Dr. Wendling has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott, BMS, Wyeth, Schering-Plough, Roche-Chugai, Nordic Pharma, Sanofi-Aventis, and Servier, and was an investigator in the tocilizumab trial OPTION in rheumatoid arthritis.
Letters to the Editor
Interleukin-6 as a therapeutic target in spondylarthritis: Comment on the article by Tanaka et al
Article first published online: 22 JAN 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis Care & Research
Volume 62, Issue 5, page 745, May 2010
How to Cite
Wendling, D. (2010), Interleukin-6 as a therapeutic target in spondylarthritis: Comment on the article by Tanaka et al. Arthritis Care Res, 62: 745. doi: 10.1002/acr.20086
- Issue published online: 29 APR 2010
- Article first published online: 22 JAN 2010
- Accepted manuscript online: 22 JAN 2010 12:00AM EST
To the Editors:
We read with great interest the recently published article in Arthritis Care & Research by Tanaka et al reporting rapid clinical and biologic improvement under tocilizumab (a humanized monoclonal anti–interleukin-6 [IL-6] receptor antibody) in a case of HLA–B27-positive severe reactive arthritis, multiresistant during 4 years to several therapeutic regimens (1). This is the first case report of the beneficial effect of tocilizumab in spondylarthritis.
There is one previous case in the literature of the beneficial effect of IL-6 blockade in severe spondylarthritis in a 46-year-old man with HLA–B27-positive oligoarthritis with enthesitis and dactylitis, elevated IL-6 serum levels, and disease resistance to corticosteroids, sulfasalazine, and methotrexate (2). Anti–tumor necrosis factor agents were not available at that time (1995), and 2 courses of 10 days of a murine anti–IL-6 monoclonal antibody (B-E8, 20 mg/day) at 1-month intervals (the second one in association with anti-CD4 antibody) led to normalization of C-reactive protein (CRP) levels, IL-6 serum levels, and clinical remission at day 120.
Serum IL-6 levels have been found to be elevated in several studies in spondylarthritis patients, and correlated with erythrocyte sedimentation rate, CRP levels (3, 4), Bath Ankylosing Spondylitis Disease Activity Index scores, leptin levels (5), and serum soluble intercellular adhesion molecule 1 levels (6). Increased expression of IL-6 has been found by François et al in the sacroiliac biopsy results of 4 patients, especially in early and active lesions (7). IL-6 contributes to Th17 expansion (8), which seems to be implicated in spondylarthritis (9).
Even if the IL-6 gene promoter polymorphism is not associated with ankylosing spondylitis (10), IL-6 blockade may represent a new therapeutic opportunity in cases of severe spondylarthritis refractory to conventional treatment.
- 1Successful treatment of reactive arthritis with a humanized anti–interleukin-6 receptor antibody, tocilizumab. Arthritis Rheum 2009; 61: 1762–4., , , , , , et al.
- 2Combination therapy of anti-CD4 and anti-IL6 monoclonal antibodies in a case of severe spondylarthropathy [abstract]. Br J Rheumatol 1996; 35: 1330., , , .
- 3Comparison of serum IL-1 β, sIL-2R, IL-6, and TNF-α levels with disease activity parameters in ankylosing spondylitis. Clin Rheumatol 2007; 26: 211–5., , , , , .
- 4Serum cytokines (IL-6, TNF-α, IL-1 β and IFN-γ) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity. Br J Rheumatol 1994; 33: 927–31., , , , , , et al.
- 5Serum leptin levels correlate with interleukin-6 levels and disease activity in patients with ankylosing spondylitis. Scand J Rheumatol 2007; 36: 101–6., , , , .
- 6Soluble intercellular adhesion molecule 1 in spondylarthropathies. Clin Rheumatol 1998; 17: 202–4., , , .
- 7Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor α in two patients with early disease and transforming growth factor β in three more advanced cases. Ann Rheum Dis 2006; 65: 713–20., , , .
- 8Interleukin 23: a key cytokine in chronic inflammatory disease. Joint Bone Spine 2008; 75: 517–9..
- 9Increased numbers of circulating polyfunctional Th17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum 2008; 58: 2307–17., , , , , .
- 10Interleukin 6 gene promoter polymorphism is not associated with ankylosing spondylitis. J Rheumatol 2000; 27: 1461–3., , , , .
Daniel Wendling MD, PhD*, * University of Franche-ComtéBesançon, France.