Standard MG Care Less Effective for Women, Danish Study Suggests

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

Share this article:

Share article via email
women and MG

Africa Studio/Shutterstock

Women with myasthenia gravis (MG) given standard treatment improve significantly less in both objective and patient-reported outcome measures than do men, a study in Denmark with nearly five years of follow-up data reported.

Notably, this sex difference was independent of age, disease duration, simultaneous health conditions (comorbidities), and prior thymectomy (surgical removal of the thymus).

While the underlying mechanisms of this difference remain unclear, the researchers noted these findings suggest that outcomes are worse for women with MG than men despite treatment, and that this difference should be considered in clinical care and when designing future clinical trials.

The study, “Gender differences in clinical outcomes in myasthenia gravis: A prospective cohort study,” was published in the journal Muscle & Nerve.

Recommended Reading
Main graphic for column titled

The Lessons I’ve Learned Since My Myasthenia Gravis Diagnosis

In MG, the immune system produces self-reactive antibodies that mistakenly attack proteins involved in the communication between nerve cells and muscle cells, leading to muscle weakness and fatigue.

Previous studies have shown that early onset MG and refractory disease, or that which fails to respond to available therapies, is more common in women than in men. In addition, patient-reported outcome scores appear to be more severe in female MG patients.

However, whether both patient-reported and objective clinical outcomes differ between men and women with MG while under standard clinical care remains unclear, and prospective studies are needed to clarify this.

Researchers at Aarhus University Hospital, in Denmark, prospectively analyzed potential clinical outcome differences between male and female MG patients given standard of care from 2012 to 2019 at their hospital.

Clinical outcomes were assessed through two objective measures — the Quantitative MG and the MG Composite — and two patient-reported measures — the MG Activities of Daily Living and the MG Quality of Life 15-Items. Other clinical characteristics were also analyzed.

Eligible participants included MG patients younger than 90, who had no comorbidities directly affecting their motor function.

A total of 107 patients (54 men and 53 women), with a median age of 62, were assessed at the study’s start. Of them, 70 completed all follow-up assessments, corresponding to 78% of eligible patients at follow-up.

At the study’s start, women were significantly younger, had significantly longer disease duration, and more often underwent a thymectomy — a standard therapeutic approach for MG patients that has been associated with durable benefits.

No significant sex differences in clinical scores and comorbidities that could affect outcome assessments at the study’s start  were evident.

Patients were followed for a mean of 4.8 years, with a minimum follow-up of 3.6 years.

At follow-up, most (71.4%) were using pyridostigmine (sold as Mestinon, among other brand names), 54.3% were given immunosuppressive agents, and 10% were treated with maintenance plasma exchange, intravenous immunoglobin, or Soliris (eculizumab). About 10% of patients failed to respond to treatment.

Results showed that while all clinical scores significantly improved with treatment in the overall patient population, women improved to a significantly lesser degree than men in all measures.

Notably, this sex difference was observed regardless of age, age of disease onset, disease duration, refractory disease, comorbidities, and prior thymectomy. In addition, women with MG were not given lower therapy doses and they changed immunosuppressive therapy less often than did men during follow-up.

Interestingly, women lost to follow-up had more severe disease at the study’s start than did men lost to follow-up, which “likely attenuated the observed gender differences rather than increased them,” the researchers wrote.

These data support “the existence of a link between female gender and less clinical improvement among patients receiving standard of care,” the researchers wrote, adding that “this gender difference in disease severity is evident on both objective measures, level of disability and quality of life.”

Associations between objective and patient-reported measure scores were also weaker in women than in men, and women improved more on objective than on patient-reported scores during follow-up.

In clinical trials, the inclusion of mostly female MG patients “may potentially mask beneficial treatment effects observed in males,” while the use of only objective measures may overestimate benefits in women, the team wrote.

“Current standard of care appears to improve objective signs of disease burden more than patient-reported outcomes in females,” emphasizing the importance of “investigating and confirming beneficial treatment effects through patient-reported outcomes” in clinical trials, the researchers added.

These findings “provide further evidence of gender differences in the underlying mechanisms of MG, potentially affecting onset and course of disease as well as the therapeutic efficacy of treatments that impact clinical outcomes,” the team wrote.

Future research is needed to identify the reasons and mechanisms behind these differences, which should be considered “in daily clinical practice and in the design of future trials,” they concluded.