Efgartigimod Monotherapy More Effective Than IVIG in Elderly Patients With Generalized Myasthenia Gravis

Efgartigimod, a neonatal Fc receptor (FcRn) inhibitor, induced greater reductions in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores at weeks 4 and 8 compared with intravenous immunoglobulin in elderly patients with generalized myasthenia gravis (gMG), according to results published by investigators in Clinical Immunology.¹

Myasthenia gravis can be debilitating for patients and cause muscle and limb weakness. | Image Credit: © Lila Patel - stock.adobe.com

In MG, one of the most observed antibodies is the acetylcholine receptor antibody, which comprises around 80% to 85% of antibodies in patients. These antibodies appear due to complement-mediated damage to the muscle membrane and antigenic modulation, leading to AChR degradation. Ultimately, they provide a target for therapies such as efgartigimod, plasma exchange (PE), and IVIG. However, the latter therapies have been associated with adverse events despite their efficacy.^1,2

Given the possible complications of PE and IVIG, efgartigimod has emerged as an alternative, particularly for patients with contraindications or who may be at higher risk of severe complications with the intense therapies. Efgartigimod is the first FcRn inhibitor to be approved by the FDA and works similarly to IVIG by reducing immunoglobulin G (IgG) levels to achieve therapeutic outcomes. Multiple studies, including the ADAPT trial, have demonstrated efgartigimod’s efficacy in gMG, but there is a lack of comparative literature examining the efficacy and safety of efgartigimod and IVIG in AChR-Ab-positive gMG patients.^1,3

This comparison is even more critical to elucidate further when considering the increasing prevalence of MG in elderly patients. In the previously mentioned ADAPT trial, the mean age of participants was about 45.9 years, which the current authors say could present a lack of representation among older patients. Therefore, the current investigation aimed to compare efgartigimod’s efficacy with IVIG in elderly gMG patients to gather valuable insights and provide better clinical guidance to providers.^1,4

In this single-center, prospective cohort study, elderly Chinese patients with AChR-Ab-positive gMG were enrolled from January 2024 to July 2024. Patients were randomly assigned to receive either efgartigimod or IVIG treatment, and the efficacy of each treatment was observed during hospitalization and post-discharge follow-up. Primary outcomes included the differences in improvements of total scores and sub scores across all muscle groups on the MG-ADL and the percentage of minimal symptom expression (MSE) in each group at weeks 4 and 8.¹

A statistically significant difference in mean MG-ADL scores was observed during the study, with patients receiving efgartigimod exhibiting lower scores compared with IVIG (2.4 vs 5.5, P < .001). Furthermore, there was also a statistically significant difference in MG-ADL scores across the 4-week period, indicating sustained and consistent improvement in efgartigimod patients (8.8 vs 6.3, P = .004. Critically, there were improvements in muscle weakness across all muscle groups, with major improvements observed in the limb (P = .011) and respiratory (P = .049) muscle groups, according to the investigators.¹

Regarding MSE, a higher proportion of patients receiving efgartigimod achieved proper MSE levels at week 4 compared with the IVIG cohort, though the difference (16% versus 6.1%, P = .34) was not statistically significant, the investigators found. Similarly, the proportion remained not statistically different between each treatment group (24% in efgartigimod versus 24.5% in IVIG, P = .34) at week 8.¹

At week 8, MG-ADL scores remained significantly different between patients receiving efgartigimod and those receiving IVIG, with the efgartigimod group indicating lower scores (2.4 vs 4.1, P = .002). Despite these sustained signs of efficacy, there was no major difference in the reduction of MG-ADL scores over the 8-week period (P = .541), and there were no major differences found in the reductions of MG-ADL scores across various muscle subgroups, the investigators found.¹

These results suggest superior efficacy in elderly AChR-Ab-positive patients with gMG with efgartigimod compared with IVIG and a preference for efgartigimod in patients who have primary manifestations of limb and respiratory muscle weakness. Importantly, the risk of infection in patients receiving FcRn inhibitors such as efgartigimod appears to be limited based on available data, but vigilance among health care providers and pharmacists is still necessary.¹

REFERENCES

1. Zhang C, Li X, Deng Y, et al. The efficacy and safety between efgartigimod and intravenous immunoglobulin in elderly generalized myasthenia gravis patients. Clinical Immunology. Available online February 21, 2025. Accessed March 4, 2025. doi:10.1016/j.clim.2025.110457

2. Pham MC, Masi G, Patzina R, et al. Individual myasthenia gravis autoantibody clones can efficiently mediate multiple mechanisms of pathology. Acta Neuropathologica. 2023;146:319-336. doi:10.1007/s00401-023-02603-y

3. Howard JF, Bril V, Vu T, et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalized myasthenia gravis (ADAPT): A multicenter, randomized, placebo-controlled, phase 3 trial. The Lancet Neurology. 2021;20(7):526-536. doi:10.1016/S1474-4422(21)00159-9

4. Bruckman D, Lee I, Schold JD, et al. Epidemiologic study of myasthenia gravis in the elderly US population: A longitudinal analysis of the Medicare claims database, 2006-2019. Neurology. 2023;103(10). doi:10.1212/WNL.000000000021000