This update summarizes a review manuscript on myasthenia gravis, highlighting five novel findings and four proposed future directions identified by the authors of that paper [1].
5 new things
1.The role of thymectomy
The MGTX trial confirmed the thymus' key role in MG and established thymectomy as a core treatment for AChR-positive patients [2]. Remission and recurrence risks in patients treated with minimally invasive surgical approaches have yet to be investigated.
2. Expanding treatment landscape
Protecting the NMJ in AChR-antibody MG
The IgG1 antibodies of AChR-antibody MG trigger complement activation, causing damage to the NMJ. Eculizumab, a monoclonal antibody (mAb) which inhibits the C5 component of the complement, was approved by the FDA and EMA in 2017 for AChR-positive MG and was later joined by two further C5 inhibitors (Ravulizumab and Zilucoplan).
Removing culprit antibodies
Two approved antibodies are: Efgartigimod, an IgG1 Fc fragment dosed as an intravenous infusion and Rozanolixizumab, a subcutaneous formulation that targets the FcRN in the form of a humanized IgG4 mAb. Just reported are the phase 3 results of the Batoclimab trial, a humanized IgG1 antibody to the FcRN.
3. Integration of new treatment into guidelines and practice
In the 2020 International Consensus Guidance integrated views on thymectomy, Rituximab, and Eculizumab were released. German guidelines from 2023 focused on validating assessment tools and use of new agents in very active or refractory patients. Nordic guidelines highlighted Rituximab's role early in disease and advised new complement and FcRN inhibitors for difficult-to-treat patients.
4. Biomarkers
Exploratory biomarkers are under investigation and not adopted for clinical use yet. The biomarkers proximal to clinical utility are the circulating immune cell and the humoral response itself.
5. Concept of MG ‘age’ and ‘stage’
Late-onset MG (LOMG) incidence is increasing. Co-morbidities may be as much a result of drug regimens as a reason for non-responsive disease. Earlier use of Rituximab in older patients was advocated.
4 Hopes
1. Progress in laboratory testing
The initial radioimmunoassays (RIAs) for AChR and MuSK antibody detection have been superseded by live cell-based assays (CBAs). Live CBAs are time-consuming and not yet adopted in clinical routine.
2. Effective protection of the NMJ
Similar to the concept ""time is brain,"" the NMJ should be protected in a timely manner.
3. Treatment in older populations
We need more knowledge and clinical trials specifically targeted to older people
4. CAR T therapy
CAR T methods are likely to expand in the coming years, but open questions include cost and the potential emergence of side effects.
Next years offer hope for more personalized and evidence-based care in MG.
Key Points:
- The authors provide a review on myasthenia gravis, highlighting 4 new developments in the last ten years and hopes for the next 5–10 years.
- The 5 new things include thymectomy, new immunotherapies, recent guidelines, progress in biomarkers, and the concept of MG ‘age’ and ‘stage’.
- The 4 hopes are: progress in laboratory testing, timely protection of the NMJ, treatment in older populations, and CAR T therapy.
- In recent years, especially, the treatment landscape in MG has expanded with already approved C5 component inhibitors, FcRN inhibitors, and emerging agents in categories already established in other autoimmune diseases (e.g., IL-6 receptor blockade), as well as novel approaches including CAR T therapy.
References:
- Binks SNM, Morse IM, Ashraghi M, Vincent A, Waters P, Leite MI. Myasthenia gravis in 2025: five new things and four hopes for the future. J Neurol. 2025 Feb 22;272(3):226. doi: 10.1007/s00415-025-12922-7. PMID: 39987373; PMCID: PMC11846739.
- Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized Trial of Thymectomy in Myasthenia Gravis [published correction appears in N Engl J Med. 2017 May 25;376(21):2097. doi: 10.1056/NEJMx170003.. [Dosage error in article text]]. N Engl J Med. 2016;375(6):511-522. doi:10.1056/NEJMoa1602489
Publish on behalf of the Scientific Panel on Muscle and NMJ disorders