Comparative effectiveness clinical trials to advance treatment of myasthenia gravis

Abstract

Myasthenia gravis (MG) presents many challenges for establishing treatment efficacy through clinical trials. Among these are the rarity and heterogeneity of the disease, spontaneous fluctuations, prolonged latency to effect for many immunosuppressive drugs, and the uncertain generalizability of results from randomized controlled trials (RCTs). Prospective observational study designs may overcome some of these limitations, but attention is required to ensure that internal validity is not compromised. Observational comparative effectiveness research (CER) utilizes data obtained during routine clinical care to evaluate the effectiveness of interventions in real-life practice conditions, thereby improving generalizability to the clinic. Compared with RCTs, observational CER studies may be less resource intensive and costly. Recent advances that have improved the feasibility of CER studies for MG are (1) the development of MG common data elements, (2) the publication of international consensus guidance for MG treatment, and (3) the development of a web-based REDCap database that can be shared and adapted to standardize data collection. This infrastructure could be used for multisite comparisons of commonly used therapies and provides longitudinal information on patient- and clinician-centered MG outcome measures. A challenge is to design studies that address the potential limitations of observational trials, such as confounding and selection and information bias.

Safety and outcomes of eculizumab for acetylcholine receptor‐positive generalized myasthenia gravis in clinical practice

“…1,2 However, data assessing generalizability of trial results to clinical practice are limited. 3 In this study, we reviewed clinical response, change in immunomodulatory therapy (IMT), and adverse events in patients at two academic centers who received eculizumab for AChR+ gMG.…”

“…The REGAIN clinical trial and its open‐label extension (OLE) demonstrated eculizumab's efficacy and favorable safety profile for the treatment of acetylcholine receptor antibody positive (AChR+) generalized myasthenia gravis (gMG) 1,2 . However, data assessing generalizability of trial results to clinical practice are limited 3 . In this study, we reviewed clinical response, change in immunomodulatory therapy (IMT), and adverse events in patients at two academic centers who received eculizumab for AChR+ gMG.…”