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

Isfahan University of Medical Sciences

Status and phase: Completed; Phase 3; Phase 2

Conditions: Neuromyelitis Optica Spectrum Disorder

Treatments: Drug: Rituximab; Drug: Azathioprine

Study type: Interventional

Funder types: Other

Identifiers

NCT03002038

395275

Details and patient eligibility

About

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.

Full 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.

Enrollment: 86 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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86 participants in 2 patient groups

Azathioprine

Experimental group

Description:

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.

Treatment:

Drug: Azathioprine

Rituximab

Experimental group

Description:

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.

Treatment:

Drug: Rituximab