Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, et al. International consensus guidance for management of myasthenia gravis: executive summary. Neurology. 2016;87:419–25. https://doi.org/10.1212/WNL.0000000000002790.

Article  PubMed  PubMed Central  Google Scholar 

• Narayanaswami P, Sanders DB, Wolfe G, Benatar M, Cea G, Evoli A, et al. International consensus guidance for management of myasthenia gravis: 2020 update. Neurology. 2021;96:114–22. https://doi.org/10.1212/WNL.0000000000011124. Most current guidelines for the management of MG.

Wolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ. Myasthenia gravis activities of daily living profile. Neurology. 1999;52:1487–9. https://doi.org/10.1212/wnl.52.7.1487.

Article  PubMed  Google Scholar 

Barohn RJ, McIntire D, Herbelin L, Wolfe GI, Nations S, Bryan WW. Reliability testing of the quantitative myasthenia gravis score. Ann N Y Acad Sci. 1998;841:769–72. https://doi.org/10.1111/j.1749-6632.1998.tb11015.x.

Article  PubMed  Google Scholar 

Burns TM, Conaway MR, Cutter GR, Sanders DB; Muscle Study Group. Construction of an efficient evaluative instrument for myasthenia gravis: the MG composite. Muscle Nerve 2008:38:1553–62. https://doi.org/10.1002/mus.21185.

Muppidi S, Wolfe GI, Conaway M, Burns TM; MG COMPOSITE AND MG-QOL15 STUDY GROUP. MG-ADL: still a relevant outcome measure. Muscle Nerve 2011:44:727–31. https://doi.org/10.1002/mus.22140.

Katzberg HD, Barnett C, Merkies IS, Bril V. Minimal clinically important difference in myasthenia gravis: outcomes from a randomized trial. Muscle Nerve. 2014;49:661–5. https://doi.org/10.1002/mus.23988.

Article  PubMed  Google Scholar 

Benatar M, Sanders DB, Burns TM, Cutter GR, Guptill JT, Baggi F, et al. Recommendations for myasthenia gravis clinical trials. Muscle Nerve. 2012;45:909–17. https://doi.org/10.1002/mus.23330.

Article  PubMed  Google Scholar 

U.S. Food and Drug Administration, Center for Drug Evaluation and Research [Internet]. Approval letter; 2007 [cited 2023 October 26]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/125166s0000_APPROV.pdf

U.S. Food and Drug Administration, Center for Drug Evaluation and Research [Internet]. Medical Review; 2007 [cited 2023 October 26]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/125166s0000_MedR.pdf

U.S. Food and Drug Administration, Center for Drug Evaluation and Research [Internet]. Review; 2007 [cited 2023 October 26]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/125166Orig1s422.pdf

Riley TR, Douglas JS, Wang C, Bowser KM. An update of the pharmacological treatment options for generalized myasthenia gravis in adults with anti-acetylcholine receptor antibodies. Am J Health Syst Pharm. 2023;80:652–62. https://doi.org/10.1093/ajhp/zxad035.

Article  PubMed  Google Scholar 

Howard JF Jr, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. Lancet Neurol. 2017;16:976–86. https://doi.org/10.1016/S1474-4422(17)30369-1.

Article  PubMed  Google Scholar 

Brandsema JF, Ginsberg M, Hoshino H, Mimaki M, Nagata S, Rao V, et al. A phase 3, open-label, multicenter study to evaluate eculizumab in adolescents with refractory generalized myasthenia gravis (S5.009). 2023.

European Medicine Agency, Committee for Medicinal Products for Human Use [Internet]. CHMP extension of indication variation assessment report; 2017 [cited 2023 October 27]. Available from: https://www.ema.europa.eu/en/documents/variation-report/soliris-h-c-791-ii-0090-epar-assessment-report-variation_en.pdf

U.S. Food and Drug Administration, Center for Drug Evaluation and Research [Internet]. Pharmacology review; 2007 [cited 2023 October 26]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/125166s0000_PharmR.pdf

Muppidi S, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, et al. Long-term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle Nerve. 2019;60:14–24. https://doi.org/10.1002/mus.26447.

Article  PubMed  PubMed Central  Google Scholar 

Wijnsma KL, Ter Heine R, Moes DJAR, Langemeijer S, Schols SEM, Volokhina EB, et al. Pharmacology, pharmacokinetics and pharmacodynamics of eculizumab, and possibilities for an individualized approach to eculizumab. Clin Pharmacokinet. 2019;58:859–74. https://doi.org/10.1007/s40262-019-00742-8.

Article  PubMed  PubMed Central  Google Scholar 

U.S. Food and Drug Administration [Internet]. Highlights of prescribing information; 2022 [cited 2023 October 27]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761108s020lbl.pdf

•• Vu T, Meisel A, Mantegazza R, Annane D, Katsuno M, Aguzzi R, et al. Terminal complement inhibitor ravulizumab in generalized myasthenia gravis. NEJM Evid. 2022. https://doi.org/10.1056/EVIDoa2100066. Phase 3 clinical trial that demonstrated the safety and efficacy of ravulizumab in AChR+ gMG.

• Meisel A, Annane D, Vu T, Mantegazza R, Katsuno M, Aguzzi R, et al. Long-term efficacy and safety of ravulizumab in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis: results from the phase 3 CHAMPION MG open-label extension. J Neurol 2023:270:3862–3875. https://doi.org/10.1007/s00415-023-11699-x. Study providing long-term data on safety and efficacy of ravulizumab in AChR+ gMG.

Wang Y, Johnston K, Popoff E, Myren KJ, Cheung A, Faria C, et al. A US cost-minimization model comparing ravulizumab versus eculizumab for the treatment of atypical hemolytic uremic syndrome. J Med Econ. 2020;23:1503–15. https://doi.org/10.1080/13696998.2020.1831519.

Article  PubMed  Google Scholar 

•• Howard JF Jr, Bresch S, Genge A, Hewamadduma C, Hinton J, Hussain Y, et al. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2023;22:395–406. https://doi.org/10.1016/S1474-4422(23)00080-7. Pivotal study that demonstrated the safety and efficacy of zilucoplan in AChR+ gMG and led to its approval.

U.S. Food and Drug Administration [Internet]. Highlights of prescribing information; 2023 [cited 2023 October 25]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216834s000lbl.pdf

U.S. Food and Drug Administration [Internet]. Highlights of prescribing information; 2021 [cited 2023 October 25]. Available from: https://www-accessdata-fda-gov.geihsl.idm.oclc.org/drugsatfda_docs/label/2021/761195s000lbl.pdf

Ulrichts P, Guglietta A, Dreier T, van Bragt T, Hanssens V, Hofman E, et al. Neonatal Fc receptor antagonist efgartigimod safely and sustainably reduces IgGs in humans. J Clin Invest. 2018;128:4372–86. https://doi.org/10.1172/JCI97911.

Article  PubMed  PubMed Central  Google Scholar 

Howard JF Jr, Bril V, Burns TM, Mantegazza R, Bilinska M, Szczudlik A, et al. Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis. Neurology. 2019;92:e2661–73. https://doi.org/10.1212/WNL.0000000000007600.

Article  PubMed  PubMed Central  Google Scholar 

•• Howard JF Jr, Bril V, Vu T, Karam C, Peric S, Margania T, et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2021;20:526–36. https://doi.org/10.1016/S1474-4422(21)00159-9. Seminal clinical trial that demonstrated the safety and efficacy of efgartigimod in AChR+ gMG leading to its approval.

Ashcraft E, Bril V, Pasnoor M, Karam C, Peric S, De Bleecker J, et al. P277 Long-term safety, tolerability, and efficacy of efgartigimod in patients with generalized myasthenia gravis: concluding analyses from the ADAPT study. Neuromuscul Disord. 2023;33:S179.

Article  Google Scholar 

U.S. Food and Drug Administration [Internet]. FDA approves new treatment for myasthenia gravis; 2021 [cited 2023 October 31]. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-myasthenia-gravis

Li G, Li Y, Vu T, Korobko D, Smilowski M, Liu L, et al. Dose selection and clinical development of efgartigimod PH20 subcutaneous in patients with generalized myasthenia gravis (P1–5.017). 2023.

ClinicalTrials.gov [Internet] Evaluating the pharmacodynamic noninferiority of efgartigimod PH20 SC administered subcutaneously as compared to efgartigimod administered intravenously in patients with generalized myasthenia gravis (ADAPTsc); 2023 [cited 2023 October 31]. Available from: https://clinicaltrials.gov/study/NCT04735432

U.S. Food and Drug Administration [Internet]. Highlights of prescribing information; 2022 [cited 2023 October 31]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761304s000lbl.pdf

Musick K, Howard J, Li G, Vu T, Korobko D, Smilowski M, et al. P276 Long-term safety, and efficacy of subcutaneous efgartigimod PH20 in patients with generalized myasthenia gravis: interim results of ADAPT-SC. Neuromuscul Disord. 2023;33:S179.

Article  Google Scholar 

ClinicalTrials.gov [Internet] Evaluating the long-term safety and tolerability of efgartigimod PH20 SC administered subcutaneously in patients with generalized myasthenia gravis (ADAPTSC+); 2023 [cited 2023 October 31]. Available from: https://clinicaltrials.gov/study/NCT04818671?intr=efgartigimod&limit=25&page=1&rank=17

Howard J, Li G, Vu T, Korobko D, Smilowski M, Liu L, et al. Long-term safety, tolerability, and efficacy of subcutaneous efgartigimod PH20 in patients with generalized myasthenia gravis: interim results of the ADAPT-SC study (P1–5.014). 2023.

ClinicalTrials.gov [Internet] An open-label study to investigate the clinical efficacy of different dosing regimens of efgartigimod IV in patients with generalized myasthenia gravis (ADAPT NXT); 2023 [cited 2023 October 31]. Available from: https://clinicaltrials.gov/study/NCT04980495

ClinicalTrials.gov [Internet] Evaluating the pharmacokinetics, pharmacodynamics, and safety of efgartigimod administered intravenously in children with generalized myasthenia gravis; 2023 [cited 2023 October 31]. Available from: https://clinicaltrials-gov.geihsl.idm.oclc.org/study/NCT04833894?intr=efgartigimod&limit=25&page=1&rank=8.

ClinicalTrials.gov [Internet] Evaluating long-term safety of efgartigimod administered intravenously in children with generalized myasthenia gravis; 2023 [cited 2023 October 31]. Available from: https://clinicaltrials.gov/study/NCT05374590?intr=efgartigimod&limit=25&page=1&rank=7

Saccà F, Dewilde S, Nivelle E, Qi C, Jacob S, Meisel A, Palace J, Claeys K, Mantegazza R, Paci S, Phillips G. Combining clinical trial and real-world data to model the benefit of efgartigimod on productivity losses [abstract]. Poster presented at: International Congress on Neuromuscular Diseases; 2022 July 5–9; Brussels, Belgium. Available from: https://content.iospress.com/download/journal-of-neuromuscular-diseases/jnd229001?id=journal-of-neuromuscular-diseases%2Fjnd229001

Qi C, Huang D, Carlton R, Phillips G. Budget impact of efgartigimod in anti-AChR antibody-positive generalized myasthenia gravis [abstract]. Poster presented at: Academy of Managed Care Pharmacy Nexus; 2022 October 11–14; National Harbor, MD. Available from: https://www.xcenda.com/-/media/assets/xcenda/english/content-assets/xcenda-publications-lists/xcenda_publication.pdf

Falzone YM, Sorrenti B, Laurini C, Strano C, Bosco L, Schito P, Scarlato M, Fazio R, Filippi M, Previtali S. A triple seronegative, refractory patient with Generalized Myasthenia Gravis successfully managed with efgartigimod [abstract] Poster presented at: National Congress of Italian Association of Myology; 2023 June 8–10; Padova, Italy. Available from: https://congressoaim2023.it/ProgrammaAIM-2023.pdf

Campbell M, Rodriguez-Hernandez A, Rizvi Z, Swerdloff M, Zakin E, Faktorovich S. Efgartigimod for pembrolizumab-induced myasthenia gravis refractory to standard therapy (P1–8.006). 2023.

Lledo-Garcia R, Dixon K, Shock A, Oliver R. Pharmacokinetic-pharmacodynamic modelling of the anti-FcRn monoclonal antibody rozanolixizumab: translation from preclinical stages to the clinic. CPT Pharmacometrics Syst Pharmacol. 2022;11:116–28. https://doi.org/10.1002/psp4.12739.

Article  PubMed  Google Scholar 

Smith B, Kiessling A, Lledo-Garcia R, Dixon KL, Christodoulou L, Catley MC, et al. Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration. MAbs. 2018;10:1111–30. https://doi.org/10.1080/19420862.2018.1505464.

Article  PubMed  PubMed Central  Google Scholar 

Kiessling P, Lledo-Garcia R, Watanabe S, Langdon G, Tran D, Bari M, et al. The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: a randomized phase 1 study. Sci Transl Med 2017:9:eaan1208. https://doi.org/10.1126/scitranslmed.aan1208.

Bril V, Benatar M, Andersen H, Vissing J, Brock M, Greve B, et al. Efficacy and safety of rozanolixizumab in moderate to severe generalized myasthenia gravis: a phase 2 randomized control trial. Neurology. 2021;96:e853–65. https://doi.org/10.1212/WNL.0000000000011108.

Article  PubMed  PubMed Central  Google Scholar 

•• Bril V, Drużdż A, Grosskreutz J, Habib AA, Mantegazza R, Sacconi S, et al. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol. 2023;22:383–94. https://doi.org/10.1016/S1474-4422(23)00077-7. Landmark study that demonstrated the safety and efficacy of rozanolixizumab in AChR+ and MuSK+ gMG leading to its approval for both conditions.

Cleanthous S, Mork AC, Regnault A, Cano S, Kaminski HJ, Morel T. Development of the Myasthenia Gravis (MG) Symptoms PRO: a case study of a patient-centred outcome measure in rare disease. Orphanet J Rare Dis. 2021;16:457. https://doi.org/10.1186/s13023-021-02064-0.

Article  PubMed  PubMed Central  Google Scholar 

U.S. Food and Drug Administration [Internet]. Highlights of prescribing information; 2023 [cited 2023 October 31]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761286s000lbl.pdf

ClinicalTrials.gov [Internet] A study to investigate the long-term safety, tolerability, and efficacy of rozanolixizumab in adult patients with generalized myasthenia gravis; 2023 [cited 2023 October 31]. Available from: https://clinicaltrials-gov.geihsl.idm.oclc.org/study/NCT04124965?intr=Rozanolixizumab&rank=4.

ClinicalTrials.gov [Internet] A phase 3, open-label, crossover study to evaluate self-administration of rozanolixizumab by study participants with generalized myasthenia gravis (gMG); 2023 [cited 2023 October 31]. Available from: https://clinicaltrials.gov/study/NCT05681715?intr=Rozanolixizumab&rank=1

• Saccà F, Pane C, Espinosa PE, Sormani MP, Signori A. Efficacy of innovative therapies in myasthenia gravis: a systematic review, meta-analysis and network meta-analysis. Eur J Neurol. 2023;30:3854–67. https://doi.org/10.1111/ene.15872. Important meta-analysis of the efficacy of eculizumab, ravulizumab, efgartigimod, rozanolixizumab, zilucoplan, and rituximab in MG, which suggested a greater effect of FcRn blockers on the QMG score short-term.