Comparison of Mycophenolate Mofetil and Cyclophosphamide for Active Takayasu’s Arteritis

Overview

Takayasu's arteritis(TAK) is a rare systemic vasculitis which can cause ischemia or inflammation of the involved organs and increase the overall mortality rate.The traditional treatment of TAK is primarily empirical. The most commonly used drugs for treating active TAK are glucocorticosteroids(GC) and immunosuppressants. However, the genital toxicity of CYC has limited its long term use. In a pilot study carried out by the principal investigator of this study has shown that mycophenolate mofetil(MMF) combined with MTX is effective and with few adverse effects. The purpose of this prospective open-label study is to compare the efficacy and safety of GC+MMF+MTX with GC+CYC followed by GC+AZA for the treatment of active TAK. 150 patients with active TAK will be recruited and randomized in a 2:1 ratio to GC+MMF+MTX group and C+CYC and AZA group. Patients were followed for 52 weeks for efficacy and safety assessment.

Full Title of Study: “Comparison of the Efficacy of Mycophenolate Mofetil Combined With Methotrexate and Cyclophosphamide for the Treatment of Takayasu’s Arteritis”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 11, 2022

Detailed Description

Takayasu's arteritis(TAK) is a rare systemic vasculitis which mainly involves aorta and its major branches. However,it is more prevalent in countries and areas along the silk road.Young women at child-bearing age is the most prevalent population.It can cause ischemia or inflammation of the involved organs and increase the overall mortality rate.Although it may be lethal in some patients,it is not well studied due to the rareness of the disease.The traditional treatment of TAK is primarily empirical. The most commonly used drugs for treating active TAK are glucocorticosteroids(GC) and immunosuppressants including cyclophosphamide(CYC), methotrexate(MTX) and azathioprine(AZA) etc. However,no of these drugs have been well studied. In addition, the genital toxicity of CYC, the first line medication for active TAK, has become the major limitation for its long term use for a chronic disease like TAK. Therefore, new immunosuppressants with less toxicity,especially with much less genital toxicity and low malignancy risk is essentially necessary. In a pilot study carried out by the principal investigator of this study has shown that mycophenolate mofetil(MMF) combined with MTX is effective and with few adverse effects. The purpose of this prospective open-label study is to compare the efficacy and safety of GC+MMF+MTX with GC+CYC followed by GC+AZA for the treatment of active TAK. 150 patients with active TAK will be recruited and randomized in a 2:1 ratio to GC+MMF+MTX group and C+CYC and AZA group. Patients were followed for 52 weeks to assess the efficacy and safety.

Interventions

  • Drug: MMF
    • Patients were treated with Glucocorticoids combined with methotrexate and mycophenolate mofetil
  • Drug: CYC
    • Patients were treated with Glucocorticoids and cyclophosphamide sequentially with azathioprine
  • Drug: Glucocorticoids
    • Patients in the experimental group and comparator group were treated with Glucocorticoids and then gradually tapered
  • Drug: MTX
    • Patients in the experimental group are treated with Glucocorticoids combined with MTX and MMF
  • Drug: AZA
    • Patients in the active comparator group were treated with Glucocorticoids combined with CYC followed by AZA

Arms, Groups and Cohorts

  • Experimental: MMF+MTX+Glucocorticoids
    • Patients were treated with Glucocorticoids combined with mycphenolate mofetil(MMF) as well as methotrexate(MTX) treatment for 52 weeks and were followed for 52 weeks.
  • Active Comparator: CYC/AZA+Glucocoticoids
    • Patients were treated with Glucocorticoids combined with cyclophosphamide(CYC)/azathioprine(AZA) for 52 weeks and were followed for 52 weeks

Clinical Trial Outcome Measures

Primary Measures

  • Proportion of patients with complete remission
    • Time Frame: 52 weeks
    • The proportion of patients who reached the pre-defined criteria of complete remission in both groups

Secondary Measures

  • Proportion of patients with partial remission
    • Time Frame: 52 weeks
    • Proportion of patients who reached the pre-defined partial remission criteria of the disease
  • Safety profile of MMF combined with MTX
    • Time Frame: 52 weeks
    • Proportion of adverse events in both treatment groups
  • Rate of complications
    • Time Frame: 52 weeks
    • Proportion of patients with complications in both treatment group

Participating in This Clinical Trial

Inclusion Criteria

1. Patients older than 18 years-old either sex 2. Patients with signed informed consent 3. Fulfill the 1990 ACR Classification Criteria for TAK 4. Patients with active disease according to GACTA criteria Exclusion Criteria:

1. Prior adverse events when treated with MTX that resulted in dose reduction or discontinuation; 2. Prior treatment with MMF but failed response to MMF; 3. Prior treatment with CYC but failed response to CYC; 4. Renal dysfunction, defined as the estimated GFR <80% or serum creatinine level higher than 1.5 times of upper normal limit; 5. Severe liver function damage defined by serum ALT or AST higher than 2 times of the upper normal limits; 6. Uncontrolled diabetes melitus; 7. Uncontrolled heart failure at baseline; 8. Active infection including tuberculosis , hepatitis B virus, hepatitis C virus, HIV or bacterial or fungal infection; 9. Active upper GI bleeding in the past 3 months.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Chinese SLE Treatment And Research Group
  • Collaborator
    • Peking Union Medical College Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: Xinping Tian, Professor of Medicine – Peking Union Medical College Hospital
  • Overall Official(s)
    • Xinping Tian, MD, Principal Investigator, Peking Union Medical College Hospital

References

Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, Lie JT, Lightfoot RW Jr, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990 Aug;33(8):1129-34. doi: 10.1002/art.1780330811.

Citations Reporting on Results

Goel R, Danda D, Mathew J, Edwin N. Mycophenolate mofetil in Takayasu's arteritis. Clin Rheumatol. 2010 Mar;29(3):329-32. doi: 10.1007/s10067-009-1333-6.

Shinjo SK, Pereira RM, Tizziani VA, Radu AS, Levy-Neto M. Mycophenolate mofetil reduces disease activity and steroid dosage in Takayasu arteritis. Clin Rheumatol. 2007 Nov;26(11):1871-5. doi: 10.1007/s10067-007-0596-z. Epub 2007 Feb 28.

Daina E, Schieppati A, Remuzzi G. Mycophenolate mofetil for the treatment of Takayasu arteritis: report of three cases. Ann Intern Med. 1999 Mar 2;130(5):422-6. doi: 10.7326/0003-4819-130-5-199903020-00013.

Ong LM, Hooi LS, Lim TO, Goh BL, Ahmad G, Ghazalli R, Teo SM, Wong HS, Tan SY, Shaariah W, Tan CC, Morad Z. Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. Nephrology (Carlton). 2005 Oct;10(5):504-10. doi: 10.1111/j.1440-1797.2005.00444.x.

Li J, Yang Y, Zhao J, Li M, Tian X, Zeng X. The efficacy of Mycophenolate mofetil for the treatment of Chinese Takayasu's arteritis. Sci Rep. 2016 Dec 7;6:38687. doi: 10.1038/srep38687.

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