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The safety and efficacy of tocilizumab in patients with neuromyelitis optica: Multicenter study (Tocilizumab in patients with neuromyelitis optica)

Tocilizumab in patients with neuromyelitis optica (Tocilizumab in patients with neuromyelitis optica)

20

In total, 20 anti-AQP4-Ab+ neuromyelitis optica patients were enrolled (18 female/ 2 male). Eighteen from NCNP hospital and 2 from Kindai hospital.

Since the start of this study (2011.10), the following number of patients were enrolled: 2011(1), 2012(7), 2013(3), 2014(4) and 2017(5).

In total, 24 adverse events were reported (Infections 16 cases, abnormal clinical test value 2 cases, others 6 cases). There were no serious cases. There was one sepsis case but treated and the patient recovered. The effect of concomitant drugs such as steroids and immunosuppressive drugs were considered.

1. Safety profiles are shown above. 2. The effect of reducing the annual relapse rate (ARR). The ARR of pretreatment period were 2.1 on average. After tocilizumab therapy, the ARR turned out to be 0.25 on average.

This is an exploratory clinical study investigating the safety profiles and efficacy of tocilizumab for refractory anti-AQP4-Ab+ neuromyelitis optica patients. In total, 20 patients were enrolled. The safety profiles included 16 infections, mostly mild and there were no unexpected severe adverse events. Clinical efficacy were apparent with significant reduction of annual relapse rates after tocilizumab treatment.

Jan. 01, 2021

April. 15, 2014

https://n.neurology.org/content/82/15/1302.short

Undecided

not determined

https://jrct.mhlw.go.jp/latest-detail/jRCTs031180152

Yamamura Takashi

National Center of Neurology and Psychiatry

4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502

yamamura@ncnp.go.jp

Sato Wakiro

National Center of Neurology and Psychiatry

4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8551

+81-42-341-2711

wakirosato@ncnp.go.jp

Complete

June. 04, 2012

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

Diagnosis of neuromyelitis optica (NMO), as defined by 2006 criteria published in NEUROLOGY vol. 66 or NMO seropositive spectrum disorder (recurrent optic neuritis or longitudinally extensive transverse myelitis). All patients must be anti-aquaporin 4 antibody seropositive.

Patients with intractable NMO who are resistant to the standard therapy or experiencing sever adverse reactions of the current therapy.

History of at least one relapse during the 1 year prior to initiation of this study.

Provision of written informed consent to participate in this study.

1) Patients with severe infection
tuberculosis, pneumocystis carinii pneumonia, nontuberculous mycobacterial infection (diagnosed by tuberculin test, beta-D glucan,chest X-ray)
When the tuberculin test shows intermediate or strong positivity, or the patients have a clinical history of contact with a patient with tuberculosis, isoniazid or rifampicin at a dose of 300 mg once daily for 6 to 9 months with pyridoxal at a dose of 10mg once daily initiated 3 weeks prior to tocilizumab.
Immunocompromised host
2) hepatitis B (positivity for HBS Ag and HBC Ab, hepatitis C (positivity for HCV Ab), or chronic active EB virus infection.
Patients with a history of tuberculosis infection or patients with pleural thickness or old tuberculin in chest X-ray.
3) Patients with a history of hypersensitivity to this drug.
4) Patients with a history of intestinal diverticulum.
5) Patients with interstitial pneumonitis.
6) Patients with leukopenia (white blood cell number less than 4000/mm3), lymphopenia (lymphocyte number less than 500/mm3) or seropositivity for beta-D-glucan in peripheral blood.
7) Pregnant women or patients with possible pregnancy.
8) Patients aged older than 20 and younger than 66 years.
9) Patients with a history of allergic reaction to tocilizumab.
10) Patients who cannot provide consent to participate in this study by themselves.
11) Patients whose EDSS are more than 7.

Both

Neuromyelitis optica

Tocilizumab is to be infused every 4 weeks at 8 mg/kg of body weight for 6 months.

D009471

1) Adverse events after the initiation of TCZ
2) Relapsing rate after the initiation of TCZ, as compared to pretreatment period

1) EDSS/FS
2) Neurological findings (neurological examination, visual acuity, VAS(1), Critical flicker frequency(2), VEP(3), SSEP(4), ABR(5), Motor functional and sensory functional test)
3) New lesions in brain and spinal cord MRI
4) Cerebral spinal fluid cytokine profiles
5) Anti-aquaporin 4 antibody titer
6) Plasmablast frequency
7) T cell cytokine profile
8) Gut microbiota

+81-42-341-2712-7828

Feb. 08, 2019

none