OBJECTIVES: Myasthenia gravis (MG) is a rare autoimmune neuromuscular disease. Standard therapy usually includes corticosteroids and acetylcholinesterase inhibition. Other non-steroidal immunosuppressive or immunomodulatory therapies are often utilized including azathioprine (AZA), cyclophosphamide (CTX), methotrexate (MTX), mycophenolate mofetil (MMF); tacrolimus (TAC), intravenous immunoglobulin (IVIg), plasma exchange (PLEX); or monoclonal antibody therapies such as rituximab (RTX) or eculizumab (ECU). Efgartigimod (EFG) is a first-in-class antibody fragment which has shown favorable efficacy versus placebo in a Phase III trial in generalized MG [gMG]. However, no comparative effectiveness data are available. The aim of this study was to evaluate the comparative effectiveness and safety of EFG in gMG.

METHODS: A comprehensive systematic literature review was conducted using biomedical databases (Embase, Medline) and other sources (conferences, Cochrane Database) to identify randomized controlled trials of the above therapies in gMG. Clinical data across studies was extracted. A network meta‐analysis was performed on efficacy and safety endpoints for studies that met pre-specified inclusion criteria.

RESULTS: 15 Studies met the inclusion criteria. Among patients with gMG, 8 weeks of EFG was associated with a similar reduction from baseline QMG relative to placebo (mean difference: -2.46, 95% Credible Interval [CrI]: -5.85 to 0.6) compared to ECU (mean difference: -3.46, 95% CrI: -7.04 to -0.52), and superior to that of all other treatments (all mean differences vs. placebo -1.09 or greater). Among all treatments, patients receiving EFG had the lowest odds of experiencing a treatment-emergent adverse event relative to placebo (odds ratio [OR]: 0.66, 95% CrI: 0.27-1.58) or serious adverse event (OR: 0.46, 95% CrI: 0.14-1.54) of all treatments analyzed.

CONCLUSIONS: Efgartigimod has a favorable comparative effectiveness and safety profile versus currently available gMG treatments. Limitations of this study include heterogeneity of study populations, differences in treatment administration, and small sample sizes across trials.