Yusuf Kemal ARSLAN, Hasan YAŞAR, Bilge EKİNCİ

Anti-tümör nekroz faktör-alfa ilaç tedavisi alan hastalarda periferik sinirlerindeğerlendirilmesi

Amaç: Anti-tümör nekroz faktör-alfa (TNF-α) ilaç tedavileri, birçok enflamatuar hastalıkta yaygın olarak kullanılmaktadır. Bu tedavilerde nadiren nörolojik komplikasyonlar bildirilmiştir. Bu çalışmadaki amacımız, bu tedaviyi alan hastalarımızda ortaya çıkan nörolojik bulguları araştırmaktı. Yöntemler: Eylül 2018-Eylül 2019 arasında (kurumsal bilgi körlendi) yürütülen bir vaka kontrol çalışmasıdır. Çalışmaya tümör nekroz faktör-alfa bloker ilaç alan 35 hasta ve benzer demografik özelliklere sahip 37 sağlıklı kontrol deneği dahil edildi. Hasta grubunun hastalık aktivite skorları ile hasta ve kontrol grubunun fiziksel fonksiyon skorları sorgulandı. Tüm hastalara detaylı fiziksel ve nörolojik muayene yapıldı. Daha sonra periferik sinirler nörofizyolojik olarak değerlendirildi. Dağılıma göre gruplar karşılaştırılırken Mann-Whitney U testi veya Independent samples t-testi kullanıldı. Kısa Form-36 ile yaş veya vücut kitle indeksi arasındaki ilişki, Spearman'ın sıra korelasyon katsayısı kullanılarak belirlendi. Bulgular: Duyusal ve motor sinir ileti incelemelerinde elde edilen sonuçlar gruplar arasında karşılaştırıldı. Antitümör nekroz faktör-alfa ilacı kullanan hastalarda periferik duyusal nöropati tespit edildi. Periferik motor sinirlerin incelemesi normal sınırlardaydı. Sonuç: Anti-tümör nekroz faktör-alfa ilaçları enflamatuar hastalıklarda oldukça etkilidir. Bu ilaçları kullanan hastalar nörolojik bulgular açısından dikkatle izlenmelidir.

Evaluation of peripheral nerves in patients receiving anti-tumor necrosis factor-alpha drug therapy

Aim: Anti-tumor necrosis factor-alpha (TNF-α) drug treatments are widely used in many inflammatory diseases. Neurological complications have rarely been reported in these treatments. Our aim in this study was to investigate the neurological findings that occurred in our patients receiving this treatment. Methods: A case-control study conducted in (institutional information was blinded) between September 2018- September 2019. The study included 35 patients receiving tumor necrosis factor-alpha blocker drug, and 37 healthy control subjects with similar demographic characteristics. The disease activity scores of the patient group and physical function scores of the patient and control groups were questioned. All patients underwent a detailed physical and neurological examination. Afterward, peripheral nerves were evaluated neurophysiologically. According to distribution Mann-Whitney U test or independent samples t-test was used when comparing groups. The relationship between Short Form-36 and age or body mass index was determined by using Spearman’s rank correlation coefficient. Results: The results obtained in sensory and motor nerve conduction examinations were compared between groups. Patients using anti-tumor necrosis factor-alpha had peripheral sensory neuropathy. Examination of peripheral motor nerves was within normal limits. Conclusions: Anti-tumor necrosis factor-alpha drugs have good effects in inflammatory diseases. These patients should be carefully monitored for neurological findings.

PDF

___

1. Feldmann M, Steinman L. Design of effective immunotherapy for human autoimmunity. Nature. 2005;435:612-619.
2. Monaco C, Nanchahal J, Taylor P, Feldmann M. Anti-TNF therapy: past, present and future. Int Immunol. 2015;27:55-62.
3. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117:244-279.
4. Keystone EC. Tumor necrosis factor-α blockade in the treatment of rheumatoid arthritis. Rheum Dis Clin North Am. 2001;27:427-443.
5. Horiuchi T, Mitoma H, Harashima Si, Tsukamoto H, Shimoda T. Transmembrane TNF-α: structure, function and interaction with antiTNF agents. Rheumatology. 2010;49:1215-1228.
6. Meroni PL, Valesini G. Tumour necrosis factor α antagonists in the treatment of rheumatoid arthritis: an immunological perspective. BioDrugs. 2014;28:5-13.
7. Kirchner S, Holler E, Haffner S, Andreesen R, Eissner G. Effect of different tumor necrosis factor (TNF) reactive agents on reverse signaling of membrane integrated TNF in monocytes. Cytokine. 2004;28:67-74.
8. Grom AA, Murray KJ, Luyrink L, Emery H, Passo MH, Glass DN, et al. Patterns of expression of tumor necrosis factor α, tumor necrosis factor β, and their receptors in synovia of patients with juvenile rheumatoid arthritis and juvenile spondylarthropathy. Arthritis Rheum. 1996;39:1703-1710.
9. Strangfeld A, Listing J. Bacterial and opportunistic infections during anti-TNF therapy. Best Pract Res Clin Rheumatol. 2006;20:1181-1195.
10. Kemanetzoglou E, Andreadou E. CNS demyelination with TNF-α blockers. Curr Neurol Neurosci Rep. 2017;17:36.
11. Tristano AG. Neurological adverse events associated with antitumor necrosis factor alpha treatment. J Neurol. 2010;257:1421-1431.
12. Bosch X, Saiz A, Ramos-Casals M, Group BS. Monoclonal antibody therapy-associated neurological disorders. Nat Rev Neurol. 2011;7:165.
13. Benatar M, Wuu J, Peng L. Reference data for commonly used sensory and motor nerve conduction studies. Muscle Nerve: Official Journal of the American Association of Electrodiagnostic Medicine. 2009;40:772-794.
14. Magnano M, Robinson W, Genovese M. Demyelination and inhibition of tumor necrosis factor (TNF). Clin Exp Rheumatol. 2004;22:134-140.
15. Mohan N, Edwards ET, Cupps TR, Oliverio PJ, Sandberg G, Crayton H, et al. Demyelination occurring during anti–tumor necrosis factor α therapy for inflammatory arthritides. Arthritis Rheum. 2001;44:2862-2869.
16. Tektonidou MG, Serelis J, Skopouli FN. Peripheral neuropathy in two patients with rheumatoid arthritis receiving infliximab treatment. Clin Rheumatol. 2007;26:258-260.
17. Seror R, Richez C, Sordet C, Rist S, Gossec L, Direz G, et al. Pattern of demyelination occurring during anti-TNF-α therapy: a French national survey. Rheumatology. 2013;52:868-874.
18. Makol A, Grover M. Adalimumab induced mononeuritis multiplex in a patient with refractory rheumatoid arthritis: a case report. Cases J. 2008;1:1-2.
19. Cámara Lemarroy CR, Guzmán de la Garza FJ, Fernández Garza NE. Molecular inflammatory mediators in peripheral nerve degeneration and regeneration. Neuroimmunomodulation. 2010;17:314-324.
20. Park KM, Bowers WJ. Tumor necrosis factor-alpha mediated signaling in neuronal homeostasis and dysfunction. Cell Signal. 2010;22:977-983.