Efficacy of azathioprine on multiple sclerosis new brain lesions evaluated using magnetic resonance imaging

Arch Neurol. 2005 Dec;62(12):1843-7. doi: 10.1001/archneur.62.12.1843.

Abstract

Background: Azathioprine is an immunosuppressive agent that reduces relapse rates in patients with multiple sclerosis (MS), but its efficacy in suppressing new brain lesions has never been evaluated.

Objective: To evaluate the efficacy of azathioprine therapy on new brain lesion suppression in MS.

Design: Open-label treatment vs baseline study.

Setting: Outpatient MS clinical center at a university hospital.

Patients: Fourteen patients with relapsing-remitting MS of short duration and at least 3 gadolinium-enhancing (Gd+) brain lesions observed within 6 months before treatment.

Intervention: Azathioprine, up to 3 mg/kg daily, individually adjusted according to blood lymphocyte number and the occurrence of adverse events.

Main outcome measures: Brain Gd+ lesions evaluated by monthly magnetic resonance imaging for 6 months before and 6 months during treatment and new T2 lesions evaluated during the same periods and after an additional 6 months.

Results: The treatment reduced to 0 the median Gd+ lesion number and volume per magnetic resonance image (P<.001 for both), resulting in a Gd+ lesion number reduction of 50% or more in 12 of 14 patients (P<.01). An equivalent reduction in the new T2 lesion number was observed (P<.02); this activity also persisted during the additional treatment period evaluated using this outcome measure (P<.01). The median azathioprine dose administered (2.6-2.8 mg/kg daily) reduced the mean blood lymphocyte count to 57% of the baseline value. Adverse events were transient or reversible with dose adjustment.

Conclusions: This study indicates for the first time that azathioprine, administered at lymphocyte-suppressing doses, is effective in reducing MS new brain inflammatory lesions and is well tolerated.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Azathioprine / administration & dosage*
  • Azathioprine / adverse effects
  • Brain / drug effects*
  • Brain / pathology*
  • Brain / physiopathology
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Encephalitis / drug therapy
  • Encephalitis / pathology
  • Encephalitis / physiopathology
  • Female
  • Gadolinium
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Lymphocyte Count
  • Lymphocytes / drug effects
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Multiple Sclerosis, Relapsing-Remitting / physiopathology
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Gadolinium
  • Azathioprine