Long-term safety and efficacy of eculizumab in generalized myasthenia gravis

Srikanth Muppidi; Kimiaki Utsugisawa; Michael Benatar; Hiroyuki Murai; Richard J. Barohn; Isabel Illa; Saiju Jacob; John Vissing; Ted M. Burns; John T. Kissel; Richard J. Nowak; Henning Andersen; Carlos Casasnovas; Jan L. de Bleecker; Tuan H. Vu; Renato Mantegazza; Fanny L. O'Brien; Jing Jing Wang; Kenji P. Fujita; James F. Howard; Claudio Gabriel Mazia; Miguel Wilken; Fabio Barroso; Juliet Saba; Marcelo Rugiero; Mariela Bettini; Marcelo Chaves; Gonzalo Vidal; Alejandra Dalila Garcia; Guy Van den Abeele; Kathy de Koning; Katrien De Mey; Rudy Mercelis; Délphine Mahieu; Linda Wagemaekers; Philip Van Damme; Annelies Depreitere; Caroline Schotte; Charlotte Smetcoren; Olivier Stevens; Sien Van Daele; Nicolas Vandenbussche; Annelies Vanhee; Sarah Verjans; Jan Vynckier; Ann D'Hondt; Petra Tilkin; Alzira Alves de Siqueira Carvalho; Igor Dias Brockhausen; David Feder; Daniel Ambrosio; Pamela César; Ana Paula Melo; Renata Martins Ribeiro; Rosana Rocha; Bruno Bezerra Rosa; Thabata Veiga; Luiz Augusto da Silva; Murilo Santos Engel; Jordana Gonçalves Geraldo; Maria da Penha Ananias Morita; Erica Nogueira Coelho; Gabriel Paiva; Marina Pozo; Natalia Prando; Debora Dada Martineli Torres; Cristiani Fernanda Butinhao; Gustavo Duran; Tamires Cristina Gomes da Silva; Luiz Otavio Maia Gonçalves; Lucas Eduardo Pazetto; Tomás Augusto Suriane Fialho; Luciana Renata Cubas Volpe; Luciana Souza Duca; Maurício André Gheller Friedrich; Alexandre Guerreiro; Henrique Mohr; Maurer Pereira Martins; Daiane da Cruz Pacheco; Luciana Ferreira; Ana Paula Macagnan; Graziela Pinto; Aline de Cassia Santos; Acary Souza Bulle Oliveira; Ana Carolina Amaral Andrade; Marcelo Annes; Liene Duarte Silva; Valeria Cavalcante Lino; Wladimir Pinto; Natália Assis; Fernanda Carrara; Carolina Miranda; Iandra Souza; Patricia Fernandes; Zaeem Siddiqi; Cecile Phan; Jeffrey Narayan; Derrick Blackmore; Ashley Mallon; Rikki Roderus

doi:https://doi.org/10.1002/mus.26447

Long-term safety and efficacy of eculizumab in generalized myasthenia gravis

Srikanth Muppidi, Kimiaki Utsugisawa, Michael Benatar, Hiroyuki Murai, Richard J. Barohn, Isabel Illa, Saiju Jacob, John Vissing, Ted M. Burns, John T. Kissel, Richard J. Nowak, Henning Andersen, Carlos Casasnovas, Jan L. de Bleecker, Tuan H. Vu, Renato Mantegazza, Fanny L. O'Brien, Jing Jing Wang, Kenji P. Fujita, James F. HowardClaudio Gabriel Mazia, Miguel Wilken, Fabio Barroso, Juliet Saba, Marcelo Rugiero, Mariela Bettini, Marcelo Chaves, Gonzalo Vidal, Alejandra Dalila Garcia, Guy Van den Abeele, Kathy de Koning, Katrien De Mey, Rudy Mercelis, Délphine Mahieu, Linda Wagemaekers, Philip Van Damme, Annelies Depreitere, Caroline Schotte, Charlotte Smetcoren, Olivier Stevens, Sien Van Daele, Nicolas Vandenbussche, Annelies Vanhee, Sarah Verjans, Jan Vynckier, Ann D'Hondt, Petra Tilkin, Alzira Alves de Siqueira Carvalho, Igor Dias Brockhausen, David Feder, Daniel Ambrosio, Pamela César, Ana Paula Melo, Renata Martins Ribeiro, Rosana Rocha, Bruno Bezerra Rosa, Thabata Veiga, Luiz Augusto da Silva, Murilo Santos Engel, Jordana Gonçalves Geraldo, Maria da Penha Ananias Morita, Erica Nogueira Coelho, Gabriel Paiva, Marina Pozo, Natalia Prando, Debora Dada Martineli Torres, Cristiani Fernanda Butinhao, Gustavo Duran, Tamires Cristina Gomes da Silva, Luiz Otavio Maia Gonçalves, Lucas Eduardo Pazetto, Tomás Augusto Suriane Fialho, Luciana Renata Cubas Volpe, Luciana Souza Duca, Maurício André Gheller Friedrich, Alexandre Guerreiro, Henrique Mohr, Maurer Pereira Martins, Daiane da Cruz Pacheco, Luciana Ferreira, Ana Paula Macagnan, Graziela Pinto, Aline de Cassia Santos, Acary Souza Bulle Oliveira, Ana Carolina Amaral Andrade, Marcelo Annes, Liene Duarte Silva, Valeria Cavalcante Lino, Wladimir Pinto, Natália Assis, Fernanda Carrara, Carolina Miranda, Iandra Souza, Patricia Fernandes, Zaeem Siddiqi, Cecile Phan, Jeffrey Narayan, Derrick Blackmore, Ashley Mallon, Rikki Roderus

Department of Medicine

Research output: Contribution to journal › Article › Research

113 Citations (Scopus)

Abstract

INTRODUCTION: Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy.

METHODS: Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients.

RESULTS: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001).

DISCUSSION: These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019.

Original language	English
Pages (from-to)	14-24
Number of pages	11
Journal	Muscle and Nerve
Volume	60
Issue number	1
DOIs	https://doi.org/10.1002/mus.26447
Publication status	Published - 1 Jul 2019

Keywords

MG-ADL
MG-QOL15
MGC
QMG
eculizumab
myasthenia gravis
Humans
Middle Aged
Male
Meningococcal Vaccines/therapeutic use
Angioedema/chemically induced
Activities of Daily Living
Adult
Female
Muscle Strength
Aspergillosis/epidemiology
Antibodies, Monoclonal, Humanized/therapeutic use
Treatment Outcome
Myasthenia Gravis/drug therapy
Injection Site Reaction/epidemiology
Disease Progression
Complement Inactivating Agents/therapeutic use
Heart Diseases/chemically induced
Meningococcal Infections/epidemiology
Quality of Life
Longitudinal Studies

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://doi.org/10.1002/mus.26447

https://ddd.uab.cat/record/226347

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Muppidi, S., Utsugisawa, K., Benatar, M., Murai, H., Barohn, R. J., Illa, I., Jacob, S., Vissing, J., Burns, T. M., Kissel, J. T., Nowak, R. J., Andersen, H., Casasnovas, C., de Bleecker, J. L., Vu, T. H., Mantegazza, R., O'Brien, F. L., Wang, J. J., Fujita, K. P., ... Roderus, R. (2019). Long-term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle and Nerve, 60(1), 14-24. https://doi.org/10.1002/mus.26447

@article{28e8971325c6410a9bfa1619020411ee,

title = "Long-term safety and efficacy of eculizumab in generalized myasthenia gravis",

abstract = "INTRODUCTION: Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy.METHODS: Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients.RESULTS: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001).DISCUSSION: These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019.",

keywords = "MG-ADL, MG-QOL15, MGC, QMG, eculizumab, myasthenia gravis, Humans, Middle Aged, Male, Meningococcal Vaccines/therapeutic use, Angioedema/chemically induced, Activities of Daily Living, Adult, Female, Muscle Strength, Aspergillosis/epidemiology, Antibodies, Monoclonal, Humanized/therapeutic use, Treatment Outcome, Myasthenia Gravis/drug therapy, Injection Site Reaction/epidemiology, Disease Progression, Complement Inactivating Agents/therapeutic use, Heart Diseases/chemically induced, Meningococcal Infections/epidemiology, Quality of Life, Longitudinal Studies",

author = "Srikanth Muppidi and Kimiaki Utsugisawa and Michael Benatar and Hiroyuki Murai and Barohn, {Richard J.} and Isabel Illa and Saiju Jacob and John Vissing and Burns, {Ted M.} and Kissel, {John T.} and Nowak, {Richard J.} and Henning Andersen and Carlos Casasnovas and {de Bleecker}, {Jan L.} and Vu, {Tuan H.} and Renato Mantegazza and O'Brien, {Fanny L.} and Wang, {Jing Jing} and Fujita, {Kenji P.} and Howard, {James F.} and Mazia, {Claudio Gabriel} and Miguel Wilken and Fabio Barroso and Juliet Saba and Marcelo Rugiero and Mariela Bettini and Marcelo Chaves and Gonzalo Vidal and Garcia, {Alejandra Dalila} and {Van den Abeele}, Guy and {de Koning}, Kathy and {De Mey}, Katrien and Rudy Mercelis and D{\'e}lphine Mahieu and Linda Wagemaekers and {Van Damme}, Philip and Annelies Depreitere and Caroline Schotte and Charlotte Smetcoren and Olivier Stevens and {Van Daele}, Sien and Nicolas Vandenbussche and Annelies Vanhee and Sarah Verjans and Jan Vynckier and Ann D'Hondt and Petra Tilkin and {Alves de Siqueira Carvalho}, Alzira and {Dias Brockhausen}, Igor and David Feder and Daniel Ambrosio and Pamela C{\'e}sar and Melo, {Ana Paula} and {Martins Ribeiro}, Renata and Rosana Rocha and {Bezerra Rosa}, Bruno and Thabata Veiga and {da Silva}, {Luiz Augusto} and {Santos Engel}, Murilo and {Gon{\c c}alves Geraldo}, Jordana and {Ananias Morita}, {Maria da Penha} and {Nogueira Coelho}, Erica and Gabriel Paiva and Marina Pozo and Natalia Prando and {Martineli Torres}, {Debora Dada} and Butinhao, {Cristiani Fernanda} and Gustavo Duran and {Gomes da Silva}, {Tamires Cristina} and {Otavio Maia Gon{\c c}alves}, Luiz and Pazetto, {Lucas Eduardo} and Fialho, {Tom{\'a}s Augusto Suriane} and {Renata Cubas Volpe}, Luciana and {Souza Duca}, Luciana and {Gheller Friedrich}, {Maur{\'i}cio Andr{\'e}} and Alexandre Guerreiro and Henrique Mohr and {Pereira Martins}, Maurer and {da Cruz Pacheco}, Daiane and Luciana Ferreira and Macagnan, {Ana Paula} and Graziela Pinto and {de Cassia Santos}, Aline and {Souza Bulle Oliveira}, Acary and {Amaral Andrade}, {Ana Carolina} and Marcelo Annes and {Duarte Silva}, Liene and {Cavalcante Lino}, Valeria and Wladimir Pinto and Nat{\'a}lia Assis and Fernanda Carrara and Carolina Miranda and Iandra Souza and Patricia Fernandes and Zaeem Siddiqi and Cecile Phan and Jeffrey Narayan and Derrick Blackmore and Ashley Mallon and Rikki Roderus",

note = "{\textcopyright} 2019 The Authors. Muscle & Nerve published by Wiley Periodicals, Inc.",

year = "2019",

month = jul,

day = "1",

doi = "https://doi.org/10.1002/mus.26447",

language = "English",

volume = "60",

pages = "14--24",

journal = "Muscle and Nerve",

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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, Mazia, CG, Wilken, M, Barroso, F, Saba, J, Rugiero, M, Bettini, M, Chaves, M, Vidal, G, Garcia, AD, Van den Abeele, G, de Koning, K, De Mey, K, Mercelis, R, Mahieu, D, Wagemaekers, L, Van Damme, P, Depreitere, A, Schotte, C, Smetcoren, C, Stevens, O, Van Daele, S, Vandenbussche, N, Vanhee, A, Verjans, S, Vynckier, J, D'Hondt, A, Tilkin, P, Alves de Siqueira Carvalho, A, Dias Brockhausen, I, Feder, D, Ambrosio, D, César, P, Melo, AP, Martins Ribeiro, R, Rocha, R, Bezerra Rosa, B, Veiga, T, da Silva, LA, Santos Engel, M, Gonçalves Geraldo, J, Ananias Morita, MDP, Nogueira Coelho, E, Paiva, G, Pozo, M, Prando, N, Martineli Torres, DD, Butinhao, CF, Duran, G, Gomes da Silva, TC, Otavio Maia Gonçalves, L, Pazetto, LE, Fialho, TAS, Renata Cubas Volpe, L, Souza Duca, L, Gheller Friedrich, MA, Guerreiro, A, Mohr, H, Pereira Martins, M, da Cruz Pacheco, D, Ferreira, L, Macagnan, AP, Pinto, G, de Cassia Santos, A, Souza Bulle Oliveira, A, Amaral Andrade, AC, Annes, M, Duarte Silva, L, Cavalcante Lino, V, Pinto, W, Assis, N, Carrara, F, Miranda, C, Souza, I, Fernandes, P, Siddiqi, Z, Phan, C, Narayan, J, Blackmore, D, Mallon, A & Roderus, R 2019, 'Long-term safety and efficacy of eculizumab in generalized myasthenia gravis', Muscle and Nerve, vol. 60, no. 1, pp. 14-24. https://doi.org/10.1002/mus.26447

TY - JOUR

T1 - Long-term safety and efficacy of eculizumab in generalized myasthenia gravis

AU - Muppidi, Srikanth

AU - Utsugisawa, Kimiaki

AU - Benatar, Michael

AU - Murai, Hiroyuki

AU - Barohn, Richard J.

AU - Illa, Isabel

AU - Jacob, Saiju

AU - Vissing, John

AU - Burns, Ted M.

AU - Kissel, John T.

AU - Nowak, Richard J.

AU - Andersen, Henning

AU - Casasnovas, Carlos

AU - de Bleecker, Jan L.

AU - Vu, Tuan H.

AU - Mantegazza, Renato

AU - O'Brien, Fanny L.

AU - Wang, Jing Jing

AU - Fujita, Kenji P.

AU - Howard, James F.

AU - Mazia, Claudio Gabriel

AU - Wilken, Miguel

AU - Barroso, Fabio

AU - Saba, Juliet

AU - Rugiero, Marcelo

AU - Bettini, Mariela

AU - Chaves, Marcelo

AU - Vidal, Gonzalo

AU - Garcia, Alejandra Dalila

AU - Van den Abeele, Guy

AU - de Koning, Kathy

AU - De Mey, Katrien

AU - Mercelis, Rudy

AU - Mahieu, Délphine

AU - Wagemaekers, Linda

AU - Van Damme, Philip

AU - Depreitere, Annelies

AU - Schotte, Caroline

AU - Smetcoren, Charlotte

AU - Stevens, Olivier

AU - Van Daele, Sien

AU - Vandenbussche, Nicolas

AU - Vanhee, Annelies

AU - Verjans, Sarah

AU - Vynckier, Jan

AU - D'Hondt, Ann

AU - Tilkin, Petra

AU - Alves de Siqueira Carvalho, Alzira

AU - Dias Brockhausen, Igor

AU - Feder, David

AU - Ambrosio, Daniel

AU - César, Pamela

AU - Melo, Ana Paula

AU - Martins Ribeiro, Renata

AU - Rocha, Rosana

AU - Bezerra Rosa, Bruno

AU - Veiga, Thabata

AU - da Silva, Luiz Augusto

AU - Santos Engel, Murilo

AU - Gonçalves Geraldo, Jordana

AU - Ananias Morita, Maria da Penha

AU - Nogueira Coelho, Erica

AU - Paiva, Gabriel

AU - Pozo, Marina

AU - Prando, Natalia

AU - Martineli Torres, Debora Dada

AU - Butinhao, Cristiani Fernanda

AU - Duran, Gustavo

AU - Gomes da Silva, Tamires Cristina

AU - Otavio Maia Gonçalves, Luiz

AU - Pazetto, Lucas Eduardo

AU - Fialho, Tomás Augusto Suriane

AU - Renata Cubas Volpe, Luciana

AU - Souza Duca, Luciana

AU - Gheller Friedrich, Maurício André

AU - Guerreiro, Alexandre

AU - Mohr, Henrique

AU - Pereira Martins, Maurer

AU - da Cruz Pacheco, Daiane

AU - Ferreira, Luciana

AU - Macagnan, Ana Paula

AU - Pinto, Graziela

AU - de Cassia Santos, Aline

AU - Souza Bulle Oliveira, Acary

AU - Amaral Andrade, Ana Carolina

AU - Annes, Marcelo

AU - Duarte Silva, Liene

AU - Cavalcante Lino, Valeria

AU - Pinto, Wladimir

AU - Assis, Natália

AU - Carrara, Fernanda

AU - Miranda, Carolina

AU - Souza, Iandra

AU - Fernandes, Patricia

AU - Siddiqi, Zaeem

AU - Phan, Cecile

AU - Narayan, Jeffrey

AU - Blackmore, Derrick

AU - Mallon, Ashley

AU - Roderus, Rikki

PY - 2019/7/1

Y1 - 2019/7/1

N2 - INTRODUCTION: Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy.METHODS: Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients.RESULTS: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001).DISCUSSION: These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019.

AB - INTRODUCTION: Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN, evaluating eculizumab's long-term safety and efficacy.METHODS: Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients.RESULTS: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN (P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (P < 0.0001).DISCUSSION: These findings provide evidence for the long-term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019.

KW - MG-ADL

KW - MG-QOL15

KW - MGC

KW - QMG

KW - eculizumab

KW - myasthenia gravis

KW - Humans

KW - Middle Aged

KW - Male

KW - Meningococcal Vaccines/therapeutic use

KW - Angioedema/chemically induced

KW - Activities of Daily Living

KW - Adult

KW - Female

KW - Muscle Strength

KW - Aspergillosis/epidemiology

KW - Antibodies, Monoclonal, Humanized/therapeutic use

KW - Treatment Outcome

KW - Myasthenia Gravis/drug therapy

KW - Injection Site Reaction/epidemiology

KW - Disease Progression

KW - Complement Inactivating Agents/therapeutic use

KW - Heart Diseases/chemically induced

KW - Meningococcal Infections/epidemiology

KW - Quality of Life

KW - Longitudinal Studies

UR - http://www.mendeley.com/research/longterm-safety-efficacy-eculizumab-generalized-myasthenia-gravis

U2 - https://doi.org/10.1002/mus.26447

DO - https://doi.org/10.1002/mus.26447

M3 - Article

C2 - 30767274

SN - 0148-639X

VL - 60

SP - 14

EP - 24

JO - Muscle and Nerve

JF - Muscle and Nerve

IS - 1

ER -

Long-term safety and efficacy of eculizumab in generalized myasthenia gravis

Abstract

Keywords

UN SDGs

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