Interval prolongation of etanercept in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: a randomized controlled trial.

OBJECTIVE: The majority of patients with a rheumatic disease treated with etanercept may be overexposed. Data regarding etanercept tapering are scarce, particularly in psoriatic arthritis (PsA) and ankylosing spondylitis (AS). We compared extending the dose interval to continuation of the standard dose and studied the success rate of etanercept discontinuation. Etanercept concentrations were measured throughout the study. METHOD: 160 patients with rheumatoid arthritis (RA), PsA, or AS with sustained minimal disease activity (MDA) were enrolled in this 18-month, open-label, randomized controlled trial. The intervention group doubled the dosing interval at baseline and discontinued etanercept 6 months later. The control group continued the standard dose for 6 months and doubled the dosing-interval thereafter. The primary outcome was the proportion of patients maintaining MDA at 6 month follow-up. RESULTS: At 6 months, MDA status was maintained in 47 patients (63%) in the intervention group and 56 (74%) in the control group (p = 0.15), with comparable results in all rheumatic diseases. And median etanercept concentrations decreased from 1.50 µg/mL (interquartile range 1.06- 2.65) to 0.46 µg/mL (0.28-0.92). In total, 40% discontinued etanercept successfully with maintained MDA for at least 6 months. CONCLUSION: Etanercept tapering can be done without losing efficacy in RA, PsA, and AS patients in sustained MDA. A substantial proportion of patients could stop etanercept for at least 6 months. In many patients, low drug concentrations proved sufficient to control disease activity. However, the risk of minor and major flares is substantial, even in patients continuing standard dosing.

Prevalence and Radiographic Progression of Hip Involvement in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors.

OBJECTIVE: To examine the prevalence of hip involvement between sexes in patients with ankylosing spondylitis (AS) treated with tumor necrosis factor inhibitors (TNFi) and to estimate the effect of TNFi on radiographic progression of hip involvement compared to the spine. METHODS: Two hundred ninety-nine patients with AS treated with TNFi (215 men; median age: 43 yrs [IQR 36-52], median disease duration: 7.6 yrs [IQR 2-15]) were evaluated for hip involvement, defined radiographically as Bath AS Radiological Hip Index (BASRI-hip) score ≥ 2. Those who received TNFi for ≥ 2 years (263/299) were assessed for radiographic progression. Radiographs of the pelvis and spine, obtained at baseline (ie, before TNFi initiation), were compared retrospectively to those obtained after 2.5 (SD 0.7) years and 7.0 (SD 2.3) years of TNFi treatment. Both hips were scored by BASRI-hip score and mean joint space width (MJSW). Spinal radiographs were scored by modified Stoke AS Spinal Score (mSASSS). RESULTS: The prevalence of hip involvement at baseline was 113/299 (38%) patients, of whom 87/215 (41%) were male and 26/84 (31%) were female (P = 0.10). In both sexes with hip involvement at baseline, BASRI-hip score and MJSW did not change significantly during follow-up. In males and females without baseline hip involvement, the BASRI-hip score remained unchanged after 2.5 (SD 0.7) years but increased significantly after 7.0 (SD 2.3) years, without reaching the cut-off of 2. In contrast, the MJSW slightly decreased at the 2 follow-up timepoints (ie, after 2.5 and 7.0 yrs). The mSASSS increased significantly during the follow-up in both sexes, regardless of hip involvement. CONCLUSION: In our study, approximately one-third of patients with AS had hip involvement, which seemed to stabilize with TNFi treatment. No sex differences in the prevalence or progression of this manifestation were found.

The effect of anti-TNF on renal function in patients with ankylosing spondylitis: a prospective cohort study.

BACKGROUND: Biologicals, such as anti-tumor necrosis factor (anti-TNF), reduce cardiovascular disease (CVD) in patients with inflammatory rheumatic diseases. Impaired renal function is a known predictor of CVD and elevated in ankylosing spondylitis (AS). OBJECTIVE: To assess the effect of anti-TNF on renal function in patients with AS and whether anti-TNF use is safe in AS patients with pre-existing risk factors for renal decline. METHOD: Biological-naïve consecutive AS patients treated with etanercept or adalimumab were prospectively followed from 2005 to 2014. Renal function was determined by calculation of the estimated glomerular filtration rate (eGFR), estimated with the abbreviated modification of diet in renal disease (MDRD) formula. The effect of anti-TNF on eGFR was analyzed using mixed model analysis. RESULTS: 211 AS patients were followed for a median of 156 (36-286) weeks. Overall mixed model analyses showed a significant decrease of eGFR over time (ß = - 0.040, p = 0.000), although this association did not remain significant after adjustment for responding to anti-TNF, alcohol use, disease duration, body mass index (BMI), C-reactive protein (CRP), and disease activity (ß = - 0.018, p = 0.094). However, patients with pre-existing risk factors for renal decline did have a significant change in eGFR over time (ß = - 0.029, p = 0.006). CONCLUSIONS: We found a significant change in eGFR over time, although this small decrease was not clinically relevant. This study further demonstrates that anti-TNF does not affect renal function in AS patients with and without existing risk factors for renal decline, which means that use of anti-TNF is safe concerning renal function in patients with AS. Key Points • Previous studies showed that biologicals, such as anti-tumor necrosis factor (anti-TNF), reduce cardiovascular disease (CVD) in patients with inflammatory rheumatic diseases, such as ankylosing spondylitis (AS). • Impaired renal function is a known predictor of CVD, and also a known concern for many AS patients. • Use of anti-TNF is safe with regard to renal function in patients with AS. • The effect of anti-TNF on CVD in AS patients does not seem to be mediated by changes in renal function.

The effect of anti-TNF treatment on body composition and insulin resistance in patients with rheumatoid arthritis.

Given the link between systemic inflammation, body composition and insulin resistance (IR), anti-inflammatory therapy may improve IR and body composition in inflammatory joint diseases. This study assesses the IR and beta cell function in rheumatoid arthritis (RA) patients with active disease compared to osteoarthritis (OA) patients and investigates the effect of anti-TNF treatment on IR, beta cell function and body composition in RA. 28 Consecutive RA patients starting anti-TNF treatment (adalimumab), and 28 age, and sex-matched patients with OA were followed for 6 months. Exclusion criteria were use of statins, corticosteroids, and cardiovascular or endocrine co-morbidity. Pancreatic beta cell function and IR, using the homeostasis model assessment (HOMA2), and body composition, using dual-energy X-ray absorptiometry (DXA) were measured at baseline and 6 months. At baseline, IR [1.5 (1.1-1.8) vs. 0.7 (0.6-0.9), 100/%S] and beta cell function (133% vs. 102%) were significantly (p < 0.05) higher in RA patients with active disease as compared to OA patients. After 6 months of anti-TNF treatment, IR [1.5 (1.1-1.8) to 1.4 (1.1-1.7), p = 0.17] slightly improved and beta cell function [133% (115-151) to 118% (109-130), p <0.05] significantly improved. Improvement in IR and beta cell function was most pronounced in RA patients with highest decrease in CRP and ESR. Our observations indicate that IR and increased beta cell function are more common in RA patients with active disease. Anti-TNF reduced IR and beta cell function especially in RA patients with highest decrease in systemic inflammation and this effect was not explained by changes in body composition.

Comparison of drug survival and clinical outcome in patients with ankylosing spondylitis treated with etanercept or adalimumab.

OBJECTIVE: To compare rates of drug survival and clinical response during 2 years of follow-up in ankylosing spondylitis (AS) patients treated with etanercept or adalimumab in routine care. METHOD: Biological-naïve consecutive AS patients treated with etanercept (n = 163) or adalimumab (n = 82) were followed. Treatment discontinuation was due to inefficacy, adverse events, loss to follow-up, planning a pregnancy, or uveitis. Disease activity was assessed by the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP). Moderate disease activity was defined as an ASDAS-CRP < 2.1. RESULTS: Twenty-seven patients (32.9%) treated with adalimumab and 30 (18.4%) with etanercept discontinued treatment. Cox regression analysis demonstrated a significant difference in survival rate between discontinuation of the drug in adalimumab patients compared with etanercept patients [hazard ratio (HR) 2.1, 95% confidence interval (CI) 1.3-4.5, p = 0.005; corrected for confounding factors: HR 2.5, 95% CI 1.3-4.5, p = 0.006]. There was no significant difference at 2 years of follow-up between the adalimumab- and the etanercept-treated patients in mean ± sd ASDAS-CRP (1.9 ± 1.1 and 2.0 ± 0.9, respectively, p = 0.624), and 23 out of 34 (67.6%) compared to 71 out of 117 (60.7%) reached ASDAS-CRP moderate disease activity (odds ratio 0.738, 95% CI 0.329-1.657, p = 0.530). CONCLUSION: No significant difference was found between AS patients treated with etanercept and those treated with adalimumab in mean ASDAS-CRP and reaching ASDAS-CRP minimal disease activity at 2 year follow-up. Drug survival rate was higher in etanercept- compared to adalimumab-treated patients. However, this should be interpreted cautiously as the risk of allocation bias cannot be excluded.

Fat Mass Lowers the Response to Tumor Necrosis Factor-α Blockers in Patients with Ankylosing Spondylitis.

OBJECTIVE: Our main objective was to assess the relationship between body composition (BC) and response to tumor necrosis factor-α (TNF-α) blocker treatment in patients with ankylosing spondylitis (AS). Our secondary objective was to evaluate the change of BC after treatment, accounting for sex and age. METHODS: All included patients fulfilled the modified New York criteria for AS and were naive to TNF-α blocker. They were followed for at least 6 months after the start of etanercept or adalimumab. The Ankylosing Spondylitis Disease Activity Score containing C-reactive protein (ASDAS-CRP) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were reported. BC was assessed by whole body dual-energy X-ray absorptiometry. Body fat percentage (BF%), fat mass index (FMI), and fat free mass index (FFMI) were reported as absolute values and as percentiles. RESULTS: Forty-one patients were included (61% men). The median followup was 14.3 months (interquartile range 8.4-19.4). After multivariate regression analysis, more fat at baseline (BF%, FMI, or FMI percentile) was significantly related with a lower chance of achieving a clinically important improvement of the ASDAS-CRP or BASDAI after treatment. The body composition did not change significantly after treatment, but there was a trend toward muscle recovery in men (FFMI change from 34.0th to 37.4th percentile). CONCLUSION: Higher body fat content at baseline was independently associated with a worse response to treatment with TNF-α blockers, measured by ASDAS-CRP and BASDAI change, and might contribute to the lower response rates in female patients. Also, there is a trend toward muscle mass recovery in male patients after treatment.

Etanercept Increases Bone Mineral Density in Ankylosing Spondylitis, but Does Not Prevent Vertebral Fractures: Results of a Prospective Observational Cohort Study.

OBJECTIVE: Ankylosing spondylitis (AS) is characterized by chronic inflammation leading to ankylosis, but also to low bone mineral density (BMD) and vertebral fractures (VFx). Treatment with tumor necrosis factor-α blockers decreases inflammation and has shown to be effective in increasing BMD. We studied the effects of etanercept (ETN) on BMD and VFx in patients with AS after 2 years of treatment. Further, we studied changes in bone turnover markers and radiological damage. METHODS: Patients with active AS, treated with ETN for 2 years, were included. BMD lumbar spine and hip were measured at baseline and after 2 years, as well as radiological damage (modified Stoke Ankylosing Spondylitis Spinal Score with the addition of the thoracic spine), VFx (Genant method), and change in bone turnover markers. RESULTS: Forty-nine patients with AS were included. After 2 years of ETN, hip BMD increased by 2.2% (p = 0.014) and lumbar spine BMD by 7.0% (p < 0.001). The Bath Ankylosing Spondylitis Disease Activity Index decreased significantly (p < 0.001), as well as C-reactive protein and erythrocyte sedimentation rate (p < 0.001). Despite ETN therapy, the number of patients with VFx more than doubled (from 6 to 15 patients, p = 0.003). Also, the radiological damage increased significantly over time (from 12.1 to 18.5, p < 0.001); however, no significant change in bone turnover markers was found. CONCLUSION: This prospective longitudinal observational cohort study showed that after 2 years of ETN, BMD of the hip and spine increased significantly, but the number of patients with VFx and the severity of VFx increased as well. Besides that, radiological progression, including the thoracic spine, increased significantly. Thus, the favorable bone-preserving effect is accompanied by unfavorable outcomes on VFx and radiological damage.

Objective evaluation of physical functioning after tumor necrosis factor inhibitory therapy in patients with ankylosing spondylitis: a selection of 3 feasible performance-based tests.

OBJECTIVE: (1) To select a limited number of performance-based tests that are reliable, show improvement in physical functioning after tumor necrosis factor inhibitor (TNFi) therapy in patients with ankylosing spondylitis (AS), and generate information equivalent to the full set of tests, and (2) are feasible for use in daily clinical practice. METHODS: Eight performance-based tests were evaluated. To eliminate redundant testing, the tests that showed adequate reliability, the highest standardized response mean (SRM), and the largest proportion of patients with an improved performance-based physical functioning were selected. The selected tests were combined into a new criterion for improvement in physical functioning (AS Performance-based Improvement; ASPI). The number and percentage of improved patients identified with the ASPI and identified with the full set of performance tests were compared. RESULTS: Reliability for all tests was adequate to excellent (ICC 0.73-0.96). The tests for bending, putting on socks, and getting up from the floor had the highest SRM (0.52-0.74) and showed the largest proportion of improved patients after TNFi therapy. The combination of these 3 tests was feasible in daily clinical practice and showed improved physical functioning after TNFi therapy in 67% of the patients. CONCLUSION: The 3 selected tests are recommended for use in daily practice because they generate information comparable to the full set. They are reliable and feasible, and the combination of these tests showed improved physical functioning after TNFi therapy in 67% of the patients. Evaluation of physical functioning might be improved by adding these tests to other AS outcome measures.

Adalimumab significantly reduces the recurrence rate of anterior uveitis in patients with ankylosing spondylitis.

OBJECTIVE: To investigate whether use of adalimumab decreases the frequency of attacks of anterior uveitis (AU) in patients with ankylosing spondylitis (AS). METHODS: Consecutive patients with AS, visiting an outpatient clinic and treated for at least 12 weeks with adalimumab, were enrolled. The number of attacks of AU in the year before start and during treatment were assessed by patient history and ophthalmological controls. RESULTS: In the 77 patients a total of 52 AU attacks occurred in the year before baseline (68 attacks per 100 patient-yrs), whereas during adalimumab treatment 19 attacks were seen (14 per 100 patient-yrs; reduction rate 80%). Twenty-six patients with AU in the year before start of adalimumab treatment had recurrent attacks, with a median number of 2.0 AU attacks per year [interquartile range (IQR) 1.00-3.00], whereas during treatment this decreased to 10 patients with a median number of 0.56 attacks per year (IQR 0.30-0.75). Hence, the number of attacks per year decreased by 72% (p = 0.000). CONCLUSION: In patients with AS, a significant reduction in the number of AU attacks, as well as in the number of attacks per patient, was observed during adalimumab treatment.

What do we miss? ASAS non-responders on anti-TNF therapy show improvement in performance-based physical function.

OBJECTIVE: A prospective study was conducted in order to establish whether AS patients, who are defined as non-responders after 3 months of anti-TNF therapy, show improvement on performance-based tests of physical functioning. METHODS: At baseline and 3 months after the start of anti-TNF therapy, AS patients completed seven performance-based tests of physical functioning, questionnaires on self-reported physical functioning (BASFI) and disease activity (BASDAI), and a pain and a global patient assessment. The concordance between ≥ 20% intra-individual improvement on the performance-based test of physical functioning and (i) response to anti-TNF therapy [Assessment of SpondyloArthritis International Society 20% (ASAS20) response] and (ii) ≥ 20% intra-individual improvement on self-reported physical functioning (BASFI) was assessed. RESULTS: One hundred AS patients were included, of which 82 patients completed all tests at both time points. After 3 months of anti-TNF therapy, 27 (32.9%) patients were categorized as non-responders according to the ASAS20 response criteria. Improvement in performance-based physical functioning was seen in 13 of the 27 non-responders (48.1%) (i.e. n = 13/82 = 15.9% of the total group). Furthermore, 30 (36.6%) patients showed no improvement on self-reported physical functioning (BASFI). However, 17 of the 30 (56.7%) patients did improve on the performance-based tests of physical functioning (i.e. n = 17/82 = 20.7% of the total group). CONCLUSION: After 3 months of anti-TNF therapy, performance-based tests of physical functioning showed improvement in 48.1% of the ASAS20 non-responders. With these performance-based tests, new information on outcome after anti-TNF therapy can be generated. Using performance-based tests alongside the BASFI could have additional value in the evaluation of outcomes for patients receiving anti-TNF therapy.

Elevated liver enzymes in patients with ankylosing spondylitis treated with etanercept.

TNF-alpha blocking agents are very effective in patients with ankylosing spondylitis (AS), but several cases of liver problems have been published. We systematically studied the frequency of this potential side effect in our AS patients treated with etanercept. Consecutive AS patients treated with etanercept for at least 3 months were included. Liver disease was defined as elevated liver enzymes more than 1.5 times the upper normal limit (UNL) and was categorised as probably, possibly, probably not or not related to etanercept treatment. Patients with and without raised liver enzymes were compared for prognostic factors. A total of 105 patients were included. Fifteen patients had elevated liver enzymes more than once. In nine cases, the liver disease was probably (five) or possibly (four) related to etanercept treatment. The liver enzyme elevations were serious (>3× UNL) in six cases and resulted in permanent cessation of etanercept in two cases. The nine patients with liver disease were compared with patients without elevated liver enzymes. No differences were found in age or use of alcohol; however, in patients with liver disease, a higher body mass index and a trend for a higher atherogenic index were observed. Hepatic steatosis was observed in five of six patients with elevated liver enzymes. Elevated serum aminotransferases, probably or possibly related to etanercept treatment, were observed in 9 % of the AS patients. An increased risk for the elevation of liver enzymes was found in patients with a higher body mass index. We recommend regular testing of liver enzymes in patients treated with etanercept.

Bone formation rather than inflammation reflects ankylosing spondylitis activity on PET-CT: a pilot study.

INTRODUCTION: Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [18F]FDG and [11C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [18F]Fluoride, which targets bone formation. In a pilot setting, the potential of PET-CT in imaging AS activity was tested using different tracers, with Magnetic Resonance Imaging (MRI) and conventional radiographs as reference. METHODS: In a stepwise approach different PET tracers were investigated. First, whole body [18F]FDG and [11C](R)PK11195 PET-CT scans were obtained of ten AS patients fulfilling the modified New York criteria. According to the BASDAI five of these patients had low and five had high disease activity. Secondly, an extra PET-CT scan using [18F]Fluoride was made of two additional AS patients with high disease activity. MRI scans of the total spine and sacroiliac joints were performed, and conventional radiographs of the total spine and sacroiliac joints were available for all patients. Scans and radiographs were visually scored by two observers blinded for clinical data. RESULTS: No increased [18F]FDG and [11C](R)PK11195 uptake was noticed on PET-CT scans of the first 10 patients. In contrast, MRI demonstrated a total of five bone edema lesions in three out of 10 patients. In the two additional AS patients scanned with [18F]Fluoride PET-CT, [18F]Fluoride depicted 17 regions with increased uptake in both vertebral column and sacroiliac joints. In contrast, [18F]FDG depicted only three lesions, with an uptake of five times lower compared to [18F]Fluoride, and again no [11C](R)PK11195 positive lesions were found. In these two patients, MRI detected nine lesions and six out of nine matched with the anatomical position of [18F]Fluoride uptake. Conventional radiographs showed structural bony changes in 11 out of 17 [18F]Fluoride PET positive lesions. CONCLUSIONS: Our PET-CT data suggest that AS activity is reflected by bone activity (formation) rather than inflammation. The results also show the potential value of PET-CT for imaging AS activity using the bone tracer [18F]Fluoride. In contrast to active RA, inflammation tracers [18F]FDG and [11C](R)PK11195 appeared to be less useful for AS imaging.

Moving instead of asking? Performance-based tests and BASFI-questionnaire measure different aspects of physical function in ankylosing spondylitis.

INTRODUCTION: Ankylosing Spondylitis (AS) is characterised by limitations in physical function. The Bath Ankylosing Spondylitis Functional Index (BASFI) is considered to be the gold-standard to assess physical function in AS patients. However, the BASFI questionnaire is a self-reported outcome measure and susceptible to subjective interpretation (under- or over-estimation). More objective outcome measures, like performance-based tests, could provide an objective outcome measurement for the evaluation of limitations in physical function. Therefore, the primary aim of this study was to determine the association between performance-based measures and the BASFI questionnaire. METHODS: In this cross-sectional study 126 AS patients completed the BASFI questionnaire and eight performance-based tests based on BASFI-items. Each test received three scores: one for performance (time or points) and a score for exertion and pain experienced during performance (using modified Borg-scale and VAS 0-100 mm, respectively). Linear regression analyses were used to assess the associations between the BASFI questionnaire and performance-based tests. RESULTS: The univariable association between performance and BASFI-score was moderate with a R-square of 0.31 and Beta of 0.56 (p's < 0.05). In a multivariable analysis, the association between performance, exertion and pain on the one hand and BASFI-score on the other was assessed; R-square increased to 0.54: the Beta's for exertion and pain during performance were 0.38 and 0.26, respectively; the Beta for performance decreased to 0.19 (p's < 0.05). CONCLUSIONS: This study demonstrates that alongside actual performance, patients seem to incorporate exertion and pain in their assessment of perceived physical function on the BASFI questionnaire. Performance-based tests could provide an objective outcome measurement for the evaluation of physical function and give relevant new information in addition to the BASFI questionnaire.

High frequency of vertebral fractures in early spondylarthropathies.

UNLABELLED: We demonstrated that vertebral fractures (VF) are commonly found in early SpA. Patients with VF had lower lumbar BMD than patients without VF. VF remained frequently 'unrecognized' and untreated. VF have been associated with more back pain, reduced Qol, and increased risk of future fractures which stresses the importance of recognition also in early stage SpA. INTRODUCTION: VF are a common complication of long-standing ankylosing spondylitis (AS). However, data of VF in early AS patients and in other spondylarthropathies (SpA) are scarce. Therefore we examined the prevalence of VF in early SpA patients and investigated the associations between VF and demographic and disease-related variables. METHODS: SpA patients were included consecutively and radiographs of the spine were made. VF were assessed according to the method of Genant et al.: fractures were defined as reduction of ≥20% of the vertebrae. Descriptive statistics, t-tests and logistic regression analyses were used to study the relationship between VF and demographic and disease-related variables, radiographic damage and BMD. RESULTS: A total of 113 early SpA patients were included with a disease duration of 7 months, a mean age of 37 years. Seventeen patients (15%) had at least one VF. Fourteen patients had one VF, three patients had two VF. Most VF were located at Th6-Th8. In patients with VF, bone mineral density (BMD) of lumbar spine was lower than BMD of patients without VF (t-test: p = 0.043). Axial Psoriatic Arthritis (PsA) was significantly associated with a higher risk for VF (odds ratio [OR]: 4.62, 95% confidence interval [CI] 1.15-18.58, p = 0.031). No significant associations were found with disease activity variables nor with radiographic severity. CONCLUSION: In a group of 113 early, young SpA patients, 15% already had at least one VF. Most VF were asymptomatic, undetected by routine diagnostic procedures and located at the mid-thoracic spine. The VF were associated with low BMD of the lumbar spine and with axial PsA.

Low bone mineral density is related to male gender and decreased functional capacity in early spondylarthropathies.

The objective of this study was to determine the prevalence and risk factors of low bone mineral density (BMD) in patients with spondylarthropathies (SpA) at an early stage of disease. In this cross-sectional study, the BMD of lumbar spine and hips was measured in 130 consecutive early SpA patients. The outcome measure BMD was defined as (1) osteoporosis, (2) osteopenia, and (3) normal bone density. Logistic regression analyses were used to investigate relations between the following variables: age, gender, disease duration, diagnosis, HLA-B27, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), extra-spinal manifestations and medication, with outcome measure low BMD (osteopenia and/or osteoporosis). The SpA population had a median time since diagnosis of 6.6 months and a disease duration of 6.3 years. In total, 9% of the early SpA patients had osteoporosis, 38% osteopenia, and 53% normal BMD. On univariate analyses, male gender, diagnosis of ankylosing spondylitis, increased CRP, high BASFI, and high BASMI were significantly associated with low BMD. Factors showing a relation with low BMD in the multivariate model were male gender (OR 4.18, 95% confidence interval (CI) 1.73-10.09), high BASMI (OR 1.54, 95% CI 1.14-2.07), and high BASFI (OR 1.18, 95% CI 1.00-1.39). In early SpA patients, a high frequency (47%) of low BMD in femur as well as in lumbar spine was found. Low BMD was associated with male gender and decreased functional capacity. These findings emphasize the need for more alertness for osteoporosis and osteopenia in spondylarthropathy patients at an early stage of the disease.

Discovertebral (Andersson) lesions in severe ankylosing spondylitis: a study using MRI and conventional radiography.

The objective of this study is to investigate the prevalence of Andersson lesions (AL) in ankylosing spondylitis (AS) patients who will start anti-tumor necrosis factor (TNF) treatment. Radiographs and magnetic resonance imaging (MRI) of the spine were performed before therapy with anti-TNF. ALs were defined as discovertebral endplate destructions on MRI, associated with bone marrow edema and fat replacement or sclerosis, a decreased signal on T1, enhancement after contrast administration (gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)), and increased signal on T2 and short tau inversion recovery (STIR). Additionally, conventional radiography showed a fracture line, irregular endplates, and increased sclerosis of adjacent vertebral bodies. Fifty-six AS patients were included, 68% males, mean age of 43 years, and mean disease duration of 11 years. The mean bath ankylosing spondylitis disease activity index was 6.4, and 24% of all patients had ankylosis. Only one patient showed a discovertebral abnormality with bone marrow edema of more than 50% of the vertebral bodies adjacent to the intervertebral disk of T7/T8 and T9/T10, a hypodense signal area on T1, and a high signal on STIR. Irregular endplates were depicted, and T1 after Gd-DTPA demonstrated high signal intensity around the disk margins. However, no fracture line was visible on conventional radiology, and therefore, this case was not considered to be an AL. No AL was detected in our AS patients, who were candidates for anti-TNF treatment. One patient showed a discovertebral abnormality on MRI, without a fracture line on conventional radiology. The relative small proportion of patients with a long-established disease might explain this finding for, particularly, an ankylosed spine is prone to develop an AL.

Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis.

BACKGROUND: COBRA (for 'COmbinatie therapie Bij Rheumatoide Artritis') combination therapy is effective for the treatment of rheumatoid arthritis (RA), but long-term safety is unknown. This study evaluates survival, comorbidities and joint damage in the original COBRA trial cohort. METHODS: In the COBRA trial, 155 patients with early RA were treated with sulfasalazine (SSZ) monotherapy (SSZ group) or a combination of step-down prednisolone, methotrexate (MTX) and SSZ (COBRA group). The current 11-year follow-up study of the COBRA trial invited all original patients and performed protocollised scrutiny of clinical records, questionnaires, physical examination, laboratory and imaging tests. RESULTS: In all, 152 out of 155 patients yielded at least partial data. After a mean of 11 years follow-up, 18 (12%) patients had died, 6 COBRA patients and 12 SSZ patients, HR 0.57 (95% CI 0.21 to 1.52). Treatment for hypertension was significantly more prevalent in the COBRA group (p=0.02) with similar trends for diabetes and cataract. Conversely, hypercholesterolaemia, cancer and infection showed a trend in favour of COBRA. Other comorbidities such as cardiovascular disease and fractures appeared in similar frequency. Radiographic findings suggest as a minimum sustained benefit for COBRA therapy, that is, difference in joint damage but similar subsequent progression rates after 5 years. Imputation to compensate for selective dropout suggests increasing benefit for COBRA, that is, difference in yearly progression rates similar to that seen in the first 5 years of follow-up. CONCLUSIONS: After 11 years, initial COBRA combination therapy resulted in numerically lower mortality and similar prevalence of comorbidity compared with initial SSZ monotherapy. In addition, lower progression of joint damage suggests long-term disease modification.

Immunogenicity does not influence treatment with etanercept in patients with ankylosing spondylitis.

BACKGROUND: Immunogenicity, specifically the onset of antibodies against tumour necrosis factor (TNF) blocking agents, seems to play an important role in non-response to treatment with these drugs. OBJECTIVES: To assess the relation of clinical response of ankylosing spondylitis (AS) to etanercept with etanercept levels, and the presence of antibodies to etanercept. METHODS: Patients with AS were treated with etanercept 25 mg twice weekly, according to the international Assessment in Ankylosing Spondylitis (ASAS) working group consensus statement. Sera were collected at baseline and after 3 and 6 months of treatment. Clinical response was defined as a 50% improvement or as an absolute improvement of 2 points on a (0-10 scale) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score. Functional etanercept levels were measured by a newly developed ELISA, measuring the binding of etanercept to TNF. Antibodies against etanercept were measured with a two-site assay and antigen binding test. Clinical data were used to correlate disease activity with serum etanercept levels. RESULTS: In all, 53 consecutive patients were included. After 3 months of treatment 40 patients (76%) fulfilled the response criteria. Mean etanercept levels were 2.7 mg/litre and 3.0 mg/litre after 3 and 6 months respectively. Characteristics and etanercept levels of responders and non-responders were similar. No antibodies to etanercept were detected with any of the assays. CONCLUSION: Etanercept levels of responders and non-responders were similar and no antibodies to etanercept were detected with any of the assays. This study indicates that etanercept is much less immunogenic compared with the other TNF-blocking agents.