Myasthenia gravis (MG) treatments are rapidly increasing. Since 2021, the FDA approved 6 new MG therapies including IV and sub-cutaneous complement inhibitors and Fc receptor (FcRN) inhibitors (Bril et al., 2023, Howard et al., 2021, Meisel et al., 2023, Vu et al., 2022). The robust MG treatment development pipeline spans at least 7 novel therapeutic classes (Hehir et al., 2022a). Traditional immunotherapies including middle to high doses of corticosteroids (e.g. prednisone), non-steroid immunosuppressants (e.g. mycophenolate and azathioprine), intravenous immunoglobulin (IVIG), plasma exchange, and B-cell inhibitors (e.g. rituximab) are also effective for patients with MG. Although comparative effectiveness research with new generation MG therapies is lacking, clinical improvement for MG patients observed in large phase 3 clinical trials of these medications appears comparable (Bril et al., 2023, Howard et al., 2017, Howard et al., 2021, Howard et al., 2023, Howard et al., 2024a, Meisel et al., 2023). Traditional immunotherapies appear effective at achieving high rates of minimal disease manifestations for patients; similar results have not been reported with newer generation MG treatments (Hehir et al., 2010, Masuda et al., 2012, Narayanaswami et al., 2024, Palace et al., 1998, Pascuzzi et al., 1984, Piehl et al., 2022, Utsugisawa et al., 2017). Patients with MG often require treatment with multiple traditional and new generation immunotherapies that induce long-term immunosuppression in order to improve strength, enhance function, and reduce hospitalization due to neuromuscular respiratory weakness (Hehir et al., 2022a). It is exciting to have many therapeutic options for our patients. However, limited numbers of comparative effectiveness trials, which to date have only focused on mycophenolate and azathioprine, present a challenge for clinicians and patients as they attempt to choose the best medical regimen for any specific MG patient (Benatar et al., 2023, Narayanaswami et al., 2024).

International MG Consensus Guidance define successful treatments as those that result in minimal disease manifestations or remission with no more than minimal adverse events (AE) (Sanders et al., 2016). As we attempt to understand the best treatments and combinations of treatments for our MG patients, it is important to consider the goals set forth in the MG Guidance. Choice of clinically meaningful change in the Myasthenia Gravis Activities of Daily Living scale (MG-ADL) as the primary outcome in recent phase 3 clinical trials in MG, rather than focus on achieving the preferred MG patient clinical status of minimal to no symptoms, has been raised as a major criticism to these trials by the MG community (Benatar et al., 2023). Early comparative effectiveness data suggest parody between mycophenolate and azathioprine with regard to improvement in strength (Narayanaswami et al., 2024). Similar improvement in the MG-ADL has been observed in the phase 3, placebo controlled trials of newer MG therapeutics (Bril et al., 2023, Howard et al., 2017, Howard et al., 2023, Howard et al., 2024a, Meisel et al., 2023). While it is outside the scope of this chapter, we suspect that future trials will attempt to understand differences in clinical outcomes among these therapies; based on existing clinical trial data, it is likely that many of these treatments will induce similar improvements in MG patient strength and reduction in MG symptoms.

Treatment value can be defined as clinical improvement and quality of life improvement divided by monetary cost, side effect burden, and treatment burden. As the new generation, high-cost MG treatments are approved for use in MG, it will be critical to develop ways to compare these treatments based on other metrics such as side effect burden, treatment burden, and monetary cost in order to inform treatment choice for our patients (Trice et al., 2021). Indeed, the Rare Disease Clinical Research Network, MGNet recently emphasized the critical need to develop new outcomes to measure the potential negative aspects of MG treatments including side effect burden, health economic impact, and impact of non-oral agents on patient treatment satisfaction (Benatar et al., 2023). This chapter will focus on the importance of measuring side effect burden in MG patients and the best strategies to measure this burden as we prepare for future comparative effectiveness clinical trials and to better measure side effects in the clinic.