rituximab

Generally, JMG treatments include Mestinon, prednisone, immunomodulatory therapies, or a thymectomy (thymus removal). However, patients with the refractory form of the disorder do not find relief with these options. Researchers wondered if rituximab, proven potentially effective for adult patients, would share the same benefits for juvenile patients.

Rituximab is a monoclonal antibody. According to the Mayo Clinic, monoclonal antibodies are:

 laboratory-produced molecules engineered to serve as substitute antibodies that can restore, enhance or mimic the immune system’s attack on [antigens].

To determine the efficacy, tolerability, and safety of rituximab for patients with JMG, researchers performed a retrospective study. First, they discovered five patients with recurrent symptoms despite treatment. Next, they analyzed how many times these patients were admitted to the hospital, disease progression and severity, and medication use. Researchers discovered:

  • Four patients had elevated acetylcholine receptor (AChR) antibodies, while the fifth patient had muscle-specific kinase (MuSK) antibodies. These commonly play a role in JMG.
  • The first four patients had double vision, muscle weakness, and dropping eyelids. The fifth experienced difficulty swallowing, as well as eye and facial weakness.
  • Patients were (on average) 11.6 years old at the time of diagnosis. They spent an average of 15.1 months attempting other treatments before rituximab use.

Treatment

Once patients began receiving rituximab, they first received two two 750 mg/m² doses around 2-3 weeks apart. After these doses, they were given intravenous immunoglobulin (IVIg) therapy. Next, patients received 375 mg/m² rituximab every 3 months.

Patients were monitored between 4 months to 2 years. During this time, no patients were hospitalized. Patients reduced average medication use to 1.6. Additionally, while patients still experienced droopy eyelids, they had a reduction in disease severity, double vision, muscle weakness, and difficulty swallowing. Patients also saw a reduction in antibody levels.

Prior to rituximab treatment, the fifth patient was hospitalized eight times. She did not respond to any of the five immunomodulatory therapies. However, after being treated with rituximab for two years, she was not hospitalized once.

Rituximab was safe and well-tolerated. Ultimately, it shows potential as a treatment for patients with JMG. However, the researchers do note that more testing should be done on a larger patient population.

Read the source article here.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

Share this post

Share on facebook
Share on twitter
Share on linkedin
Share on pinterest
Share on print
Share on email