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Leflunomide and methotrexate reduce levels of activated mmps in complexes with α2macroglobulin in serum of rheumatoid arthritis patients
  1. I Tchetverikov (i.tchetverikov{at}
  1. Leiden University Medical Centre, Netherlands
    1. M C Kraan
    1. Schering Plough Research Institute, United States
      1. B van El
      1. Quality of Llife, Business unit BioSciences, Netherlands
        1. R Hanemaaijer
        1. Quality of Llife, Business unit BioSciences, Netherlands
          1. J DeGroot
          1. Quality of Llife, Business unit BioSciences, Netherlands
            1. T WJ Huizinga (t.w.j.huizinga{at}
            1. Leiden University Medical Center, Netherlands


              Objective: To analyze the effects of leflunomide and methotrexate treatment on MMP activity levels in α2Macroglobulin/MMP (α2M/MMP) complexes in the systemic circulation of rheumatoid arthritis (RA) patients.

              Methods: One hundred and two RA patients from a prospective, double blind, randomized clinical trial comparing leflunomide and methotrexate were selected; clinical data and blood samples were collected at baseline, at 4 month and at 1 year. Serum MMP activity levels in α2M were quantified using low molecular weight fluorogenic substrates, indicating the proportion of activated MMPs which were not inhibited by specific Tissue Inhibitors of MMP (TIMP).

              Results: Patients had active disease as shown by high Disease Activity Score (DAS, mean of 6.9 and 7.0 for methotrexate and leflunomide patients respectively), which was reduced over the study period (4.2 and 5.2 respectively, P < 0.001). In leflunomide treated patients a significant reduction of MMP activity levels was observed as early as at 4 month time point persisting thereafter, whereas in methotrexate treated patients the reduction was found at 1 year.

              Conclusion: The presented results show that systemic levels of activated MMPs are reduced in RA patients upon exposure to leflunomide or methotrexate.

              • leflunomide
              • matrix metalloproteinases
              • methotrexate
              • rheumatoid arthritis

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