Myasthenia gravis (MG) is an autoimmune disease characterized by acquired neuromuscular junction transmission disorders mediated by autoantibodies (1). All skeletal muscles of the body can be affected, with clinical symptoms mainly manifesting initially as diplopia and ptosis of the upper eyelid, gradually progressing to weakness of the limbs, trunk, and respiratory muscles. Some patients may start with systemic symptoms, and in severe cases, it can be life-threatening (1, 2). About 80% of MG patients have thymic abnormalities, including thymic hyperplasia and thymoma, among which patients with MG associated with thymoma account for about 10% to 15% of MG patients (3, 4). Thymectomy is the standard treatment for thymoma associated myasthenia gravis, which can improve long-term prognosis by removing the source of autoantibody production and abnormal lymphoid tissue (5, 6). However, perioperative stress, the use of anesthetic drugs, and infection are factors that can easily trigger acute exacerbation of myasthenic symptoms. The incidence of postoperative myasthenic crisis can reach 7%-33%, significantly increasing the need for mechanical ventilation and hospital mortality (7–9). Current perioperative management largely relies on plasma exchange (PE), intravenous immunoglobulin (IVIG), and pulse therapy with glucocorticoids (10), but the above-mentioned regimens have limitations such as delayed onset of action, increased risk of infection, and hemodynamic instability, necessitating the exploration of safer and faster new immune-modulating strategies.

Efgartigimod is the world’s first approved neonatal Fc receptor (FcRn) antagonist, which accelerates the catabolism of pathogenic IgG antibodies (including AChR antibodies) by blocking the FcRn-IgG complex recycling pathway (11). In the global multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial (ADAPT) and its open-label extension study (ADAPT+), efgartigimod demonstrated significant efficacy as a monotherapy. Compared to the placebo group, the efgartigimod group showed sustained and clinically meaningful improvements in MG-ADL, QMG, and MG-QOL15r scores (12, 13). Currently, evidence on the application of efgartigimod in the perioperative management of thymoma-associated myasthenia gravis (TAMG) remains limited to small samples or case reports. Wang’s group used an innovative “2 + 2 regimen” efgartigimod which resulted in rapid, significant, and safe improvement of neuromuscular symptoms during the perioperative period, substantially reducing the risk of postoperative myasthenic crisis (14, 15). However, a prior study reported two cases of acute symptom exacerbation in TAMG patients following efgartigimod treatment previously (16). Therefore, more clinical studies are necessary to further substantiate the use of efgartigimod in the perioperative management of thymoma-associated gMG. Leveraging real-world data, this retrospective case series analyzed four thymectomy-treated gMG patients managed with a flexible efgartigimod regimen and extended follow-up. The study evaluated the protocol’s impact on perioperative symptom control, postoperative complications, medication safety, and longer-term outcomes, providing clinical insights to optimize perioperative management in thymoma-associated gMG.

In patients with gMG, the co-occurrence of thymoma is relatively common and is associated with more severe disease and a relatively poor prognosis (3, 4). Thymectomy is an important treatment option for these patients (1), however, the surgery itself carries certain risks. Particularly in patients with MG, surgery may trigger or exacerbate myasthenic crisis, increasing the risk of perioperative complications (7–9). IVIG and PE serve as conventional perioperative treatment options, with demonstrated efficacy in rapidly alleviating symptoms and reducing the incidence of myasthenic crises. However, the clinical application of IVIG faces accessibility challenges: its production relies on plasma from healthy donors, which has limited availability, and the manufacturing process is complex and costly. Furthermore, IVIG has broad indications, besides MG, it is also commonly used for other neuroimmune disorders such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, as well as hematological diseases, further straining its supply. Plasma exchange requires specialized equipment, trained personnel, and specific replacement fluids, and carries risks such as hypocalcemia, hypotension, and secondary infections, which also limit its applicability. As a novel therapeutic agent, efgartigimod works by competitively binding with high affinity to the neonatal FcRn, blocking the recycling of IgG and achieving “endogenous clearance” of IgG, thereby reducing pathogenic antibody levels and improving myasthenic symptoms. It has been hailed as “plasma exchange in a vial”. In the ADAPT and ADAPT+ studies, efgartigimod has shown tolerability and efficacy in gMG patients (12, 13). Currently, it is widely used in patients with acetylcholine receptor (AChR)-antibody-positive gMG. However, its application in TAMG remains primarily based on small-scale studies and case reports ( Table 2 ).

This case series reports on four patients with thymoma-associated gMG who were treated with efgartigimod perioperatively, all of whom were positive for AChR antibodies. Case 2 was also positive for Titin and RyR antibodies and experienced a myasthenic crisis induced by glucocorticoid pulse therapy before surgery. We administered efgartigimod treatment one or two doses to the four patients before thymoma surgery. The average MG-ADL score decreased from 5.25 ± 1.89 at admission to 2.25 ± 1.26, and the average QMG score decreased from 13.75 ± 2.60 at admission to 6.75 ± 1.71. After significant improvement in muscle weakness symptoms, the patients underwent thoracoscopic mediastinal tumor resection under general anesthesia and received their third to fourth doses of efgartigimod postoperatively. None of the four patients experienced a myasthenic crisis or respiratory failure after surgery. One week postoperatively, the average MG-ADL score was 0.50 ± 0.58, and the average MG-ADL score was 7.00 ± 2.16. Except for case 1, who developed a new pulmonary infection postoperatively and experienced a transient fluctuation in myasthenic symptoms, the other three patients showed significant improvement in myasthenic symptoms without any serious drug-related adverse events. All four patients had their drainage tubes removed within three days after thymectomy, and none experienced a myasthenic crisis, the postoperative length of stay was 8.00 ± 4.00 days. It is worth noting that Case 2, who was transferred to the ICU preoperatively due to a myasthenic crisis, showed rapid improvement in myasthenic symptoms after two doses of efgartigimod treatment. The patient successfully underwent thymectomy and achieved a favorable postoperative recovery. Notably, the observed risks of postoperative myasthenic complications (0% vs. reported rates of 7~33%), ICU admission rates (0% vs. 24.6%), and the postoperative hospital stay (8.00 ± 4.00 days vs. 9.8 ± 5.9 days) in our case series are favorably lower than the previous studies, particularly those undergoing surgery following a recent crisis (7–9, 17). All four patients reported a positive experience throughout the course of treatment. This was consistently reflected in the notes regarding their rapid symptomatic improvement, expressed satisfaction with the speed of recovery, and regained ability to perform daily activities, which significantly contributed to their preoperative confidence and postoperative morale.

A Phase II clinical study confirmed that the perioperative “2 + 2” dosing regimen of efgartigimod (two doses before and two doses after surgery) significantly reduced the incidence of postoperative myasthenic crisis (POMC) to 10% and achieved a postoperative remission rate of 82.5% in patients with TAMG, with a favorable safety profile (15). Previously, their team reported another case on the use of efgartigimod for treating TAMG (14). In our reported 4 cases of patients with thymoma-associated gMG, the application of efgartigimod significantly and rapidly controlled the patients’ symptoms, providing an opportunity for thymoma surgery. A flexible dosing strategy was adopted, in which the number of preoperative doses was tailored according to the individual’s clinical response to efgartigimod, while postoperative dosing was adjusted based on whether myasthenic symptoms worsened or complications such as infection emerged after surgery. This strategy represents a departure from the standard “2 + 2” dosing protocol, providing enhanced flexibility and the capacity for a more tailored treatment regimen. Significantly, Case 2, who was positive for anti-AChR, Titin, and anti-RyR antibodies and poorly responsive to steroid therapy, experienced a myasthenic crisis prior to surgery. The presence of multiple antibodies often suggests more severe disease, a higher risk of myasthenic crisis, and complicates both treatment and prognosis. However, treatment with efgartigimod led to rapid symptomatic improvement, which allowed the surgery to proceed successfully and resulted in a stable condition postoperatively. Di Stefano et al. reported three patients with both AChR-seropositive gMG and anti-GAD-seropositive stiff-person syndrome who were treated with efgartigimod, and all patients showed improvement in symptoms of both disorders after two cycles of treatment (18). Additionally, efgartigimod has also shown benefits in therapy-refractory autoimmune encephalitis with coexistent NMDAR and LGI1 antibodies, as well as in Morvan syndrome with positive VGKC, LGI1, and CASPR2 antibodies (19, 20). By reducing all IgG antibodies, efgartigimod offers a promising strategy for treating complex, multi-antibody-positive autoimmune disorders beyond classic gMG, as highlighted by these findings.

This study is limited by its retrospective nature and the associated incomplete data collection. Most notably, post-treatment AChR antibody titers were not routinely available, as they were not part of standard clinical care. The relationship between anti-AChR antibody titers and disease severity of MG remains controversial (21). Interestingly, Kawama et al. reported two cases where clinical deterioration following efgartigimod was accompanied by an increase in anti-AChR antibody titers beyond pre-treatment levels (16). A similar paradoxical rise in antibodies has been documented after plasma exchange (22), suggesting a complex immunological rebound phenomenon. This paradoxical phenomenon underscores the necessity for further investigations into antibody titers following efgartigimod treatment in patients with thymoma-associated gMG. Moreover, it focused solely on four cases with a relatively short follow-up period. Indeed, this preliminary data on efgartigimod in thymoma associated gMG should be confirmed on large cohorts of patients in randomized and controlled studies.

In conclusion, efgartigimod shows potential in the perioperative treatment of thymoma-associated gMG patients undergoing thymectomy, and the risk of postoperative infection should be noted. Future research should focus on determining the optimal timing, dosage, and combination strategies with other treatment methods to further optimize the treatment plan for such patients.