Objective Measures Of Inflammation Research Articles

A273 A PILOT PROSPECITVE, MULTI-CENTRE, RANDOMIZED CONTROLLED TRIAL COMPARING FECAL MICROBIOTA TRANSPLANTATION (FMT) TO PLACEBO AT INDUCING REMISSION IN MILD TO MODERATE CROHN'S DISEASE

Abstract Background FMT has shown promise at inducing remission in ulcerative colitis. The effect of FMT on inducing remission in Crohn’s disease however remains unknown. Aims To evaluate the efficacy of FMT at inducing remission in mild-to-moderate Crohn’s disease Methods This double-blind, randomized, trial conducted at 3 Canadian academic centers (Edmonton, Hamilton and Calgary) randomized. Adult patients with mild-to-moderate Crohn’s disease with modified Harvey Bradshaw Index (mHBI) score of ampersand:003E5 and at least one objective measure of inflammation (CRP ≥ 8mg/L or fecal calprotectin (FCP) ≥ 250 ug/g) on stable dosing of concomitant therapy were assigned to FMT or placebo. First assigned treatment was by colonoscopy followed by 20 [DK1] capsules weekly for 7 weeks. Endoscopic severity (SES-CD) was assessed at baseline during colonoscopic delivery of assigned treatment and at week 8 by a blinded central reader using video recording. The primary endpoint was the proportion of patients in both clinical (mHBI ampersand:003C 5) and endoscopic remission (SES-CD ≤ 5) at week 8. Responders (reduction of HBI ≥ 3 or HBI ≤ 5 and reduction of CRP or FCP by ≥ 10%) in FMT group were eligible to continue with open-label FMT capsule every 2 weeks. Non-responders in the placebo group were permitted to restart the trial at week 0 with open-label FMT. Secondary outcomes included patient reported outcomes and safety outcomes. Results Between July 2017 to Jun 2021, 28 were randomized (16 to FMT and 12 to placebo). The study team voluntarily suspended the trial twice due to Health Canada safety warnings regarding potential transmission of multi-drug resistant organisms and SARS-CoV-2 through FMT. At week 8, 0% (0/16) of patients in the FMT group versus 8.3% (1/12) in the placebo group reached the primary endpoint of combined clinical and endoscopic remission. Of the 50% (8/16) in the FMT group who achieved a clinical response and continued on open-label FMT every 2 weeks, 12.5% (1/8) achieved the primary endpoint. Of the 7 non-responders in the placebo group who restarted the trial at week 0 and received open-label FMT, 28.6% (2/7) achieved primary endpoint at week 8 on open-label FMT. No death or hospitalization were observed. The study was terminated early at the recommendation of the Data Safety Monitoring Board. Conclusions FMT was not effective at inducing remission in Crohn’s disease using the FMT regimen in this study. However, this study was limited by a small sample size and recruitment barrier during the COVID pandemic. Future studies may consider other strategies to potentially enhance treatment response, including antibiotic pre-treatment, optimized donor-recipient pairing, and concomitant anti-inflammatory diet. Funding Agencies CIHR

DOP03 Gaps between ECCO quality standards of care and the real world: the E-QUALITY survey on processes and outcomes

Abstract Background The European Crohn’s and Colitis Organisation (ECCO) Position Paper on Quality-of-Care (QoC) proposed essential standards on process and outcomes for units that manage patients with inflammatory bowel disease (IBD). The E-QUALITY taskforce investigated whether gaps between these standards and real-world practice exist. Methods A 74-question web survey accessible to all institutions affiliated with ECCO was developed. One delegate per institution was requested to respond. A descriptive analysis was done. Results From March to October 2023, 166 centres from 28 different countries replied to the survey (Fig.1). At diagnosis, disease extent is assessed by colonoscopy in 96% and completed by small bowel (SB) evaluation in 43%. At least 2 biopsies from each segment are obtained in 55%. SB investigation for Crohn’s disease (CD) takes place in 60%. 54% of centres provide access to endoscopy with deep sedation for the majority of patients. To assess treatment response, faecal calprotectin is used in 65%, endoscopy in 54%, cross-sectional imaging for CD in 36%. In the case of primary failure of any drug, therapeutic decisions are based on objective measures of inflammation in 98%. A scheduled monitoring protocol for asymptomatic patients is followed in 42%. Patients with prolonged use of corticosteroids are being switched to a steroid-sparing treatment in 84%, but there is no protocol to track or act upon high steroid exposure in 43% of centres. 72% centres monitor metabolic bone health. Only 51% of units screen IBD patients for colorectal cancer, but screening is done with high-definition endoscopy in 92%. Chromoendoscopy with targeted biopsies is performed in only 47% units. Patients with perianal fistula are managed by combined medical and surgical approach in 67%, and reassessment by clinical and endoscopy and/or pelvic MRI is done in 62%. Laparoscopic approach for intra-abdominal surgery is used in 76%, and preoperative nutritional assessment in 62%. Patients receive therapies to prevent post-operative recurrence based on risk factors in 70%, standard endoscopy within 6-12 months after surgery is done only in 52% of centres. Although only 8% of centres lack a defined protocol to manage acute severe ulcerative colitis flares, 13% lack a standard algorithm, and 36% do not involve the surgeon in this setting from day 1. 38% of centres have a paediatric to adult transition clinic. The main reason for not adhering to ECCO standards are difficulty of providing tests in a timely fashion in up to 83% of centres. Conclusion Our survey has revealed significant gaps between ECCO standards and real-world practice. These results will help ECCO improve initiatives to help institutions to provide standard QoC. 1) Fiorino et al. JCC 2020;14:1037-48

Neuroimmune Modulation Through Vagus Nerve Stimulation Reduces Inflammatory Activity in Crohn's Disease Patients: A Prospective Open-label Study.

Crohn's disease [CD] is a debilitating, inflammatory condition affecting the gastrointestinal tract. There is no cure and sustained clinical and endoscopic remission is achieved by fewer than half of patients with current therapies. The immunoregulatory function of the vagus nerve, the 'inflammatory reflex', has been established in patients with rheumatoid arthritis and biologic-naive CD. The aim of this study was to explore the safety and efficacy of vagus nerve stimulation in patients with treatment-refractory CD, in a 16-week, open-label, multicentre, clinical trial. A vagus nerve stimulator was implanted in 17 biologic drug-refractory patients with moderately to severely active CD. One patient exited the study pre-treatment, and 16 patients were treated with vagus nerve stimulation [4/16 receiving concomitant biologics] during 16 weeks of induction and 24 months of maintenance treatment. Endpoints included clinical improvement, patient-reported outcomes, objective measures of inflammation [endoscopic/molecular], and safety. There was a statistically significant and clinically meaningful decrease in CD Activity Index at Week 16 [mean ± SD: -86.2 ± 92.8, p = 0.003], a significant decrease in faecal calprotectin [-2923 ± 4104, p = 0.015], a decrease in mucosal inflammation in 11/15 patients with paired endoscopies [-2.1 ± 1.7, p = 0.23], and a decrease in serum tumour necrosis factor and interferon-γ [46-52%]. Two quality-of-life indices improved in 7/11 patients treated without biologics. There was one study-related severe adverse event: a postoperative infection requiring device explantation. Neuroimmune modulation via vagus nerve stimulation was generally safe and well tolerated, with a clinically meaningful reduction in clinical disease activity associated with endoscopic improvement, reduced levels of faecal calprotectin and serum cytokines, and improved quality of life.

Changes of inflammation in patients with psoriatic arthritis after high intensity interval training assessed by ultrasound and MRI, a randomized controlled trial

BackgroundIn psoriatic arthritis (PsA) there is a theoretical risk of increased disease activity related to strenuous physical activity, including exercise. We evaluated the effect of high intensity interval training (HIIT) on objective measures of inflammation in PsA assessed by ultrasound (US) of peripheral joints and entheses, and by bone marrow edema (BME) on MRI of the sacroiliac joints (SIJ) and spine.MethodsWe randomly assigned 67 PsA patients to an intervention group that performed structured HIIT for 11 weeks, or to a control group instructed not to change their physical exercise habits. Outcome measures included US evaluation of the total cohort and MRI in a subgroup of 41; both assessed at 3 months. We calculated the proportions with an increased US B-mode and power-doppler (PD) signal of joints and entheses and Spondyloarthritis-Research-Consortium-of-Canada (SPARCC)-BME score of the SIJ and spine for both groups.ResultsProportions with an increased US B-mode score of the joints were 32% and 28% in HIIT and control groups, respectively. Corresponding proportions of PD scores of the joints were 7% and 10% and PD scores of entheses were 32% and 31%.The proportions with increased MRI BME of the SIJ were 6% in the HIIT group and 10% in the control group. Corresponding proportions were 6% and 5% for the MRI BME of the spine.ConclusionIn PsA patients with a low to moderate disease activity, there was no clear evidence of objectively measured increased inflammation after HIIT, as evaluated by US and MRI.Trial registrationClinicalTrials.gov NCT02995460 (16/12/2016).

A74 URGENCY FOR BOWEL MOVEMENTS IS A HIGHLY DISCRIMINATORY SYMPTOM FOR ACTIVE DISEASE IN PERSONS WITH IBD (THE MANITOBA LIVING WITH IBD STUDY)

Abstract Background The Inflammatory Bowel Disease Symptom Inventory (IBDSI) is a validated patient self-reported measure used to assess IBD disease activity. Purpose We aimed to assess the prevalence of symptoms, and examine which symptoms are most associated with disease activity as measured by a symptom index and objective measure of inflammation. Method The Manitoba Living with IBD Study is a prospective study of 156 participants with confirmed IBD who completed bi-weekly Inflammatory Bowel Disease Symptom Inventory (IBDSI) surveys. Relative risks (RR) (with 95% confidence interval (CI)), positive and negative predictive values (PPV, NPV), and area under receiver operator curve (AUC) were reported for each symptom to predict active disease defined as: (1) active IBDSI, (2) self-reported flare, and (3) elevated fecal calprotectin (FCAL) (>250µg/g). Analyses were undertaken following stratification based on sex, and disease type (Crohn’s disease (CD) and ulcerative colitis (UC)). Result(s) In total, 69.2% of participants were female; 64.7% had CD. Fatigue was the most prevalent symptom in both inactive and active disease, across all 3 disease measures (IBDSI: 24.5% and 75.1%, self-reported flare: 42.2% and 72.2%, FCAL: 46.0% and 60.6%). Absence of fatigue had a high NPV for active IBDSI and self-reporting a flare in both CD and UC. Urgency had a consistently strong NPV, RR and AUC across all three disease measures in both IBD subtypes and sexes. The number of loose/liquid bowel movements predicted elevated FCAL in UC (RR in men = 3.5, 95% CI 1.2-9.9, RR in women = 1.8, 95% CI 1.2-2.7, AUC in men = 0.73, 95% CI 0.59-0.84, AUC in women = 0.65, 95% CI 0.56-0.72), as did blood in stool in females with UC (RR = 1.8, 95% CI 1.2-2.7). In men with CD, excessive bowel gas (RR = 2.0, 95% CI 1.2-3.4) and urgency (RR = 3.9, 95% CI 1.6-9.3) best predicted an elevated FCAL. No symptom was strongly predictive of elevated FCAL in females with CD. Conclusion(s) Fatigue was the most prevalent symptom irrespective of disease activity. Urgency stood out as being consistently associated with disease activity, irrespective of the disease measure. Individual symptoms have different impacts on subjective (IBDSI) and objective (FCAL) measures in IBD. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials

ObjectivesAxial spondyloarthritis (axSpA) is a complex disease with diverse manifestations, for which new treatment options are warranted. BE MOBILE 1 (non-radiographic (nr)-axSpA) and BE MOBILE 2 (radiographic axSpA (r-axSpA)) are...

POS0306 EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS REFRACTORY TO BIOLOGIC THERAPY: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE 3 TRIAL

BackgroundUpadacitinib (UPA) was shown to be safe and effective through 2 years in patients (pts) with active ankylosing spondylitis (AS) naïve to biologic disease-modifying antirheumatic drugs (bDMARDs) in the pivotal phase 2/3 SELECT-AXIS 1 trial.1,2ObjectivesTo assess the efficacy and safety of UPA in pts with active AS with an inadequate response (IR) to bDMARDs.MethodsSELECT-AXIS 2 (NCT04169373) was conducted under a master protocol and includes two separate studies (one for AS bDMARD-IR and one for non-radiographic axial spondyloarthritis [nr-axSpA]). The AS bDMARD-IR study is a randomized, double-blind, placebo (PBO)-controlled, phase 3 trial that enrolled adults ≥18 years with AS who met modified New York criteria, had BASDAI and pt’s assessment of total back pain scores ≥4 (numeric rating scale 0–10) at study entry, and had an IR to one or two bDMARDs (TNF inhibitor or IL-17 inhibitor). Pts were randomized 1:1 to receive oral UPA 15 mg once daily (QD) or PBO during the 14-week (wk) double-blind treatment period. The primary endpoint was ASAS40 response at wk 14. Multiplicity-controlled secondary endpoints evaluated at wk 14 were improvements from baseline in disease activity (ASDAS [CRP], ASDAS ID [<1.3], ASDAS LDA [<2.1], BASDAI50, ASAS20, and ASAS PR), pain (total and nocturnal back pain), function (BASFI), objective measure of inflammation (SPARCC MRI score of the spine), spinal mobility (BASMI), enthesitis (MASES), and quality of life (ASQoL and ASAS HI). Non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle intercurrent events and missing data for binary endpoints. Cochran-Mantel-Haenszel (CMH) test and mixed-effect model for repeated measures (MMRM) were used for analyzing binary and continuous endpoints, respectively. Treatment-emergent adverse events (TEAEs) assessed through wk 14 are reported for pts who had ≥1 dose of study drug.ResultsAll 420 randomized pts with active AS received assigned treatment (UPA 15 mg, n=211; PBO, n=209); 409 (97%) received study drug through wk 14. Baseline demographic and disease characteristics were generally similar between treatment groups and reflective of an active AS bDMARD-IR population (74% male; mean age 42.4 years; mean disease duration 7.7 years; 83% HLA-B27 positive; mean BASDAI 6.8). Significantly more pts achieved the primary endpoint of ASAS40 response at wk 14 with UPA vs PBO (45% vs 18%; P<0.0001; Figure 1); UPA showed onset of effect in ASAS40 as early as wk 4 (nominal P≤0.05). All multiplicity-controlled secondary endpoints met statistical significance for UPA vs PBO at wk 14 across multiple clinical domains of AS (P<0.0001; Figure 1). The rate of TEAEs was similar between treatment groups through wk 14 (UPA, 41%; PBO, 37%). TEAEs led to discontinuation in 3 (1.4%) pts treated with PBO and none with UPA. Serious infections occurred with UPA (2.4%) but not with PBO and included 4 events of COVID-19 and 1 event of uveitis. Additional events of uveitis were reported in 3 (1.4%) pts treated with PBO. Inflammatory bowel disease (IBD) occurred in 1 (0.5%) pt on UPA and none on PBO. No malignancy, major adverse cardiovascular events, venous thromboembolic events, or death were reported with UPA; 1 event of malignancy was observed with PBO.ConclusionUPA 15 mg QD was significantly more effective than PBO over 14 wks of treatment in pts with active AS and IR to bDMARDs. No new safety risks were identified with UPA compared with its known safety profile.3,4 These findings are consistent with and complementary to those of SELECT-AXIS 1 (bDMARD-naïve AS population),1,2 and support the use of UPA in pts with active AS, including those who had a previous IR to bDMARD therapy.

Mechanism underlying painful radiculopathy in patients with lumbar disc herniation.

Painful lumbar radiculopathy is a neuropathic pain condition, commonly attributed to nerve root inflammation/compression by disc herniation. The present exploratory study searched for associations between pain intensity and inflammatory markers, herniated disc size, infection, psychological factors and pain modulation in patients with confirmed painful lumbar radiculopathy scheduled for spine surgery. Prior to surgery, 53 patients underwent the following evaluation: pain intensity measured on a 0-10 numeric rating scale (NRS) and the Short-Form McGill Pain Questionnaire; sensory testing (modified DFNS protocol); pain processing including temporal summation and conditioned pain modulation (CPM); neurological examination; psychological assessment including Spielberger's Anxiety Inventory, Pain Sensitivity Questionnaire and the Pain Catastrophizing Scale. Pro-inflammatory cytokine levels (IL-1b, IL-6, IL-8, IL-17, TNFα, IFNg) and microbial infection (ELISA and rt-PCR) in blood and disc samples obtained during surgery. MRI scans assessments for disc herniation size/volume (MSU classification/ three-dimensional volumetric analysis). Complete data were available from 40 (75%) patients (15 female) aged 44.8±16.3years. Pain intensity (NRS) positively correlated with pain catastrophizing and CPM (r=0.437, p=0.006; r=0.421, p=0.007; respectively), but not with disc/blood cytokine levels, bacterial infection or MRI measures. CPM (p=0.001) and gender (p=0.029) were associated with average pain intensity (adjusted R2 =0.443). This exploratory study suggests that pain catastrophizing, CPM and gender, seem to contribute to pain intensity in patients with painful lumbar radiculopathy. The role of mechanical compression and inflammation in determining the intensity of painful radiculopathy remains obscure. Pain catastrophizing, CPM and gender rather than objective measures of inflammation and imaging seem to contribute to pain in patients with painful radiculopathy.

Qualitative study on perceptions of use of Fractional Exhaled Nitric Oxide (FeNO) in asthma reviews

Current methods to assess asthma and guide inhaled corticosteroid (ICS) dose titration mainly centre on patient-reported symptoms and lung function assessments. However, these methods correlate only weakly with airway inflammation making them unreliable predictors of future exacerbations and ICS requirement. Fractional Exhaled Nitric Oxide (FeNO) is a simple non-invasive objective measure of airways inflammation used predominantly in specialist clinics. Previous qualitative studies have mainly focused on the acceptability of FeNO in secondary care and there is limited insight to support clinicians and patients using FeNO in primary care asthma reviews. This study aimed to explore adult patient with asthma and primary care health care professional (HCP) views on introducing FeNO as part of routine asthma reviews. Twenty-three health care professionals and 22 patients were interviewed over the phone or online. Both groups reported that current asthma reviews are often seen as tick-box exercises and that introducing the FeNO test would make reviews more tailored to the individual patient, rather than relying on subjective patient reports of asthma control. Adults with asthma also highlighted support more open communication and their understanding of asthma, as they desired to feel more engaged in decisions and conversations about their asthma. HCPs reported valuing patient education and empowerment over a paternalistic approach, when time and resources allow. They also recognised FeNO to provide an objective measure of inflammation that could support them in the education and empowerment of patients. FeNO was seen by both groups as a potentially valuable addition to current asthma reviews mainly led by nurses, both for increasing their understanding of current risk of exacerbation and also to provide more tailored and personalised asthma management to patients. Our findings highlighted the need for open and clear communication about how to interpret FeNO results.

Pain: A Review of Interleukin-6 and Its Roles in the Pain of Rheumatoid Arthritis.

Pain is a major and common symptom reported as a top priority in patients with rheumatoid arthritis (RA). Intuitively, RA-related pain is often considered to be a natural consequence of peripheral inflammation, so treatment of RA is expected to manage pain concurrently as part of inflammation control. However, pain in patients with RA can be poorly correlated with objective measures of inflammation, for example, in patients who are otherwise in remission. Joint damage appears to account for only a fraction of this residual pain. Emerging evidence suggests that alteration of peripheral and central pain processing contributes to RA-related pain; this is parallel to, but somewhat independent of, joint inflammation. Interleukin (IL)-6 is a proinflammatory cytokine that contributes to the pathogenesis of RA. It exerts systemic effects via signaling through soluble forms of the IL-6 receptor (“trans-signaling”). Evidence from preclinical studies demonstrates that intra-articular IL-6 can produce long-lasting peripheral sensitization to mechanical stimulation and suggests an important role for IL-6 in central pain sensitization. This may be partly explained by its ability to activate neurons through trans-signaling, affecting nociceptive plasticity and nerve fiber regrowth. Local activity at neuron endings may culminate in altered pain processing in the central nervous system because of persistent signaling from sensitized peripheral neurons. Peripheral and central sensitization can promote the development of chronic pain, which can have a significant impact on patients’ health and quality of life. A proportion of pain in RA may be more appropriately managed as an entity separate from inflammation. Both the peripheral and central nervous systems should be recognized as important potential systems targeted by RA. The substantial burden of RA-related chronic pain suggests that pain should be a key focus in RA management and should be assessed and addressed early and separately from the inflammatory component.

Effect of tear supplements on signs, symptoms and inflammatory markers in dry eye

PurposeThree tear supplements were compared for their effects on the signs, symptoms and inflammatory status of subjects with dry eye disease. Assessments were made before and after both 2 and 4 weeks of treatment. MethodsIn this masked, randomized, 3-way crossover trial, eighteen dry eye subjects were recruited. At each visit, symptoms, tear evaporation rate, stability and osmolarity were measured and tear samples were analyzed for 7 inflammatory markers, using multiplex immunoassays. The 3 treatments included carboxymethylcellulose-glycerine-castor oil (CGC), carboxymethylcellulose (CMC) and hydroxypropyl guar (HPG). The CGC and HPG drops are emulsified lipids; CGC also contains osmoprotectants. The CMC drop is a standard aqueous polymeric supplement. ResultsSignificant improvements were seen in symptoms (OSDI) and tear stability (NITBUT) with all 3 treatments at 4 weeks. At 4 weeks post-CGC, 6 out of 7 biomarkers demonstrated a >25% reduction (in 40% of subjects). The same reduction (>25%) was seen in 10% of the subjects for CMC and in none of the subjects for HPG. No significantly different change to either evaporation rate or tear osmolarity was found following any of the three treatments. ConclusionsIn this study, the CGC treatment resulted in the greatest reduction in ocular biomarkers of inflammation, while all 3 treatments reduced symptoms and improved tear stability. These results indicate that subject-perceived symptomatic improvements are not necessarily associated with a reduction in objective measures of inflammation.

The Association of Vitamin D Status with Disease Activity in a Cohort of Crohn's Disease Patients in Canada.

We determined the association between vitamin D status as 25hydroxyvitamin D [25(OH)D] and disease activity in a cohort of 201 Crohn’s Disease (CD) patients in Saskatoon, Canada over three years. The association between high-sensitivity C-reactive protein (hs-CRP) and 25(OH)D and several disease predictors were evaluated by the generalized estimating equation (GEE) over three time-point measurements. A GEE binary logistic regression test was used to evaluate the association between vitamin D status and the Harvey-Bradshaw Index (HBI). The deficient vitamin D group (≤29 nmol/L) had significantly higher mean hs-CRP levels compared with the three other categories of vitamin D status (p < 0.05). CRP was significantly lower in all of the other groups compared with the vitamin D-deficient group, which had Coef. = 12.8 units lower (95% CI −19.8, −5.8), Coef. 7.85 units (95% CI −14.9, −0.7), Coef. 9.87 units (95% CI −17.6, −2.0) for the vitamin D insufficient, adequate, and optimal groups, respectively. The vitamin D status was associated with the HBI active disease category. However, the difference in the odds ratio compared with the reference category of deficient vitamin D category was only significant in the insufficient category (odds ratio = 3.45, p = 0.03, 95% CI 1.0, 10.8). Vitamin D status was inversely associated with indicators of disease activity in Crohn’s disease, particularly with the objective measures of inflammation.

Peripheral Findings and Retinal Vascular Leakage on Ultra-Widefield Fluorescein Angiography in Patients with Uveitis

To compare ultra-widefield fluorescein angiography (UWFFA) with simulated conventional fluorescein angiography (FA) to evaluate peripheral pathology and leakage and correlate with clinical activity in patients with uveitis. Retrospective chart review. All uveitis patients initially evaluated with UWFFA (Optos 200Tx) between May 2012 and December 2013 were included in this study, including follow-up visits through August2014. Uveitis status was deemed as having active or inactive inflammation based on clinical examination. Changes to therapy, influence on management, and clinical diagnosis were also noted. UWFFA images were compared with simulated 50-degree FA images to evaluate for peripheral lesions, and leakage location was also graded. Imaging characteristics were then correlated with clinical information. Correlation of leakage on UWFFA with clinical inflammation. An initial set of 243 uveitis patients and a total of 1008 eye images were reviewed. When UWFFA was compared with a simulated 50-degree FA image, UWFFA added additional information regarding the presence of peripheral vascular leakage in 25%, peripheral nonperfusion in 14%, peripheral lesions in 6.6%, and peripheral neovascularization in 3.9% of patients. A total of 600 eye images exhibited fluorescein leakage, of which 21% displayed central leakage only, 11% had central and peripheral leakage, 31% had peripheral leakage only, and 37% had diffuse vascular leakage. Based on peripheral findings on widefield angiography, the treatment was changed in 69 patients (28%). Corresponding eye examinations were reviewed for each imaging session, and of 600 eye images with vascular leakage, 567 eye images were also clinically active, which was 95% sensitive as a surrogate indicator of clinical inflammation. Anterior chamber cell and vitreous haze also significantly correlated with leakage on widefield angiography. Retinal vascular leakage on UWFFA reveals increased pathology and leakage compared with conventional angiography, which can influence management, and accurately identifies and correlates with active inflammation in patients with uveitis. A more objective measure of inflammation in the form of leakage exhibited on UWFFA may help standardize treatment and care of patients with uveitis.

FOCUS: Future of fecal calprotectin utility study in inflammatory bowel disease.

AIMTo evaluate the perspective of gastroenterologists regarding the impact of fecal calprotectin (FC) on the management of patients with inflammatory bowel disease (IBD).METHODSPatients with known IBD or symptoms suggestive of IBD for whom the physician identified that FC would be clinically useful were recruited. Physicians completed an online “pre survey” outlining their rationale for the test. After receipt of the test results, the physicians completed an online “post survey” to portray their perceived impact of the test result on patient management. Clinical outcomes for a subset of patients with follow-up data available beyond the completion of the “post survey” were collected and analyzed.RESULTSOf 373 test kits distributed, 290 were returned, resulting in 279 fully completed surveys. One hundred and ninety patients were known to have IBD; 147 (77%) with Crohn’s Disease, 43 (21%) Ulcerative Colitis and 5 (2%) IBD unclassified. Indications for FC testing included: 90 (32.2%) to differentiate a new diagnosis of IBD from Irritable Bowel Syndrome (IBS), 85 (30.5%) to distinguish symptoms of IBS from IBD in those known to have IBD and 104 (37.2%) as an objective measure of inflammation. FC levels resulted in a change in management 51.3% (143/279) of the time which included a significant reduction in the number of colonoscopies (118) performed (P < 0.001). Overall, 97.5% (272/279) of the time, the physicians found the test sufficiently useful that they would order it again in similar situations. Follow-up data was available for 172 patients with further support for the clinical utility of FC provided.CONCLUSIONThe FC test effected a change in management 51.3% of the time and receipt of the result was associated with a reduction in the number of colonoscopies performed.

Biomarkers of Inflammation in Inflammatory Bowel Disease

Recent observations suggest that subjective measures of disease activity in inflammatory bowel disease (IBD) are often misleading. Objective measures of inflammation are more closely associated with important long-term outcomes, but often depend upon invasive and costly procedures such as ileocolonoscopy and cross-sectional imaging by computed tomography or magnetic resonance imaging. Noninvasive, accurate, and inexpensive measures of intestinal inflammation would allow clinicians to adopt widely the paradigm of adjusting therapies with a goal of controlling inflammation. Blood, stool, and urine markers have all been explored as indicators of intestinal inflammation in IBD, and although none has been universally adopted, some have been well-characterized, and others hold great promise. Serum C-reactive protein and fecal calprotectin are among the best-studied noninvasive biomarkers of inflammation in IBD, and their test characteristics have been described in the setting of differentiating IBD from irritable bowel syndrome, for grading inflammation, to describe the response to therapy, and in demonstrating recurrent inflammation after medical or surgically induced remission. High-throughput research platforms, including gene expression arrays, metabolomics and proteomics, are also being applied to the discovery of novel biomarkers of inflammation. It is certain that biomarkers of inflammation will attain growing importance in the clinic as we strive for more effective and cost-effective strategies to treat patients with IBD.

Clinical Remission as Defined by the Mayo Score

Reply: In his comment on our article, Professor Peyrin-Biroulet raises an important point and astutely identifies some of the deficiencies of the Mayo score and inconsistencies in its use. We agree with his assertion that combining clinical and endoscopic parameters into a single index is inherently flawed. We also agree that we should be moving away from this dogmatic method of evaluating disease activity in ulcerative colitis as this type of approach increases the variability of evaluations and decreases statistical efficiency. It is also not fully validated and infrequently applied in clinical practice. However, we disagree regarding the possible solution to this problem suggested by Professor Peyrin-Biroulet. Instead of simply dividing the clinical and endoscopic Mayo components to derive additional unvalidated definitions for remission, we would be in favor of using patient-reported outcomes and endoscopy as co-endpoints. In our opinion, this approach offers several advantages. Primarily, by the nature of their generation, patient-reported outcomes can be considered more clinically meaningful than a physicians’ subjective symptom assessment as they are created and defined by patients themselves. This means that they are more readily applicable to clinical practice and, in combination with endoscopy as an objective measure of inflammation, offer the opportunity to remedy the existing disconnect in outcome assessment between trials and practice. The benefit of such convergence in goal-setting and progress evaluation is likely to grow as “treatto-target” algorithms becoming more widely adopted. When considering the most appropriate endoscopic instrument to use as a co-endpoint along side patient-reported outcomes, the systematic development and initial validation of the Ulcerative Colitis Endoscopic Index of Severity mean that it is ideally placed for this use. However, as described in our article, this would require further validation and growing adoption for routine use in clinical practice before it can be favored over the Mayo score.

The Effect of Socioeconomic Class and Immigrant Status on Disease Activity in Rheumatoid Arthritis: Data from BARFOT, a Multi-Centre Study of Early RA

Background: There have been no reports on the effect of immigrant status and socioeconomic status on outcome in rheumatoid arthritis (RA) in Sweden. Methods: Between 1992 and 2006, 2,800 patients were included in the BARFOT study on early RA in Sweden. Disease Activity Score 28 joints (DAS28), Health Assessment Questionnaire (HAQ), treatment and European League Against Rheumatism (EULAR) response criteria were registered. In 2010, 1,430 patients completed a questionnaire enquiring about demographics and lifestyle factors. Results: One hundred and thirty-nine of the 1,430 patients (9.7%) were immigrants. At baseline immigrants had higher mean HAQ (1.2 vs 0.97 for non-immigrants, p=0.001), DAS28 (5.6 vs 5.2, p=0.000), visual analog scale (VAS) pain (56 mm vs 45 mm, p=0.000), VAS global health (53 mm vs 44 mm, p=0.000) and tender joint count (TJC) (10 vs 8, p=0.000). These differences persisted for up to 2 years of follow-up (for HAQ, for up to 8 years of follow-up). Immigrant status did not have any effect on swollen joint count (SJC), ESR, CRP or EULAR response. Socioeconomic class did not have any effect on treatment or outcome. Conclusions: Immigrants scored worse in pain, function and TJC for up to 2 years of follow-up, but they did not differ from non-immigrants in objective measures of inflammation or EULAR outcome. This could be due to different perceptions of health and pain and/or the stress of immigration. Socioeconomic class had no effect on treatment or outcome, and this could be due to the relatively egalitarian society in Sweden.

Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn's disease in the SONIC trial

Background and aimsThe Crohn's Disease Activity Index (CDAI) has been criticised due to heavy weighting on subjective clinical symptoms. C-reactive protein (CRP) and endoscopic lesions are objective measures of inflammation....

AB0847 Comparison of treatment responses to TNF-blockers in axial spondyloarthritis patients with short vs long symptom duration

ObjectivesTo investigate the influence of disease duration on treatment response and on the correlation between improvement of patients’ symptoms and improvement in objective measures of inflammation in patients with axial...

FRI0078 The effect of socioeconomic class and immigrant status on disease activity in rheumatoid arthritis. data from barfot, a multicenter study of early ra.

BackgroundThere are no studies reporting the effect of immigrant status and socioeconomic status on outcome in rheumatoid arthritis (RA) in Sweden.ObjectivesWe wanted to study the effect of immigration and socioeconomic...