Neurological Side Effects of TNF-α Inhibitors Revisited: A Review of Case Reports
Abstract
:1. Introduction
Type | Mechanism of Action | Date of Approval (FDA) | Approved Indications | Administration | Pharmacodynamics | Ref. | |
---|---|---|---|---|---|---|---|
Etanercept | Dimeric soluble fusion protein—the extracellular ligand-binding portion of the human p75 TNFR (TNFR2) linked to the Fc portion of human IgG1 | Inhibits the binding of TNF-α and TNF-β to cell surface TNFRs → renders TNF biologically inactive. | 1998 | RA, JIA, PsA, PsO, AS, nr-axSpA | Subcutaneously weekly |
| [22,23,24,25,26] |
Infliximab | Chimeric IG1κ monoclonal antibody (75% human and 25% mouse) | Selectively neutralizes the biological activity of TNFα by binding to the tmTNF-α + sTNF-α → inhibits the binding of TNFα to TNFR. No binding/inactivation of TNF-β | 1998 | AS, CD, JIA, PsO, PsA, RA, UC, nr-axSpA | Intravenously every 6–8 weeks |
| [27,28,29,30,31] |
Adalimumab | Fully human IgG1 monoclonal antibody specific for human TNF-α | Binds specifically to TNF-α → blocks its interaction with the p55 and p75 cell surface TNFR (TNFR1 and TNFR2). In the presence of complement, lyses cells that express at the surface TNF. No binding/inactivation of TNF-β | 2002 | AS, CD, JIA, PsO, PsA, RA, UC, Uveitis, nr-axSpA | Subcutaneously every other week |
| [32,33,34,35,36,37,38,39,40] |
Golimumab | Fully human IgG1 κ monoclonal antibody specific for human TNF-α | Selectively neutralizes the biological activity of TNFα by binding to the tmTNF-α + sTNF-α → inhibits the binding of TNFα to TNFR. No binding/inactivation of TNF-β. | 2009 | AS, PsA, RA, UC, nr-axSpA | Subcutaneously every month |
| [41,42,43,44] |
Certolizumab pegol | Humanized antibody Fab’ fragment conjugated with two polyethylene glycol molecules, specific for human TNF-α | Selectively neutralizes the biological activity of TNFα by binding to the tmTNF-α + sTNF-α → inhibits the binding of TNFα to TNFR. No binding/inactivation of TNF-β. Does not contain a fragment-crystallizable (Fc) region = does not fix complement or cause antibody-dependent cell-mediated cytotoxicity in vitro. | 2008 | AS, CD, PsA, RA, nr-axSpA | Subcutaneously; remission induction weeks 0, 2 and 4, maintenance of remission every 4 weeks |
| [45,46,47] |
2. TNF-α Mechanism of Action
3. Research Methods
4. Results
5. Discussion
6. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Primary Disease | TNF-α Inhibitor | Age/Sex | Family History of Neurological Diseases | Neurological Symptoms/Diagnosed Conditions | Therapeutic Measures | Outcome | Ref. | |
---|---|---|---|---|---|---|---|---|
1. | RA | INFL | Not reported/M | Not reported | ALS | Discontinuation Riluzole | Progressive ALS | [59] |
2. | AS | INFL | 55/M | Not reported | ALS | Discontinuation Riluzole, alphatocopherol | Progressive ALS; death by respiratory insufficiency | [60] |
3. | RA | INFL | 65/F | Not reported | ALS | Discontinuation Riluzole not tolerated | Progressive ALS; death by respiratory insufficiency | [61] |
4. | CD | ADA | 53/F | Not reported | Demyelinating lesions/autoimmune encephalitis | Discontinuation Intravenous steroids, immunoglobulin | Resolution | [62] |
5. | AS | ADA | 30/F | Not reported | Demyelinating lesions/autoimmune encephalitis (Bickerstaff brainstem encephalitis) | Discontinuation Methylprednisolone, intravenous gamma globulin (IVIg), rituximab | Partial resolution | [63] |
6. | CD | ADA | 20/F | Not reported | Peripheral neuropathy/Henoch–Schönlein purpura with neurological involvement | Discontinuation ADA replaced with ustekinumab/methylprednisolone | Resolution | [64] |
7. | CD | INFL | 64/F | Neurofibromatosis | Acute neuropathy, encephalopathy | Discontinuation Polyvalent immunoglobulin | Partial resolution | [65] |
8. | CD | INFL | 27/F | Not reported | Non-demyelinating inflammatory CNS events/anti-NMDAR encephalitis | INFL replaced with ustekinumab Rituximab | Resolution | [66] |
9. | RA | INFL | 72/M | Not reported | Demyelinating progressive multifocal leukoencephalopathy | Discontinuation | Persistent neurologic and cognitive deficits | [67] |
10. | CD | INFL | 45/F | Not reported | Acute disseminated encephalomyelitis | Discontinuation Methylprednisolone | Resolution | [68] |
11. | RA | ADA | 66/F | Not reported | Demyelinating progressive multifocal leukoencephalopathy | Discontinuation | Worsening neurological symptoms | [67] |
12. | RA | ADA | 66/M | Not reported | Demyelinating leukoencephalopathy | Discontinuation Methylprednisolone Meloxicam | Partial resolution | [69] |
13. | AS | GOL | 45/F | Not reported | Demyelinating posterior reversible encephalopathy syndrome | Discontinuation, anti-convulsant therapy (levetiracetam) | Resolution | [70] |
14. | RA | ETA | 74/F | Not reported | Demyelinating progressive multifocal leukoencephalopathy | Discontinuation Supportive therapy | Slight improvement | [71] |
15. | RA | ETA | 47/F | Not reported | Leptomeningitis | Discontinuation Methylprednisolone, azathioprine, levetiracetam, valproic acid. | Significant resolution | [72] |
16. | RA | ADA | 77/M | Not reported | Hypertrophic pachymeningitis | Discontinuation, Prednisone | Resolution | [73] |
17. | JIA | ADA | 18/F | Not reported | Aseptic meningitis | Discontinuation Methylprednisolone | Resolution | [74] |
18. | RA | ADA | 52/F | Not reported | Acute myelopathy/paraplegia | Discontinuation Methylprednisolone (oral/i.v) | Partial resolution | [75] |
19. | CD | ADA | 52/F | Chronic myelitis | Partial resolution | |||
20. | RA | ADA | 42/M | Chronic myelitis | No response | |||
21. | RA Lupus | CZP | 54/F | Chronic myelitis | Partial resolution | |||
22. | Blau syndrome | ETA | 13/M | Not reported | Transverse myelitis | Discontinuation Methylprednisolone, prednisone | Resolution | [76] |
23. | Behcet’s disease | GOL | 34/M | Not reported | Demyelinating lesions | Discontinuation Steroid therapy | Resolution | [77] |
24. | Behcet’s disease | GOL | 51/F | Not reported | Multifocal myelitis | Discontinuation Steroid therapy | Resolution | [78] |
25. | CD | INFL | 40/M | Not reported | Extensive longitudinal myelopathy | Discontinuation Methylprednisolone, followed by oral prednisolone | Slight improvement | [79] |
26. | AS | ADA ETA | 50/M | Not reported | Rapidly progressive dementia | Discontinuation | Resolution | [80] |
27. | RA | ADA | 40/F | None | CNS demyelination | Discontinuation Methylprednisolone | Resolution | [81] |
28. | PSO | ADA | 36/F | None | CNS demyelination | Discontinuation | Resolution | [82] |
29. | PSO | ADA | 37/F | None | CNS demyelination | Discontinuation Intravenous immunoglobulin, oral corticosteroids | Resolution | [83] |
30. | RA | ADA | 39/F | Not reported | Chronic demyelinating neuropathy | Discontinuation | Resolution | [84] |
31. | CD | ADA | 34/F | None | Inflammatory demyelination | Discontinuation Steroid therapy | Slight improvement | [85] |
32. | HS | ADA | 29/M | Not reported | Demyelinating radiologically isolated syndrome | Discontinuation | Resolution | [86] |
33. | JIA | ADA | 14/M | Not reported | CNS active inflammatory process (no demyelination lesions) | Discontinuation High-dose corticosteroids | Partial resolution | [87] |
34. | PSO | ADA | 51/F | None | MS | Discontinuation high-dose corticosteroids | Partial resolution | [88] |
35. | AS | ETA | 34/M | None | CNS demyelination | Discontinuation | Slight improvement | [89] |
36. | AS | ETA | 26/F | Not reported | MOGAD | Discontinuation Methylprednisolone | Significant improvement | [90] |
37. | AS | ETA | 44/F | Not reported | Tumefactive CNS inflammatory demyelination | Discontinuation High-dose steroids | Significant improvement | [91] |
38. | AS | ETA | 36/M | MS (brother) | Acute transverse myelitis | Discontinuation Methylprednisolone | Resolution | [92] |
39. | Juvenile RA | ETA | 21/F | None | MS Optic neuritis | Discontinuation Methylprednisolone | Partial resolution | [93] |
40. | PSO | ETA | 55/M | None | MS | Discontinuation Methylprednisolone | No improvement | [94] |
41. | AS | ADA | 44/M | None | Demyelinating brain lesions | Discontinuation | Not reported | |
42. | RA | ETA | 26/F | Not reported | MS | Not reported | Not reported | [95] |
43. | AS | GOL | 41/M | None | Fulminant CNS demyelination | Discontinuation Steroid therapy Plasmapheresis | Resolution | [96] |
44. | PSO | INFL | 47/F | MS (sister) | MS | Discontinuation Steroid therapy | Partial resolution | [97] |
45. | PSO | INFL | 27/F | None | CNS demyelination | Discontinuation Steroid therapy Rituximab | Partial resolution | [98] |
46. | CD | INFL | 46/M | None | Inflammatory demyelinating polyneuropachronicth | Discontinuation Intravenous human immunoglobulin | Resolution | [99] |
47. | CD AS | INFL | 18/F | Not reported | CNS demyelination | Discontinuation | No improvement | [100] |
48. | AS Uveitis | INFL | 38/M | Not reported | Demyelinating brain lesions | Discontinuation | Resolution | [101] |
49. | RA | INFL | 56/M | Not reported | CNS demyelination | Discontinuation High-dose dexamethasone | Resolution | [102] |
50. | 66/F | Not reported | Discontinuation Oral prednisone | Significant improvement | ||||
51. | CD | INFL | 19/F | None | CNS demyelination | Discontinuation | Resolution | [103] |
52. | Uveitis JIA | ADA | 21/F | Not reported | MS | Discontinuation Cladribine | Resolution | [38] |
53. | PSO | ADA | 56/F | Not reported | MS aseptic meningitis | Discontinuation | Resolution | [104] |
54. | RA | ADA | 68/F | None | MS | Discontinuation | Resolution | [105] |
55. | Autoimmune Uveitis | ADA | 23/M | MS (family) | MS | Discontinuation Methylprednisolone, oral prednisolone | Resolution | [39] |
56. | AS | ADA | 36/M | None | MS | Discontinuation Methylprednisolone, oral prednisolone | Resolution | [106] |
57. | CD | INFL | 47/F | None | MS | Discontinuation | Resolution | [107] |
58. | UC | INFL | 35/F | MS (family) | MS | Discontinuation | Not reported | [108] |
59. | AS | INFL | 48/M | Not reported | MS | Discontinuation | Resolution | [109] |
60. | PSO | ADA | 41/M | CNS demyelination | Discontinuation | Resolution | ||
61. | PSO | ETA | 38/F | MS | Discontinuation Interferon beta-1a | Not reported | ||
62. | RA | ADA | 64/F | MS | Discontinuation | Not reported | ||
63. | AS | INFL | 34/F | Clinical isolated syndrome | Discontinuation | Resolution | ||
64. | PSO | INFL | 57/M | Peripheral demyelinating neuropathy | Discontinuation | Resolution | ||
65. | PSO | ETA | 48/M | Not reported | MS | Discontinuation | Resolution | [110] |
66. | PSO | INFL | 62/F | Not reported | Optic neuritis | Discontinuation Methylprednisolone | No improvement | [111] |
67. | PSO | INFL | 56/F | Not reported | CNS demyelination | Discontinuation Methylprednisolone | Significant improvement | [112] |
68. | PSO | CZP | 44/M | Not reported | Cranial nerve III demyelination | Discontinuation methylprednisolone | Resolution | [113] |
69. | RA | ETA | 64/F | Not reported | Myelitis optic neuritis | Discontinuation Methylprednisolone | Resolution | [114] |
70. | CD | ADA | 27/F | Not reported | Internuclear ophthalmoplegia | Discontinuation Steroid therapy | Resolution | [115] |
71. | RA | INFL | 53/F | Not reported | Optic neuritis | Discontinuation Steroid therapy | Resolution | [116] |
72. | RA | ETA | 40/F | Not reported | Neurosarcoidosis | Discontinuation Methylprednisolone, oral prednisolone | Partial resolution | [117] |
73. | RA Uveitis | ETA | 33/F | Not reported | Neurosarcoidosis | ETA replaced with INFL Steroid therapy | Significant improvement | [118] |
74. | RA | INFL | 50/F | None | Polineuropathy | Discontinuation Intravenous gammaglobulin | Slight improvement | [119] |
75. | 85/F | Mild sensory loss | Discontinuation Steroid therapy | Partial resolution | ||||
76. | 68/F | Not reported | Discontinuation | Slight improvement | ||||
77. | PSO | ADA | 65/F | Not reported | Acute bilateral symmetric phrenic neuropathy | Discontinuation Oxygen | Resolution | [120] |
78. | RA | ETA | 45/F | Not reported | Chronic inflammatory demyelinating polyneuropathy | Discontinuation Intravenous gammaglobulin | Partial resolution | [121] |
79. | INFL | 49/M | Not reported | |||||
80. | PSO | ADA | 53/F | GBS | Chronic inflammatory demyelinating polyradiculoneuropathy | Discontinuation Intravenous immunoglobulin | Resolution | [122] |
81. | RA | ADA | 52/M | Idiopathic Parkinson’s disease | DADS neuropathy | Discontinuation | Resolution | [123] |
82. | AS | GOL | 48/M | ALS (family) | Bilateral retrobulbar optic neuropathy | Discontinuation Methylprednisolone, oral prednisolone | No improvement | [124] |
83. | PSO | ADA | 42/M | Not reported | Chronic inflammatory demyelinating polyneuropathy | Discontinuation intravenous immunoglobulin | Resolution | [125] |
84. | PSO | INFL | 64/M | Not reported | Sensory polyradiculopathy | Discontinuation Intravenous immunoglobulin | Resolution | [126] |
85. | RA | INFL | 32/F | Not reported | Small-fiber neuropathies | Discontinuation | Partial resolution | [127] |
86. | 73/F | Not reported | Discontinuation Symptomatic treatment | Partial resolution | ||||
87. | 55/F | Not reported | Discontinuation | Significant improvement | ||||
88. | AS | INFL | 54/M | Not reported | MMNCB | Discontinuation | Significant improvement | [128] |
89. | UC | INFL | 30/M | None | Multifocal motor neuropathy | Discontinuation Intravenous immunoglobulin | Resolution | [128] |
90. | JIA | ETA | 12/F | Not reported | Chronic inflammatory demyelinating neuropathy | Discontinuation Intravenous immunoglobulins, steroids, plasma exchange | Limited response | [129] |
91. | RA | ADA | 44/F | Not reported | Inflammatory demyelinating neuropathy | Discontinuation Intravenous immunoglobulin | Partial resolution | [130] |
92. | CD | ADA | 37/M | Not reported | Chronic inflammatory demyelinating neuropathy | Discontinuation Intravenous immunoglobulins, steroids | Significant improvement | [131] |
93. | CD | INFL | 60/F | None | Seizures | Discontinuation | Resolution | [132] |
94. | CD | INFL | 74/M | Not reported | Seizures | Discontinuation | Resolution | [133] |
95. | RA | ETA | 74/F | Not reported | CJD | Discontinuation | Resolution | [134] |
96. | PSO | INFL | 40/M | Not reported | LSS | Discontinuation Intravenous immunoglobulin | Partial resolution | [135] |
97. | UC | INFL | 44/M | None | LSS | Discontinuation Intravenous immunoglobulin | Partial resolution | [136] |
98. | CD | INFL | 24/F | Not reported | LSS | Discontinuation Intravenous immunoglobulin | Resolution | [137] |
99. | 35/F | Not reported | ||||||
100. | RA | INFL | 77/F | Not reported | MFS | Discontinuation High-dose steroids, gabapentine | Slow improvement | [138] |
101. | UC | INFL | 43/F | Not reported | MFS | Discontinuation | Resolution | [139] |
102. | PSO | ETA | 42/F | Not reported | MFS | Discontinuation | Slow improvement | [140] |
103. | CD | ADA | 64/M | Not reported | GBS | Discontinuation | Resolution | [141] |
104. | PSO | ADA | 45/M | Not reported | GBS | Discontinuation | Partial resolution | [142] |
105. | RA | ADA | 50/F | Not reported | GBS | Discontinuation Prednisone, gabapentin | Partial resolution | [143] |
106. | CD | ADA | 37/M | Not reported | GBS | Discontinuation Intravenous immunoglobulin | Partial resolution | [144] |
107. | UC AS | INFL | 47/F | Not reported | GBS | Discontinuation intravenous immunoglobulin | Resolution | [145] |
108. | CD | ADA | 71/M | Not reported | GBS | Discontinuation Intravenous immunoglobulin, Methylprednisolone, plasmapheresis | Partial resolution | [146] |
109. | CD | ADA | 33/F | Not reported | GBS | Continuation of ADA treatment Intravenous immunoglobulin | Significant improvement | [147] |
110. | AS | ETA | 50/M | Not reported | GBS | Discontinuation Intravenous immunoglobulin, plasmapheresis | Resolution | [148] |
111. | PSO | ETA | 53/M | None | MS | Discontinuation Interferonβ Baclofen | Significant improvement | [149] |
112. | PSO | 42/M | None | MS | Discontinuation | Significant improvement | ||
113. | AS | 51/F | Not reported | Discontinuation | Mild improvement |
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© 2024 by the authors. Published by MDPI on behalf of the Lithuanian University of Health Sciences. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Gogulescu, A.; Blidisel, A.; Soica, C.; Mioc, A.; Voicu, A.; Jojic, A.; Voicu, M.; Banciu, C. Neurological Side Effects of TNF-α Inhibitors Revisited: A Review of Case Reports. Medicina 2024, 60, 1409. https://doi.org/10.3390/medicina60091409
Gogulescu A, Blidisel A, Soica C, Mioc A, Voicu A, Jojic A, Voicu M, Banciu C. Neurological Side Effects of TNF-α Inhibitors Revisited: A Review of Case Reports. Medicina. 2024; 60(9):1409. https://doi.org/10.3390/medicina60091409
Chicago/Turabian StyleGogulescu, Armand, Alexandru Blidisel, Codruta Soica, Alexandra Mioc, Adrian Voicu, Alina Jojic, Mirela Voicu, and Christian Banciu. 2024. "Neurological Side Effects of TNF-α Inhibitors Revisited: A Review of Case Reports" Medicina 60, no. 9: 1409. https://doi.org/10.3390/medicina60091409