Patients With MG Report Higher Azathioprine Discontinuation vs Other Immunosuppressants

Mycophenolate and methotrexate may be more tolerable options for patients with myasthenia gravis (MG) who experience dverse effects with azathioprine, suggest real-world, self-reported data from the United Kingdom.

Survey data from over 200 patients, published in Neuromuscular Disorders, shows that treatment discontinuation was lower for those taking mycophenolate or methotrexate than for those taking azathioprine. More than half of patients taking azathioprine—used as a first-line immunosuppressant in the UK—discontinued the treatment.¹ Mycophenolate and methotrexate are often used as second-line treatment, although some previous data have suggested that patients better tolerate these treatments.²

In this analysis, patient respondents were receiving care from 90 hospitals across the UK and had been recruited through a patient support organization | Image Credit: everythingpossible - stock.adobe.com

“With limited data comparing efficacy of these agents, choice of treatment is often based on perceived side effect profile, generally from studies in other conditions,” explained the study authors. “Studies in inflammatory bowel disease have suggested that around 26% of those given azathioprine are unable to tolerate it and discontinue the medication due to side effects, usually hepatotoxicity or myelosuppression. Other serious adverse effects include hypersensitivity and increased risk of skin cancer.”

Data from the current study show a higher discontinuation rate with azathioprine in MG, with 56% of the 166 patients taking the immunosuppressant discontinuing treatment, largely because of adverse effects (AEs). Among the 93 patients who discontinued azathioprine, 46% discontinued due to liver dysfunction and 16% due to skin problems. Patients receiving azathioprine also reported the inconvenience of frequent blood tests and vulnerability of infections and skin cancer in the long term.

Compared with the 102 patients taking mycophenolate (OR, 10.79; 95% CI, 3.95-28.64) and 40 patients taking methotrexate (OR, 8.82; 95% CI, 2.36-38.16), those taking azathioprine were more likely to discontinue treatment due to AEs. There were no significant differences in discontinuations between treatments because of a lack of efficacy.

Patients responding to the study’s survey were receiving care from 90 hospitals across the UK. They were recruited through a patient support organization, which may have resulted in inclusion of those experiencing more AEs and other issues with treatment, thus limiting the generalizability of findings, noted the researchers.

Notably, AEs were less commonly documented in medical notes than were reported by the patients themselves. Among 47 patients with additional case note review available, AEs with azathioprine were documented for 44% and self-reported for 77% of the 34 patients taking the treatment, documented for 33% and self-reported by 59% of the 24 patients taking mycophenolate, and documented for 22% and self-reported by 62% of the 9 patients taking methotrexate.

Outside of azathioprine, mycophenolate, and methotrexate, patients also reported taking pyridostigmine (98%), prednisolone (94%), ciclosporin (3%), rituximab (1%), tacrolimus (1%), and cyclophosphamide (< 0.5%) at some point for their MG.

“Steroids produced the most side effects of all of the medications, and therefore management strategies should aim to limit steroid exposure as much as possible,” wrote the researchers. “Mycophenolate and methotrexate appear to be good candidates for use in patients with MG where teratogenicity is not a concern. This tolerability data is likely to be applicable to use of these agents in other autoimmune conditions. Patients initiating immunosuppressive medication should have frequent reviews with close blood test monitoring in order to optimise therapy and limit side effects.”

Among the patients participating in the study, women were more likely to report AEs from immunosuppressant treatment. Across all patients, the most reported AE of azathioprine was liver dysfunction (23%), of mycophenolate was diarrhea (14%), and of methotrexate was fatigue (18%).

Diarrhea (42%) was the most common AE from pyridostigmine and increase in appetite/weight gain was the most common AE of prednisolone (65%). Women were more likely than men to report weight gain (72% vs 58%) and mood changes (53% vs 33%) with the steroid.

References

1. Dodd KC, Ahmed R, Ambrose P, et al. Mycophenolate and methotrexate are better tolerated than azathioprine in myasthenia gravis. Neuromuscul Disord. Published online March 21, 2024. doi:10.1016/j.nmd.2024.03.010

2. Dodd K, Miller J, Holt J, et al. Mycophenolate is better tolerated than azathioprine in myasthenia gravis. Neuromuscul Disord. 2024;38:51-57. doi:10.1016/j.nmd.2024.03.010