United States clinical practice experience with eculizumab in myasthenia gravis: symptoms, function, and immunosuppressant therapy use.
Activities of daily living
C5
Chart review
Clinical practice
Complement inhibition
Corticosteroid
Eculizumab
Immunosuppression
Myasthenia gravis
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
25 Jul 2024
25 Jul 2024
Historique:
received:
27
02
2024
accepted:
05
07
2024
revised:
28
06
2024
medline:
26
7
2024
pubmed:
26
7
2024
entrez:
25
7
2024
Statut:
aheadofprint
Résumé
The phase 3 REGAIN study and its open-label extension demonstrated the efficacy of the complement C5 inhibitor eculizumab in patients with treatment-refractory, acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG). The aim of the ELEVATE study was to assess the effectiveness of eculizumab in clinical practice in adults with MG in the United States. A retrospective chart review was conducted in adults with MG who initiated eculizumab treatment between October 23, 2017 and December 31, 2019. Outcomes assessed before and during eculizumab treatment using a pre- versus post-treatment study design included Myasthenia Gravis-Activities of Daily Living (MG-ADL) total scores; minimal symptom expression (MSE); physician impression of clinical change; minimal manifestation status (MMS); and concomitant medication use. In total, 119 patients were included in the study. A significant reduction was observed in mean MG-ADL total score, from 8.0 before eculizumab initiation to 5.4 at 3 months and to 4.7 at 24 months after eculizumab initiation (both p < 0.001). At 24 months after eculizumab initiation, MSE was achieved by 19% of patients. MMS or better was achieved by 30% of patients at 24 months. Additionally, 64% of patients receiving prednisone at eculizumab initiation had their prednisone dosage reduced during eculizumab treatment and 13% discontinued prednisone; 32% were able to discontinue nonsteroidal immunosuppressant therapy. Eculizumab treatment was associated with sustained improvements in MG-ADL total scores through 24 months in adults with MG. Prednisone dosage was reduced in approximately two-thirds of patients, suggesting a steroid-sparing effect for eculizumab.
Sections du résumé
BACKGROUND/OBJECTIVES
OBJECTIVE
The phase 3 REGAIN study and its open-label extension demonstrated the efficacy of the complement C5 inhibitor eculizumab in patients with treatment-refractory, acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG). The aim of the ELEVATE study was to assess the effectiveness of eculizumab in clinical practice in adults with MG in the United States.
METHODS
METHODS
A retrospective chart review was conducted in adults with MG who initiated eculizumab treatment between October 23, 2017 and December 31, 2019. Outcomes assessed before and during eculizumab treatment using a pre- versus post-treatment study design included Myasthenia Gravis-Activities of Daily Living (MG-ADL) total scores; minimal symptom expression (MSE); physician impression of clinical change; minimal manifestation status (MMS); and concomitant medication use.
RESULTS
RESULTS
In total, 119 patients were included in the study. A significant reduction was observed in mean MG-ADL total score, from 8.0 before eculizumab initiation to 5.4 at 3 months and to 4.7 at 24 months after eculizumab initiation (both p < 0.001). At 24 months after eculizumab initiation, MSE was achieved by 19% of patients. MMS or better was achieved by 30% of patients at 24 months. Additionally, 64% of patients receiving prednisone at eculizumab initiation had their prednisone dosage reduced during eculizumab treatment and 13% discontinued prednisone; 32% were able to discontinue nonsteroidal immunosuppressant therapy.
DISCUSSION
CONCLUSIONS
Eculizumab treatment was associated with sustained improvements in MG-ADL total scores through 24 months in adults with MG. Prednisone dosage was reduced in approximately two-thirds of patients, suggesting a steroid-sparing effect for eculizumab.
Identifiants
pubmed: 39052039
doi: 10.1007/s00415-024-12569-w
pii: 10.1007/s00415-024-12569-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
Références
Dresser L, Wlodarski R, Rezania K, Soliven B (2021) Myasthenia gravis: epidemiology, pathophysiology and clinical manifestations. J Clin Med 10:2235. https://doi.org/10.3390/jcm10112235
doi: 10.3390/jcm10112235
pubmed: 34064035
pmcid: 8196750
Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM, Verschuuren J (2019) Myasthenia gravis. Nat Rev Dis Primers 5:30. https://doi.org/10.1038/s41572-019-0079-y
doi: 10.1038/s41572-019-0079-y
pubmed: 31048702
Howard JF Jr (2018) Myasthenia gravis: the role of complement at the neuromuscular junction. Ann N Y Acad Sci 1412:113–128. https://doi.org/10.1111/nyas.13522
doi: 10.1111/nyas.13522
pubmed: 29266249
Melzer N, Ruck T, Fuhr P, Gold R, Hohlfeld R, Marx A, Melms A, Tackenberg B, Schalke B, Schneider-Gold C, Zimprich F, Meuth SG, Wiendl H (2016) Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the Guidelines of the German Neurological Society. J Neurol 263:1473–1494. https://doi.org/10.1007/s00415-016-8045-z
doi: 10.1007/s00415-016-8045-z
pubmed: 26886206
pmcid: 4971048
Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, Kuntz N, Massey JM, Melms A, Murai H, Nicolle M, Palace J, Richman DP, Verschuuren J, Narayanaswami P (2016) International consensus guidance for management of myasthenia gravis: executive summary. Neurology 87:419–425. https://doi.org/10.1212/wnl.0000000000002790
doi: 10.1212/wnl.0000000000002790
pubmed: 27358333
pmcid: 4977114
Narayanaswami P, Sanders DB, Wolfe G, Benatar M, Cea G, Evoli A, Gilhus NE, Illa I, Kuntz NL, Massey J, Melms A, Murai H, Nicolle M, Palace J, Richman D, Verschuuren J (2021) International consensus guidance for management of myasthenia gravis: 2020 update. Neurology 96:114–122. https://doi.org/10.1212/WNL.0000000000011124
doi: 10.1212/WNL.0000000000011124
pubmed: 33144515
pmcid: 7884987
Farmakidis C, Pasnoor M, Dimachkie MM, Barohn RJ (2018) Treatment of myasthenia gravis. Neurol Clin 36:311–337. https://doi.org/10.1016/j.ncl.2018.01.011
doi: 10.1016/j.ncl.2018.01.011
pubmed: 29655452
pmcid: 6690491
Johnson S, Katyal N, Narula N, Govindarajan R (2021) Adverse side effects associated with corticosteroid therapy: a study in 39 patients with generalized myasthenia gravis. Med Sci Monit 27:e933296. https://doi.org/10.12659/MSM.933296
doi: 10.12659/MSM.933296
pubmed: 34707081
pmcid: 8562011
Sharshar T, Porcher R, Demeret S, Tranchant C, Gueguen A, Eymard B, Nadaj-Pakleza A, Spinazzi M, Grimaldi L, Birnbaum S, Friedman D, Clair B (2021) Comparison of corticosteroid tapering regimens in myasthenia gravis: a randomized clinical trial. JAMA Neurol 78:426–433. https://doi.org/10.1001/jamaneurol.2020.5407
doi: 10.1001/jamaneurol.2020.5407
pubmed: 33555314
pmcid: 7871208
Murai H (2015) Japanese clinical guidelines for myasthenia gravis: putting into practice. Clin Exp Neuroimmunol 6:21–31. https://doi.org/10.1111/cen3.12180
doi: 10.1111/cen3.12180
Wiendl H, Meisel A (2022) Diagnostik und Therapie myasthener Syndrome, S2k-Leitlinie. Leitlinien für Diagnostik und Therapie in der Neurologie. https://www.awmf.org/service/awmf-aktuell/diagnostik-und-therapie-myasthener-syndrome
Jaretzki A, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, Sanders DB (2000) Myasthenia gravis: recommendations for clinical research standards. Task force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Ann Thorac Surg 70:327–334. https://doi.org/10.1016/s0003-4975(00)01595-2
doi: 10.1016/s0003-4975(00)01595-2
pubmed: 10921745
Vissing J, Jacob S, Fujita KP, O’Brien F, Howard JF (2020) ‘Minimal symptom expression’ in patients with acetylcholine receptor antibody–positive refractory generalized myasthenia gravis treated with eculizumab. J Neurol 267:1991–2001. https://doi.org/10.1007/s00415-020-09770-y
doi: 10.1007/s00415-020-09770-y
pubmed: 32189108
pmcid: 7320935
Rollins SA, Sims PJ (1990) The complement-inhibitory activity of CD59 resides in its capacity to block incorporation of C9 into membrane C5b–9. J Immunol 144:3478–3483
doi: 10.4049/jimmunol.144.9.3478
pubmed: 1691760
Thomas TC, Rollins SA, Rother RP, Giannoni MA, Hartman SL, Elliott EA, Nye SH, Matis LA, Squinto SP, Evans MJ (1996) Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv. Mol Immunol 33:1389–1401. https://doi.org/10.1016/s0161-5890(96)00078-8
doi: 10.1016/s0161-5890(96)00078-8
pubmed: 9171898
Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L (2007) Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol 25:1256–1264. https://doi.org/10.1038/nbt1344
doi: 10.1038/nbt1344
pubmed: 17989688
Howard JF Jr, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, Jacob S, Vissing J, Burns TM, Kissel JT, Muppidi S, Nowak RJ, O’Brien F, Wang JJ, Mantegazza R, REGAIN Study Group (2017) 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 16:976–986. https://doi.org/10.1016/s1474-4422(17)30369-1
doi: 10.1016/s1474-4422(17)30369-1
pubmed: 29066163
Muppidi S, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, Jacob S, Vissing J, Burns TM, Kissel JT, Nowak RJ, Andersen H, Casasnovas C, de Bleecker JL, Vu TH, Mantegazza R, O’Brien FL, Wang JJ, Fujita KP, Howard JF Jr, Regain Study Group (2019) Long-term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle Nerve 60:14–24. https://doi.org/10.1002/mus.26447
doi: 10.1002/mus.26447
pubmed: 30767274
pmcid: 6619057
Alexion Pharmaceuticals Inc. (2024) Soliris prescribing information. https://alexion.com/Documents/Soliris_USPI.pdf . Accessed 24 Apr 2024
Muppidi S (2012) The myasthenia gravis-specific activities of daily living profile. Ann N Y Acad Sci 1274:114–119. https://doi.org/10.1111/j.1749-6632.2012.06817.x
doi: 10.1111/j.1749-6632.2012.06817.x
pubmed: 23252905
Dodig D, Genge A, Selchen D, Freedman MS (2023) Complement inhibition in myasthenia gravis and neuromyelitis optica spectrum disorder. Can J Neurol Sci 50:165–173. https://doi.org/10.1017/cjn.2021.508
doi: 10.1017/cjn.2021.508
pubmed: 34895385
Kang SA, Sweeney M, Govindarajan R (2022) Academic and employment status in patients with generalized myasthenia gravis treated with eculizumab: a case series. J Clin Neuromuscul Dis 23:210–218. https://doi.org/10.1097/CND.0000000000000391
doi: 10.1097/CND.0000000000000391
pubmed: 35608645
pmcid: 9126260
Levine TD (2019) Safety of an abbreviated transition period when switching from intravenous immunoglobulin to eculizumab in patients with treatment-refractory myasthenia gravis: a case series. Am J Case Rep 20:965–970. https://doi.org/10.12659/AJCR.916424
doi: 10.12659/AJCR.916424
pubmed: 31278249
pmcid: 6628751
Oyama M, Okada K, Masuda M, Shimizu Y, Yokoyama K, Uzawa A, Kawaguchi N, Ikeguchi R, Hoshino Y, Hatano T, Ozawa Y, Nakahara J, Aizawa H, Kitagawa K, Hattori N, Kuwabara S, Murai H, Suzuki S (2020) Suitable indications of eculizumab for patients with refractory generalized myasthenia gravis. Ther Adv Neurol Disord 13:1756286420904207. https://doi.org/10.1177/1756286420904207
doi: 10.1177/1756286420904207
pubmed: 32215054
pmcid: 7081459
Suh J, Clarke V, Amato AA, Guidon AC (2022) Safety and outcomes of eculizumab for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice. Muscle Nerve 66:348–353. https://doi.org/10.1002/mus.27656
doi: 10.1002/mus.27656
pubmed: 35684980
Murai H, Suzuki S, Fukamizu Y, Osawa T, Kikui H, Utsugisawa K (2022) Safety and effectiveness of eculizumab in Japanese patients with generalized myasthenia gravis: analysis of 1-year postmarketing surveillance. Clin Exp Neuroimmunol 13:280–289. https://doi.org/10.1111/cen3.12716
doi: 10.1111/cen3.12716
Murai H, Suzuki S, Hasebe M, Fukamizu Y, Rodrigues E, Utsugisawa K (2021) Safety and effectiveness of eculizumab in Japanese patients with generalized myasthenia gravis: interim analysis of post-marketing surveillance. Ther Adv Neurol Disord 14:17562864211001996. https://doi.org/10.1177/17562864211001995
doi: 10.1177/17562864211001995
pubmed: 33796147
pmcid: 7970258
Greene E, Cutter G, Muppidi S, Juel V, Rodrigues E, Korideck H, Howard JF Jr (2023) Myasthenia gravis activities of daily living (MG-ADL) response to eculizumab treatment in patients from the generalized myasthenia gravis registry (P1-5.020). Neurology 100:2071. https://doi.org/10.1212/wnl.0000000000202295
doi: 10.1212/wnl.0000000000202295
Muppidi S, Wolfe GI, Conaway M, Burns TM (2011) MG-ADL: still a relevant outcome measure. Muscle Nerve 44:727–731. https://doi.org/10.1002/mus.22140
doi: 10.1002/mus.22140
pubmed: 22006686
Mantegazza R, Wolfe GI, Muppidi S, Wiendl H, Fujita KP, O’Brien FL, Booth HDE, Howard JF Jr, REGAIN Study Group (2021) Post-intervention status in patients with refractory myasthenia gravis treated with eculizumab during REGAIN and its open-label extension. Neurology 96:e610–e618. https://doi.org/10.1212/WNL.0000000000011207
doi: 10.1212/WNL.0000000000011207
pubmed: 33229455
pmcid: 7905790
Pulley M, Macwan S, Nowak R, Mozaffar T, Rodrigues E, Korideck H, Werneburg B, Narayanaswami P (2023) Change in concomitant therapies for generalized myasthenia gravis in patients receiving eculizumab: a retrospective analysis of registry data (P1-5.002). Neurology 100:2183. https://doi.org/10.1212/wnl.0000000000202372
doi: 10.1212/wnl.0000000000202372
Nowak RJ, Muppidi S, Beydoun SR, O’Brien FL, Yountz M, Howard JF Jr (2020) Concomitant immunosuppressive therapy use in eculizumab-treated adults with generalized myasthenia gravis during the REGAIN open-label extension study. Front Neurol 11:556104. https://doi.org/10.3389/fneur.2020.556104
doi: 10.3389/fneur.2020.556104
pubmed: 33329303
pmcid: 7732596
Lascano AM, Lalive PH (2021) Update in immunosuppressive therapy of myasthenia gravis. Autoimmun Rev 20:102712. https://doi.org/10.1016/j.autrev.2020.102712
doi: 10.1016/j.autrev.2020.102712
pubmed: 33197578
Menon D, Barnett C, Bril V (2020) Novel treatments in myasthenia gravis. Front Neurol 11:538. https://doi.org/10.3389/fneur.2020.00538
doi: 10.3389/fneur.2020.00538
pubmed: 32714266
pmcid: 7344308
US Census Bureau (2022) Population estimates: quick facts. https://www.census.gov/quickfacts/ . Accessed 25 July 2023
Vu T, Meisel A, Mantegazza R, Annane D, Katsuno M, Aguzzi R, Enayetallah A, Beasley KN, Rampal N, Howard JF Jr (2022) The terminal complement inhibitor ravulizumab in anti-acetylcholine receptor antibody–positive generalized myasthenia gravis. NEJM Evid 1:EVIDoa2100066. https://doi.org/10.1056/EVIDoa2100066
Meisel A, Annane D, Vu T, Mantegazza R, Katsuno M, Aguzzi R, Frick G, Gault L, Howard JF Jr (2023) 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 270:3862–3875. https://doi.org/10.1007/s00415-023-11699-x
doi: 10.1007/s00415-023-11699-x
pubmed: 37103755
pmcid: 10134722
Nishimura JI, Kawaguchi T, Ito S, Murai H, Shimono A, Matsuda T, Fukamizu Y, Akiyama H, Hayashi H, Nakano T, Maruyama S (2023) Real-world safety profile of eculizumab in patients with paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, or generalized myasthenia gravis: an integrated analysis of post-marketing surveillance in Japan. Int J Hematol 118:419–431. https://doi.org/10.1007/s12185-023-03630-x
doi: 10.1007/s12185-023-03630-x
pubmed: 37515657
Meisel A, Saccà F, Spillane J, Vissing J (2024) Expert consensus recommendations for improving and standardising the assessment of patients with generalised myasthenia gravis. Eur J Neurol 31:e16280. https://doi.org/10.1111/ene.16280
doi: 10.1111/ene.16280
pubmed: 38523419
Barnett C, Herbelin L, Dimachkie MM, Barohn RJ (2018) Measuring clinical treatment response in myasthenia gravis. Neurol Clin 36:339–353. https://doi.org/10.1016/j.ncl.2018.01.006
doi: 10.1016/j.ncl.2018.01.006
pubmed: 29655453
pmcid: 6697147