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A high incidence of disease flares in an open pilot study of infliximab in patients with refractory inflammatory myopathies
  1. Maryam Dastmalchi (maryam.dastmalchi{at}karolinska.se)
  1. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Sweden
    1. Cecilia Grundtman (cecilia.grundtman{at}ki.se)
    1. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Sweden
      1. Helene Alexanderson (helene.alexanderson{at}karolinska.se)
      1. Department of Physical Therapy , Karolinska University Hospital Solna, Sweden
        1. Clio P Mavragani (mavraganik{at}hss.edu)
        1. Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, United States
          1. Hildur Einarsdottir (hildure{at}landspitali.is)
          1. Department of Radiology, Karolinska University Hospital Solna, Sweden
            1. Sevim Barbasso Helmers (sevim.barbasso{at}ki.se)
            1. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Sweden
              1. Kerstin Elvin (kerstin.elvin{at}karolinska.se)
              1. Department of Clinical Immunology and tranfusion medicine, Karolinska University Hospital Solna, Sweden
                1. Mary K Crow (crowm{at}hss.edu)
                1. Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, United States
                  1. Inger Nennesmo (inger.nennesmo{at}karolinska.se)
                  1. Department of Pathology, Karolinska University Hospital Huddinge, Sweden
                    1. Ingrid E Lundberg, MD, PhD (ingrid.lundberg{at}ki.se)
                    1. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Sweden

                      Abstract

                      Objective: To investigate the effect of the tumor necrosis factor (TNF) blocking agent infliximab in patients with treatment-resistant inflammatory myopathies.

                      Methods: Thirteen patients with refractory polymyositis (PM), dermatomyositis (DM), or inclusion body myositis (IBM) were treated with four infliximab infusions (5mg/kg body weight) during 14 weeks. Outcome measures included myositis disease activity score with improvement defined according to The International Myositis Assessment and Clinical Studies Group (IMACS), and magnetic resonance imaging (MRI). Repeated muscles biopsies were investigated for cellular infiltrates, major histocompatibility complex (MHC) class I and II, TNF, interleukin (IL)-α, IL-6, high mobility group box chromosomal protein 1 (HMGB-1), interferon-γ (IFN-γ), MxA, and membrane attack complex (MAC) expression. Type I IFN activity was analysed in sera.

                      Results: Nine patients completed the study. Three patients discontinued due to adverse events and one due to a discovered malignancy. Three of the completers improved by ≥ 20% in three or more variables of the disease activity core set, four were unchanged and two worsened ≥ 30%. No patient improved in muscle strength by manual muscle test. At baseline, two completers had signs of muscle inflammation by MRI, and five at follow-up. T-lymphocytes, macrophages, cytokine expression, and MAC deposition in muscle biopsies was still evident after treatment. Type I IFN activity was increased after treatment.

                      Conclusions: Infliximab treatment was not effective in refractory inflammatory myopathies. In view of radiological and clinical worsening, and activation of the type I IFN system in several cases, infliximab is not an alternative treatment in treatment resistant myositis patients.

                      • IMACS
                      • TNF blocker
                      • dermatomyositis (DM)
                      • inclusion body myositis (IBM)
                      • polymyositis (PM)

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