Myasthenia gravis treatment in the elderly presents with a significant iatrogenic risk: a multicentric retrospective study.
Frail elderly
Iatrogenic diseases
Myasthenia gravis
Prognosis
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
10
05
2023
accepted:
08
08
2023
revised:
07
08
2023
medline:
9
11
2023
pubmed:
18
8
2023
entrez:
17
8
2023
Statut:
ppublish
Résumé
Myasthenia gravis (MG) is an autoimmune disease treated with acetylcholinesterase inhibitors and immunosuppressant/immunomodulatory drugs. MG is frequently diagnosed in elderly patients, a fragile population in which treatment adverse effects (TAE) have not been evaluated until now. We retrospectively analysed the files of all MG patients with disease onset after age 70 years in four French University Hospitals, including clinical, electrophysiological, biological, and treatment data, with an emphasis on TAE. MG outcomes were assessed using the Myasthenia Gravis Foundation of America (MGFA) status scale. We included 138 patients (59% of men) with a mean follow-up of 4.5 years (range 1-19). Mean age at diagnosis was 78 years (70-93). Anti-acetylcholine receptor antibodies were found in 87% of cases, electrophysiological abnormalities in 82%, and thymoma in 10%. MG outcome was good in a majority of cases, with 76% of treated patients presenting with alleviated symptoms at follow-up. TAE were observed in 41% of patients, including severe TAE in 14% of cases. Seven patients (5.1%) died, including four (2.9%) from MG-related respiratory failure, and three (2.2%) from MG treatment-related complications, i.e., sepsis in 2 cases and brain toxoplasmosis in 1 case. TAE were observed in 53% of patients treated with azathioprine, 23% of patients treated with corticosteroids, and 15% of patients treated with mycophenolate mofetil. This retrospective study demonstrates MG in the elderly presents with a significant iatrogenic risk, including fatal immunosuppressant-related infections.
Sections du résumé
BACKGROUND
BACKGROUND
Myasthenia gravis (MG) is an autoimmune disease treated with acetylcholinesterase inhibitors and immunosuppressant/immunomodulatory drugs. MG is frequently diagnosed in elderly patients, a fragile population in which treatment adverse effects (TAE) have not been evaluated until now.
METHODS
METHODS
We retrospectively analysed the files of all MG patients with disease onset after age 70 years in four French University Hospitals, including clinical, electrophysiological, biological, and treatment data, with an emphasis on TAE. MG outcomes were assessed using the Myasthenia Gravis Foundation of America (MGFA) status scale.
RESULTS
RESULTS
We included 138 patients (59% of men) with a mean follow-up of 4.5 years (range 1-19). Mean age at diagnosis was 78 years (70-93). Anti-acetylcholine receptor antibodies were found in 87% of cases, electrophysiological abnormalities in 82%, and thymoma in 10%. MG outcome was good in a majority of cases, with 76% of treated patients presenting with alleviated symptoms at follow-up. TAE were observed in 41% of patients, including severe TAE in 14% of cases. Seven patients (5.1%) died, including four (2.9%) from MG-related respiratory failure, and three (2.2%) from MG treatment-related complications, i.e., sepsis in 2 cases and brain toxoplasmosis in 1 case. TAE were observed in 53% of patients treated with azathioprine, 23% of patients treated with corticosteroids, and 15% of patients treated with mycophenolate mofetil.
CONCLUSIONS
CONCLUSIONS
This retrospective study demonstrates MG in the elderly presents with a significant iatrogenic risk, including fatal immunosuppressant-related infections.
Identifiants
pubmed: 37592137
doi: 10.1007/s00415-023-11925-6
pii: 10.1007/s00415-023-11925-6
doi:
Substances chimiques
Acetylcholinesterase
EC 3.1.1.7
Immunosuppressive Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5819-5826Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
Références
Narayanaswami P, Sanders DB, Wolfe G et al (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
Gilhus NE, Verschuuren JJ (2015) Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol 14:1023–1036. https://doi.org/10.1016/S1474-4422(15)00145-3
doi: 10.1016/S1474-4422(15)00145-3
pubmed: 26376969
Fan L, Ma S, Yang Y et al (2018) Clinical differences of early and late-onset myasthenia gravis in 985 patients. Neurol Res. https://doi.org/10.1080/01616412.2018.1525121
doi: 10.1080/01616412.2018.1525121
pubmed: 30311866
Suzuki S, Utsugisawa K, Nagane Y et al (2011) Clinical and immunological differences between early and late-onset myasthenia gravis in Japan. J Neuroimmunol 230:148–152. https://doi.org/10.1016/j.jneuroim.2010.10.023
doi: 10.1016/j.jneuroim.2010.10.023
pubmed: 21074862
Christensen PB, Jensen TS, Tsiropoulos I et al (1993) Incidence and prevalence of myasthenia gravis in western Denmark: 1975 to 1989. Neurology 43:1779–1783
doi: 10.1212/WNL.43.9.1779
pubmed: 8414031
Matsuda M, Dohi-Iijima N, Nakamura A et al (2005) Increase in incidence of elderly-onset patients with myasthenia gravis in Nagano Prefecture, Japan. Intern Med Tokyo Jpn 44:572–577
doi: 10.2169/internalmedicine.44.572
Vincent A, Clover L, Buckley C et al (2003) Evidence of underdiagnosis of myasthenia gravis in older people. J Neurol Neurosurg Psychiatry 74:1105–1108
doi: 10.1136/jnnp.74.8.1105
pubmed: 12876244
pmcid: 1738592
Aragonès JM, Altimiras J, Molist N et al (2019) Under-diagnosis of neuromuscular diseases in patients of 80 years and older. Rev Espanola Geriatr Gerontol 54:99–102. https://doi.org/10.1016/j.regg.2018.10.004
doi: 10.1016/j.regg.2018.10.004
Maniaol AH, Elsais A, Lorentzen ÅR et al (2012) Late onset myasthenia gravis is associated with HLA DRB1*15:01 in the Norwegian population. PLoS ONE 7:e36603. https://doi.org/10.1371/journal.pone.0036603
doi: 10.1371/journal.pone.0036603
pubmed: 22590574
pmcid: 3348874
Marx A, Pfister F, Schalke B et al (2013) The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev 12:875–884. https://doi.org/10.1016/j.autrev.2013.03.007
doi: 10.1016/j.autrev.2013.03.007
pubmed: 23535159
Somnier FE (2005) Increasing incidence of late-onset anti-AChR antibody-seropositive myasthenia gravis. Neurology 65:928–930. https://doi.org/10.1212/01.wnl.0000176067.32186.a3
doi: 10.1212/01.wnl.0000176067.32186.a3
pubmed: 16186537
Aarli JA (2008) Myasthenia gravis in the elderly: Is it different? Ann N Y Acad Sci 1132:238–243. https://doi.org/10.1196/annals.1405.040
doi: 10.1196/annals.1405.040
pubmed: 18567874
Tang Y-L, Ruan Z, Su Y et al (2023) Clinical characteristics and prognosis of very late-onset myasthenia gravis in China. Neuromuscul Disord 33:358–366. https://doi.org/10.1016/j.nmd.2023.02.013
doi: 10.1016/j.nmd.2023.02.013
pubmed: 36990040
Bowie MW, Slattum PW (2007) Pharmacodynamics in older adults: a review. Am J Geriatr Pharmacother 5:263–303. https://doi.org/10.1016/j.amjopharm.2007.10.001
doi: 10.1016/j.amjopharm.2007.10.001
pubmed: 17996666
Kojima G, Liljas AEM, Iliffe S (2019) Frailty syndrome: implications and challenges for health care policy. Risk Manag Healthc Policy 12:23–30. https://doi.org/10.2147/RMHP.S168750
doi: 10.2147/RMHP.S168750
pubmed: 30858741
pmcid: 6385767
Permpongkosol S (2011) Iatrogenic disease in the elderly: risk factors, consequences, and prevention. Clin Interv Aging 6:77–82. https://doi.org/10.2147/CIA.S10252
doi: 10.2147/CIA.S10252
pubmed: 21472095
pmcid: 3066256
Evoli A, Batocchi AP, Minisci C et al (2000) Clinical characteristics and prognosis of myasthenia gravis in older people. J Am Geriatr Soc 48:1442–1448
doi: 10.1111/j.1532-5415.2000.tb02635.x
pubmed: 11083321
Fraisse T, Labauge P, Camu W et al (2007) Myasthenia gravis in the elderly: diagnosis, comorbidity and course: 45 cases. Presse Medicale Paris Fr 1983 36:9–14. https://doi.org/10.1016/j.lpm.2006.07.003
doi: 10.1016/j.lpm.2006.07.003
Hellmann MA, Mosberg-Galili R, Steiner I (2013) Myasthenia gravis in the elderly. J Neurol Sci 325:1–5. https://doi.org/10.1016/j.jns.2012.10.028
doi: 10.1016/j.jns.2012.10.028
pubmed: 23218585
Cortés-Vicente E, Álvarez-Velasco R, Segovia S et al (2020) Clinical and therapeutic features of myasthenia gravis in adults based on age at onset. Neurology 94:e1171–e1180. https://doi.org/10.1212/WNL.0000000000008903
doi: 10.1212/WNL.0000000000008903
pubmed: 32071167
pmcid: 7220233
Melzer N, Ruck T, Fuhr P et al (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
Jaretzki A, Barohn RJ, Ernstoff RM et al (2000) Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology 55:16–23
doi: 10.1212/WNL.55.1.16
pubmed: 10891897
Sharshar T, Chevret S, Mazighi M et al (2000) Validity and reliability of two muscle strength scores commonly used as endpoints in assessing treatment of myasthenia gravis. J Neurol 247:286–290
doi: 10.1007/s004150050585
pubmed: 10836621
U.S. Department of Health and Human Services (2017) Common terminology criteria for adverse events (CTCAE) v.50. U.S. Department of Health and Human Services
Sanders DB, Arimura K, Cui L et al (2019) Guidelines for single fiber EMG. Clin Neurophysiol 130:1417–1439. https://doi.org/10.1016/j.clinph.2019.04.005
doi: 10.1016/j.clinph.2019.04.005
pubmed: 31080019
Yildiz Celik S, Durmus H, Yilmaz V et al (2020) Late-onset generalized myasthenia gravis: clinical features, treatment, and outcome. Acta Neurol Belg 120:133–140. https://doi.org/10.1007/s13760-019-01252-x
doi: 10.1007/s13760-019-01252-x
pubmed: 31811563
Mao Z-F, Mo X-A, Qin C et al (2012) Incidence of thymoma in myasthenia gravis: a systematic review. J Clin Neurol Seoul Korea 8:161–169. https://doi.org/10.3988/jcn.2012.8.3.161
doi: 10.3988/jcn.2012.8.3.161
Pascuzzi RM, Coslett HB, Johns TR (1984) Long-term corticosteroid treatment of myasthenia gravis: report of 116 patients. Ann Neurol 15:291–298. https://doi.org/10.1002/ana.410150316
doi: 10.1002/ana.410150316
pubmed: 6721451
Menon D, Bril V (2022) Pharmacotherapy of generalized myasthenia gravis with special emphasis on newer biologicals. Drugs 82:865–887. https://doi.org/10.1007/s40265-022-01726-y
doi: 10.1007/s40265-022-01726-y
pubmed: 35639288
pmcid: 9152838
Fonseca V, Havard CW (1990) Long term treatment of myasthenia gravis with azathioprine. Postgrad Med J 66:102–105. https://doi.org/10.1136/pgmj.66.772.102
doi: 10.1136/pgmj.66.772.102
pubmed: 2112245
pmcid: 2429542
Hohlfeld R, Michels M, Heininger K et al (1988) Azathioprine toxicity during long-term immunosuppression of generalized myasthenia gravis. Neurology 38:258–258. https://doi.org/10.1212/WNL.38.2.258
doi: 10.1212/WNL.38.2.258
pubmed: 3340289
Chaudhry V, Cornblath DR, Griffin JW et al (2001) Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases. Neurology 56:94–96. https://doi.org/10.1212/wnl.56.1.94
doi: 10.1212/wnl.56.1.94
pubmed: 11148242
Tandan R, Hehir MK, Waheed W, Howard DB (2017) Rituximab treatment of myasthenia gravis: a systematic review. Muscle Nerve 56:185–196. https://doi.org/10.1002/mus.25597
doi: 10.1002/mus.25597
pubmed: 28164324
Lotan I, Hellmann MA, Wilf-Yarkoni A, Steiner I (2021) Exacerbation of myasthenia gravis following corticosteroid treatment: what is the evidence? A systematic review. J Neurol 268:4573–4586. https://doi.org/10.1007/s00415-020-10264-0
doi: 10.1007/s00415-020-10264-0
pubmed: 33064188
Molimard A, Gitiaux C, Barnerias C et al (2022) Rituximab therapy in the treatment of juvenile myasthenia gravis: the french experience. Neurology 98:e2368–e2376. https://doi.org/10.1212/WNL.0000000000200288
doi: 10.1212/WNL.0000000000200288
pubmed: 35314497
Mangoni AA, Jackson SHD (2003) Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications: age-related changes in pharmacokinetics and pharmacodynamics. Br J Clin Pharmacol 57:6–14. https://doi.org/10.1046/j.1365-2125.2003.02007.x
doi: 10.1046/j.1365-2125.2003.02007.x
Sakai W, Matsui N, Ishida M et al (2016) Late-onset myasthenia gravis is predisposed to become generalized in the elderly. eNeurol Sci 2:17–20. https://doi.org/10.1016/j.ensci.2016.02.004
doi: 10.1016/j.ensci.2016.02.004
Billé-Turc F, Padovani R, Pouget J et al (1997) Late onset myasthenia: 34 cases in patients over 65 years of age. Rev Neurol (Paris) 153:129–134
pubmed: 9296125
Durand F, Camdessanché J-P, Jomir L et al (2005) Myasthenia in elderly patients: a series of 23 cases. Rev Med Internet 26:924–930. https://doi.org/10.1016/j.revmed.2005.08.009
doi: 10.1016/j.revmed.2005.08.009
Howard JF, Bril V, Vu T et al (2021) Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol 20:526–536. https://doi.org/10.1016/S1474-4422(21)00159-9
doi: 10.1016/S1474-4422(21)00159-9
pubmed: 34146511
Bril V, Benatar M, Andersen H et al (2020) Efficacy and safety of rozanolixizumab in moderate-to-severe generalised myasthenia gravis: a phase 2 RCT. Neurology. https://doi.org/10.1212/WNL.0000000000011108.10.1212/WNL.0000000000011108
doi: 10.1212/WNL.0000000000011108.10.1212/WNL.0000000000011108
pubmed: 33219142
pmcid: 7322879