results from the German Spondyloarthritis Inception Cohort

Background Functional status and spinal mobility in patients with axial spondyloarthritis (axSpA) are known to be determined both by disease activity and by structural damage in the spine. The impact of structural damage in the sacroiliac joints (SIJ) on physical function and spinal mobility in axSpA has not been studied so far. The objective of the study was to analyze the impact of radiographic sacroiliitis on functional status and spinal mobility in patients with axSpA. Methods In total, 210 patients with axSpA were included in the analysis. Radiographs of SIJ obtained at baseline and after 2 years of follow up were scored by two trained readers according to the modified New York criteria grading system (grade 0–4). The mean of two readers’ scores for each joint and a sum score for both SIJ were calculated for each patient giving a sacroiliitis sum score between 0 and 8. The Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) at baseline and after 2 years were used as outcome measures. Results Longitudinal mixed model analysis adjusted for structural damage in the spine (modified Stoke Ankylosing Spondylitis Spine Score - mSASSS), disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI and C-reactive protein level) and gender, revealed an independent association of the sacroiliitis sum score with the BASFI: b = 0.10 (95% CI 0.01–0.19) and the BASMI: b = 0.12 (95% CI 0.03–0.21), respectively, indicating that change by one radiographic sacroiliitis grade in one joint is associated with BASFI/BASMI worsening by 0.10/0.12 points, respectively, independently of disease activity and structural damage in the spine. Conclusion Structural damage in the SIJ might have an impact on functional status and spinal mobility in axSpA independently of spinal structural damage and disease activity. Trial registration ClinicalTrials.gov, NCT01277419. Registered on 14 January 2011

Effectiveness and safety of adalimumab in patients with ankylosing spondylitis or psoriatic arthritis and history of anti-tumor necrosis factor therapy

Introduction: Tumor necrosis factor (TNF) antagonists reduce the signs and symptoms of spondyloarthritides, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Our objective was to evaluate the effectiveness and safety of adalimumab, 40 mg every other week, for patients with AS or PsA and prior treatment with infliximab (IFX) and/or etanercept (ETN). Methods: Both trials were 12-week, open-label studies with an optional extension period up to week 20. Patients were stratified by history of anti-TNF treatment, prior anti-TNF therapy received (IFX, ETN, or both), and reason for discontinuation of prior TNF antagonist. ETN was discontinued >= 3 weeks, and IFX was discontinued >= 2 months before the first adalimumab administration. Effectiveness at week 12 was evaluated by using observed standard-outcome measurements for AS and PsA. Results: At week 12 of adalimumab treatment, Bath Ankylosing Spondylitis Disease Activity Index 50 responses were achieved by 40.8% of 326 patients with AS who had received prior anti-TNF therapy and by 63.0% of 924 patients with AS who were naive to TNF antagonist. Observed response rates were generally greater for patients who discontinued the prior anti-TNF therapy because of loss of response or intolerance than for patients who discontinued because of lack of response. Median changes in swollen-joint count and in enthesitis score were similar in patients with and without prior TNF-antagonist treatment. Modified PsA response criteria were fulfilled by 71.2% of 66 patients with PsA, with prior exposure to TNF antagonists, and by 78.8% of 376 patients with no history of anti-TNF therapy. The percentages of patients with PsA attaining a Physician's Global Assessment of psoriasis of "Clear/Almost clear" increased from 33.3% to 61.0% for patients with prior IFX and/or ETN treatment and from 34.6% to 69.7% for patients without anti-TNF therapy. The median change in the Nail Psoriasis Severity Index was -6 for both groups. In both studies, patterns of adverse events were similar for patients with and without prior anti-TNF therapy and were consistent with the known safety profile of adalimumab. Conclusions: Patients with AS or PsA previously treated with IFX and/or ETN experienced clinically relevant improvements of their diseases after 12 weeks of adalimumab

Diagnostic accuracy of inflammatory back pain for axial spondyloarthritis in rheumatological care

Objective: Inflammatory back pain (IBP), the key symptom of axial spondyloarthritis (axSpA), including ankylosing spondylitis, has been proposed as a screening test for patients presenting with chronic back pain in primary care. The diagnostic accuracy of IBP in the rheumatology setting is unknown. Methods: Six rheumatology centres, representing secondary and tertiary rheumatology care, included routinely referred patients with consecutive chronic back pain with suspicion of axSpA. IBP (diagnostic test) was assessed in each centre by an independent (blinded) rheumatologist; a second (unblinded) rheumatologist made the diagnosis (axSpA or no-axSpA), which served as reference standard. Results: Of 461 routinely referred patients, 403 received a final diagnosis. IBP was present in 67.3%, and 44.6% (180/403) were diagnosed as axSpA. The sensitivity of IBP according to various definitions (global judgement, Calin, Berlin, Assessment of SpondyloArthritis international Society criteria for IBP) was 74.4%-81.1 % and comparable to published figures, whereas the specificity was unexpectedly low (25.1%-43.9%). The resulting positive likelihood ratios (LR+) were 1.1-1.4 and without major differences between sets of IBP criteria. The presence of IBP according to various definitions increased the probability of axSpA by 2.5%-8.4% only (from 44.6% to 47.1%-53.0%). Conclusions: The diagnostic utility of IBP in the rheumatology setting was smaller than expected. However, this was counterbalanced by a high prevalence of IBP among referred patients, demonstrating the effective usage of IBP in primary care as selection parameter for referral to rheumatology. Notably, this study illustrates potential shifts in specificity and LR+ of diagnostic tests if these tests are used to select patients for referral

Achievement of higher thresholds of clinical responses and lower levels of disease activity is associated with improvements in workplace and household productivity in patients with axial spondyloarthritis

Background: Patients with active axial spondyloarthritis (axSpA) exhibit more absences and lower levels of productivity in the workplace and household than the general population, which can improve upon treatment. Objectives: The objective of this study is to determine the long-term impact of achieving different levels of clinical response or disease activity on workplace and household productivity in patients with axSpA. Design: RAPID-axSpA (NCT01087762) was a 204-week phase III trial evaluating the safety and efficacy of certolizumab pegol (CZP) in adult patients with active axSpA. Methods: The impact of axSpA on workplace and household productivity was evaluated using the validated arthritis-specific Work Productivity Survey. Outcomes included the percentage of patients achieving Assessment of SpondyloArthritis International Society (ASAS) response and Ankylosing Spondylitis Disease Activity Score (ASDAS) thresholds. This post hoc study used a generalised estimating equations model to determine the association between the threshold of clinical response achieved and patient productivity. Results: Of 218 CZP-randomised patients, 65.1% completed week 204. At baseline, 72.0% were employed outside the home. Of the patients who were unemployed, 42.6% were unable to work due to arthritis. Achievement of higher treatment response thresholds, such as clinical remission, was associated with fewer days affected by workplace absenteeism (ASAS-partial remission: 4.0 days, ASAS40: 8.6 days, ASAS20 but not reaching ASAS40 response: 29.4 days, ASAS20 non-response: 69.2 days; ASDAS-inactive disease: 5.0 days, ASDAS-low disease activity: 15.6 days, ASDAS-high disease activity: 32.7 days, ASDAS-very high disease activity: 93.4 days). Similar associations were found for workplace presenteeism, and household absenteeism and presenteeism. Conclusions: Over 4 years, achievement of higher clinical response thresholds and lower levels of disease activity was associated with fewer cumulative days affected by absenteeism or presenteeism, with clinical remission associated with the greatest improvements in productivity. This highlights the importance of targeting these thresholds to limit the burden of axSpA on society and on patients’ daily lives

Incorporation of the anteroposterior lumbar radiographs in the modified Stoke Ankylosing Spondylitis Spine Score improves detection of radiographic spinal progression in axial spondyloarthritis

Background: To evaluate the performance of the extended modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) incorporating information from anteroposterior (AP) lumbar radiographs as compared to the conventional mSASSS in detection of radiographic spinal progression in patients with axial spondyloarthritis (axSpA) Methods: A total of 210 patients with axSpA, 115 with radiographic axSpA (r-axSpA), and 95 with non-radiographic axSpA (nr-axSpA), from the GErman SPondyloarthritis Inception Cohort (GESPIC), were included in the analysis based on the availability of spinal radiographs (cervical spine lateral, lumbar spine lateral, and AP views), at baseline and year 2. Two trained readers independently scored lateral cervical and lumbar spine images according to the mSASSS system (0-3 per vertebral corner, 0-72 in total). In addition, all vertebral corners of vertebral bodies visible on lumbar AP radiographs (lower T12 to upper S1) were assessed according to the same scoring system that resulted in a total range for the extended mSASSS from 0 to 144. Reliability and sensitivity to detect radiographic spinal progression of the extended mSASSS as compared to the conventional mSASSS were evaluated. Results: The reliability of conventional and extended scores was excellent with intraclass correlation coefficients (ICCs) of 0.926 and 0.927 at baseline and 0.920 and 0.933 at year 2, respectively. The mean ± SD score for mSASSS and extended mSASSS at baseline were 4.25 ± 8.32 and 8.59 ± 17.96, respectively. The change score between baseline and year 2 was 0.73 ± 2.34 and 1.19 ± 3.73 for mSASSS and extended mSASSS, respectively. With the extended mSASSS, new syndesmophytes after 2 years were detected in 4 additional patients, new syndesmophytes or growth of existing syndesmophytes in 5 additional patients, and progression by ≥ 2 points in the total score in 14 additional patients meaning a 25%, 28%, and 46% increase in the proportion of patients with progression according to the respective definition as compared to the conventional score. Conclusions: Incorporation of lumbar AP radiographs in the assessment of structural damage in the spine resulted into detection of additional patients with radiographic spinal progression not captured by the conventional mSASSS score

Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease which affects primarily the sacroiliac joints and the spine. In patients with active disease, magnetic resonance imaging (MRI) of the spine shows areas of bone marrow edema, the histopathological equivalent of which is unknown. In this study we correlate inflammation in the spine of patients with AS as revealed by histological examination with bone marrow edema as detected by MRI. We have compared the histopathological findings of zygapophyseal joints from 8 patients with AS (age: 30 to 64, disease duration 7 to 33 years) undergoing spinal surgery with findings in MRI. For histopathological analysis, we quantified infiltrates of CD3+, CD4+ and CD8+ T cells as well as CD20+ B cells immunohistochemically. Bone marrow edema was evaluated in hematoxylin and eosin stained sections and quantified as the percentage of the bone marrow area involved. All patients with AS showed interstitial mononuclear cell infiltrates and various degrees of bone marrow edema (range from 10% to 60%) in histopathological analysis. However, in only three of eight patients histopathological inflammation and edema in the zygapophyseal joints correlated with bone marrow edema in zygapophyseal joints of the lumbar spine as detected by MRI. Interestingly, two of these patients showed the highest histological score for bone marrow edema (60%). This first study correlating histopathological changes in the spine of patients with AS with findings in MRI scans suggests that a substantial degree of bone marrow inflammation and edema is necessary to be detected by MRI

Serum levels of biomarkers of bone and cartilage destruction and new bone formation in different cohorts of patients with axial spondyloarthritis with and without tumor necrosis factor-alpha blocker treatment

INTRODUCTION: Recent data about radiographic progression during treatment with tumor necrosis factor-alpha (TNF-α) blocker agents in patients with ankylosing spondylitis (AS) have prompted an intensive discussion about the link between inflammation/bone destruction and new bone formation and the order of events. Therefore, we analysed parameters of cartilage degradation, neoangiogenesis, and new bone formation in different cohorts of patients with axial spondyloarthritis with and without treatment with TNF-α blocker agents. METHOD: TNF-α blocker-naïve AS patients were investigated for serum levels of metalloproteinase-3 (MMP-3) (n = 71), vasoendothelial growth factor (VEGF) (n = 50), and bone-specific alkaline phosphatase (BALP) (n = 71) at baseline and after 1 and 2 years. This was compared with 34 adalimumab-treated patients with axial spondyloarthritis (22 AS and 12 non-radiographic axial spondyloarthritis patients) before and after 36 to 52 weeks of treatment. RESULTS: There were no significant changes in serum levels of MMP-3 (P > 0.05), VEGF (P > 0.05), and BALP (P > 0.05) in a large cohort of TNF-α blocker-naïve AS patients followed for 2 years. In contrast, adalimumab-treated spondyloarthritis (AS and non-radiographic axial spondyloarthritis) patients had a significant decrease of VEGF (P < 0.001) and MMP-3 (P = 0.022) after 36 to 52 weeks of therapy. Most interestingly, the level of BALP increased significantly after 36 to 52 weeks of therapy (P < 0.001). A decrease in MMP-3 serum levels correlated significantly to an increase of BALP (r = -0.398, P = 0.02). In the case of VEGF, there was a negative correlation without significance (r = -0.214, P > 0.05). CONCLUSIONS: Rising levels of BALP and the negative correlation between MMP-3 and BALP in spondyloarthritis patients with TNF-α blocker treatment indicate that new bone formation in AS occurs if inflammation is successfully treated and might be part of a healing process

Spinal radiographic progression over 2years in ankylosing spondylitis patients treated with secukinumab : a historical cohort comparison

ObjectiveThe aim of this study was to compare radiographic progression in patients with ankylosing spondylitis (AS) treated for up to 2years with secukinumab (MEASURE 1) with a historical cohort of biologic-naive patients treated with NSAIDs (ENRADAS).MethodsBaseline and 2-year lateral cervical and lumbar spine radiographs were independently evaluated using mSASSS by two readers, who were blinded to the chronology and cohort of the radiographs. The primary endpoint was the proportion of patients with no radiographic progression (mSASSS change 0 from baseline to year 2). The Primary Analysis Set included patients with baseline (day 30) and post-baseline day 31-743 radiographs. Sensitivity analyses were performed to assess the robustness of the comparison between the two cohorts, as follows: Sensitivity Analysis Set 1 included all patients with baseline (day 30) and year 2 (days 640-819) radiographs; Sensitivity Analysis Set 2 included all patients with baseline and post-baseline (>day 30) radiographs.ResultsA total of 168 patients (84%) from the MEASURE 1 cohort and 69 (57%) from the ENRADAS cohort qualified for the Primary Analysis Set. Over 2years, the LS (SE) mean change from baseline in mSASSS for the primary analysis was 0.55 (0.139) for MEASURE 1 vs 0.89 (0.216) for ENRADAS (p=0.1852). Mean changes from baseline in mSASSS were lower in MEASURE 1 vs ENRADAS for the primary and sensitivity analyses. The proportion of patients with no radiographic progression was consistently higher in the MEASURE 1 vs ENRADAS cohort across all cutoffs for no radiographic progression (change in mSASSS from baseline to year 2 of 0, 0.5, 1, and 2), but the differences were not statistically significant.ConclusionSecukinumab-treated patients demonstrated a numerical, but statistically non-significant, higher proportion of non-progressors and lower change in mSASSS over 2years versus a cohort of biologic-naive patients treated with NSAIDs