Neuromyelitis optica relapses: Race and rate, immunosuppression and impairment

Tackley, George; O’Brien, Fanny; Rocha, João Carlos da; Woodhall, Mark; Waters, Patrick; Chandratre, S; Halfpenny, Christopher; Hemingway, Cheryl; Wassmer, Evangeline; Wasiewski, Warren W.; Leite, Maria Isabel; Palace, Jacqueline

doi:10.1016/j.msard.2016.02.014

Cited by 36 publications

(32 citation statements)

References 14 publications

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“…Similar to previous studies [ 3 – 10 ], MMF therapy significantly reduced ARR in 87% of patients, and 64% were relapse-free during a median course of 20 months (average 27) therapy with MMF. Our results confirmed that MMF therapy significantly decreased the risks of severe relapses, in terms of disability, as recently reported [ 9 , 10 , 13 ].…”

Section: Discussionsupporting

confidence: 92%

Dose effects of mycophenolate mofetil in Chinese patients with neuromyelitis optica spectrum disorders: a case series study

et al. 2018

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BackgroundNeuromyelitis optica (NMO) spectrum disorder (NMOSD) is a devastating autoimmune inflammatory disorder of the central nervous system, which can result in blindness or paralysis. Currently, there is a dire need for new treatment options in the clinic. Several case series have shown that mycophenolate mofetil (MMF) may be an effective treatment for NMOSD patients. The dosing of MMF in the treatment of NMOSD has been poorly studied. Therefore, we evaluated the efficacy, tolerability, influential factors and optimal dosage of MMF in Chinese patients with NMOSD.MethodsA case series of 109 NMO or NMOSD (limited forms of NMO with seropositive AQP4-IgG) patients were retrospectively analyzed and followed up. Out of the 109 patients, 86 patients had received MMF for 6 months or longer and were included for efficacy assessment.ResultsWhen comparing the annualized relapse rate (ARR) of MMF treatment with that of pre-MMF treatment period, MMF was found to significantly reduce ARR in 75 (87%) patients (p < 0.0001). The median pre-treatment Expanded Disability Status Scale (EDSS) score in remission decreased from 3 (range, 0–8.5) to 2.5 (range, 0–8) at the last follow-up (p = 0.006), yet no significant difference was found in the visual score. The higher doses of MMF (1750 mg/d to 2000 mg/d) significantly lowered the relapse risks compared with lower doses (1000 mg/d or less, p < 0.0001) or moderate doses (1250 to 1500 mg/d, p = 0.031). Coexisting with systemic autoimmune diseases (HR, 2.418; p = 0.0345) and attack number before MMF initiation (HR, 1.117; p = 0.02) were important risk factors for relapses. MMF was generally well tolerated with adverse effects occurring in 21 patients (19%). While four patients decreased their daily doses because of the adverse effects, only one patient stopped MMF treatment.ConclusionsMMF is generally effective and well tolerated in Chinese NMOSD patients. High-dose MMF was more potent than the lower dose for NMOSD patients, with 1750 mg of daily MMF being the recommended dosage for Chinese patients with NMOSD. MMF treatment reduces the frequency of relapses and improves the quality of life for patients with this debilitating disease.Electronic supplementary materialThe online version of this article (10.1186/s12883-018-1056-x) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Dose effects of mycophenolate mofetil in Chinese patients with neuromyelitis optica spectrum disorders: a case series study

et al. 2018

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“…Treatment was changed from AZA to RTX in eight patients. This could have generated a bias in favour of a low ARR in the AZA subgroup, as patients who responded well to the treatment might have remained on therapy more often as reported in another cohort; 31 in addition, patients with a high ARR under AZA treatment might have been switched to RTX. Moreover, we cannot completely exclude that patients with more aggressive disease were more commonly treated with RTX than AZA based on the presumption of treatment superiority.…”

Section: Discussionmentioning

confidence: 99%

Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response

Stellmann

Krumbholz

Friede

et al. 2017

J Neurol Neurosurg Psychiatry

131

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ObjectiveTo analyse predictors for relapses and number of attacks under different immunotherapies in patients with neuromyelitis optica spectrum disorder (NMOSD).DesignThis is a retrospective cohort study conducted in neurology departments at 21 regional and university hospitals in Germany. Eligible participants were patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD. Main outcome measures were HRs from Cox proportional hazard regression models adjusted for centre effects, important prognostic factors and repeated treatment episodes.Results265 treatment episodes with a mean duration of 442 days (total of 321 treatment years) in 144 patients (mean age at first attack: 40.9 years, 82.6% female, 86.1% aquaporin-4-antibody-positive) were analysed. 191 attacks occurred during any of the treatments (annual relapse rate=0.60). The most common treatments were rituximab (n=77, 111 patient-years), azathioprine (n=52, 68 patient-years), interferon-β (n=32, 61 patient-years), mitoxantrone (n=34, 32.1 patient-years) and glatiramer acetate (n=17, 10 patient-years). Azathioprine (HR=0.4, 95% CI 0.3 to 0.7, p=0.001) and rituximab (HR=0.6, 95% CI 0.4 to 1.0, p=0.034) reduced the attack risk compared with interferon-β, whereas mitoxantrone and glatiramer acetate did not. Patients who were aquaporin-4-antibody-positive had a higher risk of attacks (HR=2.5, 95% CI 1.3 to 5.1, p=0.009). Every decade of age was associated with a lower risk for attacks (HR=0.8, 95% CI 0.7 to 1.0, p=0.039). A previous attack under the same treatment tended to be predictive for further attacks (HR=1.5, 95% CI 1.0 to 2.4, p=0.065).ConclusionsAge, antibody status and possibly previous attacks predict further attacks in patients treated for NMOSD. Azathioprine and rituximab are superior to interferon-β.

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“…Previous research has shown that certain races, specifically Afro-Caribbeans, have greater relapse rates [17]. This may drive providers to treat non-Caucasian patients more aggressively and favor first-line rituximab in this patient population.…”

Section: Discussionmentioning

confidence: 99%

Use of rituximab and risk of re-hospitalization for children with neuromyelitis optica spectrum disorder

Gmuca

Xiao

Weiss

et al. 2018

Mult Scler Demyelinating Disord

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Background Treatment algorithms for neuromyelitis optica spectrum disorder (NMOSD) vary, and sparse data exist regarding the impact of initial treatments on disease course. We aimed to determine whether administration of rituximab during first hospitalization reduces 1-year readmission rates. Methods We conducted a retrospective cohort study of subjects with NMOSD using the Pediatric Health Information System database from 2005-2015. Subjects were ages 1 to 21 years who received glucocorticoids and an ICD-9-CM code indicating neuromyelitis optica (NMO) during first hospitalization. All subjects had at least 12 months of continuous enrollment. The primary exposure was ≥1 rituximab dose during first hospitalization. We tested for the association of rituximab use with all-cause re-hospitalization, the primary outcome, using survival analysis. Re-hospitalization was considered if a hospital admission occurred > 30 days after initial discharge with exclusion of admissions with re-dosing of rituximab and data were censored at 12 months. Secondary outcomes included time to and median duration of re-hospitalization using 25th percentiles of survival time and the Wilcoxon-rank sum test, respectively. Results Of 180 subjects who met inclusion criteria, 71.7% were female and the median age was 13 years (IQR: 10, 15). 52 subjects (28.9%) received rituximab during first hospitalization, and there was an increasing trend in rituximab use over time (p<0.01). Overall, 36.7% of children were readmitted and time to readmission was a median of 365 days (IQR: 138, 365). Rituximab exposure was not associated with re-hospitalization (adjusted HR: 0.71: 95% CI: 0.38, 1.34) nor a reduced time to re-hospitalization. Median duration of re-hospitalization was 2 days shorter in the rituximab exposed group (p=0.02). Receipt of physical therapy, a surrogate marker for neurologic impairment, during first hospitalization was associated with re-admission within 12 months (adjusted HR: 4.81; 95% CI: 1.14, 20.29). Conclusions Among children with NMOSD, first-line administration of rituximab was not associated with risk of or time to re-hospitalization. Rituximab use was found to be associated with a shorter duration of re-hospitalization. Need for physical therapy during first hospitalization was independently associated with an increased risk of re-admission.

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Neuromyelitis optica relapses: Race and rate, immunosuppression and impairment

Abstract: Relapse rates in NMO are influenced by multiple factors, including age, ethnicity and disease duration. Current immunosuppressive treatments reduce but do not abolish relapses, however, they appear to additionally lessen the chronic disabling effect of a relapse.

Cited by 36 publications

References 14 publications

Dose effects of mycophenolate mofetil in Chinese patients with neuromyelitis optica spectrum disorders: a case series study

Dose effects of mycophenolate mofetil in Chinese patients with neuromyelitis optica spectrum disorders: a case series study

Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response

Use of rituximab and risk of re-hospitalization for children with neuromyelitis optica spectrum disorder

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