Clinical trial NCT03002038: Comparison of Clinical Effects of Azathioprine and Rituximab NMO-SD Patients
Official title: Comparison of Annual Relapse Rate, Expanded Disability Status Scale, and Side Effects Between Azathioprine and Rituximab in Patients With Neuromyelitis Optica Spectrum Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Neuromyelitis Optica Spectrum Disorder
Keywords: neuromyelitis optica spectrum disorder
azathioprine
rituximab
clinical trial
annual relapse rate
expanded disability status scale
Lead sponsor: Isfahan University of Medical Sciences
Sponsor class: OTHER
First posted: 2016-12-23
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Annual Relapse Rate
timeFrame: one year
Secondary outcomes:
measure: Expanded Disability Status Scale
timeFrame: one year
Other outcomes:
measure: Number of Participants With Adverse Drug Reactions
timeFrame: one year
Locations:
city: Isfahan
country: Iran, Islamic Republic of
facility: Kashani Hospital
Study officials:
affiliation: Department of Neurology, School of Medicine, Isfahan University of Medical Sciences
name: Vahid Shaygannejad, M.D.
role: STUDY_CHAIR
References:
citation: 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.
citation: Morrow MJ, Wingerchuk D. Neuromyelitis optica. J Neuroophthalmol. 2012 Jun;32(2):154-66. doi: 10.1097/WNO.0b013e31825662f1.
citation: 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.
citation: 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.
citation: 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.
citation: Katz Sand I. Neuromyelitis Optica Spectrum Disorders. Continuum (Minneap Minn). 2016 Jun;22(3):864-96. doi: 10.1212/CON.0000000000000337.
citation: 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.