Assessment Of Disease Activity Research Articles

Circulating immune profile in granulomatosis with polyangiitis reveals distinct patterns related to disease activity

Granulomatosis with polyangiitis (GPA) is an autoimmune disorder characterized by recurrent relapses that can cause severe tissue damage and life-threatening organ dysfunction. Multiple immune cells and cytokines/chemokines are involved in the different stages of the disease. Immune profiling of patients may be useful for tracking disease activity, however, reliable immune signatures for GPA activity are lacking. In this study, we examined circulating immune profiles in GPA patients during active and remission disease states to identify potential immune patterns associated with disease activity.The distribution and phenotypic characteristics of major circulating immune cells, and the profiles of circulating cytokines/chemokines, were studied on cryopreserved peripheral blood mononuclear cells from GPA patients (active, n = 20; remission, n = 20) and healthy controls (n = 20) leveraging a 40-color optimized multicolor immunofluorescence panel (OMIP-69) and in serum using a 46-plex Luminex multiplex assay, respectively.Deep phenotyping uncovered a distinct composition of major circulating immune cells in active GPA and GPA in remission, with the most significant findings emerging within the monocyte compartment. Our detailed analysis revealed circulating monocyte diversity beyond the conventional monocyte subsets. We identified eight classical monocyte populations, two intermediate monocyte populations, and one non-classical monocyte population. Notably, active GPA had a higher frequency of CD45RA+CCR5+CCR6−CCR7+/lowCD127−HLA-DR+CD2− classical monocytes and a lower frequency of CD45RA−CCR5-/lowCCR6−CCR7−CD127−HLA-DR+CD2+/− classical monocytes, which both strongly correlated with disease activity. Furthermore, serum levels of CXCL1, CXCL2, and CCL20, all linked to monocyte biology, were elevated in active GPA and correlated strongly with disease activity.These findings shed light on the circulating immune profile of GPA and may lead to immune signature profiles for assessing disease activity. Monocytes in particular may be studied further as potential markers for monitoring GPA.

Clinical disease activity index versus disease activity score (28 joints) for assessment of disease activity in obese patients of rheumatoid arthritis

Background: Measurement of disease activity by Disease Activity Score 28 joints -Erythrocyte Sedimentation Rate (DAS28-ESR), Disease Activity Score (28 joints)-C-Reactive Protein (DAS28-CRP), and Clinical Disease Activity Index (CDAI) has become an integral part of management of Rheumatoid Arthritis (RA), by ‘Treatment to Target’ approach. With the exception of CDAI, the other two use inflammatory markers ESR and CRP to measure disease activity. Obesity is also known to increase inflammatory markers like CRP. We undertake this study to examine if obesity confounds the disease activity measurement in RA leading to overestimation of disease activity. Methods: A cross-sectional observation study was conducted on one hundred patients of RA (40 obese and 60 non obese) in remission or low disease activity as defined by CDAI. They were divided into obese and non-obese groups based on Indian standards (BMI>25kg/m2). ESR and CRP were measured in both the groups. DAS28-ESR and DAS28-CRP were calculated and compared using relevant statistical tests. Results: DAS28-ESR and DAS-28-CRP scores were significantly higher in the obese subjects, despite both groups having comparable CDAI scores. Similar findings were also observed with inflammatory markers ESR and CRP, both being higher in obese patients. Conclusions: We conclude that indices incorporating inflammatory markers, like DAS28 overestimate disease activity in obese RA patients. Treatment decisions regarding escalation or addition of DMARDs should be taken after considering the same. CDAI appears to be better suited for disease activity measurements in obese RA patients as compared to DAS 28.

Reliability and Responsiveness of Clinical and Endoscopic Outcome Measures in Crohn's Disease.

Regulatory guidance for Crohn's disease trials recommends coprimary efficacy end points that evaluate both symptoms and mucosal inflammation. We aimed to characterize the operating properties of commonly used disease activity assessments alone and in combination. Endoscopic and clinical data were available for 129 participants from the Study of Biologic and Immunomodulator Naïve Patients in Crohn's Disease trial. Readers scored the Simple Endoscopic Score for Crohn's Disease and the Crohn's Disease Endoscopic Index of Severity using standardized conventions. Index reliability was determined using intraclass correlation coefficients. Index responsiveness was assessed using standardized effect sizes based upon treatment assignment. Outcomes were evaluated for optimal sensitivity to treatment effect. Substantial inter-rater reliability was observed when the Simple Endoscopic Score for Crohn's Disease and Crohn's Disease Endoscopic Index of Severity were used as continuous measures (intraclass correlation coefficient, 0.64; 95% confidence interval [CI], 0.50-0.73; and 0.62 95% CI, 0.36-0.77) compared with moderate reliability when dichotomized (0.46; 95% CI, 0.26-0.65; and 0.51; 95% CI, 0.00-0.78). The Simple Endoscopic Score for Crohn's Disease, Crohn's Disease Endoscopic Index of Severity, patient-reported outcome-2, and Crohn's Disease Activity Index were similarly responsive (standardized effect size, 0.43, 95% CI, 0.05-0.81; 0.38, 95% CI, 0.0-0.76; 0.53, 95% CI, 0.15-0.91). A composite outcome of Crohn's Disease Activity Index score <150 and Crohn's Disease Endoscopic Index of Severity score <6 was most sensitive to treatment effect (28.9%; 95% CI, 11.0%-46.8%; P = .003). Endoscopic indices were more reliable as continuous measures. Composite outcomes including endoscopy improved sensitivity to treatment effect.

Addition of constitutional symptoms to the SLEDAI-2K improves overall disease activity assessment: A pilot study.

Constitutional symptoms (fatigue, lymphadenopathy, and weight loss) are not included in the SLE disease activity index-2000 (SLEDAI-2K). In this pilot study, we assessed the concurrent and construct validity of a revised SLEDAI-2K (SLED-R) that included these symptoms with the original SLEDAI-2K (SLED-O), using the physician global assessment of disease activity (PGA) as the reference. Our revised SLED-R substituted the SLED-O's fever descriptor with a constitutional descriptor that included fever, fatigue, lymphadenopathy, and/or weight loss. SLED-O, SLED-R, PGA and patient global assessment (PtGA) scores were collected prospectively. Bland-Altman correlations for repeated measures were calculated and Meng's z-test was used to compare correlations between dependent and overlapping correlation coefficients. Associations between constitutional symptoms and disease activity measures were analyzed using Mann-Whitney U, Kruskal-Wallis, Chi-square tests and repeated measures correlations. 1123 SLED-O, SLED-R, PGA, and 1066 PtGA were collected in 239 subjects. The new descriptor was scored in 45 subjects (18.8%) and 92 instances (8.1%), while the original descriptor, fever, was scored in only 4 subjects (1.7%) and 5 instances (0.4%). Mean SLED-O, PGA and PtGA scores were higher when the constitutional descriptor was scored versus not (p < .001). The correlation between SLED-R and PGA was marginally higher than between SLED-O and PGA (p < .001). Fatigue contributed most to this increase (p = .001) and associated with both higher PGA and PtGA scores (p < .001). Mean SLED-O and PGA scores were higher when ≥1 constitutional symptom(s) were scored versus not (p < .002). Correlations between PGA and PtGA when the new descriptor was scored versus not were similar (p = .860). The frequency of concordance between PGA and PtGA was lower when the new descriptor was scored (55%) versus not (72.5%), with PGA > PtGA when the new descriptor was scored (p < .001). The addition of constitutional symptoms to SLEDAI-2K, particularly fatigue, resulted in a marginal increase in its correlation with PGA, and new constitutional symptoms associated with higher SLED-O and PGA scores. As fatigue is subjective and difficult to attribute to SLE, its validity and inter-rater reliability in scoring remains uncertain. The clinical utility of SLED-R remains unclear, and further studies of its validity and reliability are needed.

E041 Feasibility and acceptability of electronic patient reported outcome measures in the routine care of people with inflammatory arthritis: Haywood Arthritis Portal study

Abstract Background/Aims Electronic patient-reported outcome measures (ePROMs) assessing disease activity, function, pain, and quality of life can facilitate innovative inflammatory arthritis (IA) care, such as automating patient-initiated follow-up. This mixed-methods study evaluated whether their use is feasible and acceptable in routine care of people with inflammatory arthritis in an NHS setting. Methods The Haywood Arthritis Portal (HAP) is an NHS co-designed online patient platform, enabling people with IA under the Midlands Partnership University NHS Foundation Trust (MPFT) to enter ePROMs using any internet-enabled device. People with IA attending recruiting clinics from January-October 2023 received text message/letter invitations to complete HAP pre-appointment. Non-completers could complete HAP on tablets at the clinic. Consenters also completed a survey assessing ePROMs acceptability and HAP usability. Responses were summarised as proportions, stratified by age, gender, IA type, and home/clinic-completion status. Purposively sampled survey-completers participated in semi-structured interviews, providing deeper understanding of ePROMs/HAP feasibility/acceptability. This abstract presents data from an interim analysis of consenting patients with available survey and case report form data. Results Survey Population: 210 patients were included: 107 (51%) home-completers; 98 (47%) clinic-completers; 5 (2%) HAP non-completers; 70% female; mean age 60 years. Most had RA (70%), followed by Axial SpA (15%), undifferentiated IA (8%), and PsA/other SpA (7%). ePROMs Acceptability: 86% rated ePROMs acceptable/completely acceptable; 82% felt their completion required little/no effort; 87% agreed/strongly agreed their answers were likely to help their care. Fewer people aged &amp;gt;70 years rated ePROMs acceptable/completely acceptable (70%) compared with younger age groups (ranging 82%-100%); the same was the case for clinic-completers (79%) vs. home-completers (93%). Perceived ePROMs Use by Clinicians: 58% agreed/strongly agreed their healthcare professional had looked at their ePROMs. This was proportionally more in people aged 18-40 (79%) than older age groups (ranging 48%-58%), in axial SpA (70%) than other IA types (ranging 50%-54%), and in males (67%) vs. females (53%). HAP Usability: 78% agreed/strongly agreed HAP was easy to use. This was higher in those aged 18-40 years (93%) than those aged &amp;gt;70 years (70%), and in home-completers (89%) than clinic-completers (67%), Interviews: involved 11 participants and findings supported quantitative results, in that participants generally considered ePROMs acceptable, HAP easy to use, yet they were uncertain if their entries were used by their healthcare professional. In addition, participants were reassured that HAP was NHS-developed and secure, and expressed interest in completing ePROMs more regularly. Conclusion Using ePROMs in routine NHS care is acceptable to most people with IA, particularly younger people and those able to enter them on their own devices. The next step in this study is to consider healthcare professionals’ perspectives on ePROMs, including how they can be best integrated into consultations to ensure patients feel their entries are considered. Disclosure N. Cox: None. C. Kettle: None. H. Wang: None. S. Dutta: None. J. Packham: None. J. Galloway: None. J. Hill: None. S. Muller: None. S. Hider: None. Z. Paskins: None. L. Bullock: None. I.C. Scott: None.

E058 Disease activity measurement in rheumatoid arthritis - simpler in not always better!

Abstract Background/Aims Rheumatoid arthritis is one of the commonest inflammatory arthritis (1). The traditional method of disease activity assessment would incorporate activity measures like DAS 28, CDAI and SDAI which have been validated in clinical research (2). All these indices use 28 joint assessment method. These measures use different aspects of disease activity including swollen joint count, tender joint count, patient global scores and physician global assessment scores and inflammatory markers are included in some of the measures. We conducted a small study to compare these outcome measures in patients with moderate RA (per DAS criteria) who were recruited for disease activity assessment through MSK ultrasound. Methods Of the 30 biologic naive patients recruited, 27 were included in this study. Patients with moderate disease activity (per DAS criteria) were recruited for MSK ultrasound evaluation by a single rheumatologist. Patients with a diagnosis of fibromyalgia were excluded. These patients had been reviewed by two assessors prior to USS assessment and disease activity measures updated. Patient data was collected through electronic patient records. Data was analysed through MS Excel. Results The median age was 63. There were 66% females and 34% male patients. Majority were sero positive for either RhF, Anti CCP or both (77%). Mean DAS-28 score was 4.4 and corresponding mean CDAI and SDAI scores were 22.8 and 23.5 respectively. Mean HAQ score 1.08 and median CRP was 8.6. The median composite EULAR OMERACT synovitis score was 9.18. The average physician global assessment score for disease activity before USS was 4.9/10 and it correlated well with decision to escalate treatment in 41% patients as a result of USS assessment. Conclusion With a small sample size, this project shows that simplified disease activity measures do not necessarily provide clear evidence of disease activity and are heavily influenced by patient reported outcome measures (tender joint count and global pain scores). CDAI scores can be slightly higher compared to DAS and SDAI scores for the similar patients. Physician assessment and ultrasound can provide robust evaluation of disease activity and help in decision-making. A multicentric study with a large simple size to evaluate these findings would be helpful. Judicious use of clinical evaluation and imaging can help in tailoring treatment according to patient’s clinical condition and can also save money. Disclosure H. Crawshaw: None. E. Gates: None. C. Acebes: None. M. Jamal: None.

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.

OA23 Time to address the challenge of difficult-to-treat psoriatic arthritis: results from an international survey

Abstract Background/Aims The term difficult-to-treat psoriatic arthritis (D2TPsA) is increasingly used to describe a small but growing number of patients who fail to respond to multiple biological disease-modifying treatments (bDMARDs). There is, however, no consensus on the scope and treatment of so-called D2TPsA. This study aimed to explore international rheumatologists’ emerging perceptions of the terminology, scope and treatment of D2TPsA Methods A web-based survey consisting of 19 questions, including multiple choice and free text responses was designed, peer-reviewed and piloted by a team of expert rheumatology consultants with a special interest in PsA. The purpose of the survey was to characterise rheumatologist opinions of D2TPsA. The survey was distributed internationally via professional organisations, mailing lists and social media between 1st June - 31stJuly 2023. Results were analysed using R Studio. Results Two-hundred and forty-four (244) rheumatologists responded to the survey across 5 continents (Europe=79.4%, South America=11.5%, Asia=3.7%, North America=3.3%, Australia=0.8%). The majority (96.2%) were aged 30-69, therefore reflecting opinions spanning the entirety of the workforce, including junior trainees and senior consultants. Most (72.5%) worked in academic/teaching institutions and 37.5% cared for &amp;gt;300 PsA patients in their service. Despite this, only 20.5% of clinicians worked in a combined rheumatology/dermatology service.[HMO1] There was a range of opinion on what constituted D2TPsA, the most popular definition being failure of ≥ 2 b/tsDMARD classes (34.8%) with 68.3% wanting failure of ≥ 1 csDMARD to be included. Considering the subgroup with true resistant or refractory disease, 74.3% supported a more pragmatic definition, that being “failure of all available bDMARD classes”. Nearly all respondents felt that “low disease activity” was a more realistic target to achieve than “remission” (86.5%). There was disagreement on use of single (38.1%) vs. composite measures (40.6%) for the assessment of disease activity, and thus treatment response. Of note, 41% preferred the term “difficult-to-manage” as opposed to “difficult-to-treat” as this would encompass factors other than drug non-response such as presence of comorbidities, mental health and lack of efficacy. Others suggested that a holistic approach to the diagnosis and management of D2TPsA was important. Yet, most physicians felt that the diagnosis and treatment of D2TPsA should include reference to relevant physical and psychosocial comorbidities such as cardiometabolic disease, mental health, infection and malignancy. Conclusion This survey showcases the breadth of rheumatologist opinions of what may constitute D2T PsA, highlighting commonalities and disagreements in the terminology. These now require further discussion and debate in a consensus working group including allied specialties and patient representatives in order to agree a standardized definition for D2TPsA to be used in the clinical and research settings and enable guidelines and management pathways to be developed. Disclosure H. Marzo-Ortega: Honoraria; HMO recieved honoraria/speaker fees from AbbVie, Biogen, Eli-Lily, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB. Grants/research support; HMO received grant support from Janssen, Novartis and UCB. S.R. Harrison: Honoraria; SRH recieved fees from Novartis and Janssen to give a non-promotional educational lecture. Other; SRH received support from UCB and Janssen to attend EULAR conference. G. Nagy: Honoraria; •GN has received consulting/speaker’s fees from Abbvie, Amgen, Astra Zeneca, Lilly, Janssen, Miltényi, Novartis, Pfizer, Richter, Roche, Sobi and Swixx. P.M. Machado: Honoraria; PMM has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB. D.G. McGonagle: None. S.Z. Aydin: Consultancies; SZA received consultancy feeds from: AbbVie, Janssen, Lilly, Novartis, Pfizer, Fresenius-Kabi, UCB. Grants/research support; SZA received research grants from AbbVie, Lilly, Novartis, UCB, Pfizer, Fresenius-Kabi. R. Almodovar: Honoraria; RA has received consulting/speaker’s fees from Abbvie, Almirall, Amgen, Galápagos, Gebro, Janssen, Lilly, MSD, Nordic, Novartis, Pfizer, UCB. W. Bautista-Molano: None. L. Gossec: Consultancies; LG recieved consultancy fees from: AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB. Grants/research support; LG received research grants from: AbbVie, Biogen, Lilly, Novartis, UCB. E. Lobrano: None. P. Nash: None. F. Pimentel dos Santos: None. E. Soriano: Consultancies; ERS has received consulting/speaker’s fees and/or grant support from Abbvie, Amgen, BMS, Lilly, Janssen, Novartis, Pfizer, Roche and UCB. S. Siebert: Consultancies; SS has recieved consultancy/ speakers fees from: consultancy/speaker fees from AbbVie, Amgen, AstraZeneca, Eli Lilly, GSK, Janssen, UCB. Grants/research support; SS has received institutional research grants from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GSK, Janssen and UCB.

E073 The use of magnetic resonance imaging to assess disease activity in axial spondyloarthritis- data from a tertiary rheumatology centre

Abstract Background/Aims The role of MRI of the spine and sacroiliac joints to aid the diagnosis of axial spondyloarthritis (axSpA) is now well established. However, its utility in disease monitoring, in particular assessment of treatment non-response is unclear with limited and conflicting data on the relationship between inflammatory changes suggestive of disease activity on MRI and outcome measures such as ASDAS-CRP and BASDAI. Although the most recent ASAS/EULAR guidelines recommend against routine use of MRI in the assessment of treatment response in axSpA, this is a pragmatic approach often undertaken in NHS clinics with substantial cost implications. We aimed to explore the current use of MRI to assess disease activity in axSpA in a large tertiary centre, in particular its utility in exploring treatment non-response and its impact on treatment switching decision. Methods As part of a service evaluation audit, MRIs performed under the “inflammatory back pain protocol” at Leeds Teaching Hospitals Trust between December 2021 and May 2023 were identified from radiology request data. Patients with axial spondyloarthritis (nr-axSpA, r-axSpA or axial psoriatic spondyloarthritis [axPsA]), were identified. Demographic data, baseline MRI findings, current medications, repeat MRI findings for ongoing axial symptoms, outcome measures and inflammatory markers were extracted from the clinical notes. Data on MRI findings consistent with inflammatory or structural changes related to axSpA or alternative findings, were extracted from the radiologist’s report. Results Overall, 111 patients had an MRI to assess disease activity, 93 had axSpA (49 r-axSpA, 44 nr-axSpA) and 18 axPsA. Patients were predominantly male (58.5%) and HLA-B27 positive (65.8%), 25.2% and 27.9% current smokers and ex-smokers respectively. A history of psoriasis was documented in 25.2% and peripheral arthritis in 42.3%. Baseline MRI was available on 76 patients (68.9%), of which 61 (80.3%) had spinal or sacroiliac inflammation as per the radiologist report. In total, 79 patients were on bDMARD therapy, with TNFi the commonest class (n = 59, 52.7%). Repeat MRI demonstrated active inflammation in the spine or sacroiliac joints in 58.6% (n = 65) as per the radiologist report. Patients with active inflammation in the repeat scan were more likely to have their bDMARD switched or treatment escalated (54% vs 36%). Other important findings included spinal stenosis (n = 4), disc disease (n = 15), vertebral fractures (n = 2) and potential malignancy (n = 1). Conclusion In our practice, MRI is of utility in the monitoring and assessment of non-response in axSpA in two-thirds of cases, aiding treatment decision making by leading to a switch of bDMARD in half of patients and excluding alternative pathologies, such as vertebral fractures and disc disease which may also affect components of disease activity scores. Further research exploring association of MR findings with clinical outcomes, including economic evaluation of routine MRI to assess disease activity in axSpA is warranted. Disclosure J. Weddell: None. R. Shah: None. P. Robinson: None. A. Barr: None. C. Vandevelde: None. J. Freeston: None. D. McGonagle: None. H. Marzo-Ortega: None.

E068 Achievement of low disease activity over 52 weeks in patients with active axial spondyloarthritis on bimekizumab treatment: results from the phase 3 studies BE MOBILE 1 and BE MOBILE 2

Abstract Background/Aims The recommended treatment target for axial spondyloarthritis (axSpA) is remission/low disease activity (LDA) according to Ankylosing Spondylitis Disease Activity Score (ASDAS) levels (ASDAS&amp;lt;2.1); however, remission is difficult to achieve for many patients. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) remains commonly used in clinical practice to assess disease activity, although limited data exist to validate cut-offs. Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. BKZ has demonstrated consistent and sustained efficacy up to Week (Wk)52 in the BE MOBILE 1 and 2 phase 3 studies, including achievement of LDA according to ASDAS by &amp;gt; 50% of patients with non-radiographic (nr-)axSpA and radiographic (r-)axSpA. Here, we report achievement of LDA, as assessed by either ASDAS&amp;lt;2.1, BASDAI&amp;lt;4, or both, to Wk52 with BKZ across the spectrum of axSpA in two phase 3 studies. Methods BE MOBILE 1 (NCT03928704) and BE MOBILE 2 (NCT03928743) comprised a 16-wk placebo (PBO)-controlled and 36-wk maintenance period. BE MOBILE 1 (nr-axSpA) patients met Assessment of SpondyloArthritis international Society (ASAS) classification criteria and had objective inflammation (MRI and/or elevated C-reactive protein). BE MOBILE 2 (r-axSpA) patients met modified New York and ASAS classification criteria. All patients had active disease (BASDAI≥4 and spinal pain≥4 [BASDAI item 2]) at baseline. Patients were randomised to subcutaneous BKZ 160 mg every 4 weeks (Q4W) or PBO. Patients randomised to PBO switched to BKZ from Wk16 (‘PBO/BKZ-switchers’). The proportion of patients that achieved LDA to Wk52, as defined by either ASDAS&amp;lt;2.1, BASDAI&amp;lt;4, or both, are presented (non-responder imputation). Results Overall, 254 patients with nr-axSpA (BKZ: 128/PBO: 126) and 332 with r-axSpA (BKZ: 221/PBO: 111) were randomised. Most had high (ASDAS≥2.1-≤3.5) or very high (ASDAS&amp;gt;3.5) disease activity at baseline (nr-axSpA: BKZ: 99.2%/PBO: 97.6%; r-axSpA: BKZ: 98.6%/PBO: 100%). At Wk16, a greater proportion of BKZ vs PBO-treated patients achieved ASDAS&amp;lt;2.1 (nr-axSpA: BKZ: 46.1%/PBO: 19.8%; r-axSpA: BKZ: 42.1%/PBO: 17.1%), BASDAI&amp;lt;4 (nr-axSpA: BKZ: 52.3%/PBO: 31.7%; r-axSpA: BKZ: 55.7%/PBO: 41.4%) and both (nr-axSpA: BKZ: 43.8%/PBO: 19.0%; r-axSpA: BKZ: 41.6%/PBO: 17.1%). Results were sustained/improved across continuous BKZ-treated patients and PBO/BKZ-switchers to Wk52, with achievement of ASDAS&amp;lt;2.1 (nr-axSpA: BKZ: 53.9%/switchers: 47.6%; r-axSpA: BKZ: 50.2%/switchers: 61.3%), BASDAI&amp;lt;4 (nr-axSpA: BKZ: 60.2%/switchers: 54.0%; r-axSpA: BKZ: 65.6%/switchers: 68.5%) and both (nr-axSpA: BKZ: 49.2%/switchers: 45.2%; r-axSpA: BKZ: 49.8%/switchers: 58.6%). Achievement of BASDAI&amp;lt;4 was consistently higher than ASDAS&amp;lt;2.1, regardless of treatment arm. Conclusion Across the full axSpA disease spectrum, BKZ resulted in rapid achievement of LDA vs PBO to Wk16, as assessed by ASDAS&amp;lt;2.1, BASDAI&amp;lt;4, or both; improvements continued to Wk52. Most patients achieving ASDAS&amp;lt;2.1 also achieved BASDAI&amp;lt;4. These data suggest ASDAS&amp;lt;2.1 is a more stringent criterion for LDA, relevant for consideration of BKZ in the context of a potential treat-to-target approach for axSpA in daily practice. Disclosure X. Baraliakos: Consultancies; AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer and UCB Pharma ; grant/research support from: Novartis and UCB Pharma. Member of speakers’ bureau; AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma. Other; Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, MSD, Novartis, Pfizer and UCB Pharma. S. Ramiro: Grants/research support; AbbVie, Galapagos, MSD, Novartis, Pfizer and UCB Pharma; Consultant for AbbVie, Eli Lilly, Novartis, Pfizer, Sanofi and UCB Pharma. M. Magrey: Consultancies; AbbVie, BMS, Eli Lilly, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie, BMS and UCB Pharma. M. Rudwaleit: Consultancies; AbbVie, Eli Lilly, Novartis and UCB Pharma. Member of speakers’ bureau; AbbVie, Boehringer Ingelheim, Chugai, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. N. Haroon: Consultancies; AbbVie, Eli Lilly, Janssen, Novartis and UCB Pharma. C. Fleurinck: Other; Employees of UCB Pharma. U. Massow: Other; Employees of UCB Pharma. N. de Peyrecave: Other; Employees of UCB Pharma. T. Vaux: Other; Employees of UCB Pharma. H. Marzo-Ortega: Consultancies; AbbVie, Biogen, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB Pharma. Honoraria; AbbVie, Biogen, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB Pharma. Grants/research support; Janssen, Novartis and UCB Pharma. V. Navarro-Compán: Consultancies; AbbVie, Eli Lilly, Galapagos, MoonLake, MSD, Novartis, Pfizer and UCB Pharma. Member of speakers’ bureau; AbbVie, Eli Lilly, Fresenius Kabi, Janssen, MSD, Novartis, Pfizer and UCB Pharma. Grants/research support; AbbVie and Novartis.

Intestinal ultrasound scan predicts corticosteroid failure and colectomy risk in patients with ulcerative colitis.

Intestinal ultrasound (IUS) is an emerging modality for assessing disease activity, extent, and treatment response in ulcerative colitis. This study aimed to evaluate the potential of IUS in predicting severe flares, the need for rescue therapy (corticosteroid failure), and colectomy in patients with ulcerative colitis. We conducted a retrospective review of medical records, collecting clinical and IUS data. The Milan Ultrasound Criteria (MUC) score was used to assess ulcerative colitis severity. Group comparisons were performed to identify differences in MUC scores between mild-to-moderate and severe ulcerative colitis, between steroid responders and nonresponders, and between patients who underwent colectomy and those who did not. Receiver operating characteristic (ROC) analysis was used to predict outcomes in patients with ulcerative colitis. This analysis included 102 patients with ulcerative colitis categorized as mild/moderate (60) or severe (42). MUC scores were significantly higher in the severe ulcerative colitis group compared with the mild/moderate group ( P < 0.001). Analysis (using ROC) identified a cutoff MUC score of >8.54 to indicate severe ulcerative colitis with good sensitivity (64.29%) and excellent specificity (93.33%). Similarly, a cutoff of MUC > 10.54 showed promise in predicting corticosteroid failure, with acceptable sensitivity (50%) and high specificity (90.91%). Finally, a cutoff MUC score >12.5 demonstrated potential for predicting colectomy, exhibiting moderate sensitivity (55.56%) but excellent specificity (96.97%). IUS may be useful for differentiating severe ulcerative colitis from mild-to-moderate disease, identifying early stage failure of corticosteroid therapy, and predicting the potential need for colectomy.

A novel ultrasound-based score for assessing carotid artery activity in Takayasu's arteritis.

The role of ultrasonography for evaluating vessel wall inflammation in Takayasu's arteritis (TAK) is well-recognised; however, an effective approach for the quantitative assessment of disease activity remains lacking. This study aimed to develop a novel ultrasound-based score for determining TAK activity. TAK patients with carotid artery involvement were prospectively followed-up for 6 months. Our proposed ultrasonographic activity score (ULTRAS, range between 0-12) consisted of wall thickness (TS, range between 0-8) and semi-quantitative echogenicity scores (ES, range between 0-4). The diagnostic performance of ULTRAS for disease activity was evaluated in terms of area under the receiver operating characteristic curve (AUC). Internal validation was subsequently performed. The patients were divided into training and validation groups (n=136 and 30. respectively). In the training group, 83 (61.0%) had active disease. At an optimal cut-off of 7, ULTRAS showed good diagnostic accuracy for active TAK (AUC, 0.88; 95% CI, 82-94). Improved diagnostic performance was achieved when combined with ESR (AUC, 0.91; 95% CI, 86-96) or CRP (AUC, 0.90; 95%CI, 86-95). In the verification group, the AUCs were 0.88, 0.95, and 0.92 for ULTRAS, ESR plus ULTRAS, and CRP plus ULTRAS, respectively. At post-treatment follow-up, the TS, ES, and ULTRAS paralleled the patients' disease remission and symptom recovery. At 3-month follow-up, an improvement in wall thickness of ≥0.3 mm correlated with symptom recovery in 50% of the patients. Our proposed ultrasound-based score carries the potential in the detection of active disease among TAK patients.

Evaluation of Simplified Geboes Score in Ulcerative Colitis

Background: Ulcerative colitis (UC) is a chronic inflammatory disease of unknown etiology characterized by a relapsing and remitting course. Assessment of disease activity is based on combination of clinical features, endoscopic scoring and histological scoring. Over the years, Histological healing has replaced mucosal healing as the therapeutic endpoint in UC. Various histological parameters have their own significance in predicting treatment outcomes and prognosis. Many histologic scoring systems have been proposed with one such validated score being Geboes score. However, in view of its complexity to use the Simplified Geboes Score (SGS) was developed in 2016. Aim &amp; Objectives: To assess the interobserver agreement of SGS in ulcerative colitis. Methods: This was retrospective study of 6 years duration. Relevant clinical and endoscopic details were documented. 41 cases of UC were included in the study. The SGS scoring was done by two pathologists independently. Agreement for individual grades of SGS and for the detection of Histologic activity (score &gt;3.1) was compared between both pathologists using Cohen’s kappa coefficient. Results: Majority of the patients were in the age group of 15-72 years with male preponderance. Left sided colon was more commonly involved with loose stools being most common symptom. Cohen’s test showed moderate to good agreement for individual grades and good agreement for Histologic activity. Conclusion: The SGS is simple to use and shows good interobserver agreement for histological activity and moderate to good agreement for individual parameter. Therefore, it can be adopted for routine reporting of all biopsies in ulcerative colitis. Keywords: Histological healing, Mucosal healing, Simplified Geboes Score, Ulcerative colitis

Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics.

To assess the drug survival and change of disease activity using a second Janus kinase inhibitor (JAKi) after failure to a JAKi and subsequent biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with difficult-to-treat rheumatoid arthritis (RA). This retrospective cohort study included 32 patients with difficult-to-treat RA who failed to a JAKi and subsequently to one or more bDMARDs and then switched to a second JAKi. To assess drug survival, electronic medical records of each patient were reviewed. Data on whether the second JAKi was discontinued, and the reasons for discontinuation were collected. The change of disease activity was assessed by analyzing changes in tender joint count (TJC), swollen joint count (SJC), patient's global assessment of disease activity on a visual-analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Disease Activity Score for 28 joints with ESR (DAS28-ESR), and DAS28-CRP from baseline to that at six months from initiation of the second JAKi. Overall, discontinuation of the second JAKi occurred in 20 (62.5%) patients. Primary failure, secondary failure, adverse events, and insurance coverage issues were the reasons for discontinuation in 9 (45.0%), 5 (25.0%), 2 (10.0%), and 4 (20.0%) patients, respectively. The estimated 2-year drug survival rate was 39.3%. In terms of change of disease activity, the second JAKi significantly improved TJC (p < 0.001), SJC (p < 0.001), VAS (p < 0.001), CRP (p = 0.026), DAS28-ESR (p < 0.001), and DAS28-CRP (p < 0.001) at 6-month compared with that at the baseline. Second JAKi could be a therapeutic option in patients with difficult-to-treat RA who have failed to a JAKi and subsequent bDMARDs.

Cut-Offs for Disease Activity States in Axial Spondyloarthritis With Ankylosing Spondylitis Disease Activity Score (ASDAS) Based on C-Reactive Protein and ASDAS Based on Erythrocyte Sedimentation Rate: Are They Interchangeable?

Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) is recommended over ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1, and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs. We used data from patients with axSpA from 9 European registries initiating a tumor necrosis factor inhibitor. ASDAS-ESR cut-offs were estimated using the Youden index. The level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other. In 3664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9, and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data. We estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR.

Tracking Fat Grafts by Magnetic Resonance Imaging: A Comparative Study of Adolescent and Adult Patients with Stable Localized Scleroderma.

The optimal timing of reconstruction for patients with facial localized scleroderma is uncertain. The purpose of this study was to compare the outcomes of autologous fat transplantation in adolescent and adult patients with stable localized scleroderma. Adolescent (age 10-19 years) and adult (age >19 years) patients with no previous surgery were enrolled (n = 10, each group). Preoperative magnetic resonance imaging (MRI), blood tests and dermatological assessments were used for disease activity assessment. All patients underwent autologous fat transplantation for anatomic facial fat restoration with preoperative MRI planning. Preoperative, immediate and one-year postoperative 3D Dixon MRI scans with image registration and fusion techniques were used for fat graft tracking. Patient satisfaction was assessed with a 5-point Likert scale. There was no significant difference in sex, body mass index, disease severity, or volume of injected fat between the two groups (p > 0.05), except for age (p < 0.05). The one-year postoperative fat graft retention rate was not significantly different, with 36.6 ± 2.4% (ranging from 25.3 to 49.3%) in the adolescent group and 32.9 ± 1.7% (ranging from 27.3 to 40.1%) in the adult group (p > 0.05). Surgical outcomes were favorable in all patients, with satisfaction scores of 3.8 ± 0.2 points in the adolescent group and 3.6 ± 0.2 points in the adult group (p > 0.05). In stable localized scleroderma, the initial autologous fat transplantation was equally effective for facial contour deformity improvement, with no significant difference in fat graft retention or satisfaction.

64Cu]Cu-PEG-FUD peptide for noninvasive and sensitive detection of murine pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease resulting in irreversible scarring within the lungs. However, the lack of biomarkers that enable real-time assessment of disease activity remains a challenge in providing efficient clinical decision-making and optimal patient care in IPF. Fibronectin (FN) is highly expressed in fibroblastic foci of the IPF lung where active extracellular matrix (ECM) deposition occurs. Functional upstream domain (FUD) tightly binds the N-terminal 70-kilodalton domain of FN that is crucial for FN assembly. In this study, we first demonstrate the capacity of PEGylated FUD (PEG-FUD) to target FN deposition in human IPF tissue ex vivo. We subsequently radiolabeled PEG-FUD with 64Cu and monitored its spatiotemporal biodistribution via μPET/CT imaging in mice using the bleomycin-induced model of pulmonary injury and fibrosis. We demonstrated [64Cu]Cu-PEG-FUD uptake 3 and 11 days following bleomycin treatment, suggesting that radiolabeled PEG-FUD holds promise as an imaging probe in aiding the assessment of fibrotic lung disease activity.

Neurofilaments as biomarkers in neurological disorders - towards clinical application.

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies. Progress has now moved the measurement of neurofilaments to the doorstep of routine clinical practice for the evaluation of individuals. In this Review, we first outline current knowledge on the structure and function of neurofilaments. We then discuss analytical and statistical approaches and challenges in determining neurofilament levels in different clinical contexts and assess the implications of neurofilament light chain (NfL) levels in normal ageing and the confounding factors that need to be considered when interpreting NfL measures. In addition, we summarize the current value and potential clinical applications of neurofilaments as a biomarker of neuro-axonal damage in a range of neurological disorders, including multiple sclerosis, Alzheimer disease, frontotemporal dementia, amyotrophic lateral sclerosis, stroke and cerebrovascular disease, traumatic brain injury, and Parkinson disease. We also consider the steps needed to complete the translation of neurofilaments from the laboratory to the management of neurological diseases in clinical practice.

Enrolment of the first paediatric cohort into the Australian lupus registry and biobank: A single-centre experience.

We aim to report on the feasibility of establishment of the first paediatric cohort as part of the longitudinal database of the Australian Lupus Registry and Biobank (ALRB) and to describe the enrolment data with a focus on clinical characteristics, serological data, treatment strategies and patient/parent-reported outcome measures. All patients under the age of 18years with a diagnosis of systemic lupus erythematosus (SLE) attending the paediatric rheumatology service of a single, tertiary hospital were identified. Patients were enrolled in the ALRB if they met ≥4/11 of the American College of Rheumatology (ACR) 1997 SLE classification criteria or the Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria. Enrolment data including demographics, clinical characteristics, serological profiles, disease activity and damage assessments were recorded. Peds-QL Rheumatology and General Modules were used to assess patient and parent-reported outcomes. Twenty-seven patients were eligible for inclusion, with 26 patients (96%) consenting for enrolment. Twenty-five patients (92%) consented for biobanking. Twenty patients (77%) were female. The median age at enrolment was 16years (interquartile range (IQR) 13.7, 17.4). The median disease duration from diagnosis was 3.2years (IQR 1.4, 5.3). Sixteen patients (62%) had synovitis, 16 (62%) had cutaneous involvement, 4 (15%) had serositis, 17 (65%) had haematological involvement and 7 (27%) had renal involvement at enrolment. Nineteen patients (73%) were prescribed at least two disease-modifying anti-rheumatic medications (DMARDs). Hydroxychloroquine (n = 22, 85%) and mycophenolate mofetil (n = 9, 35%) were the most commonly prescribed DMARDs. The median SLEDAI-2K score was 2 (IQR 2, 4). Six patients (23%) had active disease (SLEDAI-2K ≥6) at enrolment. Three patients (11.5%) had reported damage using the SLICC/ACR Damage Index. Twenty-three children (88%) and eighteen parents (69%) completed the Paediatric Quality of Life Inventory. Quality of life scores reported across domains of physical, emotional, social and school functioning at enrolment were comparable to previously studied paediatric cohorts with SLE and other chronic diseases. We have established our centre as the first paediatric participating site of the ALRB, providing contemporary data on the clinical characteristics, serological profile and health-related quality of life outcomes of Australian children with SLE. Paediatric involvement with this national registry will provide a unique perspective for future clinical and scientific research. Collection of Australian-specific paediatric longitudinal data will also enable a broader understanding of SLE within a multicultural Australian population.

Circulating extracellular vesicles as biomarker for diagnosis, prognosis, and monitoring in glioblastoma patients.

Extracellular vesicles (EVs) obtained by noninvasive liquid biopsy from patient blood can serve as biomarkers. Here, we investigated the potential of circulating plasma EVs to serve as an indicator in the diagnosis, prognosis, and treatment response of glioblastoma patients. Plasma samples were collected from glioblastoma patients at multiple timepoints before and after surgery. EV concentrations were measured by nanoparticle tracking analysis and imaging flow cytometry. Tumor burden and edema were quantified by 3D reconstruction. EVs and tumors were further monitored in glioma-bearing mice. Glioblastoma patients displayed a 5.5-fold increase in circulating EVs compared to healthy donors (P < .0001). Patients with higher EV levels had significantly shorter overall survival and progression-free survival than patients with lower levels, and the plasma EV concentration was an independent prognostic parameter for overall survival. EV levels correlated with the extent of peritumoral fluid-attenuated inversion recovery hyperintensity but not with the size of the contrast-enhancing tumor, and similar findings were obtained in mice. Postoperatively, EV concentrations decreased rapidly back to normal levels, and the magnitude of the decline was associated with the extent of tumor resection. EV levels remained low during stable disease, but increased again upon tumor recurrence. In some patients, EV resurgence preceded the magnetic resonance imaging detectability of tumor relapse. Our findings suggest that leakiness of the blood-brain barrier may primarily be responsible for the high circulating EV concentrations in glioblastoma patients. Elevated EVs reflect tumor presence, and their quantification may thus be valuable in assessing disease activity.