Recent European consensus guidelines for improving and standardizing the assessment of gMG recommend the consistent use of the MG-ADL score across clinical settings: “Consistent use of the MG-ADL scale should be applied in clinical practice to understand gMG disease burden; if the MG-ADL indicates worsening gMG, the QMG scale can be used to provide greater clinical understanding and support onward decisions. It is advised that an additional scale should follow the MG-ADL in clinical practice to determine patient satisfaction with symptom state and treatment; the MG-QoL-15r, PASS or EQ-5D-VAS can be used effectively in this setting.”

Abbreviations

gMG, generalized MG; MG, myasthenia gravis; MG-ADL, MG activities of daily living; MG-QoL-15r, MG – quality of life – revised 15; QMG, quantitative MG.

Reference

Meisel A, et al. Eur J Neurol. 2024;31:e16280.

A key burden of treatment in MG is that it can take a long time for the effect of treatment to be seen with conventional therapies.¹ Indeed, treatment with corticosteroids may take 6 months or more to attain maximal improvement;² similarly, treatment with azathioprine may take up to 18 months to attain maximal benefit.^2,3 This is further emphasized by Prof. Michael Nicolle: “Prednisone is effective, but in my opinion, takes several months before it produces optimal benefit. The non-steroidal immunosuppressives can take more than that – 6 to 18 months before they produce optimal benefit.”⁴

Of note, about 10–20% of patients with MG do not achieve an adequate response or are intolerant to conventional therapies.⁵ Pyridostigmine’s side effects are primarily neuromuscular or gastrointestinal;⁶ it does not require daily monitoring for hyperglycemia.⁷ Corticosteroids for the chronic treatment of MG are usually administered orally, and are only rarely used intravenously.^6,8 

Abbreviation

MG, myasthenia gravis.

References

1. Sacca F, et al. Eur J Neurol. 2024;31:e16180.
2. Farmakidis C, et al. Neurol Clin. 2018;36:311–37. 
3. Alhaidar MK, et al. J Clin Med. 2022;11:1597.
4. Prof. Michael Nicolle, Oral communication, 7 March 2025.
5. Schneider-Gold C, et al. Ther Adv Neurol Disord. 2019;12:1756286419832242. 
6. Kaminski HJ, Denk J. Front Neurol. 2022;13:886625.
7. FDA. Prescribing information. Available at: www.accessdata.fda.gov/scripts/cder/daf/index.cfm (accessed 6 February 2025). 
8. Murai H, et al. Ann N Y Acad Sci. 2018;1413:35–40.

In the ADAPT trial, 84% of patients with AChR+ gMG who were shown to be MG-ADL responders (defined as ≥2 point improvement [reduction] in MG-ADL score, sustained for ≥4 consecutive weeks with first improvement occurring by week 4 of the cycle [1 week after fourth infusion]) after receiving efgartigimod (n=44) demonstrated a response by week 2.¹ Likewise, the MycarinG phase III trial investigating the use of rozanolixizumab (7 mg/kg or 10 mg/kg) vs placebo in patients with gMG (N=200) demonstrated a significant and sustained improvement in MG-ADL scores in both patients who were AChR+, as well as patients who were MuSK+.^2,3 Two other emerging FcRn inhibitors, nipocalimab and batoclimab, have also demonstrated benefit in phase III clinical trials.^4,5 Evidence in these clinical trials shows a rapid onset of action with FcRn inhibitors, typically within weeks of treatment initiation.^1–5 

There are currently no head-to-head trials comparing FcRn inhibitors with C5 complement inhibitors; however, evidence suggests comparable efficacy and safety.⁶ 

Abbreviations

AChR, acetylcholine receptor; C5, C5 component of complement; FcRn, neonatal Fc receptor; gMG, generalized MG; MG, myasthenia gravis; MG-ADL, MG activities of daily living; MuSK, muscle specific kinase.

References

1. Howard JF, et al. Lancet Neurol. 2021;20:526–36.
2. Bril V, et al. Lancet Neurol. 2023;22:383–94.
3. Bril V, et al. J Neuromuscul Dis. 2025;doi:10.1177/22143602241305511
4. Antozzi C, et al. Lancet Neurol. 2025;24:105–16.
5. Yan C, et al. JAMA Neurol. 2024;81:336–45.
6. Huntemann N, et al. J Neurol Neurosurg Psychiatry. 2025;96:310–21.

Based on the MycarinG phase III trial, rozanolixizumab (7 mg/kg or 10 mg/kg) has demonstrated a significant and sustained improvement in MG-ADL scores in both patients who were AChR+, as well as patients who were MuSK+, compared with placebo.^1,2 It is currently the only approved FcRn inhibitor in patients who are MuSK+.^3,4 As the anti-MuSK antibodies are IgG4, which does not bind complement, there is no role for the use of complement inhibitors in MuSK+ MG.⁵ 

Abbreviations

AChR, acetylcholine receptor; MG, myasthenia gravis; MG-ADL, MG activities of daily living; MuSK, muscle specific kinase.

References

1. Bril V, et al. Lancet Neurol. 2023;22:383–94.
2. Bril V, et al. J Neuromuscul Dis. 2025;doi:10.1177/22143602241305511
3. FDA. Prescribing information. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2023/761286s000lbl.pdf (accessed 6 February 2025).
4. EMA. Summary of product characteristics. Available at: www.ema.europa.eu/en/documents/product-information/rystiggo-epar-product-information_en.pdf (accessed 26 March 2025).
5. DeHart-McCoyle M, et al. BMJ Med. 2023;2:e000241.

C5 inhibitors mandate completed meningococcal vaccination ≥2 weeks before initiation due to Neisseria meningitidis infection risk.^1,2 FcRn inhibitors do not require pretreatment meningococcal vaccination,^1,2 making them an appropriate choice for patients needing urgent therapy without prior immunization. A clinical trial confirmed preserved vaccine responses during treatment with efgartigimod,³ aligning with this patient’s remote living situation and lack of prior vaccination.

Abbreviation

C5, C5 component of complement; FcRn, neonatal Fc receptor.

References

1. FDA. Prescribing information. Available at: www.accessdata.fda.gov/scripts/cder/daf/index.cfm (accessed 6 February 2025).
2.  EMA. Summary of product characteristics. Available at: www.ema.europa.eu/en/medicines (accessed 26 March 2025).
3. Guptill JT, et al. Autoimmunity. 2022;55:620–31.