Inflammation and ankylosis: still an enigmatic relationship in spondyloarthritis.

The introduction of targeted therapies against cytokine tumour necrosis factor (TNF) alpha has dramatically changed the management, prognosis and perspectives of patients with ankylosing spondylitis (AS) and related forms of spondyloar-thritis. 1 Both the soluble TNF receptor etanercept and the different anti-TNF antibodies are highly successful in reducing the signs and symptoms of disease, thereby improving quality of life, participation in the work force and the overall wellbeing of patients. 2 3 Clinical evidence suggests that anti-TNF therapies are more successful and the effect more sustained than in other diseases such as rheumatoid arthritis (RA) and infl ammatory bowel disease. 4 However, in contrast to what is seen in patients with RA, anti-TNF does not appear to have an impact on the structural progression of disease, a process characterised by ankylosis of the spine and sacroiliac joints in spondyloarthritis patients. 5–7 This aspect of the disease contrasts with the typical pattern of erosive joint destruction seen in patients with RA and with the associated protective effect of anti-TNF. 8 Two hypotheses have been put forward to explain this clinical conundrum. The fi rst hypothesis states that infl ammation, including the upregulation of TNF, triggers local damage and subsequently repair leading to new bone formation and ankylosis, thereby establishing a causal coupling between infl ammation and this process of ankylosis. 9 A decrease in infl ammation may be necessary for repair to occur, with TNF acting as a brake on the specifi c mechanisms involved. 10 The second hypothesis states that a common trigger is responsible for both infl ammation and new bone formation, but that both phenomena further develop in a largely molecularly independent way. 11 The question asked by these hypotheses is critical for the management of spondyloarthritis, because the former hypothesis would mean that early or preventive treatment with anti-TNF could have an effect on structural disease progression, whereas the latter suggests that the identifi cation of a common but unknown trigger may lead to the development of new therapies. In their paper published in this journal, van der Heijde et al 12 try to answer some of the lingering questions on the relationship between infl ammation and the progression of ankylosis with a detailed study on MRI of infl ammation in AS patients treated with the TNF inhibitor infl iximab. Their data indicate that the presence of infl ammation on the MRI in a vertebral unit (defi …