Treatment Patterns in Patients With Myasthenia Gravis Are Consistent Between US and Italy

A new study found that treatment for most patients with myasthenia gravis was mostly in line with guideline recommendations.

Most patients with myasthenia gravis (MG) are treated with pyridostigmine alone or in combination with prednisone, azathioprine and vitamin D, a pattern that is in line with US data, according to a population-based retrospective cohort study in Italy. The results were published in the Journal of Clinical Medicine.¹

“MG can have a significant impact on the quality of life and functional status of patients and requires lifelong treatment with immunosuppressive agents, symptomatic drugs, or both,” the authors wrote. "However, there is limited evidence on the optimal pharmacological management of MG, especially for individuals who are refractory to conventional therapies or have comorbidities."

The study covered a region of 10 million inhabitants and was part of a project funded by the Italian government to evaluate the effectiveness and safety of drugs used in rare neuromuscular and neurodegenerative diseases.

The researchers examined treatment for 2369 MG patients using health care administrative data from 2013-2019. Patients were included if they met one of the following criteria: discharge from hospital with a primary diagnosis of MG or a secondary diagnosis in combination with discharge from a hospital neurology ward; or discharge from the emergency department with a primary diagnosis of MG. Researchers compared therapy regimens at the time of MG diagnosis and during the first year of follow-up. The 2 years prior to the index date were defined as the look-back period and the 12 months after the index date as the follow-up period.

Patients evaluated in the study included 910 pyridostigmine prevalent users (defined as with at least one pyridostigmine dispensation in the look-back and follow-up periods), 521 pyridostigmine incident users (defined as with at least one pyridostigmine dispensation in the follow-up and no dispensation during look-back)and 938 pyridostigmine non-users.

Results were as follows: Prevalent and incident pyridostigmine users were 38.4% and 22.0%, respectively. In the first year of follow-up, prednisone was used in 74.5% of pyridostigmine prevalent users and in 82.0% of pyridostigmine incident users, respectively; azathioprine was used in 24.9% and 23.0%, respectively; and the use of vitamin D was observed in 53.3% and 48.2%, respectively. Among 910 pyridostigmine prevalent users, 13.1% also used azathioprine, prednisone, and vitamin D, while 15.3% used none of these. Among 938 non-pyridostigmine users, 2.7% used azathioprine, prednisone, and vitamin D, while 53.8% used none of these. During the first year, an increase in combined therapies was evident in incident pyridostigmine users.

Use of corticosteroids and immunosuppressants increased in both prevalent and incident pyridostigmine users during the observation period. MG patients who do not exhibit symptom control by standard immunosuppressive therapies may benefit from rituximab and eculizumab, new treatments being developed that combine a rapid onset of benefit with long-term and consistent disease control, the authors said. Less than 1% of medications reported by the study included rituximab and eculizumab because these medications had not yet been approved in Italy. Other biological products had been approved but were mainly administered in hospitals, and the study did not have access to inpatient data.

“The findings are in line with new recommendations for clinical guidelines for the use of rituximab, eculizumab, and methotrexate and for the early immunosuppression in ocular MG and MG associated with immune checkpoint inhibitor treatment,” the authors stated.

According to the most recent international consensus guidance for management of MG, ophthalmoparesis or ptosis in ocular MG that is non-responsive to anticholinesterase agents should be treated with immunosuppressant agents if symptoms are functionally limiting or troublesome to the patient; corticosteroids should be used as the initial immunosuppressive agent in ocular MG; steroid-sparing immunosuppressive agents may be needed when corticosteroids alone are ineffective, contraindicated, or not tolerated; low-dose corticosteroids may be effective for ocular MG and may avoid side effects associated with high-dose corticosteroids.²

The Italian study results also pointed to the potential effectiveness of vitamin D in treating MG.

“Our study indicates that the prescription of vitamin D in individuals with MG may serve dual purposes," they wrote. "Firstly, it could potentially mitigate adverse effects resulting from prolonged corticosteroid therapy. Secondly, it may offer benefits such as fatigue reduction and symptom remission. Existing research suggests that restoring vitamin D levels, especially in MG patients with plasma levels below 30 ng/mL, might contribute to alleviating the proinflammatory milieu associated with autoimmune disorders and potentially impacting disease progression."

References

1. Finocchietti M, Crescioli G, Paoletti O, et al. Drug use patterns in myasthenia gravis: a real-world population-based cohort study in Italy. J Clin Med. 2024;13(11):3312. doi:10.3390/jcm13113312
2. Narayanaswami P, Sanders D, Wolfe G, et al. International consensus guidance for management of myasthenia gravis. Neurology. 2021;96(3):114-122. doi:10.1212/WNL.0000000000011124