Promising Early Efgartigimod Response Data for Generalized Myasthenia Gravis

Reductions in both Myasthenia Gravis Activities of Daily Living (MG-ADL) score and Quantitative Myasthenia Gravis (QMG) scores reflect efgartigimod’s ability to spur response in patients who have myasthenia gravis, with earlier responses more likely with shorter disease duration and in the presence of severe bulbar (speaking, swallowing, breathing) symptoms.

Investigators published the results of their new multicenter, real-world, retrospective, observational study in the Journal of Neurology, explaining that despite the known efficacy of the neonatal Fc receptor blocker, data are lacking on factors indicating early therapeutic response. For their study population of 115 patients with acetylcholine receptor antibody–positive generalized myasthenia gravis, symptom improvement was defined as at least a 2-point improvement on MG-ADL score and at least a 3-point increase in QMG score; early responders were those who showed improvement after the first of 4 overall infusions, and an MG-ADL score of 0 or 1 indicated minimal symptom expression.

Over a 4-week period between September 2023 and June 2024, patients received a 10-mg/kg infusion of efgartigimod weekly for 4 weeks, with assessments made at baseline and after 1, 2, 3, and 4 weeks of treatment. Beyond bulbar symptoms, respiratory, limb, diplopia, ptosis, eye closure, axial muscle, and limb response subdomains were measured. Sixty-seven percent of patients had a disease onset after age 50; 22.6% had a history of thymectomy; the most common Myasthenia Gravis Foundation of American disease classifications at baseline were class IIB (39.1%), class IIA (20.0%), or class IIIB disease 17.4%); and common therapies at baseline were treatment that did not include immunosuppressants (33.9%), steroids only (27.0%), and immunosuppression added to efgartigimod infusion (26.1%).

“Since the first cycle of efgartigimod treatment was effective in most patients,” the study authors explained, “the onset of efficacy 1 week after the first infusion was used as the primary end point for exploring associated factors.”

Of the original study population of 115 patients, 109 patients were evaluated for MGL treatment response and 76 for QMG response. The median (IQR) scores at baseline were 7 (5-9) for MG-ADL and 14 (10-17) for QMG.

One week after the first infusion, 72.5% of patients had at least a 2-point improvement on the MG-ADL scale, and this percentage continued to rise to 86.0% in the week after the second infusion, nearly 88% after the third infusion, and 93.3% after the fourth infusion. Corresponding rates of at least a 3-point improvement on the QMG index were 60.5%, 77.0%, nearly 80%, and 87.5%.

Minimal symptom expression also rose continuously, from 11.9% after the first efgartigimod infusion to 44.8% after the final efgartigimod infusion.

Significant improvements were also seen on all of the evaluable MG-ADL subdomains: bulbar (speech/voice, swallowing, chewing), respiratory (breathing), limb (ability to brush teeth or comb hair and arise from a chair), diplopia, and ptosis (P < .001). As well in most of the evaluable QMG subdomains, except respiratory symptoms: diplopia, ptosis, eye closure, axial muscle (head-lift), limb (right and left arms outstretched, hand grip strength, right and left legs outstretched), and bulbar (swallowing and speech) (P < .001).

Overall, bulbar, axial muscle, eye closure, and ptosis improved the most after the first infusion, while no significant respiratory improvements were seen over the entire treatment period.

Early efgartigimod responders per MG-ADL had several disease characteristics in common: short disease duration (P = .032), history of thymectomy (P = .036), and more severe MG-ADL scores (P = .005) and bulbar symptoms (P = .002) at baseline. Per QMG, having severe facial (P = .029) and bulbar (P = .021) symptoms at baseline indicated early efgartigimod response.

Lastly, multivariate logistic regression analysis connected 3 patient characteristics to early efgartigimod response:

• Short disease duration (OR, 0.989; 95% CI, 0.978-0.999; P = .031)
• High baseline MG-ADL bulbar score (OR, 1.335; 95% CI, 1.040-1.762; P = .022)
• High baseline QMG bulbar score (OR, 1.698; 95% CI, 1.044-2.761; P = .033)

Their results, the authors explained, echo previous research on the efficacy and safety of efgartigimod,^2-4 as well as being some of the first findings to demonstrate efgartigimod early response and that early intervention in generalized myasthenia gravis may yield greater therapeutic benefits, “possibly due to less extensive neuromuscular damage or preserved functional reserves.”

However, there are limitations. The small sample size and lack of long-term follow-up restrict applicability to a wider patient population, and patient discontinuations may have impacted the true effectiveness rate of efgartigimod.

Still, these data suggest, the authors concluded, “a potential for widespread use of efgartigimod in clinical practice and indicates good efficacy not only for patients with myasthenic crisis or refractory disease, but also for those with mild to moderate diseases.”

References

1. Zhu W, Chen Y, Tian C, et al. Factors associated with early response to efgartigimod in patients with generalized myasthenia gravis: a multicenter retrospective observational study. J Neurol. 2025;272(9):622. doi:10.1007/s00415-025-13367-8
2. Howard JF Jr, Bril V, Vu T, et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2021;20(7):526-536. doi:10.1016/s1474-4422(21)00159-9
3. Fuchs L, Shelly S, Vigiser I, et al. Real-world experience with efgartigimod in patients with myasthenia gravis. J Neurol. 2024; 271(6):3462-3470. doi:10.1007/s00415-024-12293-5
4. Stetefeld H, Schroeter M. SOP myasthenic crisis. Neurol Res Pract. 2019;1:19. doi:10.1186/s42466-019-0023-3