Clinical evaluation of rituximab treatment for neuromyelitis optica

Abstract

Introduction: Neuromyelitis optica is an inflammatory and usually relapsing demyelinating autoimmune disease of the central nervous system that targets the optic nerves and spinal cord. Rituximab has been used for different neurological diseases that are probably immunemediated or involving humoral immunity. The objective of this study is to evaluate the efficacy and safety of rituximab as treatment for neuromyelitis optica in a tertiary hospital. Methods:Retrospective study of patients with neuromyelitis optica treated with rituximab 1000 mg on days 1 and 15, repeated every 6-8 months. We recorded EDSS score, relapse rate, overall condition, CD19+ count, presence of anti-NMO antibodies, and possible adverse reactions.Results: Six patients were treated; all were women with a median age of 46 years (range 38-58). Anti-NMO antibodies were detected in 3 patients (50%). Baseline EDSS was 4 (range 2.0-5.5). Two patients had previously been treated with an immunomodulatory drug. Median time from the first rituximab infusion to first relapse was 3.7 years (range 1.7-6.9). Two patients had infusion reactions after the first dose of rituximab. Four patients remained relapse-free and their EDSS score did not progress during rituximab treatment, one patient showed no clinical improvement, and one patient could not be evaluated.Conclusion: Rituximab can be considered an attractive therapeutic alternative for patients with neuromyelitis optica as there are no approved treatments for this disease. Further studies with rituximab are needed to establish the role of this drug in treating neuromyelitis optica. Evaluación del uso de rituximab en la neuromielitis óptica ResumenIntroducción: La neuromielitis óptica es un trastorno autoinmune, inflamatorio y desmielinizante del sistema nervioso central que afecta a la médula espinal y al nervio óptico, de carácter recurrente. Rituximab ha sido utilizado en el tratamiento de varias enfermedades neurológicas de probable naturaleza autoinmune o donde la inmunidad humoral estaba implicada. El objetivo de este estudio es evaluar la eficacia y seguridad de rituximab en el tratamiento de la neuromielitis óptica en un hospital terciario.Métodos: Estudio retrospectivo de pacientes con neuromielitis óptica tratadas con 2 infusiones de rituximab 1.000 mg separadas por 15 días, cada 6-8 meses. Se evaluó la puntuación EDSS, la existencia de brotes, el estado general, el recuento de CD19+, la presencia de anticuerpos anti-NMO y las reacciones adversas.Resultados: Se trataron 6 pacientes, todas mujeres (mediana de edad 46 años; rango 38-58).En 3 de ellas (50%) se detectó la presencia de anticuerpos anti-NMO. La EDSS basal fue de 4 (rango 2-5,5). Dos pacientes recibieron previamente algún fármaco inmumodulador. La mediana desde el primer brote hasta el tratamiento con rituximab fue de 3,7 años (rango 1,7-6,9); 2 pacientes presentaron alguna reacción adversa tras la primera infusión del fármaco. En cuanto a la respuesta, 4 pacientes no volvieron a tener brotes y su EDSS no progresó, en una paciente no...

Clinical efficacy and safety of single cycle rituximab as induction therapy for aggressive neuromyelitis optica spectrum disorder in a resource limited center: a preliminary study

“…This patient was on maintenance azathioprine from 2010 to 2016 when she developed transaminitis. Azathioprine was withheld, and she was on prednisolone 10 mg daily when the disease relapsed there have been several studies assessing the effectiveness of monoclonal antibody therapy, targeting CD20 epitope of the B cell lineage that is important in the pathogenesis of the disease [8,9,13,[15][16][17] . In these studies, there was reduction in annualized relapse rates and improvement in disability as measured by the EDSS.…”

“…Previous studies practiced either prescheduled RTX induction regimen every 6 months, or retreatment based on B cell depletion monitoring [6][7][8][16][17][18] . CD19, CD20 and CD27 are among the commonly used treatment-related biomarkers [13,14,16,17] . However, our center lacks the facilities to monitor treatment with these tests though we are aware of the need to objectively test this for treatment response.…”

“…At the initiation of treatment, the medication was given as a slow intravenous (IV) infusion of two doses 2 weeks apart at 1000 mg each. A similar regime was applied by Cree et al [6] and other RTX studies [5,[12][13][14] . Patients were given premedication which consisted of IV promethazine 12.5 mg, IV hydrocortisone 100 mg and oral acetaminophen 1000 mg before the start of RTX infusion.…”

A meta-analysis on efficacy and safety of rituximab for neuromyelitis optica spectrum disorders

“…Cabre et al 2018 [2] Prospective 32 30/2 39.9 (12.1) 20 NC 2 yr Dastjerdi et al 2018 [5] Prospective 56 46/10 36.86 30 87.60 ± 59.65 mo 6/12 mo Fernández-Megía et al 2015 [6] Retrospective 6 6/0 46 (38-58) 3 NC NC Jacob et al 2008 [7] Retrospective 25 22/3 38 (7-65) 14 4.5 (0.8-17) yr 19 (6-40) mo Kim et al 2015 [3] Retrospective 100 92/8 43 (11) 94 11 (5) yr 67 (9-108) mo Nikoo et al 2017 [8] RCT 33 29/4 35.33 (8.98) 13 6.23 (4.29) yr 12 mo Shaygannejad et al 2019 [9] Prospective 44 35/9 37.2 ± 10.4 14 6.3 ± 4.1 yr 31.6 ± 7.3 mo Zephir et al 2015 [10] Retrospective 32 27/5 45 ± 12.1 28 6.5 (1-410) mo 28.7 ± 21 mo Zhang et al 2017 [11] Retrospective 31 23/8 42.2 ± 16.9 25 4.05 ± 2.11 yr >2 yr Annovazzi et al 2016 [12] Retrospective 73 64/9 46.5 ± 12.5 53 6 ± 7.2 yr 35.6 ± 27 Pellkofer et al 2011 [13] Prospective 9 8/1 36.1 (11.5) 9 11 (7.7) yr 29.6 (14.5) mo Lindsey et al 2012 [14] Retrospective 8 7/1 37.6 (14.4) 4 65.1 (53.7) mo 39.9 (40.7) mo Ip et al 2013 [15] Retrospective 7 6/1 52 (22-62) 4 57 (40-272) mo 24 (1-42) mo Jeong et al 2016 [16] Retrospective 55 50/5 42 (15-68) 52 41.7 (2.1-231.5) mo 64.7 (6.2-99.8) mo Collongues et al 2016 [17] Retrospective 21 19/2 37.8 (15.5) 19 46.9 (51.2) mo 31 (18) mo Cohen et al 2017 [18] Prospective [20] Retrospective 23 21/2 37.1 ± 14.6 15 114 (13-266) mo 32.5 (7-63) mo Casallas-Vanegas et al 2020 [21] Retrospective 66 54/12 36.2 ± 12.01 44 5.85 ± 4.03 yr NC Correa Diaz et al 2019 [22] Retrospective 21 18/2 36.7 (13.3) NC NC 24.8 (6-47) mo Flores et al 2012 [23] NC 13 12/1 33.3 ± 13.8 NC NC 24 mo Kim et al 2009 [24] NC 27 24/3 33.5 ± 11.6 NC 5.6 ± 3.6 yr NC Kim et al 2013 [25] Retrospective 30 27/3 38 (23-58) NC 61 (49-82) mo NC Lin et al 2018 [26] RCT 14 NC 32.9 ± 13.6 NC 20.5 ± 6.8 mo NC Wu and Niu 2019 [27] Retrospective 15 13/2 31.8 ± 13.2 NC 1-144 mo NC Xiao et al 2020 [28] Retrospective 36 NC NC NC NC 19.83 ± 7.74 mo Bai 2016 [29] RCT 9 9 38.28 NC NC 7-40 mo Li 2019 [30] Retrospective 29 27/2 38.3 ± 13.9 27 NC 3.1/2.1 yr Liu 2017 [31] RCT 1...…”