Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial.
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SUBMITTER: Zhang C
PROVIDER: S-EPMC7935423 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
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Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial.
Zhang Chao C Zhang Meini M Qiu Wei W Ma Hongshan H Zhang Xinghu X Zhu Zilong Z Yang Chun-Sheng CS Jia Dongmei D Zhang Tian-Xiang TX Yuan Meng M Feng Yan Y Yang Li L Lu Wenli W Yu Chunshui C Bennett Jeffrey L JL Shi Fu-Dong FD
The Lancet. Neurology 20200501 5
<h4>Background</h4>Azathioprine is used as a first-line treatment to prevent relapses of neuromyelitis optica spectrum disorder (NMOSD). Tocilizumab has been reported to reduce NMOSD disease activity in retrospective case reports. We aimed to compare the safety and efficacy of tocilizumab and azathioprine in patients with highly relapsing NMOSD.<h4>Methods</h4>We did an open-label, multicentre, randomised, phase 2 trial at six hospitals in China. We recruited adult patients (aged ≥18 years) with ...[more]
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Project description:Objective:This pilot study preliminarily examined the efficacy and tolerability of cetirizine as an add-on to standard therapy for neuromyelitis optica (NMO). Methods:Eligible participants met the Wingerchuk 2006 diagnostic criteria or had a single typical episode along with positive NMO immunoglobulin G. After baseline clinical and laboratory assessments, participants began treatment with cetirizine 10 mg orally daily, in addition to their usual disease-modifying therapy for NMO, and continued for 1 year. The primary end point was the annualized relapse rate (ARR) while on the same disease-modifying therapy before starting cetirizine compared with after taking cetirizine. Additional end points included disability (Expanded Disability Status Scale [EDSS]), relapse severity, tolerability, especially with respect to drowsiness measured by the Epworth Sleepiness Scale (ESS), and laboratory parameters. Results:The ARR before cetirizine was 0.4 ± 0.80 and after cetirizine was 0.1 ± 0.24 (p = 0.047). There was no statistically significant difference in the EDSS (mean 3.9 ± 2.18 before the start of the study and 3.2 ± 2.31 at the conclusion of the study, p = 0.500). The ESS remained fairly consistent throughout the study (mean 6.5 ± 5.33 at baseline and 6.9 ± 4.50 at month 12, p = 0.740). Laboratory studies were unrevealing. Conclusions:In this pilot study, cetirizine was well tolerated, and the prespecified primary efficacy end point was satisfied. However, the open-label design and the small sample size of this pilot study preclude definitive conclusions. Further research is needed. Classification of evidence:This study provides Class IV evidence that in patients with NMO, the addition of cetirizine to standard therapy is safe, well tolerated, and reduces relapses.
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Project description:IntroductionAs an autoimmune central nervous system disease characterized by inflammation and demyelination, neuromyelitis optica (NMO) has been extensively investigated. A specific antigenic target, astrocytic water channel aquaporin-4 (AQP4) has already been identified, and it can be recognized explicitly by the autoantibody marker NMO-IgG. Along with the immune attacks, clinical disabilities would gradually accumulate. As there has been no validated and well-recognized therapy for NMO till now, preventing and postponing attack using immunosuppressive therapies is the primary treatment option.MethodsIn the current retrospective study, the effect of immunosuppressive agents was investigated through a long-term follow-up. To assess the long-term effectiveness and safety of rituximab (RTX), azathioprine (AZA), and mycophenolate mofetil (MMF) therapies, all 129 patients with NMO spectrum disorders (NMOSD) who received at least one of these treatments were studied, including 55 seropositive for AQP4-Ab and 74 seronegative for AQP4-Ab.ResultsThe median post-treatment annualized relapse rate (ARR) was lower than the pre-treatment rates in all AQP4+Ab groups (from 1.0 to 0.7 in RTX, from 0.8 to 0.3 in AZA, and from 0.85 to 0.35 in MMF). Meanwhile, the ARR also decreased in all AQP4-Ab groups (from 0.3 to 0.2 in RTX, from 0.9 to 0.5 in AZA, and from 0.9 to 0.4 in MMF). Disability condition improved in the Expanded Disability Status Scale (EDSS) in all AQP4+Ab groups (from 4.0 to 2.75 in RTX, from 3.5 to 2.5 in AZA, and from 3.0 to 2.0 in MMF) and in all AQP4-Ab groups (from 3.0 to 2.5 in RTX, from 3.0 to 2.5 in AZA, and from 3.5 to 2.0 in MMF). There was no statistically significant difference between the post-treatment and pre-treatment changes of EDSS and ARR in the RTX, AZA, and MMF groups (P > 0.05). However, according to Kaplan-Meier survival analysis, RTX-treated patients were more likely to be relapse-free after long-term follow-up than those who received AZA or MMF therapy. Meanwhile, adverse effects were noted in three out of 23 patients with RTX treatment, five of 32 with AZA treatment, and three of 21 with MMF treatment. No serious adverse events were observed in all treatment groups during the study.ConclusionsRTX, AZA, and MMF therapies efficiently lowered the relapse frequency and disability in both of the AQP4-Ab seropositive or seronegative patients with NMO. Furthermore, low dosage of RTX is recommended for the patients with NMO owing to its long-term effectiveness and safety.
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Project description:BackgroundInterleukin-6 receptor blockade is effective in reducing the risk of relapses in neuromyelitis optica spectrum disorder (NMOSD). However, its efficacy during acute attacks of NMOSD remains elusive.ObjectiveWe investigated the effects of tocilizumab on disability during acute attacks, as well as its maintenance, in patients with moderate-to-severe myelitis.MethodsNineteen patients with NMOSD received tocilizumab treatment as add-on to high-dose methylprednisolone (HDMP) in acute myelitis and twenty-two patients who only received HDMP were compared. Disease disability was assessed using a multi-level scaling system that included the expanded disability status scale (EDSS), Hauser ambulation index (HAI), modified Rankin scale (mRS), pain numerical rating scale (NRS), functional assessment of chronic illness therapy-fatigue scale (FACIT-F), activity of daily living (ADL), EuroQol five-dimensions-three-level questionnaire (EQ-5D-3L), and sensory function score and bowel and bladder function score in Kurtzke functional systems scores (FSS).ResultsImproved EDSS, HAI, and mRS, as well as increased ADL and EQ-5D-3L were significant in patients on tocilizumab compared with those on steroids as monotherapy at 3 months (p < 0.05). Both groups of patients showed improved pain, fatigue, sensory function, and autonomic function at follow-ups, compared with baseline respectively. The changes in NRS, FACIT-F, and sensory and autonomic FSS showed no significant differences between the two groups. Tocilizumab significantly lowered the risk of relapses (HR = 0.21, 95% CI 0.06-0.76, p = 0.017) and reduced the annualized relapse rate compared with those by steroids (0.1 ± 0.2 vs 0.5 ± 0.6, p = 0.013).ConclusionEarly initiation of tocilizumab provided a safe and effective add-on alternative during attacks, and its maintenance contributed to a significant reduction of relapse rate in NMOSD.
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Project description:ObjectiveTo address a novel lower-dose rituximab (RTX) therapy strategy based on our clinical experience and assess its efficacy and safety in neuromyelitis optica spectrum disorder (NMOSD).MethodsA multicenter, open-label, self-controlled, prospective follow-up study. Totally, 108 NMOSD patients were enrolled and a lower-dose RTX strategy was applied including 100 mg weekly for 3 weeks and then reinfusions every 6 months. Annualized relapse rate (ARR), the expanded disability status scale (EDSS) score and length of spinal cord lesions were included to evaluate the efficacy. Side effects were recorded to assess the safety profile.ResultsOf 108 patients, 80 (74.1%) initiated low-dose RTX therapy immediately after acute attack treatment and 33 (30.6%) initiated it after the first attack. During a median treatment period of 35.5 (22.0-48.8) months, significant decreases were observed in median ARR (1.1 [0.8-2.0] versus 0 [0-0.2], p < 0.001), EDSS score (3.5 [2.5-4.0] versus 2.0 [1.0-3.0], p < 0.001) and spinal cord lesion segments (5.0 [4.0-8.0] versus 3.0 [1.0-6.0], p < 0.001). The cumulative risk of relapses significantly decreased during the post- versus pre-RTX period (HR 0.238, 95%CI 0.160-0.356, p < 0.001) and on early therapy initiated within 24 months after disease onset versus delayed therapy (HR 0.506, 95%CI 0.258-0.994, p = 0.041). No serious side effects were recorded and all the subjects did not discontinue treatment due to RTX-related side effects.ConclusionOur research provided evidence supporting the lower-dose RTX strategy in treating NMOSD and reopened the issues of optimal dosage and therapy initiation timing.
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