Niels Tvede

Responsiveness of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and clinical and MRI measures of disease activity in a 1-year follow-up study of patients with axial spondyloarthritis treated with tumour necrosis factor α inhibitors

Objectives To investigate construct validity and responsiveness of the novel ankylosing spondylitis (AS) disease activity score (ASDAS) in patients with spondyloarthritis (SpA). Methods In a 46-week prospective longitudinal multicentre study of 60 patients with SpA (80% men, median age 40 years (range 21–62)) treated with tumour necrosis factor α (TNFα) inhibitors (infliximab, n=41; etanercept, n=13; adalimumab, n=6), the responsiveness of ASDAS, conventional clinical measures of disease activity and treatment response and the Berlin MRI sacroiliac joint (SIJ) and lumbar spine inflammation scores were compared. Results After 22 weeks, 58.3% of the patients were clinical responders (50% or 20 mm reduction in the Bath AS Disease Activity Index (BASDAI)). At baseline, clinical responders had significantly higher median (range) ASDAS than non-responders (4.15 (1.98–6.04) vs 2.99 (2.05–6.19), p=0.008). Changes in ASDAS correlated with changes in clinical measures of disease activity (including BASDAI (ρ=0.76) and C-reactive protein (CRP) (0.79)), MRI SIJ inflammation (0.46) and MRI total inflammation scores (0.34). Patients with higher BASDAI or Assessment of SpondyloArthritis International Society (ASAS) responses obtained more profound reductions in ASDAS. ASDAS had the highest responsiveness with an effect size of 2.04 and a standardised response mean of 1.45, whereas BASDAI (effect size 1.86; standardised response mean 1.36) and CRP (effect size 0.63; standardised response mean 0.70) were less responsive. Linear regression showed that a change in BASDAI of 20 mm or 50% corresponded to a change in ASDAS of 1.38 and 1.95, respectively. Conclusion ASDAS demonstrates construct validity and high responsiveness during treatment with TNFα inhibitors in patients with SpA. The proposed thresholds for disease activity and treatment response need further validation. Trial registration number NCT00133315.

ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors

Objectives To investigate the relation between ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) and treatment response and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40), angiogenesis (vascular endothelial growth factor (VEGF)), cartilage (C-terminal crosslinking telopeptide of type II collagen (CTX-II), matrix metalloproteinase-3 (MMP-3), total aggrecan, cartilage oligomeric matrix protein) and bone (C-terminal crosslinking telopeptide of type I collagen, osteocalcin) turnover in 60 patients with axial spondyloarthritis initiating tumour necrosis factor alpha (TNFα) inhibitor therapy. Methods ASDAS (CRP-based), BASDAI and biomarkers were determined before and seven times during 46 weeks of TNFα inhibitor therapy. Results Very high ASDAS were associated with high levels of inflammatory biomarkers, while high BASDAI were not related to any biomarkers. Mixed modeling demonstrated significant longitudinal associations between ASDAS and IL-6, VEGF, MMP-3 and osteocalcin and between BASDAI and CRP, IL-6 and VEGF. Major improvement in ASDAS was associated with larger percentage decreases in biomarkers of inflammation, angiogenesis, MMP-3 and increases in aggrecan and osteocalcin. BASDAI response was associated with larger decreases in CRP and IL-6. Biomarkers with moderate/high differences in responsiveness for major versus no/clinically important improvement in ASDAS were CRP, IL-6, VEGF, aggrecan and osteocalcin, and VEGF and CTX-II for BASDAI response versus non-response. Conclusion Levels and changes of 10 biomarkers in patients with axial spondyloarthritis during anti-TNFα therapy were documented. Construct validity and responsiveness of IL-6, VEGF, MMP-3, total aggrecan and osteocalcin were demonstrated. ASDAS was more associated with these biomarkers than BASDAI, and may better reflect the inflammatory disease processes. ClinicalTrials.gov identifier NCT00133315.

Immune dysfunction in multiple myeloma. Reduced natural killer cell activity and increased levels of soluble interleukin-2 receptors.

Multiple myeloma (MM) is characterized by an increased susceptibility to infections and to other malignancies. Selected related immune functions were studied. Spontaneous and interleukin‐2‐stimulated natural killer (NK) cell activities were normal in 19 patients with MM compared with 62 controls. In contrast, interferon‐stimulated NK cells had a significantly lower increase in activity in MM than in controls. The normal improvement in lytic NK cell activity after addition of indomethacin to the mononuclear cell cultures (to inhibit prostaglandin‐mediated suppression) was not observed in cultures from MM patients. As reported for other lymphoproliferative disorders, the levels of soluble interleukin‐2 receptors in serum were significantly higher in MM (600 U/ml median value) compared with controls (317 U/ml median value), P < 0.0001, and the concentration of interleukin‐2 receptors was significantly correlated with the concentration of monoclonal immunoglobulin in serum. Blood monocyte chemotactic responsiveness was significantly lower in MM patients with both zymosan‐activated serum and f‐Met‐Leu‐Phe as cytotaxins, suggesting reduced ability to accumulate at inflammatory foci. In contrast, release of reactive oxygen radicals, believed to be associated with the killing ability of monocytes, was normal after in vitro stimulation.

Cardiac Abnormalities in Adult Patients With Polymyositis or Dermatomyositis as Assessed by Noninvasive Modalities

Cardiac events are a major cause of death in patients with idiopathic inflammatory myopathies. The study objective was in a controlled setting to describe cardiac abnormalities by noninvasive methods in a cohort of patients with polymyositis (PM) or dermatomyositis (DM) and to identify predictors for cardiac dysfunction.

Traditional Cardiovascular Risk Factors and Coronary Artery Calcification in Adults With Polymyositis and Dermatomyositis: A Danish Multicenter Study

To determine the occurrence of traditional cardiovascular (CV) risk factors and coronary artery calcification (CAC) in adults with polymyositis (PM) or dermatomyositis (DM) compared to healthy controls and to assess the association between CV risk factors, PM/DM, and CAC score.

Interleukin‐2 stimulation of blood mononuclear cells from patients with inflammatory bowel disease

The functional capacity of biologically active, high‐affinity interleukin‐2 receptors (IL‐2R) was studied by means of interleukin‐2 (IL‐2) stimulation of blood mononuclear cells (BMC) from 22 patients with inflammatory bowel disease (IBD) and 24 controls. The spontaneous, as well as the IL‐2‐induced, proliferative responses were significantly decreased in patients with active IBD, whereas the expressions of biologically inactive, low‐affinity IL‐2R (i.e. TAC antigen or CD25) were significantly increased in the same BMC cultures. In contrast, no significant differences were seen between patients and controls when BMC were stimulated with a nonspecific mitogen (phytohemagglutinin). The results suggest that a downregulation of IL‐2 responsiveness may contribute to decreased BMC proliferation in vitro in active IBD.

THU0239 Cardiovascular risk factors in adults with polymyositis and dermatomyositis – a multicenter study

Background CVD is a major cause of death among patients with PM or DM. Still, data on prevalence and types of cardiovascular involvement and corresponding risk factors are limited and no systematic studies of subclinical coronary atherosclerosis have been performed in adults with PM or DM. Objectives Our purpose was to determine the distribution of traditional CVD risk factors and to assess CAC in adults with PM or DM. Methods In a cross-sectional, observational study of 76 prevalent patients with PM (n=51) or DM (n=25) clinical and immunological variables and the following traditional CVD risk factors were assessed: age, sex, CVD family history, smoking (current, former or never), body mass index (BMI), blood pressure (BP), total cholesterol (TC), LDL cholesterol (LDL-C), and mean blood glucose (mBG) calculated from HbA1c. Further, CAC were quantified by means of non-contrast enhanced cardiac CT scan and reported as a CAC score with the following ranges; no calcifications (CAC score =0 U); low CAC score (1-399 U); or high CAC score (≥400 U). High CAC score is consistent with severe coronary atherosclerosis. Results The mean age of the patients was 60 years (range 33-85) and 65% were women. A CVD family history was reported in 20% of the patients and 25% were current smokers; 28% were former smokers. Overweight (25≤BMI<30) was observed in 23 (30%) whereas 33 (43%) were obese (BMI>30). High systolic blood pressure (>140 mmHg) was observed in 35 (47%); 54 (74%) had high TC (>4.95 mmol/L), and 41 (59%) high LDL-C as well. mBG was increased (>6.95 mmol/L) in 16 (21%) patients. A CAC score >0 was noticed in 46 (61%) of whom 15 (20%) had a high score. Conclusions We report that a significant proportion of patients with PM or DM have a high burden of CVD risk factors and evidence of clinically significant calcium deposits in their coronary arteries. Several chronic inflammatory rheumatic diseases are associated with accelerated atherosclerosis, which may also apply to PM/DM. To what extent the increased CAC score is related to disease severity, the burden of CVD risk factors, prednisolone treatment or combinations hereof cannot be decided from this cross-sectional study. However, these preliminary data indicate that a prospective assessment of the CV system is warranted in PM and DM. Disclosure of Interest None Declared