Skip to main content
Erschienen in: Journal of Neurology 9/2017

22.08.2017 | Original Communication

Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder: a randomized clinical trial

verfasst von: Zahra Nikoo, Shervin Badihian, Vahid Shaygannejad, Nasrin Asgari, Fereshteh Ashtari

Erschienen in: Journal of Neurology | Ausgabe 9/2017

Einloggen, um Zugang zu erhalten

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) often follows a relapsing course. As disability in NMOSD is attack-related, effective treatments are needed. We aimed to compare the efficacy of azathioprine (AZA) and rituximab (RIT) as maintenance therapy in NMOSD patients. An open, randomized clinical trial was conducted during September 2015 to December 2016, in Isfahan, Iran. Initially, 100 NMOSD patients were approached, 86 entered the study, and 68 cases completed the trial. All patients had a relapsing–remitting course with expanded disability extended scale (EDSS) ≤7 (median 2.75, range = 0–7). Patients were randomized into two groups, which did not differ according to age, gender distribution, and disease duration. In the AZA group, 35 patients [20 aquaporin-4 (AQP4)-IgG positive] were started on 50 mg/day oral AZA and increased to 2–3 mg/kg/day (with oral prednisolone as adjunctive therapy). In the RIT group, 33 patients (13 aquaporin-4-IgG positive) received 1 g intravenous rituximab and repeated 2 weeks later and then every 6 months. Annualized relapse rate (ARR) was measured as the primary outcome and EDSS as the secondary outcome after 12 months of intervention. The mean ARR [standard deviation (SD)] in the AZA group decreased from 1 (0.38) to 0.51 (0.55) (P value <0.001) and in the RIT group decreased from 1.30 (0.68) to 0.21 (0.42) (P value <0.001). ARR after intervention minus ARR before intervention [mean (SD)] was 1.09 (0.72) in RIT group and 0.49 (0.59) in AZA group (P value <0.001). EDSS after intervention minus EDSS before intervention [mean (SD)] was 0.98 (1.14) in RIT group and 0.44 (0.54) in AZA group (P value <0.001). Nineteen patients (54.3%) in AZA group and 26 patients (78.8%) in RIT group became relapse-free after intervention (P value = 0.033). AZA and RIT can both effectively decrease ARR and EDSS in NMOSD patients. RIT was significantly more effective than AZA treatment.
Trial Registration Name of registry: clinicaltrials.gov; ID: NCT03002038; URL: https://​clinicaltrials.​gov/​ct2/​show/​NCT03002038.
Literatur
1.
Zurück zum Zitat Bedi GS, Brown AD, Delgado SR, Usmani N, Lam BL, Sheremata WA (2011) Impact of rituximab on relapse rate and disability in neuromyelitis optica. Mult Scler J 17:1225–1230CrossRef Bedi GS, Brown AD, Delgado SR, Usmani N, Lam BL, Sheremata WA (2011) Impact of rituximab on relapse rate and disability in neuromyelitis optica. Mult Scler J 17:1225–1230CrossRef
2.
Zurück zum Zitat Bichuetti DB, de Oliveira EML, Oliveira DM, de Souza NA, Gabbai AA (2010) Neuromyelitis optica treatment: analysis of 36 patients. Arch Neurol 67:1131–1136CrossRefPubMed Bichuetti DB, de Oliveira EML, Oliveira DM, de Souza NA, Gabbai AA (2010) Neuromyelitis optica treatment: analysis of 36 patients. Arch Neurol 67:1131–1136CrossRefPubMed
3.
Zurück zum Zitat Carreón-Guarnizo E, Hernández-Clares R, Palazón-Cabanes B, Carrasco-Torres R, Salgado G, Jimenez-Veiga J, León-Hernández A, Martín-Fernández JJ, Meca-Lallana J (2015) Safety of rituximab as first-line therapy in neuromyelitis optica (NMO) and NMO-spectrum disorders: five years of experience (P5. 264). Neurology 84(P5):264 Carreón-Guarnizo E, Hernández-Clares R, Palazón-Cabanes B, Carrasco-Torres R, Salgado G, Jimenez-Veiga J, León-Hernández A, Martín-Fernández JJ, Meca-Lallana J (2015) Safety of rituximab as first-line therapy in neuromyelitis optica (NMO) and NMO-spectrum disorders: five years of experience (P5. 264). Neurology 84(P5):264
4.
Zurück zum Zitat Costanzi C, Matiello M, Lucchinetti CF, Weinshenker BG, Pittock SJ, Mandrekar J, Thapa P, McKeon A (2011) Azathioprine tolerability, efficacy, and predictors of benefit in neuromyelitis optica. Neurology 77:659–666CrossRefPubMed Costanzi C, Matiello M, Lucchinetti CF, Weinshenker BG, Pittock SJ, Mandrekar J, Thapa P, McKeon A (2011) Azathioprine tolerability, efficacy, and predictors of benefit in neuromyelitis optica. Neurology 77:659–666CrossRefPubMed
5.
Zurück zum Zitat Cree B, Lamb S, Morgan K, Chen A, Waubant E, Genain C (2005) An open label study of the effects of rituximab in neuromyelitis optica. Neurology 64:1270–1272CrossRefPubMed Cree B, Lamb S, Morgan K, Chen A, Waubant E, Genain C (2005) An open label study of the effects of rituximab in neuromyelitis optica. Neurology 64:1270–1272CrossRefPubMed
6.
Zurück zum Zitat Elsone L, Kitley J, Luppe S, Lythgoe D, Mutch K, Jacob S, Brown R, Moss K, McNeillis B, Goh YY (2014) Long-term efficacy, tolerability and retention rate of azathioprine in 103 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients: a multicentre retrospective observational study from the UK. Mult Scler J 20:1533–1540CrossRef Elsone L, Kitley J, Luppe S, Lythgoe D, Mutch K, Jacob S, Brown R, Moss K, McNeillis B, Goh YY (2014) Long-term efficacy, tolerability and retention rate of azathioprine in 103 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients: a multicentre retrospective observational study from the UK. Mult Scler J 20:1533–1540CrossRef
7.
Zurück zum Zitat Hinson S, Pittock SJ, Lucchinetti CF, Roemer S, Fryer J, Kryzer T, Lennon VA (2007) Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology 69:2221–2231CrossRefPubMed Hinson S, Pittock SJ, Lucchinetti CF, Roemer S, Fryer J, Kryzer T, Lennon VA (2007) Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology 69:2221–2231CrossRefPubMed
8.
Zurück zum Zitat Jeong IH, Park B, Kim S-H, Hyun J-W, Joo J, Kim HJ (2015) Comparative analysis of treatment outcomes in patients with neuromyelitis optica spectrum disorder using multifaceted endpoints. Mult Scler J 22:329–339CrossRef Jeong IH, Park B, Kim S-H, Hyun J-W, Joo J, Kim HJ (2015) Comparative analysis of treatment outcomes in patients with neuromyelitis optica spectrum disorder using multifaceted endpoints. Mult Scler J 22:329–339CrossRef
9.
Zurück zum Zitat Kanesalingam R, Chia Y, Eow G, Easaw P, Rafia M (2013) The spectrum of neuromyelitis optica. J Neurol Sci 333:e363CrossRef Kanesalingam R, Chia Y, Eow G, Easaw P, Rafia M (2013) The spectrum of neuromyelitis optica. J Neurol Sci 333:e363CrossRef
10.
Zurück zum Zitat Kim S-H, Huh S-Y, Lee SJ, Joung A, Kim HJ (2013) A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol 70:1110–1117CrossRefPubMed Kim S-H, Huh S-Y, Lee SJ, Joung A, Kim HJ (2013) A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol 70:1110–1117CrossRefPubMed
11.
Zurück zum Zitat Kim S-H, Kim W, Li XF, Jung I-J, Kim HJ (2011) Repeated treatment with rituximab based on the assessment of peripheral circulating memory B cells in patients with relapsing neuromyelitis optica over 2 years. Arch Neurol 68:1412–1420CrossRefPubMed Kim S-H, Kim W, Li XF, Jung I-J, Kim HJ (2011) Repeated treatment with rituximab based on the assessment of peripheral circulating memory B cells in patients with relapsing neuromyelitis optica over 2 years. Arch Neurol 68:1412–1420CrossRefPubMed
12.
Zurück zum Zitat Lucchinetti CF, Mandler RN, McGavern D, Bruck W, Gleich G, Ransohoff RM, Trebst C, Weinshenker B, Wingerchuk D, Parisi JE (2002) A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain 125:1450–1461CrossRefPubMedPubMedCentral Lucchinetti CF, Mandler RN, McGavern D, Bruck W, Gleich G, Ransohoff RM, Trebst C, Weinshenker B, Wingerchuk D, Parisi JE (2002) A role for humoral mechanisms in the pathogenesis of Devic’s neuromyelitis optica. Brain 125:1450–1461CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Mandler RN, Ahmed W, Dencoff JE (1998) Devic’s neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology 51:1219–1220CrossRefPubMed Mandler RN, Ahmed W, Dencoff JE (1998) Devic’s neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology 51:1219–1220CrossRefPubMed
14.
Zurück zum Zitat Mealy MA, Wingerchuk DM, Palace J, Greenberg BM, Levy M (2014) Comparison of relapse and treatment failure rates among patients with neuromyelitis optica: multicenter study of treatment efficacy. JAMA Neurol 71:324–330CrossRefPubMed Mealy MA, Wingerchuk DM, Palace J, Greenberg BM, Levy M (2014) Comparison of relapse and treatment failure rates among patients with neuromyelitis optica: multicenter study of treatment efficacy. JAMA Neurol 71:324–330CrossRefPubMed
15.
Zurück zum Zitat Pittock SJ, Weinshenker BG, Lucchinetti CF, Wingerchuk DM, Corboy JR, Lennon VA (2006) Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol 63:964–968CrossRefPubMed Pittock SJ, Weinshenker BG, Lucchinetti CF, Wingerchuk DM, Corboy JR, Lennon VA (2006) Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol 63:964–968CrossRefPubMed
16.
Zurück zum Zitat Qiu W, Kermode AG, Li R, Dai Y, Wang Y, Wang J, Zhong X, Li C, Lu Z, Hu X (2015) Azathioprine plus corticosteroid treatment in Chinese patients with neuromyelitis optica. J Clin Neurosci 22:1178–1182CrossRefPubMed Qiu W, Kermode AG, Li R, Dai Y, Wang Y, Wang J, Zhong X, Li C, Lu Z, Hu X (2015) Azathioprine plus corticosteroid treatment in Chinese patients with neuromyelitis optica. J Clin Neurosci 22:1178–1182CrossRefPubMed
17.
Zurück zum Zitat Radaelli M, Moiola L, Sangalli F, Esposito F, Barcella V, Ferrè L, Rodegher M, Colombo B, Fazio R, Martinelli V (2015) Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients. Mult Scler J 22:511–519CrossRef Radaelli M, Moiola L, Sangalli F, Esposito F, Barcella V, Ferrè L, Rodegher M, Colombo B, Fazio R, Martinelli V (2015) Neuromyelitis optica spectrum disorders: long-term safety and efficacy of rituximab in Caucasian patients. Mult Scler J 22:511–519CrossRef
18.
Zurück zum Zitat Sahraian M, Moinfar Z, Khorramnia S, Mohammad Ebrahim M (2010) Relapsing neuromyelitis optica: demographic and clinical features in Iranian patients. Eur J Neurol 17:794–799CrossRefPubMed Sahraian M, Moinfar Z, Khorramnia S, Mohammad Ebrahim M (2010) Relapsing neuromyelitis optica: demographic and clinical features in Iranian patients. Eur J Neurol 17:794–799CrossRefPubMed
19.
Zurück zum Zitat Sand IK (2016) Neuromyelitis optica spectrum disorders. CONTINUUM: lifelong learning. Neurology 22:864–896 Sand IK (2016) Neuromyelitis optica spectrum disorders. CONTINUUM: lifelong learning. Neurology 22:864–896
20.
Zurück zum Zitat Sato DK, Lana-Peixoto MA, Fujihara K, Seze J (2013) Clinical spectrum and treatment of neuromyelitis optica spectrum disorders: evolution and current status. Brain Pathol 23:647–660CrossRefPubMed Sato DK, Lana-Peixoto MA, Fujihara K, Seze J (2013) Clinical spectrum and treatment of neuromyelitis optica spectrum disorders: evolution and current status. Brain Pathol 23:647–660CrossRefPubMed
21.
Zurück zum Zitat Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, Borisow N, Kleiter I, Aktas O, Kümpfel T (2014) Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol 261:1–16CrossRefPubMed Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, Borisow N, Kleiter I, Aktas O, Kümpfel T (2014) Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol 261:1–16CrossRefPubMed
22.
Zurück zum Zitat Waters P, Jarius S, Littleton E, Leite MI, Jacob S, Gray B, Geraldes R, Vale T, Jacob A, Palace J (2008) Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neurol 65:913–919CrossRefPubMed Waters P, Jarius S, Littleton E, Leite MI, Jacob S, Gray B, Geraldes R, Vale T, Jacob A, Palace J (2008) Aquaporin-4 antibodies in neuromyelitis optica and longitudinally extensive transverse myelitis. Arch Neurol 65:913–919CrossRefPubMed
23.
Zurück zum Zitat Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, De Seze J, Fujihara K, Greenberg B, Jacob A (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85:177–189CrossRefPubMedPubMedCentral Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, De Seze J, Fujihara K, Greenberg B, Jacob A (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85:177–189CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Zéphir H, Bernard-Valnet R, Lebrun C, Outteryck O, Audoin B, Bourre B, Pittion S, Wiertlewski S, Ouallet JC, Neau J-P (2015) Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability. J Neurol 262:2329–2335CrossRefPubMed Zéphir H, Bernard-Valnet R, Lebrun C, Outteryck O, Audoin B, Bourre B, Pittion S, Wiertlewski S, Ouallet JC, Neau J-P (2015) Rituximab as first-line therapy in neuromyelitis optica: efficiency and tolerability. J Neurol 262:2329–2335CrossRefPubMed
Metadaten
Titel
Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder: a randomized clinical trial
verfasst von
Zahra Nikoo
Shervin Badihian
Vahid Shaygannejad
Nasrin Asgari
Fereshteh Ashtari
Publikationsdatum
22.08.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 9/2017
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-017-8590-0

Weitere Artikel der Ausgabe 9/2017

Journal of Neurology 9/2017 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Neu im Fachgebiet Neurologie

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.