Disease Activity In Patients Research Articles

P259. Improvement of Patient's Disease Activity in Paediatric Inflammatory Disease (pIBD) after adoption of ImproveCareNow (ICN) Quality Improvement (QI) Tool

P259. Improvement of Patient's Disease Activity in Paediatric Inflammatory Disease (pIBD) after adoption of ImproveCareNow (ICN) Quality Improvement (QI) Tool

Exercise Decreases Risk of Future Active Disease in Patients with Inflammatory Bowel Disease in Remission:

Exercise Decreases Risk of Future Active Disease in Patients with Inflammatory Bowel Disease in Remission:

How to Differentiate Inactive from Active Disease in Patients of Primary Multidrug-resistant Tuberculosis with Persistent Cavity after Anti-tuberculous Therapy

How to Differentiate Inactive from Active Disease in Patients of Primary Multidrug-resistant Tuberculosis with Persistent Cavity after Anti-tuberculous Therapy

Elevated levels of serum sCXCL16 in systemic lupus erythematosus; potential involvement in cutaneous and renal manifestations.

The aim of this study was to investigate the levels and clinical significance of serum soluble chemokine (C-X-C motif) ligand 16 (sCXCL16) in patients with systemic lupus erythematosus (SLE), as well as the sCXCL16 molecule's associations with disease activity and organ damage. Thirty-five patients with SLE, 16 patients with rheumatoid arthritis (RA), and 15 healthy controls were included in this study. The demographic and clinical features of the patients were recorded. The serum levels of sCXCL16 were determined. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI), and organ damage was evaluated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI). The serum levels of sCXCL16 in the patients with SLE were higher than those in the patients with RA (P = 0.002) or healthy controls (P < 0.0001). The levels in the patients with active SLE were higher than those in the disease inactive patients (P = 0.008). Positive correlations were identified between serum sCXCL16 concentrations and both SLEDAI (r = 0.564; P < 0.0001) and SDI scores (r = 0.396; P = 0.018). Both SLEDAI (P = 0.021) and serum levels of CXCL16 (P = 0.023) decreased after conventional treatment in 12 initial onset cases of SLE patients. Elevated serum sCXCL16 levels were discovered in the SLE patients with cutaneous (P = 0.006) and renal involvement (P = 0.032). Soluble CXCL16 may become a useful serological marker of disease activity and skin and renal involvement in SLE patients; thus, it may be used for evaluation of therapeutic interventions.

FRI0548 Costs of Early Juvenile Idiopathic Arthritis (JIA)

BackgroundJIA is the most common chronic inflammatory rheumatic disease in childhood. It carries a high risk for life-long morbidity and disability. Longitudinal cost-of-illness studies are crucial, given the availability of...

FRI0071 Effect of Biological Therapy on Fatigue in Patients with Rheumatoid Arthritis

BackgroundFatigue is a frequent symptom among patients with rheumatoid arthritis (RA) and contributes to decreased quality of life in these patients [1].There are various questionnaires to assess fatigue in rheumatic...

FRI0291 Effects of Tnf-Inhibitors (INFLIXIMAB) on CD147 Expression and MMP-3 Level in Rheumatoid Arthritis Patients

BackgroundTumor necrosis factor (TNF) antagonists are highly effective for the treatment of rheumatoid arthritis (RA), but their mechanisms of action are not completely clear. Increased expression of CD147 on monocytes/macrophages...

OP0104 Low-Dose Interleukin-2 Therapy Caused Selective Expansion of Regulatory T Cells Together with RAPID Reduction of Disease Activity in A Patient with Severe Refractory Sle

BackgroundSLE is characterized by the breakdown of immune tolerance towards nuclear autoantigens. Aberrant activation of autoreactive T and B cells leads to uncontrolled inflammation and production of autoantibodies ultimately resulting...

Assessment of serum vitamin D level in patients with systemic lupus erythematosus

To evaluate the serum level of vitamin D in patients with systemic lupus erythematosus (SLE) and its relationship with disease activity. Forty patients suffering from SLE were enrolled in this study (group I). They were further divided into two subgroups according to the SLE disease activity index (SLEDAI) score: group Ia with respect to disease activity and group Ib with respect to disease remission. Another 20 age-matched and sex-matched healthy individuals were chosen as control group II. All patients underwent complete medical history taking and thorough clinical examination; the disease activity was assessed by the use of SLEDAI score. Serum vitamin D level in all patients and controls was measured. Vitamin D level was significantly higher in controls than in patients. The vitamin D deficiency was highly prevalent among patients with disease activity than in the remission group. There was highly significant inverse correlation between vitamin D level and SLEDAI score in the patient group. Vitamin D level correlated inversely with C reactive protein (CRP) and anti-dsDNA in the disease activity group, whereas it correlated positively with C3. Vitamin D deficiency is prevalent in SLE patients more than in healthy controls; vitamin D deficiency is highly prevalent among patients with disease activity than in the remission group, and vitamin D level correlated inversely with disease activity, which suggest that inadequate vitamin D level, among other factors, probably contributed to the development of active disease in patients with SLE.

Utilidad clínica de la cuantificación de infliximab y anticuerpos antiquiméricos humanos

Introductioninfliximab (IFX), a chimeric antibody against tumour necrosis factor-alpha, is used in the treatment of patients with several inflammatory diseases, but it can lead to the formation of human anti-chimeric antibodies (HACA). HACA and low IFX serum levels have been associated with lack or loss of response, and infusion reactions. The usefulness of measuring the IFX and HACA concentrations is evaluated. Material and methodsIFX and HACA were measured using a relatively new ELISA technique in a cohort of 110 patients treated with IFX. Serum samples were collected immediately before patients were given the next drug infusion. The patients had received a median dose of 5mg/kg, with dose intervals adjusted to the patient's disease activity, usually every 8 weeks. The median number of infusions was 17. ResultsHACA were identified in 10 patients, and therapeutic IFX concentrations were observed in 37 patients. Eight out of 10 positive HACA patients had gastrointestinal disorders, and the therapy was discontinued in 9 of them. The concomitant use of immunosuppressants did not reduce the risk of HACA formation. Among 100 patients with no HACA, 79 continued on the same dose, 16 required a dose adjustment, 2 discontinued treatment, and 3 were switched to another biological agent. ConclusionsBlood IFX and HACA concentrations should be monitored in patients receiving IFX, as it may be useful to optimize dose regimens or avoid use of inadequate therapy.

Open-label study on treatment with 20 % subcutaneous IgG administration in polymyositis and dermatomyositis

The objective of this study is to describe the benefit of 20 % subcutaneous infusions of immunoglobulin (SCIg) in patients with dermatomyositis (DM) or polymyositis (PM) after a switch from previous 16 % SCIg treatment. Eight patients with DM or PM, who met the Bohan and Peter's criteria, previously treated with 16 % SCIg, were switched to weekly 20 % SCIg infusions (Hizentra®; CSL Behring) at doses equivalent to their previous subcutaneous treatment. A standardised protocol was used to evaluate patients, disease activity and treatment response. The disease remained stable in three and improved in four other patients, as documented by increased Medical Research Council scores and normal serum CK levels. No relapse of disease occurred. Local reactions were mild and self-limiting. No serious adverse events were reported. The mean duration of infusion per week was significantly lower compared to the mean duration of the 16 % SCIg preparation. A specifically designed questionnaire documented the patients' satisfaction with treatment. The weekly administration of 20 % SCIg is effective in maintaining a quiescent disease in patients with DM or PM with no increased safety concerns. SCIg therapy is particularly attractive for patients because it does not require venous access and hospitalisation and requires less assistance from healthcare provider services. The administration of 20 % SCIg was beneficial and safe in maintaining a quiescent disease and in inducing a complete remission in moderately active disease in patients with DM or PM. The treatment with 20 % SCIg led to the possibility to discontinue and to reduce the use of glucocorticoids and/or the immunosuppressants. Patients reported their satisfaction in terms of contact with health professionals, quality of treatment-related information and administration convenience, with an improved quality of life.

Correlation of Health‐Related Quality of Life in Children With Inflammatory Bowel Disease, Their Parents, and Physician as Measured by a Visual Analog Scale

Inflammatory bowel disease has been shown to affect children's health-related quality of life (HRQOL) through the use of lengthy questionnaires. We examined whether a pediatric patient's HRQOL, measured by a rapid visual analog scale ("feeling thermometer"), correlates with the perceptions of the HRQOL as determined by the patient's pediatric gastroenterologist and parent(s). Additionally, we attempted to determine whether the HRQOL correlates with the patient's disease activity as determined by validated activity indices. A cross-sectional study of pediatric patients (ages 7-21 years) who were diagnosed as having Crohn disease, ulcerative colitis, or indeterminate colitis was conducted from January 2011 to May 2011. Each participant (patient, parent(s), and treating pediatric gastroenterologist) completed feeling thermometers to determine the symptom burden as well as therapeutic burden of the patient. The parent(s) and doctor were blinded to the patient's results. Pediatric Ulcerative Colitis Activity Index or a Short Pediatric Crohn Disease Activity Index (S-PCDAI) was calculated. Correlations between the participant's perceived burdens as well as their calculated disease activity were determined. Sixty-seven children and their families participated, resulting in 101 visits. Patients had a mean age of 15.0 years, and there were 38 boys. There was a strong significant correlation between the patient's perceived symptom burden and that of the parent's (ρ 0.59, P < 0.001) and physician (ρ 0.48, P < 0.001). Similarly, there was a strong significant correlation between patient's perceived treatment burden and that of the parent treatment burden (ρ 0.49, P < 0.001) and, to a lesser degree, the physician (ρ 0.29, P < 0.003). The correlation coefficient was strongest between the physician's perception of the patient's symptom burden against the standard disease activity indices Pediatric Ulcerative Colitis Activity Index (ρ 0.69, P < 0.001) and Short Pediatric Crohn Disease Activity Index (ρ 0.65, P < 0.001). The patient's HRQOL was highly correlated to both the physician's and parent's perceptions as well as their disease activity. The feeling thermometer is a quick, easy-to-use, visual analog scale that can be implemented in everyday practice to measure a pediatric patient's HRQOL.

Hypertension is associated with serologically active disease in patients with systemic lupus erythematosus: role of increased Th1/Th2 ratio and oxidative stress

Objectives: To determine whether disease activity verified by laboratorial parameters is associated with a higher frequency of hypertension in patients with systemic lupus erythematosus (SLE) without renal impairment and to investigate factors that could influence this hypertension.Method: This study included 102 controls, 70 patients with inactive SLE, and 53 patients with active SLE without renal impairment. We evaluated T helper type 1 (Th1)/Th2 lineage cytokines, nitric oxide (NO), insulin resistance (IR), and oxidative stress.Results: Patients with active SLE had a higher probability of developing hypertension compared to controls [odds ratio (OR) 3.833, 95% confidence interval (CI) 1.806–8.137, p < 0.0003] and patients with inactive SLE (OR 2.215, 95% CI 1.032–4.752, p = 0.0394). Active SLE patients had a higher interleukin (IL)-12/IL-4 ratio (p < 0.05) than both controls and inactive SLE patients. Protein oxidation was significantly higher in patients with active SLE than in the control group and in patients with inactive SLE (p < 0.01 and p < 0.05, respectively). Multivariate analysis revealed an association between the presence of hypertension and he levels of glucose (p = 0.0276), insulin (p = 0.0498), hydroperoxides (p = 0.0221), IFN-γ (p = 0.0494), IL-17 (p = 0.0272), IL-12/IL-10 (p = 0.0373), IFN-γ/IL-10 (p = 0.0142), IFN-γ/IL-4 (p = 0.0320), and adiponectin (p = 0.0433).Conclusions: Patients with active SLE without renal impairment had an increased frequency of high blood pressure (43.4%) compared with patients with inactive SLE (25.7%) and controls (16.7%). Hypertension was associated with serologically active disease and was influenced by an increased Th1/Th2 ratio and oxidative stress.

PET/CT Imaging of Inflammatory Bowel Disease

PET/CT imaging has become an important part of the evaluation of patients with many types of cancer. This imaging modality can also be used to image areas of active inflammation, such as those occurring in patients with active inflammatory bowel disease (IBD) (Crohn's disease and ulcerative colitis). The standard methods of determining a patient's disease activity are either indirect, such as blood and stool tests, or invasive, such as colonoscopy. FDG-PET imaging is a noninvasive, direct method of evaluating bowel inflammation and represents a significant advancement in the care of these patients. The PET/CT technique is very similar to that used for oncology imaging. Minor changes can be instituted to improve the accuracy, as well as to reduce the radiation exposure to the patient. This paper reviews the literature on the use of FDG-PET imaging in IBD in both the adult and pediatric populations. Future improvements in the technique should focus on decreasing the radiation dose to the patient and on decreasing the cost of the examination. The FDG-PET/CT technique is an excellent method for the noninvasive quantification of bowel inflammation in patients with IBD.

Validation of the Auto-Inflammatory Diseases Activity Index (AIDAI) for hereditary recurrent fever syndromes

ObjectivesTo validate the Auto-Inflammatory Diseases Activity Index (AIDAI) in the four major hereditary recurrent fever syndromes (HRFs): familial Mediterranean fever (FMF), mevalonate kinase deficiency (MKD), tumour necrosis factor receptor-associated periodic...

TPL-2–ERK1/2 Signaling Promotes Host Resistance against Intracellular Bacterial Infection by Negative Regulation of Type I IFN Production

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of mortality and morbidity worldwide, causing ≈ 1.4 million deaths per year. Key immune components for host protection during tuberculosis include the cytokines IL-12, IL-1, and TNF-α, as well as IFN-γ and CD4(+) Th1 cells. However, immune factors determining whether individuals control infection or progress to active tuberculosis are incompletely understood. Excess amounts of type I IFN have been linked to exacerbated disease during tuberculosis in mouse models and to active disease in patients, suggesting tight regulation of this family of cytokines is critical to host resistance. In addition, the immunosuppressive cytokine IL-10 is known to inhibit the immune response to M. tuberculosis in murine models through the negative regulation of key proinflammatory cytokines and the subsequent Th1 response. We show in this study, using a combination of transcriptomic analysis, genetics, and pharmacological inhibitors, that the TPL-2-ERK1/2 signaling pathway is important in mediating host resistance to tuberculosis through negative regulation of type I IFN production. The TPL-2-ERK1/2 signaling pathway regulated production by macrophages of several cytokines important in the immune response to M. tuberculosis as well as regulating induction of a large number of additional genes, many in a type I IFN-dependent manner. In the absence of TPL-2 in vivo, excess type I IFN promoted IL-10 production and exacerbated disease. These findings describe an important regulatory mechanism for controlling tuberculosis and reveal mechanisms by which type I IFN may promote susceptibility to this important disease.

AB0719 Active synovitis at the wrist level detected by doppler ultrasound (us) is the most common finding in patients with inflammatory arthritis, irrespective of their underlying diagnosis – results from a cohort study.

BackgroundThe possibility to identify patterns of joint involvement in different types of inflammatory arthritis without obvious clinical synovitis has a practical approach, giving the possibility to implement simplified protocols for...

490 Prevalence of Antibodies to Adalimumab (ATA) and Correlation Between Ata and Low Serum Drug Concentration on CRP and Clinical Symptoms in a Prospective Sample of IBD Patients

BACKGROUND: Measurement of antibodies to infliximab (ATI) and the correlation observed between serum drug concentration and disease status have provided both insight into infliximab (IFX) immunogenicity and clinical utility to these markers for managing IBD patients on IFX. For adalimumab, such data are not readily available nor is clinical utility known. The prevalence of antibodies to adalimumab (ATA) in IBD patients is sparsely reported outside of one company sponsored clinical trial (2.6%). Correlation between ATA/ drug concentration and objective markers of inflammation (CRP) as well as clinical symptoms is poorly described. METHODS: An independent investigator-initiated cross-sectional study prospectively recruited 54 IBD patients on ADA (2 with ulcerative colitis) from a tertiary center to determine 1) prevalence of detectable ATA and drug concentration; 2) correlation between ATA /drug concentration and an objective measure of inflammation, C-reactive protein (CRP); and 3) whether stratified category of ATA/ drug concentration correlated with patient's self-described symptoms (remission, response, active flare). Patients were approached based on use of ADA for Crohn's or ulcerative colitis and not clinical status (remission, response, active). Questionnaire of symptoms, IBD history, ADA dosing, weight and CRP measurement were conducted within two weeks of ATA/drug concentration measurement. ATA/drug concentration blood draw was performed at trough, just prior to next ADA dose, and processed by Prometheus Laboratories. Detectable ATA was defined as .= 1U/ml and detectable drug as .=1 mcg/ml. RESULTS: The prevalence of detectable ATA was 22.2% (n=12/54) and detectable ADA concentration was 90.7% (n=49/54). Serum concentration of ,5 mcg/ml of ADA was associated with an elevated CRP (p=0.001). Detectable ATA was positively associated with an elevated CRP, and notably this correlation was independent of drug concentration (p=0.002) (Figure). Stratification of patients based on ATA/drug concentration demonstrated more active disease in patients with low drug concentration (,5 mcg/ml) and/or detectable ATA (p=0.01). CONCLUSION: Antibodies to adalimumab in ADA-treated IBD patients are more prevalent than reported in clinical trials and almost all patients on ADA have a detectable drug concentration. Both detectable ATA and ADA drug concentration ,5 mcg/ml have an important association with increased inflammation. The observation that detectable ATA correlates with elevated CRP independent of drug concentration is a novel finding and suggests preventing ATA may be the more critical of the two variables to address for maximizing clinical efficacy. That detectable ATA/ low drug concentration correlates with active disease suggests there may be clinical utility in obtaining these measurements, however longer-term data are needed.

491 Prediction of Clinical Response and Mucosal Healing At One Year by Faecal Calprotectin Assay After Induction With Anti-TNF Alpha Agents in IBD Patients

BACKGROUND: Measurement of antibodies to infliximab (ATI) and the correlation observed between serum drug concentration and disease status have provided both insight into infliximab (IFX) immunogenicity and clinical utility to these markers for managing IBD patients on IFX. For adalimumab, such data are not readily available nor is clinical utility known. The prevalence of antibodies to adalimumab (ATA) in IBD patients is sparsely reported outside of one company sponsored clinical trial (2.6%). Correlation between ATA/ drug concentration and objective markers of inflammation (CRP) as well as clinical symptoms is poorly described. METHODS: An independent investigator-initiated cross-sectional study prospectively recruited 54 IBD patients on ADA (2 with ulcerative colitis) from a tertiary center to determine 1) prevalence of detectable ATA and drug concentration; 2) correlation between ATA /drug concentration and an objective measure of inflammation, C-reactive protein (CRP); and 3) whether stratified category of ATA/ drug concentration correlated with patient's self-described symptoms (remission, response, active flare). Patients were approached based on use of ADA for Crohn's or ulcerative colitis and not clinical status (remission, response, active). Questionnaire of symptoms, IBD history, ADA dosing, weight and CRP measurement were conducted within two weeks of ATA/drug concentration measurement. ATA/drug concentration blood draw was performed at trough, just prior to next ADA dose, and processed by Prometheus Laboratories. Detectable ATA was defined as .= 1U/ml and detectable drug as .=1 mcg/ml. RESULTS: The prevalence of detectable ATA was 22.2% (n=12/54) and detectable ADA concentration was 90.7% (n=49/54). Serum concentration of ,5 mcg/ml of ADA was associated with an elevated CRP (p=0.001). Detectable ATA was positively associated with an elevated CRP, and notably this correlation was independent of drug concentration (p=0.002) (Figure). Stratification of patients based on ATA/drug concentration demonstrated more active disease in patients with low drug concentration (,5 mcg/ml) and/or detectable ATA (p=0.01). CONCLUSION: Antibodies to adalimumab in ADA-treated IBD patients are more prevalent than reported in clinical trials and almost all patients on ADA have a detectable drug concentration. Both detectable ATA and ADA drug concentration ,5 mcg/ml have an important association with increased inflammation. The observation that detectable ATA correlates with elevated CRP independent of drug concentration is a novel finding and suggests preventing ATA may be the more critical of the two variables to address for maximizing clinical efficacy. That detectable ATA/ low drug concentration correlates with active disease suggests there may be clinical utility in obtaining these measurements, however longer-term data are needed.

Sleep Disturbance and Risk of Active Disease in Patients With Crohn's Disease and Ulcerative Colitis

Impairment of sleep quality is common in patients with inflammatory bowel diseases (IBDs) (eg, Crohn's disease [CD] and ulcerative colitis [UC]), even during clinical remission. Sleep impairment can activate inflammatory pathways. Few prospective studies have examined the role of sleep disturbance on risk of relapse in IBD. We analyzed data from 3173 patients with IBD (1798 in clinical remission at baseline) participating in the Crohn's and Colitis Foundation of America Partners study, a longitudinal, Internet-based cohort. Sleep disturbance was measured using a subset of questions from the Patient Reported Outcomes Measurement Information Systems sleep disturbance questionnaire. Disease activity was assessed using the short Crohn's Disease Activity Index and the simple clinical colitis activity index for CD and UC, respectively. Logistic regression was used to identify predictors of sleep quality and examine the effect of sleep quality at baseline among patients in remission on risk of active disease at 6 months. Disease activity, depression, female sex, smoking, and use of corticosteroids or narcotics were associated with sleep disturbance at enrollment. Among 1291 patients whose CD was in remission at baseline, those with impaired sleep had a 2-fold increase in risk of active disease at 6 months (adjusted odds ratio, 2.00; 95% confidence interval, 1.45-2.76); however, no effect was observed in patients with UC (odds ratio, 1.14; 95% confidence interval, 0.75-1.74). These findings persisted in a number of sensitivity analyses. Sleep disturbance was associated with an increased risk of disease flares in CD but not UC. These findings indicate that the evaluation and treatment of sleep disturbance in patients with CD might improve outcomes.