Clinical Measures Of Disease Activity Research Articles

Sonographic and Disease Activity Findings Related With Medication Change in JIA: A Historical Cohort Study.

Musculoskeletal ultrasound (MSUS) is increasingly used to evaluate pediatric inflammatory arthritis. This study aimed to explore the relationship between MSUS findings with medication modifications in patients with juvenile idiopathic arthritis (JIA) and clinical disease activity measurements (clinical Juvenile Arthritis Disease Activity Score [cJADAS-10], active joint count [AJC], patient/parent global assessment [PPGA], and physician global assessment [PGA]). Data from patients with JIA who underwent a 12-joint (bilateral second and third metacarpophalangeal, wrist, elbow, knee, and ankle) MSUS examination during a 57-month period were collected. Patients were categorized into 2 groups: a medication change group and a control group (patients without medication change). A pediatric-specific MSUS scoring system was used to assess MSUS findings. The association between clinical and MSUS findings was examined for the study groups. A total of 38 patients, 23 in the medication change group and 15 in the control group were included. The medication change group had higher AJC, PGA, and cJADAS-10. These patients also had a statistically significant presence of abnormal knee MSUS findings. For other joints, the frequency of abnormal MSUS findings was slightly higher in patients with a medication change, but the difference was not statistically significant. No strong correlation was observed between MSUS findings and clinical disease activity measurements. Abnormal MSUS findings were not observed to be higher in patients with a change in medication except for the involvement of the knee joint. Further longitudinal studies are needed to understand the role of MSUS in the medical decision-making process in JIA.

Predictive accuracy of fecal calprotectin for histologic remission in ulcerative colitis.

Accurate assessment of disease activity is crucial for effective management and treatment of ulcerative colitis (UC). This study evaluated the correlation between clinical, endoscopic, and histologic measures of disease activity in UC. Clinical, biochemical, endoscopic, and histologic disease activity was studied in 347 patients with UC. Agreements among various histologic classification systems, namely the Geboes Score (GS), Continuous GS, Nancy Index (NI), and Robarts Histopathology Index (RHI), were analyzed. The predictive accuracy of fecal calprotectin (FC) for endoscopic and histologic remission was assessed. We demonstrate a fair to moderate correlation between clinical, endoscopic, and histologic measures of disease activity in UC. There was a robust concordance among GS, Continuous GS, NI, and RHI in distinguishing between patients in histologic remission or activity. The NI detected 75% of patients who met the remission criteria according to the RHI, whereas the RHI identified all patients in remission as defined by the NI. FC levels below 150 μg/g had >70% accuracy in predicting endoscopic remission. FC levels below 150 μg/g showed ≥80% accuracy, and FC levels below 100 μg/g demonstrated ≥ 85% accuracy in predicting histologic remission, regardless of the scoring index applied. Elevated FC levels were associated with both acute and chronic inflammatory infiltrates in biopsy samples. FC is a reliable predictor of histologic remission, with higher accuracy at lower thresholds. The GS, Continuous GS, NI, and RHI demonstrate comparable performance. FC could help stratify patients' need for colonoscopy for the assessment of endoscopic and histologic remission.

B-103 Correlation of Novel Markers, Anti-Sa (Citrullinated Vimentin) and Anti-CarP (Carbamylated Protein), with High Vectra® DA Disease Activity Scores in Rheumatoid Arthritis (RA)

Abstract Background Citrullination and carbamylation are post-translational modifications where autoantibodies against citrullinated and carbamylated proteins in RA have been associated with more aggressive disease. At the same time, Vectra® DA is blood test that yields a RA disease activity score from 1 to 100. Here, 120 patient samples were analyzed to assess the relationship of disease activity as measured by Vectra® score and the presence of Anti-Sa (Citrullinated Vimentin) and Anti-CarP (Carbamylated Protein). Methods Serum samples were analyzed for Vectra® DA (which is validated for adults with RA) where 12 biomarker measurements (VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, MMP-1, YKL-40, Leptin, Resistin, SAA, CRP) together with patient age, gender and adiposity are used to generate a score where established categories are low for 1 to 29, moderate for 30 to 44, and high for 45 to 100. Anti-Sa and Anti-CarP were by ELISA lab-developed tests (LDT) with a cut-off for positive of >20 Units (U). Results Anti-Sa and Anti-CarP for 40 samples from each Vectra® DA category are reported. Patients with the highest Vectra® scores (mean 58.2, range 46.8 - 87.5) had highest rates of positivity for Anti-Sa (52.5%) and Anti-CarP (35%). In contrast, the group with the lowest Vectra® scores (mean 11.8, range 3.8 - 18.1) were infrequently positive for Anti-Sa (17.5%) and Anti-CarP (0%). Frequencies with moderate Vectra® scores (mean 37.1, range 32.4 - 41.8) were mid-range: Anti-Sa (25%) and 7.5% for Anti-CarP (7.5%). Of note, positivity of Anti-Sa was analytically stronger, i.e. higher titer, in patients with moderate or high Vectra® (mean 90.0U or 81.7U), compared to values seen in those with low Vectra® (mean 60.4 U). Conclusions Our analysis of 120 patient samples demonstrates that high disease activity as determined by Vectra® DA corresponds to higher positivity of novel autoantibody markers, Anti-Sa and Anti-CarP. High Vectra® DA scores (>44) are associated with a 20% 1-year risk of radiographic progression while low scores (<30) carry only a 1% risk. Here, we found that patients with high Vectra® scores were 3 times more likely to test positive for Anti-Sa than those with low disease activity scores. At the same time, Anti-CarP occurred in high frequency (35%) with high Vectra® in contrast to zero positivity observed with low Vectra® scores. Thus, our findings support Anti-CarP’s reported association with more active disease with higher risk of developing joint erosions. Also of note, patients with high Vectra® scores had particularly high Anti-Sa positivity - both a 52.5% positivity rate as well as higher Anti-Sa levels (titers) than the group with lower Vectra® scores. These data corroborate other studies where Anti-Sa not only predicted more aggressive, rapid disease progression, but its titers correlated with clinical measures of disease activity. Taken together, our data support the consistency and clinical usefulness of the Vectra® score along with novel autoantibody markers, Anti- Anti-Sa and Anti-CarP, in order to assess RA severity, prognosis, and patient-specific treatment strategies.

Correlations between ultrafast power Doppler perfusion imaging variables and clinical disease activity in rheumatoid arthritis: potential applications for diagnosing and treating patients in deep clinical remission.

This study aimed to evaluate the ability of ultrafast power Doppler (PD) to assess disease activity in rheumatoid arthritis (RA) by examining the correlations between variables from ultrafast PD perfusion imaging and clinical measures of disease activity. Thirty-three RA patients underwent clinical assessments of disease activity and ultrasound scans of bilateral wrists using both ultrafast and conventional PD systems. A spatial singular value decomposition filter was applied to the ultrafast PD imaging. Singular vectors representing perfusion and fast flows were selected to produce perfusion images. All images were quantitatively analyzed with computer assistance and scored semiquantitatively (0-3) by a physician for synovial vascularity. The Pearson correlation coefficients between image variables and clinical indices were calculated. The correlation coefficients ranged from weakly to moderately positive between ultrafast PD variables and clinical indices (r=0.221-0.374, all P<0.05). The strongest correlations were observed for synovial PD brightness with the 28-joint Disease Activity Score based on C-Reactive Protein (DAS28-CRP) and the Simplified Disease Activity Index (SDAI). In patients within the deep clinical remission (dCR) subgroup, synovial PD brightness showed stronger correlations with DAS28-CRP, the Clinical Disease Activity Index, and SDAI (r=0.578-0.641, all P<0.001). The correlation coefficients between conventional PD variables and clinical indices were similar to those observed with ultrafast PD variables. Ultrafast PD imaging effectively extracts capillary blood signals and generates perfusion images. In the RA population, ultrafast PD variables exhibit weak-to-moderate correlations with clinical indices, with these correlations being notably stronger in dCR patients.

Exploratory analysis of the potential disconnect between objective inflammatory response and clinical response following certolizumab pegol treatment in patients with active axial spondyloarthritis

IntroductionThis post hoc analysis evaluated the relationship between objective measures of inflammation and clinical outcomes following 12 weeks of certolizumab pegol (CZP) treatment in patients with active axial spondyloarthritis (axSpA).MethodsWe...

Regional variations in psoriatic arthritis: Insights from a nationwide multicenter analysis in Türkiye.

The study aimed to investigate and compare clinical features, disease activity, and the overall disease burden among psoriatic arthritis (PsA) patients across seven distinct geographic regions in Türkiye. A multicenter cross-sectional study involving 1,134 PsA patients from 25 referral centers across seven regions was conducted. Demographic and clinical characteristics, comorbidities, joint involvement, extra-articular manifestations, and disease activity measures were evaluated across regions. A total of 1134 PsA patients from seven different geographic regions in Türkiye participated in this study. The highest number of participants was from the Marmara region (n=409), with subsequent representation from Central Anatolia (n=370), Aegean (n=139), Mediterranean (n=60), Black Sea (n=60), Eastern Anatolia (n=60), and Southeastern Anatolia (n=36) regions. There were significant variations in demographic profile, including age, body mass index, age of disease onset, educational status, comorbidities, and family history of both psoriasis and PsA. Clinical features, such as enthesitis, dactylitis, uveitis, and joint involvement, demonstrated significant variation across regions. Additionally, disease activity measures, including pain, patient and physician global assessments, acute phase reactants, disease activity indices, quality of life, and functional status, displayed considerable regional differences. This nationwide study revealed substantial regional diversity in demographic data, clinical characteristics, disease activity, and quality of life among PsA patients in Türkiye. These findings stress the need to customize treatment approaches to address regional needs and to conduct further research to uncover reasons for disparities. It is crucial to enhance region-specific approaches to improve patient care and outcomes for PsA.

Clinical characteristics and disease burden of African, Caribbean, and Black people with multiple sclerosis in Toronto, Canada

BackgroundDifferent racial and ethnic groups have demonstrated heterogeneity in the clinical course of multiple sclerosis(MS). ObjectiveWe aimed to evaluate disease characteristics in African, Caribbean, and Black people with MS(ACB-MS) followed at a single centre in Toronto, Canada. MethodsACB-MS were compared with age- and sex-matched people with MS (pwMS) of European descent(EUR-MS) identified through the clinic registry. Results344 PwMS were included(n = 172 ACB-MS, n = 172 EUR-MS; mean age 43 years, 68 % female). Baseline mean Expanded disability status scale (EDSS) scores (ACB-MS 2.3 ± 2.3 vs. EUR-MS 2.2 ± 2.0, p = 0.38) and subsequent clinical and radiological measures of disease activity were similar between groups, including annualized relapse rate (ARR)(ACB-MS 0.47 ± 0.47 vs. EUR-MS 0.41 ± 0.34, p = 0.2) and most recent EDSS (ACB-MS 2.7 ± 2.2 vs. EUR-MS 2.3 ± 2.1, p = 0.10). However, the proportion of MRI brain demonstrating new disease activity was higher(37% vs. 26 %, p < 0.05) and disability progression greater in ACB-MS vs. EUR-MS(43% vs. 33 %,p < 0.05) but measures of disease severity including MS Severity Score(3.17 vs. 2.58, p = 0.3) and Progression Index(PI) (0.27 vs. 0.30, p = 0.5) were comparable. Conclusion: Disability progression was seen more commonly in ACB-MS, though clinical disease activity and severity were generally comparable between ACB-MS and EUR-MS patients in Toronto, Canada. These findings partially differ from prior studies demonstrating more overtly aggressive MS disease courses in Black and African American PwMS, necessitating further studies to understand how structural determinants of health drive these disparities.

Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study

ObjectivesTo assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population.MethodsIn this multicentre...

P175 The Psoriatic Arthritis Impact of Disease 12-item questionnaire can replace other patient-reported outcome measures to facilitate disease monitoring in clinical practice

Abstract Background/Aims The Psoriatic Arthritis Impact of Disease 12-item questionnaire (PsAID-12) was developed and validated to improve assessment of disease activity from the patient’s perspective. Several patient-reported outcome measures (PROMs) are relevant to PsA but completing several questionnaires at each clinic visit creates a time and administrative burden for patients and clinicians. Furthermore, the Minimal Disease Activity (MDA) for assessing disease activity in PsA requires the Health Assessment Questionnaire (HAQ) to be collected; however, a Canadian study found that PsAID-12 can replace HAQ in the MDA using a cut-off of &amp;lt; 3.7. A previous study also found sex-specific differences in PsAID-12 scores, with scores being higher in females. The aim of this study was to assess whether PsAID-12 correlates well and could replace other PROMs in clinical practice, and to validate previously published findings related to the use of PsAID-12 instead of HAQ in determining MDA, and sex-specific differences in PsAID-12 scores. Methods Clinical data were collected from 75 consecutive patients attending a PsA clinic in a tertiary centre at their first review in 2023. Clinical characteristics, PROMs, examination findings, and measures of disease activity were recorded. Correlation with PsAID-12 was assessed using Spearman’s rank correlation coefficient. Sex-specific differences were assessed using Mann-Whitney U tests. Bonferroni correction was used to adjust for multiple comparisons. Results PsAID-12 scores were significantly correlated with all PROMs, and with composite measures of disease activity (DAPSA, MDA), but not with clinical measures of disease activity (TJC, SJC, PASI, BSA), or acute-phase reactants (CRP, ESR). PsAID-12 scores were not affected by age or disease duration. There was no sex-dependent difference in PsAID-12 scores; however, female patients had significantly higher HAQ and HAD scores. MDA scores using PsAID-12 correlated significantly with MDA scores using HAQ. Conclusion PsAID-12 is a suitable replacement for other PROMs in clinical practice, and for HAQ when determining MDA status to reduce the time and administrative burden on patients and clinicians, and to facilitate monitoring of disease activity in patients with PsA regardless of age or disease duration. Contrary to previous studies, there were no sex-dependent differences in PsAID-12 scores. Disclosure R.M. Hum: None. K. Hasanein: None. L.T. Hao: None. J.C. Williams: None. A. Cheung: None. A. Adhikarla: None. A. Choyce: None. A. Newton: None. C. Clegg: None. A. Barton: None. P. Ho: None.

Methotrexate treatment strategies for rheumatoid arthritis: a scoping review on doses and administration routes

BackgroundTo describe the evidence of methotrexate (MTX) initiation strategies in patients with rheumatoid arthritis (RA) and, in the case of non-responders, analyse the efficacy and safety of route and dose optimisation.MethodsWe conducted a comprehensive scoping review of randomised controlled trials according to PRISMA Scoping Reviews Checklist and the framework proposed by Arksey and O’Malley. PubMed, EMBASE, and Cochrane were searched without language restriction, and hand searches of relevant articles were examined.ResultsWe identified 1,367 potentially eligible studies, of which 12 were selected based on the titles and abstracts and then on the full-length articles. In naïve-MTX patients, a linear dose-response relationship for starting dose was found between 5 mg/m2/week (7.5–10 mg/week) and 10 mg/m2/week (15–22 mg/week), without toxicity correlation. A higher initial dose of MTX (25 mg vs. 15 mg) was more effective, resulting in fewer dose increases due to ineffectiveness and more dose reductions due to higher remission rates. There was also a trend towards increased gastrointestinal toxicity. Comparing different routes of administration of MTX, subcutaneous MTX showed a statistically higher ACR20 response (85%) in comparison with oral MTX (77%) (p < 0.05). The clinical efficacy and safety of accelerated and conventional start MTX regimens were comparable between 7.5 and 15 mg with a 2,5 mg dose increase every two weeks. In RA patients who have failed the initial treatment with MTX, the stepwise increase in MTX doses is associated with a higher ACR20 response and sustained remission rate than other strategies. In MTX non-responders, optimisation to SC MTX was associated with improvements in ACR20 and ACR50 rates with similar toxicity between groups. In the early RA patients subgroup, SC MTX showed higher ACR20 response rates than oral MTX, and intensive oral methods have a much higher sustained remission rate, shorter mean time to remission, and better clinical disease activity measures than conventional treatments.ConclusionsHigher starting doses of MTX and initial subcutaneous MTX made better performance in improving the ACR20 response, although the clinical effectiveness and safety of other MTX start regimens are comparable. This scoping review provides evidence in support of optimising MTX treatment in terms of route and dose prior to concluding that MTX treatment in RA patients has failed.

Long-term efficacy of a 2-year MRI treat-to-target strategy on disease activity and radiographic progression in patients with rheumatoid arthritis in clinical remission: 5-year follow-up of the IMAGINE-RA randomised trial

ObjectiveTo investigate whether a 2-year MRI treat-to-target strategy targeting the absence of osteitis combined with clinical remission, compared with a conventional treat-to-target strategy targeting clinical remission only (IMAGINE-rheumatoid arthritis (RA)...

ALOX5 drives the pyroptosis of CD4+ T cells and tissue inflammation in rheumatoid arthritis.

Pyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4+ T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotriene A4 (LTA4), were increased in CD4+ T cells from patients with RA and, among patients with RA, were lowest in those in clinical remission. Knockdown or pharmacological inhibition of ALOX5 suppressed CD4+ T cell pyroptosis and improved symptoms in two rodent models of RA. Mechanistically, the increase in ALOX5 activity in RA CD4+ T cells enhanced the production of the LTA4 derivative LTB4, which stimulated Ca2+ influx through ORAI3 channels, leading to the activation of NLRP3 inflammasomes and pyroptosis. Our findings reveal a role for ALOX5 in RA and provide a molecular basis for further exploring the clinical utility of ALOX5 inhibition in RA and for using ALOX5 as a biomarker to distinguish active disease and remission in RA.

P368 Correlation between patient-reported outcome measures in inflammatory bowel disease and other measures of disease activity: a systematic review

Abstract Background The clinical activity of inflammatory bowel disease (IBD) has traditionally been evaluated by healthcare professionals. To allow direct reporting of symptoms by patients, several patient-reported outcome measures (PROMs) have been developed. We evaluated the correlation between IBD-specific PROMs and measures of endoscopic activity. Methods A systematic review of the literature was performed up to June 2022. Searches were conducted in three databases (PubMed, Scopus and Web of Science). The search protocol was registered in PROSPERO (CRD42022383899). Studies reporting the correlation between self-administered, IBD-specific PROMs and endoscopic scores were included. A descriptive analysis was performed by assessing the correlation between PROMs and IBD endoscopic activity. PROMs used in Crohn’s disease (CD) and ulcerative colitis (UC) were considered separately. Results Seventeen PROMs were identified encompassing a series of IBD signs and symptoms, mainly abdominal pain (n=10), stool frequency (n=6) and rectal bleeding (n=4). Twenty-two studies assessed correlations of PROMs with existing clinical measures of disease activity and/or their accuracy in predicting remission. The mainly used endoscopic indices were Simple Endoscopic Score for CD (SES-CD) and Mayo endoscopic subscore (MES) (n=11), and clinical indices were Harvey–Bradshaw Index for CD (n=7) and SCCAI for UC (n=7). Most studies used more than one comparator as standard for validation. A marked heterogeneity in the study design and statistical methods was observed. In CD, five studies analysed correlations between PROMs and SES-CD. They generally found weak correlations with PROMs (PRO2, n=2; mobile Health Index [mHI]-CD, n=1) (Figure), except for one which found a negative moderate correlation between PRO2 and SES-CD. The strongest correlation was with the stool frequency item of the Monitor IBD at home (MIAH) questionnaire. In UC, four studies assessed the correlation between PROMs and MES. Positive weak-to-moderate correlations were found with PRO2, MIAH rectal bleeding item and mHI-UC MES in four studies. Conclusion In CD, PROMs poorly correlate with endoscopic activity. However, in UC, rectal bleeding reasonably correlates with endoscopic status. It is well known that IBD symptoms overlap with those of other digestive diseases as functional disorders, especially in CD. In line with this, our data suggest that PROMs cannot substitute endoscopic data to monitor disease activity in IBD, especially in CD patients. Nonetheless, they represent a valuable complementary instrument to comprehensively describe disease control by capturing patient perspective. More studies are needed to better evaluate correlations between PROMs and clinical disease activity measures.

Global Functioning in Axial Spondyloarthritis is Stronger Associated With Disease Activity and Function Than With Mobility and Radiographic Damage.

The Assessment of Spondyloarthritis International Society Health Index (ASAS HI) is a validated patient-reported outcome (PRO) for global functioning of patients with axial spondyloarthritis (axSpA). The Epionics SPINE (ES) is an electronic device for assessment of axial mobility that provides an objective measure of spinal mobility by assessing range of motion (RoM) and range of kinematics (RoK). The aim of this study is to investigate the relationship between global functioning and clinical measures of disease activity, physical function, spinal mobility, and radiographic damage. In a cross-sectional study design, consecutive patients with radiographic and nonradiographic axSpA were included, and the following established tools were assessed: Bath ankylosing spondylitis (AS) disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrology index (BASMI), ASAS HI, and RoM and RoK using ES. Structural damage of spine and sacroiliac joints (SIJ) were assessed by counting the number of syndesmophytes and by New York grading of sacroiliitis. Kendall's tau correlation coefficients were calculated. In 103 patients with axSpA, ASAS HI scores correlated significantly with PRO scores (BASDAI, r = 0.36; BASFI, r = 0.48; and back pain, r = 0.41; all P < 0.001). In contrast, no significant correlation between ASAS HI and RoM and RoK (r between -0.08 and 0.09) and radiographic damage in SIJ and spine (all r between 0.03 and 0.004) were seen, respectively. BASMI scores correlated weakly (r = 0.14; P = 0.05). This study shows that axSpA disease-specific PROs have an impact on global functioning, whereas spinal mobility scores, even if objectively assessed by the ES, have limited impact on patient reported-global functioning. The results also suggest that global functioning is, in this cohort, not much dependent on the degree of structural damage in the axial skeleton.

Association of Juvenile Dermatomyositis Disease Activity With the Expansion of Blood Memory B and T Cell Subsets Lacking Follicular Markers.

This study was undertaken to identify blood markers of juvenile dermatomyositis (DM) disease activity (DA), which are needed to improve disease management. The study comprised a total of 123 juvenile DM patients and 53 healthy controls. Results of laboratory tests (aldolase, creatinine kinase, lactate dehydrogenase [LDH], aspartate aminotransferase) and clinical measures of DA in patients with juvenile DM, including the Manual Muscle Testing in 8 muscles (MMT-8), Childhood Myositis Assessment Scale (CMAS), and disease activity scores (DAS) (total DAS for juvenile DM, the muscle DAS, and the skin DAS), were recorded when available. Surface phenotype of peripheral blood mononuclear cells was assessed using flow cytometry. Whole blood transcriptional profiles were studied using either RNA-sequencing or microarrays. Differential gene expression was determined using DESeq and compared by pathway and gene ontology analyses. Conventional memory (CD27+IgD-) B cells expressing low CXCR5 levels (CXCR5low/- CM B cells) were significantly increased in frequency and absolute numbers in 2 independent cohorts of juvenile DM patients compared with healthy controls. The frequency of CD4+ Th2 memory cells (CD45RA-CXCR5-CCR6-CXCR3-) was also increased in juvenile DM, especially in patients who were within <1 year from diagnosis. The frequency of CXCR5low/- CM B cells correlated with serum aldolase levels and with a blood interferon-stimulated gene transcriptional signature. Furthermore, both the frequency and absolute numbers of CXCR5low/- CM B cells correlated with clinical and laboratory measures of muscle DA (MMT-8, CMAS, aldolase, and LDH). These findings suggest that both CM B cells lacking the CXCR5 follicular marker and CXCR5- Th2 cells represent potential biomarkers of DA in juvenile DM and may contribute to its pathogenesis.

P188 Measurement of response to treatment in axial spondyloarthritis using quantitative imaging biomarkers: a prospective observational cohort study

Abstract Background/Aims Objective assessments of disease activity and response to treatment in axial spondyloarthritis (axSpA) remain a challenge. Diffusion-weighted magnetic resonance imaging (DW-MRI) and chemical shift-encoded MRI (CSE-MRI) inform on bone marrow oedema and fat content and could provide more accurate assessments of disease activity and therapeutic response. This study aims to determine the responsiveness and validity of quantitative imaging biomarkers (QIBs) obtained from DW-MRI and CSE-MRI using the partially-automated Bone Edema and Adiposity Characterisation with Histograms (BEACH) tool in patients with axial spondyloarthritis undergoing biologic therapy. Methods Conventional MRI, DWI and CSI was performed on 30 patients with active axSpA at baseline and after 12 - 16 weeks of biologic treatment. Apparent diffusion coefficient (ADC) and proton density fat fraction (PDFF) measures were analysed using the BEACH tool. Conventional MR images were assessed using established visual scoring methods. QIBs were assessed in terms of change after treatment and correlation with clinical and conventional MRI measures of disease activity. Results There were significant reductions for ADC values, while PDFF-scores showed nonsignificant reductions. Responsiveness to therapy was moderate for ADC measures and comparable to established visual scoring methods for bone marrow oedema. ADC and PDFF correlated well with conventional bone marrow oedema and fatty change scores respectively. Inter-observer variability was lower for QIBs compared with conventional visual scores methods. Conclusion ADC measures are sensitive to changes in inflammation in axSpA following biologic therapy and show promise as a biomarker of disease activity in axSpA. Disclosure A. Jones: None. T.J.P. Bray: None. N. Sakai: None. A. Bainbridge: None. C. Ciurtin: None. M.A. Hall-Craggs: None.

SAkuraBONSAI: Protocol design of a novel, prospective study to explore clinical, imaging, and biomarker outcomes in patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorder receiving open-label satralizumab.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that produces acute, unpredictable relapses causing cumulative neurological disability. Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced NMOSD relapse risk vs. placebo in two Phase 3 trials: SAkuraSky (satralizumab ± immunosuppressive therapy; NCT02028884) and SAkuraStar (satralizumab monotherapy; NCT02073279). Satralizumab is approved to treat aquaporin-4 IgG-seropositive (AQP4-IgG+) NMOSD. SAkuraBONSAI (NCT05269667) will explore fluid and imaging biomarkers to better understand the mechanism of action of satralizumab and the neuronal and immunological changes following treatment in AQP4-IgG+ NMOSD. SAkuraBONSAI will evaluate clinical disease activity measures, patient-reported outcomes (PROs), pharmacokinetics, and safety of satralizumab in AQP4-IgG+ NMOSD. Correlations between imaging markers (magnetic resonance imaging [MRI] and optical coherence tomography [OCT]) and blood and cerebrospinal fluid (CSF) biomarkers will be investigated. SAkuraBONSAI is a prospective, open-label, multicenter, international, Phase 4 study that will enroll approximately 100 adults (18-74 years) with AQP4-IgG+ NMOSD. This study includes two patient cohorts: newly diagnosed, treatment-naïve patients (Cohort 1; n = 60); and inadequate responders to recent (<6 months) rituximab infusion (Cohort 2; n = 40). Satralizumab monotherapy (120 mg) will be administered subcutaneously at Weeks 0, 2, 4, and Q4W thereafter for a total of 92 weeks. Disease activity related to relapses (proportion relapse-free, annualized relapse rate, time to relapse, and relapse severity), disability progression (Expanded Disability Status Scale), cognition (Symbol Digit Modalities Test), and ophthalmological changes (visual acuity; National Eye Institute Visual Function Questionnaire-25) will all be assessed. Peri-papillary retinal nerve fiber layer and ganglion cell complex thickness will be monitored using advanced OCT (retinal nerve fiber layer and ganglion cell plus inner plexiform layer thickness). Lesion activity and atrophy will be monitored by MRI. Pharmacokinetics, PROs, and blood and CSF mechanistic biomarkers will be assessed regularly. Safety outcomes include the incidence and severity of adverse events. SAkuraBONSAI will incorporate comprehensive imaging, fluid biomarker, and clinical assessments in patients with AQP4-IgG+ NMOSD. SAkuraBONSAI will provide new insights into the mechanism of action of satralizumab in NMOSD, while offering the opportunity to identify clinically relevant neurological, immunological, and imaging markers.

Association of Higher Ocrelizumab Exposure With Reduced Disability Progression in Multiple Sclerosis.

Ocrelizumab improved clinical and MRI measures of disease activity and progression in three phase 3 multiple sclerosis (MS) studies. Post hoc analyses demonstrated a correlation between the ocrelizumab serum concentration and the degree of blood B-cell depletion, and body weight was identified as the most influential covariate on ocrelizumab pharmacokinetics. The magnitude of ocrelizumab treatment benefit on disability progression was greater in lighter vs heavier patients. These observations suggest that higher ocrelizumab serum levels provide more complete B-cell depletion and a greater delay in disability progression. The current post hoc analyses assessed population exposure-efficacy/safety relationships of ocrelizumab in patients with relapsing and primary progressive MS. Patients in OPERA I/II and ORATORIO were grouped in exposure quartiles based on their observed individual serum ocrelizumab level over the treatment period. Exposure-response relationships were analyzed for clinical efficacy (24-week confirmed disability progression (CDP), annualized relapse rate [ARR], and MRI outcomes) and adverse events. Ocrelizumab reduced new MRI lesion counts to nearly undetectable levels in patients with relapsing or primary progressive MS across all exposure subgroups, and reduced ARR in patients with relapsing MS to very low levels (0.13-0.18). A consistent trend of higher ocrelizumab exposure leading to lower rates of CDP was seen (0%-25% [lowest] to 75%-100% [highest] quartile hazard ratios and 95% confidence intervals; relapsing MS: 0.70 [0.41-1.19], 0.85 [0.52-1.39], 0.47 [0.25-0.87], and 0.34 [0.17-0.70] vs interferon β-1a; primary progressive MS: 0.88 [0.59-1.30], 0.86 [0.60-1.25], 0.77 [0.52-1.14], and 0.55 [0.36-0.83] vs placebo). Infusion-related reactions, serious adverse events, and serious infections were similar across exposure subgroups. The almost complete reduction of ARR and MRI activity already evident in the lowest quartile, and across all ocrelizumab-exposure groups, suggests a ceiling effect. A consistent trend of higher ocrelizumab exposure leading to greater reduction in risk of CDP was observed, particularly in the relapsing MS trials, and was not associated with a higher rate of adverse events. Higher ocrelizumab exposure may provide improved control of disability progression by reducing disease activity below that detectable by ARR and MRI, and/or by attenuating other B-cell-related pathologies responsible for tissue damage. This analysis provides Class III evidence that higher ocrelizumab serum levels are related to greater reduction in risk of disability progression in patients with multiple sclerosis. The study is rated Class III because of the initial treatment randomization disclosure that occurred after inclusion in the open-label extension. ClinicalTrials.gov Identifier: NCT01247324 (OPERA I), NCT01412333 (OPERA II), and NCT01194570 (ORATORIO).

Urine proteomics by mass spectrometry identifies proteins involved in key pathogenic pathways in patients with juvenile dermatomyositis.

To identify and validate biomarkers in JDM patients using a multiplexing tandem mass tag urine proteome profiling approach. First morning void urine samples were collected from JDM patients (n = 20) and healthy control subjects (n = 21) and processed for analysis using a standardized liquid chromatography-tandem mass spectrometry approach. Biomarkers with significantly altered levels were correlated with clinical measures of myositis disease activity and damage. A subset of candidate biomarkers was validated using commercially available ELISA kits. In total, 2348 proteins were detected in the samples, with 275 proteins quantified across all samples. Among the differentially altered proteins, cathepsin D and galectin-3 binding protein were significantly increased in the urine of JDM patients (adjusted P < 0.05), supporting previous findings in myositis patients. These two candidate biomarkers were confirmed with ELISAs. Cathepsin D positively correlated with Myositis Damage Index (r = 0.57, P < 0.05) and negatively correlated with the Childhood Myositis Assessment Scale (r = -0.54, P < 0.05). We also identified novel JDM candidate biomarkers involved with key features of myositis, including extracellular matrix remodelling proteins. This study confirmed the presence of several proteins in the urine of JDM patients that were previously found to be elevated in the blood of myositis patients and identified novel candidate biomarkers that require validation. These results support the use of urine as a source for biomarker development in JDM.

Correlation between ultrasonographic scores and American college of rheumatology recommended rheumatoid arthritis disease activity measures: a systematic review and network meta-analysis.

To validate and facilitate ultrasound examinations on rheumatoid arthritis (RA) disease activity measurements in routine clinical practice. A systematic review and network meta-analysis (NMA) of ultrasound examinations on joints and its correlation with clinical RA disease activity was performed. PubMed, Embase and Cochrane library were searched for literatures published up to May 01st 2021. Bayesian random-effect NMA was conducted to pool the correlations of ultrasonographic assessment scores with composite RA disease activity measurements. Fifteen studies evaluating twelve different existing ultrasonographic measurements on joints evaluation for RA disease activity scoring were included in this NMA. For comparisons with clinical disease activity index and simplified disease activity index, synovitis gray scale ultrasound 7 joints (GSUS7) demonstrated modest correlation of 0.30[- 0.74, 1.23] and 0.46[- 0.45, 1.15] respectively, followed by synovitis power Doppler ultrasound 7 joints (PDUS7) (0.25[- 0.57, 1.14], 0.31[- 0.46, 1.24]) and power Doppler ultrasound 12 joints (PDUS12) (0.23[- 1.36, 0.83], 0.25[- 1.18, 0.88]). As for disease activity score using 28 joint counts, PDUS12 showed the biggest correlation of 0.53[- 0.09, 1.11], followed by ultrasound 7 joints (US7) (0.50[0.06, 0.93]), PDUS7 (0.49[- 0.24, 1.12]), power Doppler ultrasound 6 joints (PDUS6) (0.42[- 0.29, 1.21]), synovitis PDUS7 (0.47[- 0.09, 1.27]) and synovitis GSUS7 (0.40[0.01, 0.86]). Comparative validity was observed on fewer joints ultrasonic evaluation for RA disease activity measurements, such as synovitis GSUS7 and synovitis PDUS7. Ultrasonographic measurements can be complementary for clinical RA disease activity measures with clinical efficiency, and technical guidelines were in need for clinical routine practice.