Long-term Therapy With Interleukin 6 Receptor Blockade in Highly Active Neuromyelitis Optica Spectrum Disorder.
Marius Ringelstein,Ilya Ayzenberg,Jens Harmel,Ann-Sophie Lauenstein,Eckart Lensch,Florian Stögbauer,Kerstin Hellwig,Gisa Ellrichmann,Mark Stettner,Andrew T. Chan,Hans-Peter Hartung,Bernd C. Kieseier,Ralf Gold,Orhan Aktas,Ingo Kleiter +14 more
Reads0
Chats0
TLDR
Prolonged tocilizumab therapy may be safe and effective from early treatment phases onward for otherwise therapy-resistant highly active NMO and NMO spectrum disorder.Abstract:
Importance Neuromyelitis optica (NMO) is characterized by disabling relapses of optic neuritis and myelitis and the presence of aquaporin 4 antibodies (AQP4-abs). Interleukin 6, which is significantly elevated in serum and cerebrospinal fluid of patients with NMO, induces AQP4-ab production by plasmablasts and represents a novel therapeutic target. Objective To evaluate the long-term safety and efficacy of tocilizumab, a humanized antibody targeting the interleukin 6 receptor, in NMO and NMO spectrum disorder. Design, Setting, and Participants Retrospective observational study with 10 to 51 months of follow-up between December 2010 and February 2015, in neurology departments at tertiary referral centers. Participants were 8 female patients of white race/ethnicity with highly active AQP4-ab–seropositive NMO (n = 6) and NMO spectrum disorder (n = 2) whose disease had been resistant to previous medications, including B-cell depletion, and who switched to tocilizumab (6-8 mg/kg of body weight per dose). Main Outcomes and Measures Annualized relapse rate, Expanded Disability Status Scale score, spinal cord and brain magnetic resonance imaging, AQP4-ab titers, pain levels (numerical rating scale), and adverse effects. Results Patients were followed up for a mean (SD) of 30.9 (15.9) months after switching to tocilizumab. Two of eight patients received add-on therapy with monthly corticosteroid pulses (temporary) or azathioprine, respectively. During tocilizumab treatment, the median annualized relapse rate significantly decreased from 4.0 (interquartile range, 3.0-5.0) in the year before tocilizumab therapy to 0.4 (interquartile range, 0.0-0.8) ( P = .008), and the median Expanded Disability Status Scale score significantly decreased from 7.3 (interquartile range, 5.4-8.4) to 5.5 (interquartile range, 2.6-6.5) ( P = .03). Active magnetic resonance imaging lesions were seen in 6 of 8 patients at tocilizumab initiation and in 1 of 8 patients at the last magnetic resonance imaging. Three patients remained relapse free during tocilizumab treatment. In 5 patients, a total of 8 relapses occurred, 4 within the first 2½ months of therapy. Five attacks were associated with delayed tocilizumab administration (≥40 days), and 6 attacks were associated with reduced tocilizumab dosage (6 vs 8 mg/kg). The AQP4-ab titers ( P = .02) and pain levels ( P = .02) dropped significantly during tocilizumab treatment. Adverse effects included moderate cholesterol elevation in 6 of 8 patients, infections in 4 of 8 patients, and deep venous thrombosis and neutropenia in one patient each. Conclusions and Relevance Prolonged tocilizumab therapy may be safe and effective from early treatment phases onward for otherwise therapy-resistant highly active NMO and NMO spectrum disorder. Relapse patterns indicate that adherence to a regular therapeutic regimen with monthly infusions of tocilizumab (8 mg/kg) may increase efficacy.read more
Citations
More filters
Journal ArticleDOI
Astrocytes in chronic pain and itch
TL;DR: The cellular and molecular mechanisms through which astrocytes contribute to the induction and maintenance of chronic pain and itch are described and targeting the specific pathways that are responsible for astrogliopathy is suggested.
Journal ArticleDOI
Diagnosis and treatment of NMO spectrum disorder and MOG-encephalomyelitis
TL;DR: Recommendations include antibody and further laboratory testing, MR imaging and optical coherence tomography, as well as longterm immunosuppressive treatment, including azathioprine, rituximab, and immunoglobulins.
Journal ArticleDOI
Tocilizumab in Autoimmune Encephalitis Refractory to Rituximab: An Institutional Cohort Study
Woo Jin Lee,Woo Jin Lee,Soon-Tae Lee,Soon-Tae Lee,Jangsup Moon,Jangsup Moon,Jun Sang Sunwoo,Jun Sang Sunwoo,Jung Ick Byun,Jung Ick Byun,Jung Ah Lim,Jung Ah Lim,Tae Joon Kim,Tae Joon Kim,Yong Won Shin,Yong Won Shin,Keon-Joo Lee,Keon-Joo Lee,Jin-Sun Jun,Jin-Sun Jun,Han Sang Lee,Han Sang Lee,Soyun Kim,Kyung Il Park,Keun Hwa Jung,Keun Hwa Jung,Ki-Young Jung,Ki-Young Jung,Manho Kim,Manho Kim,Sang Kun Lee,Sang Kun Lee,Kon Chu,Kon Chu +33 more
TL;DR: Tocilizumab might be a good treatment strategy for treating AE refractory to conventional immunotherapies and rituximab, and manifests as early at 1 month after treatment initiation.
Journal ArticleDOI
Treatment strategies for autoimmune encephalitis
TL;DR: In this review, the agents used for first- and second-line immunotherapy are discussed and recent attempts at finding new treatment options are introduced.
Journal ArticleDOI
Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial.
Chao Zhang,Meini Zhang,Wei Qiu,Hongshan Ma,Xinghu Zhang,Zilong Zhu,Chun-Sheng Yang,Dongmei Jia,Tian-Xiang Zhang,Meng Yuan,Yan Feng,Li Yang,Wenli Lu,Chunshui Yu,Jeffrey Bennett,Fu-Dong Shi,Fu-Dong Shi,Tango Study Investigators +17 more
TL;DR: An open-label, multicentre, randomised, phase 2 trial at six hospitals in China to compare the safety and efficacy of tocilizumab and azathioprine in patients with highly relapsing NMOSD.
References
More filters
Journal ArticleDOI
Rating neurologic impairment in multiple sclerosis An expanded disability status scale (EDSS)
TL;DR: A new Expanded Disability Status Scale (EDSS) is presented, with each of the former steps (1,2,3 … 9) now divided into two (1.0, 1.5, 2.0 … 9).
Journal ArticleDOI
Revised diagnostic criteria for neuromyelitis optica
TL;DR: Revised diagnostic criteria for definite neuromyelitis optica (NMO) that require optic neuritis, myelitis, and at least two of three supportive criteria: MRI evidence of a contiguous spinal cord lesion 3 or more segments in length, onset brain MRI nondiagnostic for multiple sclerosis, or NMO-IgG seropositivity.
Journal ArticleDOI
IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel.
TL;DR: It is shown that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier, which may represent the first example of a novel class of autoimmune channelopathy.
Journal ArticleDOI
The spectrum of neuromyelitis optica
Dean M. Wingerchuk,Vanda A. Lennon,Claudia F. Lucchinetti,Sean J. Pittock,Brian G. Weinshenker +4 more
TL;DR: Data suggest that autoantibodies to aquaporin 4 derived from peripheral B cells cause the activation of complement, inflammatory demyelination, and necrosis that is seen in neuromyelitis optica.
Journal ArticleDOI
Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial
Josef S Smolen,André D. Beaulieu,Andrea Rubbert-Roth,Cesar Ramos-Remus,Josef Rovensky,Emma Alecock,Thasia G. Woodworth,Rieke Alten +7 more
TL;DR: Tocilizumab could be an effective therapeutic approach in patients with moderate to severe active rheumatoid arthritis.
Related Papers (5)
International consensus diagnostic criteria for neuromyelitis optica spectrum disorders
Dean M. Wingerchuk,Brenda Banwell,Jeffrey Bennett,Philippe Cabre,William M. Carroll,Tanuja Chitnis,Jérôme De Seze,Kazuo Fujihara,Benjamin Greenberg,Anu Jacob,Sven Jarius,Marco Aurélio Lana-Peixoto,Michael J. Levy,Jack H. Simon,Silvia Tenembaum,Anthony Traboulsee,Patrick Waters,Kay E. Wellik,Brian G. Weinshenker +18 more