Comparison of Clinical Effects of Azathioprine and Rituximab NMO-SD Patients

NCT ID: NCT03002038

Last Updated: 2020-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2016-12-31

Brief Summary

The purpose of this study is to compare annual relapse rate, expanded disability status scale, and side effects of azathioprine and rituximab in patients with neuromyelitis optica spectrum disorder during a one year follow up through a randomized clinical trial.

Detailed Description

Neuromyelitis Optica Spectrum Disorder (NMO-SD) is a recurrent inflammatory demyelinating disease affecting the central nervous system. The disease is clinically recognized by optic neuritis and transverse myelitis and is associated with high risk of mortality. Each attack worsens patients' disability. This means that after 5 years of the disease onset, half of patients need to use wheelchair and approximately 50% of them become blind.

Considering that the disease can be disabling for patients, the maintenance treatment should be applied in addition to treatment of acute attacks, in order to prevent future recurrences. Acute attacks are usually treated with high doses of intravenous corticosteroids. Plasmapheresis is also used when patients fail to response to corticosteroids. B lymphocyte inhibitors are used as the maintenance therapy in these patients. First line therapeutic medications include azathioprine and rituximab which are being recommended for long term therapy and second line medications include methotrexate and mycophenolate mofetil.

Azathioprine is an immune-modulatory agent which is available in the oral form and don't require hospitalization to be administered, however, because of side effects such as bone marrow suppression and hepatotoxicity, periodic check of blood cells and liver enzymes are needed. Rituximab is a cluster of differentiation antigen 20 inhibitor which leads to decreased B lymphocytes and antibody in patients. This medication is only available in the injectable form and needs hospitalization to be administered. Close monitory is needed during the administration considering severe side effects such as allergic reactions and respiratory distress. However, laboratory tests are not needed in patients taking rituximab although it is more expensive than azathioprine. No clinical trial has been performed previously to compare clinical efficacy of these two drugs in NMO-SD patients. Therefore, we aimed to compare their efficacy through a randomized clinical trial.

Conditions

Neuromyelitis Optica Spectrum Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Azathioprine

Patients in this group will receive 50 mg of azathioprine, two times each day and gradually increased to maximum dose of 3 g daily with the aim of lymphocytes count less than 1500.

Group Type: EXPERIMENTAL

Azathioprine

Intervention Type: DRUG

Patients are started with Azathioprine 50 mg tablets, taken orally twice a day. The medication dose is increased gradually with the aim of lymphocytes count bellow 1500 and to the maximum dose of 3 g Azathioprine per day. Cell blood count is checked once a week in the first month of treatment, once every two weeks in the second month of treatment, and monthly in the third month of treatment to make decision about medication dose.

Rituximab

Patients in this group will receive 1g of Rituximab in 500 cc normal saline serum through intravenous infusion with two weeks intervals (as one course) and each course of treatment is repeated every 6 months.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Patients will receive 1 g of Rituximab (two vials of RediTux 500 mg/50 ml) in 500 cc normal saline serum through intravenous infusion and this will be repeated two weeks later. This cycle will be repeated every 6 months.

Interventions

Azathioprine

Patients are started with Azathioprine 50 mg tablets, taken orally twice a day. The medication dose is increased gradually with the aim of lymphocytes count bellow 1500 and to the maximum dose of 3 g Azathioprine per day. Cell blood count is checked once a week in the first month of treatment, once every two weeks in the second month of treatment, and monthly in the third month of treatment to make decision about medication dose.

Intervention Type: DRUG

Rituximab

Patients will receive 1 g of Rituximab (two vials of RediTux 500 mg/50 ml) in 500 cc normal saline serum through intravenous infusion and this will be repeated two weeks later. This cycle will be repeated every 6 months.

Intervention Type: DRUG

Other Intervention Names

Azathioprine Mehrdaru®; RediTux®

Eligibility Criteria

Inclusion Criteria

• Diagnosis of neuromyelitis optica spectrum disorder based on the recent guidelines in 2015
• Expanded disability status scale between 0 and 7
• Age between 18 and 50 years old

Exclusion Criteria

• Pregnancy or lactation during the study
• Deciding to leave the study by patient
• Lack of consent to enter the study
• Lack of cooperation for follow up
• Severe side effect of the medication
• Treatment with other immunosuppressant medications (including but not limited to cyclophosphamide, mycophenolate mofetil, methotrexate, others) within two months before intervention
• Taking any other immunosuppressant or other type of medication (including herbal drugs) without permission of the physician during the study.
• Presence of other autoimmune disease (including but not limited to Behcet disease, systemic lupus erythematosus, rheumatoid arthritis, and others)
• Presence of liver disorders
• Presence of hematologic disorders
• Presence of heart failure
• Receipt of a live vaccine within 4 weeks prior to intervention
• Previous treatment with Azathioporine or Rituximab
• History of HIV, hepatitis B, or hepatitis C
• Ongoing daily steroid use
• History of severe allergic or anaphylactic reaction to monoclonal antibodies

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Isfahan University of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Vahid Shaygannejad

Associate Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Vahid Shaygannejad, M.D.

Role: STUDY_CHAIR

Department of Neurology, School of Medicine, Isfahan University of Medical Sciences

Locations

Kashani Hospital

Isfahan, , Iran

Countries

Iran

References

Sato DK, Lana-Peixoto MA, Fujihara K, de Seze J. Clinical spectrum and treatment of neuromyelitis optica spectrum disorders: evolution and current status. Brain Pathol. 2013 Nov;23(6):647-60. doi: 10.1111/bpa.12087.

Reference Type: BACKGROUND

PMID: 24118482 (View on PubMed)

Morrow MJ, Wingerchuk D. Neuromyelitis optica. J Neuroophthalmol. 2012 Jun;32(2):154-66. doi: 10.1097/WNO.0b013e31825662f1.

Reference Type: BACKGROUND

PMID: 22617743 (View on PubMed)

Costanzi C, Matiello M, Lucchinetti CF, Weinshenker BG, Pittock SJ, Mandrekar J, Thapa P, McKeon A. Azathioprine: tolerability, efficacy, and predictors of benefit in neuromyelitis optica. Neurology. 2011 Aug 16;77(7):659-66. doi: 10.1212/WNL.0b013e31822a2780. Epub 2011 Aug 3.

Reference Type: BACKGROUND

PMID: 21813788 (View on PubMed)

Trebst C, Jarius S, Berthele A, Paul F, Schippling S, Wildemann B, Borisow N, Kleiter I, Aktas O, Kumpfel T; Neuromyelitis Optica Study Group (NEMOS). Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). J Neurol. 2014 Jan;261(1):1-16. doi: 10.1007/s00415-013-7169-7. Epub 2013 Nov 23.

Reference Type: BACKGROUND

PMID: 24272588 (View on PubMed)

Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013 Sep 1;70(9):1110-7. doi: 10.1001/jamaneurol.2013.3071.

Reference Type: BACKGROUND

PMID: 23897062 (View on PubMed)

Katz Sand I. Neuromyelitis Optica Spectrum Disorders. Continuum (Minneap Minn). 2016 Jun;22(3):864-96. doi: 10.1212/CON.0000000000000337.

Reference Type: BACKGROUND

PMID: 27261687 (View on PubMed)

Nikoo Z, Badihian S, Shaygannejad V, Asgari N, Ashtari F. Comparison of the efficacy of azathioprine and rituximab in neuromyelitis optica spectrum disorder: a randomized clinical trial. J Neurol. 2017 Sep;264(9):2003-2009. doi: 10.1007/s00415-017-8590-0. Epub 2017 Aug 22.

Reference Type: DERIVED

PMID: 28831548 (View on PubMed)

Other Identifiers

395275

Identifier Type: -

Identifier Source: org_study_id