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

Phase 2

Completed

Conditions: Neuromyelitis Optica Spectrum Disorder

Interventions: Drug: Azathioprine
Drug: Rituximab

Registration Number: NCT03002038

Lead Sponsor: Isfahan University of Medical Sciences

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 86

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Azathioprine	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.
Rituximab	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.

Primary Outcome Measures

Name	Time	Method
Annual Relapse Rate	one year	annual relapse rate will be measured in the baseline (according to patients' history in the last year) and after 12 months of intervention.

Secondary Outcome Measures

Name	Time	Method
Expanded Disability Status Scale	one year	expanded disability status scale will be measured in the baseline and after 12 months of intervention. Expanded disability status scale (EDSS) is a measure of disability for patients. The score ranges from 0-10, with 0 showing normal neurological exam and 10 showing death due to the disabling disease. Thus, higher scores represent more profound levels of disability.