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Purpose: The aims of this study were (1) to assess the frequency and duration of drug-free remission and efficacy of etanercept (ETA) treatment after flare in patients with early active axial spondyloarthritis who were treated with ETA (n=40) versus sulfasalazine (SSZ, n=36) for 48 weeks and (2) to analyse the efficacy of ETA treatment in patients in year 2 who did not reach remission at week 48., Method: At week 48, patients who reached study remission (Assessment of Spondyloarthritis international Society (ASAS) plus MRI remission) were followed up without active treatment up to 1 year. In case of a flare, patients were treated with ETA for another year. All patients who were not in ASAS plus MRI remission at week 48 were treated with ETA in year 2., Results: ASAS plus MRI remission at week 48 was reached significantly more often in ETA-treated compared to SSZ-treated patients (33% vs 11%, p=0.03). However, the flare rate was not different between these two groups: 69% in the ETA group versus 75% in the SSZ group. Only 8% of patients initially treated with ETA versus 3% of those initially treated with SSZ reached permanent drug-free remission (not significant). After treatment with ETA over 1 year, patients with flare showed an improvement in all clinical and imaging variables., Conclusion: Patients with axial spondyloarthritis treated with ETA over 1 year did not reach drug-free remission in a higher percentage compared to patients from a control group treated with SSZ.

Spondyloarthritis (SpA) is a large family of chronic inflammatory diseases characterized by inflammation of the axial skeleton, a typically asymmetric peripheral arthritis of the lower limbs, enthesitis, typical extra-articular manifestations, and shared genetic background. The prevalence in the general population is up to 2% for the entire group. SpA, particularly ankylosing spondylitis, has been associated with a diagnostic delay of up to 10 years. Important efforts toward shortening this delay have been made, including the development of new classification criteria. This article discusses the current concept of the disease, typical manifestations, advances in diagnosis, and current treatment recommendations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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 acute-phase reactants, and cigarette smoking were all independently associated with spinal radiographic progression in patients with early axial SpA., (Copyright © 2012 by the American College of Rheumatology.)

Introduction: The molecular mechanisms of syndesmophyte formation in ankylosing spondylitis (AS) are yet to be characterised. Molecules involved in bone formation such as Wnt proteins and their antagonists probably drive syndesmophyte formation in AS., Methods: This study investigated sequential serum levels of functional dickkopf-1 (Dkk1), a potent Wnt antagonist involved in bone formation in arthritis, by capture ELISA with its receptor LRP6 in 65 AS patients from the German Spondyloarthritis Inception Cohort. Dkk1 levels were then related to structural progression (syndesmophyte formation) as well as sclerostin and C-reactive protein (CRP) levels., Results: Functional Dkk1 levels were significantly (p=0.025) higher in patients with no syndesmophyte growth (6.78 ± 5.48 pg/ml) compared with those with syndesmophyte growth (4.13 ± 2.10 pg/ml). Dkk1 levels were highly correlated to serum sclerostin levels (r=0.71, 95% CI 0.53 to 0.82; p<0.001) but not to CRP (r=0.15, 95% CI -0.10 to 0.38; p=0.23)., Conclusion: AS patients with no syndesmophyte formation show significantly higher functional Dkk1 levels suggesting that blunted Wnt signalling suppresses new bone formation and consequently syndesmophyte growth and spinal ankylosis. Similar to serum sclerostin levels, the functional Dkk1 level thus emerges as a potential biomarker for structural progression in patients with AS.

The diagnosis of axial spondyloarthritis (SpA) or ankylosing spondylitis (AS) is often delayed by 5-10 years after the first symptoms have appeared. In order to improve the early diagnosis of SpA an evidenced-based algorithm including clinical, laboratory and imaging parameters was developed. Moreover, the recently published ASAS criteria for axial and peripheral SpA should give rheumatologists more confidence in making the diagnosis of SpA and provide further support for the SpA concept. Furthermore, an easy strategy for the recognition of patients with a high probability of AS/SpA on the primary care level has been developed and recently validated.

Objective: To evaluate 2 referral strategies for axial spondyloarthritis (SpA) in patients with chronic low back pain at the primary care level., Methods: Referral physicians (n = 259) were randomly assigned to either Strategy 1 or Strategy 2 in order to refer patients with chronic back pain (duration > 3 months), age at onset of back pain < 45 years, and no diagnosis of axial SpA, to a cooperating rheumatologist (n = 43). According to Strategy 1, suitable patients were referred if at least 1 of the following screening criteria was present: inflammatory back pain, HLA-B27, or sacroiliitis detected by imaging. According to Strategy 2, patients were referred if 2 out of 5 criteria were positive: the same 3 criteria from Strategy 1 and additionally a positive family history of ankylosing spondylitis (AS) or a good treatment response to nonsteroidal antiinflammatory drugs. The final diagnosis of the rheumatologist was used as the "gold standard.", Results: In total, 560 consecutively referred patients were included in the analysis. Among 318 patients referred by Strategy 1, 41.8% (95% CI 36.5%-47.3%) were diagnosed with definite axial SpA. Among 242 patients referred by the second strategy, definite axial SpA was diagnosed in 36.8% (95% CI 31.0%-43.0%) of the cases., Conclusion: Both referral strategies demonstrated comparable performance in identification of patients with axial SpA. Strategy 1 might be preferred as an easy and reliable screening method for axial SpA at the primary care level.

Objective: To assess the progression of radiographic sacroiliitis in a cohort of patients with early axial spondyloarthritis over a period of 2 years and to explore predictors of progression., Methods: 210 patients with axial spondyloarthritis from the German Spondyloarthritis Inception Cohort have been selected for this analysis based on availability of radiographs at baseline and after 2 years of follow-up. Radiographs were centrally digitised and the sacroiliac joints were scored independently according to the grading system of the modified New York criteria for ankylosing spondylitis (AS) by two trained readers. The readers scored both time points simultaneously but were blinded for the time point and for all clinical data., Results: 115 patients (54.8%) fulfilled the modified New York criteria for AS in their radiographic part in the opinion of both readers at baseline, while 95 patients (45.2%) were classified as non-radiographic axial spondyloarthritis. More patients with non-radiographic spondyloarthritis (10.5%) compared with AS (4.4%) showed an estimated 'true' progression by at least one grade according to both readers, although the difference between the two groups was statistically non-significant. The rate of progression from non-radiographic axial spondyloarthritis to AS was 11.6% over 2 years. An elevated level of C-reactive protein (CRP) at baseline was a strong positive predictor of radiographic sacroiliitis progression in non-radiographic axial spondyloarthritis and AS (OR 3.65 and 5.08, respectively, p<0.05)., Conclusion: 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.

Aim: To investigate the relationship between active inflammatory lesions on whole-body MRI (wb-MRI) and new development of chronic lesions on T1 MRI in patients with early axial spondyloarthritis (SpA) treated either with etanercept (ETA) or sulfasalazine (SSZ)., Methods: Wb-MRIs of 65 patients treated either with ETA (n=35) or SSZ (n=30) over 1 year were scored for active inflammation, fatty lesions, erosions and ankylosis in the 23 vertebral units (VUs) of the spine and in the sacroiliac joints (SI joints). Scoring was performed by two blinded radiologists., Results: If there was no previous inflammation in the bone no new fatty lesions occurred in SI joint quadrants and only a few (0.6%) in spine VUs. There was a significant relationship between disappearance of inflammation and the appearance of fatty lesions: if baseline inflammation resolved fatty lesions occurred in 10.5% of SI joint quadrants and 17.9% of VUs. If inflammation did not resolve over 1 year, fatty lesions occurred less frequently: 2.4% (SI joint quadrants) and 7.2% (VUs). There was a significantly higher increase of the mean fatty lesion score between baseline and week 48 in the ETA (4.0 vs 4.8 for the SI joints and 1.9 vs 2.7 for the spine) compared to the SSZ (3.0 vs 3.2 for the SI joints and 1.1 vs 1.2 for the spine, respectively) group (p=0.001 and p=0.020 for the differences). No significant changes in the erosion or ankylosis score were observed in any of the two groups during this time., Conclusions: These data indicate that there is a close interaction between inflammation, tumour necrosis factor blockade and the development of fatty lesions in subchondral bone marrow of patients with axial SpA.

Introduction: In the last couple of years, the number of patients with chronic inflammatory rheumatic diseases being treated with TNF α antagonist has increased dramatically. Adalimumab, a fully human monoclonal antibody against TNF α, is one of the most frequently administered TNF α antagonists. Yet, unresolved issues are the long-term safety of TNF α antagonists and high treatment costs., Areas Covered: The authors summarize the available data on short- and long-term efficacy and safety of adalimumab in the treatment of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The reader will find a comprehensive overview on the safety and efficacy of adalimumab for these conditions. Clinically relevant questions of adalimumab therapy are discussed. A special focus of this review is on the safety of adalimumab therapy., Expert Opinion: Adalimumab is effective and reasonably safe in the short- and long-term treatment of patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis who do not respond to the standard therapy. It inhibits radiographic progression in rheumatoid and psoriatic arthritis. Treatment with a TNF α inhibitor such as adalimumab is associated with high treatment costs.

Purpose of Review: Despite overall good efficacy of currently available treatment [nonsteroidal anti-inflammatory drugs, tumor necrosis factor (TNF) α inhibitors] for ankylosing spondylitis (AS) and other spondyloarthritides (SpAs), up to 40% of the treated patients do not achieve an acceptable clinical improvement during the therapy. Here we discuss the most attractive new targets, which might become an alternative for AS/SpA patients in whom anti-TNFα therapy has failed or is contraindicated., Recent Findings: Although B-cell depletion showed a moderate efficacy in a pilot trial in anti-TNF-naïve patients with AS, inhibition of T-cell costimulation seems to be ineffective in AS but might be effective in psoriatic arthritis (PsA). Interleukin (IL)-17 blockade showed promising results in a small clinical trial in AS, anti-IL-12/23 drugs demonstrated good efficacy in PsA. Clinical trials investigating the efficacy of IL-17 blockade in PsA, as well as studies with IL-6 and IL-12/23 antagonists in AS, are currently ongoing., Summary: IL-6, IL-17, IL-12/23 and, to a latter extend, B-cells are the most promising new targets in the treatment of AS and other SpAs.

The principal clinical and radiological feature of all axial spondyloarthritis is an involvement of the axial skeleton (sacroiliac joints and spine) and, to a lesser extent, the hip joints. Immunohistochemical studies provide worthwhile information regarding disease mechanisms in axial spondyloarthritis. Immunohistochemical investigation of sacroiliac joints, spine and hip joints suggested an important role of T-cells in the development of acute inflammatory lesions. Furthermore, activated angiogenesis and macrophage/osteoclast activation also play a relevant role in the development of early active inflammatory lesions. Nonetheless, the mechanisms leading to activation of osteoproliferation with subsequent syndesmophyte and ankylosis formation in patients with spondyloarthritis remains unclear. It is suggested that the Wnt pathway is actively involved in this process due to decreased expression of new bone formation inhibitors such as sclerostin. However, to understand the full picture of the interrelationship between inflammation and new bone formation, and to explore new treatment targets for suppression of the excessive bone formation as well, further investigations are needed., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: This study was aimed at comparing high sensitivity C reactive protein (hsCRP) measurement with routine C reactive protein (CRP) evaluation as disease activity parameters in patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nrSpA)., Methods: A total of 269 patients (153 with AS and 116 with nrSpA) were included. Level of hsCRP was measured using particle-enhanced immunoturbidimetric method with the lowest detected level of 0.1 mg/litre. The hsCRP values were compared to results of routine turbidimetric CRP test with the lowest detected level of 6 mg/litre., Results: In the whole group of patients with AS, hsCRP showed a better than routine CRP correlation with clinical parameters. In the whole group of patients with nrSpA, hsCRP correlated with the level of enthesitis-related tenderness only. In the AS subgroup with a negative routine CRP (<6 mg/litre) there was a clear trend for an increased level of pain, stiffness and functional impairment in patients with higher hsCRP concentration. Such a trend was less pronounced in patients with nrSpA., Conclusions: hsCRP correlates better than routine CRP with clinical disease activity parameters in patients with axial SpA, especially in AS. Therefore, hsCRP could be superior to standard CRP in assessing disease activity in axial SpA.

Non-steroidal anti-inflammatory drugs (NSAIDs) play different roles in the management of patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). In RA there is minimal evidence that NSAIDs are able to alter the course of disease or prevent joint destruction and, therefore, they should mostly be used as a short-term bridging therapy. In contrast to RA, in AS NSAIDs are considered as a cornerstone of the treatment not only because of a high symptomatic efficacy, but also because they might even retard osteoproliferation and radiographic progression. Considering younger age of AS patients and lower prevalence of comorbidities, they are probably at lower risk for cardiovascular and gastrointestinal side effects of short- and long-term NSAID therapy in comparison to RA.