Commentary: Efgartigimod for generalized myasthenia gravis: a comprehensive review of clinical evidence and future perspectives
Year: 2026
Type: editorial
Abstract: I read with great interest the comprehensive review by Jiang and colleagues 1 , which offers a timely and well-structured synthesis of the clinical evidence supporting efgartigimod in generalized myasthenia gravis (gMG). I wish to open this commentary by directing attention to a less discussed situation: the management of this disease in the acute postoperative setting. I am referring to a patient with poorly controlled myasthenia gravis who develops acute respiratory failure in the postoperative period; myasthenic and/or cholinergic crisis should not be treated as a diagnosis of exclusion, but as a condition warranting immediate priority intervention once clinically suspected.The review by Jiang et al. 1 offers a valuable synthesis of the evidence supporting this principle, from the pivotal ADAPT trial through to real-world experience across diverse patient subgroups, and the authors are to be commended for consolidating a rapidly expanding body of literature, particularly the treatment of thymoma-associated disease and its perioperative management (thymectomy), where efgartigimod has demonstrated a clear capacity to stabilize patients before and after surgery. However, I wish to highlight a gap that I believe merits further discussion: the lack of specific evidence addressing the postoperative setting, particularly following urgent abdominal surgery in these immunosuppressed patients, a situation likely to become increasingly common as more patients with difficult-to-control gMG are maintained on biologic therapy. The reviewed evidence largely addresses elective surgery, without developing the perspective of urgent abdominal surgery and severe sepsis, such as perforated diverticulitis 1 . Several additional mechanisms may compound the risk of crisis in this population, summarized in Figure 1: masking of clinical and septic signs by immunosuppression, infection-driven autoantibody production 7 , nutritional deficits from prolonged fasting-including hypophosphatemia, which directly impairs diaphragmatic contractility and is further favored by refeeding syndrome 9,12 -and sepsis-related oxidative stress affecting the motor endplate 10,11 .The review appropriately highlights that myasthenic crisis is a life-threatening complication requiring rapid antibody reduction, citing successful rescue with efgartigimod, mostly in thymectomy-related settings. Little specific guidance exists on crisis precipitated by intraabdominal sepsis after emergency laparotomy, a scenario with distinct confounding factors: postoperative sedation and pain mask oculobulbar signs; ileus introduces uncertainty regarding pyridostigmine absorption, complicating the distinction between myasthenic and cholinergic crisis; and biologic therapy raises the question of whether plasma exchange (PLEX) remains appropriate as first-line rescue, given its potential to also remove circulating biologic agents.The review, in line with most of the literature it cites, implicitly assumes that oculobulbar findings will accompany or precede respiratory failure and thereby prompt early suspicion of crisis. In my clinical experience, myasthenic crisis in the critically ill postoperative patient can present as isolated hypercapnic respiratory failure, without any oculobulbar signs. In the intubated patient on mechanical ventilation (MV), where formal cooperation-dependent pulmonary function testing is not feasible, bedside diaphragmatic ultrasonography 2,3 may be a rapid, repeatable, and readily available tool to support the diagnosis. Its findings can either support or exclude the suspicion of myasthenic crisis, in either case orienting toward the correct diagnosis and avoiding unnecessary delays in management. This tool deserves more explicit consideration in future guidance on myasthenic crisis recognition in postoperative intensive care units (ICU).But I would like to raise what I consider the central clinical dilemma: the appropriate sequencing of exclusion versus treatment (Figure 1). A recurring pattern is the instinct to sequentially rule out competing explanations for respiratory failure-fluid overload, uncontrolled sepsis, cholinergic excess, mechanical or pulmonary causes-before committing to crisis-specific immunotherapy.Even when a congestive component coexists, pure fluid overload rarely accounts on its own for the need for intubation: one would expect a response to diuretics and noninvasive ventilation (NIV), together with a distinct lung ultrasound pattern 8 , and the two entities are not mutually exclusive, since respiratory muscle weakness can amplify the impact of even mild fluid overload.The correct approach is therefore to address possible myasthenic crisis in parallel, not after a congestive cause is fully excluded.In a patient with poorly controlled gMG on biologic therapy and acute hypercapnic respiratory failure of neuromuscular pattern in the early postoperative period, the pretest probability of crisis is high enough that specific treatment should be initiated in parallel with, rather than subordinate to, the exclusion of alternative diagnoses. The systematic review by Tang and colleagues 4 , describing consistent improvement across twenty patients treated with efgartigimod for myasthenic crisis, the prospective case series by Song and colleagues 5 , reporting successful ventilator weaning within a mean of 10.4 days, and the finding that absence of MG-specific immunosuppressive treatment at ICU admission is independently associated with prolonged weaning 6 , collectively support initiating specific treatment without delay, rather than awaiting resolution of the septic process or an extensive differential diagnosis.The question of PLEX versus neonatal Fc receptor (FcRn) antagonism in patients already receiving biologic therapy also warrants further elaboration. The review touches on this issue only in the context of a single perioperative case involving a retroperitoneal mass, and does not extend the discussion to patients on rituximab or other B-cell-depleting agents who may develop crisis outside the thymic surgical context. Given that PLEX nonspecifically removes circulating immunoglobulins and biologic agents alike, efgartigimod may represent a more mechanistically coherent first-line rescue option in this subgroup, rather than a therapy reserved for cases refractory to PLEX, as is commonly practiced. I propose that future reviews and clinical guidance address, more explicitly, the recognition and management of myasthenic crisis arising in the context of urgent abdominal surgery, including the role of diaphragmatic ultrasonography in atypical presentations lacking oculobulbar signs, and the rationale for prioritizing FcRn antagonism over PLEX in patients previously treated with biologic therapy.
Source: Frontiers in Neurology
Author: Ana Belén Fernández
Institution: Hospital Universitario Nuestra Señora de Candelaria
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7222589860