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Published in: European Archives of Oto-Rhino-Laryngology 2/2020

01-02-2020 | Audiometry | Otology

Intratympanic infliximab is a safe and effective rescue therapy for refractory immune-mediated hearing loss

Authors: Nieves Mata-Castro, Lorena Sanz-López, David Varillas-Delgado, Alfredo García-Fernández

Published in: European Archives of Oto-Rhino-Laryngology | Issue 2/2020

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Abstract

Purpose

To determine the efficacy and safety of the intratympanic infiltration of infliximab at the hearing threshold of patients in follow-up for refractory immune-mediated hearing loss.

Methods

17 patients were collected with relapses, despite maintenance treatment with oral azathioprine associated or not with oral prednisone at low doses (between 5 and 7.5 ml/day) or refractory relapses to previous intratympanic corticoid treatment being 19 affected ears infiltrated. We measured the hearing threshold by Pure-Tone Average (PTA) 500–3000 Hz, 125–8000 Hz and 250–8000 Hz in pre-infiltration (baseline) and follow-up 3 weeks post-infiltration with auditory threshold at frequencies 125–8000 Hz.

Results

The average age was 50.68 years (±15.23 years). After the administration of intratympanic infliximab, an improvement of the hearing threshold was showed in the Pure-Tone Average (PTA) calculated at 500–3000 Hz (p = 0.004), 125–8000 Hz (p = 0.001) and 250–8000 Hz (p = 0.006). An immediate improvement in low frequencies also was observed: 125, 250 and 500 Hz (p = 0.009, p = 0.002 and p < 0.001 respectively) also at 1000 Hz (p = 0.004) and a persistence of the effect at 3 months in the low frequencies: 125 Hz (p = 0.020), 250 Hz (p = 0.006) and 500 Hz (p = 0.002).

Conclusions

Infliximab intratympanic infiltration improves the hearing threshold in patients with immune-mediated hearing loss. The effect of improving the hearing threshold is higher in low frequencies and persists within 3 months of the infiltration. The administration of intratympanic infliximab is an effective and safe technique.
Literature
1.
go back to reference Chau JK, Cho JJ, Fritz DK (2012) Evidence-based practice: management of adult sensorineural hearing loss. Otolaryngol Clin North Am 45:941–958CrossRef Chau JK, Cho JJ, Fritz DK (2012) Evidence-based practice: management of adult sensorineural hearing loss. Otolaryngol Clin North Am 45:941–958CrossRef
2.
go back to reference Vambutas A, Pathak S (2016) AAO: Autoimmune and Autoinflammatory (Disease) in Otology: What is New in Immune-Mediated Hearing Loss. Laryngoscope Investig Otolaryngol 1:110–115CrossRef Vambutas A, Pathak S (2016) AAO: Autoimmune and Autoinflammatory (Disease) in Otology: What is New in Immune-Mediated Hearing Loss. Laryngoscope Investig Otolaryngol 1:110–115CrossRef
3.
go back to reference Garcia-Berrocal JR, Ibanez A, Rodriguez A, Gonzalez-Garcia JA, Verdaguer JM, Trinidad A, Ramirez-Camacho R (2006) Alternatives to systemic steroid therapy for refractory immune-mediated inner ear disease: a physiopathologic approach. Eur Arch Otorhinolaryngol 263:977–982CrossRef Garcia-Berrocal JR, Ibanez A, Rodriguez A, Gonzalez-Garcia JA, Verdaguer JM, Trinidad A, Ramirez-Camacho R (2006) Alternatives to systemic steroid therapy for refractory immune-mediated inner ear disease: a physiopathologic approach. Eur Arch Otorhinolaryngol 263:977–982CrossRef
4.
go back to reference Rahman MU, Poe DS, Choi HK (2001) Autoimmune vestibulo-cochlear disorders. Curr Opin Rheumatol 13:184–189CrossRef Rahman MU, Poe DS, Choi HK (2001) Autoimmune vestibulo-cochlear disorders. Curr Opin Rheumatol 13:184–189CrossRef
5.
go back to reference Lobo D, Garcia-Berrocal JR, Trinidad A, Verdaguer JM, Ramirez-Camacho R (2013) Review of the biologic agents used for immune-mediated inner ear disease. Acta Otorrinolaringol Esp 64:223–229CrossRef Lobo D, Garcia-Berrocal JR, Trinidad A, Verdaguer JM, Ramirez-Camacho R (2013) Review of the biologic agents used for immune-mediated inner ear disease. Acta Otorrinolaringol Esp 64:223–229CrossRef
6.
go back to reference Demirhan E, Eskut NP, Zorlu Y, Cukurova I, Tuna G, Kirkali FG (2013) Blood levels of TNF-alpha, IL-10, and IL-12 in idiopathic sudden sensorineural hearing loss. Laryngoscope 123:1778–1781CrossRef Demirhan E, Eskut NP, Zorlu Y, Cukurova I, Tuna G, Kirkali FG (2013) Blood levels of TNF-alpha, IL-10, and IL-12 in idiopathic sudden sensorineural hearing loss. Laryngoscope 123:1778–1781CrossRef
7.
go back to reference Satoh H, Firestein GS, Billings PB, Harris JP, Keithley EM (2003) Proinflammatory cytokine expression in the endolymphatic sac during inner ear inflammation. J Assoc Res Otolaryngol 4:139–147CrossRef Satoh H, Firestein GS, Billings PB, Harris JP, Keithley EM (2003) Proinflammatory cytokine expression in the endolymphatic sac during inner ear inflammation. J Assoc Res Otolaryngol 4:139–147CrossRef
8.
go back to reference Fujioka M, Okano H, Ogawa K (2014) Inflammatory and immune responses in the cochlea: potential therapeutic targets for sensorineural hearing loss. Front Pharmacol 5:287CrossRef Fujioka M, Okano H, Ogawa K (2014) Inflammatory and immune responses in the cochlea: potential therapeutic targets for sensorineural hearing loss. Front Pharmacol 5:287CrossRef
9.
go back to reference Yoshida K, Ichimiya I, Suzuki M, Mogi G (1999) Effect of proinflammatory cytokines on cultured spiral ligament fibrocytes. Hear Res 137:155–159CrossRef Yoshida K, Ichimiya I, Suzuki M, Mogi G (1999) Effect of proinflammatory cytokines on cultured spiral ligament fibrocytes. Hear Res 137:155–159CrossRef
10.
go back to reference Okano T (2014) Immune system of the inner ear as a novel therapeutic target for sensorineural hearing loss. Front Pharmacol 5:205CrossRef Okano T (2014) Immune system of the inner ear as a novel therapeutic target for sensorineural hearing loss. Front Pharmacol 5:205CrossRef
11.
go back to reference Monaco C, Nanchahal J, Taylor P, Feldmann M (2015) Anti-TNF therapy: past, present and future. Int Immunol 27:55–62CrossRef Monaco C, Nanchahal J, Taylor P, Feldmann M (2015) Anti-TNF therapy: past, present and future. Int Immunol 27:55–62CrossRef
12.
go back to reference Hess A, Bloch W, Huverstuhl J, Su J, Stennert E, Addicks K, Michel O (1999) Expression of inducible nitric oxide synthase (iNOS/NOS II) in the cochlea of guinea pigs after intratympanical endotoxin-treatment. Brain Res 830:113–122CrossRef Hess A, Bloch W, Huverstuhl J, Su J, Stennert E, Addicks K, Michel O (1999) Expression of inducible nitric oxide synthase (iNOS/NOS II) in the cochlea of guinea pigs after intratympanical endotoxin-treatment. Brain Res 830:113–122CrossRef
13.
go back to reference Warchol ME (1999) Immune cytokines and dexamethasone influence sensory regeneration in the avian vestibular periphery. J Neurocytol 28:889–900CrossRef Warchol ME (1999) Immune cytokines and dexamethasone influence sensory regeneration in the avian vestibular periphery. J Neurocytol 28:889–900CrossRef
14.
go back to reference Warchol ME, Kaplan BA (1999) Macrophage secretory products influence the survival of statoacoustic neurons. NeuroReport 10:665–668CrossRef Warchol ME, Kaplan BA (1999) Macrophage secretory products influence the survival of statoacoustic neurons. NeuroReport 10:665–668CrossRef
15.
go back to reference Van den Brande JM, Braat H, van den Brink GR, Versteeg HH, Bauer CA, Hoedemaeker I, van Montfrans C, Hommes DW, Peppelenbosch MP, van Deventer SJ (2003) Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease. Gastroenterology 124:1774–1785CrossRef Van den Brande JM, Braat H, van den Brink GR, Versteeg HH, Bauer CA, Hoedemaeker I, van Montfrans C, Hommes DW, Peppelenbosch MP, van Deventer SJ (2003) Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease. Gastroenterology 124:1774–1785CrossRef
16.
go back to reference Lavigne P, Lavigne F, Saliba I (2016) Intratympanic corticosteroids injections: a systematic review of literature. Eur Arch Otorhinolaryngol 273:2271–2278CrossRef Lavigne P, Lavigne F, Saliba I (2016) Intratympanic corticosteroids injections: a systematic review of literature. Eur Arch Otorhinolaryngol 273:2271–2278CrossRef
17.
go back to reference Huon LK, Fang TY, Wang PC (2012) Outcomes of intratympanic gentamicin injection to treat Meniere's disease. Otol Neurotol 33:706–714CrossRef Huon LK, Fang TY, Wang PC (2012) Outcomes of intratympanic gentamicin injection to treat Meniere's disease. Otol Neurotol 33:706–714CrossRef
18.
go back to reference Van Wijk F, Staecker H, Keithley E, Lefebvre PP (2006) Local perfusion of the tumor necrosis factor alpha blocker infliximab to the inner ear improves autoimmune neurosensory hearing loss. Audiol Neurootol 11:357–365CrossRef Van Wijk F, Staecker H, Keithley E, Lefebvre PP (2006) Local perfusion of the tumor necrosis factor alpha blocker infliximab to the inner ear improves autoimmune neurosensory hearing loss. Audiol Neurootol 11:357–365CrossRef
19.
go back to reference Harris JP, Weisman MH, Derebery JM, Espeland MA, Gantz BJ, Gulya AJ, Hammerschlag PE, Hannley M, Hughes GB, Moscicki R, Nelson RA, Niparko JK, Rauch SD, Telian SA, Brookhouser PE (2003) Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate: a randomized controlled trial. JAMA 290:1875–1883CrossRef Harris JP, Weisman MH, Derebery JM, Espeland MA, Gantz BJ, Gulya AJ, Hammerschlag PE, Hannley M, Hughes GB, Moscicki R, Nelson RA, Niparko JK, Rauch SD, Telian SA, Brookhouser PE (2003) Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate: a randomized controlled trial. JAMA 290:1875–1883CrossRef
20.
go back to reference Hamid M, Trune D (2008) Issues, indications, and controversies regarding intratympanic steroid perfusion. Curr Opin Otolaryngol Head Neck Surg 16:434–440CrossRef Hamid M, Trune D (2008) Issues, indications, and controversies regarding intratympanic steroid perfusion. Curr Opin Otolaryngol Head Neck Surg 16:434–440CrossRef
21.
go back to reference Mata-Castro N, Gavilanes-Plasencia J, Ramirez-Camacho R, Garcia-Fernandez A, Garcia-Berrocal JR (2018) Azathioprine reduces the risk of audiometric relapse in immune-mediated hearing loss. Acta Otorrinolaringol Esp 69:260–267CrossRef Mata-Castro N, Gavilanes-Plasencia J, Ramirez-Camacho R, Garcia-Fernandez A, Garcia-Berrocal JR (2018) Azathioprine reduces the risk of audiometric relapse in immune-mediated hearing loss. Acta Otorrinolaringol Esp 69:260–267CrossRef
22.
go back to reference Ghossaini SN, Liu JP, Phillips B (2013) Round window membrane permeability to golimumab in guinea pigs: a pilot study. Laryngoscope 123:2840–2844CrossRef Ghossaini SN, Liu JP, Phillips B (2013) Round window membrane permeability to golimumab in guinea pigs: a pilot study. Laryngoscope 123:2840–2844CrossRef
23.
go back to reference Salt AN, Plontke SK (2018) Pharmacokinetic principles in the inner ear: Influence of drug properties on intratympanic applications. Hear Res 368:28–40CrossRef Salt AN, Plontke SK (2018) Pharmacokinetic principles in the inner ear: Influence of drug properties on intratympanic applications. Hear Res 368:28–40CrossRef
24.
go back to reference Plontke SK, Biegner T, Kammerer B, Delabar U, Salt AN (2008) Dexamethasone concentration gradients along scala tympani after application to the round window membrane. Otol Neurotol 29:401–406CrossRef Plontke SK, Biegner T, Kammerer B, Delabar U, Salt AN (2008) Dexamethasone concentration gradients along scala tympani after application to the round window membrane. Otol Neurotol 29:401–406CrossRef
25.
go back to reference Sanz L, Murillo-Cuesta S, Cobo P, Cediel-Algovia R, Contreras J, Rivera T, Varela-Nieto I, Avendano C (2015) Swept-sine noise-induced damage as a hearing loss model for preclinical assays. Front Aging Neurosci 7:7PubMedPubMedCentral Sanz L, Murillo-Cuesta S, Cobo P, Cediel-Algovia R, Contreras J, Rivera T, Varela-Nieto I, Avendano C (2015) Swept-sine noise-induced damage as a hearing loss model for preclinical assays. Front Aging Neurosci 7:7PubMedPubMedCentral
26.
go back to reference Wang X, Truong T, Billings PB, Harris JP, Keithley EM (2003) Blockage of immune-mediated inner ear damage by etanercept. Otol Neurotol 24:52–57CrossRef Wang X, Truong T, Billings PB, Harris JP, Keithley EM (2003) Blockage of immune-mediated inner ear damage by etanercept. Otol Neurotol 24:52–57CrossRef
27.
go back to reference Eren SB, Dogan R, Yenigun A, Veyseller B, Tugrul S, Ozturan O, Aydin MS (2017) Evaluation of ototoxicity of intratympanic administration of Methotrexate in rats. Int J Pediatr Otorhinolaryngol 100:132–136CrossRef Eren SB, Dogan R, Yenigun A, Veyseller B, Tugrul S, Ozturan O, Aydin MS (2017) Evaluation of ototoxicity of intratympanic administration of Methotrexate in rats. Int J Pediatr Otorhinolaryngol 100:132–136CrossRef
28.
go back to reference Mata-Castro N, Garcia-Chilleron R, Gavilanes-Plasencia J, Ramirez-Camacho R, Garcia-Fernandez A, Garcia-Berrocal JR (2018) Analysis of audiometric relapse-free survival in patients with immune-mediated hearing loss exclusively treated with corticosteroids. Acta Otorrinolaringol Esp 69:214–218CrossRef Mata-Castro N, Garcia-Chilleron R, Gavilanes-Plasencia J, Ramirez-Camacho R, Garcia-Fernandez A, Garcia-Berrocal JR (2018) Analysis of audiometric relapse-free survival in patients with immune-mediated hearing loss exclusively treated with corticosteroids. Acta Otorrinolaringol Esp 69:214–218CrossRef
29.
go back to reference Lee KY, Nakagawa T, Okano T, Hori R, Ono K, Tabata Y, Lee SH, Ito J (2007) Novel therapy for hearing loss: delivery of insulin-like growth factor 1 to the cochlea using gelatin hydrogel. Otol Neurotol 28:976–981CrossRef Lee KY, Nakagawa T, Okano T, Hori R, Ono K, Tabata Y, Lee SH, Ito J (2007) Novel therapy for hearing loss: delivery of insulin-like growth factor 1 to the cochlea using gelatin hydrogel. Otol Neurotol 28:976–981CrossRef
30.
go back to reference Yamamoto N, Nakagawa T, Ito J (2014) Application of insulin-like growth factor-1 in the treatment of inner ear disorders. Front Pharmacol 5:208CrossRef Yamamoto N, Nakagawa T, Ito J (2014) Application of insulin-like growth factor-1 in the treatment of inner ear disorders. Front Pharmacol 5:208CrossRef
31.
go back to reference Martin-Saldana S, Palao-Suay R, Aguilar MR, Ramirez-Camacho R, San Roman J (2017) Polymeric nanoparticles loaded with dexamethasone or alpha-tocopheryl succinate to prevent cisplatin-induced ototoxicity. Acta Biomater 53:199–210CrossRef Martin-Saldana S, Palao-Suay R, Aguilar MR, Ramirez-Camacho R, San Roman J (2017) Polymeric nanoparticles loaded with dexamethasone or alpha-tocopheryl succinate to prevent cisplatin-induced ototoxicity. Acta Biomater 53:199–210CrossRef
32.
go back to reference Murillo-Cuesta S, Garcia-Alcantara F, Vacas E, Sistiaga JA, Camarero G, Varela-Nieto I, Rivera T (2009) Direct drug application to the round window: a comparative study of ototoxicity in rats. Otolaryngol Head Neck Surg 141:584–590CrossRef Murillo-Cuesta S, Garcia-Alcantara F, Vacas E, Sistiaga JA, Camarero G, Varela-Nieto I, Rivera T (2009) Direct drug application to the round window: a comparative study of ototoxicity in rats. Otolaryngol Head Neck Surg 141:584–590CrossRef
33.
go back to reference Staecker H, Brough DE, Praetorius M, Baker K (2004) Drug delivery to the inner ear using gene therapy. Otolaryngol Clin North Am 37:1091–1108CrossRef Staecker H, Brough DE, Praetorius M, Baker K (2004) Drug delivery to the inner ear using gene therapy. Otolaryngol Clin North Am 37:1091–1108CrossRef
Metadata
Title
Intratympanic infliximab is a safe and effective rescue therapy for refractory immune-mediated hearing loss
Authors
Nieves Mata-Castro
Lorena Sanz-López
David Varillas-Delgado
Alfredo García-Fernández
Publication date
01-02-2020
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Oto-Rhino-Laryngology / Issue 2/2020
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-019-05716-x

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