‘Minimal symptom expression’ in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab

John Vissing; Saiju Jacob; Kenji P. Fujita; Fanny O’Brien; James F. Howard; The REGAIN Study Group; Claudio Gabriel Mazia; Miguel Wilken; Fabio Barroso; Juliet Saba; Marcelo Rugiero; Mariela Bettini; Marcelo Chaves; Gonzalo Vidal; Alejandra Dalila Garcia; Jan De Bleecker; 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’Hont; 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; Henning Andersen; Thomas Harbo; Lotte Vinge; Susanne  Krogh; Anita  Mogensen; John Vissing; Joan Højgaard; Nanna Witting; Anne Mette Ostergaard  Autzen; Jane Pedersen; Michael Weiss

doi:10.1007/s00415-020-09770-y

‘Minimal symptom expression’ in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab

John Vissing, Saiju Jacob, Kenji P. Fujita, Fanny O’Brien, James F. Howard, The REGAIN Study Group, Claudio Gabriel Mazia, Miguel Wilken, Fabio Barroso, Juliet Saba, Marcelo Rugiero, Mariela Bettini, Marcelo Chaves, Gonzalo Vidal, Alejandra Dalila Garcia, Jan De Bleecker, Guy Van den Abeele, Kathy de Koning, Katrien De Mey, Rudy MercelisDélphine 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’Hont, 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, Henning Andersen, Thomas Harbo, Lotte Vinge, Susanne Krogh, Anita Mogensen, John Vissing, Joan Højgaard, Nanna Witting, Anne Mette Ostergaard Autzen, Jane Pedersen, Michael Weiss

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

Background: The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension. Methods: Attainment of ‘minimal symptom expression’ was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. ‘Minimal symptom expression’ was defined as MG-ADL total score of 0–1 or MG-QOL15 total score of 0–3. Results: At REGAIN week 26, more eculizumab-treated patients achieved ‘minimal symptom expression’ versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension, the proportion of patients in the placebo/eculizumab group who achieved ‘minimal symptom expression’ increased after initiating eculizumab treatment and was sustained through 130 weeks of open-label eculizumab (MG-ADL: 1.7 to 27.8%; MG-QOL15: 1.7 to 19.4%). At extension study week 130, similar proportions of patients in the eculizumab/eculizumab and placebo/eculizumab groups achieved ‘minimal symptom expression’ (MG-ADL: 22.9% and 27.8%, respectively, p = 0.7861; MG-QOL15: 14.3% and 19.4%, respectively, p = 0.7531). The long-term tolerability of eculizumab was consistent with previous reports. Conclusions: Patients with AChR+ refractory gMG who receive eculizumab can achieve sustained ‘minimal symptom expression’ based on patient-reported outcomes. ‘Minimal symptom expression’ may be a useful tool in measuring therapy effectiveness in gMG. Trial registration: ClinicalTrials.gov NCT01997229, NCT02301624.

Originalsprog	Engelsk
Tidsskrift	Journal of Neurology
Vol/bind	267
Sider (fra-til)	1991-2001
ISSN	0340-5354
DOI	https://doi.org/10.1007/s00415-020-09770-y
Status	Udgivet - 2020

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10.1007/s00415-020-09770-yLicens: CC BY

‘Minimal symptom expression’ in patients with acetylcholine receptor antibody‑positive refractory generalized myasthenia gravis treated with eculizumabForlagets udgivne version, 640 KBLicens: CC BY

Citationsformater

Vissing, J., Jacob, S., Fujita, K. P., O’Brien, F., Howard, J. F., The REGAIN Study Group, Mazia, C. G., Wilken, M., Barroso, F., Saba, J., Rugiero, M., Bettini, M., Chaves, M., Vidal, G., Garcia, A. D., De Bleecker, J., Van den Abeele, G., de Koning, K., De Mey, K., ... Weiss, M. (2020). ‘Minimal symptom expression’ in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab. Journal of Neurology, 267, 1991-2001. https://doi.org/10.1007/s00415-020-09770-y

Vissing, J, Jacob, S, Fujita, KP, O’Brien, F, Howard, JF, The REGAIN Study Group, Mazia, CG, Wilken, M, Barroso, F, Saba, J, Rugiero, M, Bettini, M, Chaves, M, Vidal, G, Garcia, AD, De Bleecker, J, 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’Hont, A, Tilkin, P, Alves de Siqueira Carvalho, A, Dias Brockhausen, I, Feder, D, Ambrosio, D, César, P, Melo, AP, Martins Ribeiro, R, Rocha, R, Rosa, BB, Veiga, T, da Silva, LA, Andersen, H, Harbo, T, Vinge, L, Krogh, S, Mogensen, A, Vissing, J, Højgaard, J, Witting, N, Autzen, AMO, Pedersen, J & Weiss, M 2020, '‘Minimal symptom expression’ in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab', Journal of Neurology, bind 267, s. 1991-2001. https://doi.org/10.1007/s00415-020-09770-y

@article{cb2f85d98ac349d694c24ddfedefc8ff,

title = "{\textquoteleft}Minimal symptom expression{\textquoteright} in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab",

abstract = "Background: The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension. Methods: Attainment of {\textquoteleft}minimal symptom expression{\textquoteright} was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. {\textquoteleft}Minimal symptom expression{\textquoteright} was defined as MG-ADL total score of 0–1 or MG-QOL15 total score of 0–3. Results: At REGAIN week 26, more eculizumab-treated patients achieved {\textquoteleft}minimal symptom expression{\textquoteright} versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension, the proportion of patients in the placebo/eculizumab group who achieved {\textquoteleft}minimal symptom expression{\textquoteright} increased after initiating eculizumab treatment and was sustained through 130 weeks of open-label eculizumab (MG-ADL: 1.7 to 27.8%; MG-QOL15: 1.7 to 19.4%). At extension study week 130, similar proportions of patients in the eculizumab/eculizumab and placebo/eculizumab groups achieved {\textquoteleft}minimal symptom expression{\textquoteright} (MG-ADL: 22.9% and 27.8%, respectively, p = 0.7861; MG-QOL15: 14.3% and 19.4%, respectively, p = 0.7531). The long-term tolerability of eculizumab was consistent with previous reports. Conclusions: Patients with AChR+ refractory gMG who receive eculizumab can achieve sustained {\textquoteleft}minimal symptom expression{\textquoteright} based on patient-reported outcomes. {\textquoteleft}Minimal symptom expression{\textquoteright} may be a useful tool in measuring therapy effectiveness in gMG. Trial registration: ClinicalTrials.gov NCT01997229, NCT02301624.",

keywords = "Acetylcholine receptor, Eculizumab, Minimal symptom expression, Myasthenia gravis, Refractory",

author = "John Vissing and Saiju Jacob and Fujita, {Kenji P.} and Fanny O{\textquoteright}Brien and Howard, {James F.} and {The REGAIN Study Group} 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 Jan De Bleecker and {Van den Abeele}, Guy and Kathy de Koning and Katrien De Mey and Rudy Mercelis and D{\'e}lphine Mahieu and Linda Wagemaekers and Philip Van Damme and Annelies Depreitere and Caroline Schotte and Charlotte Smetcoren and Olivier Stevens and Sien Van Daele and Nicolas Vandenbussche and Annelies Vanhee and Sarah Verjans and Jan Vynckier and Ann D{\textquoteright}Hont and Petra Tilkin and {Alves de Siqueira Carvalho}, Alzira and Igor Dias Brockhausen and David Feder and Daniel Ambrosio and Pamela C{\'e}sar and Melo, {Ana Paula} and Renata Martins Ribeiro and Rosana Rocha and Rosa, {Bruno Bezerra} and Thabata Veiga and da Silva, {Luiz Augusto} and Henning Andersen and Thomas Harbo and Lotte Vinge and Susanne Krogh and Anita Mogensen and John Vissing and Joan H{\o}jgaard and Nanna Witting and Autzen, {Anne Mette Ostergaard} and Jane Pedersen and Michael Weiss",

year = "2020",

doi = "10.1007/s00415-020-09770-y",

language = "English",

volume = "267",

pages = "1991--2001",

journal = "Journal of Neurology",

issn = "0340-5354",

publisher = "Springer Medizin",

}

TY - JOUR

T1 - ‘Minimal symptom expression’ in patients with acetylcholine receptor antibody-positive refractory generalized myasthenia gravis treated with eculizumab

AU - Vissing, John

AU - Jacob, Saiju

AU - Fujita, Kenji P.

AU - O’Brien, Fanny

AU - Howard, James F.

AU - The REGAIN Study Group

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 - De Bleecker, Jan

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’Hont, 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 - Rosa, Bruno Bezerra

AU - Veiga, Thabata

AU - da Silva, Luiz Augusto

AU - Andersen, Henning

AU - Harbo, Thomas

AU - Vinge, Lotte

AU - Krogh, Susanne

AU - Mogensen, Anita

AU - Vissing, John

AU - Højgaard, Joan

AU - Witting, Nanna

AU - Autzen, Anne Mette Ostergaard

AU - Pedersen, Jane

AU - Weiss, Michael

PY - 2020

Y1 - 2020

N2 - Background: The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension. Methods: Attainment of ‘minimal symptom expression’ was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. ‘Minimal symptom expression’ was defined as MG-ADL total score of 0–1 or MG-QOL15 total score of 0–3. Results: At REGAIN week 26, more eculizumab-treated patients achieved ‘minimal symptom expression’ versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension, the proportion of patients in the placebo/eculizumab group who achieved ‘minimal symptom expression’ increased after initiating eculizumab treatment and was sustained through 130 weeks of open-label eculizumab (MG-ADL: 1.7 to 27.8%; MG-QOL15: 1.7 to 19.4%). At extension study week 130, similar proportions of patients in the eculizumab/eculizumab and placebo/eculizumab groups achieved ‘minimal symptom expression’ (MG-ADL: 22.9% and 27.8%, respectively, p = 0.7861; MG-QOL15: 14.3% and 19.4%, respectively, p = 0.7531). The long-term tolerability of eculizumab was consistent with previous reports. Conclusions: Patients with AChR+ refractory gMG who receive eculizumab can achieve sustained ‘minimal symptom expression’ based on patient-reported outcomes. ‘Minimal symptom expression’ may be a useful tool in measuring therapy effectiveness in gMG. Trial registration: ClinicalTrials.gov NCT01997229, NCT02301624.

AB - Background: The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension. Methods: Attainment of ‘minimal symptom expression’ was evaluated using patient-reported outcome measures of gMG symptoms [MG activities of daily living scale (MG-ADL), 15-item MG quality of life questionnaire (MG-QOL15)] at the completion of REGAIN and during the open-label extension. ‘Minimal symptom expression’ was defined as MG-ADL total score of 0–1 or MG-QOL15 total score of 0–3. Results: At REGAIN week 26, more eculizumab-treated patients achieved ‘minimal symptom expression’ versus placebo [MG-ADL: 21.4% vs 1.7%; difference 19.8%; 95% confidence interval (CI) 8.5, 31.0; p = 0.0007; MG-QOL15: 16.1% vs 1.7%; difference 14.4%; 95% CI 4.3, 24.6; p = 0.0069]. During the open-label extension, the proportion of patients in the placebo/eculizumab group who achieved ‘minimal symptom expression’ increased after initiating eculizumab treatment and was sustained through 130 weeks of open-label eculizumab (MG-ADL: 1.7 to 27.8%; MG-QOL15: 1.7 to 19.4%). At extension study week 130, similar proportions of patients in the eculizumab/eculizumab and placebo/eculizumab groups achieved ‘minimal symptom expression’ (MG-ADL: 22.9% and 27.8%, respectively, p = 0.7861; MG-QOL15: 14.3% and 19.4%, respectively, p = 0.7531). The long-term tolerability of eculizumab was consistent with previous reports. Conclusions: Patients with AChR+ refractory gMG who receive eculizumab can achieve sustained ‘minimal symptom expression’ based on patient-reported outcomes. ‘Minimal symptom expression’ may be a useful tool in measuring therapy effectiveness in gMG. Trial registration: ClinicalTrials.gov NCT01997229, NCT02301624.

KW - Acetylcholine receptor

KW - Eculizumab

KW - Minimal symptom expression

KW - Myasthenia gravis

KW - Refractory

U2 - 10.1007/s00415-020-09770-y

DO - 10.1007/s00415-020-09770-y

M3 - Journal article

C2 - 32189108

AN - SCOPUS:85085089028

SN - 0340-5354

VL - 267

SP - 1991

EP - 2001

JO - Journal of Neurology

JF - Journal of Neurology

ER -