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Azathioprine, rituximab superior to interferon-β in treatment of NMOSD

Stephen Padilla
27 Jul 2017

The predictors of further attacks in patients being treated for neuromyelitis optica spectrum disorder (NMOSD) are age, antibody status and possible previous attacks, according to recent study. Additionally, azathioprine and rituximab perform better than interferon-β in the treatment of NMOSD.

Researchers analysed a total of 265 treatment episodes with a mean 442 days duration (total of 321 treatment years) in 144 patients (mean age at first attack, 40.9 years; 82.6 female; 86.1 percent aquaporin-4-antibody-positive). [J Neurol Neurosurg Psychiatry 2017;88:639-647]

The most commonly used treatments for NMOSD 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). There were 191 attacks during any of the treatments (annual relapse rate [ARR], 0.60).

Compared with interferon-β, azathioprine (hazard ratio [HR], 0.4; 95 percent CI, 0.3 to 0.7; p=0.001) and rituximab (HR, 0.6; 0.4 to 1.0; p=0.034) attenuated the risk of attack, but mitoxantrone and glatiramer acetate did not.

“Overall, we found moderate to low unadjusted ARRs under rituximab and azathioprine, the two most commonly used drugs for NMOSD in our cohort,” researchers said. “This is in line with other studies reporting ARRs under these therapies of between 0.1 and 0.9.” [Neurol Neuroimmunol Neuroinflamm 2014;1:88; J Neurol 2015;262:2329–35; Mult Scler 2016;22:955–9; Mult Scler 2014;20:1533–40; JAMA Neurol 2015;72:989–95; Neurology 2011;77:659–66]

Interestingly, two previous studies suggested the superiority of rituximab over azathioprine. In the current study, mainly Caucasian patients were included, but the two other retrospective cohorts included African or predominantly Asian patients. It is thought that genetic differences contribute to the rituximab therapy response in NMOSD. [JAMA Neurol 2014;71:324–30; Mult Scler 2016;22:329–39; JAMA Neurol 2015;72:989–95]

Patients who were positive for aquaporin-4-antibody had an increased risk of attacks (HR, 2.5; 1.3 to 5.1; p=0.009), whereas every decade of age correlated with a reduced risk of attacks (HR, 0.8; 0.7 to 1.0; p=0.039). Furthermore, previous attack under the same treatment appeared to predict further attacks (HR, 1.5; 1.0 to 2.4; p=0.065).

“This is in line with a previous study that did not detect an association between attack risk and aquaporin-4-antibody in azathioprine-treated and mycophenolate mofetil-treated patients, but described a decrease of attack risk with age,” according to researchers. In addition, nonresponders to first-line therapy with azathioprine or mycophenolate mofetil had less relapses on subsequent therapy with rituximab. [Multi Scler 2017;doi:10.1177/1352458516687403]

In this retrospective cohort study, researchers analysed patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD to determine predictors for relapses and number of attacks under different immunotherapies.

A rare autoimmune disease of the central nervous system, NMOSD is primarily characterized by recurrent attacks of optic neuritis and longitudinally extensive transverse myelitis. Aquaporin-4-antibodies were identified as pathogenic, and their detection, along with typical clinical manifestation, is a hallmark of the recently updated diagnostic criteria, according to researchers. [Clin Exp Immunol 2014;176:149–64; Brain Pathol 2013;23:661–83; Neurology 2015;85:177–89; Neurol Neuroimmunol Neuroinflamm 2015;2:e110]

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