Myasthenia gravis (MG) is an autoimmune disease in which autoantibodies mediate an acquired impaired neuro-muscle junction transmission1. In recent years, many breakthroughs have been made in the diagnosis and treatment of MG, more evidence-based medical evidence has been accumulated, and the treatment of MG has been pushed to a higher goal, that is, to achieve the "double goal" of symptom control and side effect minimization.
At the 76th Annual Meeting of the American Academy of Neurology (AAN) held in April, a real-world study on the long-term treatment of agamod attracted extensive attention from scholars and experts in the field of neuroimmunology, bringing new solutions to better meet the needs of patients and achieve the goal of "double target" in MG treatment.
Focus on the "double standard" and pay attention to the long-term application of glucocorticoids
In recent years, the concept of "double standard" has gradually been recognized by international and domestic clinical trials. The goal of "double achievement" includes symptom compliance and side effect compliance1-5. Among them, glucocorticoids, although widely used in the international treatment of MG, can improve the condition of most MG patients. However, long-term use of glucocorticoids can cause a range of adverse effects, the severity of which is proportional to the dose and duration of administration5.
A retrospective study published in 2021 investigated data from patients with gMG who were treated in a single center in the United States from January 2014 to December 2015. Corticosteroid-related adverse reactions (AEs) have been shown to be common in patients with generalized myasthenia gravis (gMG) who have been treated with oral glucocorticoids for a long period of time (≥1 year), and some of these AEs can have serious medical consequences6. In the study, the mean duration of prednisone treatment was 14.3 months, and the average daily dose was 36.0 mg6. All patients (39) experienced at least one AE, with an average of 2.3 AEs per patient, with a maximum of 6 AEs per patient. The types and frequency of patient-reported corticosteroid AEs can be seen in the figure below, with the most common AEs being prediabetes, weight gain, foot edema, and insomnia.6
Figure 1.Corticosteroid-related adverse reactions reported in patients with myasthenia gravis (n=39)6
Therefore, while controlling the symptoms of MG, how to avoid the use of high-dose corticosteroids or reduce the dosage of corticosteroids and reduce the side effects caused by long-term use of corticosteroids have become the current treatment goals6.
Preliminary studies have shown that long-term use of agamod can improve clinical scores and reduce hormone dosage
Agamod is the world's first FcRn antagonist approved for the treatment of generalized myasthenia gravis in adults, which can accurately block IgG recirculation and exert efficacy, bringing a new treatment option to gMG patients. To explore the efficacy of long-term use of agamod in the treatment of gMG and whether it can reduce the amount of hormone used, researchers have conducted and published a number of real-world studies, which are summarized as follows:
➤ Evidence from the latest real-world research in the United States shows that:
Long-term use of agamod significantly improves patients' clinical scores and reduces the amount of corticosteroids
In November 2023, evidence from a real-world study of agamod in the treatment of gMG in the United States was released. The study reviewed 17 cases of gMG treated with agamod between January 2022 and June 2023. The study showed a sustained and significant improvement in the Mean Myasthenia Gravis Scale of Daily Activity (MG-ADL) score at 3 and 6 months. And, during the study, all patients treated with steroids at baseline were able to reduce their daily dose of steroids; In patients (11/17) who used prednisone at baseline and continued to take agamod throughout the study period, the mean daily dose of prednisone decreased by 14.1 mg/day at 3 months (p = 0.2) and by 18.1 mg/day at 6 months (p = 0.03)7.
➤ Italian single-center real-world studies have shown that:
Maintenance of agamod can provide clinically meaningful clinical score improvement in patients with gMG; Average hormone reduction of 33%
The study, conducted from November 2021 to January 2023 in a single-center real-world setting in Italy, investigated the efficacy of agamod in 19 patients with gMG with up to 14 months of follow-up. Long-term use of agamod has been shown to provide rapid and clinically meaningful improvements in patients' MG-ADL, Myasthenia Gravis Composite Score (MGC), and Revised Myasthenia Gravis 15-Item Quality of Life Scale (MG-QoL15r) scores. At the same time, at 7-8 months, patients (15/19 patients treated with prednisone as concomitant therapy) achieved an average hormone reduction of 33%8.
Both of these studies confirmed that long-term treatment with agamod reduces the amount of hormones used in patients.
Add a new certificate! Large, real-world studies have shown that agamod can reduce hormone dosage
At this year's AAN Congress, a new real-world study of reducing oral glucocorticoids was released. The study was designed to evaluate the real-world dosage of oral glucocorticoids (OCS) over 6 months after treatment with egatimod in patients with gMG9.
In this retrospective cohort study, which included patients treated with agamod for gMG in the U.S. Medical and Drug Claims Database from April 2016 to November 2023, the mean daily dose (ADD) of OCS at the following time points was analyzed :(1) during the first 3 months of treatment; (2) 3 months after treatment; (3) 6 months after treatment. This study evaluated the change from baseline in ADD and the proportion of patients with an ADD reduction of ≥5 mg after 3 and 6 months of egaltimod treatment9.
Of the 842 patients with gMG who started agamod treatment between January 1, 2022 and December 31, 2022 and continued treatment for ≥ 6 months, 316 were treated with OCS at baseline (before agamod treatment) and were included in the study. The median age of patients was 65 years, and 54.7% were male9.
The results showed that 125 (40%) and 144 (46%) patients had a reduction of ≥5 mg of ADD at 3 and 6 months after egamod treatment, respectively. The average daily dose of OCS was significantly lower at 3 months and 6 months than before treatment. In addition, the proportion of patients with ADD 0-5 mg increased nearly threefold after initiation of egamod therapy (baseline 13% vs. 34% at 6 months after ejamod treatment) and the proportion of patients with ADD > 20 mg decreased by 38% (baseline 37% vs. 23% at 6 months after agamod treatment) (Figure 2)9.
Figure 2. Changes in the distribution of OCS ADD after EFG treatment9
In summary, the dose of OCS can be reduced 3 months after treatment with agamod in patients with gMG, and after 6 months of treatment with agamod, 34% of patients can achieve OCS dose reduction of 0-5 mg, and 46% of patients can achieve OCS dose reduction of ≥5 mg.
Expert commentary
Expert Profile
Prof. Yuying Zhao
- Chief physician of the Department of Neurology, Qilu Hospital, Shandong University, and director of the subspecialty of genetic metabolic diseases and rare diseases
- Head of the Rare Disease Diagnosis and Treatment Center of Qilu Hospital of Shandong University
- Deputy head of the Neuropathology Group of the Neurology Branch of the Chinese Medical Association
- Secretary-General of the Nervous System Rare Disease Committee of the China Alliance for Rare Diseases
- He is a member of the Standing Committee of the Rare Disease Branch of the Chinese Hospital Association
- He is a member of the Standing Committee of the Neuroscience Committee of the Chinese Association of Research Hospitals
- Vice President of Shandong Association for the Prevention and Treatment of Rare Diseases
- Chairman of the Nervous System Rare Disease Branch of Shandong Association for Rare Disease Prevention and Control
- Vice Chairman of the Rare Disease Branch of Shandong Medical Association
- Member of the Corresponding Editorial Board of the Chinese Journal of Neurology
- Member of the editorial board of the Chinese Journal of Modern Neurological Diseases
- Member of the editorial board of the Journal of Rare Diseases
- In 2019, he was a visiting scholar at the Department of Neuromuscular Pathology at the Mayo Clinic in the United States, focusing on rare diseases of the nervous system, especially genetic metabolic diseases and neuromuscular diseases
“
Glucocorticoids are still the first-line drugs for the treatment of MG, which can significantly improve the symptoms of 70%~80% of patients1. The main ones are oral prednisone acetate and methylprednisolone1. However, long-term use of glucocorticoids can cause symptoms such as increased food intake, weight gain, central obesity, hypertension, and hyperglycemia, which should be taken seriously.
In order to better meet the needs of MG patients and achieve the "double goal" of symptom control and side effect minimization, controlling the dosage of hormones has become a key task, and clinicians need to formulate individualized treatment plans according to the patient's disease condition and symptom severity. The above clinical studies have confirmed that agamod can control symptoms while effectively reducing the dose of glucocorticoids during maintenance therapy, which provides an encouraging treatment plan to achieve "double target" and help patients achieve a better quality of life.
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Bibliography:
- Neuroimmunology Branch of Chinese Society of Immunology. Guidelines for the diagnosis and treatment of myasthenia gravis in China (2020 edition)[J]. Chinese Journal of Neuroimmunology and Neurology, 2021, Volume 28(1):1-12.
- Sanders DB, et al. International consensus guidance for management of myasthenia gravis: Executive summary. Neurology. 2016 Jul 26; 87(4):419-25.
- Evoli A, et al. Italian recommendations for the diagnosis and treatment of myasthenia gravis. Neurol Sci. 2019 Jun; 40(6):1111-1124.
- Supervised by the Japan Society of Neurology: Myasthenia gravis/Lambert-Eaton Myasthenic Syndrome Clinical Practice Guidelines 2022, p.54, 2022, Nankodo.
- De Bleecker JL, et al. Recommendations for the management of myasthenia gravis in Belgium. Acta Neurol Belg. 2024 Apr 22.
- Johnson S, et al. Adverse Side Effects Associated with Corticosteroid Therapy: A Study in 39 Patients with Generalized Myasthenia Gravis. Med Sci Monit. 2021 Oct 28; 27:e933296.
- Singer M, et al. Single institution experience with efgartigimod in patients with myasthenia gravis: Patient selection, dosing schedules, treatment response, and adverse events. Muscle Nerve. 2024 Jan; 69(1):87-92.
- Frangiamore R, et al. Efgartigimod in generalized myasthenia gravis: A real-life experience at a national reference center. Eur J Neurol. 2024 Apr; 31(4):e16189.
- Neelam Goyal ,et al. Real-world reduction in oral corticosteroid utilization following efgartigimod initiation in patients living with generalized myasthenia gravis，2024，AAN.
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