MG treatment side effects common, especially in women: Survey

Patients more likely to discontinue azathioprine, UK study finds

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by Steve Bryson, PhD |

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Patients, especially women, experience a high degree of side effects from myasthenia gravis (MG) treatment, according to a U.K. survey examining real-world use of the medications.

As steroid-sparing agents, mycophenolate mofetil (sold as CellCept) and methotrexate (sold as Trexall, among others) were less likely to be discontinued than azathioprine (sold as Imuran, among others) due to side effects.

“Strategies to minimise the risk of treatment failure in azathioprine should be utilised, but mycophenolate and methotrexate appear to be alternatives with lower risk of adverse effects,” the researchers wrote.

The findings “will provide clinicians and patients with more information when deciding between different steroid-sparing agents,” they wrote.

Details of the MG patient survey were detailed in the study, “Mycophenolate and methotrexate are better tolerated than azathioprine in myasthenia gravis,” published in the journal Neuromuscular Disorders.

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Immunosuppressants prescribed as steroid-sparing options

MG is an autoimmune condition in which the immune system mistakenly attacks proteins necessary for nerve-muscle communication, resulting in the hallmark MG symptoms of muscle weakness and fatigue.

Medicines like Mestinon (pyridostigmine bromide), which are designed to boost nerve-muscle communication and enhance muscle strength, are generally the first-line treatment for MG. If these medicines are not effective or well tolerated, patients can take immune-suppressing corticosteroids.

Because of the potential side effects of steroids, immunosuppressants like azathioprine are recommended to keep the disease in remission, while allowing steroid doses to be reduced. Under these circumstances, mycophenolate mofetil and methotrexate are often considered second-line, steroid-sparing options.

Researchers across the U.K. came together to conduct a nationwide survey of MG patients to examine the real-world use of these immunosuppressive agents, the prevalence of side effects, and the reasons for discontinuation.

The survey was completed by 235 patients, with a mean age of 61 years and a mean disease duration of 12.3 years. About a third of the patients (31%) had early-onset MG, meaning they started experiencing symptoms of the disease before the age of 50, while 42% had late-onset MG, meaning the first disease manifestations occurred after the age of 50.

In 18% of the patients, MG was associated with abnormalities in the thymus gland — an organ that’s part of the immune system and is thought to be involved in the production of self-reactive antibodies that drive MG.

Most patients (78%) reported ongoing MG symptoms, while nearly all (96%) reported symptoms of generalized MG at some stage in their illness. A third (33%) had previously undergone surgery to remove the thymus gland (thymectomy).

Frequent co-existing medical conditions included other autoimmune conditions (37%), high blood pressure (37%), depression (37%), cancer/tumor (28%), and type-2 diabetes (20%).

Nearly all (98%) patients had taken pyridostigmine at some point, followed by the steroid prednisolone (94%), then azathioprine (71%), mycophenolate mofetil (43%), methotrexate (17%), and other immunosuppressants.

Azathioprine was more than five times more likely to be discontinued than mycophenolate mofetil. Discontinuations due to side effects were more than 10 times more frequent in patients treated with azathioprine than with mycophenolate mofetil and more than eight times more common as compared with methotrexate. Side effects leading to azathioprine discontinuation included liver dysfunction (46%) and skin problems (16%).

No differences were noted in discontinuations occurring due to a lack of efficacy.

The most common side effect reported for azathioprine was liver dysfunction (23%), diarrhea for mycophenolate mofetil (14 %), and fatigue for methotrexate (18%).

Patients were significantly more likely to report no side effects from mycophenolate mofetil as compared with azathioprine (41% vs. 23%). While men were significantly more likely to report no side effects from methotrexate than women (60% vs. 24%), no other sex-related differences in side effects were noted with mycophenolate or azathioprine, or with discontinuations.

Women and younger patients were more likely to experience prednisolone-related weight gain or mood changes. Diarrhea related to mycophenolate mofetil was reported much more often by women than men (22% vs. 5%), but no age-related differences were found.

Azathioprine-related liver dysfunction was almost four times more likely to occur in patients over 50.

“This study demonstrates that current therapies used for MG pose high risk of adverse effects, which are seen more commonly in female” patients, the researchers wrote. “Mycophenolate and methotrexate are less likely to be discontinued than azathioprine due to adverse effects, but no more likely to be discontinued due to lack of efficacy,” they wrote.