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Objectives To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. Methods An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. Results In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. Conclusion This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.

Objectives To define chronic ultrasound lesions of the axillary artery (AA) in long-standing giant cell arteritis (GCA) and to evaluate the reliability of the new ultrasound definition in a web-based exercise. Methods A structured Delphi, involving an expert panel of the Large Vessel Vasculitis subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group was carried out. The reliability of the new definition was tested in a 2-round web-based exercise involving 23 experts and using 50 still images each from AA of long-standing and acute GCA patients, as well as 50 images from healthy individuals. Results The final OMERACT ultrasound definition of chronic changes was based on measurement and appearance of the intima-media complex. The overall reliability of the new definition for chronic ultrasound changes in longstanding GCA of the AA was good to excellent with Light's kappa values of 0.79-0.80 for inter-reader reliability and mean Light's-kappa of 0.88 for intra-reader reliability. The mean inter-rater and intra-rater agreements were 86-87% and 92%, respectively. Good reliabilities were observed comparing the vessels with longstanding versus acute GCA with a mean agreement and kappa values of 81% and 0.63, respectively. Conclusion The new OMERACT ultrasound definition for chronic vasculitis of the AA in GCA revealed a good to excellent inter- and intra-reader reliability in a web-based exercise of experts.

Objectives To investigate whether GCA is associated with increased all-cause and cause-specific mortality. Methods A nationwide, population-based cohort study in Denmark using medical and administrative registries. GCA cases were defined as patients aged ≥50 years from 1996–2018 with a first-time discharge diagnosis of GCA and ≥3 prescriptions for prednisolone within 6 months following diagnosis. Each GCA patient was matched based on age, sex and calendar time to 10 persons without a history of GCA. Index date was the date for the third prednisolone prescription. We used a pseudo-observation approach to calculate all-cause and cause-specific mortality, adjusted risk differences (RDs) and relative risks (RRs). Results We included 9908 GCA patients and 98 204 persons from the general population. The median time for GCA patients to redeem the third prednisolone prescription was 74 days [interquartile range (IQR: 49–106)]. Among GCA patients, the overall mortality was 6.4% (95% CI: 5.9, 6.9) 1 year after index date and 45% (95% CI: 44, 47) after 10 years. Compared with the reference cohort, adjusted RDs and RRs of deaths in the GCA cohort were 2.2% (95% CI: 1.7, 2.7) and 1.49 (95% CI: 1.36, 1.64) after 1 year, and 2.1% (95% CI: 1.0, 3.3) and 1.03 (95% CI: 1.00, 1.05) 10 years after index date. GCA patients had a higher risk of death due to infectious, endocrine, cardiovascular and gastrointestinal diseases. Conclusions GCA is associated with increased all-cause mortality, particularly within the first year following the diagnosis. Cause-specific mortality indicates that mortality in GCA may in part be due to glucocorticoid-related complications.

Purpose To investigate the positive predictive value (PPV) of the giant cell arteritis (GCA) diagnosis in the Danish National Patient Registry (DNPR). Patients and methods A total of 293 patients aged ≥50 years with a first-time diagnosis of GCA in the DNPR between January 2012 and December 2017 were included. Patients were sampled from two secondary and one tertiary care hospitals in the Central Region Denmark. Two independent investigators (PH & PT) reviewed all medical files, including medical records, treatment, biochemistry, histopathology and imaging, and either confirmed or dismissed the diagnosis of GCA. In case of disagreement, a consensus agreement was reached. Sub-analyses including number of redeemed prescriptions performed temporal artery biopsies (TABs), and number of GCA-related hospital contacts were performed. Results We confirmed the diagnosis of GCA in 183/293 patients resulting in a PPV of 62% (95% CI: 57-68). In patients with ≥3 redeemed prescriptions of glucocorticoids (GCs), we confirmed the diagnosis in 166/214 resulting in a PPV of 78% (95% CI: 71-83). In patients with ≥3 redeemed prescriptions of GCs and ≥3 GCA-related hospital contacts, we confirmed the diagnosis in 88/95 resulting in a PPV of 93% (95% CI: 85-96); however, this only included 88/183 confirmed GCA patients. Conclusion This is the first study to validate the diagnostic code of GCA in the DNPR. The overall PPV of GCA in the DNPR was 62%. Requiring redeemed prescriptions of GCs and/or GCA-related hospital contacts increase the PPV, but also excludes a significant number of GCA patients.

ObjectivesTo develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties.MethodsThe OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima–media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24.ResultsAgreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72–0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from −1.19 to −2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff0.37–0.48).ConclusionWe developed a provisional OGUS for potential use in clinical trials.

Objectives: To investigate the risk of ocular manifestations leading to hospital contacts among patients with giant cell arteritis (GCA). Methods: A Danish, nationwide, register-based cohort study including 14,574 GCA patients diagnosed 1996–2018 and 145,740 general population referents, matched on sex and date of birth. Cumulative incidence proportions (CIPs) and relative risks (RRs) of ocular manifestations with 95% confidence intervals (CIs) were calculated using a pseudo-observation approach. Results: A total of 1026/14,574 (7.0%) GCA patients were registered with ocular manifestations within ±1 year of the diagnosis; 392/1026 (38%) being before and 634/1026 (62%) after the GCA diagnosis, and 744/1026 (73%) were registered within ±1 month of the diagnosis. The diagnoses were 336/1026 (33%) retinal vascular occlusions, 300/1026 (29%) disorders of the optic nerve, 177/1026 (17%) visual impairment, 90/1026 (9%) diplopia, and 123/1026 (12%) amaurosis fugax. The CIP for ocular manifestations among GCA patients after 3, 6, and 12 months following the diagnosis were 4.0% (95% CI: 3.6–4.3), 4.2% (95% CI: 3.9–4.6), and 4.6% (95% CI: 4.2–4.9). The 1-year RR of ocular manifestations among GCA patients was 28.0 (95% CI: 24.0–32.7), with age above 70 years, male sex, and a positive temporal artery biopsy being risk factors. Treatment with low-dose aspirin was not associated with a reduced 1-year RR of incident ocular manifestations. Conclusions: In GCA, most cases of ocular manifestations leading to hospital contacts occur close to the time of diagnosis, with over one-third of cases occurring before the diagnosis, emphasizing the need for early recognition and treatment.

Objectives The diagnostic accuracy of axillary artery US in the diagnosis of large-vessel (LV)-GCA using 18F-fluorodeoxyglucose (FDG) PET/CT as reference standard was prospectively evaluated in GCA-suspected patients. As an exploratory analysis, the diagnostic accuracy of cranial artery FDG PET/CT was evaluated. Methods Briefly, the inclusion criteria were age ≥50 years, raised inflammatory markers and potential GCA symptoms. Patients in immunosuppressive therapy or with a previous diagnosis of GCA or PMR were excluded. Examinations were performed pre-treatment. LV-GCA reference diagnosis was a clinical diagnosis of GCA and PET-proven LV inflammation. GCA patients fulfilling ACR criteria were considered as cranial-GCA (c-GCA). Patients without GCA were considered controls. Receiver operating characteristic curve analysis of the US-measured axillary intima-media thickness was performed. FDG uptake in temporal, maxillary and vertebral arteries was also assessed. Results Forty-six patients were diagnosed with LV-GCA, 10 with isolated c-GCA, and in 34 patients GCA was dismissed. Axillary US yielded a sensitivity of 76% and a specificity of 100% for LV-GCA. An axillary intima-media thickness cut-off of 1.0 mm yielded a sensitivity of 74% and a specificity of 92%. Adding LV US to temporal assessment increased sensitivity from 71% to 97% (all GCA patients). Cranial artery PET showed a diagnostic sensitivity of 78% and specificity of 100% for c-GCA. Conclusion Axillary artery US shows high accuracy for the LV-GCA diagnosis. Building upon the recent EULAR recommendations, we propose a diagnostic algorithm with US as the first-line confirmatory test, not only in c-GCA-suspected patients, but in all patients suspected of GCA.

Objective To assess the risk of aortic aneurysms (AA), aortic dissections (AD) and peripheral arterial disease (PAD) among patients with GCA. Methods In this nationwide, population-based cohort study using Danish national health registries, we identified all incident GCA patients ≥50 years between 1996 and 2018 who redeemed three or more prescriptions for prednisolone. Index date was the date of redeeming the third prednisolone prescription. Case definition robustness was checked through sensitivity analysis. We included general population referents matched 1:10 by age, sex and calendar time. Using a pseudo-observation approach, we calculated 5-, 10- and 15-year cumulative incidence proportions (CIP) and relative risks (RR) of AA, AD and PAD with death as a competing risk. Results We included 9908 GCA patients and 98 204 referents. The 15-year CIP of thoracic AA, abdominal AA, AD and PAD in the GCA cohort were 1.9% (95% CI 1.5, 2.2), 1.8% (1.4–2.2), 1.0% (0.7–1.2) and 4.8% (4.2–5.3). Compared with the referents, the 15-year RR were 11.2 (7.41–16.9) for thoracic AA, 6.86 (4.13–11.4) for AD, 1.04 (0.83–1.32) for abdominal AA and 1.53 (1.35–1.74) for PAD. Among GCA patients, female sex, age below 70 years and positive temporal artery findings were risk factors for developing thoracic AA. The median time to thoracic AA was 7.5 years (interquartile range 4.4–11.2) with a number needed to be screened of 250 (167–333), 91 (71–111) and 53 (45–67) after 5, 10 and 15 years. Conclusion Patients with GCA have a markedly increased risk of developing thoracic AA and AD, but no increased risk of abdominal AA.

Aim The study investigated the development over time of the incidence, diagnostic imaging, and treatment of giant cell arteritis (GCA). Method This nationwide, population-based cohort study was conducted in Denmark using medical and administrative registries. Incident GCA cases from 1996–2018 were defined as patients aged ≥50 years registered with a first-time GCA diagnosis and ≥3 prescriptions for glucocorticoids (GCs) within 6 months after diagnosis. We determined incidence rates of GCA, the proportion of patients still receiving GCs >2 years after diagnosis, the proportion of patients receiving temporal artery biopsies (TAB) and diagnostic imaging including ultrasound, positron emission tomography, magnetic resonance, and/or computed tomography angiography at the time of diagnosis. Results We identified 9908 incident GCA cases. The incidence rates of GCA remained stable at 19–25 per 100,000 people aged >50 years from 1996–2018. The proportion of GCA patients receiving a TAB remained constant until 2016, after which it promptly declined from 70–80% to 29–39%. In contrast, the proportion of patients receiving diagnostic imaging increased from 2% to 66% from 2000–2018. The proportion of GCA patients remaining in GC treatment has steadily decreased from 1996–2016, but remains high at 64%, 40%, and 34% after 2, 5, and 10 years following the diagnosis, respectively. The cumulative GC dose has remained relatively stable. Conclusion Incidence rates of GCA have remained stable since 1996 despite increasing use of diagnostic imaging. There is a clear discrepancy between current international GCA treatment guidelines and the clinical practice up to 2018.

Background: Giant cell arteritis (GCA) is the most common primary systemic vasculitis predominantly affecting large and medium sized vessels. In rare cases, the vasculitis can affect the vessels of the brain. Results: We describe four cases of GCA with involvement of the cerebral vessels causing stroke. These cases were unresponsive to aggressive immunosuppression and we opted to treat with endovascular balloon dilatation of the stenotic areas. The procedure was safe. The four patients were treated in nine sessions and a total of 16 vessels were treated. We observed two dissections with no clinical influence on the patients. Discussion: In patients with stroke due to progressive GCA that is non-responsive to immunosuppression, endovascular therapy is feasible.

Objectives This study aimed to characterize the association between HLA alleles and ANCA-associated vasculitis (AAV) in a genetically homogeneous population, and to analyse the contribution of specific HLA molecule amino acid sequences to the risk of AAV. Methods We included 187 Danish patients with AAV and 1070 healthy controls. All were HLA typed at two-field resolution. The association of HLA alleles to PR3- or MPO-AAV was analysed. The contribution of the dominant molecular motifs of the HLA-DPB1 molecule to the risk of AAV was investigated by association studies that included specific amino acid sequences of the hypervariable regions in exon 2. Results Ninety-four percent of patients with PR3-AAV were carriers of HLA-DPB1*04:01 while all patients with PR3-AAV were carriers of an HLA-DPB1*04 allele, and 85% were homozygous. This was significantly more than in the control group (P < 0.0001). The association was even stronger when HLA-DPB1*04:02 and -DPB1*23:01 were included. HLA-DPB1*04:01, -DPB1*04:02 and -DPB1*23:01 share amino acids in positions 8–9, 69, 76 and 84–87 within the hypervariable regions, but only positions 69 and 84–87 contributed significantly to the disease risk. HLA-DRB1*15 was associated with an increased risk of developing PR3-AAV, while HLA-DRB1*04, -DRB1*07 and -DQB1*03 were associated with a reduced risk of kidney involvement in PR3-AAV. MPO-AAV was only weakly associated with HLA class I alleles. Conclusion PR3-AAV is strongly associated with the HLA-DPB1 alleles HLA-DPB1*04:01, -DPB1*04:02 and -DPB1*23:01, which share amino acid sequences crucial for the peptide-binding groove.

OBJECTIVES: To examine whether MRI assessed inflammation and damage in the wrist of patients with early rheumatoid arthritis (RA) are associated with patient-reported outcomes (PROs).METHODS: Wrist and hand MRIs of 210 patients with early RA from two investigator-initiated, randomised controlled studies (CIMESTRA/OPERA) were assessed according to the Outcome Measures in Rheumatology RA MRI score (RAMRIS) for synovitis, tenosynovitis, osteitis, bone erosions and joint space narrowing (JSN) at baseline, 1 and 5 years follow-up. These features, and changes therein, were assessed for associations with health assessment questionnaires (HAQ), patient global visual analogue scales (VAS-PtGlobal) and VAS-pain using Spearman's correlations, generalised estimating equations and univariate/multivariable linear regression analyses. MRI features were further tested for trends against specific hand-related HAQ items using Jonckheere trend tests.RESULTS: MRI inflammation, but not damage, showed statistically significant associations with HAQ, VAS-PtGlobal and VAS-pain for status and change scores, independently of C reactive protein and swollen joint count. MRI-assessed synovitis was most consistently associated with PROs, particularly VAS-PtGlobal and VAS-pain. MRI-assessed synovitis and tenosynovitis mean scores were positively associated with patient-reported difficulty to cut meat and open a milk carton (pCONCLUSIONS: MRI-assessed inflammation, but not damage, in early RA wrists is associated with patient-reported physical impairment, global assessment of disease activity and pain and influences the physical function in the hand.TRIAL REGISTRATION NUMBER: NCT00660647.

Background: Giant cell arteritis (GCA) is the most frequent systemic vasculitis[1]. The diagnosis is clinical and based on symptoms, histopathology, biochemistry and imaging. In Denmark, diagnostic codes for all in- and out-patient hospital diagnoses are registered in the Danish National Patient Registry (DNPR) [2]. Since GCA can be difficult to diagnose and treatment is initiated on suspicion, we hypothesized that the overall positive predictive value (PPV) of the GCA diagnosis code in the DNPR is low. High data quality is important for future epidemiological research in GCA. Objectives: To establish PPV of the diagnostic code of GCA in the DNPR. Furthermore, to identify characteristics associated with a high PPV of the diagnostic code. Methods: 293 patients aged ≥50 years with a first-time register-based GCA diagnosis were included from the DNPR in the period January 2012-January 2018. Patients were sampled based on the ICD-10 codes (M31.5 and M31.6) from two regional hospitals and one university hospital in the Central Region of Denmark. As gold standard we used the medical records (including biochemistry, histopathology and imaging results) and categorized each patient as true GCA or non-GCA. Based on the data from the prescription database, patients were divided into four categories depending on the number of prednisolone prescriptions they received. Two independent investigators (PH and PT) reviewed the medical records. In case of disagreement the final diagnosis was reached by consensus or by expert opinion (ITH). To test how the PPV varied, sub-analyses were performed for number of prescriptions, specific symptoms, temporal artery biopsies (TAB), number of visits and number of prescriptions.. Results: We confirmed 183 of 293 diagnoses resulting in a PPV of 62.8% (95% CI: 57.1-68.2). In patients having at least three admissions, 95 of 110 diagnoses were confirmed (PPV: 86.4%; 95% CI: 78.5-91.7). We confirmed 82 of 95 patients with at least three visits and a TAB. This resulted in a PPV of 86.3% (95% CI: 77.7-91.9). The highest PPV was observed in patients with at least 3 visits and ≥3 prescriptions of prednisolone. In this sub-analysis we confirmed 88 of 95 diagnoses resulting in a PPV of 92.6% (95% CI: 85.2-96.5). Conclusion: This is the first study to validate the diagnostic code of GCA in the DNPR. The overall PPV of a first-time diagnosis of GCA in the DNPR is low. The probability of identifying true cases of GCA increases substantially when diagnostic codes are combined with 3 visits and ≥3 prescriptions of prednisolone. References [1] Gonzalez-Gay, M.A., et al., Epidemiology of giant cell arteritis and polymyalgia rheumatica. Arthritis Rheum, 2009. 61(10): p. 1454-61. [2] Schmidt, M., et al., The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol, 2015. 7: p. 449-90. Acknowledgement: A special thanks to Mette Norgaard for her help. Disclosure of Interests: None declared

Background Although older studies argue that fluorine-18-fluorodeoxyglucose (FDG) positron emissions tomography (PET)/CT cannot demonstrate inflammation in cranial arteries the spatial resolution of modern PET systems have greatly improved allowing for more precise diagnostics of small structures. FDG PET/CT is widely used to diagnose large-vessel (LV) giant cell arteritis (GCA). Recognising FDG uptake in cranial arteries potentially adds to FDG PET/CTs diagnostic accuracy for GCA. Objectives To evaluate the diagnostic accuracy of conventional FDG PET/CT of the cranial arteries in GCA. Methods In a cohort of consecutively included glucocorticoid-naive patients suspected of new-onset GCA, patients full-filling 1990 ACR criteria for GCA were identified. Conventional FDG PET/CT and clinical assessment was performed before treatment. Controls were age- and sex-matched patients with malignant melanoma (MM) who had a metastatic-disease-free follow-up FDG PET/CT≥6 months after MM resection. All PET images were evenly cropped to include only head and neck. Images were randomly assessed by 2 nuclear medicine physicians (10 years experience) blinded to clinical symptoms and findings. Training included review of 5 GCA-PET examinations (not part of cohort). Temporal (TA), maxillary (MA) and vertebral (VA) arteries were visually scored bilaterally. Arterial FDG uptake above surrounding tissue was considered indicative of inflammation and graded low or high. If disagreement between readers occurred, final score was settled by an expert nuclear medicine physician. Student t test was used for quantitative data. Inter-reader agreement was evaluated by Cohens weighted kappa (disagreement on diagnosis weighted 0, disagreement on FDG uptake intensity weighted 0.2). Results A total of 44 patients and 44 controls were identified. In both case and control group, the mean age was 69 years (p=0.45) and 25/44 were women. Large-vessel involvement was seen in 39/42 patients, and 35/42 were temporal artery biopsy positive. GCA patients’ median global assessment of disease activity was 8 (IQR: 5–10) and median CRP was 70 (95% CI: 58; 85) mg/L. Considering only FDG uptake in TA and/or MA, diagnostic sensitivity and specificity was 66% (95% CI: 50%–80%) and 100% (95% CI: 92%–100%). Including VA, sensitivity increased to 86% (95% CI: 73%–95%) and specificity remained high, 98% (95% CI: 88% to 100%). Cohens weighted kappa was 0.82 (agreement 93%, p=0.000) in a per segment analysis and kappa was 0.84 (agreement 92%, p=0.000) in diagnosis. Conclusions Inter-reader agreement on FDG uptake in cranial arteries is almost perfect, and cranial arteritis in glucocorticoid-naive GCA patients can be readily and accurately diagnosed by conventional FDG PET/CT. The high diagnostic specificity suggests that TAB can be avoided in patients with FDG uptake in cranial arteries. Moreover, FDG PET/CT performed in patients with suspected vasculitis should always include head and neck. Disclosure of Interest None declared

PURPOSE: To evaluate the in-treatment diagnostic accuracy of FDG PET/CT in large-vessel giant cell arteritis (LV-GCA) by serial scans before and after a short course of high-dose glucocorticoid treatment.METHODS: Twenty-four glucocorticoid-naïve patients with new-onset PET/CT verified LV-GCA (pre-treatment baseline PET) were prospectively included. Excluded were patients with a previous history of GCA or polymyalgia rheumatica, LV-GCA-mimicking conditions and patients on immunosuppressive therapy. All patients were treated with 60 mg of oral prednisolone daily and assigned for in-treatment FDG PET/CT after either 3 (PET3) or 10 days (PET10). Two experienced nuclear medicine physicians, blinded to patients' clinical data, reviewed the FDG PET/CT images. A visual semi-quantitative approach was used. Segmental and homogenous FDG uptake in the wall of the aorta and/or supra-aortic branches with higher uptake intensity than liver was considered consistent with vasculitis. Inter-reader reliability was evaluated.RESULTS: Although glucocorticoid treatment attenuated FDG uptake in large vessels, LV-GCA was accurately diagnosed in 10/10 patients after 3 days of treatment, but only in 5/14 patients after 10 days of treatment (p CONCLUSIONS: Within 3 days of high-dose glucocorticoid treatment, FDG PET/CT can diagnose LV-GCA with high sensitivity. This window of opportunity ensures that prompt glucocorticoid treatment can be initiated to avoid debilitating GCA complications with a limited effect on diagnostic accuracy. After 10 days of treatment, FDG PET/CT sensitivity decreases significantly.

Background The temporal artery biopsy (TAB) remains the gold standard in the diagnosis of giant cell arteritis (GCA) and is part of the ACR Classification criteria for GCA. However, TABs are false-negative in 10–60% of cases [1]. Cellular studies have shown that activated immune cells upregulate the acetylcholinesterase (AChE) expression [2]. If AChE is upregulated in the active GCA vessel wall, it may potentially improve the TAB as a diagnostic tool. Objectives To investigate the in-situ expression of acetylcholinesterase (AChE) in the vessel wall of patients with biopsy-positive GCA and compare to non-GCA patients. Methods In this histological case-control study, TABs from a total of 24 TAB-positive GCA and 44 TAB-negative non-GCA patients (21 patients with a final diagnosis of PMR, 23 patients with other diagnosis) were retrospectively selected from TABs performed between January 2012 and December 2015. A total of 295 TABs were assed for inclusion. Only positive TABs showing clear transmural inflammation were included. Patients treated with >7 days of prednisolone prior to the TAB were excluded. Clinical data were obtained from electronic patient records to confirm or dismiss clinical diagnosis. TAB-HE-stains were reviewed by a pathologist with expertise in vasculitis. Immunohistochemical methods were used to determine the AChE expression. The histological inflammation and AChE expression were assessed and graded on 0–1-2 scale, blinded to histological and clinical data. Solitary AChE staining of the media was not included in the assessment. Results 24 positive and 44 negative TABs, with corresponding clinical positive and negative GCA diagnosis, were included in this study. We found that 10/24 positive TABs showed high AChE expression (grade 2) and 14/24 showed moderate AChE expression (grade 1). No AChE expression was observed outside the media in negative TABs from non-GCA patients (i.e. grade 0). The AChE expression was in 79% agreement with the degree of histological inflammation with a kappa value of 0.58. Prednisolone treatment for up to 7 days did not suppress the AChE expression. Neither the AChE expression, nor the histological inflammation showed correlation to any clinical or biochemical findings. Conclusions Our study shows that high to moderate AChE expression was observed in all 24 biopsies from TAB-positive GCA patients and that the AChE expression was in good agreement with the histological inflammation. No non-specific AChE expression was observed outside the media in any of the 44 TABs from TAB-negative non-GCA patients. This indicates that AChE could play a significant role in the inflammatory process in GCA and may be a potential biomarker in inflammatory diseases such as GCA. References Luqmani, R., et al., The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study. Health Technol Assess, 2016. 20(90): p. 1–238. Fujii, T., et al., Expression of acetylcholine in lymphocytes and modulation of an independent lymphocytic cholinergic activity by immunological stimulation. Biogenic Amines, 2003. 17(4–6): p. 373–386. Disclosure of Interest None declared

Background Fluorine-18-fluorodeoxyglucose (FDG) PET/CT is increasingly used to diagnose large vessel GCA (LV-GCA) due to its excellent diagnostic accuracy[1]. However, PET/CT is not always readily available, which may compel the clinician to 1) either delay steroid treatment at the risk of GCA related complications, or 2) initiate treatment at the expense of diagnostic sensitivity of the FDG PET/CT study. Objectives To evaluate if FDG PET/CT can accurately diagnose LV-GCA after 3 or 10 days of high-dose steroid treatment. Methods Twenty-four treatment-naive patients (16 women) with a mean age of 69 (range 57–84) years with FDG PET/CT (PET0) proven LV-GCA repeated FDG PET/CT after either 3 (PET3, n=10) or 10 days (PET10, n=14) of treatment with oral prednisolone 60 mg daily. Prior to treatment, clinical examination and laboratory tests were performed to confirm GCA and exclude differential diagnoses. A temporal artery biopsy (TAB) was performed in all patients. Two experienced nuclear medicine physicians blinded to clinical data reviewed the FDG PET/CT images. LV-GCA was suspected if increased FDG uptake in the wall of the aorta and/or supra-aortic branches was observed. A semi-quantitative approach was applied (a.m. Meller) in which FDG uptake was graded on a 5-point scale (0; no uptake, 1; ≤ blood pool, 2; > blood pool, ≤ liver, 3; ≥ liver, 4; ≥2xliver). A score ≥3 was considered consistent with vasculitis[2]. Vascular composite scores (CS) was calculated summarizing grades from assessed vascular regions; Aortic: Aorta ascendens, aorta descendens and aortic arch; aorticbranches: Vertebral, carotic and subclavian/axillary artery. Results Mean CRP and ESR were 72 (95% CI: 55; 94) mg/l and 81 (95% CI: 72; 90) mm/h, respectively. ACR criteria for GCA was fulfilled by 18/24 patients and 17/21 had a positive TAB. Mean number of prednisolone doses before the post-treatment FDG PET/CT were 3.1 (SD 0.3) (PET3) and 10.3 (SD 0.7) (PET10). Vascular CS in aorta did not decrease at PET3 (9 (IQR 9–9) vs. 9 (IQR 6–9)) whereas a significant decrease was observed in aortic branches at PET3 (6.5 (IQR 6–8) vs 5.5 (IQR 5–7), p At day 10, VAS global was significantly higher in patients with positive PET10 compared to patients with negative PET10 (5.2 (95% CI 3.6; 7.0) vs. 2.7 (95% CI 1.2; 4.2), p Interrater reliability of visual FDG-uptake-grading was substantial (agreement 90%, Cohens weighted kappa 0.67). Conclusions In LV-GCA, high-dose steroid treatment for three or ten days differentially attenuates the regional uptake of FDG but diagnostic accuracy remains within the first three days. References Puppo et al. BioMed research international 2014. Stellingwerff MD et al. Medicine 2015. Acknowledgements Assesment of PET scans by Stine Kramer and Tronds Bogsrud is mostly appreciated. Disclosure of Interest None declared

OBJECTIVE: The long-term cancer risk for patients treated for granulomatosis with polyangiitis (GPA) is not well characterized. We assessed the risk of early and late-occurring cancers among 293 patients diagnosed with GPA from 1973 to 1999 and followed throughout 2010.METHODS: Cancer incidence in the cohort was determined by linkage with the Danish Cancer Registry and compared with that in the general population by calculation of standardized incidence ratios (SIRs).RESULTS: The median duration of follow-up was 9.7 years (range 0-36). Seventy-three cancers occurred, of which 30 were non-melanoma skin cancers (NMSCs) and 11 were bladder carcinomas. A high occurrence of NMSC was observed from the second year of follow-up onwards, with a SIR of 7.0 (95% CI 2.3, 16) for cases diagnosed ≥20 years after GPA. The incidence of bladder cancer increased after 5-9, 10-14 and 15-19 years of follow-up, with SIR estimates for these latency periods of 5.3 (95% CI 1.1, 15), 14.4 (95% CI 5.3, 31) and 10.5 (95% CI 1.2, 38), respectively. The incidence of myeloid leukaemia was significantly increased during years 5-9 [SIR 23.9 (95% CI 2.7, 86)]. Increased incidence of NMSC, bladder cancer and myeloid leukaemia was observed among patients exposed to cumulative CYC doses >36 g, while the only malignancy type observed in excess among those treated with lower CYC doses was NMSC. The cancer risk among CYC-naive patients was not significantly increased.CONCLUSION: GPA patients experience a greater than expected number of specific malignancies following conventional therapies. Our analyses demonstrate a substantially increased risk of very late-occurring NMSC and bladder cancer in this patient group.

OBJECTIVES: To investigate whether a treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid injections suppresses MRI inflammation and halts structural damage progression in patients with early rheumatoid arthritis (ERA), and whether adalimumab provides an additional effect.METHODS: In a double-blind, placebo-controlled trial, 85 disease-modifying antirheumatic drug-naïve patients with ERA were randomised to receive methotrexate, intra-articular glucocorticosteroid injections and placebo/adalimumab (43/42). Contrast-enhanced MRI of the right hand was performed at months 0, 6 and 12. Synovitis, osteitis, tenosynovitis, MRI bone erosion and joint space narrowing (JSN) were scored with validated methods. Dynamic contrast-enhanced MRI (DCE-MRI) was carried out in 14 patients.RESULTS: Synovitis, osteitis and tenosynovitis scores decreased highly significantly (pCONCLUSIONS: A treat-to-target strategy with methotrexate and intra-articular glucocorticosteroid in patients with ERA effectively decreased synovitis, osteitis and tenosynovitis and halted structural damage progression as judged by MRI. The findings suggest that addition of adalimumab is associated with further suppression of osteitis and tenosynovitis.

OBJECTIVES: An investigator-initiated, double-blinded, placebo-controlled, treat-to-target protocol (Clinical Trials:NCT00660647) studied whether adalimumab added to methotrexate and intra-articular triamcinolone as first-line treatment in early rheumatoid arthritis (ERA) increased the frequency of low disease activity (DAS28CRPMETHODS: In 14 Danish hospital-based clinics, 180 disease-modifying anti-rheumatic drugs (DMARD)-naïve ERA patients (RESULTS: Baseline characteristics were similar between groups. In the adalimumab group/placebo group the 12-month cumulative triamcinolone doses were 5.4/7.0 ml (p=0.08). Triple therapy was applied in 18/27 patients (p=0.17). At 12 months, DAS28CRPCONCLUSIONS: Adalimumab added to methotrexate and intra-articular triamcinolone as first-line treatment did not increase the proportion of patients who reached the DAS28CRP

Objective.To study the association between polymorphisms in the mannose-binding lectin gene (MBL2)and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA).Methods.Patients with early RA (n = 158) not previously treated with disease modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion forMBL2pooled structural genotypes (O/O, A/O, A/A), regulatoryMBL2promoter polymorphism in position −221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score).Results.Eight patients were homozygousMBL2defective (O/O), 101 belonged to an intermediate group, and 49 wereMBL2high producers (YA/YA). Anti-CCP was present in 93 patients (59%). High scores of disease activity, C-reactive protein-based DAS28 (p = 0.02), and physical disability by HAQ (p = 0.01) were associated with highMBL2expression genotypes in a gene-dose dependent way, but only in anti-CCP-positive patients. At this early stage of the disease there was no association with erosion score from radiographs.Conclusion.The results point to a synovitis-enhancing effect of MBL in anti-CCP-positive RA, whereas such an effect was not demonstrated for joint erosions.

The term anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) covers a group of rare diseases with inflammation in the small vessels and associated with the presence of ANCA. The patients can present with signs and symptoms from almost all organs. In primary care as well as in hospitals AAV is important to acknowledge as differential diagnosis to cancer and infectious diseases, because low morbidity and mortality related to AAV is dependent on early diagnosis and timely treatment. Patients suspected of AAV should be finally diagnosed and treated at specialized centres.

The incidence and case fatality rates of meningococcal disease were assessed in the county of Northern Jutland, Denmark, during the 16-year period from 1980 to 1995. A total of 320 patients were identified from the Meningococcal Research Database, which comprises information from the following sources: (i) the Department of Public Health, to whom notification of meningococcal disease is obligatory; (ii) the Regional Hospital Discharge Registry; and (iii) the register of the regional department of clinical microbiology. In order to assess prognostic indicators assessable at admission, information was collected for each patient from hospital records regarding contacts, symptoms and signs on arrival, laboratory data, and course of disease. The mean incidence was 4.3 cases per 100000 persons per year (range, 2.7-7.7). The incidence increased slightly during the period studied. Overall, the case fatality rate was 9.7%, with a significant rise occurring during the period (P=0.016) and a peak occurring in 1992. Advanced age (or = 50 years), seizures, impaired consciousness, and skin bleeding on arrival at hospital were predictors of death.

Objective : To assess the effect of pre-hospital antibiotic treatment given by general practitioners to patients with meningococcal disease. Design : A 16-year population-based historical follow-up study based on referral letters and hospital records in the County of North Jutland, Denmark. Subjects : 320 patients with meningococcal disease, of whom 302 were examined by a general practitioner before admission to hospital. Main outcome measures : Death. Results : 44 patients (14.6%) were given antibiotic treatment by the referring general practitioner. Nine of these (20.5%) died, compared with 16 (6.2%) patients who did not receive pre-hospital antibiotic treatment. The presence of skin bleeding, petechiae, and impaired consciousness were strongly associated with case fatality. Even after adjustment for these variables the odds ratio (OR) for death in patients treated with antibiotics was high (OR = 3.2; 95% CI, 0.9–10.6). In the 15 patients with skin bleeding (ecchymoses, suggillations) the case fatality rate was 100% in patients treated with antibiotics, and 50% in patients who did not receive antibiotics before hospitalization. If skin bleeding was replaced in the models by the presence of disseminated intravascular coagulation on admission, the OR for death in patients with pre-hospital antibiotic treatment was 35.9 (95% CI, 2.9–441.8) in the presence of disseminated intravascular coagulation and 1.9 (95% CI, 0.2–19.5) in its absence. Conclusions : Pre-hospital treatment is mainly given to the most severe cases with expected high case fatality, and this confounding by indication was probably not fully adjusted for with the available data. The results contradict previous findings but provide reason to doubt the benefit of pre-hospital antibiotic treatment in patients with meningococcal disease.

Background Magnetic Resonance Imaging (MRI) osteitis and synovitis have been identified as predictors of structural damage progression in rheumatoid arthritis (RA)1,2, but the predictive value of MRI joint space narrowing (JSN, a measure of cartilage damage) and tenosynovitis (TS) needs further investigation. Objectives To investigate the predictive value of baseline MRI inflammatory and damage parameters on 2 year MRI and X-ray damage progression in an early RA (eRA) cohort following a non biologic treat-to-target strategy. Methods In 129 eRA ( Results Independent predictors of structural damage progression are presented in table 1. If MRI JSN was not included in the model, MRI osteitis score was statistically significant independent predictor of X-ray progression (coefficient 0.32, p=0.001, vs TSS progression). Conclusions This trial is the first to report that MRI JSN independently predicts both X-ray and MRI damage progression in early RA. Further studies are needed to confirm early MRI-determined cartilage damage as predictor of progressive joint destruction in RA. References Hetland et al, Ann Rheum Dis 2009 Boyesen et al, Ann Rheum Dis 2011 Haavardsholm et al, Ann Rheum Dis 2007 Disclosure of Interest None declared

Meningococcal disease (MCD) is registered in two population-based information systems in Denmark because of the interest in long-term surveillance as a means of following trends, and in public health intervention such as chemoprophylaxis and vaccination. The two systems are the Notifiable System of Communicable Diseases (NSCD) and the Hospital Discharge Register for in-patients (HDR). The aim of the present study was to assess the data quality of the two systems over a 14-year period in the County of Northern Jutland, Denmark. All records of patients registered in the two systems were reviewed with respect to the criteria for the diagnosis of MCD. In addition, records from the local clinical microbiology department, where all microbiological examinations were carried out, were reviewed. The degree of completeness for the HDR system was 89.8% and for the NSCD system was 92.2%. In the in-patient HDR, 296 cases were registered, but only 254 cases (85.8%) fulfilled the criteria for MCD. In the notifiable system, 273 cases were registered, but only 261 cases (95.6%) fulfilled the criteria for MCD. A capture-recapture analysis showed that one to two cases apparently escaped registration.

The IGF-IR density on CD4+T-lymphocytes was studied using flow cytometry in 40 early steroid- and DMARD-naïve rheumatoid arthritis (RA) patients before and after 52 weeks of treatment with methotrexate+placebo or methotrexate+cyclosporine A and in 15 controls. RA patients had increased IGF-IR density on CD4+T-lymphocytes at week 0 and week 52, irrespective of treatment. IGF-IR-positive CD4+T-lymphocytes fraction decreased during treatment, but neither at week 0 nor at week 52 did it differ from healthy controls. No correlations were found to disease activity parameters.

Objective.Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte-suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings.Methods.A total of 160 patients with newly diagnosed RA who were naive to disease-modifying antirheumatic drugs were included in the CIMESTRA trial. Ninety healthy blood donors served as controls. Demographic and disease measures including Disease Activity Score in 28 joints, IgM rheumatoid factor, anti-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years.Results.Median baseline COMP was higher in patients with RA [9.8 U/l (interquartile range 8.96, 10.5)] compared with controls [8.3 U/l (IQR 7.84, 8.9); p < 0.001] and remained elevated at 4 years [10.8 U/l (IQR 10.2, 11.7); p < 0.001]. At baseline, anti-CCP-positive patients had lower COMP than anti-CCP-negative patients (p = 0.048). In anti-CCP-positive patients, COMP exhibited a parabolic course over 4 years, while COMP in anti-CCP-negative patients had an almost linear course. In anti-CCP-positive patients, COMP was associated with MRI edema and erosion score, while COMP was correlated with synovitis score in anti-CCP-negative individuals.Conclusion.Our study provides additional evidence for the existence of different disease pathways in anti-CCP-positive and anti-CCP-negative subsets of RA, and evidence that anti-CCP antibodies may be implicated in the disease process by modifying cartilage metabolism.

Udgivelsesdato: 2010-May-5 OBJECTIVE: /st> At 5 years' follow-up of early ( 139 patients completed 5 years' follow-up with maintained double-blinding and a strict synovitis suppressive treatment strategy with intra-articular betamethasone injections (intra-articular glucocorticosteroid (GC)) and escalation of disease-modifying anti-rheumatic drug treatment. Disease activity, total Sharp-van der Heijde Score (TSS) of hands, wrists and forefeet were assessed at baseline and after 3, 4 and 5 years. MRI of the wrist and anti-cyclic citrullinated peptide (anti-CCP) were assessed at baseline. RESULTS: /st> At 5 years, TSS progression rate was Early and strict synovitis suppressive treatment with MTX and intra-articular GC lead to high remission rates and halting of erosive progression at 5 years. No additional effect of initial combination therapy with CSA was found. The results parallel those reported for tumour necrosis factor alpha antagonists. Baseline MRI-bone oedema, TSS and anti-CCP predicted radiographic progression.

Udgivelsesdato: 2010-Jan OBJECTIVE: To compare tumor necrosis factor alpha inhibitors directly regarding the rates of treatment response, remission, and the drug survival rate in patients with rheumatoid arthritis (RA), and to identify clinical prognostic factors for response. METHODS: The nationwide DANBIO registry collects data on rheumatology patients receiving routine care. For the present study, we included patients from DANBIO who had RA (n = 2,326) in whom the first biologic treatment was initiated (29% received adalimumab, 22% received etanercept, and 49% received infliximab). Baseline predictors of treatment response were identified. The odds ratios (ORs) for clinical responses and remission and hazard ratios (HRs) for drug withdrawal were calculated, corrected for age, disease duration, the Disease Activity Score in 28 joints (DAS28), seropositivity, concomitant methotrexate and prednisolone, number of previous disease-modifying drugs, center, and functional status (Health Assessment Questionnaire score). RESULTS: Seventy percent improvement according to the American College of Rheumatology criteria (an ACR70 response) was achieved in 19% of patients after 6 months. Older age, concomitant prednisolone treatment, and low functional status at baseline were negative predictors. The ORs (95% confidence intervals [95% CIs]) for an ACR70 response were 2.05 (95% CI 1.52-2.76) for adalimumab versus infliximab, 1.78 (95% CI 1.28-2.50) for etanercept versus infliximab, and 1.15 (95% CI 0.82-1.60) for adalimumab versus etanercept. Similar predictors and ORs were observed for a good response according to the European League Against Rheumatism criteria, DAS28 remission, and Clinical Disease Activity Index remission. At 48 months, the HRs for drug withdrawal were 1.98 for infliximab versus etanercept (95% 1.63-2.40), 1.35 for infliximab versus adalimumab (95% CI 1.15-1.58), and 1.47 for adalimumab versus etanercept (95% CI 1.20-1.80). CONCLUSION: Older age, low functional status, and concomitant prednisolone treatment were negative predictors of a clinical response and remission. Infliximab had the lowest rates of treatment response, disease remission, and drug adherence, adalimumab had the highest rates of treatment response and disease remission, and etanercept had the longest drug survival rates. These findings were consistent after correction for confounders and sensitivity analyses and across outcome measures and followup times.

Objective.Rheumatoid arthritis (RA) is a systemic chronic inflammatory joint disease, whereas osteoarthritis (OA) is a local joint disease with low-level inflammatory activity. The pathogenic role of the adipocytokine adiponectin is largely unknown in these diseases. We hypothesized (1) that plasma adiponectin concentrations differ in healthy controls and patients with early disease-modifying antirheumatic drug (DMARD)-naive RA, chronic RA, and OA; (2) that changes in adiponectin are observed during methotrexate (MTX) treatment of chronic RA; and (3) that adiponectin correlates to disease activity measures in RA.Methods.Plasma adiponectin was analyzed with a validated in-house immunoassay. We measured adiponectin in healthy controls (n = 45) and patients with early DMARD-naive RA (n = 40), chronic RA (n = 74), and OA (n = 35). In a subgroup of patients with chronic RA (n = 31), the longitudinal effect of MTX treatment on adiponectin (Week 0 vs Week 28) was investigated.Results.Adiponectin differed significantly between healthy controls (mean 4.8 ± SD 2.7 mg/l) and the 3 groups, with 8.9 ± 4.8 mg/l in early RA, 11.6 ± 5.6 mg/l in chronic RA, and 14.1 ± 6.4 mg/l in OA. Longitudinally, MTX treatment increased adiponectin significantly from 9.7 ± 4.5 mg/l at Week 0 to 11.0 ± 4.5 mg/l at Week 28 in chronic RA. No correlations to disease activity measures were found.Conclusion.Both early DMARD-naive and chronic RA were associated with higher plasma adiponectin compared to healthy controls, but lower plasma adiponectin than OA. Adiponectin increased 13% during MTX treatment. In patients with RA and OA body mass index, age, sex, and disease activity measures failed to explain the findings.

Background The long-term cancer-risk of patients treated for granulomatosis with polyangiitis (Wegener9s; GPA) is not well characterized. Objectives We assessed the risk of early and late-occurring cancers among 293 patients diagnosed with GPA during 1973-1999 and followed throughout 2010. Methods The cancer-incidence in the cohort was determined by linkage with the Danish Cancer Registry and compared to that in the general population by calculation of standardized incidence ratios (SIRs). Results The median duration of follow-up was 9.7 (range: 0-36) years. 73 cancers occurred, of which 30 were non-melanoma skin cancers (NMSC) and 11 were bladder carcinomas. A high occurrence of NMSC was observed from the second year of follow-up onwards, with a SIR of 7.0 (95% CI: 2.3-16) for cases diagnosed ≥20 years after GPA. The incidence of bladder cancer was increased after 5-9, 10-14, and 15-19 years of follow-up, with SIR estimates for these latency-periods of 5.3 (95% CI: 1.1-15), 14.4 (95% CI: 5.3-31), and 10.5 (95% CI: 1.2-38), respectively. The incidence of myeloid leukemia was significantly increased during year 5-9 (SIR: 23.9 (95% CI: 2.7-86)). Increased incidence of NMSC, bladder cancer, and myeloid leukemia was observed among patients exposed to cumulative cyclophosphamide-doses >36 gram, while the only malignancy-type observed in excess among those treated with lower cyclophosphamide-doses was NMSC. The cancer-risk among cyclophosphamide-naive patients was not significantly increased. Conclusions GPA patients experience a greater-than-expected number of cancers following conventional therapies, including an increased number of very late-occurring malignancies. The risk of specific cancer-types rises with the cumulative cyclophosphamide-dose administered. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5439

Recent studies on blood vessels, the heart, trachea and esophagus have shown that these organs in the zero-stress state are not closed circular cross-sections of rings, but open sectors. Any analysis of stress and strain must begin with organs in the zero-stress state. This report presents data on morphometry of the zero-stress and no-load states of the porcine ureter, and on residual strains and opening angles. The zero-stress state of the ureter is demonstrated by cutting the ureter into rings and cutting the rings into sectors; each sector is characterized by an opening angle. The outer and inner circumferences, the cross-sectional area of the ureteral wall and the number of buckles showed axial variation, with the highest values proximally in the ureter. Residual strain in the circumferential direction was significant, but showed no axial variation. The opening angles were approximately 30 degrees at the most distal and proximal sites and approximately 90 degrees in mid-ureter. The opening angle showed positive correlation to the wall thickness in the zero-stress state, residual strain at the outer circumference and negative correlation to the length of the outer circumference in the zero-stress state. Residual strains must be taken into account when studying physiological problems in which the stresses and strains are important, e.g. the urine transport function of the ureter.

Background Recently we reported, that DAS28CRP rd month triple therapy with MTX, sulphasalazine (SZS) and hydroxychloroquine (HCQ) 1 . Addition of adalimumab (ADA) at baseline yielded even better clinical responses and remission rates after treatment for one year. Objectives The purpose of the present investigation was to study whether the improved clinical response obtained by adding ADA to MTX + i.a. TRIAM injections can be maintained after withdrawal of ADA. Methods Patients with ERA were randomized to receive i.a. TRIAM (40 mg/ml) in any swollen joint in combination with MTX (20 mg/wk) for two years and placebo-ADA (MTX+PLA) or MTX+ADA (40 mg eow) during the first year. Peroral glucocorticoid was not allowed. After 1 yr, ADA/PLA was withdrawn. If patients had swollen joints and DAS28(CRP)>3.2 during yr 2, SZS and HCQ were added, and if active disease persisted, ADA (40 mg eow) replaced SZS and HCQ in both treatment arms. Clinical response was assessed by DAS28(CRP), CDAI, SDAI and ACR/EULAR remission criteria. Analysis was by ITT with last observation carried forward. Medians (5%/95% percentiles) or percentage. Mann-Whitney or Pearson’s chi-square tests. Results Baseline characteristics were similar in the MTX+PLA and MTX+ADA groups (DAS28(CRP) 5.6 (3.8-7.3) vs. 5.5 (3.8-7.8), NS). Table shows 1 and 2 years results. Serious adverse events were seen in 10 MTX+PLA patients (malignancy: 2, infections: 5, other: 2) and in 16 MTX+ADA patients (malignancy: 3, infections: 5, other: 8). Conclusions Combined MTX and i.a. TRIAM provided excellent disease control at 2 years’ follow-up of ERA patients. The improved clinical responses observed during additional ADA administration could not be maintained after withdrawal of ADA. Radiographic data are needed to evaluate the overall effect of 1 yr of ADA as induction therapy in combination with MTX and i.a. TRIAM in ERA References Horslev-Petersen K et al. Ann Rheum Dis 2012: Disclosure of Interest None Declared

Background In the CIMESTRA Study patients with early rheumatoid arthritis (RA) were treated with methotrexate (MTX) and intra-articular glucocorticoid. This led to results comparable to biological trials with 34%/28% of pts in DAS28/ACR remission after 1 year (1,2). Objectives We studied if addition of adalimumab (ADA) to the CIMESTRA strategy is of further therapeutic benefit. Methods DMARD naive early RA patients with disease duration 3.2 after three months. Efficacy was assessed by DAS28(CRP), CDAI, SDAI and ACR/EULAR Boolean remission criteria. Primary analysis was by ITT with last observation carried forward. Completer analysis and ITT without imputations gave similar results (not shown). Values are medians (5%/95% percentiles) or percentage. We used Mann-Whitney or Pearson’s chi-square tests. Results Baseline characteristics were similar between MTX+PLA/MTX+ADA groups: Women: 69%/63%; age: 54.4/56.2 years; disease duration: 83/84 days; anti-CCP positive: 70%/60%; IgM-RF positive: 74%/70%; DAS28(CRP): 5.6/5.5; HAQ: 1.0/1.1 (all NS). Triple therapy was added in 25/17 patients (p=0.25). Treatment target was reached in 46%/58% (MTX+PLA/MTX+ADA) at 1 month, 63%/73% (2 months), 70%/76% (3 months), and 76%/80% (12 months) (NS between groups at all time points). However, in the MTX+ADA group significantly more patients achieved rapid and sustained clinical remission as assessed by DAS28, CDAI, SDAI and ACR/EULAR remission criteria (table). Number needed to treat (NNT) with ADA to achieve remission in one extra patient at 1 year was 4 to 5.9 depending on remission criteria. Conclusions Low disease activity was achieved by $≈ $80% in both groups, but remission rates increased considerably by adding adalimumab to methotrexate and intraarticular glucocorticoid injections in DMARD naive patients with early RA. References Hetland et al: Arthritis Rheum 2006;54:1401-09. Hetland et al: Ann Rheum Dis 2008;67:815-22. Disclosure of Interest K. Horslev-Petersen Grant/Research support from: Abbott, M. Hetland Grant/Research support from: Abbott, Bristol-Meyers Squibb, Roche, Schering-Plough/MSD, UCB-Nordic, and Wyeth/Pfizer, Speakers Bureau: Abbott, Centocor, Roche,Schering-Plough/MSD, UCB-Nordic, and Wyeth/Pfizer, P. Junker: None Declared, J. Podenphant: None Declared, T. Ellingsen: None Declared, P. Ahlquist: None Declared, H. Lindegaard Speakers Bureau: Roche, A. Linauskas: None Declared, A. Schlemmer Speakers Bureau: MSD, Roche, M. Dam: None Declared, I. Hansen: None Declared, H. Horn: None Declared, A. Jorgensen: None Declared, S. Krintel: None Declared, J. Raun: None Declared, C. Ammitzboll: None Declared, J. Johansen: None Declared, M. Ostergaard Grant/Research support from: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genmab, Glaxo-Smith-Kline, Mundipharma, Novo, Pfizer, Roche, Schering-Plough, UCB and Wyeth., Speakers Bureau: Abbott, Amgen, Bristol-Myers Squibb, Centocor, Genmab, Glaxo-Smith-Kline, Mundipharma, Novo, Pfizer, Roche, Schering-Plough, UCB and Wyeth., K. Stengaard-Pedersen Grant/Research support from: Abbott

Udgivelsesdato: 2010-Mar-8 ABSTRACT: INTRODUCTION: Surfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously, we reported low circulating SP-D in early rheumatoid arthritis (RA), and the present investigation aims to extend these data by serial SP-D serum measurements, studies on synovial fluid, SP-D size distribution and genotyping in patients with early RA. METHODS: One-hundred-and-sixty disease-modifying antirheumatic drug (DMARD) naïve RA patients with disease duration less than six months were studied prospectively for four years (CIMESTRA (Ciclosporine, Methotrexate, Steroid in RA) trial) including disease activity measures (C-reactive protein, joint counts and Health Assessment Questionnaire (HAQ) score), autoantibodies, x-ray findings and SP-D. SP-D was quantified by enzyme-linked immunosorbent assay (ELISA) and molecular size distribution was assessed by gel filtration chromatography. Further, SP-D Met11Thr single nucleotide polymorphism (SNP) analysis was performed. RESULTS: Serum SP-D was significantly lower in RA patients at baseline compared with healthy controls (P < 0.001). SP-D increased slightly during follow-up (P < 0.001), but was still subnormal at four years after adjustment for confounders (P < 0.001). SP-D in synovial fluid was up to 2.5-fold lower than in serum. While multimeric variants were detected in serum, SP-D in synovial fluid comprised trimeric subunits only. There were no significant associations between genotype distribution and SP-D. Baseline SP-D was inversely associated to CRP and HAQ score. A similar relationship was observed regarding temporal changes in SP-D and CRP (zero to four years). SP-D was not associated to x-ray findings. CONCLUSIONS: This study confirms that circulating SP-D is persistently subnormal in early and untreated RA despite a favourable therapeutic response obtained during four years of follow-up. SP-D correlated negatively to disease activity measures, but was not correlated with x-ray progression or SP-D genotype. These observations suggest that SP-D is implicated in RA pathogenesis at the protein level. The exclusive presence of trimeric SP-D in affected joints may contribute to the maintenance of joint inflammation. TRIAL REGISTRATION: (j.nr NCT00209859).

OBJECTIVES: To investigate the in-situ expression of acetylcholinesterase (AChE) in the inflamed vessel wall of patients with biopsy-positive giant cell arteritis (GCA) as compared to biopsy-negative non-GCA patients, and to evaluate the in-vivo expression of AChE in patients with large-vessel GCA (LVGCA) by 11C-donepezil (AChE inhibitor) positron emission tomography/computed tomography (PET/CT).METHODS: Twenty-four biopsy-positive GCA and 44 biopsy-negative non-GCA patients were included for AChE histology. Immunohistochemical methods were used to determine the AChE expression. The histological inflammation and the AChE expression were assessed by an experienced pathologist on a 3-point scale. Two patients with newly diagnosed 18F-fluorodeoxyglucose (18F-FDG) PET/CT verified LVGCA were included for 11C-donepezil PET/CT. PET images were assessed by an experienced nuclear medicine physician.RESULTS: AChE was expressed in all 24 positive temporal artery biopsies, 10/24 showed high AChE expression (grade 2) and 14/24 showed moderate AChE expression (grade 1). No AChE expression was observed outside the media smooth muscle cells (grade 0) in any of the biopsy-negative non-GCA patients. The AChE expression was in 86% agreement with the histological inflammation. The AChE expression was not associated with any clinical or biochemical findings. In both LV-GCA patients, PET/CT revealed extensive vascular FDG uptake but no 11C-donepezil uptake.CONCLUSIONS: AChE is highly expressed in the inflamed vessel wall of patients with GCA. Although, 11C-donepezil PET/CT showed no vascular uptake in the FDG PET/CT verified LV-GCA patients, histological findings raise the possibility that AChE can be used in the development of new diagnostic and disease monitoring tools for GCA.

Using a multiparameter flow cytometry assay enumerating cells positive for CD13, CD14 and CD66 antigens, we determined the asynchronous CD14/CD66 co-expression in unselected bone marrow and peripheral blood samples with suspected malignant blood disorders. CD14/CD66 co-expression >5% were found in 131/691 bone marrow samples. Only 55 of these exhibited an identifiable population in 2-parameter flow cytometry histograms. Of the 55 samples 43 (78%) came from patients with myeloid disorders; e.g. 11 with myelodysplastic syndromes, 15 with chronic myeloproliferative disorders and 17 with acute myeloid leukaemia. Only one of these 17 cases was a de novo case, while 8 were secondary to another malignant haematological disease and 8 were from the period after cytoreductive therapy. Notably, CD14/CD66 co-expression patterns were related to disease categories; e.g. in chronic myelomonocytic leukaemia and acute myeloid leukaemia following a dysplastic phase the co-expression displayed two subsets in peripheral blood, low-avidity CD14 and low-avidity CD66, respectively. The latter disease category also exhibited these 2 subsets in bone marrow. In all other cases, the CD14/CD66 co-expression in bone marrow was heterogeneous. In conclusion, abnormal CD14/CD66 co-expression might be a valuable parameter in defining asynchronous myelopoiesis in malignant myeloid disorders, especially myeloproliferative disorders and secondary acute myeloid leukemias.