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Gepubliceerd in: Quality of Life Research 8/2019

Open Access 23-03-2019 | Brief Communication

Eculizumab improves fatigue in refractory generalized myasthenia gravis

Auteurs: Henning Andersen, Renato Mantegazza, Jing Jing Wang, Fanny O’Brien, Kaushik Patra, James F. Howard Jr., The REGAIN Study Group

Gepubliceerd in: Quality of Life Research | Uitgave 8/2019

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Abstract

Purpose

To evaluate the effect of eculizumab on perceived fatigue in patients with anti-acetylcholine receptor antibody-positive, refractory, generalized myasthenia gravis (MG) using the Quality of Life in Neurological Disorders (Neuro-QOL) Fatigue subscale, and to evaluate correlations between improvements in Neuro-QOL Fatigue and other clinical endpoints.

Methods

Neuro-QOL Fatigue, MG Activities of Daily Living (MG-ADL), Quantitative MG (QMG), and the 15-item MG Quality of Life (MG-QOL15) scales were administered during the phase 3, randomized, placebo-controlled REGAIN study (eculizumab, n = 62; placebo, n = 63) and subsequent open-label extension (OLE). Data were analyzed using repeated-measures models. Correlations between changes in Neuro-QOL Fatigue and in MG-ADL, QMG, and MG-QOL15 scores were determined at REGAIN week 26.

Results

At REGAIN week 26, eculizumab-treated patients showed significantly greater improvements in Neuro-QOL Fatigue scores than placebo-treated patients (consistent with improvements in MG-ADL, QMG, and MG-QOL15 scores previously reported in REGAIN). Improvements with eculizumab were sustained through OLE week 52. Correlations between Neuro-QOL Fatigue and MG-QOL15, MG-ADL, and QMG scores were strong for eculizumab-treated patients at REGAIN week 26, and strong, moderate, and weak, respectively, for placebo-treated patients.

Conclusions

Compared with placebo, eculizumab was associated with improvements in perceived fatigue that strongly correlated with improvements in MG-specific outcome measures.
Trial ID Registration: NCT01997229, NCT02301624.
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Literatuur
1.
go back to reference Conti-Fine, B. M., Milani, M., & Kaminski, H. J. (2006). Myasthenia gravis: Past, present, and future. Journal of Clinical Investigation, 116(11), 2843–2854. CrossRef Conti-Fine, B. M., Milani, M., & Kaminski, H. J. (2006). Myasthenia gravis: Past, present, and future. Journal of Clinical Investigation, 116(11), 2843–2854. CrossRef
2.
go back to reference Howard, J. F. Jr. (2018). Myasthenia gravis: The role of complement at the neuromuscular junction. Annals of the New York Academy of Sciences, 1412(1), 113–128. CrossRef Howard, J. F. Jr. (2018). Myasthenia gravis: The role of complement at the neuromuscular junction. Annals of the New York Academy of Sciences, 1412(1), 113–128. CrossRef
3.
go back to reference Elsais, A., Wyller, V. B., Loge, J. H., & Kerty, E. (2013). Fatigue in myasthenia gravis: Is it more than muscular weakness? BMC Neurology, 13, 132. CrossRef Elsais, A., Wyller, V. B., Loge, J. H., & Kerty, E. (2013). Fatigue in myasthenia gravis: Is it more than muscular weakness? BMC Neurology, 13, 132. CrossRef
4.
go back to reference Paul, R. H., Cohen, R. A., Goldstein, J. M., & Gilchrist, J. M. (2000). Fatigue and its impact on patients with myasthenia gravis. Muscle & Nerve, 23(9), 1402–1406. CrossRef Paul, R. H., Cohen, R. A., Goldstein, J. M., & Gilchrist, J. M. (2000). Fatigue and its impact on patients with myasthenia gravis. Muscle & Nerve, 23(9), 1402–1406. CrossRef
5.
go back to reference Symonette, C. J., Watson, B. V., Koopman, W. J., Nicolle, M. W., & Doherty, T. J. (2010). Muscle strength and fatigue in patients with generalized myasthenia gravis. Muscle & Nerve, 41(3), 362–369. CrossRef Symonette, C. J., Watson, B. V., Koopman, W. J., Nicolle, M. W., & Doherty, T. J. (2010). Muscle strength and fatigue in patients with generalized myasthenia gravis. Muscle & Nerve, 41(3), 362–369. CrossRef
6.
go back to reference Hoffmann, S., Ramm, J., Grittner, U., Kohler, S., Siedler, J., & Meisel, A. (2016). Fatigue in myasthenia gravis: Risk factors and impact on quality of life. Brain and Behavior. 6(10), e00538. CrossRef Hoffmann, S., Ramm, J., Grittner, U., Kohler, S., Siedler, J., & Meisel, A. (2016). Fatigue in myasthenia gravis: Risk factors and impact on quality of life. Brain and Behavior. 6(10), e00538. CrossRef
7.
go back to reference Tran, C., Bril, V., Katzberg, H. D., & Barnett, C. (2018). Fatigue is a relevant outcome in patients with myasthenia gravis. Muscle & Nerve, 58(2), 197–203. CrossRef Tran, C., Bril, V., Katzberg, H. D., & Barnett, C. (2018). Fatigue is a relevant outcome in patients with myasthenia gravis. Muscle & Nerve, 58(2), 197–203. CrossRef
8.
go back to reference Muppidi, S. (2012). The myasthenia gravis-specific activities of daily living profile. Annals of the New York Academy of Sciences, 1274, 114–119. CrossRef Muppidi, S. (2012). The myasthenia gravis-specific activities of daily living profile. Annals of the New York Academy of Sciences, 1274, 114–119. CrossRef
9.
go back to reference Barohn, R. J., McIntire, D., Herbelin, L., Wolfe, G. I., Nations, S., & Bryan, W. W. (1998). Reliability testing of the quantitative myasthenia gravis score. Annals of the New York Academy of Sciences, 841, 769–772. CrossRef Barohn, R. J., McIntire, D., Herbelin, L., Wolfe, G. I., Nations, S., & Bryan, W. W. (1998). Reliability testing of the quantitative myasthenia gravis score. Annals of the New York Academy of Sciences, 841, 769–772. CrossRef
10.
go back to reference Burns, T. M., Grouse, C. K., Conaway, M. R., & Sanders, D. B. (2010). Construct and concurrent validation of the MG-QOL15 in the practice setting. Muscle & Nerve, 41(2), 219–226. Burns, T. M., Grouse, C. K., Conaway, M. R., & Sanders, D. B. (2010). Construct and concurrent validation of the MG-QOL15 in the practice setting. Muscle & Nerve, 41(2), 219–226.
11.
go back to reference Cella, D., Lai, J. S., Nowinski, C. J., Victorson, D., Peterman, A., Miller, D., et al. (2012). Neuro-QOL: Brief measures of health-related quality of life for clinical research in neurology. Neurology, 78(23), 1860–1867. CrossRef Cella, D., Lai, J. S., Nowinski, C. J., Victorson, D., Peterman, A., Miller, D., et al. (2012). Neuro-QOL: Brief measures of health-related quality of life for clinical research in neurology. Neurology, 78(23), 1860–1867. CrossRef
12.
go back to reference Miller, D. M., Bethoux, F., Victorson, D., Nowinski, C. J., Buono, S., Lai, J. S., et al. (2016). Validating Neuro-QoL short forms and targeted scales with people who have multiple sclerosis. Multiple Sclerosis, 22(6), 830–841. CrossRef Miller, D. M., Bethoux, F., Victorson, D., Nowinski, C. J., Buono, S., Lai, J. S., et al. (2016). Validating Neuro-QoL short forms and targeted scales with people who have multiple sclerosis. Multiple Sclerosis, 22(6), 830–841. CrossRef
13.
go back to reference Victorson, D., Cavazos, J. E., Holmes, G. L., Reder, A. T., Wojna, V., Nowinski, C., et al. (2014). Validity of the neurology quality-of-life (Neuro-QoL) measurement system in adult epilepsy. Epilepsy & Behavior, 31, 77–84. CrossRef Victorson, D., Cavazos, J. E., Holmes, G. L., Reder, A. T., Wojna, V., Nowinski, C., et al. (2014). Validity of the neurology quality-of-life (Neuro-QoL) measurement system in adult epilepsy. Epilepsy & Behavior, 31, 77–84. CrossRef
14.
go back to reference Nowinski, C. J., Siderowf, A., Simuni, T., Wortman, C., Moy, C., & Cella, D. (2016). Neuro-QoL health-related quality of life measurement system: Validation in Parkinson’s disease. Movement Disorders, 31(5), 725–733. CrossRef Nowinski, C. J., Siderowf, A., Simuni, T., Wortman, C., Moy, C., & Cella, D. (2016). Neuro-QoL health-related quality of life measurement system: Validation in Parkinson’s disease. Movement Disorders, 31(5), 725–733. CrossRef
16.
go back to reference Rother, R. P., Rollins, S. A., Mojcik, C. F., Brodsky, R. A., & Bell, L. (2007). Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nature Biotechnology, 25(11), 1256–1264. CrossRef Rother, R. P., Rollins, S. A., Mojcik, C. F., Brodsky, R. A., & Bell, L. (2007). Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nature Biotechnology, 25(11), 1256–1264. CrossRef
17.
go back to reference Howard, J. F. Jr., Utsugisawa, K., Benatar, M., Murai, H., Barohn, R. J., Illa, I., et al. (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 Neurology, 16(12), 976–986. CrossRef Howard, J. F. Jr., Utsugisawa, K., Benatar, M., Murai, H., Barohn, R. J., Illa, I., et al. (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 Neurology, 16(12), 976–986. CrossRef
19.
go back to reference Gao, X., Schwartz, T. A., Preisser, J. S., & Perin, J. (2017). GEEORD: A SAS macro for analyzing ordinal response variables with repeated measures through proportional odds, partial proportional odds, or non-proportional odds models. Computer Methods and Programs in Biomedicine, 150, 23–30. CrossRef Gao, X., Schwartz, T. A., Preisser, J. S., & Perin, J. (2017). GEEORD: A SAS macro for analyzing ordinal response variables with repeated measures through proportional odds, partial proportional odds, or non-proportional odds models. Computer Methods and Programs in Biomedicine, 150, 23–30. CrossRef
20.
go back to reference Swinscow, T. D. V. (1997). Statistics at square one, ninth edition. London: BMJ Publishing Group. Swinscow, T. D. V. (1997). Statistics at square one, ninth edition. London: BMJ Publishing Group.
21.
go back to reference Kluger, B. M., Krupp, L. B., & Enoka, R. M. (2013). Fatigue and fatigability in neurologic illnesses: Proposal for a unified taxonomy. Neurology, 80(4), 409–416. CrossRef Kluger, B. M., Krupp, L. B., & Enoka, R. M. (2013). Fatigue and fatigability in neurologic illnesses: Proposal for a unified taxonomy. Neurology, 80(4), 409–416. CrossRef
Metagegevens
Titel
Eculizumab improves fatigue in refractory generalized myasthenia gravis
Auteurs
Henning Andersen
Renato Mantegazza
Jing Jing Wang
Fanny O’Brien
Kaushik Patra
James F. Howard Jr.
The REGAIN Study Group
Publicatiedatum
23-03-2019
Uitgeverij
Springer International Publishing
Gepubliceerd in
Quality of Life Research / Uitgave 8/2019
Print ISSN: 0962-9343
Elektronisch ISSN: 1573-2649
DOI
https://doi.org/10.1007/s11136-019-02148-2