The Effect of Fingolimod (FTY720) Treatment on Liver Enzyme Levels in Relapsing-Remitting Multiple Sclerosis Patients

Year 2020, Volume: 22 Issue: 3, 175 - 179, 30.12.2020

Duygu Tap Menderes Yusuf Terzi , Taşkın Duman

https://doi.org/10.18678/dtfd.775966

Abstract

Aim: Multiple sclerosis (MS) is a chronic inflammatory pathology affecting the central nervous system. Many therapeutic options have been approved against MS until today. In this study, it was aimed to investigate the effect of fingolimod treatment (FT) on the liver enzyme levels of relapsing-remitting multiple sclerosis (RRMS) patients.
Material and Methods: Body mass index, FT (0.5 mg/day) duration, and liver enzyme (alanine aminotransferase, ALT; gamma glutamyl transferase, GGT) levels of 102 RRMS patients (66 female, 36 male, mean age was 40.9±10.9 years) were gathered from polyclinic records retrospectively.
Results: The FT duration of MS patients was between 0.5 and 6 years. Increased ALT and GGT levels were detected in RRMS patients after >3 month-long FT. After FT, ALT and GGT levels elevated in males almost 2 times higher than in females. It was observed that ALT and GGT levels increased by 1.3 and 1.5 times in females, while 1.6 and 1.9 times in males, respectively. Of the MS patients with increased transaminases post-FT, 7 (23.3%) males and 8 (17.4%) females were at upper limit of normal for ALT whereas 9 (34.6%) males and 14 (32.6%) females as for GGT. Age and FT duration did not affect ALT and GGT levels.
Conclusion: Overall, FT elevated ALT and GGT levels of RRMS patients. Thus, it is of high importance to monitor MS patients throughout FT. So that, we suggest tracking ALT and GGT levels during and after FT to prevent possible liver damage or the occurrence of other systemic diseases.

Keywords

Relapsing-remitting multiple sclerosis, fingolimod, liver enzyme, ALT, GGT

Fingolimod (FTY720) Tedavisinin Relapsing-Remitting Multipl Skleroz Hastalarında Karaciğer Enzim Düzeylerine Etkisi

Abstract

Amaç: Multipl skleroz (MS) merkezi sinir sistemini etkileyen kronik inflamatuvar bir patolojidir. Günümüze kadar MS’e karşı birçok tedavi seçeneği onaylanmıştır. Bu çalışmada, fingolimod tedavisinin (FT) relapsing-remitting multipl skleroz (RRMS) hastalarının karaciğer enzim düzeylerine etkisinin araştırılması amaçlanmıştır.
Gereç ve Yöntemler: Yüz iki RRMS hastasının (66 kadın, 36 erkek, ortalama yaş 40,9±10,9 yıl) vücut kitle indeksi, FT (0,5 mg/gün) süreleri ve karaciğer enzim (alanin aminotransferaz, ALT; gama glutamil transferaz, GGT) seviyeleri poliklinik kayıtlarından geriye dönük olarak incelendi.
Bulgular: MS hastalarının FT süresi 0,5 ile 6 yıl arasındaydı. Üç ay ve daha fazla FT süresi olan RRMS hastalarında ALT ve GGT seviyelerinin arttığı tespit edildi. FT sonrası, ALT ve GGT seviyeleri erkeklerde kadınlara kıyasla yaklaşık olarak 2 kat daha yüksekti. Kadınlarda ALT ve GGT seviyelerinin sırasıyla 1,3 ve 1,5 kat, erkeklerde ise bu seviyelerin 1,6 ve 1,9 kat arttığı görüldü. FT sonrası transaminaz seviyesi artan MS hastalarından 9 (%34,6) erkek ve 14 (%32,6) kadın GGT için normalin üst seviyesindeyken, 7 (%23,3) erkek ve 8 (%17,4) kadın ALT için normalin üst seviyesindeydi. Yaş ve FT süresi, ALT ve GGT seviyelerini etkilemiyordu.
Sonuç: Sonuç olarak, FT RRMS hastalarının ALT ve GGT seviyelerini yükseltmiştir. Bundan dolayı, MS hastalarının FT süresince takibi oldukça önemlidir. Bu yüzden, MS hastalarında olası karaciğer hasarı ya da diğer sistemik hastalıkların önlenmesi için FT sırasında ve sonrasında ALT ve GGT seviyelerinin takip edilmesini öneriyoruz.

Keywords

Relapsing-remitting multipl skleroz, fingolimod, karaciğer enzimi, ALT, GGT

References

• Leray E, Moreau T, Fromont A, Edan G. Epidemiology of multiple sclerosis. Rev Neurol (Paris). 2016;172(1):3-13.
• Ingwersen J, Aktas O, Kuery P, Kieseier B, Boyko A, Hartung HP. Fingolimod in multiple sclerosis: mechanisms of action and clinical efficacy. Clin Immunol. 2012;142(1):15-24.
• Cohen JA, Chun J. Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis. Ann Neurol. 2011;69(5):759-77.
• Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature. 2004;427(6972):355-60.
• Pitman MR, Woodcock JM, Lopez AF, Pitson SM. Molecular targets of FTY720 (fingolimod). Curr Mol Med. 2012;12(10):1207-19.
• Bascuñana P, Möhle L, Brackhan M, Pahnke J. Fingolimod as a treatment in neurologic disorders beyond multiple sclerosis. Drugs R D. 2020;20(3):197-207.
• Schwab SR, Cyster JG. Finding a way out: lymphocyte egress from lymphoid organs. Nat Immunol. 2007;8(12):1295-301.
• Yang CC, Ro LS, Tsai NW, Lin CC, Huang WN, Tsai CP, et al. Real-world evidence on the safety and effectiveness of fingolimod in patients with multiple sclerosis from Taiwan. J Formos Med Assoc. 2020;120(1):542-50.
• Lattanzi S, Rocchi C, Danni M, Taffi R, Cerqua R, Carletti S, et al. Long-term outcome in multiple sclerosis patients treated with fingolimod. Mult Scler Relat Disord. 2020;45:102416.
• Rojas JI, Patrucco L, Miguez J, Cristiano E. Real-world safety and patient profile of fingolimod in relapsing-remitting multiple sclerosis: a prospective analysis in Buenos Aires, Argentina. Clin Neuropharmacol. 2017;40(6):251-4.
• Baroncini D, Zaffaroni M, Annovazzi PO, Baldini S, Bianchi A, Minonzio G, et al. A real world experience with fingolimod in active RRMS patients naïve to second-line agents: a 2 years, intention-to-treat, observational, single center study. Mult Scler Demyelinating Disord. 2016;1(1):4.
• Calabresi PA, Radue EW, Goodin D, Jeffery D, Rammohan KW, Reder AT, et al. Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13(6):545-56.
• Saida T, Kikuchi S, Itoyama Y, Hao Q, Kurosawa T, Nagato K, et al. A randomized, controlled trial of fingolimod (FTY720) in Japanese patients with multiple sclerosis. Mult Scler. 2012;18(9):1269-77.
• Fazekas F, Berger T, Fabjan TH, Ledinek AH, Jakab G, Komoly S, et al. Fingolimod in the treatment algorithm of relapsing remitting multiple sclerosis: a statement of the Central and East European (CEE) MS Expert Group. Wien Med Wochenschr. 2012;162(15-16):354-66.
• Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med. 2000;342(17):1266-71.
• Verslype C. Evaluation of abnormal liver-enzyme results in asymptomatic patients. Acta Clin Belg. 2004;59(5):285-9.
• McNicholas N, Hutchinson M, McGuigan C, Chataway J. 2017 McDonald diagnostic criteria: A review of the evidence. Mult Scler Relat Disord. 2018;24:48-54.
• Hersh CM, Hara-Cleaver C, Rudick RA, Cohen JA, Bermel RA, Ontaneda D. Experience with fingolimod in clinical practice. Int J Neurosci. 2015;125(9):678-85.
• Sonne SJ, Smith BT. Incidence of uveitis and macular edema among patients taking fingolimod 0.5 mg for multiple sclerosis. J Ophthalmic Inflamm Infect. 2020;10(1):24.
• Kira J, Itoyama Y, Kikuchi S, Hao Q, Kurosawa T, Nagato K, et al. Fingolimod (FTY720) therapy in Japanese patients with relapsing multiple sclerosis over 12 months: results of a phase 2 observational extension. BMC Neurol. 2014;14:21.
• Yamout BI, Zeineddine MM, Tamim H, Khoury SJ. Safety and efficacy of fingolimod in clinical practice: The experience of an academic center in the Middle East. J Neuroimmunol. 2015;289:93-7.
• Manni A, Direnzo V, Iaffaldano A, Di Lecce V, Tortorella C, Zoccolella S, et al. Gender differences in safety issues during fingolimod therapy: evidence from a real-life relapsing multiple sclerosis cohort. Brain Behav. 2017;7(10):e00804.
• Quinn PG, Johnston DE. Detection of chronic liver disease: costs and benefits. Gastroenterologist. 1997;5(1):58-77.
• Kappos L, Radue EW, O'Connor P, Polman C, Hohlfeld R, Calabresi P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010;362(5):387-401.
• Joni SS, Cheshmavar M, Shoureshi P, Zamani Z, Taoosi N, Akbari M, et al. Effects of fingolimod treatments on alanine transaminase and aspartate transaminase levels in patients with multiple sclerosis. Int J Physiol Pathophysiol Pharmacol. 2020;12(3):88-94.
• Ordoñez-Boschetti L, Rey R, Cruz A, Sinha A, Reynolds T, Frider N, et al. Safety and tolerability of fingolimod in Latin American patients with relapsing-remitting multiple sclerosis: The Open-Label FIRST LATAM Study. Adv Ther. 2015;32(7):626-35.
• Francis MM, Hummer TA, Liffick E, Vohs JL, Mehdiyoun NF, Visco AC, et al. Effects of fingolimod, a sphingosine-1-phosphate (S1P) receptor agonist, on white matter microstructure, cognition and symptoms in schizophrenia. Brain Imaging Behav. 2020;[Epub ahead of print]. doi: 10.1007/s11682-020-00375-7.
• Berry JD, Paganoni S, Atassi N, Macklin EA, Goyal N, Rivner M, et al. Phase IIa trial of fingolimod for amyotrophic lateral sclerosis demonstrates acceptable acute safety and tolerability. Muscle Nerve. 2017;56(6):1077-84.