Search

The article discusses the emerging role of FcRn inhibitors in the treatment of myasthenia gravis, highlighting their ability to rapidly reduce Immunoglobulin G (IgG) levels and improve clinical outcomes. Topics include the development and clinical approval of FcRn inhibitors, their mechanism of action in accelerating IgG catabolism, and the benefits of these inhibitors over traditional immunomodulatory treatments, such as faster onset and better safety profiles.

Background: Myasthenic crisis (MC) refers to rapid deterioration of myasthenia gravis (MG), affecting lung and bulbar muscles and causing breathing difficulties. Currently, efgartigimod has shown good therapeutic effects in patients with generalized myasthenia gravis (GMG). This retrospective real-world study explored the effectiveness of efgartigimod in patients with MC. Method: Reviewing the clinical data of five patients (including four patients with refractory MC) with MC who received efgartigimod at the First Affiliated Hospital of Sun Yat-sen University, all of these patients were admitted from September 2023 to December 2023. Results: Each patient received 20 mg/kg of efgartigimod on the first and fifth day. After discharge, all patients showed a clinically meaningful decrease in Myasthenia Gravis Activities of Daily Living (MG-ADL) scale (a decrease of ≥ 2 points) and an improvement in their lung function. Additionally, all patients had a decrease in IgG levels (58.59 ± 18.48% after one cycle of efgartigimod). We also explored the ICU stay and mechanical ventilation (MV) duration for these five patients, and found no significant improvement compared to a large sample data. In terms of safety, four patients experienced adverse events (AEs), all of which were mild. At the last follow-up, four patients achieved the minimal symptom expression (MSE) status (an MG-ADL score of 0 or 1) after 6.25 ± 3.30 weeks. Only one patient experienced a worsening of symptoms in the second week after discharge, but she also achieved the MSE status after receiving a second cycle of efgartigimod treatment. Conclusions: Given the conclusion that intravenous efgartigimod is a non-invasive fast-acting treatment with fewer AEs, this may provide NICU workers with another option for managing patients with MC. [ABSTRACT FROM AUTHOR]

Guillain–Barré syndrome (GBS) is a serious neurological condition with limited treatment options. A recent report demonstrated successful treatment with efgartigimod alone in two patients with GBS, although it did not significantly shorten the disease duration. This case series investigates the effects of sequential efgartigimod administration in patients with different GBS phenotypes and varying levels of disease severity. All three patients tested positive for immunoglobulin G (IgG) antibodies against serum gangliosides. In Case 1, the patient was treated with 0.4 g/kg of intravenous immunoglobulin (IVIg) for 5 days, showing minimal recovery. After receiving 3 weekly doses of efgartigimod (10 mg/kg), the patient achieved independent ambulation 19 days post-onset, with a reduction in serum ganglioside antibody titers and total IgG levels. Case 2 involved a middle-aged man with Miller Fisher syndrome (MFS)-GBS overlap, who experienced worsened autonomic dysfunction following IVIg treatment. After three doses of efgartigimod, the patient showed symptom improvement within 1 month, alongside a reduction in IgG antibody levels. In Case 3, a 27-year-old male with MFS-GBS overlap, initially unresponsive to IVIg, showed significant improvement in ophthalmoplegia following two doses of efgartigimod, with his serum ganglioside antibodies eventually becoming undetectable. Our findings suggest that sequential efgartigimod treatment may effectively reduce serum anti-ganglioside antibody titers and potentially shorten the disease course in severe GBS and MFS-GBS overlap syndrome. Additionally, it may offer clinical benefits for patients with GBS who have a poor or no response to IVIg, particularly in treating ophthalmoplegia. [ABSTRACT FROM AUTHOR]

Background: Efgartigimod is an approved biologic for generalized myasthenia gravis (gMG), which is an autoimmune disease and can potentially be life-threatening. However, the therapeutic response to efgartigimod among the acetylcholine receptor gMG (AChR-gMG) subtypes remains inconclusive. Objective: To explore the patterns and predictors for the therapeutic response to efgartigimod among AChR-gMG subtypes. Design: This prospective, observational study included AChR-gMG patients treated with efgartigimod at 15 centers in China with a follow-up for at least 20 weeks. Methods: The primary outcome was the proportion of minimal symptom expression (MSE) responders, denoted by a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 0 or 1 within 4 weeks and maintained for ⩾4 weeks. AChR antibody-positive MG (AChR-MG) subtypes were classified into early onset myasthenia gravis (EOMG), late-onset myasthenia gravis (LOMG), and thymoma-associated myasthenia gravis (TAMG). The predictive factors for MSE responders were identified by univariate and multivariate logistic regression analysis. Results: One hundred sixteen patients were included with a median follow-up duration of 238 days (172.5–306.3). There were 50 (43.1%) patients with EOMG, 28 (24.1%) with LOMG and 38 (32.8%) with TAMG. After efgartigimod initiation, 35 (30.2%) patients were MSE responders, and the proportion of MSE responders was highest in the LOMG group (42.9%). The MG-ADL score reduction in the LOMG group was more significant than in the EOMG group by weeks 16 and 20 (both p = 0.022). Response patterns to efgartigimod among the AChR-MG subtypes differed as measured by the proportion of improved patients and MSE. LOMG presented sustained symptom control, while EOMG and TAMG showed more fluctuations. Eight TAMG patients (21.1%) switched to another biologic (p = 0.005). Baseline MG-ADL was an independent predictor for therapeutic response to efgartigimod (p < 0.001). Conclusion: Our findings revealed patterns of treatment responses among AChR-gMG subtypes, with LOMG patients potentially presenting a more sustained response. These findings likely provide preliminary data for precision therapy in MG in the era of biologics. Trial registration: NCT04535843. Plain language summary: Patterns and predictors of therapeutic response to efgartigimod in AChR generalized myasthenia gravis Myasthenia Gravis (MG) is an autoimmune disorder that can lead to potentially life-threatening complications. Efgartigimod is an approved biologic for generalized myasthenia gravis (gMG). However, the patterns and predictors of therapeutic response to efgartigimod among the acetylcholine receptor-generalized MG (AChR-gMG) subtypes remain inconclusive. Our findings revealed patterns of treatment responses among AChR-gMG subtypes, with LOMG patients potentially presenting a more sustained response. [ABSTRACT FROM AUTHOR]

Introduction: This case describes successful response to efgartigimod in the treatment of myasthenic crisis secondary to paraneoplastic disease, and in the perioperative setting. Methods: An elderly female presented with speech difficulties, cessation of eating and 10kg weight loss over 4 months. Results: Examination revealed ptosis, dysarthria, nasal speech, and weakness in limbs and neck flexors. Single fiber electromyography demonstrated abnormal jitter response in the orbicularis oculi muscle. Nicotinic acetylcholine receptor antibodies were detected in serum. The patient was diagnosed with very-late-onset myasthenia gravis (MG) in a myasthenic crisis and later required intubation and admission to intensive care but was unresponsive to plasma exchange. Paraneoplastic disease was suspected and computed tomography revealed a bladder mass. Efgartigimod 10 mg/kg was administered intravenously to stabilize her condition before surgery. The patient's Myasthenia Gravis Activities of Daily Living (MG-ADL) score decreased from 19 to 14 after the first dose and she subsequently underwent surgical removal of the bladder tumor without complication. Her condition continued to improve post-operatively with completion of the first treatment cycle. Four cycles of efgartigimod over 10 months resulted in an MG-ADL score of 3. Discussion: Efgartigimod may be a novel treatment for perioperative management of MG, myasthenic crisis, and paraneoplastic MG. Further study is warranted. [ABSTRACT FROM AUTHOR]

Efgartigimod is a human IgG1 antibody Fc-fragment that lowers IgG levels through blockade of the neonatal Fc receptor (FcRn) and is being evaluated for the treatment of patients with severe autoimmune diseases mediated by pathogenic IgG autoantibodies. Engineered for increased FcRn affinity at both acidic and physiological pH, efgartigimod can outcompete endogenous IgG binding, preventing FcRn-mediated recycling of IgGs and resulting in increased lysosomal degradation. A population pharmacokinetic-pharmacodynamic (PKPD) model including FcRn binding was developed based on data from two healthy volunteer studies after single and repeated administration of efgartigimod. This model was able to simultaneously describe the serum efgartigimod and total IgG profiles across dose groups, using drug-induced FcRn receptor occupancy as driver of total IgG suppression. The model was expanded to describe the PKPD of efgartigimod in cynomolgus monkeys, rabbits, rats and mice. Most species differences were explainable by including the species-specific in vitro affinity for FcRn binding at pH 7.4 and by allometric scaling of the physiological parameters. In vitro-in vivo scaling proved crucial for translation success: the drug effect was over/underpredicted in rabbits/mice when ignoring the lower/higher binding affinity of efgartigimod for these species versus human, respectively. Given the successful model prediction of the PK and total IgG dynamics across species, it was concluded that the PKPD of efgartigimod can be characterized by target binding. From the model, it is suggested that the initial fast decrease of measurable unbound efgartigimod following dosing is the result of combined clearance of free drug and high affinity target binding, while the relatively slow terminal PK phase reflects release of bound drug from the receptor. High affinity target binding protects the drug from elimination and results in a sustained PD effect characterized by an increase in the IgG degradation rate constant with increasing target receptor occupancy. [ABSTRACT FROM AUTHOR]

Introduction: Efgartigimod has been approved for the treatment of acetylcholine receptor antibodies-positive generalized myasthenia gravis (AChR-Ab+gMG), but its efficacy in patients with ocular myasthenia gravis (OMG) is not known. Case presentation: We describe 2 cases of patients with AChR-Ab+ OMG who showed unfavorable responses to corticosteroids and tacrolimus. Within 2 weeks of initiating efgartigimod, both patients showed rapid improvement and minimal symptom expression was achieved in weeks 3 to 4, which was maintained up to week 12. Conclusion: The 2 cases described herein provide preliminary evidence for the effectiveness of efgartigimod for the treatment of OMG for patients who do not respond or are intolerant to conventional medications. Large-scale studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: China has a large number of myasthenia gravis (MG) patients, creating an urgent need for rapid and tolerable treatment options. As the first-approved Fc receptor antagonist, efgartigimod has bright prospects for treating MG. However, real-world evidence on its application within the Chinese MG population are limited. Objective: This study aims to evaluate the rapid efficacy and safety of efgartigimod in Chinese MG population. Design: This single-center prospective study enrolled Chinese MG patients aged 18 and older who were treated with efgartigimod, classified as Myasthenia Gravis Foundation of America I–IV, with a baseline Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 4. Methods: Patients received efgartigimod at a dose of 10 mg/kg infused once weekly for 4 weeks. During the treatment, the corticosteroids dosage could be adjusted as appropriate or the non-steroidal immunosuppressive therapies (NSISTs) added. Prior to each infusion, patients' MG-ADL scores, IgG levels, and routine laboratory tests were evaluated, while also recording the prednisone tapering and any adverse events occurring during the treatment. Results: Twenty five Chinese MG patients were enrolled between November 2023 and June 2024, including 3 with ocular MG (OMG) and 22 with generalized MG (GMG). During the 8-week follow-up, in GMG patients, whether positive for acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) antibodies, the overall efficacy was significant. Within one treatment cycle, 18 (82%) patients showed a reduction of at least 2 points in MG-ADL scores and sustained for at least 4 weeks, and 6 (27%) attained minimal symptom expression (MSE) and sustained for at least 4 weeks. Only 1 patient experienced exacerbation. Among OMG patients, 1 achieved MSE within the treatment cycle, while 2 showed minor improvements. Patients who added tacrolimus concurrently with efgartigimod did not achieve better improvement in MG-ADL scores compared to others. The average reduction in prednisone dosage was 27.4%. Only one patient experienced transient vomiting and diarrhea, with no serious adverse reactions reported. Conclusion: This study confirmed the short-term efficacy and safety of efgartigimod in Chinese MG patients. However, in clinical practice, careful consideration is needed regarding its application in OMG and whether to add NSISTs regimen during the treatment. Efgartigimod could potentially serve as an alternative to long-term corticosteroids therapy. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction/Aims Methods Results Discussion Neonatal Fc receptor (FcRn) inhibitors represent a promising treatment option for patients with generalized myasthenia gravis (gMG); however, data on clinical use are limited. The aim of this report is to describe one center's approach to efgartigimod dosing in patients with gMG.Medical records of patients with acetylcholine receptor antibody‐positive (AChR‐Ab+) gMG whose symptoms were not adequately controlled by oral medications and/or intravenous immunoglobulin who received efgartigimod between January 2022 and January 2024 were retrospectively evaluated. The first three efgartigimod cycles (10 mg/kg IV) were initiated at fixed intervals (4 once‐weekly infusions, with 4 weeks between cycles). After the third cycle, initiation of subsequent treatment cycles and time between cycles were determined individually by clinical evaluation. Effectiveness was measured by the Myasthenia Gravis Activities of Daily Living (MG‐ADL) scale. Adverse events and changes to concomitant therapies were monitored.Nineteen patients were included and received a mean of 4.4 efgartigimod cycles, including two patients who discontinued after two cycles. All patients exhibited a clinically meaningful improvement in MG‐ADL total score from baseline to the end of the last cycle, with a mean improvement of 5.8 points. Seven (37%) patients achieved minimal symptom expression (MSE, MG‐ADL 0–1). From baseline to the end of the last cycle, daily prednisone dose was decreased or it was discontinued, while two patients initiated prednisone. Efgartigimod was generally well tolerated.This approach to efgartigimod dosing resulted in substantial MG‐ADL score improvement in these patients with AChR‐Ab+ gMG as well as reduced daily dose and/or discontinuation of concomitant corticosteroids. [ABSTRACT FROM AUTHOR]

Abstract Background Anti-NMDA receptor encephalitis is an autoimmune, antibody-mediated inflammatory disease of the brain characterized by the presence of IgG antibodies targeting the excitatory N-methyl-D-aspartate receptor (NMDAR). Previous research has established that the neonatal Fc receptor (FcRn) regulates the transport and circulation of immunoglobulins (IgG). Efgartigimod, an FcRn antagonist, has been shown to enhance patient outcomes by promoting IgG clearance, and it has exhibited substantial clinical efficacy and tolerability in the treatment of myasthenia gravis. Efgartigimod has demonstrated potential efficacy in the treatment of various IgG-mediated autoimmune diseases. Nonetheless, to date, no studies have investigated the use of efgartigimod in the treatment of anti-NMDAR encephalitis. Case presentation We present a case of a 42-year-old male patient diagnosed with anti-NMDAR encephalitis, initially treated with intravenous methylprednisolone(IVMP) and human immunoglobulin (IVIG) without clinical improvement. Subsequent administration of efgartigimod resulted in rapid clinical improvement; however, the patient experienced a relapse upon discontinuation of efgartigimod. Reintroduction of efgartigimod led to rapid and significant clinical improvement, accompanied by a marked decrease in anti-NMDAR antibodies and serum IgG levels in both serum and cerebrospinal fluid. The patient remained relapse-free during a 2-month follow-up period. Conclusion This case demonstrates that efgartigimod is a potentially rapid and effective therapy for the treatment of the acute phase of anti-NMDAR encephalitis.

Abstract Background Neuromyelitis Optica Spectrum Disorders (NMOSD) comprise a group of autoimmune-mediated, inflammatory, demyelinating central nervous system diseases caused by aquaporin-4 (AQP4) IgG autoantibodies. Efgartigimod is a human IgG Fc fragment that reduces antibody titers by targeting the neonatal Fc receptor (FcRn). This study documents the efficacy of efgartigimod combined with intravenous methylprednisolone (IVMP) in the acute phase of NMOSD. Methods In this retrospective study, the medical records of NMOSD patients with acute attack who received efgartigimod plus IVMP or IVMP were reviewed. Treatment efficacy was assessed by the Expanded Disability Scale Score (EDSS) before and one month after treatment. Any side effects that occurred during the treatment period were recorded. Results This study was performed on 11 patients (efgartigimod plus IVMP group [n = 4] and IVMP group [n = 7]). Efgartigimod plus IVMP was effective and had a satisfactory safety profile. EDSS was reduced by 0.5 ± 0.32 compared with the IVMP group (0.27 ± 0.02). Immunoglobulin was decreased in three patients, and the immunoglobulin G (IgG) levels gradually increased approximately 8 weeks after the last administration. Hyperlipidemia and elevated white blood cell count were common side effects. No infections or deaths occurred. Conclusions Efgartigimod plus IVMP treatment is safe and well-tolerated in patients with acute-phase NMOSD.

Abstract Impending myasthenic crisis (IMC) is an emergent situation requiring aggressive management to prevent patients from developing myasthenic crisis (MC) in patients with myasthenia gravis (MG). Efgartigimod has been proved to be well tolerated and efficacious in MG patients. The present study aimed to compare the efficacy of efgartigimod and intravenous immunoglobulin (IVIg) in rescuing IMC. IMC patients treated with efgartigimod or IVIg were retrospectively enrolled. The primary outcome was determined as the mean change in MG activities of daily living (MG-ADL) score from baseline to week 1 and 4 after treatment, respectively. Safety was assessed based on medical records during the hospitalization to monitor the adverse events. A total of 9 patients treated with efgartigimod and 10 patients treated with IVIg were enrolled. There were no significant differences in the clinical characteristics at baseline between the two groups (P > 0.05). Compared with the IVIg group, the efgartigimod group had a greater reduction in the MG-ADL score at week 1 (P = 0.035) and week 4 (P = 0.005). One patient in the efgartigimod group had an upper respiratory infection. These findings suggest that efgartigimod is a treatment option for IMC in addition to IVIg and plasma exchange.

In acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (gMG), neonatal Fc-receptor (FcRn) inhibition has broadened the therapeutic spectrum. Myasthenic crisis (MC), heralded by an impending myasthenic crisis (iMC), is a critical condition requiring treatments with rapid onset and sustained efficacy. Currently treatments used for iMC, including intravenous immunoglobulins and plasma exchange/immunoadsorption, have limitations, such as delayed onset of action and potential side effects. So far, there is limited data on the use of FcRn inhibitors in the management of impending or manifest MC (mMC). Here, we present a case of AChR antibody-positive gMG with iMC, where subcutaneous administration of the FcRn inhibitor efgartigimod resulted in rapid clinical remission. Within 24 h of administration, the patient exhibited significant improvement in respiratory and bulbar muscle function, preventing progression to manifest MC and the need for mechanical ventilation. This rapid response was accompanied by a marked reduction in AChR antibody level by 89.8% within 4 weeks. This case supports the potential of efgartigimod as a fast-acting and effective treatment option for managing iMC, offering an alternative to existing therapies. [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis Optica Spectrum Disorders (NMOSD) comprise a group of autoimmune-mediated, inflammatory, demyelinating central nervous system diseases caused by aquaporin-4 (AQP4) IgG autoantibodies. Efgartigimod is a human IgG Fc fragment that reduces antibody titers by targeting the neonatal Fc receptor (FcRn). This study documents the efficacy of efgartigimod combined with intravenous methylprednisolone (IVMP) in the acute phase of NMOSD. Methods: In this retrospective study, the medical records of NMOSD patients with acute attack who received efgartigimod plus IVMP or IVMP were reviewed. Treatment efficacy was assessed by the Expanded Disability Scale Score (EDSS) before and one month after treatment. Any side effects that occurred during the treatment period were recorded. Results: This study was performed on 11 patients (efgartigimod plus IVMP group [n = 4] and IVMP group [n = 7]). Efgartigimod plus IVMP was effective and had a satisfactory safety profile. EDSS was reduced by 0.5 ± 0.32 compared with the IVMP group (0.27 ± 0.02). Immunoglobulin was decreased in three patients, and the immunoglobulin G (IgG) levels gradually increased approximately 8 weeks after the last administration. Hyperlipidemia and elevated white blood cell count were common side effects. No infections or deaths occurred. Conclusions: Efgartigimod plus IVMP treatment is safe and well-tolerated in patients with acute-phase NMOSD. [ABSTRACT FROM AUTHOR]

Background: The prevalence of patients positive for muscle-specific kinase antibody (hereafter, MuSK-Ab) accounts for 5–8% of all myasthenia gravis (MG) cases. Currently, efgartigimod has shown good therapeutic effects in MUSK-Ab-positive MG patients in a phase III clinical trial. However, phase III clinical trials tend to exclude MG patients in exacerbation, and there are only few real-world studies on the efficacy of efgartigimod in MuSK-Ab-positive myasthenic crisis (MC) patients. This retrospective, real-world study aimed to explore the efficacy of efgartigimod in MuSK-Ab-positive MG with exacerbation. Methods: We reviewed the clinical data of four MuSK-Ab-positive patients with exacerbation of MG who received efgartigimod at the First Affiliated Hospital of Sun Yat-sen University, including two patients with MC. All patients were admitted between September 2023 and May 2024. Most patients are simultaneously undergoing rituximab treatment. Results: Each patient completed one cycle of efgartigimod. After the first administration, four patients showed a clinically meaningful decrease in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score (a reduction of more than 4 points compared to baseline), and all patients showed a decrease in IgG levels after one cycle of efgartigimod. Regarding safety, none of the patients experienced any obvious adverse effects. At the final follow-up, all patients achieved the minimal symptom expression status (an MG-ADL score of 0 or 1) following the first administration of efgartigimod for 8.75 ± 5.56 weeks. This article presents a case involving a patient who exhibited prompt alleviation of symptoms following the administration of a high dose of efgartigimod (20 mg/kg, given on days 1 and 5), without the use of any other fast-acting treatment. Conclusion: This retrospective real-world study demonstrates the effectiveness and safety of efgartigimod in these four MuSK-Ab-positive, female Asian patients with exacerbation of MG, as well as in patients experiencing MC. It is important to note that efgartigimod should not be viewed as a substitute for foundational immunotherapy; rather, it is intended as a rescue treatment during exacerbations and as an adjunctive therapy in the context of long-term immunotherapy. This non-invasive approach has the potential to become another treatment option for MuSK-Ab-positive MG patients. [ABSTRACT FROM AUTHOR]

Introduction: This study used network meta-analysis (NMA) to inform and compare the number needed to treat (NNT), number needed to harm (NNH), and cost per improved outcome (CPIO) associated with more recently approved treatments for anti-acetylcholine receptor antibody-positive (anti-AChR Ab+) generalized myasthenia gravis (gMG). Methods: Clinical trials of neonatal Fc receptor (FcRn) inhibitors, efgartigimod intravenous (IV) and rozanolixizumab, and complement inhibitors, ravulizumab and zilucoplan, versus placebo (with background conventional treatment) were included in the primary NMA to compare efficacy and safety outcomes. The outputs from the NMAs were used to estimate NNT and NNH of each treatment versus placebo. CPIO (2024 USD) was estimated for a ≥ 3- or ≥ 5-point reduction from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores. Sensitivity analyses were performed adding efgartigimod PH20 subcutaneous (SC) and eculizumab to the NMA. Results: Efgartigimod IV had the lowest NNT versus placebo for achieving a ≥ 3- and ≥ 5-point reduction in QMG, as well as a ≥ 5-point reduction in MG-ADL, whereas rozanolixizumab had the lowest NNT for a ≥ 3-point reduction in MG-ADL. The NNH versus placebo was similar across comparator treatments. Efgartigimod IV had the lowest CPIO among all treatments for all assessed efficacy outcomes. Sensitivity analyses yielded results consistent with primary analysis and indicated that efgartigimod PH20 SC had comparable NNT and CPIO values to efgartigimod IV, whereas eculizumab had comparable NNT and higher CPIO values compared to other complement inhibitors. Conclusions: FcRn inhibitors and complement inhibitors assessed in this study all demonstrated clinical benefit in terms of NNT as well as an acceptable safety profile in terms of NNH. Within the limitations of this meta-analysis, efgartigimod was associated with a favorable benefit–risk profile as well as a better economic value compared to ravulizumab, rozanolixizumab, and zilucoplan as treatments for anti-AChR Ab+ gMG. [ABSTRACT FROM AUTHOR]

Immune-mediated necrotizing myopathy (IMNM) with anti-HMGCR antibody positivity is characterized by proximal extremity weakness, increased creatine kinase, and extensive muscle edema. There is an urgent need to find more appropriate treatment options for anti-HMGCR IMNM patients who do not respond well to conventional therapy in the acute phase. With the advent of targeted biologics, new treatment options are available. We report on a 66-year-old anti-HMGCR IMNM patient who initially presented with a 1-month history of progressive proximal extremity weakness and dysphagia with markedly elevated creatine kinase. The patient did not respond to conventional high-dose glucocorticoid and intravenous immunoglobulin therapy, and his symptoms rapidly deteriorated over the 2 weeks after this treatment, with worsening limb weakness that prevented walking, marked proximal muscle atrophy, and weight loss. After one cycle (four infusions) of efgartigimod, the patient's symptoms improved markedly and he has since (for several months) remained in a good clinical state. [ABSTRACT FROM AUTHOR]

Impending myasthenic crisis (IMC) is an emergent situation requiring aggressive management to prevent patients from developing myasthenic crisis (MC) in patients with myasthenia gravis (MG). Efgartigimod has been proved to be well tolerated and efficacious in MG patients. The present study aimed to compare the efficacy of efgartigimod and intravenous immunoglobulin (IVIg) in rescuing IMC. IMC patients treated with efgartigimod or IVIg were retrospectively enrolled. The primary outcome was determined as the mean change in MG activities of daily living (MG-ADL) score from baseline to week 1 and 4 after treatment, respectively. Safety was assessed based on medical records during the hospitalization to monitor the adverse events. A total of 9 patients treated with efgartigimod and 10 patients treated with IVIg were enrolled. There were no significant differences in the clinical characteristics at baseline between the two groups (P > 0.05). Compared with the IVIg group, the efgartigimod group had a greater reduction in the MG-ADL score at week 1 (P = 0.035) and week 4 (P = 0.005). One patient in the efgartigimod group had an upper respiratory infection. These findings suggest that efgartigimod is a treatment option for IMC in addition to IVIg and plasma exchange. [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis Optica Spectrum Disorder (NMOSD) is an autoimmune demyelinating disease characterized by recurrent myelitis and optic neuritis. It is associated with high rates of relapse and disability. The main treatment strategies for acute attacks include intravenous methylprednisolone pulse (IVMP) treatment and rescue treatment with plasma exchange (PLEX). Recently, the blockade of neonatal Fc receptor (FcRn)-IgG interaction has gained momentum as a therapeutic strategy. Efgartigimod, the first approved FcRn inhibitor for treating generalized myasthenia gravis, has shown impressive safety, efficacy, and tolerability, and is being regarded as "PLEX in a bottle". Case description: We report a 65-year-old female patient who was diagnosed with anti-AQP4 antibody positive NMOSD. Add-on treatment with efgartigimod to IVMP and intravenous immunoglobulin (IVIG) at the second acute relapse showed favorable results. Conclusion: This case suggests that efgartigimod is a potentially effective add-on therapy in acute attacks of AQP4-IgG-positive NMOSD. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore the efficacy and safety of efgartigimod in patients with refractory immune-mediated necrotizing myopathy (IMNM). Methods: This open-label pilot observational study included seven patients with refractory IMNM, all of whom received intravenous efgartigimod treatment. The clinical response was assessed after 4 weeks of efgartigimod treatment according to the 2016 American College of Rheumatology–European League Against Rheumatism response criteria for adult idiopathic inflammatory myopathy. Serum levels of immunoglobulin as well as anti–signal recognition particle (SRP) and anti–3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies were measured using enzyme-linked immunosorbent assays and commercial line immunoblot assays. Safety assessments included evaluations of adverse events and severe adverse events. Results: The seven patients with refractory IMNM included five cases with anti-HMGCR antibodies and two cases within anti-SRP antibodies. Four of the seven patients achieved clinical responses. The total improvement score for the responders at 4 weeks were 32.5, 40.0, 47.5, and 70.0, and those at 8 weeks were 27.5, 47.5, 57.5, and 70.0. In comparison to the responsive patients, the non-responsive patients had longer durations [8 (-) versus 2 (1–5) years, P = 0.03], and more chronic myopathic features by muscle biopsy (67% versus 0%, P = 0.046). Serum immunoglobulin G levels (11.2 ± 2.5 versus 5.7 ± 2.5, P = 0.007) and anti-HMGCR/SRP antibody levels (97.2 ± 6.9 versus 41.8 ± 16.8, P = 0.002) were decreased after treatment compared with baseline levels. Adverse events were reported in one of the seven patients, who showed mild headache. Conclusions: Despite its small size, our study demonstrated that promoting the degradation of endogenous immunoglobulin G may be effective for patients with IMNM. Efgartigimod may be a promising option for cases of refractory IMNM to shorten duration and minimize chronic myopathic features. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune encephalitis (AE) comprises a group of inflammatory brain disorders mediated by autoimmune responses. Anti-N-methyl-Daspartate receptor (NMDAR) encephalitis, anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, and anti-g-aminobutyric acid-B receptor (GABABR) encephalitis are the most prevalent forms, characterized by the presence of antibodies against neuronal cell-surface antigens. Efgartigimod, an antagonist of the neonatal Fc receptor, has proven efficacy in myasthenia gravis treatment. This clinical case report describes the clinical progression and functional outcomes of AE in three patients who received efgartigimod treatment. Case presentations: Case 1 was a 60-year-old man exhibiting memory impairment and psychiatric disturbances over 11 days. Case 2 was a 38-yearold man with a 1-month history of rapid cognitive decline and seizures. Case 3 was a 68-year-old woman with mental behavioral changes and seizures for 4 months. Anti-GABABR, anti-LGI1, and anti-NMDAR antibodies were confirmed in the respective patients' cerebrospinal fluid or serum. All three patients experienced marked and swift symptomatic relief after four cycles of efgartigimod treatment, with no complication. Conclusion: Current first-line and second-line treatments for AE have limitations, and efgartigimod has demonstrated potential in the rapid and efficacious treatment of AE, emerging as a promising option for the management of this disease. [ABSTRACT FROM AUTHOR]

IntroductionThis case describes successful response to efgartigimod in the treatment of myasthenic crisis secondary to paraneoplastic disease, and in the perioperative setting.MethodsAn elderly female presented with speech difficulties, cessation of eating and 10kg weight loss over 4 months.ResultsExamination revealed ptosis, dysarthria, nasal speech, and weakness in limbs and neck flexors. Single fiber electromyography demonstrated abnormal jitter response in the orbicularis oculi muscle. Nicotinic acetylcholine receptor antibodies were detected in serum. The patient was diagnosed with very-late-onset myasthenia gravis (MG) in a myasthenic crisis and later required intubation and admission to intensive care but was unresponsive to plasma exchange. Paraneoplastic disease was suspected and computed tomography revealed a bladder mass. Efgartigimod 10 mg/kg was administered intravenously to stabilize her condition before surgery. The patient’s Myasthenia Gravis Activities of Daily Living (MG-ADL) score decreased from 19 to 14 after the first dose and she subsequently underwent surgical removal of the bladder tumor without complication. Her condition continued to improve post-operatively with completion of the first treatment cycle. Four cycles of efgartigimod over 10 months resulted in an MG-ADL score of 3.DiscussionEfgartigimod may be a novel treatment for perioperative management of MG, myasthenic crisis, and paraneoplastic MG. Further study is warranted.

IntroductionEfgartigimod has been approved for the treatment of acetylcholine receptor antibodies-positive generalized myasthenia gravis (AChR-Ab+gMG), but its efficacy in patients with ocular myasthenia gravis (OMG) is not known.Case presentationWe describe 2 cases of patients with AChR-Ab+ OMG who showed unfavorable responses to corticosteroids and tacrolimus. Within 2 weeks of initiating efgartigimod, both patients showed rapid improvement and minimal symptom expression was achieved in weeks 3 to 4, which was maintained up to week 12.ConclusionThe 2 cases described herein provide preliminary evidence for the effectiveness of efgartigimod for the treatment of OMG for patients who do not respond or are intolerant to conventional medications. Large-scale studies are needed to confirm these findings.

Abstract Background Generalized myasthenia gravis (gMG) can be managed with acetylcholinesterase inhibitors (AChEis; e.g., pyridostigmine), corticosteroids, other immunosuppressive drugs (e.g., tacrolimus), and their combinations. Intravenous immunoglobulin (IVIg) or plasmapheresis (PLEX) may be administered if symptoms persist. PLEX and IVIg are also mainstays of treatment for myasthenic crisis. Recently, efgartigimod was approved in Japan for treating adults with gMG (irrespective of the antibody status) who do not have a sufficient response to corticosteroids and nonsteroidal immunosuppressive therapies. Efgartigimod is generally safe and well tolerated. However, since phase III trials of efgartigimod excluded those with myasthenic crisis, the efficacy of efgartigimod in treating myasthenic crisis is still unclear. Moreover, there are no reports that efgartigimod therapy can reduce the dose of corticosteroids needed to achieve a minimal manifestation status. Case presentation We report the case of a 70-yeat-old woman with gMG who developed a myasthenic crisis. After she was diagnosed with gMG, the patient had been treated with oral corticosteroids and tacrolimus for 1 year. However, she refused to continue taking the medication, and two weeks later, she developed ptosis, dysphagia and dyspnea. The patient was intubated and treated with efgartigimod in combination with steroid therapy, and she recovered without PLEX or IVIg. Afterward, when she experienced worsening of fatigue and increased levels of anti-acetylcholine receptor antibodies, efgartigimod therapy was effective. The patient achieved minimal manifestation status even after the reduction of corticosteroids and showed improvements in the Myasthenia Gravis Activities of Daily Living scales after 4 cycles of efgartigimod infusion. Conclusions Our case suggests that efgartigimod can be an alternative drug for achieving minimal manifestation status in patients with myasthenic crisis. Considering its strong efficacy and safety, efgartigimod could be expanded to use as bridging therapy in the acute and chronic phases of gMG.

Immunoglobulin G (IgG) autoantibodies can lead to the formation of autoimmune diseases through Fab and/or Fc-mediated interactions with host molecules as well as activated T cells. The neonatal Fc receptor (FcRn) binds at acidic pH IgG and albumin, and the mechanism for prolonging serum IgG half-life is making IgG re-entry into circulation by prompting it not to be degraded by lysosomes and back to the cell surface. Given the FcRn receptor's essential role in IgG homeostasis, one of the strategies to promote the quick degradation of endogenous IgG is to suppress the function of FcRn, which is beneficial to the treatment of IgG-driven autoimmune disorders like myasthenia gravis (MG), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), stiff person syndrome, and immune thrombocytopenia (ITP). We elaborately read the literature about efgartigimod and systematically reviewed the research progress and clinical application of this novel FcRn inhibitor in autoimmune diseases. Efgartigimod is the firstly FcRn antagonist developed and was approved on 17 December 2021 by the United States for the therapy of acetylcholine receptor-positive MG. In January 2022, efgartigimod received its second regulatory approval in Japan. In addition, the market authorization application in Europe was submitted and validated in August 2021. China's National Medical Products Administration officially accepted the marketing application of efgartigimod on July 13, 2022. To suppress the function of FcRn, which is beneficial to the treatment of IgG-driven autoimmune disorders like MG, CIDP, ITP, and stiff person syndrome. We review the rationale, clinical evidence, and future perspectives of efgartigimod for the treatment of autoimmune disease. [ABSTRACT FROM AUTHOR]

We report the long‐term treatment of a 38‐year‐old man with generalized thymoma‐associated myasthenia gravis who was treated with efgartigimod. He received chemotherapy and oral prednisolone before the thymectomy. However, after initial improvement in symptoms, he deteriorated and needed continuous noninvasive positive‐pressure ventilation, with the highest Myasthenia Gravis‐Activities of Daily Living score of 14. Immunosuppressive therapy and plasma exchange showed limited benefit, and the anti‐acetylcholine receptor antibody titer peaked to 130 nmol/L. Seven cycles of efgartigimod treatment were administered, which improved the symptoms, achieving a Myasthenia Gravis‐Actvities of Daily Living score of 0. The anti‐acetylcholine receptor antibody titer fluctuated until the end of the fifth cycle, thereafter, plateauing at 22 nmol/L. These findings allowed the prednisolone dose to be tapered and the interval between the treatment cycles to be increased. [ABSTRACT FROM AUTHOR]

Background: Anti leucine-rich, glioma inactivated 1 (LGI1) antibody-associated autoimmune encephalitis (AE) is the second most common AE, where the trafficking and recycling of the pathogenic immunoglobulin (IgG) can be controlled by the neonatal crystallizable fragment receptor (FcRn), making the latter as a candidate therapeutic target. Efgartigimod is an antagonist of FcRn, its ability to increase the degradation of IgGs and improve the health and quality of life of patients. ADAPT trail indicated its rapid efficacy and safety on myasthenia gravis. However, there is currently no case reported using efgartigimod for the treatment of anti-LGI1-associated AE. Case description: The patient presented with five episodes of generalized tonic–clonic seizures in the past 2 weeks. The patient had no abnormal signs on magnetic resonance imaging. Electroencephalogram examinations showed an increase in bilateral symmetric or asymmetric slow activity, without any clear epileptic waves. The cerebrospinal fluid (CSF) examination results indicated a slight increase in protein (47 mg/dL). The anti-LGI1 antibody titer in serum was 1:100 and that in CSF was 1:3.2. The treatment with intravenous methylprednisolone 1000 mg once a day combined with levetiracetam tablets failed to completely control the patient's seizures. Thus, 10 mg/kg efgartigimod was administered intravenously once a week for 2 weeks. After 2 weeks of treatment, serum levels of anti-LGI1 antibody and IgG decreased and the patient's epilepsy did not recur in the next 3 months. Conclusions: This is the first case report of using efgartigimod to treat anti-LGI1-associated AE. The combination of efgartigimod and methylprednisolone resulted in favorable outcomes, indicating that this is an optional treatment plan. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Efgartigimod, a neonatal Fc‐receptor inhibitor, has recently been approved as treatment for myasthenia gravis (MG). In this retrospective cohort study, we aimed to systematically assess short‐ and long‐term effectiveness of efgartigimod in patients with refractory MG. Methods: Sixteen patients with refractory autoimmune acetylcholine receptor MG were treated with efgartigimod. Data were collected from January 2021 to March 2023 on Myasthenia Gravis Activities of Daily Living (MG‐ADL), Quantitative Myasthenia Gravis score (QMG), Myasthenia Gravis Composite score (MGC) and the 15‐item revised version of the Myasthenia Gravis Quality of Life questionnaire (MG‐QoL15r). Results: A favorable outcome was seen in 56% of patients at the last measurement. Out of 16 patients, 50% were an MG‐ADL responder after the first treatment cycle. After 4 weeks, a clinically meaningful improvement compared to baseline was seen on the MG‐ADL, QMG, and MGC. There was a statistically significant improvement on the MGQoL15r from baseline to week 4. The improvement was maintained until the last measurement for the MGC and the MGQoL15r. At the last visit, all patients had discontinued 4‐weekly dosages, shifting to administration frequencies of 1, 2, or 3 weeks. Drug doses could be decreased for prednisolone (n = 7), azathioprine (n = 2), and intravenous immunoglobulin (n = 9). Frequency of plasma exchange was decreased in nine patients. Discussion: In patients with refractory MG, efgartigimod was effective for at least half of all patients. Patients required more frequent dosing compared to the ADAPT phase 3 trial. In 80% of the patients concurrent medication could be reduced or discontinued. [ABSTRACT FROM AUTHOR]

Background: Generalized myasthenia gravis (gMG) can be managed with acetylcholinesterase inhibitors (AChEis; e.g., pyridostigmine), corticosteroids, other immunosuppressive drugs (e.g., tacrolimus), and their combinations. Intravenous immunoglobulin (IVIg) or plasmapheresis (PLEX) may be administered if symptoms persist. PLEX and IVIg are also mainstays of treatment for myasthenic crisis. Recently, efgartigimod was approved in Japan for treating adults with gMG (irrespective of the antibody status) who do not have a sufficient response to corticosteroids and nonsteroidal immunosuppressive therapies. Efgartigimod is generally safe and well tolerated. However, since phase III trials of efgartigimod excluded those with myasthenic crisis, the efficacy of efgartigimod in treating myasthenic crisis is still unclear. Moreover, there are no reports that efgartigimod therapy can reduce the dose of corticosteroids needed to achieve a minimal manifestation status. Case presentation: We report the case of a 70-yeat-old woman with gMG who developed a myasthenic crisis. After she was diagnosed with gMG, the patient had been treated with oral corticosteroids and tacrolimus for 1 year. However, she refused to continue taking the medication, and two weeks later, she developed ptosis, dysphagia and dyspnea. The patient was intubated and treated with efgartigimod in combination with steroid therapy, and she recovered without PLEX or IVIg. Afterward, when she experienced worsening of fatigue and increased levels of anti-acetylcholine receptor antibodies, efgartigimod therapy was effective. The patient achieved minimal manifestation status even after the reduction of corticosteroids and showed improvements in the Myasthenia Gravis Activities of Daily Living scales after 4 cycles of efgartigimod infusion. Conclusions: Our case suggests that efgartigimod can be an alternative drug for achieving minimal manifestation status in patients with myasthenic crisis. Considering its strong efficacy and safety, efgartigimod could be expanded to use as bridging therapy in the acute and chronic phases of gMG. [ABSTRACT FROM AUTHOR]

Background: Efgartigimod (Efgartigimod alpha fcab, Vyvgart™) is a pioneering neonatal Fc receptor (FcRn) antagonist for the treatment of severe autoimmune diseases mediated by pathogenic immunoglobulin G (IgG) autoantibodies, including myasthenia gravis (MG). It is a well-tolerated drug with minor side effects, such as headache and upper respiratory (lung) and urinary tract infections. Here, we present a case of Kaposi's varicelliform eruption (KVE) and herpetic conjunctivitis related to efgartigimod in a 60-year-old patient with ocular MG (OMG). Case description: A 60-year-old Chinese male suffered from acetylcholine receptor antibody positive (AChR Ab+) OMG for 8 years. During this period, he underwent first-line treatment with systemic corticosteroids, cyclosporine, cyclophosphamide, and so on, but had poor symptom improvement. On the recommendation of his attending neurologist, he received one cycle of intravenous efgartigimod (10mg/kg, once weekly for 4 weeks). The patient experienced fever, widespread painful blisters, and edema on the face on the third day after his last intravenous infusion. The patient also complained of increased secretions and a foreign body sensation in both eyes. Laboratory tests confirmed infection with herpes simplex virus (HSV). A diagnosis of efgartigimod-associated KVE and herpetic conjunctivitis was made. After intravenous administration (5mg/kg, 3 times a day, every 8 hours) for 10 days, the patient was cured without residual complications. Conclusions: This case is the first report of a patient with KVE and herpetic conjunctivitis related to efgartigimod in PubMed. This is rare and unusual. Clinicians should be alert to the rare symptoms related to efgartigimod. [ABSTRACT FROM AUTHOR]

Introduction: Efgartigimod is effective and well-tolerated in patients with anti-acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (MG). However, the therapeutic potential and the safety profile of efgartigimod in myasthenic crisis (MC) remained largely unknown. Methods: This is an observational, prospective, multicenter, real-world study to follow 2 MC patients who initiated efgartigimod as a first-line rescue therapy and 8 cases who used it as an add-on therapy. Baseline demographic features and immunotherapies were collected, and the MG-activities of daily living (MG-ADL) scale was evaluated every week since efgartigimod treatment for 8 weeks. Additionally, serum IgG and anti-AChR antibody levels and the peripheral CD4+ T lymphocytes were measured before and after one cycle of treatment. Results: Ten patients with MC were enrolled in the study, including 9 anti-AChR antibody positive and 1 anti-muscle-specific kinase (MuSK) positive. All patients were successfully weaned from the ventilation after receiving efgartigimod treatment, with a length of 10.44 ± 4.30 days. After one cycle of infusions, the MG-ADL score reduced from 15.6 ± 4.4 at the baseline to 3.4 ± 2.2, while the corticosteroid dose was tapered from 55.0 ± 20.7 mg to 26.0 ± 14.1 mg. The proportions of regulatory T cells and naïve T cells (% in CD4+ T) significantly decreased post-efgartigimod treatment (5.48 ± 1.23 vs. 6.90 ± 1.80, P=0.0313, and 34.98 ± 6.47 vs. 43.68 ± 6.54, P=0.0313, respectively). Conclusion: These findings validated the rapid action of efgartigimod in facilitating the weaning process with a good safety profile in patients with MC. [ABSTRACT FROM AUTHOR]

Background and purpose: This study was undertaken to highlight neonatal Fc receptor inhibition (efgartigimod) as a valuable therapeutic option for patients with refractory seronegative myasthenia gravis (MG) and to emphasize the concept that seronegative MG is greatly constrained by the limitations of currently available diagnostic methods and therapeutic measures. Methods: We describe the first refractory, generalized MG (gMG) patient successfully treated with efgartigimod after testing negative on standard autoantibody detection tests. Results: Our patient presented with severe fluctuating bulbar and generalized weakness, resulting in multiple myasthenic crises requiring intubation. After a 28‐year medical history of multiple failed lines of treatment, our patient was started on efgartigimod. Over five treatment cycles, a definite improvement in her clinical condition was observed (Myasthenia Gravis Foundation of America class: IIIb to IIb; MG‐Activities of Daily Living score: 11 to 0; MG‐Quality of Life 15 score: 30 to 0; Quantitative MG score: 28 to 6). Standard autoantibody detection tests failed to detect known pathogenic autoantibodies, but cell‐based assay (CBA) identified autoantibodies against clustered adult acetylcholine receptor (AChR). Conclusions: In light of recent approvals of efgartigimod by the European Medicines Agency and US Food and Drug Administration exclusively for AChR‐positive gMG forms, our case highlights evidence suggesting that such an approach might be shortsighted and could limit therapeutic options for patients with refractory seronegative gMG. Additionally, introducing more sensitive analytical techniques, exemplified by CBA, may help bridge the gap between seronegative and seropositive patients. This represents an urgent unmet need for gMG patients, as the antibody profile dramatically influences the therapeutic approach. [ABSTRACT FROM AUTHOR]

Background: Despite the efficacy of efgartigimod demonstrated in ADAPT phase 3 trial, data specifically derived from Chinese participants are not available. Therefore, we aimed to evaluate the efficacy and safety of efgartigimod in Chinese patients with generalized myasthenia gravis (gMG). Methods: This is a prospective cohort study conducted in 8 hospitals across China. gMG patients received weekly intravenous infusions of efgartigimod (10  mg/kg) under a named patient program (NPP). The present study is an 8-week study, consisting of 4 consecutive doses of efgartigimod administered over 3  weeks (one cycle), followed by a 5-week follow-up period to assess the tolerability of efgartigimod’s therapeutic effects. The primary outcome was the mean change in MG activities of daily living (MG-ADL) total score from baseline to 4  weeks. MG-ADL responder was defined as a ≥  2-point improvement that persisted for 4  weeks, starting by week 4. Safety evaluations encompassed the monitoring of adverse events (AE) and serious AE (SAE) throughout the study. Results: Between 5 July 2022 and 25 August 2023, a total of 14 gMG patients were included. The mean age was 57.7  years, with a mean MG-ADL score of 10.86  ±  3.32. At week 4, MG-ADL scores showed a mean reduction of 6 points, reaching a maximum decline of 13 points. Among the patients, 85.7% (12/14) achieved MG-ADL responder status after one cycle of treatment. The most significant reduction in quantitative MG (QMG) scores also occurred at week 4, with a mean decrease of 7 points. Notably, the improvements in MG-ADL and QMG scores persisted until week 8. During treatment and follow-up period, only two mild neck rashes occurred and resolved promptly. No infections or SAE were reported. Discussion: A single cycle of efgartigimod treatment demonstrates effectiveness and the tolerability through week 8, with no new safety signals observed in Chinese gMG patients. [ABSTRACT FROM AUTHOR]

BackgroundThe prevalence of patients positive for muscle-specific kinase antibody (hereafter, MuSK-Ab) accounts for 5–8% of all myasthenia gravis (MG) cases. Currently, efgartigimod has shown good therapeutic effects in MUSK-Ab-positive MG patients in a phase III clinical trial. However, phase III clinical trials tend to exclude MG patients in exacerbation, and there are only few real-world studies on the efficacy of efgartigimod in MuSK-Ab-positive myasthenic crisis (MC) patients. This retrospective, real-world study aimed to explore the efficacy of efgartigimod in MuSK-Ab-positive MG with exacerbation.MethodsWe reviewed the clinical data of four MuSK-Ab-positive patients with exacerbation of MG who received efgartigimod at the First Affiliated Hospital of Sun Yat-sen University, including two patients with MC. All patients were admitted between September 2023 and May 2024. Most patients are simultaneously undergoing rituximab treatment.ResultsEach patient completed one cycle of efgartigimod. After the first administration, four patients showed a clinically meaningful decrease in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score (a reduction of more than 4 points compared to baseline), and all patients showed a decrease in IgG levels after one cycle of efgartigimod. Regarding safety, none of the patients experienced any obvious adverse effects. At the final follow-up, all patients achieved the minimal symptom expression status (an MG-ADL score of 0 or 1) following the first administration of efgartigimod for 8.75 ± 5.56 weeks. This article presents a case involving a patient who exhibited prompt alleviation of symptoms following the administration of a high dose of efgartigimod (20 mg/kg, given on days 1 and 5), without the use of any other fast-acting treatment.ConclusionThis retrospective real-world study demonstrates the effectiveness and safety of efgartigimod in these four MuSK-Ab-positive, female Asian patients with exacerbation of MG, as well as in patients experiencing MC. It is important to note that efgartigimod should not be viewed as a substitute for foundational immunotherapy; rather, it is intended as a rescue treatment during exacerbations and as an adjunctive therapy in the context of long-term immunotherapy. This non-invasive approach has the potential to become another treatment option for MuSK-Ab-positive MG patients.

Immune-mediated necrotizing myopathy (IMNM) with anti-HMGCR antibody positivity is characterized by proximal extremity weakness, increased creatine kinase, and extensive muscle edema. There is an urgent need to find more appropriate treatment options for anti-HMGCR IMNM patients who do not respond well to conventional therapy in the acute phase. With the advent of targeted biologics, new treatment options are available. We report on a 66-year-old anti-HMGCR IMNM patient who initially presented with a 1-month history of progressive proximal extremity weakness and dysphagia with markedly elevated creatine kinase. The patient did not respond to conventional high-dose glucocorticoid and intravenous immunoglobulin therapy, and his symptoms rapidly deteriorated over the 2 weeks after this treatment, with worsening limb weakness that prevented walking, marked proximal muscle atrophy, and weight loss. After one cycle (four infusions) of efgartigimod, the patient’s symptoms improved markedly and he has since (for several months) remained in a good clinical state.

IntroductionAutoimmune encephalitis (AE) comprises a group of inflammatory brain disorders mediated by autoimmune responses. Anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis, anti–leucine-rich glioma-inactivated 1 (LGI1) encephalitis, and anti–γ-aminobutyric acid-B receptor (GABABR) encephalitis are the most prevalent forms, characterized by the presence of antibodies against neuronal cell-surface antigens. Efgartigimod, an antagonist of the neonatal Fc receptor, has proven efficacy in myasthenia gravis treatment. This clinical case report describes the clinical progression and functional outcomes of AE in three patients who received efgartigimod treatment.Case presentationsCase 1 was a 60-year-old man exhibiting memory impairment and psychiatric disturbances over 11 days. Case 2 was a 38-year-old man with a 1-month history of rapid cognitive decline and seizures. Case 3 was a 68-year-old woman with mental behavioral changes and seizures for 4 months. Anti-GABABR, anti-LGI1, and anti-NMDAR antibodies were confirmed in the respective patients’ cerebrospinal fluid or serum. All three patients experienced marked and swift symptomatic relief after four cycles of efgartigimod treatment, with no complication.ConclusionCurrent first-line and second-line treatments for AE have limitations, and efgartigimod has demonstrated potential in the rapid and efficacious treatment of AE, emerging as a promising option for the management of this disease.

ObjectiveWe aimed to explore the efficacy and safety of efgartigimod in patients with refractory immune-mediated necrotizing myopathy (IMNM).MethodsThis open-label pilot observational study included seven patients with refractory IMNM, all of whom received intravenous efgartigimod treatment. The clinical response was assessed after 4 weeks of efgartigimod treatment according to the 2016 American College of Rheumatology–European League Against Rheumatism response criteria for adult idiopathic inflammatory myopathy. Serum levels of immunoglobulin as well as anti–signal recognition particle (SRP) and anti–3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies were measured using enzyme-linked immunosorbent assays and commercial line immunoblot assays. Safety assessments included evaluations of adverse events and severe adverse events.ResultsThe seven patients with refractory IMNM included five cases with anti-HMGCR antibodies and two cases within anti-SRP antibodies. Four of the seven patients achieved clinical responses. The total improvement score for the responders at 4 weeks were 32.5, 40.0, 47.5, and 70.0, and those at 8 weeks were 27.5, 47.5, 57.5, and 70.0. In comparison to the responsive patients, the non-responsive patients had longer durations [8 (-) versus 2 (1–5) years, P = 0.03], and more chronic myopathic features by muscle biopsy (67% versus 0%, P = 0.046). Serum immunoglobulin G levels (11.2 ± 2.5 versus 5.7 ± 2.5, P = 0.007) and anti-HMGCR/SRP antibody levels (97.2 ± 6.9 versus 41.8 ± 16.8, P = 0.002) were decreased after treatment compared with baseline levels. Adverse events were reported in one of the seven patients, who showed mild headache.ConclusionsDespite its small size, our study demonstrated that promoting the degradation of endogenous immunoglobulin G may be effective for patients with IMNM. Efgartigimod may be a promising option for cases of refractory IMNM to shorten duration and minimize chronic myopathic features.

Myasthenia gravis with positive MuSK antibody often involves the bulbar muscles and is usually refractory to acetylcholinesterase inhibitors. For MuSK-MG patients who experience acute exacerbations and do not respond to conventional treatments, there is an urgent need to find more suitable treatment options. With the advent of biologic agents, efgartigimod has shown promising results in the treatment of MG. We report a 65-year-old MuSK-MG patient who presented with impaired eye movements initially, and the symptoms rapidly worsened within a week, affecting the limbs and neck muscles, and had difficulties in chewing and swallowing. Lymphoplasmapheresis did not achieve satisfactory results, but after a cycle of efgartigimod treatment, the patient’s symptoms gradually improved and remained in a good clinical state for several months. [ABSTRACT FROM AUTHOR]

• Efgartigimod showed efficacy for generalized myasthenia gravis. • Effect of efgartigimod in seronegative generalized myasthenia gravis is unknown. • 16 seronegative generalized myasthenia gravis patients treated with efgartigimod. • Myasthenia gravis activities of daily living scores improved from 9.2 to 7.4. • There were no serious adverse events. The effect of treatment with efgartigimod in seronegative myasthenia gravis (MG) remains unclear. This retrospective study aimed to evaluate symptomatic changes and safety of treatment with efgartigimod in patients with generalized MG (gMG) double-seronegative for acetylcholine receptor antibody and muscle-specific kinase antibody. We reviewed the medical records of double-seronegative gMG treated with 10 mg/kg efgartigimod once/week per cycle (4 weeks) from June 2022 to June 2023. A total of 16 patients were included. MG–activities of daily living (ADL) scores improved from 9.2 to 7.4. Mean prednisolone dose was reduced from 5.4 to 4.1 mg/day. The duration before MG–ADL deterioration after the end of a cycle was 6.1 weeks. Five patients had mild adverse events. This retrospective study revealed no significant treatment benefit in the outcomes of patients with double-seronegative gMG treated with efgartigimod. [ABSTRACT FROM AUTHOR]

Background: Guillain–Barré Syndrome (GBS) is caused by immunoglobulin G (IgG) autoantibodies. Efgartigimod, a human IgG antibody Fc fragment that acts as a natural ligand for the FcRn, can increase IgG degradation, which thus may be a promising therapeutic drug for GBS. Case presentation: The two patients presented with postinfectious and acute flaccid paralysis. On admission, they were bedridden. Nerve conduction studies indicated peripheral neuropathy. GBS was suspected and they are treated with two doses of efgartigimod (10 mg/kg) within 5 days. Their muscle strength improved gradually and 4 weeks after the initial dose, they could walk independently. Following the first dose, Patient 1 complaint of muscle soreness, which subsided the next morning. Patient 2 was intubated due to respiratory failure the day after the initial dose, and did not report other adverse effects. Discussion: In GBS patients, two doses of efgartigimod (10 mg/kg) were effective in rapidly improving muscle strength, with a satisfactory safety profile. The findings suggest a potential role for efgartigimod in modifying the disease process in GBS patients. Conclusion: Efgartigimod seems effective and safe in the treatment of GBS. This study indicates the potential role of efgartigimod as a novel treatment option for GBS. Well-designed clinical trials should be conducted. [ABSTRACT FROM AUTHOR]

Recommendations for the treatment of myasthenia gravis (MG) have been difficult to develop because of limited evidence from large randomized controlled trials. New drugs and treatment approaches have recently been shown to be effective in phase 3 studies in seropositive generalized (g) MG. One such drug is efgartigimod, a human-Fc-fragment of IgG1, with a high affinity for the endosomal FcRn. We conducted a multicenter study to evaluate the real-world clinical and safety effects of efgartigimod in 22 gMG patients. We evaluated the strategies for the timing of re-treatment with it. The participants received a total of 59 efgartigimod -treatment cycles. The median number of cycles was 2 (range 1–6). Twenty patients (86.3%) improved by at least 2 MG-ADL points after the first treatment cycle. The median MG-ADL score at baseline was 6.5 (range: 3–17) and 2.5 (range: 0–9) post-treatment (p < 0.001). A consistent improvement of at least 2 points in the MG-ADL score after each cycle occurs in 18 patients. The effect duration of the treatment was usually between 4 and 12 weeks. Two major clinical patterns of treatment response were found. Treatment with efgartigimod was also associated with significant reductions of prednisone doses Overall, the treatment was safe and associated with only minor adverse events. The single fatality was apparently due tosevere respiratory failure. We found that efgartigimod is clinically effective, may be used as a steroid sparing agent and is generally safe for gMG patients. We recommend a personalized preventive treatment approach until clinical stabilization, followed by discontinuation and periodic evaluations. [ABSTRACT FROM AUTHOR]