COPENHAGEN, Denmark—New data from clinical and preclinical studies of ankylosing spondylitis (AS) and spondyloarthritis (SpA) reported at the 2009 EULAR meeting suggest that controlling these syndromes may require a 2-pronged approach: cooling inflammation and preventing osteoproliferation.

“In this paradigm, the development of SpA is dependent on a multi-step process which leads to chronic or recurrent inflammation but also to the triggering of new tissue formation, completely or partially independent of inflammation.”—Rik J. Lories, MD, PhD
Joachim Sieper, MD, put the current situation into clinical perspective.1 “TNF-blockers are very effective in the suppression of inflammation and in the improvement of signs and symptoms in ankylosing spondylitis (AS), however, unlike in rheumatoid arthritis, they are not able to stop radiographic progression in AS, measured by new bone formation (ankylosis) of the spine. Because it is clear that TNF-blockers do not inhibit osteoblasts and the formation of bone, the key question is how inflammation and new bone formation are linked,” he said.

TNF inhibitors suppress inflammation, but don't stop ankylosis

Studies of serum biomarkers and MRIs in AS patients with and without TNF-blocker treatment indicate a close interaction in AS between inflammation and new bone formation. Dr. Sieper said that an important research objective will be to investigate whether the initial approach in AS treatment should be early anti-inflammatory interventions or a combination of anti-inflammatory and anti-osteoproliferative drugs.

Dr. Sieper is Professor in Rheumatology in the Medical Department I, Charité - Campus Benjamin Franklin, in Berlin, Germany.

Animal models may help answer these questions. Rik J. Lories, MD, PhD, of the Division of Rheumatology, KU Leuven, Leuven, Belgium, reported studies in a mouse spontaneous arthritis model used to study the molecular mechanisms of ankylosing enthesitis.2

Two-step process: inflammation and tissue remodeling

Dr. Lories proposed that the primary event that triggers SpA is still unknown but that this “entheseal stress” both triggers new tissue formation and stimulates production of pro-inflammatory molecules. The new tissue formation can either restore tissue integrity or lead to tissue remodeling. The proinflammatory signals can develop into a chronic inflammatory process mediated by cytokines such as TNF. Factors that can contribute to the chronicity include HLA-B27, inflammatory bowel disease or infection, and polymorphisms in cytokines and cytokine processing molecules. Without a genetic predisposition, entheseal stress would generally not lead to chronic changes, and homeostasis would probably be restored.

“In this paradigm, the development of SpA is dependent on a multi-step process which leads to chronic or recurrent inflammation but also to the triggering of new tissue formation, completely or partially independent of inflammation,” Dr. Lories said. “In this view, additional strategies will be required to control new tissue formation in order to adequately treat AS and other SpA patients in the long term.”

References
1. Sieper J. Inflammation and new bone formation in ankylosing spondylitis. Presented at: 2009 EULAR meeting, Copenhagen, June 10, 2009. Presentation no. SP0019.
2. Lories RJ. Inflammation and new bone formation in animal models. Presented at: 2009 EULAR meeting, Copenhagen, June 10, 2009. Presentation no. SP0018.