Search

Objectives To delineate the impact of peripheral musculoskeletal manifestations on stratification of disease phenotype and outcome in new-onset spondyloarthritis (SpA), using a prospective observational nationwide inception cohort, the BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant). Methods Newly diagnosed adult SpA patients, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral SpA, were included in Be-Giant and prospectively followed every six months. Peripheral involvement (defined as arthritis, enthesitis and/or dactylitis) was determined in relation to clinically similar patient subsets at baseline and disease activity patterns during two-year follow-up, identified through K-means cluster analysis and latent class growth analysis. Results From November 2010 to March 2020, 367 patients were enrolled in Be-Giant, of whom 162 (44%) had peripheral manifestations. Two patient clusters [A, axial predominant (n = 248) and B, peripheral predominant (n = 119)] were identified at diagnosis. Longitudinal analysis (n = 115) revealed two trajectories of disease activity in each cluster: one with persistently high disease activity over time (‘High’), the other rapidly evolving to low disease activity (‘Low’). In cluster A patients, peripheral manifestations predisposed to the ‘High’ trajectory [odds ratio (OR) = 2.0, 95% CI: 1.3, 3.1, P = 0.001], despite more rapid initiation of biologics compared with patients without peripheral manifestations (hazard ratio (HR) = 2.1, 95% CI: 1.0, 4.4, P = 0.04 – Cox proportional-hazards model). Conclusion Peripheral musculoskeletal manifestations are major determinants of phenotypical diversity in new-onset SpA. Intriguingly, stratification of axial SpA according to concomitant peripheral involvement identified an endotype with an unfavorable outcome despite more prompt therapeutic intensification with biologics. These observations justify an endotype-tailored approach beyond current ASAS/EULAR management recommendations.

IL-23 is a key cytokine in the pathogenesis of spondyloarthritides, including PsA and axial spondyloarthritis, as well as related conditions, such as psoriasis and IBD. Genetic associations, animal models and translational studies in humans demonstrate the key role played by IL-23, especially when coupled with downstream overexpression of IL-17 via stimulation of T helper 17 (Th17) and other cells by IL-23. Whereas IL-23 inhibition has shown clear-cut benefit in psoriasis and peripheral manifestations of PsA, trials of IL-23 inhibitors have failed in the treatment of ankylosing spondylitis. More recently, exploratory data from PsA patients with axial symptoms suggests that improvement may occur, but needs confirmation in dedicated axial spondyloarthritis (axSpA) trials. Hypotheses for these apparently conflicting findings about IL-23 inhibition in various forms of spondylitis are discussed.

Objectives PsA is characterized by enthesitis, synovitis and osseous involvement in the peripheral and axial joints. Few studies have examined axial involvement in PsA using imaging techniques. Here we examined axial involvement in PsA patients using MRI. In addition, we determined the efficacy of 24 week adalimumab treatment in improving the MRI findings of spondylitis and sacroiliitis. Methods This was a prospective, open-label, single-arm study in patients with PsA. Adalimumab was administered to patients for a total of 24 weeks. MRI examinations were conducted at baseline and at week 24 of adalimumab treatment. Results Thirty-seven patients with PsA were included in this study. Spondylitis was observed in at least one site of the positive scan in 91% (n = 31) of patients with PsA. The number of arthritic sites in the cervical, thoracic and lumbar regions of the spine was 48, 67 and 53, respectively. All patients had MRI-determined sacroiliitis of grade ≥1 severity while 28 patients (82%) had grade ≥2 sacroiliitis in at least one sacroiliac region. Sacroiliac arthritis was statistically more severe on the right side than on the left side (P Conclusion Treatment with adalimumab for 24 weeks resulted in improvement in spondylitis and sacroiliitis.

Objective Golimumab immunogenicity was extensively studied during clinical development. As anti-drug antibody (ADA) detection with the standard bridging EIA (original-EIA) can yield false-negative results or underestimate ADA incidence and titres due to drug interference, a more sensitive assay was needed to determine clinical impact. Methods A highly sensitive drug-tolerant EIA (DT-EIA) was developed and cross-validated against the original-EIA. Samples from phase-3 subcutaneous golimumab rheumatological trials (GO-FORWARD-rheumatoid arthritis, GO-REVEAL-psoriatic arthritis, GO-RAISE-ankylosing spondylitis) were then retested. Associations between ADAs and golimumab pharmacokinetics, efficacy and safety were assessed. Results The DT-EIA was more sensitive than the original-EIA and capable of detecting ADAs amid golimumab concentrations far exceeding those in immunogenicity test samples. Consequently, an 8-fold increase in the incidence of ADAs was observed with the DT-EIA (31.7%) vs original-EIA (4.1%) in the studies. Most ADA-positive patients identified by the DT-EIA had lower antibody titres, while most with higher titres were previously identified as ADA-positive by the original-EIA. With the DT-EIA, ADA-positive patients generally had lower trough serum golimumab concentrations than ADA-negative patients; however, ADA impact on serum golimumab concentrations was more notable at higher ADA titres (⩾100). No impact of ADAs on clinical efficacy or injection-site reactions was evident. Conclusion ADA incidence was expectedly higher using the DT-EIA vs original-EIA; newly detected ADAs were characterized mostly by low titres, with no impact on clinical efficacy or injection-site reactions, consistent with previously observed original-EIA results. Golimumab immunogenicity with the DT-EIA is consistent with existing knowledge regarding the clinical relevance of ADAs detected with the original-EIA in patients with rheumatological disorders. Trial registration NCT00264550, NCT00265096, NCT00265083.

Infectious spondylodiscitis is characterized by vertebral osteomyelitis, spondylitis, and discitis. Patients present with persistent low back pain, fever, or neurological findings. Diagnosis is made with a combination of clinical, radiological, and laboratory findings. Magnetic resonance tomography (MRI) has high sensitivity and specificity in diagnosis and differentiation of the type of spondylodiscitis and may reveal signs of spondylodiscitis even in very early stages. Infectious spondylodiscitis responds to antimicrobial therapy well if diagnosed early before development of neurological deficit and requirement of surgical intervention. We present a clinical case of spondylodiscitis developing in a young immunocompetent man without any predisposing factors.

Objectives AS and PsA share clinical and immunological features centred on enthesitis. However, a strong association between PsA and preceding injury has been recognized. The aim of this study was to test the hypothesis that the entheseal damage seen by US is commoner in PsA patients than in AS patients. Methods Seventy-nine AS and 85 PsA patients had US scans of 1640 entheses to calculate entheseal inflammation (hypoechogenicity, thickening and Doppler) and damage scores (calcifications, enthesophytes and erosions). Regression modelling was done to evaluate the effect of diagnoses on outcomes, controlling for age, gender, BMI, clinical enthesitis, HLA-B27, and anti-TNF use. Results Both inflammation and damage scores on US were correlated with BMI (r = 0.392; r = 0.320) and age (r = 0.308; r = 0.538) (P < 0.001), and men had higher inflammation scores than women [12.3 (7.5) vs 8.9 (7.3), P = 0.001]. In multivariate analysis, despite similar (anti-TNF-treated patients) or slightly less inflammation (anti-TNF-naive patients) in the PsA group, they had 4.22 times more US damage than their counterparts with AS. The difference was even higher in the anti-TNF-naive patients (5.6 times). Conclusion On US assessment, PsA patients have greater entheseal insertion damage scores compared with AS, suggesting potential differences in tissue repair, immunobiology or response to injury at insertions.

Objectives. To describe the distribution of prevalent syndesmophytes and bridges, and the occurrence of new ones in a prevalence cohort of patients with AS. Methods. Clinical and radiological data from 132 patients from the Outcome in Ankylosing Spondylitis International Study of which complete sets of radiographs were available at baseline and at 2- and 4-year follow-up were used. Results. At baseline, 81 (61%) patients, of which 17 (45%) were females and 64 (65%) males (P = 0.03), had prevalent (bridging) syndesmophytes. Both syndesmophytes and bridges were found at all vertebral levels. Syndesmophytes were more frequently seen in the cervical spine compared with the lumbar spine (mean per vertebral level 17.5 vs 11.2%, respectively, P = 0.01). Bridges were more frequently seen in the lumbar spine compared with the cervical spine (mean per vertebral level 16.9% vs 12.1%, P = 0.02). With increasing disease duration more (bridging) syndesmophytes were found, occurring similarly at the lumbar and cervical spines. After 2- and 4-years of follow-up, new (bridging) syndesmophytes developed throughout the entire cervical and lumbar spines. Conclusion. In general, syndesmophytes occur more frequently in the cervical spine and bridges more frequently in the lumbar spine, but neither a specific predilection site nor any particular order for occurrence and development of syndesmophytes could be detected.

Etanercept 50 mg a week is approved in the treatment of AS. Increasing the etanercept dose to 100 mg/week improves efficacy in cutaneous psoriasis, a clinical manifestation related to the spondylarthritis family, while maintaining its safety profile. The purpose of this study was to evaluate the efficacy and safety of etanercept 100 vs 50 mg/week in patients with AS.Adult patients with AS were randomized to receive etanercept 50 mg twice a week (biw), or etanercept 50 mg once a week (qw) for 12 weeks. The primary efficacy endpoint was Ankylosing Spondylitis Assessment Study (ASAS20) response at Week 12; secondary endpoints included ASAS40, ASAS50, ASAS70 and ASAS5/6 responses, partial remission and quality of life. Safety was assessed until 15 days after the last visit.A total of 108 patients were randomly selected and treated, 54 in each arm. At 12 weeks, ASAS20 response was achieved by 34 (71%) out of 48 patients of the etanercept 50 mg biw group and by 37 (76%) out of 49 patients of the etanercept 50 mg qw group (not statistically significant differences). Other efficacy variables improved significantly over time, but not between treatment groups. Fifty-six patients experienced at least one adverse event (generally, infections and infestations, gastrointestinal disorders and injection site reactions), most of them mild or moderate.High-dose (100 mg/week) etanercept in the treatment of AS for 12 weeks is as safe as the standard dose (50 mg/week). However, it does not significantly increase its efficacy. Trial Registration. Clinicaltrials.gov, http://clinicaltrials.gov/, NCT00873730.

OBJECTIVES To report for the first time on the efficacy and safety of anti-TNF therapy after 8 years of follow-up in patients with active AS, and analyse possible short-term predictors for long-term clinical outcomes. METHODS In this open-label extension of a randomized controlled trial, proportions of the initially included 69 patients with active AS were treated with infliximab 5 mg/kg i.v./6 weeks for 8 years. The last report was published after 5 years. All analyses were based on completers. RESULTS Overall, 33 (48%) patients completed 8 years. Their mean (s.d.) BASDAI [2.6 (1.9)], BASFI [3.3 (2.6)] and BASMI [2.7 (2.4)] remained low at Year 8. At the end of Year 8, most patients were either in partial remission (n = 8, 24%) or had low disease activity (BASDAI < 3; n = 21, 64%). No new serious adverse events occurred within the past 3 years. Adverse events were the most frequent reason for dropout (56%). There were no differences between completers and dropouts at baseline, but the latter had higher BASFI values at dropout. No baseline parameter was associated with good long-term response to infliximab, but lower BASDAI levels after 12 weeks were predictive of a higher probability of partial remission [odds ratio (OR) 2.9, 95% CI 1.3, 6.3, P = 0.007], low disease activity (OR 1.7, 95% CI 1.2, 2.3, P = 0.005) or remaining on treatment (OR 0.79, 95% CI 0.61, 1.01, P = 0.06) after 8 years. CONCLUSION Almost half of the initially treated patients remained on anti-TNF therapy for 8 years, and almost 90% were in partial remission or had low disease activity. Short-term response (low BASDAI at 3 months) is predictive of outcome after 8 years. Infliximab therapy was safe over 8 years.

Objective. To investigate the role of HLA-G in AS. Methods. Serum levels of soluble HLA-G (sHLA-G) were measured in 80 AS patients and 30 healthy controls. The expression of HLA-G on the peripheral blood mononuclear cell (PBMC) surface was investigated in the same 80 AS patients and 40 healthy controls by flow cytometry. The response of HLA-G after 3 months of TNF-a blocker therapy (adalimumab) was evaluated in 14 AS patients. We evaluated Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Patient Global Score (BAS-G), physical mobility, ESR and CRP levels. Results. Serum levels of sHLA-G were significantly lower in 80 AS patients than 30 healthy controls [mean (S.D.) 22.47 (26.8) vs 34.78 (32.01) U/ml, P ¼ 0.028], and correlated significantly with modified Schober index (r ¼ 0.326; P ¼ 0.009), chest expansion (r ¼ 0.319; P ¼ 0.011), lateral lumbar flexion (r ¼ 0.377; P ¼ 0.002), cervical rotation (r ¼ 0.396; P ¼ 0.004), whereas inversely correlated with fingertip-to-floor distance (r ¼� 0.282; P ¼ 0.026) and tragus-to-wall distance (r ¼� 0.270; P ¼ 0.031). The expression of HLA-G on PBMCs was significantly higher in 80 AS patients than 40 healthy controls [mean (S.D.) 18.5 (6.10)% vs 15.41 (4.84)%; P ¼ 0.012], and correlated significantly with ESR (r ¼ 0.421; P < 0.001) and CRP (r ¼ 0.419; P < 0.001). The expression of HLA-G on PMBCs decreased significantly after 3 months of adalimumab therapy [third month vs baseline, 13.46 (5.38)% vs 19.87 (7.31)%; P ¼ 0.016]. Conclusions. Lower serum levels of sHLA-G contribute to susceptibility to AS, and predispose to poor spinal mobility. The expression of HLA-G on PMBCs is up-regulated in AS, correlates with acute phase reactants and decreases after TNF-a blocker therapy, suggesting an index of disease activity.

OBJECTIVE The Danish DANBIO registry has developed open-source software for touch screens in the waiting room. The objective was to assess the validity of outcomes from self-explanatory patient questionnaires on touch screen in comparison with the traditional paper form in routine clinical care. METHODS Fifty-two AS patients and 59 RA patients completed Visual Analogue Scales (VASs) for pain, fatigue and global health, and Bath measures on Ankylosing Spondylitis Disease Activity Index (BASDAI) and Function Index (BASFI) (AS patients) or HAQs (RA patients) on touch screen and paper form in random order with a 1-h interval. Intra-class correlation coefficients (ICCs), 95% CIs and smallest detectable differences (SDDs) were calculated. RESULTS ICC ranged from 0.922 to 0.988 (P < 0.001). The mean differences (95% CI) were: BASDAI [-0.5 (-14.5, 13.5) mm]; BASFI [-1.1 (-10.6, 8.4) mm]; Item 5 [-1.7 (-23.6, 20.2) mm] and Item 6 [-0.7 (-14.7, 13.3) mm] from BASDAI; HAQ score [0.023 (-0.183, 0.229)]. For VAS -0.4 to -2.8 mm (no significance for all except VAS global and VAS fatigue in RA). SDD for BASDAI was 14.0 mm; BASFI 9.5 mm; Item 5 21.8 mm; Item 6 14.0 mm; HAQ 0.206; VAS 11.1-18.8 mm. CONCLUSIONS Self-explanatory touch screens based on the DANBIO open-source system generates valid results in AS and RA patients on completion of BASDAI, BASFI, HAQ and VAS scores for pain, fatigue and global health when compared with the traditional paper form. Implementation of touch screens in clinical practice is feasible and patients need no instruction.

Although clinicians recognize hip involvement, which frequently leads to hip replacement surgery, as an important feature of AS, data on the epidemiology, nature of the disease and therapeutic strategies are scarce. We aimed to describe the epidemiology of clinical and radiological hip involvement and define the risk factors for the hip replacement surgery in AS patients., 0, Journal Article, Research Support, Non-U.S. Gov't, ASPECT-REGISPONSER-RESPONDIA working group, info:eu-repo/semantics/published

To assess the annual direct, indirect and total societal costs, quality of life (QoL) of AS in a Chinese population in Hong Kong and determine the cost determinants.A retrospective, non-randomized, cross-sectional study was performed in a cohort of 145 patients with AS in Hong Kong. Participants completed questionnaires on sociodemographics, work status and out-of-pocket expenses. Health resources consumption was recorded by chart review. Functional impairment and disease activity were measured using the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), respectively. Patients' QoL was assessed using the Short Form-36 (SF-36).The mean age of the patients was 40 yrs with mean disease duration of 10 yrs. The mean BASDAI score was 4.7 and BASFI score was 3.3. Annual total costs averaged USD 9120. Direct costs accounted for 38% of the total costs while indirect costs accounted for 62%. Costs of technical examinations represented the largest proportion of total cost. Patients with AS reported significantly impaired QoL. Functional impairment became the major cost driver of direct costs and total costs.There is a substantial societal cost related to the treatment of AS in Hong Kong. Functional impairment is the most important cost driver. Treatments that reduce functional impairment may be effective to decrease the costs of AS and improve the patient's QoL, and ease the pressure on the healthcare system.

Objectives. To quantify the sibling risk of RA, SLE and AS. To analyse the concordant and discordant associations between RA, SLE and AS. Methods. Follow-up study of all individuals and their siblings born in or after 1932 and hospitalized for RA, SLE or AS between 1973 and 2004 (32 yrs). Data were retrieved from a comprehensive dataconstructed by using several national Swedish data registers, including the Total Population Register, the Swedish Hospital Discharge Register and the Multigeneration Register. Standardized incidence ratios (SIRs) were used to estimate sibling risks. Results. For males, the overall significant SIRs were 4.72, 4.35 and 4.14 for RA, SLE and AS, respectively, if a sibling was affected by any inflammatory disease. The corresponding significant SIRs for females were 4.12, 3.73 and 4.73. The concordant significant SIRs in siblings were 5.12, 17.02 and 17.14 for RA, SLE and AS, respectively. There were also discordant associations between RA and SLE, whereas AS was only associated with AS. Conclusions. This study was able objectively to quantify the sibling risk of RA, SLE and AS, which represents useful knowledge for clinicians and geneticists. The analysis of concordant and discordant associations may be useful in future studies aimed at finding specific genes associated with these diseases.

Objectives. Many AS patients report periods of perceived higher disease activity (flares). This pilot study aims to document disease activity patterns reported by AS patients and examine associations with disease-specific health status measures.Methods. Consecutive AS patients (n = 114) were asked whether they experience flares, and if they experience symptoms of AS between flares. They were shown the Flare Illustration of disease patterns over time and asked to select the pattern that best described their disease (i) since symptom onset and (ii) in the past year. Associations between reported disease pattern and disease activity (Bath AS Disease Activity Index, BASDAI); functional impairment (Bath AS Functional Index, BASFI); AS Quality of Life (ASQoL); Back Pain (Nocturnal and Overall) and demographic features were assessed in a subsample (n = 83) (statistical significance defined at P ≤ 0.05).Results. Since disease onset 108/113 patients (96%) reported flares, and 82/99 (83%) reported symptoms of AS between flares. Flares typically lasted days or weeks. When patients were asked to characterize their disease pattern using the Flare Illustration, patterns with constant symptoms predominated (>70% of patients) and patterns with constant symptoms since onset (vs intermittent symptoms) were associated with worse health status (ASQoL: P = 0.007; BASDAI: P = 0.029; BASFI: P = 0.013, overall back pain: P = 0.025).Conclusions. Almost all AS patients report flares in disease activity: 70-80% report constant symptoms with single/repeated flares, while 20-30% report flares with no intermittent symptoms. The former is associated with a significantly poorer health status. These findings will be validated in a prospective study.

Objectives. Increased incidence of cardiovascular disease (CVD) has been observed in AS. The reasons of this increase are not fully understood (greater prevalence of traditional cardiovascular risks, consequences of treatment (NSAID) or biological inflammation). The objectives of this study are to assess intima–media thickness (IMT) and arterial stiffness (i.e augmentation index AIx), markers of sub-clinical atherosclerosis in AS patients and to examine the effects of TNF-� inhibitors on arterial stiffness in active AS patients. Methods. Sixty AS patients were enrolled with 60 healthy controls. Their BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) scores, ESR and CRP levels were recorded. Subclinical atherosclerosis was assessed by measurement of AIx by pulse wave analysis and IMT by carotid echography. Results. We found significantly increased IMT in the AS group compared with healthy controls. After adjustment for confounding factors, an underlying trend towards increased IMT was still present (P ¼ 0.06). No difference was found in arterial stiffness between the two groups. AS patients, treated or not with anti-TNF-� at baseline, had significantly increased IMT and AIx or a trend towards increase. IMT was positively correlated with tobacco use, WHR and blood pressure but not correlated with CRP level. Despite improvement in markers of disease activity, arterial stiffness was unchanged after 14 weeks of treatment with TNF antagonists. Conclusion. This study shows a trend towards increased subclinical atherosclerosis in AS patients. TNF-� blockade does not seem to improve arterial stiffness in AS patients, but our results lack statistical power.

OBJECTIVE To investigate long-term health effects in AS patients treated with (224)Ra. METHODS A prospective epidemiological study has been carried out on 1471 AS patients treated with repeated intravenous injections of (224)Ra between 1948 and 1975. These patients have been followed together with a control group of 1324 AS patients not treated with radioactive drugs and/or X-rays. Numbers of malignancies expected in a normal population were computed from German and Danish cancer registry data. RESULTS After a mean follow-up time of 26 yrs in the exposed group or 25 yrs in the control group, causes of death have been ascertained for 1006 exposed patients and 1072 controls. In particular, 19 cases of leukaemia were observed in the exposure group (vs 6.8 cases expected, P < 0.001) compared to 12 cases of leukaemia in the control group (vs 7.5 cases expected). Further subclassification of the leukaemia cases demonstrated a high increase of myeloid leukaemia in the exposure group (11 cases observed vs 2.9 cases expected, P < 0.001), especially a high excess of acute myeloid leukaemias (7 cases observed vs 1.8 cases expected, P = 0.003), whereas in the controls the observed cases are within the expected range (4 myeloid leukaemias vs 3.1 cases expected). CONCLUSIONS The enhanced leukaemia incidence in the exposed group is in line with results from experiments in mice injected with varying amounts of the bone-seeking alpha-emitter (224)Ra. In these studies, in animals exposed to lower doses of (224)Ra, i.e. at doses lower than those found to induce osteosarcomas, an increased risk of leukaemia was observed.

Ankylosing spondylitis (AS), the prototypic seronegative arthropathy, is known to be highly heritable, with >90% of the risk of developing the disease determined genetically. As with most common heritable diseases, progress in identifying the genes involved using family-based or candidate gene approaches has been slow. The recent development of the genome-wide association study approach has revolutionized genetic studies of such diseases. Early studies in ankylosing spondylitis have produced two major breakthroughs in the identification of genes contributing roughly one third of the population attributable risk of the disease, and pointing directly to a potential therapy. These exciting findings highlight the potential of future more comprehensive genetic studies of determinants of disease risk and clinical manifestations, and are the biggest advance in our understanding of the causation of the disease since the discovery of the association with HLA-B27.

Objectives. The objective of this study was to assess the humanistic impact of ankylosing spondylitis (AS), and compare the effect of etanercept 50 mg once-weekly (QW), etanercept 25 mg twice-weekly (BIW) and placebo on patient-reported outcomes (PROs).Methods. In a 12-week, double-blind, placebo-controlled multicenter study, 356 patients with active AS received etanercept 50 mg QW, etanercept 25 mg BIW or placebo (3 : 3 : 1 randomization, respectively). PROs were assessed using Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Activity Index fatigue item, EuroQOL-5D (EQ-5D) utility, EQ-5D visual analog scale and the Medical Outcomes Short Form Questionnaire (SF-36) scores at baseline and at regular intervals. Mean changes from baseline in PROs were analysed using analysis of covariance to assess differences between etanercept and placebo, or between the two etanercept groups.Results. Consistent with earlier reports, AS was associated with quality of life (QOL) impairment and functional limitations, similar to or worse than cancer, congestive heart failure, diabetes or depression. Treatment with etanercept 50 mg QW or 25 mg BIW significantly improved QOL and functional status compared with placebo. High proportions of patients achieved clinically meaningful improvements in all PRO measures, including physical function, fatigue, pain, psychosocial domains and general health status. Improvements were similar with the two etanercept dose regimens.Conclusions. The more convenient etanercept 50 mg QW dose regimen significantly improves function and QOL in patients with AS, similarly to the standard dosing of 25 mg BIW, supporting its use for AS therapy.

Objective To assess bone mineral density (BMD), serum levels of soluble receptor activator of nuclear factors-kappaB ligand (sRANKL) and osteoprotegerin (OPG) in patients with ankylosing spondylitis (AS), and to determine their relationships with disease activities. Methods Serum levels of sRANKL and OPG in AS were measured by sandwich enzyme-linked immunosorbent assay. The disease activities were determined using Bath Ankylosing Spondylitis Disease Activity Score Index, Bath Ankylosing Spondylitis Functional Index , Bath Ankylosing Spondylitis Metrology Index and Bath Ankylosing Spondylitis Patient Global Score. BMD of femur and lumbar spine was measured by dual energy X-ray absorptiometry. Radiological grading was determined by New York criteria for sacroiliitis and modified Stoke Ankylosing Spondylitis Spine Score. Results Osteoporosis and osteopaenia of femoral neck were found in 33 and 41% of patients, respectively. BMD of femoral neck showed negative correlation with disease activity indexes, erythrocyte sedimentation rate and C-reactive protein. The serum sRANKL levels and the ratio of sRANKL to OPG were significantly higher in patients with AS than those of controls. The sRANKL/OPG ratio tended to increase in patients with reduced BMD and radiological findings of active inflammation. Conclusion About 74% of AS patients have reduced BMD and this change reflects disease activity. Serum sRANKL levels and sRANKL/OPG ratios are up-regulated in patients with AS and have relationship with BMD and radiological changes. These results suggest that the imbalance between RANKL and OPG might be involved in the pathogenesis and clinical courses of osteoporosis in AS.

Objectives Magnetic resonance imaging (MRI) and computed tomography (CT) are useful for initial assessment of bacterial spondylodiscitis. However, clinical relevance of imaging changes during treatment is less well-documented. Methods Between October 1997 and March 2005, 29 patients with documented bacterial spondylodiscitis were prospectively enrolled. They had clinical, biological and imaging examinations (MRI and/or CT) at M0 and M3, and in 22 cases, at M6. Results Mean age was 58 yrs. Antimicrobial chemotherapy lasted an average of 98 days. The median follow-up was 18 months, including 12 months after the completion of treatment. Infection was cured in every patient. Biological markers of inflammation returned to normal at M3. Six patients had painful and/or neurological sequelae. Decreased disc height was a consistent and early sign, and remained stable during the follow-up. Vertebral oedema, present in 100% of cases initially, persisted in 67 and 15% of cases at M3 and M6, respectively. Discal abscesses and paravertebral abscesses, present in 65 and 39% of cases initially, persisted in, respectively, 42 and 9% of cases at M3 and in 18 and 3% of cases at M6. Epidural abscesses were present at diagnosis in 30% of cases, and had always disappeared by M3. Imaging abnormalities found at M0 and M3 did not differ between patients with and without late neurological or painful sequelae. Conclusions Imaging abnormalities often persist in patients with bacterial spondylodiscitis despite a favourable clinical and biological response to antibiotic treatment. They are not associated with relapses, neurological sequelae or persistent pain. Imaging controls are not necessary when bacterial spondylodiscitis responds favourably to treatment.

Objective. To submit serum levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) to statistical analyses to test their exact degrees of clinical usefulness as biomarkers for detecting high disease activity in ankylosing spondylitis (AS), comparing them with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Methods. Serum levels of MMP-1, -3, -9 and TIMP-1 and -2 were measured in 42 AS patients and 20 healthy controls. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) provided the gold standard for measuring disease activity. Patients with BASDAI ¸4 were regarded as having high disease activity. The results were compared with results for a separate cohort of 41 AS patients. Results. Only MMP-3 levels were significantly higher in AS patients than in healthy controls (P

Objectives. In this study, our objectives were to investigate whether patients with ankylosing spondylitis (AS) have a poorer dynamic balance than normal subjects, and to study the relationship between balance and posture. Methods. Seventy patients (57 men, 13 women) with AS and 35 (31 men, 4 women) controls matched for age, weight, height and body mass index were tested using the Biodex Stability System (Biodex Medical Systems, Shirley, NY, USA). Anteroposterior (AP), mediolateral (ML) and overall (OA) indices were obtained with bilateral stance at platform stabilities of 8 and 4. Subjects were tested with 'eyes open' at all times. Correlation analyses were performed between stability indices (OA, AP, ML) and disease duration, cervical rotation (CR), tragus to wall distance (TWD), lumbar side flexion (LSF), lumbar flexion (LF), intermalleolar distance (IMD) and Bath Ankylosing Spondylitis Metrology Index (BASMI) total score. Results. No significant difference was found between the AS patients and healthy subjects with respect to all three stability indices at levels 4 and 8. A positive correlation was found only between ML stability index and TWD at level 8 (r, 0.249; P=0.038). No other positive correlation was detected between stability indices and CR, TWD, LSF, LF, IMD, total BASMI score and disease duration. Conclusions. AS has no negative effect on postural stability. The only clinically significant association was found between dynamic postural balance and TWD.

Objective. Infliximab, a monoclonal antibody against tumour necrosis factor a (TNF-a), is approved in Europe for the treatment of patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy. This report provides analyses from a 3-yr extension study, as a follow-up to both the 1- and 2-yr open label extensions of the original 3-month randomized controlled trial of infliximab in patients with AS. Methods. Of the 49 patients with AS who completed the second year of the study, 46 continued treatment with infliximab 5 mg/kg every 6 weeks up to week 156. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index, the Bath AS Metrology Index, patient’s and physician’s global assessments, quality of life (Short Form-36), C-reactive protein (CRP) and erythrocyte sedimentation rate were assessed throughout the study period. Results. The improvement of signs and symptoms observed in the majority of the patients during the first and second year was sustained throughout the third year of the study. Forty-three patients (62% of the 69 patients enrolled at baseline and 93% of the patients who started the third year) completed week 156. In the intention-to-treat analysis, an ASAS ‘5 out of 6’ and ASAS 40% response was seen by 46% and 50% of the patients, respectively. The scores for other efficacy assessments were similar to the values observed at weeks 54 and 102. Median CRP levels remained low (1.5 mg/l at week 156). There were no relevant side-effects and no discontinuation because of drug-related adverse events during the third year of the study. Conclusions. Patients with AS receiving infliximab for 3 yr showed a durable clinical response without loss of efficacy. Long-term infliximab treatment was well tolerated by patients in this study.