Mizoribine Synchronized Methotrexate Therapy should be Considered when Treating Rheumatoid Arthritis Patients with an Inadequate Response to Various Combination Therapies

Intern Med. 2017;56(10):1147-1152. doi: 10.2169/internalmedicine.56.7886. Epub 2017 May 15.

Abstract

Objective The objective of this study was to confirm the efficacy of low-dose mizoribine (MZR), an inhibitor of inosine monophosphate dehydrogenase, as part of synchronized methotrexate (MTX) therapy for rheumatoid arthritis (RA) patients with an inadequate response to various combination therapies of MTX, other synthetic disease-modifying anti-rheumatic drugs (DMARDs) and biological DMARDs. Methods Low-dose MZR was administered to 56 uncontrolled RA patients being treated with MTX and various biological DMARDs. The observation period was 12 months, and the disease activity was evaluated based on the Disease Activity Score in 28 joints (DAS28)-ESR, Simplified Disease Activity Index (SDAI) and serum MMP-3 level. Results All of the disease activity indices were significantly improved within three months, and the serum MMP-3 levels were also significantly decreased around four months after starting low-dose MZR therapy. No patients experienced any adverse effects. Conclusion The present preliminary findings suggest that low-dose MZR therapy with MTX should be considered for the treatment of RA patients with an inadequate response to various combination therapies including MTX, other synthetic DMARDs and biological DMARDs or in whom increasing the dose of MTX is difficult for reasons such as adverse effects and complications.

Keywords: DMARDs; methotrexate; mizoribine; remission; rheumatoid arthritis.

MeSH terms

  • Aged
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 3 / metabolism
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Pilot Projects
  • Ribonucleosides / administration & dosage
  • Ribonucleosides / therapeutic use*
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Ribonucleosides
  • mizoribine
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • Methotrexate