Objective. Ankylosing spondylitis (AS) is diagnosed late, because radiographs of the sacroiliac joints often do not show definite sacroiliitis at the time of disease onset. The aim of this study was to investigate whether patients without definite radiographically defined sacroiliitis, referred to as nonradiographic axial spondylarthritis (SpA), are different from patients with AS with regard to clinical manifestations and disease activity measures. Moreover, we sought to identify determinants of the development of radiographic sacroiliitis.Methods. In a cross-sectional analysis of 462 patients, we compared 226 patients with nonradiographic axial SpA (symptom duration <5 years) and 236 patients with AS (symptom duration <10 years) who are participants in the German Spondyloarthritis Inception Cohort. Radiographs of the sacroiliac joints and the spine were assessed by 2 readers in a blinded manner. Logistic regression analysis was applied to identify parameters associated with structural damage.Results. The 2 groups did not differ in the frequency of HLA-B27 positivity, inflammatory back pain, arthritis, enthesitis, and uveitis and had similar levels of disease activity, using measures such as the Bath Ankylosing Spondylitis Disease Activity Index. In both groups, HLA-B27 positivity determined the age at disease onset. Conclusion. Clinical manifestations and disease activity measures are highly comparable between patients with early nonradiographic axial SpA and those with early AS, suggesting that these 2 entities are part of the same disease. Male sex and an elevated CRP level are associated with structural damage on radiographs, whereas HLA-B27 positivity determines the age at disease onset.

Objective. To assess prospectively the rates and to explore predictors of spinal radiographic progression over 2 years in a cohort of patients with early axial spondylarthritis (SpA).Methods. Two hundred ten patients with axial SpA from the German Spondyloarthritis Inception Cohort were selected for this analysis based on the availability of radiographs at baseline and after 2 years of followup. Spinal radiographs were scored by 2 trained readers in a blinded, randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Spinal radiographic progression was defined as worsening of the mean mSASSS by >2 units over 2 years.Results. Among the patients with axial SpA, 14.3% showed spinal radiographic progression after 2 years (20% of those with AS and 7.4% of those with nonradiographic axial SpA). The following parameters were independently associated with spinal radiographic progression: presence of syndesmophytes at baseline (odds ratio [OR] 6.29, P < 0.001), elevated levels of markers of systemic inflammation (for the erythrocyte sedimentation rate, OR 4.04, P ‫؍‬ 0.001; for C-reactive protein level time-averaged over 2 years, OR 3.81, P ‫؍‬ 0.001), and cigarette smoking (OR 2.75, P ‫؍‬ 0.012). These associations were confirmed by multivariate logistic regression analysis. No clear association with spinal radiographic progression was observed for HLA-B27 status, sex, age, disease duration, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, presence of peripheral arthritis, enthesitis, psoriasis, treatment with nonsteroidal antiinflammatory drugs, or treatment with disease-modifying antirheumatic drugs at baseline.Conclusion. The presence of radiographic damage at baseline (syndesmophytes), elevated levels of acutephase reactants, and cigarette smoking were all independently associated with spinal radiographic progression in patients with early axial SpA.The term axial spondylarthritis (SpA) refers to patients with radiographic sacroiliitis fulfilling the modified New York criteria for ankylosing spondylitis (AS) (1) and patients with nonradiographic axial SpA (i.e., patients without definite radiographic changes in the sacroiliac joints) (2).

Objective. There is increasing evidence that tumor necrosis factor ␣ (TNF␣) is centrally involved in the pathogenesis of ankylosing spondylitis (AS) and other spondylarthritides. This study was designed to investigate the efficacy of anti-TNF␣ therapy with etanercept, a 75-kd receptor fusion protein, in active AS.Methods. This multicenter trial had 2 phases: an initial placebo-controlled period of 6 weeks' duration and an observational phase lasting 24 weeks. Thirty patients with active AS were included. They were randomized into 2 groups, which received either etanercept (25 mg twice weekly) (n ‫؍‬ 14) or placebo (n ‫؍‬ 16) for 6 weeks. Then both groups were treated with etanercept. Nonsteroidal antiinflammatory drug (NSAID) treatment could be continued, but disease-modifying antirheumatic drugs (DMARDs) and steroids had to be withdrawn prior to the study. All patients received etanercept for a total of 12 weeks and were followed up for at least 24 weeks. The Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index, Bath AS Metrology Index, pain level on a numeric rating scale, quality of life by the Short Form 36, and C-reactive protein (CRP) level were assessed. The primary outcome parameter was a >50% improvement in the BAS-DAI.Results. Treatment with etanercept resulted in at least a 50% regression of disease activity in 57% of these patients at week 6, versus 6% of the placebo-treated patients (P ‫؍‬ 0.004). After the placebo-treated patients switched to etanercept, 56% improved. The mean ؎ SD BASDAI improved from 6.5 ؎ 1.2 at baseline to 3.5 ؎ 1.9 at week 6 in the etanercept group, with no improvement in the placebo group (P ‫؍‬ 0.003 between groups). Similarly, pain, function, mobility, and quality of life improved with etanercept but not with placebo at week 6 (P < 0.05). Mean CRP levels decreased significantly with etanercept but not with placebo (P ‫؍‬ 0.001). There was ongoing improvement in all parameters in both groups until week 12 and week 18, respectively (i.e., throughout the period of etanercept treatment). Disease relapses occurred a mean ؎ SD of 6.2 ؎ 3.0 weeks after cessation of etanercept. No severe adverse events, including major infections, were observed during the trial.Conclusion. This study shows that on a shortterm basis (3 months), treatment with etanercept is clearly efficacious in patients with active AS who are receiving NSAID therapy but not DMARDs or steroids. After cessation of therapy, almost all patients experienced a relapse within a few weeks. Thus, it seems probable that etanercept must be administered continuously in most AS patients to achieve permanent inhibition of the inflammatory process.Ankylosing spondylitis (AS), the prototype of the spondylarthritides (SpA), is a chronic inflammatory rheumatic disease. In the past, the prevalence of SpA has been underestimated (1); more recently, the prevalence of the group of SpA as a whole has been calculated

Progression of radiographic sacroiliitis by at least one grade after 2 years occurs only in a small percentage of patients with early axial spondyloarthritis. An elevated level of CRP was found to be a strong positive predictor of sacroiliitis progression.

Objective. Osteocytes are considered to be sensors of bone damage and regulators of bone mass by specifically expressing sclerostin, an inhibitor of bone formation. The contribution of osteocytes in regulating local bone remodeling in arthritis is unknown. The aim of this study was to investigate the role of osteocytes as contributors to bone remodeling in ankylosing spondylitis (AS).Methods. Sclerostin expression and osteocyte death were assessed by immunohistochemistry in joints derived from patients with AS, patients with rheumatoid arthritis (RA), and patients with osteoarthritis (OA), as well as from control subjects. In addition, the serum level of sclerostin was assessed by enzyme-linked immunosorbent assay in healthy subjects and patients with AS; this assessment included the longitudinal correlation of sclerostin serum levels and radiographic progression in the spine of patients with AS.Results. Sclerostin expression was confined exclusively to osteocytes. Whereas the majority of osteocytes in healthy individuals and patients with RA were sclerostin positive, expression was significantly reduced in patients with OA and was virtually absent in patients with AS. Moreover, serum levels of sclerostin were significantly lower in patients with AS than in healthy individuals. Importantly, low serum sclerostin levels in patients with AS were significantly associated with the formation of new syndesmophytes (P ‫؍‬ 0.007).Conclusion. Sclerostin expression is impaired in patients with AS, suggesting a specific alteration of osteocyte function in this disease. A low serum level of sclerostin in the setting of AS is linked to increased structural damage, emphasizing the role of sclerostin in the suppression of bone formation.Ankylosing spondylitis (AS) is an inflammatory disease that predominantly affects axial joints and intervertebral spaces. AS is characterized by tight interplay between chronic inflammation and bone formation (1), which is only partly understood. Local inflammation appears to be crucial for bony proliferations along periosteal and entheseal sites (1). Inflammatory lesions are typically located in the subchondral bone marrow (2-4) and are preferentially seen at sites that later develop bony proliferations and ankylosis (3,4), suggesting a link between inflammation and bone formation.These observations, which suggest a functional link between inflammatory lesions inside the cortical bone barrier and bony proliferations outside this barrier, indicate that there is certain kind of "communication"Drs.