Results Summary
What was the research about?
Myasthenia gravis, or MG, is a rare disease of the immune system that causes muscle weakness. MG can cause droopy eyelids and trouble swallowing, chewing, talking, and breathing.
Medicines that suppress the immune system can help relieve MG symptoms. These medicines require routine monitoring for adverse events, such as liver damage or stomach issues. Questions remain about how these medicines compare with each other.
In this study, the research team compared two medicines for adults with MG: azathioprine, or AZT, versus mycophenolate mofetil, or MMF. The team wanted to learn how these medicines affected patient quality of life, symptoms, and other health outcomes.
What were the results?
After two years, patients who took AZT and patients who took MMF had better quality of life and fewer symptoms. Patients who took MMF reported more improvement in quality of life than patients who took AZT. But the difference was small and not meaningful.
Patients who took AZT and patients who took MMF didn’t differ in:
- Symptom improvement and muscle strength as assessed by clinicians
- Ability to do daily activities
- Number of hospital stays for MG
Among patients who took AZT, 32 percent had an adverse event. The most common event was liver damage. Among patients who took MMF, 19 percent had an adverse event. The most common event was stomach issues, such as cramps or diarrhea.
Who was in the study?
The study included 82 adult patients with MG. Of these patients, 96 percent were White, 2 percent were Asian, 1 percent were Black, and 1 percent were of unknown race. The average age was 66, and 61 percent were men.
What did the research team do?
The research team enrolled patients with MG who were receiving care at one of 19 MG clinics in the United States and Canada. As part of regular care, clinicians prescribed either AZT or MMF to patients. At the start of the study and again two years later, patients completed surveys about their quality of life and ability to do daily activities. Clinicians completed surveys about patients’ symptoms, muscle strength, hospital stays, and adverse events caused by the medicines.
Patients with MG, clinicians, health insurers, and patient organizations helped design and carry out the study.
What were the limits of the study?
The research team enrolled fewer patients in the study than planned, which made it hard to detect differences between AZT and MMF. The study took place at MG clinics. Forty percent of patients had the form of MG that affects only eye muscles. Results may differ in other types of clinics and for patients with other forms of MG.
Future research could include patients with other forms of MG and those receiving care at other types of clinics.
How can people use the results?
Patients with MG and their clinicians can use these results when considering medicines to treat MG.
Professional Abstract
Objective
To compare the effect of two immunosuppressive medicines for adults with myasthenia gravis (MG) on patient-reported quality of life and clinician-reported clinical improvement
Study Design
| Design Element | Description |
|---|---|
| Design | Observational: cohort study |
| Population | 82 patients ages 18 and older with acquired autoimmune MG |
| Interventions/ Comparators |
|
| Outcomes |
Primary: patient-reported quality of life; composite clinician-reported clinical outcome, which included clinical improvement, defined as symptomatic improvement with mild adverse events Secondary: muscle strength, activities of daily living, and hospitalization from MG |
| Timeframe | 2-year follow-up for primary outcomes |
MG is a rare autoimmune disease that weakens certain muscles necessary for activities of daily living, such as seeing, swallowing, and breathing. MG reduces quality of life and requires long-term treatment with immunosuppressive medicines as well as routine monitoring for adverse events. This prospective, observational cohort study compared the effectiveness of two medicines—azathioprine (AZT) and mycophenolate mofetil (MMF)—on improving patient-reported quality of life and a composite clinician-reported clinical outcome among adults with MG.
Researchers enrolled adult patients receiving care at one of 19 MG clinics in the United States and Canada. As part of routine clinical care, clinicians prescribed either AZT or MMF to patients. At baseline and again two years later, patients completed surveys about quality of life and activities of daily living. Clinicians assessed whether patients achieved adequate symptom improvement with mild adverse events, and muscle strength. They also reported on hospitalizations for MG.
The study included 82 adult patients with MG. Among patients, 96% were White, 2% were Asian, 1% were Black, and 1% were of unknown race. The average age was 66, and 61% were male.
Patients with MG, clinicians who treat MG, health insurers, and patient organizations helped design and conduct the study.
Results
After two years, compared with patients prescribed AZT, patients prescribed MMF had a statistically significant improvement in quality of life (p<0.05), but these differences were not clinically meaningful at the predefined threshold of 5 or more survey points. Between baseline and two years, patients in both groups had clinically meaningful changes in quality of life.
Patients prescribed AZT and patients prescribed MMF also did not differ significantly in the composite clinician-reported clinical outcome. Patients in both groups achieved symptomatic improvement. About 32% of patients prescribed AZT and 19% of patients prescribed MMF experienced an adverse event. The most frequent adverse event for AZT was hepatoxicity; the most frequent adverse event for MMF was gastrointestinal disturbance.
Patients in both groups had clinically meaningful changes in secondary outcomes; however, the two groups did not differ significantly.
Limitations
Researchers enrolled fewer patients than planned, which limited their ability to detect differences between treatments. The study took place in academic medical centers, and 40% of patients had the form of MG that affects only eye muscle strength. Results may differ for patients receiving care at other medical centers and those with other forms of MG.
Conclusions and Relevance
In this study, AZT and MMF did not lead to clinically meaningful differences in quality of life; however, both medicines improved quality of life and helped patients with MG achieve symptomatic improvement. More patients who received AZT experienced adverse events.
Future Research Needs
Future research could include patients with other forms of MG receiving care at other types of medical centers.
Final Research Report
This project's final research report is expected to be available by August 2023.
Peer-Review Summary
Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.
The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.
Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following:
- Reviewers noted that the study found a statistically significant difference between the two treatments for Myasthenia Gravis, but the researchers did not consider that difference to be clinically meaningful. They asked the researchers to provide more support for this conclusion and postulate on the reasons for the smaller-than-expected difference between groups. The researchers added text to the report indicating that their difficulties with meeting their enrollment goals during the COVID-19 pandemic led to a loss of study power and was probably a main reason for the lack of a clinically meaningful difference between the two treatments.
- The reviewers asked for more information on the involvement of patients and stakeholders as research partners in the study. The researchers added details to the engagement section of the report describing how their three stakeholders were involved starting at the point of study development when they helped to identify the outcome measures. This advisory group continued to meet with the researchers every three months to discuss issues related to the study and to provide feedback on their study recruitment plans as well as on abstracts and papers stemming from the project.
- The reviewers questioned how the researchers could conclude that the study results were due specifically to the interventions for Myasthenia Gravis when patients might also be affected by the COVID-19 pandemic, either by contracting the illness or through side effects from the vaccinations. The researchers explained that the outcome measures they used were specific to Myasthenia Gravis. They did record occurrences of other medical illnesses during the study and no patients reported having COVID-19 in that time.