Expanding the Tool Kit in gMG: Optimizing Outcomes Through MOA-Based Strategies

The treatment of generalized myasthenia gravis (gMG) is undergoing a paradigm shift driven by a deeper understanding of the underlying immunopathogenesis of the disease. Once managed primarily with broad-spectrum immunosuppressants and symptom-based approaches, gMG is now recognized as a highly heterogeneous autoimmune condition that warrants individualized, mechanism of action (MOA)–informed care.¹ Advances in immunopathology have illuminated the distinct roles of antibody subtypes, complement activation, and neonatal Fc receptor (FcRn) pathways in disease pathogenesis, leading to the development of targeted biologics such as complement component 5 (C5) inhibitors and FcRn antagonists.¹ At the same time, emerging real-world and clinical trial data are underscoring the significance of patient-specific factors, such as body mass index (BMI), antibody profile, sex, and surgical history, in predicting disease course and treatment response.^2-6

The FDA has approved the following 6 drugs for gMG in recent years:

• efgartigimod alfa-fcab (Vyvgart; argenx BV), zilucoplan (Zilbrysq; UCB, Inc), eculizumab (Soliris; Alexion Pharmaceuticals), and ravulizumab (Ultomiris; AstraZeneca) for adults who test positive for the anti–acetylcholine receptor (AChR+) antibody^7,8;
• rozanolixizumab-noli (Rystiggo; UCB, Inc) for adults who are AChR+ or positive for the anti–muscle-specific tyrosine kinase (MuSK+) antibody⁹; and
• nipocalimab-aahu (Imaavy; Janssen Biotech, Inc) for patients 12 years and older who are AChR+ or MuSK+.¹⁰

And as the therapeutic landscape continues to expand with potential agents such as inebilizumab-cdon (Uplizna; Viela Bio, Inc), a monoclonal antibody that depletes CD19+ B cells,^11,12 clinicians are gaining an even broader tool kit—but also navigating the challenges of complex treatment algorithms, therapeutic inertia, and payer-driven barriers to patient access.¹

This article examines the transformation of gMG management in light of recent immunopathologic insights and the development of targeted therapies. It aims to give readers a deeper understanding of gMG heterogeneity and highlight evidence supporting individualized MOA-informed treatment strategies.

Navigating the Evolving gMG Treatment Landscape

The approval of multiple targeted therapies in the past few years for gMG has expanded treatment options and added complexity to treatment decisions. Clinicians must now navigate a range of factors—including traditional therapeutic objectives, patient preferences, and their own experiences—when selecting the best treatment for each patient. These targeted agents offer distinct efficacy, safety, and administration profiles. They differ fundamentally from traditional off-label immunosuppressants because they act more precisely by interfering with specific molecular mechanisms that drive disease progression. Complement inhibitors (eg, eculizumab, ravulizumab, and zilucoplan) act by binding to C5, inhibiting activation of the complement cascade, whereas FcRn inhibitors (eg, efgartigimod and rozanolixizumab) interfere with the normal recycling process of autoantibodies mediated by the FcRn, leading to a reduction in the levels of circulating IgG and pathogenic autoantibodies.¹

Despite the availability of these targeted agents, real-world prescribing patterns often continue to favor conventional immunosuppressants, such as azathioprine and mycophenolate mofetil (CellCept; Genentech USA, Inc), particularly in first-line settings. In a recent US-based survey of 81 neuromuscular specialists, FcRn and complement inhibitors were most commonly employed as bridge therapies, with cost and lack of clinical familiarity cited as key barriers to broader adoption. Once these initial hurdles are addressed, the specialists noted that affordability and safety profiles are paramount in determining their choice of novel agents in the first line.^1,13

Some have suggested that the emergence of these therapies calls for a redefinition of treatment goals in gMG, emphasizing early intervention to maintain quality of life (QOL) and minimize long-term disease burden. Lessons learned from other neuroimmune conditions, such as multiple sclerosis and neuromyelitis optica spectrum disorder, support a “flipping the pyramid” approach, ie, prioritizing early use of high-efficacy treatments rather than gradual escalation through lower-efficacy options. “A similar approach could be extrapolated to gMG,” wrote Gutiérrez-Gutiérrez et al, which could help preserve neuromuscular junction (NMJ) integrity and prevent therapeutic cycling between low-efficacy treatments.¹

Understanding Disease Heterogeneity in gMG

MG is a chronic autoimmune disorder marked by fluctuating, often debilitating, muscle weakness and fatigability that involves facial, bulbar, cervical, axial, and limb muscles, with the most common initial presentation being ocular weakness. Progression to generalized weakness (ie, gMG) commonly occurs within 2 years of disease onset.¹ The most common autoimmune disorder of the NMJ,¹⁴ MG has steadily increased in prevalence over the past 50 years and is estimated to affect 150 to 200 people per million.¹⁵

Further, understanding the clinical variability of MG is essential, as subtypes defined by antibody status differ in therapeutic response and risk profiles. Autoantibodies most commonly target proteins at the NMJ, including nicotinic AChRs (nAChRs), MuSK, and LRP4. The agrin–LRP4–MuSK complex plays a critical role in the formation and maintenance of the NMJ by regulating AChR distribution and clustering. Thymoma is present in approximately 10% of patients with MG and is associated with autoantibody production.¹⁶

MG can be classified into distinct subgroups based on clinical presentation and the specific antibodies involved, with each subgroup exhibiting different treatment responses and prognostic implications, as follows¹⁶:

• Early-onset MG: Onset before aged 50 years, typically associated with thymic hyperplasia
• Late-onset MG: Onset after aged 50 years, often accompanied by thymic atrophy
• Thymoma-associated MG
• MG with anti-MuSK antibodies
• Ocular MG (oMG): Limited to symptoms affecting the periocular muscles
• MG with no detectable AChR or MuSK antibodies

These differences underscore the importance of selecting therapies with MOA and safety profiles tailored to patient subtype and disease course.

MG also affects men and women differently, exhibiting notable differences in incidence and disease trajectory. Regarding incidence, MG most commonly impacts women younger than 40 years and men older than 50 years. The immunomodulatory role of estrogen may influence this observed pattern, and the hormone’s role in enhancing autoimmune activity may contribute to the higher incidence of MG in women. Regarding disease trajectory, shifting hormone levels in women with MG may worsen hallmark symptoms such as fatigue and contribute to a higher overall disease burden while also influencing treatment response. Women also report greater psychological burden, including anxiety and depression, and are more likely to experience comorbid autoimmune conditions. The interplay of all these factors contributes to a significantly reduced QOL for women vs men with MG.³

The pathophysiology of MG is driven by autoantibodies—most commonly directed against AChR—that disrupt neuromuscular transmission through receptor blockade, internalization, or complement-mediated destruction; less commonly, autoantibodies target MuSK or LRP4. Each subtype of MG often presents with distinct clinical features and may require unique therapeutic considerations.^1,2

In AChR+ MG, the complement system plays a crucial role in pathophysiology. IgG1 and IgG3 AChR auto­antibodies trigger activation of the classical complement cascade, culminating in the formation of the membrane attack complex (MAC) and, as Jacob et al wrote, the “architectural destruction of the [NMJ].” Therapies that inhibit C5 (eg, eculizumab or zilucoplan) have been shown to prevent MAC formation and significantly ameliorate clinical symptoms.⁵

Real-world data demonstrate that MG severity is influenced by a range of sociodemographic and clinical factors. In a cross-sectional analysis of 421 patients with gMG across the US and Europe, progression to a more severe disease state was associated with such factors as older age, prior misdiagnosis, longer time between symptom onset and both the initial consultation and the gMG diagnosis, and the presence of specific symptoms at diagnosis (eg, eye muscle weakness). Moreover, patients with a history of myasthenic crisis or prior intensive care unit admission were more likely to report severe symptoms, underscoring the importance of early intervention and close monitoring of at-risk subpopulations.⁶

Recent research has also highlighted the impact of BMI on disease presentation and prognosis in patients with MG, showing that a higher baseline BMI was associated with an increased risk of oMG progressing to gMG. In a 2025 observational, multicenter, prospective cohort study of 940 patients categorized by baseline BMI (high or low), the primary outcome was time to generalization of oMG, and secondary outcomes were time to Activities of Daily Living (ADL) response and time to Minimal Symptom Expression (MSE). The investigators found that baseline BMI helped predict the risk of progressing to gMG (HR, 1.06; 95% CI, 1.01-1.11; P = .026), with “each additional 1 kg/m² increasing the risk of generalization by 6%.” Chen et al noted, however, that baseline BMI was not associated with the risk of ADL response or MSE.⁴

Tailoring Treatment Based on Patient-Specific Factors

Targeted therapies represent a significant shift in the treatment paradigm for gMG, allowing for a more personalized approach based on individual patient factors such as disease subtype and antibody status. A closer examination of a few of these factors is warranted.

BMI. As noted previously, Chen et al found that a higher baseline BMI was associated with an increased risk of generalization of oMG.⁴ Given that obesity is a modifiable factor, these data suggest potential value in integrating metabolic interventions and weight management into the broader multidisciplinary care of patients with MG.

Seronegative MG subtype with blocking AChR antibodies. AChR antibodies impair receptor function by binding, blocking, or modulating its activity. Blocking antibodies are usually found alongside binding antibodies and are rarely present in isolation.¹⁵

Liu et al recently found that patients with seronegative oMG or gMG with elevated titers of blocking AChR antibodies are “predisposed to more severe manifestations.”The 2025 study examined the presence and clinical significance of blocking AChR antibodies in 148 patients stratified by MG subtype (oMG: n = 76; gMG: n = 72). The investigators noted that thymic abnormalities (ie, thymomas) were more common in the gMG group but that the difference was not statistically significant. Blocking AChR antibodies were detected in 43.24% of patients overall, with a significantly higher prevalence in the gMG group (58.33%). Importantly, blocking AChR antibodies were strongly correlated with severe clinical manifestations, including myasthenic crises. Liu et al concluded that their findings highlight blocking AChR antibodies as a “potential biomarker for monitoring MG severity” but that further research is needed to validate these results, explore the role of these antibodies in seronegative MG, and “refine diagnostic and therapeutic strategies for MG management.”¹⁷

AChR+ or MuSK+ gMG Subtypes: FcRn Inhibition

Rozanolixizumab. Rozanolixizumab is a humanized FcRn receptor blocker that enhances the degradation of pathogenic IgG by up to 78%, comparable to plasma exchange.¹⁸ It is the first FcRn blocker approved for both AChR+ and MuSK+ gMG. It is administered subcutaneously (SC), with most treatment-emergent adverse events (AEs) being mild to moderate, including headache and gastrointestinal issues.¹⁸ Data from the randomized, double-blind, placebo-controlled phase 3 MycarinG trial (NCT03971422) in patients with AChR+ or MuSK+ gMG showed that higher proportions of participants treated with rozanolixizumab vs placebo achieved a 2-point or higher increase in MG-ADL score and a 3-point or higher increase in quantitative MG (QMG) score, with robust and sustained clinical benefit through day 43 (ie, the end of one 6-week cycle of rozanolixizumab). Notably, rozanolixizumab demonstrated clinical efficacy in patients with MuSK+ gMG, a subgroup with limited treatment options.¹⁹

The long-term benefit of rozanolixizumab was further confirmed in 2 open-label phase 3 extension studies (MG0004 [NCT04124965] and MG0007 [NCT04650854]), with patients maintaining or achieving minimal symptom expression across multiple treatment cycles.^19,20 Despite promising data, real-world experience with rozanolixizumab remains limited, and cost-effectiveness analyses are pending, with the price per 2-mL vial exceeding $6000 (list price is $3101/mL).^18,21 Ongoing clinical trials in pediatric populations (MG0006 [NCT06149559]) and comparative studies with other FcRn agents such as efgartigimod and nipocalimab will further inform rozanolixizumab’s place in therapy.^18,22

In one such comparative study of FcRn agents in patients with MG, Li et al found that “rozanolixizumab, despite its superior efficacy,” was associated with a higher incidence of AEs. The FDA has since approved nipocalimab to treat gMG in adults and pediatric patients 12 years and older who are AChR+ or MuSK+.¹⁰

Nipocalimab. The FDA approval of nipocalimab on April 30, 2025, was based on results from the multicenter, randomized, double-blind, placebo-controlled Vivacity-MG3 trial (NCT04951622), which evaluated the long-term safety and efficacy of nipocalimab in patients with gMG inadequately controlled with standard-of-care (SOC) therapy (MG-ADL score ≥ 6). Following a 24-week double-blind period during which nipocalimab plus SOC therapy significantly improved MG-ADL scores vs placebo plus SOC (least squares mean difference, −1.45; P = .002), 137 autoantibody-positive participants (AChR+, MuSK+, or LRP4+) entered the ongoing open-label extension (OLE).²³

Sustained improvement in MG-ADL was observed during the OLE. The mean (SE) change in MG-ADL from double-blind baseline to OLE week 24 was −5.73 (0.401) (n = 81), and it was −5.97 (0.681) (n = 37) at week 48. Nipocalimab also continued to show a favorable safety profile, with no new safety signals emerging during extended treatment. The investigators concluded that nipocalimab demonstrated “sustained disease control over 72 weeks across double-blind and open-label phases” in a broad population of autoantibody-positive patients with gMG.²³

Efgartigimod. Efgartigimod is approved for the treatment of adults with AChR+ gMG. Both intravenous (IV) and SC formulations have shown clinical efficacy and safety in phase 3 trials.²⁴

In the phase 3 ADAPT study (NCT03669588), IV efgartigimod significantly improved MG symptoms and reduced disease burden while also improving health-related QOL. The IV formulation of efgartigimod also demonstrated consistent, clinically meaningful improvement over the long term (up to 17 treatment cycles) and a favorable safety profile, with the most common AEs being headache and infections.²⁴

The subsequent phase 3 ADVANCE SC+ trial (NCT04812925) evaluated efgartigimod coformulated with recombinant human hyaluronidase PH20, which allows for SC administration. This SC formulation demonstrated noninferiority to the IV formulation in reducing total IgG levels, with efficacy and tolerability consistent with IV efgartigimod over repeated dosing. Injection-site reactions were the most common AE with the SC formulation.²⁴

These trial findings support the use of efgartigimod as a flexible, well-tolerated, and effective treatment option offering both IV and SC routes of administration, sustained symptom relief, and manageable safety outcomes. Further long-term data will help define the agent’s continued role in chronic disease management.²⁴

More recently, a 2025 real-world study conducted by Sgarzi et al at an Italian public hospital adds further insight into FcRn inhibition using efgartigimod in patients with AChR+ gMG. In a 12-patient cohort, MG-ADL and QMG scores significantly improved following 2 or more cycles of efgartigimod, with greater responses observed in patients with higher baseline AChR antibody titers, prior thymectomy, and nonocular symptom predominance. In patients who had undergone thymectomy compared with those who had not, MG-ADL improved by 62% vs 22% (P < .01) and QMG improved by 45% vs 3.5% (P < .01) during the first 2 cycles. Notably, patients with predominantly ocular symptoms had the least improvement, suggesting that these patients “may respond less robustly to efgartigimod, potentially due to distinct underlying mechanisms or reduced involvement of pathogenic antibodies in ocular symptoms,” the investigators wrote. Sgarzi et al concluded that serological and surgical history may help guide therapeutic decision-making in FcRn-targeted therapy and that these study results “underscore the need for larger studies to validate these observations and optimize patient selection.”²⁵

AChR+ gMG Subtype: Complement Inhibition With Steroid-Sparing Potential

Zilucoplan. Patients with AChR+ gMG who completed the 12-week double-blind treatment period in either the phase 2 RA101495-02.201 trial (NCT03315130) or phase 3 RAISE study (NCT04115293) of the C5 inhibitor zilucoplan could opt to enter the phase RAISE-XT study (NCT04225871), where they self-administered SC zilucoplan 0.3 mg/kg daily. After the initial 12 weeks of the RAISE-XT study—during which doses of corticosteroids and nonsteroidal immunosuppressive therapies (NSISTs) were kept stable—adjustments could be made at the investigator’s discretion. Hewamadduma et al found that more than 60% (n = 33/54) of patients on corticosteroids at double-blind baseline reduced or discontinued them by week 120 of the RAISE-XT study (mean dose reduction, 15.5 mg/day). Importantly, this was achieved via sustained improvements in MG-ADL and QMG scores (mean changes, −6.55 and −7.57, respectively, at week 120). Additionally, 29.8% of patients on an NSIST at double-blind baseline reduced or discontinued 1 or more NSIST by week 120 while maintaining stable clinical outcomes.²⁶

In another study of SC zilucoplan, the single-arm, open-label, phase 3b MG0017 trial (NCT05514873), Freimer et al evaluated the safety, efficacy, and tolerability of switching from IV C5 inhibitors to SC zilucoplan. Twenty-six clinically stable patients with AChR+ gMG (16 on eculizumab, 10 on ravulizumab) switched to daily SC zilucoplan 0.3 mg/kg for 12 weeks. Complement inhibition was achieved (> 95%) by week 2 and maintained through week 12. The primary end point was the incidence of treatment-emergent AEs in 19 of 26 (73.1%) patients, and were mostly mild. Change from baseline in the MG-ADL score at week 12, the secondary end point, showed a statistically significant improvement (least squares mean change, −1.15; 95% CI, −2.11 to −0.19; P = .0217), whereas improvements in QMG, an additional measure of efficacy using change in baseline, did not reach statistical significance overall (−1.24; 95% CI, −2.64 to 0.16; P = .0802). However, among patients who switched from ravulizumab, clinically meaningful improvements were observed in both mean MG-ADL (−2.41; 95% CI, −4.52 to −0.30; P = .0307) and QMG (−3.52; 95% CI, −6.14 to −0.90; P = .0149) scores. Exploratory end points were treatment preference at week 12 and treatment satisfaction (assessed using the 9-item Treatment Satisfaction Questionnaire for Medication [TSQM-9] survey). At week 12, 76.9% of participants expressed a preference for SC injection vs IV infusion; also at week 12, mean (SD) changes from baseline in TSQM-9 global satisfaction, effectiveness, and convenience subscores had improved by 19.410 (27.429), 13.889 (21.534), and 21.739 (19.955), respectively. The researchers concluded that switching to SC zilucoplan could be an option for patients with MG who would prefer self-injections, but emphasized the need for longer-term studies to confirm these initial findings.²⁷

Eculizumab and ravulizumab. Data from a 2025 real-world cohort reinforce the steroid-sparing potential of complement inhibitors. In an analysis by Marini et al of 69 patients with AChR+ gMG on corticosteroids treated with azathioprine, mycophenolate mofetil, or a complement inhibitor (eculizumab or ravulizumab), pairwise comparisons using the Mann-Whitney U test revealed significant differences between those treated with complement inhibitors and mycophenolate mofetil at 3, 6, and 9 months and with complement inhibitors and azathioprine at 6 months. At 6 months, the median (IQR) daily steroid dose in the complement inhibitor subgroup had decreased from 20.0 (15.0-27.5) mg at baseline to 15.0 (10.0-16.25) mg; overall, 84.2% (16/19) of patients in this subgroup were able to taper their steroid dose, with 13 of the 19 patients also receiving NSISTs. These reductions were maintained or further improved at 12 months, with 1 patient discontinuing steroids and another patient on eculizumab discontinuing azathioprine.²⁸

Ravulizumab. A 2025 comparative analysis by Scheiner et al of symptom trajectories using data from the phase 3 CHAMPION-MG trial (NCT03920293) of ravulizumab and the ADAPT trial (NCT03669588) of efgartigimod showed that patients with gMG receiving fixed-dose ravulizumab spent more time in stable or improving health states based on MG-ADL, QMG, and MG-QOL 15-item revised (MG-QOL15r) scoring (100%, 91%, and 79% of the year, respectively) vs worsening states (0%, 9%, 21%); patients on efgartigimod also spent more time in stable or improving health states (83%, 75%, 77%, respectively) compared with worsening states (17%, 25%, 23%). Ravulizumab, however, demonstrated less variation in symptom control over time than efgartigimod. These findings, concluded Scheiner et al, “contribute to a better understanding of the burdens experienced by patients living with gMG and their caregivers and would be important to consider as part of clinical decision-making to complement traditional trial end points and assist clinicians and patients when choosing an optimal treatment option.”²⁹

Expanding the Tool Kit for AChR+ or MuSK+ gMG Subtypes: CD19+ B-Cell Depletion

Inebilizumab. Inebilizumab, an anti-CD19 monoclonal antibody that depletes a broad population of B cells, has not been FDA approved for the treatment of gMG but has shown promise in clinical trials. In the randomized, double-blind, placebo-controlled phase 3 MINT trial (NCT04524273), investigators evaluated the efficacy and safety of inebilizumab in adults with AChR+ or MuSK+ gMG. A total of 238 participants were randomly assigned 1:1 to receive IV inebilizumab (300 mg on days 1 and 15 for all and at day 183 for AChR+ individuals) or a matching placebo for 52 weeks in AChR+ individuals or 26 weeks in MuSK+ individuals. Glucocorticoid tapering to 5 mg/day was initiated at week 4.¹²

At 26 weeks, patients treated with inebilizumab had experienced significantly greater improvements in MG-ADL scores compared with placebo, with a least squares mean change of –4.2 vs –2.2, respectively (adjusted difference, –1.9; 95% CI, –2.9 to –1.0; P < .001), and a greater reduction in QMG scores, with a least squares mean change of –4.8 vs –2.3, respectively (adjusted difference, –2.5; 95% CI, –3.8 to –1.2; P < .001).Inebilizumab was also generally well tolerated; the most common AEs were headache, cough, nasopharyngitis, infusion-related reactions, and urinary tract infections. No increased risk of serious AEs was observed.¹²

In an editorial by Wolfe and Shelly, the authors noted that before inebilizumab was investigated, rituximab (Rituxan; Genentech, Inc) was used as a B-cell depletion approach in gMG. Rituximab, an anti-CD20 monoclonal antibody, first showed promise more than 2 decades ago, when findings from retrospective studies suggested it led to marked improvement and reduced relapse rates in gMG, especially in MuSK+ disease. However, a Yale University–sponsored phase 2 trial (NCT02110706) of rituximab in AChR+ gMG failed to meet end points, possibly due to participants with mild disease, permissive prednisone tapering rules, or rituximab’s inability to target autoantibody-producing plasma cells. Later, a small Swedish trial in mostly patients with AChR+ gMG with new-onset disease found rituximab superior to placebo for a composite primary end point, hinting that earlier intervention might be more effective for this therapy.³⁰

Inebilizumab, on the other hand, targets a broader spectrum of B-lineage cells, including plasmablasts and plasma cells. In the MINT trial, inebilizumab significantly improved MG-ADL scores, with effect sizes comparable to eculizumab and efgartigimod trials.¹² Most secondary outcomes also favored inebilizumab, and serious AEs were less frequent than with placebo.¹² The authors noted that the dosing schedule of 2 initial infusions followed by infrequent redosing may offer convenience and potential cost advantages.³⁰ According to Wolfe and Shelly as well as Nowak et al, these findings from the MINT trial support the potential of inebilizumab as a therapeutic option for patients with AChR+ or MuSK+ gMG and the potential role of B-cell depletion in the long-term management of gMG.^12,30

Nonpharmacologic Approaches: The Role of Pulmonary Rehabilitation

In addition to pharmacologic therapies, pulmonary rehabilitation may benefit patients with gMG, particularly those with respiratory muscle involvement. Despite evidence suggesting that physical activity supports respiratory health, data on structured aerobic interventions in MG remain limited. The aim of a randomized controlled trial was to analyze the effects of low-intensity aerobic exercise using a cycle ergometer, education on lifestyle changes, and breathing exercises in patients with MG over an 8-week period. The study enrolled 17 patients with Myasthenia Gravis Foundation of America class I to IIb MG who were randomly assigned to the treatment or control group. Lung function parameters (forced vital capacity [FVC], forced expiratory volume in 1 second [FEV₁], and forced expiratory volume ratio [FEVR]) were measured before and after 8 weeks of exercise and compared to those of the control group. The control group did not receive exercise but did receive education on lifestyle changes and breathing exercises.³¹

The investigators observed significant improvements in FVC in the treatment group and no significant change in the control group, a significant increase in FEV₁ in both groups, and no improvement in FEVR in either group after 8 weeks. However, the treatment group demonstrated significantly greater improvements in FVC and FEV₁ vs the control group, but FEVR values did not differ significantly between groups. These findings suggest that 8 weeks of low-intensity aerobic exercise using a cycle ergometer significantly improved FVC and FEV₁ in patients with MG. Notably, no AEs or disease exacerbations were reported during the study, supporting the safety of incorporating structured aerobic training into multidisciplinary MG care.³¹

Conclusion

The treatment of gMG has evolved substantially, shifting from symptom-based, broad-spectrum immunosuppression toward precision, MOA-driven care informed by advances in immunopathology and a growing recognition of patient-specific disease variability. The expansion of the therapeutic armamentarium—including FcRn antagonists, complement inhibitors, and emerging B-cell–depleting agents—offers unprecedented opportunities to improve outcomes, preserve NMJ integrity, and reduce long-term disease burden.

However, optimizing the use of these therapies will require overcoming barriers such as cost, therapeutic inertia, and variability in payer policies. Incorporating modifiable risk factors such as BMI, addressing sex-based disparities in QOL, and exploring adjunctive nonpharmacologic interventions may further individualize care. As evidence from clinical trials and real-world practice continues to accumulate, early, targeted, and multidisciplinary treatment approaches have the potential to redefine standards of care in gMG, shifting the treatment paradigm toward sustained remission, improved QOL, and reduced reliance on chronic corticosteroid and immunosuppressive use.

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