New Therapeutic Targets in Rheumatoid Arthritis

1. Front Matter

   Pages i-xii

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2. B cell targets in rheumatoid arthritis

   • Edward M. Vital, Shouvik Dass, Paul Emery

   Pages 1-26

3. Co-stimulatory pathways in the therapy of rheumatoid arthritis

   • Eric M. Ruderman, Richard M. Pope

   Pages 27-43

4. Immunobiology of IL-6 — Tocilizumab (humanised anti-IL-6 receptor antibody) for the treatment of rheumatoid arthritis

   • Yoshiyuki Ohsugi, Tadamitsu Kishimoto

   Pages 45-57

5. Role of IL-1 in erosive arthritis, lessons from animal models

   • Wim B. van den Berg, Leo A. B. Joosten, Fons A. J. van de Loo

   Pages 59-74

6. Interleukin-15

   • Jagtar Nijar Singh, Iain B. McInnes

   Pages 75-88

7. IL-17 and Th17 cells, key players in arthritis

   • Pierre Miossec, Ling Toh, Saloua Zrioual

   Pages 89-101

8. Role of IL-18 in inflammatory diseases

   • Charles A. Dinarello

   Pages 103-127

9. Chemokines and chemokine receptors

   • Zoltán Szekanecz, Alisa E. Koch

   Pages 129-153

10. Signaling pathways in rheumatoid arthritis

    • Jean-Marc Waldburger, Gary S. Firestein

    Pages 155-180

11. Targeting oncostatin M in the treatment of rheumatoid arthritis

    • Theresa C. Barnes, Robert J. Moots

    Pages 181-191

12. Targeting the epigenetic modifications of synovial cells

    • Lars C. Huber, Astrid Jüngel, Steffen Gay

    Pages 193-206

13. Perspectives in targeted therapy

    • Edward C. Keystone

    Pages 207-220

14. Back Matter

    Pages 221-228

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During the past decades important breakthroughs have been made in the treatment of rheumatoid arthritis (RA). First, the implementation of low-dose methotrexate and other conventional disease-modifying anti-rheumatic drugs was introduced as an effective treatment. Second, it was recognized that early immunomodu- tory treatment is crucial for controlling the disease and its long-term destructive effects more effectively. Parallel advances in research on the pathogenesis of RA and cytokine biology converged in identifying tumor necrosis factor (TNF) as a key factor in inflammation and matrix destruction. The concept arose that elevated TNF concentrations at the sites of inflammation were driving disease pathology, and the removal of excess TNF from sites of inflammation became a therapeutic goal. Clearly, TNF blockade has revolutionized the treatment of RA, as well as other immune-mediated inflammatory diseases. Anti-TNF treatment results in cli- cal benefit in a significant proportion of the patients, and it has provided proof of concept for the principle of targeted therapy. Despite the impressive disease-modifying effects of the TNF blockers, not all patients respond, and patients who exhibited an initial response may lose response due to the development of anti-drug antibodies (human anti-chimeric antibodies and human anti-human antibodies, respectively) and perhaps as a result of escape mechanisms related to the disease process. In fact, the majority of the patients still have disease activity in at least one or two actively inflamed joints.

• Arthritis
• Chemokine
• Drug Target
• Interleukine
• Rheumatology
• antibody
• cell
• clinical trial
• diseases
• drug
• immunobiology
• immunology
• inflammation
• research
• rheumatoid arthritis

• Division of Clinical Immunology and Rheumatology EULAR & FOCIS Center of Excellence Academic Medical Center, University of Amsterdam, AZ Amsterdam, The Netherlands

  Paul-Peter Tak

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