Rapid efficacy of efgartigimod for generalized myasthenia gravis patients in acute exacerbations/worsening: multicenter real-world retrospective study

Abstract

Background and objectives

Acute exacerbations/worsening of generalized myasthenia gravis (gMG) require urgent intervention to prevent progression to life-threatening myasthenic crisis. This multicenter study evaluate the efficacy and safety of efgartigimod in gMG patients experiencing acute exacerbations/worsening to validate its potential as a rapid-acting therapeutic option.

Methods

In this multicenter retrospective study (Jan 2024–Feb 2025), 61 gMG patients with acute exacerbations/worsening received weekly efgartigimod infusions for 4 weeks. Efficacy was assessed at baseline (W0) and weekly throughout the treatment cycle (W1–W7) using Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS), Quantitative Myasthenia Gravis (QMG), and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores, along with prednisone dosage reductions. Safety assessments were concurrently performed.

Results

Median age was 56 years (range: 39–68 years). Pulmonary infection (16/61, 26.2%) was the predominant trigger of myasthenic crisis (MC) red flgs. Median duration from symptom deterioration to efgartigimod initiation was 18 days. Clinical meaningful improvement occurred in 81.9% at W1 (post-single dose), 98.1% at W4, and 91.9% at W7. MG-ADL and QMG scores decreased substantially from baseline (W4: 80.86% and 55.81% reduction; W7: 70.78% and 47.76% reduction), Patients with MC red flags achieved comparable outcomes. Greater MG-ADL imrovements were observed in those with thymoma history, severe MGFA classification, prior MC, or MC red flags. No treatment-related allergic reactions, infections, or serious adverse events were observed.

Conclusion

Efgartigimod demonstrates rapid, significant efficacy in gMG acute exacerbations/worsening, supporting its role as a valuable therapeutic option for this high-risk population.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00415-026-13695-3.

Introduction

Myasthenia gravis (MG) is a neuromuscular junction disorder primarily caused by pathogenic autoantibodies, most commonly anti-acetylcholine receptor (AChR) antibodies. Approximately 5–8% of patients possess antibodies directed against muscle-specific receptor tyrosine kinase (MuSK). These antibodies impair postsynaptic structures at the neuromuscular junction [1, 2]. Clinically, MG is characterized by fluctuating weakness and fatigue. Acute exacerbations or worsening of symptoms in patients with MG are often precipitated by infections, surgical procedures, or other external factors [3, 4]. In cases where muscle weakness rapidly worsens, leading to dysphagia and respiratory failure, myasthenic crisis (MC) may occur, posing a potentially life-threatening condition for patients with MG.

Poor symptom control, acute exacerbations or worsening, and MC are the primary reasons for hospitalization and represent significant aspects of the disease burden in patients with MG [5, 6]. Progression from acute exacerbation or worsening to impending MC and ultimately to MC typically occurs as a continuous process [7]. The progression rate from acute exacerbation to MC is 41.9%, whereas the rate of progression from impending MC to MC is 72.4% [8]. In cases of acute exacerbation or worsening, particularly when red flag signs of impending MC are present [9], prompt intervention and treatment are essential to prevent progression to MC and improve patient outcomes [10].

Intravenous immunoglobulin (IVIG) and plasma exchange (PE) have demonstrated efficacy in treating 70% of patients with MC, with rapid therapeutic effects observed as early as the fourth or fifth day of IVIG administration, or following the second or third session of plasmapheresis [11–14]. However, challenges remain regarding the accessibility and high cost of blood products. The emergence of novel biological agents has facilitated the development of more rapid, selective, and target-specific immunotherapies for patients with MG [15].

Efgartigimod, a neonatal Fc receptor (FcRn) inhibitor, received regulatory approval in China in 2023 for adult patients with AChR antibody–positive generalized myasthenia gravis (gMG). Evidence from the pivotal phase III ADAPT clinical trial and recent clinical studies has indicated that efgartigimod has rapid and effective clinical improvement across various MG patient sub groups, including those in pre-crisis states and those experiencing MC [16–22]. Therefore, given the enhanced accessibility and lower overall cost-effectiveness of efgartigimod compared to conventional rescue therapies such as IVIG and PE, along with its rapid and efficient action [23–25], further investigation into the efficacy of efgartigimod for managing acute exacerbations or deterioration in gMG patients is recommended to optimize the provision of timely and effective treatment options.

This multicenter retrospective study aimed to evaluate the efficacy and safety of efgartigimod in treating seropositive gMG patients experiencing episodes of acute exacerbation or deterioration.

Methods

Study design

This multicenter retrospective study was conducted across nine centers in China from January 2024 to February 2025. The inclusion criteria were as follows: 1) confirmed diagnosis of gMG classified as class II-V according to the Myasthenia Gravis Foundation of America (MGFA) criteria [26, 27]; 2) exacerbation defined as a ≥ 3-point increase in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score and a ≥ 3-point elevation in the Quantitative Myasthenia Gravis (QMG) score from baseline compared to pre-exacerbation levels; and 3) participants received at least one cycle of intravenous efgartigimod with 4-week post-treatment follow-up. The exclusion criteria included pregnant or lactating individuals, patients with known hypersensitivity to biological agents, individuals with significant hepatic dysfunction, and those who had received PE or IVIG therapy within one month prior to efgartigimod administration. Worsening is defined as a significant increase in clinical manifestations from the pre-treatment baseline or substantial escalation in MG-related medication doses to maintain disease stability. The study has been approved by the Clinical Investigation Committee at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (Approval Number: TJ-IRB202407056) and conformed to the principles of the Declaration of Helsinki. Written or oral informed consent for the publication of this study was obtained from the patient and/or their family.

Treatment, follow-up and assessment

All participants were administered a weekly injection of efgartigimod at a dosage of 10 mg/kg, following a 4-dose cycle per treatment regimen as adjunctive therapy to their baseline immunosuppressive regimens. Patients underwent standardized weekly monitoring, with assessments conducted at pre-exacerbation, baseline, during each treatment cycle, and throughout the 4-week post-treatment follow-up period. Data encompassing demographic details, clinical presentation, antibody profiles, thymoma status, comorbidities, and MGFA classification before pre-exacerbation and at baseline, as well as treatment medications prior to exacerbation, were systematically recorded. Treatment efficacy was evaluated at each visit using MG-ADL scores and QMG scores.

Minimal symptom expression (MSE) is defined as an MG-ADL score of 1 or less [28]. QMG assessments were systematically performed 6–8 h following pyridostigmine administration to minimize the potential influence of anticholinesterase medications. The term 'baseline' refers to the pre-treatment period prior to the initial administration of efgartigimod, during which symptom exacerbation is typically observed.‌ ‌Clinical Meaningful Improvement (CMI)‌ is operationally defined as a reduction of ≥ 2-points in the MG-ADL score from the baseline assessment[29]. The primary efficacy endpoint was the proportion of CMI at W4. Infection is defined as either a pulmonary infection or the initiation of anti-infective therapy. ‌Red flags of impending MC defined as the new onset or acute exacerbation of the following symptoms within 2 weeks in MG patients: a) Infections requiring anti-infective therapy; b) Choking or dysphagia; c) Cough and weak expectoration; d) Dysarthria; e) Head drop sign; f) Mandibular droop; g) Facial weakness; h) Breathing difficulty [9]. All treatment-emergent adverse events were systematically recorded and classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, which includes infectious, non-infectious, and hypersensitivity reactions.

Statistical analysis

Statistical analysis were performed using R version 4.4.1. Quantitative data with normal distributions were presented as mean ± standard deviation (Mean ± SD), and intergroup comparisons were conducted using independent samples t-tests or analysis of variance (ANOVA), as appropriate. For quantitative data with skewed distributions, results are expressed as medians with interquartile ranges (M [Q1, Q3]), and comparisons between groups were performed using the Mann–Whitney U test or the Kruskal–Wallis rank sum test. Categorical variables are summarized as frequencies and percentages. The random forest imputation algorithm was used to handle missing data (< 20%) to ensure data integrity and analytical precision. Indicators with missing data > 20% were only described descriptively. The significance level was set at p = 0.05. p < 0.05 was considered to be statistically significant.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Results

Clinical characteristics of gMG patients prior to acute exacerbation /worsening

A total of 61 patients with gMG experiencing acute exacerbation or worsening were included, comprising 34 females (55.7%) and 27 males (44.3%). The median age at baseline was 56 years (range: 39–68 years), whereas the median age at disease onset was 53 years (range: 37–63 years). Among these, 25 patients (41.0%) exhibited early-onset MG (onset age < 50 years), whereas 36 patients (59.0%) belonged to late-onset MG (onset age ≥ 50 years). The median disease duration was 8.0 months (range: 3.0–41.0 months). Extraocular muscle involvement was the initial symptom in 37 patients (60.7%). All patients were seropositive: 44 (72.1%) tested positive exclusively for AChR antibodies, and 15 (24.6%) were double-positive for AChR and other antibodies (Titin/RyR). Thymoma was detected in 22 patients (36.1%), of whom 19 (86,4%) underwent thymectomy. The pathological subtypes were as follows: AB type in 2 cases, B1 type in 5 cases, B2 type in 10 cases, and B3 type in 2 cases. Among them, 1 patient underwent surgery after efgartigimod treatment, while the rest had thymectomy during prior disease course. Comorbidities were present in 28 patients (45.9%), including 11 with hypertension, 6 with diabetes mellitus, and 6 with connective tissue disease. Nine patients (14.8%) experienced MC during the disease course. The mean number of acute exacerbations within one year was 1.11 ± 0.41. Prior medical history included 12 patients with IVIG/PE treatments, 40 with non-steroidal immunosuppressive therapies (NSISTs): tacrolimus (27), mycophenolate mofetil (10), azathioprine (2), and methotrexate (1); and six with biological agents: telitacicept (2), rituximab (1), ofatumumab (1), satralizumab (1), and a combination of rituximab and telitacicept (1). Before acute exacerbation, 19 patients exhibited well-controlled symptoms and achieved minimal manifestation status (MMS), corresponding to MGFA class 0. ‌At baseline, the median daily doses of pyridostigmine bromide and prednisone were 180 mg and 20.7 mg, respectively. ‌Pulmonary infection (16/61, 26.2%) was a prominent red flag for impending MC. The detailed demographic and clinical characteristics are presented in Table 1.

Table 1.

Baseline characteristics of patients with acute exacerbation/worsening of gMG (N = 61)

	N = 61	Without red flags (n = 25)	With red flags& (n = 36)	P
Gender, n (%)				0.973
Male	27 (44.3%)	11 (44.0%)	16 (44.4%)
Female	34 (55.7%)	14 (56.0%)	20 (55.6%)
Onset age(Y), median (Q1, Q3)	53.0 (37.0, 63.0)	51.0 (38.0, 60.0)	53.5 (36.0, 68.0)	0.495
Current age(Y), median (Q1, Q3)	56.0(39.0,68.0)	60.0(42.0,64.0)	56.0(39.0,69.5)	0.519
Disease duration(M), median (Q1,Q3)	8.0 (3.0, 41.0)	6.0 (2.0, 36.0)	8.0 (3.5, 41.0)	0.965
Onset symptoms, n (%)				0.173
Extraocular muscles	37 (60.7%)	17 (68.0%)	20 (55.6%)
Limb and Trunk muscles	12 (19.7%)	6 (24.0%)	6 (16.7%)
Respiratory muscles	3 (4.9%)	0 (0.0%)	3 (8.3%)
Bulbar muscles	4 (6.6%)	2 (8.0%)	2 (5.6%)
Mixed	5 (8.2%)	0 (0.0%)	5 (13.9%)
Antibody profile, n (%)				0.060
Only AChR-Ab positive	44 (72.1%)	22 (88.0%)	22 (61.1%)
AChR + Titin-Ab positive	14(23.0%)	3(12%)	11(30.6%)
AChR + RYR-Ab positive	1	0	1
AChR + Titin + LRP4-Ab positive	1	0	1
AChR + Titin + RYR-Ab positive	1	0	1
Thymoma, n (%)	22 (36.1%)	5 (20.0%)	17 (47.2%)	0.029
Thymectomy, n (%)	19 (31.0%)	5 (20.0%)	14 (38.9%)	0.138
History of MC, n (%)	9 (14.8%)	2 (8.0%)	7 (19.4%)	0.286
History of rescue treatment with IVIG/PE, n (%)	12 (19.7%)	3 (12.0%)	9(25.0%)	0.401
Comorbidities, n (%)
Hypertension	11 (18.0%)	6 (24.0%)	5 (13.9%)	0.333
Diabetes mellitus	6 (9.8%)	1 (4.0%)	5 (13.9%)	0.386
Autoimmune diseases	6 (9.8%)	3 (12.0%)	3 (8.3%)	0.682
Tumor	5 (8.2%)	2 (8.0%)	3 (8.3%)	1.000
MGFA classification (before exacerbation) , n (%)				< 0.001
0	19 (31.2%)	7 (28.0%)	12 (33.3%)
I	13 (21.3%)	12 (48.0%)	1 (2.8%)
II	23(37.7%)	6 (24.0%)	17 (47.2%)
III	6 (9.8%)	0 (0.0%)	6 (16.7%)
Treatment medications before exacerbation
Acetylcholinesterase inhibitor	58 (95.1%)	22 (88.0%)	36 (100.0%)	0.064
Corticosteroids	45 (73.8%)	18 (72.0%)	27 (75.0%)	0.793
NSIST	40 (65.6%)	16 (64.0%)	24 (66.7%)	0.829
Biological agents	6 (9.8%)	2 (8.0%)	4 (11.1%)	1.000
MGFA classification at baseline				< 0.001
II	23 (37.7%)	18 (72.0%)	5 (13.9%)
III	23 (37.7%)	7 (28.0%)	16 (44.4%)
IV	11 (18.0%)	0 (0.0%)	11 (30.6%)
V	4 (6.6%)	0 (0.0%)	4 (11.1%)
PIS status at baseline, n (%)				0.090
Acute exacerbation	47 (77.1%)	22 (88.0%)	25 (69.4%)
worsening	14 (22.9%)	3 (12.0%)	11 (30.6%)
Median dosage of Pyridostigmine(mg/d) (Q1,Q3)	180.0 (180.0,240.0)	180.0 (180.0,270.0)	210.0 (180.0,240.0)	0.741
Average dosage of corticosteroids (mg/d)	20.7(12.6)	22.9(15.6)	18.9(9.5)	0.678
Red flags of impending-MC, n (%)				–
Pulmonary infection	16(26.2)	–	16(26.2)
Other signs	20(32.8)	–	20(32.8)
Median duration between exacerbation to add-on efgartigimod therapy (days) (Q1,Q3)	18.0(9.0,30.0)	16.0(8.0,30.0)	19.0(10.0,38.0)	0.664

MG, myasthenia gravis; SD, standard deviation; IQR, interquartile range; AChR-Abs, anti-acetylcholine receptor antibodies; MuSK, muscle-specific kinase; MGFA, myasthenia gravis foundation of American; PIS, post-invention status; MC myasthenic crisis; IVIG, intravenous immune globulin; PE, plasma exchange; NSIST, nonsteroidal immunosuppressive therapy

^&red flags of impending-crisis defined as the new onset or acute exacerbation of the following symptoms within 2 weeks in MG patients: a) Infections requiring anti-infective therapy; b) Choking or dysphagia; c) Cough and weak expectoration; d) Dysarthria; e) Head drop sign; f) Mandibular droop; g)Facial weakness; h) Breathing difficulty

^*comparison between MG patients with or without red flags of impending-crisis

Baseline features (W0) during acute exacerbations/worsening

Among all patients with gMG, 47 cases (77.1%) presented with acute exacerbations, whereas 14 cases (22.9%) exhibited symptom worsening. Among the 36 patients who experienced acute exacerbations, red flags indicating impending MC were identified, including 16 cases (26.2%) of pulmonary infection and other red flag signs in 32.8% of cases. Patients presenting red flag signs were more frequently classified as MGFA II/III (63.9%) prior to acute exacerbation and demonstrated a higher prevalence of thymoma. At baseline, these patients also exhibited more severe MGFA classifications, with 41.7% classified as type IV or V (Table 1) and higher MG-ADL scores (With Red flags vs without: 10.36 ± 3.49 vs 6.00 ± 1.58, p < 0.001). The primary causes of symptom exacerbation or worsening included infection (22 cases), medication discontinuation (6 cases), surgical procedures (2 cases), and stress or fatigue (1 case). Notably, the majority of cases (18 cases) lacked a clear identifiable cause (Table 2).

Table 2.

Causes of acute exacerbation/worsening in gMG

Causes of acute exacerbation/worsening	N = 61 (n, %)
Infection	22 (36.1%)
MG medication reduction or discontinuation	6 (9.8%)
Surgery	2 (3.3%)
Stress or fatigue	1 (1.6%)
Systematic disease	2 (3.3%)
Unclear causes	18 (29.5%)
Others	4 (6.6%)
NA	6(9.8%)

At baseline, the mean MG-ADL and QMG scores were 8.57 ± 3.59 and 16.67 ± 5.37, respectively. Relative to pre-exacerbation or worsening, the mean MG-ADL score increased by 6.05 ± 3.13, while the mean QMG score increased by 7.95 ± 4.61. These changes reflected clinical deterioration in the ocular, bulbar, and truncal/limb muscle groups, with variable degrees of respiratory muscle (Table S1). Baseline MGFA classifications were as follows: Type II, 23 cases (37.7%); Type III, 23 cases (37.7%); Type IV, 11 cases (18.0%); and Type V, 4 cases (6.6%). Among the four patients classified as MGFA type V, the mean MG-ADL score before exacerbation was 5.50 ± 3.11, while at baseline, it was 16.00 ± 1.15. The mean prednisone dosage at baseline was 20.7 ± 12.6 mg/d, and the mean pyridostigmine bromide dosage was 180.0 (interquartile range: 180.0, 240.0 mg/d). Additionally, co-administered immunosuppressants included tacrolimus in 28 cases and mycophenolate mofetil in 9 cases.

Therapeutic responses with one cycle of efgartigimod add-on therapy

All participants completed one cycle of efgartigimod injections (W0-W3), followed by a four-week clinical follow-up period (W4-W7). At the W1 follow-up, following a single dose of efgartigimod, 50 patients (81.9%) exhibited CMI with 6 cases (9.8%) achieving MMS. At the W4 follow-up, after completion of one treatment cycle, 52 patients (98.1%) exhibited CMI, with 31 cases (58.5%) achieving MMS, 21 cases (39.6%) showing improvement, and 1 case (1.9%) remaining unchanged. At the W7 follow-up, 91.9% of patients continued to exhibit CMI, with 22 cases (59.5%) achieving MMS, 12 cases (32.4%) showing sustained improvement, and 1 patient experiencing symptom fluctuation (Fig. 1).

Fig. 1.

Changes in MG-PIS among seropositive gMG patients after add-on efgartigimod therapy during acute exacerbation/worsening at different follow-up. Abbreviations: MGFA-PIS: Myasthenia Gravis Foundation of America Post-Intervention Status; gMG: generalized MG; MMS: minimal manifestation status

In patients with acute exacerbation or worsening of MG, both the MG-ADL and QMG scores were significantly reduced at the first follow-up (W1) after the addition of efgartigimod treatment compared to the baseline (W0) (MG-ADL: W0, 8.57 ± 3.58; W1, 4.87 ± 3.73, p < 0.001; QMG: W0, 16.62 ± 5.26; W1, 11.59 ± 5.24, p < 0.001). The mean total MG-ADL and QMG scores remained significantly reduced from W2 to W4 (MG-ADL: W2, 3.31 ± 3.52; W3, 2.20 ± 2.48; W4, 1.61 ± 2.04; QMG: W2, 9.25 ± 4.86; W3, 8.05 ± 4.12; W4, 7.16 ± 3.75). Although some degree of symptom recurrence was observed after W5, both the MG-ADL and QMG scores at W7 remained significantly lower than the baseline scores (MG-ADL: W7, 2.05 ± 2.47, p < 0.001; QMG: W7, 7.19 ± 3.86, p < 0.001) (Fig. 2a, b). Furthermore, the proportions of patients achieving MSE at W1, W4, and W7 were 9.8%, 58.5%, and 59.5%, respectively.

Fig. 2.

Clinical improvement assessed by MG-ADL and QMG after add-on efgartigimod therapy during acute exacerbation/worsening in seropositive gMG patients. a, c Changes in MG-ADL after add-on efgartigimod therapy during acute exacerbation/worsening at different fellow-up. b, d Changes in QMG after add-on efgartigimod therapy during acute exacerbation/worsening at different fellow-up. *P value < 0.05, **P value < 0.01, ***P value < 0.001. Abbreviations: MG-ADL, Myasthenia Gravis Activities of Daily Living; QMG, quantitative myasthenia gravis

The most pronounced reductions in the MG-ADL and QMG scores occurred at W4, with reductions of -80.86 ± 23.57% and -55.81 ± 21.99%, respectively, followed by a certain degree of recovery from W5. However, at W7, the reductions in the MG-ADL and QMG scores compared to baseline were -70.78 ± 31.64% and −47.76 ± 27.85%, respectively (Fig. 2c, d). When analyzing individual muscle groups, the most significant changes in the MG-ADL and QMG scores were observed in the respiratory and bulbar muscles, followed by the ocular and limb/trunk muscle groups (Figs. S1 and S2).

Furthermore, patients presenting with red flags exhibited a similarly rapid response to efgartigimod treatment, as evidenced by significant improvements in QMG and MG-ADL scores starting from W1, with maximal improvement at W4 (Change from baseline to W4: QMG: −11.55, p < 0.001; MG-ADL: −8.53, p < 0.001). At W7, a significant improvement compared to W0 remained evident. However, no difference in response was observed when compared to patients without red flags of impending MC (Fig. 3).

Fig. 3.

Changes of MG-ADL and QMG after add-on efgartigimod therapy during acute exacerbation/worsening in seropositive gMG patients, with or without red flags. a, b Changes in MG-ADL and QMG after add-on efgartigimod therapy during acute exacerbation/worsening at different fellow-up, with or without red flags. *P value < 0.05, **P value < 0.01, ***P value < 0.001. Abbreviations: MG-ADL, Myasthenia Gravis Activities of Daily Living; QMG, quantitative myasthenia gravis

Besides, no statistically significant changes were observed about the mean dosage of corticosteroid during the threatment cycle (W0, 20.7 ± 12.6; W1, 19.7 ± 12.4; W2, 19.2 ± 12.0; W3, 18.4 ± 11.7; W4, 18.2 ± 11.2; W5, 17.6 ± 10.6; W6, 17.1 ± 10.5; W7, 18.2 ± 11.4). The dosage of the underlying immunosuppressant was not adjusted for all patients during the treatment and follow-up period.

Efficacy of efgartigimod across different MG subgroups

Subsequently, statistical analysis were performed across different MG subgroups. The analysis revealed no significant subgroup-by-time interaction or subgroup effect for MG-ADL and QMG scores when assessing patients by onset ages (early- or late-onset), disease durations (< 1 year, 1–3 years, ≥ 3 years), thymoma status, presence of infection, baseline MG-ADL socres(MG-ADL ≤ 9, ≥ 10) and treatment history(newly diagnosed vs. previously treated). This Indicates that the treatment effect of efartigimod was consistent across these diverse patient populations. A significant time effect was observed (p < 0.001), reflecting a substantial and consistent reduction in both MG-ADL and QMG scores after baseline following efgartigimod treatment (Tables 3 and S2).

Table 3.

Clinical response assessed by MG-ADL mean values in different populations following add-on efgartigimod therapy during acute exacerbation/worsening in seropositive gMG patients

Subgroup	Week 0	Week 4	Week 7	group	Period	Group*period
Age (years)
< 50	8.68 ± 3.66	1.20 ± 1.63	1.76 ± 2.15	Z = 0.16, p = 0.114	Z = 21.61, p < 0.001	Z = 0.01, p = 0.911
50–65	7.73 ± 2.85	1.64 ± 1.99	2.50 ± 2.60
≥ 65	9.71 ± 4.30	2.29 ± 2.67	2.57 ± 2.1
F	2.57	1.37	0.37
P	0.114	0.247	0.545
Disease course (years)
< 1	9.31 ± 3.59	1.06 ± 1.44	1.81 ± 1.33	Z = 0.04, p = 0.846	Z = 15.38, p < 0.001	Z = 0.00, p = 0.981
1–3	7.76 ± 2.86	2.71 ± 2.64	3.59 ± 2.74
≥ 3	8.64 ± 3.96	1.25 ± 1.71	1.61 ± 2.17
F	0.01	0.50	0.18
P	0.924	0.482	0.672
Thymoma
Yes	9.91 ± 3.93	1.55 ± 2.22	1.77 ± 2.33	Z = 5.50, p = 0.019	Z = 70.17, p < 0.001	Z = 6.02, p = 0.014
No	7.82 ± 3.17	1.64 ± 1.97	2.46 ± 2.28
t	2.13	−0.17	−1.12
P	0.040	0.867	0.270
MGFA classification
II	6.61 ± 1.95	1.61 ± 1.64	2.87 ± 2.47	Z = 27.18, p < 0.001	Z = 0.51, p = 0.473	Z = 22.41, p < 0.001
III	8.35 ± 2.95	0.87 ± 1.10	1.52 ± 2.06
≥ IV	11.93 ± 4.08	2.73 ± 3.08	2.27 ± 2.22
F	1.87	1.04	28.08
P	0.177	0.311	< 0.001
Red flags for impending-MC
Yes	10.36 ± 3.49	1.83 ± 2.25	2.28 ± 2.47	Z = 36.90, p < 0.001	Z = 61.64, p < 0.001	Z = 23.33, p < 0.001
No	6.00 ± 1.58	1.28 ± 1.70	2.12 ± 2.09
t	−6.59	−1.09	−0.27
P	< 0.001	0.278	0.789
History of MC
Yes	11.44 ± 3.97	2.78 ± 2.95	2.44 ± 2.35	Z = 7.15, P = 0.007	Z = 105.36, p < 0.001	Z = 5.68, p = 0.017
No	8.08 ± 3.29	1.40 ± 1.81	2.17 ± 2.32
t	−2.40	−1.35	−0.32
P	0.037	0.208	0.755
New diagnosis
Yes	8.64 ± 3.96	1.25 ± 1.71	1.61 ± 2.17	Z = 0.28, p = 0.597	Z = 58.70, p < 0.001	Z = 1.39, p = 0.239
No	8.52 ± 3.28	1.91 ± 2.27	2.73 ± 2.32
t	−0.14	1.29	1.95
P	0.893	0.202	0.056
Infection
Yes	8.68 ± 3.92	2.09 ± 2.64	2.09 ± 2.09	Z = 0.19, p = 0.660	Z = 83.77, p < 0.001	Z = 0.11, p = 0.745
No	8.51 ± 3.42	1.33 ± 1.59	2.28 ± 2.44
t	−0.17	−1.23	0.32
P	0.867	0.229	0.748
Baseline ADL
≤ 9	6.63(1.5)	1.33(1.66)	2.26(2.25)	Z = 83.76, p < 0.001	Z = 123.56, p < 0.001	Z = 55.34, p < 0.001
≥ 10	13.22(2.67)	2.28(2.7)	2.11(2.49)
t	−9.85	−1.39	0.21
P	< 0.001	0.177	0.833

P value < 0.001 for time effect

MG-ADL, Myasthenia gravis activities of daily living; MGFA, Myasthenia gravis foundation of American; MC, Myasthenic crisis

Among patients with MG a history of thymoma, severe MGFA classification, a history of MC, and red flags for impending MC, a more pronounced reduction in MG-ADL scores was observed (p < 0.05). Additionally, for QMG scores, patients with severe MGFA classification and red flags for impending MC exhibited the most significant decreasing trend (Table S2).

Safety of efgartigimod treatment in MG patients with acute exacerbation/worsening

During the treatment and follow-up periods, no adverse events such as allergic reactions, infections, or infusion-related reactions were reported. All patients tolerated the efgartigimod therapy well. Post-treatment serum biomarker assessment revealed that the mean serum immunoglobulin G (IgG) concentrations were 19.39 ± 27.84 g/L at W0, 7.25 ± 10.34 g/L at W4, and 17.74 ± 29.83 g/L at W7. No significant changes were observed in immunoglobulin M (IgM), immunoglobulin A (IgA), lipid profiles (including total cholesterol and low-density lipoprotein), albumin levels, or white blood cell counts following treatment (Fig. 4). Among patients with acute exacerbations complicated by infection, efgartigimod treatment demonstrated a comparable safety profile, with no significant differences in white blood cell counts or IgG concentration changes compared to patients without infection (Table 4).

Fig. 4.

Changes in immunological and serum markers after add-on efgartigimod therapy during acute exacerbation/worsening in seropositive gMG patients. A–C No significant changes in IgM, IgA after add-on efgartigimod therapy during acute exacerbation/worsening at different fellow-up. While serum IgG level decreased14.30 g/l in week 4 and followed by a increase at week 7. D, E No significant changes in total cholesterol and low-density lipoprotein (LDL) after add-on efgartigimod therapy during acute exacerbation/worsening at different fellow-up. F, G No significant changes in serum albumin level and white cell counts after add-on efgartigimod therapy during acute exacerbation/worsening at different fellow-up. Abbreviations: MG, myasthenia gravis; IgM, Immunoglobulin M; IgA, Immunoglobulin A; IgG, Immunoglobulin G; LDL, low-density lipoprotein

Table 4.

Impact of Efgartigimod on Leukocytes and IgG in patients with or without Infection

	Without infection (n = 39)	Infection (n = 22)	P
WBC*109
Baseline	8.70 ± 3.47	8.03 ± 2.68	0.438
Week 4	9.62 ± 3.80	7.88 ± 2.49	0.141
Week 7	9.74 ± 4.94	8.34 ± 1.91	0.330
IgG (g/L)
Baseline	24.25 ± 37.80	14.79 ± 12.64	0.339
Week 4	11.00 ± 14.50	5.06 ± 2.34	0.127
Week 7	22.10 ± 34.43	6.38 ± 1.72	0.126

Discussion

In this multicenter retrospective study, we assessed the efficacy and safety of efgartigimod in seropositive patients with gMG experiencing acute exacerbations or symptom worsening. Administration of a single treatment cycle (four doses) of efgartigimod in our study demonstrated several key findings: 1) a rapid onset of action, with significant improvements in patient MG-ADL and QMG scores observed as early as the first follow-up following the initial dose; 2) a high response rate, with the majority of patients (98.1%) achieving CMI following completion of one treatment cycle, and this improvement sustained through the final follow-up at W7; 3) clinical improvement across a broad range of symptoms, encompassing extraocular, limb, trunk, bulbar, and pharyngeal muscle involvement; and 4) comprehensive efficacy of efgartigimod across all populations, regardless of age at onset, disease duration, MGFA classification, presence of thymoma, history of MC, or whether the disease was newly diagnosed or pre-existing.

For patients with gMG experiencing acute exacerbations or symptom worsening, early initiation of rapidly acting therapies can significantly improve their clinical condition and mitigate the risk of MC. In the ADAPT study, 68% of patients with gMG treated with efgartigimod were classified as MG-ADL responders during the first treatment cycle, with significant improvements in both the MG-ADL and QMG scores observed as early as week one [16]. Comparable clinical efficacy has been reported in other Phase III trials of FcRn antagonists, such as rozanolixizumab, nipocalimab, and batoclimab [30–32]. The rapid therapeutic effects observed in our multicenter real-world study exceed those of the ADAPT study, likely due to its primary focus on patients with acute exacerbations/worsening combined with immunosuppressive therapy, which may further enhance treatment efficacy. Similar clinical responses have been documented in other real-world investigations [33]. Notably, efgartigimod might be represents a promising therapeutic option for patients with MG experiencing acute exacerbation or symptom worsening who require urgent symptomatic relief. Moreover, rapid reductions in IgG serum concentrations have been observed in these clinical trials [16, 30, 31, 34]. Our research also demonstrated that a single cycle of efgartigimod treatment led to a substantial decrease in IgG levels. In addition to the classical immunomodulatory effect of reducing IgG, emerging studies indicate that efgartigimod may also enhance clinical outcomes by inducing B cell differentiation into plasma cells with a regulatory phenotype (LAG3 + /IL-12a +), thereby potentially representing another important therapeutic mechanism [35].

In addition, our study evaluated the proportion of patients achieving MSE. Evidence suggests that achieving MMS/MSE at an earlier stage in patients with MG is associated with sustained disease stability and a reduced risk of subsequent MC [36]. A large-scale German cohort study reported that achieving MSE within one year significantly decreased the incidence of MC and clinical deterioration [37]. In contrast, traditional immunosuppressant therapies for patients with MG have been reported to achieve lower MMS rates with prolonged median treatment durations. Among patients with low disease burden (MG-ADL < 6), the one-year MMS achievement rate was 21% [38], while a Chinese MG cohort reported a median time to MMS achievement of 26 months [39]. Notably, rapid-onset therapeutic approaches, including novel monoclonal antibodies, facilitate earlier target attainment and higher MMS achievement rates [40]. For example, in the ADAPT study, 40% of patients receiving efgartigimod achieved MSE by week four [16], and other FcRn antagonists demonstrated MSE rates of approximately 26% after the first treatment cycle (6 weeks) [30, 32]. However, C5 complement inhibitors (eculizumab and zilucoplan) achieved MMS/MSE target rates of 19.6–25.6%, with a time to target ranging from 12 to 26 weeks [41, 42]. Furthermore, a recent multicenter study in China found that multiple cycles of efgartigimod led to a higher proportion of patients achieving MSE (73.3%) and a shorter median time to MSE (0.7 months) [43]. Despite the absence of head-to-head comparison data, efgartigimod exhibits a significant advantage in achieving early and rapid target attainment (MMS/MSE) compared with other treatments, including traditional immunosuppressants, C5 complement inhibitors, and other FcRn antagonists.

Recent studies have demonstrated that efgartigimod provides rapid therapeutic efficacy in patients with MC or those at risk of impending-MC [17–19]. In our cohort, four patients with gMG classified as MGFA-V exhibited improvement in the Myasthenia Gravis-Patient Information Scale (MG-PIS) following a single treatment cycle. Furthermore, in patients with gMG experiencing acute exacerbations or worsening, the early identification of red flags for impending MC is crucial, as it facilitates the prompt initiation of rescue interventions and may mitigate the risk of crisis development [9]. To our knowledge, this study is the first to highlight the significance of these red flags from the perspective of clinical assessment scores. We also investigated the therapeutic response to efgartigimod in patients with red flags for impending MC. Our observations indicated that all patients, irrespective of the presence of red flags, responded favorably to efgartigimod, with mean reductions in MG-ADL scores from baseline at week 4 of −82.67 ± 20.00% and −78.24 ± 28.16% for those with and without red flags, respectively. However, due to their significantly higher baseline scores, patients with red flags still exhibited higher MG-ADL scores at week 4 compared to those without red flags. This finding suggests that additional treatment cycles may be necessary to achieve the treatment goal of MSE in patients presenting with red flags.

Another key finding of our study was the rapid and comprehensive efficacy of efgartigimod across all populations, regardless of age at onset, disease duration, MGFA classification, presence of thymoma, history of MC, or whether the disease was newly diagnosed or pre-existing. In the time-group model encompassing all populations, a significant time effect was observed, indicating a notable decrease in both the MG-ADL and QMG scores following treatment. Additionally, patients with a history of MC, severe MGFA classification, or red flags for impending MC exhibited a more pronounced therapeutic response to efgartigimod. According to the 2023 European guidelines, it is recommended that patients with gMG exhibiting highly active (including refractory) disease initiate therapy with medications of higher efficacy, such as FcRn antagonists or C5 complement inhibitors [44]. Highly active disease is characterized by elevated MGFA scores and the presence of severe exacerbations or MC. Furthermore, a recent cross-sectional study indicated that early initiation of targeted therapy in patients with acute exacerbations or worsening (as evidenced by a high MG-ADL score) can reduce the severity of MG by facilitating rapid symptom control, thereby preventing disease progression and reducing healthcare resource utilization [45]. Additionally, in our study, several patients with double or triple antibody positivity achieved favorable outcomes following efgartigimod therapy.

One patient exhibited a transient improvement in the MG-ADL scores at W2 and W3 following efgartigimod administration but subsequently experienced relapse, with no sustained change observed in the MG-PIS during follow-up. This finding suggests the presence of persistent treatment resistance in a subset of patients. An additional relapse was observed at W7, suggesting potential limitations in the long-term durability of efgartigimod’s efficacy. With growing clinical experience, such phenomena have been increasingly recognized, prompting ongoing investigations into maintenance dosing strategies. The ADAPT-NXT study demonstrated that continuous dosing regimens achieved clinically meaningful improvements in MG-ADL scores, highlighting the need for further research into individualized regimens to optimize sustained therapeutic benefits [46]. ‌During both the treatment and observation phases of our study, no treatment-related adverse events, such as infections, allergic reactions, or injection site reactions, were reported, indicating a favorable safety profile.

This study has several limitations: 1) Retrospective study inherent selection bias and multicenter data heterogeneity with variable completeness and standardizaton; 2) Median efgartigimod initiation delay (20 days) due to patients presentation lag and clinical decision-making, potentially confounding baseline severity assessment; 3) Single treatment cycle observation limited to acute exacerbation response, precluding evaluation of maintenance therapy efficacy; 4) We did not monitor changes in patient’s AChR antibody titers during follow-up; 5) Two patients experienced poor responses to efgartigimod, but further analysis is required to identify predictors of poor response; Despite providing real-world evidence for efgartigimod in acute exacerbations, these limitations highlight the need for prospective randomized controlled trials with standardized data collection. Future studies may further incorporate patients of different ages and antibody subtypes to enhance the generalizability of the results.

Conclusion

Efgartigimod exhibits rapid and potential clinical efficacy in gMG patients experiencing acute exacerbations or disease progression, supporting its potential as a viable therapy for such patients.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

Jing Lin, Juanjuan Zhang: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Lianchen Xiao, Jinquan Hu, Li Di, Chunsheng Yang, Yan Wu, Yan Jiang: Major role in the acquisition of data; Analysis or interpretation of data; Ting Chang, Bitao Bu: Study concept or design; Analysis or interpretation of data; Zhijun Li: Drafting/revision of the manuscript for content, including medical writing for content; Study concept or design.

Funding

This work was supported by the National Science Foundation of China (82371411), the Beijing Medical Award Foundation (YXJL-2024–0387-0085), and the Beijing Life Oasis Public Service Center (P119-003).

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Declarations

Conflicts of interest

All authors claim that there are no conflicts of interest.

Ethical approval

The study has been approved by the Clinical Investigation Committee at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (Approval Number: TJ-IRB202407056) and conformed to the principles of the Declaration of Helsinki.

Informed consent

Written or oral informed consent for the publication of this study was obtained from the patient and/or their family.