53 research outputs found
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
Study protocol: Comparison of the effect of treatment with Nonsteroidal anti- inflammatory drugs added to anti-tumour necrosis factor a therapy versus anti- tumour necrosis factor a therapy alone on progression of Structural damage in the spine over two years in patients with ankyLosing spondylitis (CONSUL) – an open-label randomized controlled multicenter trial
Introduction There is some evidence that non-steroidal anti-inflammatory drugs
(NSAIDs), in particular celecoxib, might possess not only a symptomatic
efficacy but also disease-modifying properties in ankylosing spondylitis (AS),
retarding the progression of structural damage in the spine if taken
continuously. In contrast, this remains controversial for tumour necrosis
factor alpha (TNF-α) inhibitors, despite their good clinical efficacy. The
impact of a combined therapy (a TNF inhibitor plus an NSAID) on radiographic
spinal progression in AS is unclear. Methods and analysis The aim of this
study is to evaluate the impact of treatment with an NSAID (celecoxib) when
added to a TNF inhibitor (golimumab) compared with TNF inhibitor (golimumab)
alone on progression of structural damage in the spine over 2 years in
patients with AS. The study consists of a 6-week screening period, a 12-week
period (phase I: run-in phase) of treatment with golimumab for all subjects
followed by a 96-week controlled treatment period (phase II: core phase) with
golimumab plus celecoxib versus golimumab alone, and a safety follow-up period
of 4 weeks. At week 108, the primary study endpoint radiographic spinal
progression (as assessed by the change in the modified Stoke Ankylosing
Spondylitis Spine Score after 2 years) will be evaluated. Ethics and
dissemination The study will be performed according to the principles of good
clinical practice and the German drug law. The written approval of the
independent ethics committee and of the German federal authority have been
obtained. On study completion, results are expected to be published in a peer-
reviewed journal. Trial registration number ClinicalTrials.gov register
(NCT02758782) and European Union Clinical Trials Register (EudraCT No
2016-000615-33)
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
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
Distinct Effects of Interleukin-1β Inhibition upon Cytokine Profile in Patients with Adult-Onset Still’s Disease and Active Articular Manifestation Responding to Canakinumab
Adult-onset Still’s disease (AOSD) is a systemic auto-inflammatory disease characterized by the presence of immunologically mediated inflammation and deficient resolution of inflammation. Canakinumab is an approved IL-1β inhibitor in the treatment of AOSD with a balanced efficacy and safety profile. Since inflammatory cytokines play a major role in the pathogenesis of AOSD, we investigated the effects of canakinumab on the cytokine profile of AOSD patients from a randomized controlled trial. Multiplex analysis and ELISA were used to test the concentrations of several cytokines at three time points—week 0 (baseline), week 1 and week 4—in two patient groups—placebo and canakinumab. Two-way repeated-measures analysis of variance revealed a significant temporal effect on the concentrations of MRP 8/14, S100A12, IL-6 and IL-18 with a significant decrease at week 4 in the canakinumab group exclusively. Comparing responders with non-responders to canakinumab showed a significant decrease in MRP 8/14, IL-1RA, IL-18 and IL-6 in responders at week 4, while S100A12 levels decreased significantly in responders and non-responders. In summary, canakinumab showed a striking effect on the cytokine profile in patients with AOSD, exhibiting a clear association with clinical response
Screening strategies in SpA Personal non-commercial use only
ABSTRACT. 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
Clinical and functional remission: even though biologics are superior to conventional DMARDs overall success rates remain low – results from RABBIT, the German biologics register
We investigated the frequency of remission according to the disease activity score (DAS28) definition, modified American Rheumatology Association (ARA) criteria, and the frequency of an achievement of a functional status above defined thresholds ('functional remission', 'physical independence') in rheumatoid arthritis (RA) patients treated with either biologics or conventional DMARDs. We used the data of a prospective cohort study, the German biologics register RABBIT (German acronym for Rheumatoid Arthritis – Observation of Biologic Therapy) to investigate the outcomes in RA patients with two or more DMARD failures who received new treatment with biologics (BIOL; n = 818) or a conventional DMARD (n = 265). Logistic regression analysis was applied to adjust for differences in baseline risks. Taking risk indicators such as previous DMARD failures or baseline clinical status into account, we found that biologics doubled the chance of remission compared to conventional DMARD therapies (DAS28 remission, adjusted odds ratio (OR) 1.95 (95% confidenece interval (CI) 1.2–3.2)); ARA remission, OR 2.05 (95% CI 1.2–3.5)). High remission rates (DAS28 remission, 30.6%; ARA remission, 16.9%) were observed in BIOL patients with a moderate disease activity (DAS28, 3.2 to 5.1) at the start of treatment. These rates decreased to 8.5% in patients with DAS28 > 6. Sustained remission at 6 and 12 months was achieved in <10% of the patients. Severely disabled patients (≤50% of full function) receiving biologic therapies were significantly more likely to achieve a status indicating physical independence (≥67% of full function) than controls (OR 3.88 (95% CI 1.7–8.8)). 'Functional remission' (≥83% of full function) was more often achieved in BIOL than in controls (OR 2.18 (95% CI 1.04–4.6)). In conclusion, our study shows that biologics increase the chance to achieve clinical remission and a status of functional remission or at least physical independence. However, temporary or even sustained remission remain ambitious aims, which are achieved in a minority of patients only
Impact of disease activity and treatment of comorbidities on the risk of myocardial infarction in rheumatoid arthritis
Background The aim was to estimate the impact of individual risk factors and
treatment with various disease-modifying antirheumatic drugs (DMARDs) on the
incidence of myocardial infarction (MI) in patients with rheumatoid arthritis
(RA). Methods We analysed data from 11,285 patients with RA, enrolled in the
prospective cohort study RABBIT, at the start of biologic (b) or conventional
synthetic (cs) DMARDs. A nested case–control study was conducted, defining
patients with MI during follow-up as cases. Cases were matched 1:1 to control
patients based on age, sex, year of enrolment and five cardiovascular (CV)
comorbidities. Generalized linear models were applied (Poisson regression with
a random component, conditional logistic regression). Results In total, 112
patients developed an MI during follow-up. At baseline, during the first 6
months of follow-up and prior to the MI, inflammation markers (erythrocyte
sedimentation rate (ESR) and C-reactive protein (CRP)) but not 28-joint-count
disease activity score (DAS28) were significantly higher in MI cases compared
to matched controls and the remaining cohort. Baseline treatment with DMARDs
was similar across all groups. During follow-up bDMARD treatment was
significantly more often discontinued or switched in MI cases. CV
comorbidities were significantly less often treated in MI cases vs. matched
controls (36 % vs. 17 %, p < 0.01). In the adjusted regression model, we found
a strong association between higher CRP and MI (OR for log-transformed CRP at
follow-up: 1.47, 95 % CI 1.00; 2.16). Furthermore, treatment with prednisone
≥10 mg/day (OR 1.93, 95 % CI 0.57; 5.85), TNF inhibitors (OR 0.91, 95 % CI
0.40; 2.10) or other bDMARDs (OR 0.85, 95 % CI 0.27; 2.72) was not associated
with higher MI risk. Conclusions CRP was associated with risk of MI. Our
results underline the importance of tight disease control taking not only
global disease activity, but also CRP as an individual marker into account. It
seems irrelevant with which class of (biologic or conventional) DMARD
effective control of disease activity is achieved. However, in some patients
the available treatment options were insufficient or insufficiently used -
regarding DMARDs to treat RA as well as regarding the treatment of CV
comorbidities
study protocol for a randomized controlled trial
Background Osteoarthritis (OA) is a heterogeneous group of conditions with
disturbed integrity of articular cartilage and changes in the underlying bone.
The pathogenesis of OA is multifactorial and not just a disease of older
people. Hydroxychloroquine (HCQ) is a disease-modifying anti-rheumatic drug
(DMARD) typically used for the treatment of various rheumatic and dermatologic
diseases. Three studies of HCQ in OA, including one abstract and one letter,
are available and use a wide variety of outcome measures in small patient
populations. Despite initial evidence for good efficacy of HCQ, there has been
no randomized, double-blind, and placebo-controlled trial in a larger patient
group. In the European League Against Rheumatism (EULAR), evidence-based
recommendations for the management of hand OA, HCQ was not included as a
therapeutic option because of the current lack of randomized clinical trials.
Methods/Design OA TREAT is an investigator-initiated, multicenter, randomized,
double-blind, placebo-controlled trial. A total of 510 subjects with
inflammatory and erosive hand OA, according to the classification criteria of
the American College of Rheumatology (ACR), with recent X-ray will be
recruited across outpatient sites, hospitals and universities in Germany.
Patients are randomized 1:1 to active treatment (HCQ 200 to 400 mg per day) or
placebo for 52 weeks. Both groups receive standard therapy (non-steroidal
anti-inflammatory drugs [NSAID], coxibs) for OA treatment, taken steadily two
weeks before enrollment and continued further afterwards. If disease activity
increases, the dose of NSAID/coxibs can be increased according to the drug
recommendation. The co-primary clinical endpoints are the changes in
Australian-Canadian OA Index (AUSCAN, German version) dimensions for pain and
hand disability at week 52. The co-primary radiographic endpoint is the
radiographic progression from baseline to week 52. A multiple endpoint test
and analysis of covariance will be used to compare changes between groups. All
analyses will be conducted on an intention-to-treat basis. Discussion The OA
TREAT trial will examine the clinical and radiological efficacy and safety of
HCQ as a treatment option for inflammatory and erosive OA over 12 months. OA
TREAT focuses on erosive hand OA in contrast to other current studies on
symptomatic hand OA, for example, HERO [Trials 14:64, 2013]
- …