There are a number of unanswered questions for researchers and clinicians involved with myasthenia gravis (MG), from understanding the cause of the disease to finding an ideal treatment option for patients, according to a physician.
Pedro J. Modrego, MD, from Miguel Servet University Hospital in Zaragoza, Spain, discusses this issue in an editorial titled, “Myasthenia gravis: the unmet needs of a paradigmatic autoimmune disease,” published in the journal Neurodegenerative Disease Management.
In spite of new developments in the treatment of MG in the last 10 years, no breakthroughs have emerged in this field, leading to unanswered questions that should be addressed in future studies, he said.
Modrego has broken down these questions into seven broad issues.
The first issue he raises is the need to truly understand the role of the thymus gland in MG. This gland, located in the neck, plays an important role in the development of the immune system in early life. Some patients with MG develop thymomas — tumors of the thymus gland. But it is not known if thymoma is what causes MG in these patients or if it is a consequence of MG.
Additionally, while one clinical trial study has shown that patients with thymomas have better outcomes when they undergo a thymectomy (removal of the thymus gland) plus alternate-day corticosteroid therapy (prednisone) compared to alternative-day prednisone alone, future clinical trials need to address which subset of patients actually benefit from the procedure.
One of the main questions is when to perform a thymectomy and what to expect from it.
Another unanswered question is what triggers immunogenicity — the immune reaction caused by medications, vaccines, infections, and other factors — in patients with myasthenia gravis.
Furthermore, studies need to address why this immunogenicity becomes chronic in these patients. Understanding this issue is the key to preventing and treating the disease.
Third, Modrego emphasizes that there is a need for new biomarkers that can predict long-term prognosis and the risk of myasthenic crisis.
The fourth issue addressed by Modrego is the need for a surveillance program for patients on long-term immunosuppressive drugs. Medical treatment for MG usually involves either corticosteroids — such as prednisone — or immunosuppresants.
However, long-term therapy with prednisone is associated with many potential side effects, leading physicians to replace prednisone with immunosuppressants such as azathioprine. While azathioprine is known to be a well-tolerated drug, surveillance programs are needed for patients that take it for 10 years or more.
Fifth, Modrego said there is a need for the community to establish a preference for certain immunosuppressants over others. While azathioprine is a well-tolerated therapy for myasthenia gravis, some patients do not tolerate or respond to it. In this case, there should be a recommended list of immunosuppressants — such as cyclosporine, tacrolimus, mycophenolate, and Rituxan (rituximab) — that can be administered.
The sixth issue that Modrego discusses is “the need to share information among clinicians for better indication of drugs by means of appropriate registries.”
In particular, there is a lack of clinical of trials that have tested the efficacy and safety of a range of immunosuppressants. Therefore, Modrego writes, “it would be very useful to create registries so as to share the experience among colleagues.”
To address this issue, the Myasthenia Gravis Foundation of America has created a patient registry of MG, which will serve as an important source of information for clinicians.
The seventh and final issue that Modrego raises is that MG clinicians and researchers need to learn from other autoimmune diseases.
“Despite the new developments in MG, no breakthroughs have emerged in the last decade in this field and there are several unmet needs that should be addressed in further research,” Modrego said.