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The applicability of the myasthenia gravis patient registry data to disease burden and medication changes in clinical practice

Patient registries are important to study rare diseases such as myasthenia gravis (MG). The collection of detailed data on disease course, medications, comorbidity, therapeutic response, and family history improves understanding of the disease by physicians, patients, researchers, insurance companies, and the pharmaceutical industry. The Myasthenia Gravis Patient Registry (MGR) was established in 2013 by the Myasthenia Gravis Foundation of America in collaboration with the University of Alabama at Birmingham. The MGR was modeled after the North American Research Committee on Multiple Sclerosis Registry and includes information provided by patients obtained through questionnaires. MGR enrollment is voluntary. Participants report basic demographic information, disease-related history, treatment data, insurance status, and outcome measures, including the MG Activities of Daily Living (MG-ADL) and the 15-item MG Quality of Life (MG-QOL-15) scale instruments. In this issue of the Journal, Lee et al report on a 1-year follow-up of disease burden and medication changes in patients with MG to determine the degree to which participants achieve minimal symptom expression (MSE), defined as an MG-Activities of Daily Living (MGADL) total score of 0 or 1, and the factors associated with achieving MSE. MGR participants were grouped into either a high-burden group (MG-ADL score ≥6) or a low-burden group (MG-ADL score <6), based on their initial questionnaire MG-ADL score. An MG-ADL score of 6 or more is commonly used as an inclusion criterion for generalized myasthenia gravis clinical trials. The MG-ADL score in the MGR represents participants' experience over the last 4 weeks. The revised version of the MG-QOL-15 (MG-QOL-15R) has been used instead of the MG-QOL-15 from 2018 onward. The authors compared the demographics, disease history, and medication use at enrollment between the highand low-burden groups. In addition, use of MG medications was compared between three groups of males, females at least 45 years of age, and females less than 45 years of age, to evaluate differences in medication use based on gender and childbearing potential. Several key results of the study are noted: First, both groups improved to a similar degree using greater than 20% decrease in the MG-ADL as the criterion of comparison. This occurred despite the demographic, disease characteristic, and treatment differences between the highand low-burden groups. The authors used a decrease of greater than 20% in the MG-ADL as an outcome to circumvent the floor effect in the MG-ADL score. The floor effect refers to the MG-ADL reaching the lowest possible score while the quantitative myasthenia gravis score continues to improve, as noted in the MGTX study. Second, although there was an overall improvement in both groups, worsening of clinical status also occurred. Twenty-seven percent (19 of 71) of the low-burden group participants who were at MSE at baseline did not maintain MSE status at 12 months. The cause of worsening MG-ADL score is unclear from the study. Identifying the cause of the worsening requires dissecting individual patient data in the MGR. Furthermore, the MG-ADL increased, reflecting patient worsening, in three patients between 6 and 12 months in the low-burden group, and in nine patients in the high-burden group. The definition of escalation of treatment according to the study is imperfect as it does not consider the frequency or dosages of medications. Escalation of treatment was to be expected in all patients in the high-burden group; however, escalation occurred in only 55% of the high-burden group participants at 6 months. Assuming the goal of treating MGR participants is minimal manifestations or better with no more than grade 1 Common Terminology Criteria for Adverse Events medication side effects, and not MSE, the reasons for the lack of escalation of therapy are unclear and cannot inform clinical practice. Also, Lee et al analyzed data up to July 13, 2018, at which time only eculizumab was approved by the US Food and Drug Administration. It is unclear how many participants used eculizumab. We now have more medications that we can use, including complement inhibitors and efgartigimod, as bridging therapy while awaiting a response to oral immunosuppression. These therapies are changing the landscape of management of MG patients and their full spectrum of use in MG is still evolving. Third, multivariate logistic regression showed that a lower burden of disease and improvement of MG-ADL at 6 months was associated with a significantly increased likelihood of achieving MSE, and any use of pyridostigmine was associated with a significantly lower likelihood of MSE. The authors postulated that pyridostigmine may not be effective in achieving remission over 1 year, but it is also possible that patients were using pyridostigmine merely because their disease was not in remission. Finally, contrary to what may be expected, females of childbearing age (<45 years) used mycophenolate mofetil and prednisone as frequently as males. Interrogating physician preferences given the teratogenic potential of mycophenolate in this age group may inform the basis for this finding. Abbreviations: ADL, activities of daily living; MG, myasthenia gravis; MG-QOL-15R, 15-item Myasthenia Gravis Quality of Life---Revised; MGR, Myasthenia Gravis Patient Registry; MSE, minimal symptom expression. Received: 11 July 2022 Revised: 19 July 2022 Accepted: 24 July 2022