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Treatment of spondyloarthropathies with antibodies against tumour necrosis factor α: first clinical and laboratory experiences
  1. Jürgen Braun,
  2. Jian Xiang,
  3. Jan Brandt,
  4. Hardy Maetzel,
  5. Hildrun Haibel,
  6. Peihua Wu,
  7. Siegfried Kohler,
  8. Martin Rudwaleit,
  9. Stefanie Siegert,
  10. Andreas Radbruch,
  11. Andreas Thiel,
  12. Joachim Sieper
  1. Department of Medicine, Rheumatology, Benjamin Franklin Hospital, Free University Berlin, and German Rheumatology Research Centre, Berlin, Germany
  1. Professor Braun (jbraun{at}zedat.fu-berlin.de)

https://doi.org/10.1136/ard.59.suppl_1.i85

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    Drug treatment of patients with spondyloarthropathies (SpA), especially ankylosing spondylitis (AS) has limited capacity.1 Pain but not disease activity can be reduced by non-steroidal anti-inflammatory drugs (NSAIDs), in severe cases very high doses are needed.2 By examination of sacroiliac biopsy specimens we have shown that, in correlation to disease activity assessed by magnetic resonance imaging (MRI), T cells and macrophages3 and tumour necrosis factor α (TNFα) mRNA4 and protein (fig 1) but no bacterial DNA5 is present in these joints that are pathognomonically involved in AS.6 Furthermore, anti-TNFα monoclonal antibodies (mAb) have recently been shown to be efficacious in Crohn's disease7—a disease that is strongly linked to AS because more than 60% of AS patients have clinically often silent gut lesions resembling Crohn's colitis.8 Furthermore, in another chronic inflammatory rheumatic disease, rheumatoid arthritis (RA), anti-TNF treatment has proved efficacious and even seems to prevent joint damage.9

    Figure 1

    Immunohistological examination of a sacroiliac biopsy specimen obtained by computed tomography guided biopsy of a 23 year old patient with ankylosing spondylitis, four years disease duration, with inflammatory back pain grade 6 on a visual analogue scale (0–10). The red staining indicates a mononuclear cell positive for TNFα (APAAP staining technique).

    TNFα is a cytokine that is mainly produced by monocytes and macrophages and to a lesser degree by T cells. There are two specific receptors, a 55 kDa and a 75 kDa present on many cell types. TNFα mediates inflammatory and immunoregulatory activities. Effects on cells such as lymphocyte activation and fibroblast proliferation, on mediators such as other cytokines like interleukin 1(IL1), IL6 and IL8, chemokines, prostaglandins, metalloproteinases, on the vasculature by promoting angiogenesis and on upregulation of adhesion molecules and transendothelial migration of leucocytes are well described. In in vitro and in …

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