Efficacy and safety of long-term treatment with low-dose rituximab for neuromyelitis optica spectrum disorder_Chinese Journal of Ocular Fundus Diseases

Authors：

Wang Junqing , Xu Quangang , Zhou Huanfen , Feng Hui , Lai Mengying ,  Wei Shihui

Department of Ophthalmology, Chinese PLA General Hospital, Beijing 100853, China;

Corresponding author：

Wei Shihui, Email: weishihui706@hotmail.com

Keywords：

Neuromyelitis optica/drug therapy; Antigens, CD20/administration & dosage; Protective agents; Recurrence

DOI：

10.3760/cma.j.issn.1005-1015.2018.02.011

Video：

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Objective To evaluate the efficacy and safety of repeated treatments with low-dose rituximab for relapsing neuromyelitis optica spectrum disorder (NMOSD). Methods A perspective study. 21 patients who were diagnosed with NMOSD one year ago were recruited for rituximab treatment. Of 21 patients, one was male, 20 were females. Onset age was 10 - 51 years, the mean onset age was (26.2±12.0) years. Duration of disease was 2.3 - 25.8 years, the mean duration was (9.2±5.9) years. Best corrected vision activity (BCVA), expanded disability status scale (EDSS), annualized relapsing rate (ARR) were valued to investigate the efficacy and safety of repeated treatments with low-dose rituximab. The BCVA was examined using Snellen chart, and converted to logMAR. The mean BCVA was 1.13±1.09, the mean BCVA in better eyes was 0.4±0.68, the mean BCVA in latter eyes was 1.87±0.90. The mean EDSS was 3.09±0.70. The mean ARR was 1.04±0.65. All patients underwent two cycles of RTX treatment. The annually induction treatment was RTX 100 mg per week for 4 weeks. Of 21 patients, 12 patients had treatment within one month after attack. The mean follow-up period was (28.4±4.9) months. The side effects were recorded, BCVA, EDSS, ARR were valued to investigate the efficacy and safety of repeated treatments with low-dose rituximab. Paired t test, independent sample t test and Chi-squared test were used. Results The mean BCVA at last follow-up was 0.62±0.91, the mean BCVA in better eye was 0.62±0.91, the BCVA in latter eye was 1.0±1.01. The mean EDSS was 2.26±1.07. The mean ARR was 0.21 ± 0.3. After the treatment, patient had significant improvement on BCVA in worst eye (t=4.256), ARR (t=2.900), EDSS (t=4.620) with the significant differences (P＜0.05).Thirteen relapses in 9 patients were observed. B lymph cells were more than 0.01% in all relapses. There was no significant difference on the BCVA in better eye (t=1.840, P＞0.05). There were 9 patients had relapse, 13 times in total. Of 13 relapses, B lymph cell count was performed in 12 relapses, and the counts were 0.01% - 0.14%. There were no significant difference between relapsed patients and non-relapsed patients on onset age (t=0.67, P=0.51), whether underwent plasma exchange treatment (χ²=1.61, P＞0.05), with/without auto-immune antibody ratio (χ²=1.61, P＞0.05). Of 21 patients, 8 patients had side effects, including 5 patients with infection, 4 patients with chest congestion, 3 patients with hair losing, 2 patients with skin rashes, headache and short of breath, 1 patient with tinnitus, palpitation and fatigue. Four patients had more than one symptom. Of all patients who had side effects, slowing down the infusion speed of RTX or infusing 5 mg of dexamethasone could relieve the discomfort. Conclusion Lose-dose rituximab reduces the frequency of NMOSD relapses and is well tolerated.

Citation： Wang Junqing, Xu Quangang, Zhou Huanfen, Feng Hui, Lai Mengying, Wei Shihui. Efficacy and safety of long-term treatment with low-dose rituximab for neuromyelitis optica spectrum disorder. Chinese Journal of Ocular Fundus Diseases, 2018, 34(2): 155-158. doi: 10.3760/cma.j.issn.1005-1015.2018.02.011 Copy

1.	Sepúlveda M, Armangue T, Sola-Valls N, et al. Neuromyelitis optica spectrum disorders: comparison according to the phenotype and serostatus[J/OL]. Neurol Neuroimmunol Neuroinflamm, 2016, 3(3): 225[2016-04-14]. http://europepmc.org/abstract/MED/27144216. DOI: 10.1212/NXI.0000000000000225.
2.	Weinshenker BG, Wingerchuk DM. Neuromyelitis spectrum disorders[J]. Mayo Clin Proc, 2017, 92(4): 663-679. DOI: 10.1016/j.mayocp.2016.12.014.
3.	Harjunpää A, Junnikkala S, Meri S. Rituximab (anti-CD20) therapy of B-cell lymphomas: direct complement killing is superior to cellular effector mechanisms[J]. Scand J Immunol, 2000, 51(6): 634-641.
4.	Jade JD, Bansi S, Singhal B. Rituximab in neuromyelitis optica spectrum disorders: our experience[J]. Ann Indian Acad Neurol, 2017, 20(3): 229-232. DOI: 10.4103/aian.AIAN_499_16.
5.	Pavanello F, Zucca E, Ghielmini M. Rituximab: 13 open questions after 20 years of clinical use[J]. Cancer Treat Rev, 2017, 53: 38-46. DOI: 10.1016/j.ctrv.2016.11.015.
6.	Yang CS, Yang L, Li T, et al. Responsiveness to reduced dosage of rituximab in Chinese patients with neuromyelitis optica[J]. Neurology, 2013, 81(8): 710-713. DOI: 10.1212/WNL.0b013e3182a1aac7.
7.	Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders[J]. Neurology, 2015, 85(2): 177-189. DOI: 10.1212/WNL.0000000000001729.
8.	Zhou H, Xu Q, Zhao S, et al. Distinct clinical characteristics of atypical optic neuritis with seronegative aquaporin-4 antibody among Chinese patients[J]. Br J Ophthalmol, 2017, 101(12): 1-6. DOI: 10.1136/bjophthalmol-2017-310157.
9.	Guo Y, Weigand SD, Popescu BF, et al. Pathogenic implications of cerebrospinal fluid barrier pathology in neuromyelitis optica[J]. Acta Neuropathol, 2017, 133(4): 1-16. DOI: 10.1007/s00401-017-1682-1.
10.	Tradtrantip L, Yao X, Su T, et al. Bystander mechanism for complement-initiated early oligodendrocyte injury in neuromyelitis optica[J]. Acta Neuropathol, 2017, 134(1): 1-10. DOI: 10.1007/s00401-017-1734-6.
11.	Pittock SJ, Lucchinetti CF. Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later[J]. Ann N Y Acad Sci, 2015, 1366(1): 20-39. DOI: 10.1111/nyas.12794.
12.	Cree BA, Lamb S, Morgan K, et al. An open label study of the effects of rituximab in neuromyelitis optica[J]. Neurology, 2005, 64(7): 1270–1272. DOI: 10.1212/01.WNL.0000159399.81861.D5.
13.	Kim SH, Huh SY, Lee SJ, et al. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder[J]. JAMA Neurol, 2013, 70(9): 1110-1118. DOI: 10.1001/jamaneurol.2013.3071.
14.	Damato V, Evoli A, Iorio R. Efficacy and safety of rituximab therapy in neuromyelitis optica spectrum disorders[J]. JAMA Neurol, 2016, 73(11): 1342-1347. DOI: 10.1001/jamaneurol.2016.1637.
15.	Longoni G, Banwell B, Filippi M, et al. Rituximab as a first-line preventive treatment in pediatric NMOSDs[J/OL]. Neurol Neuroimmunol Neuroinflamm, 2014, 1(4): 46[2014-12-11]. http://europepmc.org/abstract/MED/25520954. DOI: 10.1212/NXI.0000000000000046.
16.	Collongues N, De Seze J. An update on the evidence for the efficacy and safety of rituximab in the management of neuromyelitis optica[J]. Ther Adv Neurol Disord, 2016, 9(3): 180-188. DOI: 10.1177/1756285616632653.
17.	Kim SH, Jeong IH, Hyun JW, et al. Treatment outcomes with rituximab in 100 patients with neuromyelitis optica[J]. JAMA Neurology, 2015, 72(9): 989-995. DOI: 10.1001/jamaneurol.2015.1276.

1. Sepúlveda M, Armangue T, Sola-Valls N, et al. Neuromyelitis optica spectrum disorders: comparison according to the phenotype and serostatus[J/OL]. Neurol Neuroimmunol Neuroinflamm, 2016, 3(3): 225[2016-04-14]. http://europepmc.org/abstract/MED/27144216. DOI: 10.1212/NXI.0000000000000225.
2. Weinshenker BG, Wingerchuk DM. Neuromyelitis spectrum disorders[J]. Mayo Clin Proc, 2017, 92(4): 663-679. DOI: 10.1016/j.mayocp.2016.12.014.
3. Harjunpää A, Junnikkala S, Meri S. Rituximab (anti-CD20) therapy of B-cell lymphomas: direct complement killing is superior to cellular effector mechanisms[J]. Scand J Immunol, 2000, 51(6): 634-641.
4. Jade JD, Bansi S, Singhal B. Rituximab in neuromyelitis optica spectrum disorders: our experience[J]. Ann Indian Acad Neurol, 2017, 20(3): 229-232. DOI: 10.4103/aian.AIAN_499_16.
5. Pavanello F, Zucca E, Ghielmini M. Rituximab: 13 open questions after 20 years of clinical use[J]. Cancer Treat Rev, 2017, 53: 38-46. DOI: 10.1016/j.ctrv.2016.11.015.
6. Yang CS, Yang L, Li T, et al. Responsiveness to reduced dosage of rituximab in Chinese patients with neuromyelitis optica[J]. Neurology, 2013, 81(8): 710-713. DOI: 10.1212/WNL.0b013e3182a1aac7.
7. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders[J]. Neurology, 2015, 85(2): 177-189. DOI: 10.1212/WNL.0000000000001729.
8. Zhou H, Xu Q, Zhao S, et al. Distinct clinical characteristics of atypical optic neuritis with seronegative aquaporin-4 antibody among Chinese patients[J]. Br J Ophthalmol, 2017, 101(12): 1-6. DOI: 10.1136/bjophthalmol-2017-310157.
9. Guo Y, Weigand SD, Popescu BF, et al. Pathogenic implications of cerebrospinal fluid barrier pathology in neuromyelitis optica[J]. Acta Neuropathol, 2017, 133(4): 1-16. DOI: 10.1007/s00401-017-1682-1.
10. Tradtrantip L, Yao X, Su T, et al. Bystander mechanism for complement-initiated early oligodendrocyte injury in neuromyelitis optica[J]. Acta Neuropathol, 2017, 134(1): 1-10. DOI: 10.1007/s00401-017-1734-6.
11. Pittock SJ, Lucchinetti CF. Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later[J]. Ann N Y Acad Sci, 2015, 1366(1): 20-39. DOI: 10.1111/nyas.12794.
12. Cree BA, Lamb S, Morgan K, et al. An open label study of the effects of rituximab in neuromyelitis optica[J]. Neurology, 2005, 64(7): 1270–1272. DOI: 10.1212/01.WNL.0000159399.81861.D5.
13. Kim SH, Huh SY, Lee SJ, et al. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder[J]. JAMA Neurol, 2013, 70(9): 1110-1118. DOI: 10.1001/jamaneurol.2013.3071.
14. Damato V, Evoli A, Iorio R. Efficacy and safety of rituximab therapy in neuromyelitis optica spectrum disorders[J]. JAMA Neurol, 2016, 73(11): 1342-1347. DOI: 10.1001/jamaneurol.2016.1637.
15. Longoni G, Banwell B, Filippi M, et al. Rituximab as a first-line preventive treatment in pediatric NMOSDs[J/OL]. Neurol Neuroimmunol Neuroinflamm, 2014, 1(4): 46[2014-12-11]. http://europepmc.org/abstract/MED/25520954. DOI: 10.1212/NXI.0000000000000046.
16. Collongues N, De Seze J. An update on the evidence for the efficacy and safety of rituximab in the management of neuromyelitis optica[J]. Ther Adv Neurol Disord, 2016, 9(3): 180-188. DOI: 10.1177/1756285616632653.
17. Kim SH, Jeong IH, Hyun JW, et al. Treatment outcomes with rituximab in 100 patients with neuromyelitis optica[J]. JAMA Neurology, 2015, 72(9): 989-995. DOI: 10.1001/jamaneurol.2015.1276.

Chinese Journal of Ocular Fundus Diseases

Efficacy and safety of long-term treatment with low-dose rituximab for neuromyelitis optica spectrum disorder

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