Inactive Status Research Articles

A6: Tapering and Withdrawal of Tocilizumab in Patients With Systemic Juvenile Idiopathic Arthritis in Inactive Disease: Results From an Alternative Dosing Regimen in the TENDER Study

Background/Purpose:The TENDER clinical trial is a 3‐part, 5‐year, phase 3 study with tocilizumab (TCZ) in patients with active systemic juvenile idiopathic arthritis (sJIA). After 2 years of treatment, sJIA patients who have maintained clinically inactive disease for 3 months are given the option to participate in an alternative TCZ dosing regimen aimed at spacing the infusions and eventually withdrawing TCZ. Herein we describe the patients registered to participate in the optional alternative dosing schedule in the TENDER study.Methods:To qualify for the optional alternative dosing schedule, patients had to be in the study for 2 years and had to achieve American College of Rheumatology JIA inactive disease status. Among the 112 patients enrolled, 39 (35%) entered the optional alternative dosing regimen. This entailed a staged prolongation of the time interval between TCZ infusions from 2 weeks (standard interval) to 3 weeks, then 4 weeks, with the option of terminating TCZ after the discontinuation of any treatment.Results:Twenty‐three male and 16 female patients entered the optional alternative dosing schedule. Their mean baseline characteristics were 14.2 active joints, 15.4 joints with limitation of motion, physician global VAS score of 58.5, CHAQ‐DI score of 1.62, and erythrocyte sedimentation rate (ESR) of 56.8. Fifteen had fever. Of these 39 patients, 13 patients lost clinically inactive disease status while on the optional alternative dosing schedule. In these 13 patients, the time to loss of inactive disease status ranged from 1.4 to 16.8 months from initiation of the optional alternative dosing schedule (n = 4 on 3‐week dosing; n = 6 on 4‐week dosing; n = 3 off TCZ). Risk for losing inactive disease status on the optional alternative dosing schedule was similar in patients treated with methotrexate (6/16, 37.5% flared) and in those not treated with methotrexate (7/23, 30.4% flared). Inactive disease status was maintained in 26 of the 39 patients entering the optional alternative dosing schedule. Dosing intervals were every 3 weeks in 3 patients and every 4 weeks in 14 patients; 9 patients have been able to discontinue TCZ (range of time since discontinuation: 3.6–13.4 months). At baseline, these 9 patients were clinically similar to other patients entering the optional alternative dosing schedule (mean characteristics: age 9.1 years, 10.9 active joints, 10.9 joints with limitation of motion, physician global VAS score of 45.4, CHAQ‐DI score of 1.4, ESR of 47.2; 4 patients with fever at baseline).Conclusion:Patients with sJIA who maintain clinically inactive disease status can progressively space TCZ infusions, with one‐fourth of them able to discontinue all treatments, including TCZ.

A148: A Multi‐Center, Double‐Blind, Randomized‐Withdrawal Trial of Subcutaneous Golimumab in Pediatric Patients With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy: Week 48 Results

Background/Purpose:To assess efficacy and safety of SC golimumab (GLM) in polyarticular pediatric juvenile idiopathic arthritis pts (aged 2 to <18 yrs) with active arthritis despite MTX for ≥3 months.Methods:In GO‐KIDS, a 3‐part randomized double‐blind, PBO‐controlled, withdrawal trial in pts with active JIA with a polyarticular course (≥5 active joints) and disease duration of ≥6 months despite current MTX (10–30 mg/m2/wk). In Part 1(wk 0–12), all pts received open‐label (OL) 30 mg/m2 GLM SC (max 50 mg) q4 wks with stable MTX dose. At wk 16, pts with ACR JIA 30 response entered Part 2 (wk 16–48). In Part 2, pts were randomized to continue GLM or switch to PBO q4 wks. Upon Part 2 completion at wk 48 or ACR JIA flare in Part 2, pts received OL GLM in Part 3. Primary endpoint was proportion of ACR JIA 30 responders at wk 16 without a JIA flare in Part 2 using wk 16 as baseline measurement. Secondary outcomes were ACR JIA 30/50/70/90 response rates and inactive disease rates at wk 16 and wk 48 by group and safety.Results:173 pts (Caucasian 87.9%, 75.7% females; age [median/range] 12 yrs/2–17 yrs) with moderately active disease were enrolled (Table ); 19 (11%) were d/c in Part 1 (lack of efficacy n = 14, AE n = 4, withdrawal of consent n = 1). In Part 1, 151 of 173 (87.3%) achieved an ACR JIA 30 response and 36.1% inactive disease status (Table ). There were 154 pts randomized double‐blind in Part 2 (PBO n = 76; continued GLM n = 78). At the end of Part 2, no significant differences between groups in JIA ACR non‐flare rates and trial did not meet primary endpoint [PBO‐grp vs. GLM‐grp: 52.6% vs. 59.0%, p = 0.41) nor were there differences for major secondary endpoints (Table 2). In contrast, sustained response in both groups (PBO, GLM) relative to wk 0 (Table 1 and 2). 6.5% (10 of 154) of pts d/c therapy after wk16 through wk 48. Through wk 48, AEs, serious AE (SAE), and serious infections were reported in 87.9%, 13.3%, and 2.9% of all randomized pts, respectively. Most common SAE was JIA exacerbation. No deaths, active TB or malignancies were reported (1). GLM‐treated pt experienced SAE of toxic hepatitis and 1 had SAE of hepatic enzyme increase. One pt switched from PBO to GLM experienced SAE of serum sickness reaction, resulting in GLM d/c. Proportion of pts with ≥1 injection site reaction was 8.1%. None of the reactions were serious, severe, or led to GLM d/c. At Baseline (All enrolled patients n=173) At wk16 (All randomized patients prior to randomization, n=154) At wk48 Values are medians (interquartile range) PBO + MTX (n=76) GLM + MTX (n=78) Physicians global assessment 5.40 (3.90; 7.00) 0.50 (0.10; 1.30) 0.30 (0.00; 1.00) 0.30 (0.00; 1.30) Patient/parent global assessment 4.50 (2.80; 6.10) 0.90 (0.30, 2.30) 0.60 (0.20; 1.65) 0.45 (0.10; 1.70) Number of active joints 12.0 (8.0; 18.0) 1.0 (0.0; 3.0) 1.0 (0.0; 3.0) 0.0 (0.0; 2.0) Number of joints with limited range of motion 8.0 (6.0; 15.0) 1.0 (0.0, 4.0) 0.5 (0.00; 4.0) 1.0 (0.0; 3.0) Physical function by CHAQ 0.94 (0.38; 1.50) 0.25 (0.00; 0.75) 0.13 (0.00; 0.63) 0.00 (0.00; 0.63) ESR (mm/hr) 16.00 (8.00; 28.00) 9.00 (5.00; 19.00) 9.50 (5.00; 16.50) 10.00 (5.00; 19.00) Methotrexate (mg/wk) 15t(5.00; 30.00) 15t(5.00; 30.00) 15t(5.00; 30.00) 15t(5.00; 30.00) ACR JIA response and flare rates PART 1 [WK 0ndash;16] Percentage of ACR JIA responders at end of Part 1 [WK 16] (n = 173) JIA ACR 30 87.3%t(151) JIA ACR 50 79.2%t(137) JIA ACR 70 65.9%t(114) JIA ACR 90 36.4%t(63) Inactive disease 36.1%t(62) PART 2 [WK 16ndash;48] Percentage of ACR JIA 30 responders without flare in Part 2 (n = 154) PBO + MTX (n=76) 52.6%t(40) P=0.41 GLM + MTXt(n=78) 59.0%t(46) Inactive disease 21.6%/39.7% Clinical remission 11.8%/12.8% Percentage of ACR JIA responders at WK48 (vs. wk0) by treatment in Part 2 [PBO +MTX/GLM +MTX] JIA ACR 30 95.9%/89.0% JIA ACR 50 91.8%/86.3% JIA ACR 70 78.1%/78.1% JIA ACR 90 53.4%/56.2% Pts experiencing flares/those considered treatment failures due to protocol violations are considered ACR non‐responders from the flair/failure visit to wk 48 Observed dataConclusion:JIA pts with active polyarticular dis ease demonstrated rapid response to GLM with 16 wks of OL treatment, resulting in inactive disease in 36% of the pts. The lack of differences in flare rates between GLM and PBO arms from wk 16 to 48 among OL GLM responders needs further evaluation. Safety profile was acceptable and injections well tolerated.

Physiological Oxygen Prevents Frequent Silencing of the DLK1-DIO3 Cluster during Human Embryonic Stem Cells Culture

Genetic and epigenetic alterations are observed in long-term culture (>30 passages) of human embryonic stem cells (hESCs); however, little information is available in early cultures. Through a large-scale gene expression analysis between initial-passage hESCs (ihESCs, <10 passages) and early-passage hESCs (ehESCs, 20-30 passages) of 12 hESC lines, we found that the DLK1-DIO3 gene cluster was normally expressed and showed normal methylation pattern in ihESC, but was frequently silenced after 20 passages. Both the DLK1-DIO3 active status in ihESCs and the inactive status in ehESCs were inheritable during differentiation. Silencing of the DLK1-DIO3 cluster did not seem to compromise the multilineage differentiation ability of hESCs, but was associated with reduced DNA damage-induced apoptosis in ehESCs and their differentiated hepatocyte-like cell derivatives, possibly through attenuation of the expression and phosphorylation of p53. Furthermore, we demonstrated that 5% oxygen, instead of the commonly used 20% oxygen, is required for preserving the expression of the DLK1-DIO3 cluster. Overall, the data suggest that active expression of the DLK1-DIO3 cluster represents a new biomarker for epigenetic stability of hESCs and indicates the importance of using a proper physiological oxygen level during the derivation and culture of hESCs.

HBsAg quantification: useful for monitoring natural history and treatment outcome

The template of hepatitis B virus transcription, the covalently closed circular DNA (cccDNA), plays a key role in the life cycle of the virus and permits the persistence of infection. It has been suggested that hepatitis B surface antigen (HBsAg) quantification reflects the concentration of cccDNA in the liver. In hepatitis B e antigen (HBeAg) positive chronic hepatitis B, HBsAg levels are higherduring the immune tolerance phase than during the immune clearance phase. During the natural history of chronic hepatitis B, serum HBsAg declines progressively from the immune-tolerant to the low replicative phase. In HBeAg negative patients, the combination of low hepatitis B virus (HBV) DNA (<2000IU/ml) and low HBsAg levels (<1000IU/ml) can predict inactive carrier status, low risk of hepatocellular carcinoma, and the probability of HBsAg loss. HBsAg in combination with HBV DNA predicts the outcome of Peg-Interferon therapy: An absence of decline at week 12 is a good predictor of non-response and to stop therapy. Any decline at week 24, suggests that therapy should be continued to 48weeks. Although the decrease in HBsAg decline slow with nucleos(t)ide analogue therapy, a rapid decline can predict future HBsAg seroclearance. A level <100IU/ml during six consecutive months could be a marker of a sustained response after treatment cessation.

PReS-FINAL-2152: Biomarkers as predictors of early inactive disease in children with juvenile idiopathic arthritis

Results After a 12 months follow-up, 106 children were diagnosed with inactive and 85 children with active disease. Of the biomarkers measured in sera collected at inclusion, only a higher ESR at baseline (median 27 vs. 19 mm/h, p = 0.013) was significantly associated with a persistently active disease at 12 months follow-up. While none of the cytokine levels revealed significant differences, both MRP8/14 (median 1,145 vs. 815 ng/ml, p = 0.041) and S100A12 levels (120 vs. 87 ng/ml, p = 0.032) in sera collected after 3 months of specialized care were significantly higher in patients who did not reach inactive disease status after 12 months. ROC analyses for MRP8/14 (area under curve, AUC 0.618, 95% CI 0.510-0.726, p = 0.041) and for S100A12 (AUC 0.651, 95% CI 0.514-0.717, p = 0.033) revealed a moderate but robust predictive power of these biomarkers.

Psychological distress in women with breast and gynecological cancer treated with radical surgery

The objective of this study is to compare psychological distress (body image disturbance,self-esteem, depression, and anxiety) in women with breast or gynecological cancer treated by radical surgery. Additionally, another objective is to analyze the association between psychological distress and sociodemographic characteristics, medical history, and social support to produce a prediction model for the outcome measures. A cross-sectional study was carried out with 100 women who had undergone radical surgery for breast or gynecological cancer. Both groups were divided into the following: younger than 50 years old and 50 years old or older. Body Image Scale, Rosenberg's Self-Esteem Scale, Beck Depression Inventory, and Beck Anxiety Inventory were used. Age had a significant main effect on psychological distress but the type of cancer did not.Younger women showed significantly greater distress than older women (p-values<0.001). A significant interaction between age and type of cancer was found, indicating that older women with breast cancer had worse body image and more depression than those with gynecological cancer (p-values 0.001); no significant differences were found between younger groups.The prediction model for increased body image disturbance and depression included the joint effect of the following variables: being younger, inactive occupational status, and post-adjuvant therapy side effects. For lower self-esteem, the variables were: being younger, post-adjuvant therapy side effects,and dissatisfaction with social support. And for higher anxiety, the sole variable included was post-adjuvant therapy side effects. Both mastectomy and hysterectomy/oophorectomy cause similar psychological distress in younger women, but mastectomy causes greater distress in older women than hysterectomy/oophorectomy.

The Transcription Repressor Gfi1 Directly Interacts With and Is Phosphorylated By Aurora A Kinase, Which Abrogates Myeloma-Induced Gfi1 Repression Of The Runx2 Promoter In Pre-Osteoblasts

Multiple myeloma (MM) is a plasma cell malignancy that is the most frequent cancer to involve the skeleton. MM bone disease is characterized by the formation of lytic bone lesions adjacent to MM cells that rarely heal even when patients are in long-term remission. This is due to the persistent suppression of bone marrow stromal cell (BMSC) differentiation into osteoblasts. We previously reported that MM cells induce long-lasting suppression of osteoblast differentiation by repression of the Runx2 gene through elevated expression of the transcriptional repressor Gfi1. However, how Gfi1 activity in BMSC is regulated by MM cells remains unclear. Using bioinformatics analysis, we found that there are three putative phosphorylation sites in the Gfi1 protein for Aurora A kinase (AurA) at S216, S326, and T418. We confirmed that Gfi1 was phosphorylated by AurA at multiple sites using an in vitro kinase assay. Co-immunoprecipitation assays revealed that AurA physically interacted with Gfi1 and phosphorylated Gfi1 protein. The interaction with AurA stabilized Gfi1 protein by blocking Gfi1 protein turnover, thereby extending the Gfi1 half-life from 2 hrs to 6 hrs. Further, co-transfection studies using wildtype and mutant AurA and Gfi1 showed that AurA inhibition of Gfi1 protein turnover was dependent on AurA kinase activity and phosphorylation of the S326 and T418 amino acid residues of Gfi1. Studies with co-transfected Myc-ubiquitin, FLAG-Gfi1, and HA-AurA revealed that AurA decreased Gfi1 ubiquitination, thereby leading to increased Gfi1 protein stability. Amino acids S326 and T418 are in Gfi1 zinc fingers (ZF) 3 and 6, respectively. It is known that Gfi1 ZF3, 4, and 5 are required for DNA binding, and that the K403R mutation in ZF6 interferes with DNA binding. Therefore we investigated if AurA phosphorylation of Gfi1 interferes with DNA binding. Chromatin immunoprecipitation and mRunx2 promoter oligo-pull down assays demonstrated that phosphorylated Gfi1 can still bind the Runx2 promoter. However, co-transfection studies with AurA and Gfi1 expression vectors with mRunx2-promoter luciferase reporters demonstrated that AurA phosphorylation of Gfi1 blocked repression of the Runx2 promoter. These data indicate that although AurA increased the amount of Gfi1 protein present on Runx2, AurA phosphorylation of Gfi1 appeared to lock Gfi1 in an “Off” (inactive) status and abrogated Gfi1 repression of Runx2 expression in osteoblast precursor cells. Since AurA phosphorylation of Gfi1 is not blocking DNA binding, the difference between Gfi1 “OFF” and “ON” status probably involves altered protein-protein interactions between Gfi1 and other factors that regulate Runx2 transcription. TNFa treatment, which we showed also represses Runx2 via Gfi1 activity, decreased the AurA protein level in MC-4 osteoblast precursor cells. Importantly, we found that AurA mRNA was decreased in both MC-4 cells treated with MM cells in vitro, and in bone marrow stromal cells isolated from MM patients. In conclusion, these data indicate that MM cells lower the levels of AurA in bone marrow stromal cells, thereby decreasing AurA phosphorylation of Gfi1. This helps to maintain Gfi1 in the “ON” status and allows Gfi1 repression of the Runx2 gene, thereby preventing osteoblast differentiation. These data suggest that AurA is an important regulator of Gfi1 function in MM bone disease. Disclosures:Roodman:Amgen: Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Research Funding.

Do changes in socioeconomic factors lead to changes in mental health? Findings from three waves of a population based panel study

BackgroundThere has been little investigation of changes in socioeconomic measures and mental health (MH)/illness over time within individuals using methods that control for time-invariant unobserved confounders. We investigate whether changes...

The Transcription Repressor Gfi1 Directly Interacts With and Is Phosphorylated By Aurora A Kinase, Which Abrogates Myeloma-Induced Gfi1 Repression Of The Runx2 Promoter In Pre-Osteoblasts

Multiple myeloma (MM) is a plasma cell malignancy that is the most frequent cancer to involve the skeleton. MM bone disease is characterized by the formation of lytic bone lesions adjacent to MM cells that rarely heal even when patients are in long-term remission. This is due to the persistent suppression of bone marrow stromal cell (BMSC) differentiation into osteoblasts. We previously reported that MM cells induce long-lasting suppression of osteoblast differentiation by repression of the Runx2 gene through elevated expression of the transcriptional repressor Gfi1. However, how Gfi1 activity in BMSC is regulated by MM cells remains unclear. Using bioinformatics analysis, we found that there are three putative phosphorylation sites in the Gfi1 protein for Aurora A kinase (AurA) at S216, S326, and T418. We confirmed that Gfi1 was phosphorylated by AurA at multiple sites using an in vitro kinase assay. Co-immunoprecipitation assays revealed that AurA physically interacted with Gfi1 and phosphorylated Gfi1 protein. The interaction with AurA stabilized Gfi1 protein by blocking Gfi1 protein turnover, thereby extending the Gfi1 half-life from 2 hrs to 6 hrs. Further, co-transfection studies using wildtype and mutant AurA and Gfi1 showed that AurA inhibition of Gfi1 protein turnover was dependent on AurA kinase activity and phosphorylation of the S326 and T418 amino acid residues of Gfi1. Studies with co-transfected Myc-ubiquitin, FLAG-Gfi1, and HA-AurA revealed that AurA decreased Gfi1 ubiquitination, thereby leading to increased Gfi1 protein stability. Amino acids S326 and T418 are in Gfi1 zinc fingers (ZF) 3 and 6, respectively. It is known that Gfi1 ZF3, 4, and 5 are required for DNA binding, and that the K403R mutation in ZF6 interferes with DNA binding. Therefore we investigated if AurA phosphorylation of Gfi1 interferes with DNA binding. Chromatin immunoprecipitation and mRunx2 promoter oligo-pull down assays demonstrated that phosphorylated Gfi1 can still bind the Runx2 promoter. However, co-transfection studies with AurA and Gfi1 expression vectors with mRunx2-promoter luciferase reporters demonstrated that AurA phosphorylation of Gfi1 blocked repression of the Runx2 promoter. These data indicate that although AurA increased the amount of Gfi1 protein present on Runx2, AurA phosphorylation of Gfi1 appeared to lock Gfi1 in an “Off” (inactive) status and abrogated Gfi1 repression of Runx2 expression in osteoblast precursor cells. Since AurA phosphorylation of Gfi1 is not blocking DNA binding, the difference between Gfi1 “OFF” and “ON” status probably involves altered protein-protein interactions between Gfi1 and other factors that regulate Runx2 transcription. TNFa treatment, which we showed also represses Runx2 via Gfi1 activity, decreased the AurA protein level in MC-4 osteoblast precursor cells. Importantly, we found that AurA mRNA was decreased in both MC-4 cells treated with MM cells in vitro, and in bone marrow stromal cells isolated from MM patients. In conclusion, these data indicate that MM cells lower the levels of AurA in bone marrow stromal cells, thereby decreasing AurA phosphorylation of Gfi1. This helps to maintain Gfi1 in the “ON” status and allows Gfi1 repression of the Runx2 gene, thereby preventing osteoblast differentiation. These data suggest that AurA is an important regulator of Gfi1 function in MM bone disease. Disclosures:Roodman:Amgen: Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Research Funding.

EFFICIENCY AND SAFETY OF HUMAN MONOCLONAL ANTIBODIES TO TNF-Α IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS IN PRIMARY AND SECONDARY INEFFECTIVENESS OF OTHER BIOLOGICALS

To evaluate the safety and efficiency of adalimumab in children with severe refractory JIA with primary inefficiency, partial effect or loss of the effectiveness of other biologicals. The article presents the results of the retrospective observational study of the efficacy and safety of adalimumab in 68 patients aged 10 (3, 17) years with various embodiments of JIA, with the primary inefficiency or partial or loss of the effectiveness of other biologicals. JIA diagnosis established on the basis of criteria ILAR (International League of Associations for Rheumatology). Efficacy was assessed during 1 year in 68 and 2 years--in 56 patients . At the 24th week we observed the improvement by criteria AKR 30, 50.70 in 100, 91 and 74% of patients, respectively, and at the 52th week--in 100, 96 and 90%, respectively. Inactive disease status was recorded in 55.8, 66.1 and 98.2% of study participants after 6 months, 1 and 2 years, respectively. Remission was achieved in 55.8 and 96.4% of patients after 1 and 2 years of observation, respectively. Adalimumab was effective and well tolerated by patients with primary inefficiency, partial and loss of efficiency of other biologicals. In clinical practice, patients with non-systemic JIA transition to the second TNF-alpha blocker can restore the biological effect of the first drug without increasing the frequency of infectious AEs.

Reactivation of Х chromosome upon reprogramming leads to changes in the replication pattern and 5hmC accumulation

Once set, the inactive status of the X chromosome in female somatic cells is preserved throughout subsequent cell divisions. The inactive status of the X chromosome is characterized by many features, including late replication. In contrast to induced pluripotent stem cells (iPSCs) in mice, the X chromosome in human female iPSCs usually remains inactive after reprogramming of somatic cells to the pluripotent state, although recent studies point to the possibility of reactivation of the X chromosome. Here, we demonstrated that, during reprogramming, the inactive X chromosome switches from late to synchronous replication, with restoration of the transcription of previously silenced genes. This process is accompanied by accumulation of a new epigenetic mark or intermediate of the DNA demethylation pathway, 5-hydroxymethylcytosine (5hmC), on the activated X chromosome. Our results indicate that the active status of the X chromosome is better confirmed by early replication and the reappearance of 5hmC, rather than by appearance of histone marks of active chromatin, removal of histone marks of inactive chromatin, or an absence of XIST coating.

AB0170 Anti-cyclic citrullinated peptide and rheumatoid factor in patients with chronic hepatitis b and hepatitis b carriers

BackgroundRheumatoid factor (RF) positivity that may occur in a number of patients with HBV infection poses challenges in terms of differential diagnosis with rheumatoid arthritis (RA). On the other hand,...

Pension Reform in Chile: A Difference in Difference Matching Estimation

The present paper estimates the effect over participation outcomes of the new reform to the pension system made in Chile in 2008, using a difference in difference matching estimation. The main results found that the treated group shows a higher withdrawal from the labor market and that they worked an average of 8 percentage points (pp) fewer months than the control group in 2009. The treated group also contributed 18 pp fewer months than the control group, and they have, on average, 6 pp more months in inactive status. Looking at the difference in per capita income, the treated group has an average of US$34 more per month than the control group in 2009.

AB0193 Plasma chemerin levels in rheumatoid arthritis are correlated with disease activity rather than obesity

BackgroundChemerin is an adipokine that is linked to adipogenesis and chemotaxis of the innate immune system. It is expressed on macrophage, dendritic cells, and synovial lining and sublining cells. It...

AB0198 Plasma leucine-rich alpha-2 glycoprotein is a useful disease activity biomarker in rheumatoid arthritis

BackgroundLeucine-rich α2-glycoprotein (LRG) is a plasma protein which contains leucine-rich repeats (LRRs). Though physiological functions of LRG have not been clarified yet, it has been reported that LRG could be...

AB0444 Elevated plasma chemerin levels are correlated with disease activity in rheumatoid arthritis

BackgroundChemerin is an adipokine that is linked to adipogenesis and chemotaxis of the innate immune system. It is expressed on macrophage, dendritic cells, and synovial lining and sublining cells. It...

FRI0418 How important is the assessment of asdas in the long-term evaluation of disease activity in ankylosing spondylitis? a comparison with currently used clinical parameters

BackgroundMeasures for disease activity (BASDAI) or response to therapy (ASAS partial remission (PR)) are widely used in the assessment of patients with ankylosing spondylitis (AS). The recently developed ASDAS is...

AB0165 Plasma soluble triggering receptor expressed on myeloid cells-1 (strem-1) levels are correlated with disease activity in rheumatoid arthritis

BackgroundTriggering receptor expressed on myeloid cells 1 (TREM-1) is an immunoglobulin-like cell surface receptor mainly expressed on neurtophils, monocytes and macrophages. TREM-1 serves as a critical amplifier of inflammatory signaling,...

THU0286 Clinical efficacy and safety of infliximab – first results after a decade of continuous treatment in ankylosing spondylitis

BackgroundThe efficacy of anti-TNF therapy in patients with active ankylosing spondylitis (AS) has been established for short and longer-term periods.ObjectivesThis is the final report of the first clinical trial with...

Trends in the Inactive Kidney Transplant Waitlist and Implications for Candidate Survival

In November 2003, OPTN policy was amended to allow kidney transplant candidates to accrue waiting time while registered as status 7, or inactive. We evaluated trends in inactive listings and the association of inactive status with transplantation and survival, studying 262,824 adult first-time KT candidates listed between 2000 and 2011. The proportion of waitlist candidates initially listed as inactive increased from 2.3% prepolicy change to 31.4% in 2011. Candidates initially listed as inactive were older, more often female, African American, and with higher body mass index. Postpolicy change, conversion from initially inactive to active status generally occurred early if at all: at 1 year after listing, 52.7% of initially inactive candidates had been activated; at 3 years, only 66.3% had been activated. Inactive status was associated with a substantially higher waitlist mortality (aHR 2.21, 95%CI:2.15-2.28, p<0.001) and lower rates of eventual transplantation (aRR 0.68, 95%CI:0.67-0.70, p<0.001). In summary, waitlist practice has changed significantly since November 2003, with a sharp increase in the number of inactive candidates. Using the full waitlist to estimate organ shortage or as a comparison group in transplant outcome studies is less appropriate in the current era.