Patient-reported Disease Activity Research Articles

Therapeutic sequencing in inflammatory bowel disease: Determining the optimal position of vedolizumab for long-term Crohn's disease control using real-world evidence.

Several biologics are available for the treatment of moderate to severe Crohn's disease, but data to optimize their use are scarce. Vedolizumab (VDZ) is a gut-selective anti-lymphocyte trafficking monoclonal antibody that was approved in 2014 for the treatment of moderate to severe Crohn's disease. Based on real-world evidence, a model was developed to examine the effect of VDZ's position in the treatment sequence on clinical outcomes. The aim of this study was to develop a model using real-world data to investigate how the positioning of VDZ in a sequence of biologic therapies for CD affects clinical effectiveness outcomes of quality-adjusted life-years (QALYS), patient-reported disease activity, and surgery rates. A semi-Markov sequential model was developed to identify the optimal position of VDZ in a treatment sequence that included corticosteroids (CS), two biologics, and best supportive care (BSC). Using real-world data, three sequences were compared: VDZ as first (position), second, and last biologic (with anti-tumor necrosis factor alpha agents adalimumab (ADA) and infliximab (IFX) and the anti-interleukin-12 and -23 agent ustekinumab (UST) as alternative biologic treatments). Published real-world evidence informed model inputs. Vedolizumab sequences were compared and ranked based on QALYS, patient-reported outcomes from Crohn's disease activity index scores, or proportion of patients undergoing surgery by the 10-year time horizon for model simulation. Sensitivity analyses were used to evaluate the impact of model input uncertainty. Vedolizumab as the first biologic was the optimal position for this treatment according to all criteria, including yielding the highest QALYs (5.09) versus VDZ in second (4.97) and third (4.96) biologic sequence positions in sequences containing CS, anti-TNFα (aggregated data), UST, and BSC; 1780/2000 (89%) probabilistic simulations. In sequences containing ADA, VDZ, and UST biologics, ADA and VDZ in the first-line biologic position yielded QALYs of 5.09 versus 5.07, respectively. Adalimumab as the first biologic was best for clinical remission. This simulation model using real-world evidence indicates that positioning VDZ or ADA as the first biologic is likely to lead to improved long-term patient outcomes when compared to administering these treatments later or starting with IFX monotherapy.

P107 Real world clinical outcomes of patients with moderate-to-severe rheumatoid arthritis initiating upadacitinib in the United Kingdom: Interim analysis from a prospective observational cohort study (ENDEAVOUR)

Abstract Background/Aims Upadacitinib (UPA) 15 mg, a once-daily Janus kinase inhibitor (JAKi), is approved by NICE for treating adults with moderate-to-severe rheumatoid arthritis (RA) unresponsive to conventional Disease Modifying Antirheumatic Drugs (DMARDs). This study aims to evaluate UPA's real-world effectiveness in the UK. Methods ENDEAVOUR is a prospective observational cohort study which recruited 97 patients with moderate to severe RA whom the managing health care professional has decided to treat with UPA in line with marketing authorisation across 14 sites in the UK. Patient demographics, comorbidities, concomitant therapies and patient reported disease activity were collected at baseline, three months, and six months. Patient Reported Outcomes (PROs) were collected using an app hosted by UMotif. Primary objective was the proportion of patients achieving clinical remission (defined as DAS28<2.6) with upadacitinib at six months. The study is ongoing and therefore not all patients have completed study visits at three and six months yet however this interim analysis reports the baseline demographics of 77 patients whose data has been cleaned thus far and clinical outcomes and safety of UPA 47 adult patients at three months. Data are as observed. Results Data were available for 77 adults at baseline: 42% had moderate and 58% had severe RA based on DAS28-CRP scores. Patients' average age was 55 years, 64 (83%) were female, and most had at least one comorbidity, such as hypertension (16,21%) or asthma (12,16%). 32 (42%) had prior biologic therapy, with treatment failure the most commonly reported reason for switch (26/33, 79%). Of the 47 participants with three-month data, 18 (38%) achieved DAS28 remission. The proportion of patients with high disease activity decreased markedly from 45 (58%) at baseline to three (6%) at three months and moderate disease activity from 32 (42%) at baseline to 14 (30% at three months). Concurrent corticosteroid use declined, from 13 (17%) patients at baseline to just three (5%) by three months. The mean exposure time was six months (IQR five to seven). Nine patients (9%) stopped UPA during the study period, (5/9 due to adverse events, 4/9 due to patient or physician choice). One case of shingles occurred, with temporary treatment interruption. Reports of serious adverse events were low (4% patients of events reported) with cases of serious and opportunistic infections reported most frequently (three cases). There were no reports of MACE or venous thromboembolic events. 1 report of malignancy (extranodal marginal zone B-cell lymphoma) was considered unrelated to treatment. Conclusion This preliminary analysis of an observational study provides valuable insights into the real-world effectiveness of UPA for treatment of moderate to severe RA with similar early efficacy to that observed in clinical trials. 38% of patients achieved clinical remission by 3 months, and adverse events were infrequent. Disclosure J. Taylor: None. S. Srirangan: None. M. Bukhari: Honoraria; M.B has received honoraria for speaking and attended advisory boards with Bristol-Myers Squib, UCB celltech, Roche/Chugai, Pfizer, AbbVie, Merck, Mennarini, Sanofi-aventis, Eli-Lilly, Janssen, Amgen, Novartis and Gilead. Other; M.B. has been sponsored to attend regional, national and international meetings by UCB celltech, Roche/Chugai, Pfizer, Abbvie, Merck, Mennarini, Janssen, Bristol-Myers Squib, Novartis and Eli-lilly. S. Bilgrami: Other; S.B. has received professional and financial support from Eli Lilly, UCB & Pfizer. M.K. Nisar: Other; M.K.N undertakes clinical trials and received support (including attendance at conferences, speaker fees and honoraria) from Roche, Chugai, MSD, AbbVie, Pfizer, BMS, Novartis, Celgene, UCB and, Lilly. S. McDonald: None. N. Goodson: None. A. Allard: Other; A.A. has received payment for services, sponsorship, funding, grants or worked on clinical trials for AbbVie, Eli Lilly, Pfizer, Novartis, BMS, Roche. A. Kinder: None. M. Green: None. L. Hunt: None. S. Raizada: Honoraria; S.R. has received honoraria from AbbVie. B. Kirkham: Consultancies; B.K. has received consultant/speaker fees from AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB. Grants/research support; B.K. has received research support from Eli Lilly and Novartis. E. Thomas: Other; E.T. has been on advisory boards for Janssen and Galapagos. R. Horsfall: None. S. Bartlett: None. R. Millward: None. V. Burton: None. J. Galloway: Consultancies; J.G. has received speaker/consultancy for AbbVie, Galapagos, Janssen, Lilly, Pfizer, UCB and Vifor. Grants/research support; He has received research grants for AbbVie, Galapagos, GSK, Janssen, Lilly, Pfizer.

P118 Patient-reported outcomes, disease activity and safety in UK patients with rheumatoid arthritis treated with filgotinib: up to six-month interim results from a prospective observational study (FILOSOPHY)

Abstract Background/Aims FILOSOPHY (NCT04871919), an ongoing, observational Phase 4 study, will assess the effectiveness and safety of filgotinib, a JAK1-preferential inhibitor, in patients with RA in a real-world setting in Europe. We report interim UK data. Methods FILOSOPHY will enroll approximately 1,500 adults with moderate-to-severe active RA, upon first exposure to filgotinib, prescribed according to the product label and local standard-of-care. DAS28-CRP and CDAI were assessed at baseline, Month one, three and six and pain (visual analog scale [VAS]) and FACIT-Fatigue score at baseline, Week one, two and three and Month one, three and six. A reduction of ≥ 10 mm in VAS pain or increase of ≥ 4 in FACIT-Fatigue score were considered a clinically meaningful change from baseline (CFB). Treatment-emergent adverse events (TEAEs) on study were reported. Results By January 31, 2023, 130 patients had been treated in the UK; baseline characteristics and study treatment are reported in the Table. Median (IQR) CFB in DAS28-CRP was -1.1 (-2.5, -0.5) at Month one (N = 29), -1.7 (-2.6, -1.2) at Month 3 (N = 32) and -2.5 (-3.2, -1.0) at Month six (N = 27). Median (IQR) CFB in CDAI was -15.0 (-26.0, -8.0) at Month one (N = 31), -17.0 (-27.0, -12.0) at Month three (N = 31) and -25.0 (-30.0, -16.0) at Month 6 (N = 30). The proportion of patients with a clinically meaningful CFB in FACIT-Fatigue score was 45.0% (n = 18/40) at Week 1 and 65.6% (n = 21/32) at Month six. For VAS pain, the proportions were 47.5% (n = 19/40) at Week 1 and 66.7% (n = 22/33) at Month six. Similar trends were seen in the monotherapy and combination groups. No unexpected TEAEs occurred. Six patients discontinued the study prematurely; there was one death (lobar pneumonia); none were lost to follow-up. Conclusion Interim UK data showed pain and fatigue improved with filgotinib treatment as early as Week one and disease activity as early as Month one, the first timepoint that DAS28-CRP and CDAI were assessed; improvements were maintained up to Month six. While conclusions regarding safety cannot be made due to the short follow-up and small sample size, no new safety findings were observed. Long-term follow-up is needed to further evaluate effectiveness and safety. Disclosure B. Kirkham: Consultancies; AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB. Grants/research support; Eli Lilly, Novartis. N.D. McKay: Consultancies; Gilead, UCB. Member of speakers’ bureau; Galapagos. Other; Registration for conference fees from AbbVie, Novartis, UCB. His department has received grants and payments from a wide range of pharmaceutical companies for research and education. A.G. Pratt: Consultancies; Inflection Biosciences (paid to Newcastle University). Grants/research support; Galapagos, GSK, Pfizer (paid to Newcastle University). J. Barry: Other; Employee of Galapagos. O. Bouzid: Consultancies; Galapagos. T.P.A. Debray: Consultancies; Biogen, Daiichi Sankyo, Galapagos, Gilead. S. Bhat: None. L. Robertson: Other; Financial support for conference attendance from UCB. J. Galloway: Consultancies; AbbVie, Galapagos, Janssen, Lilly, Pfizer. Honoraria; AbbVie, Galapagos, Janssen, Lilly, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Galapagos, Janssen, Lilly, Pfizer, UCB. Grants/research support; AstraZeneca, Janssen, Pfizer.

Clinical value of the Patient Global Assessment with Ankylosing Spondylitis: A cross-sectional study.

To analyze the factors associated with the overall patient condition and explore the clinical value of the Patient Global Assessment (PGA) index for assessing the disease state in patients with Ankylosing Spondylitis (AS). This cross-sectional study used a standardized questionnaire to record the basic information of patients with AS. The collected data included the Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP), ASDAS-erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), PGA, and other clinical indicators. Statistical analysis was performed using SPSS 25.0 software, and the scale was assessed for retest reliability and structural validity. The Kruskal-Wallis H test and Spearman or Pearson correlation analysis were used to analyze the factors influencing PGA scores. The receiver operator characteristic (ROC) curve was used to identify the cutoff value of the PGA for predicting disease activity in AS. The patient age, disease duration, family history, and history of ocular inflammation significantly differed between PGA groups (P < .05). The median PGA was significantly lower in patients with disease remission than in those with disease activity (P < .01). The various clinical indexes significantly differed between PGA groups (P < .01). The PGA was significantly correlated with various clinical indicators (P < .01). The area under the ROC curve (AUC) for disease activity based on the ASDAS-CRP was 0.743 (P < .01) with a PGA cutoff value of 1.38; the AUC for disease activity based on the BASDAI was 0.715 (P < .01) with a PGA cutoff value of 1.63. The PGA was significantly correlated with patient-reported outcomes, disease activity, function, and psychological status, and may indicate the level of inflammation in patients with AS. A PGA of around 1.5 indicates disease activity.

Exploring the Potential of IL-4 and IL-13 Plasma Levels as Biomarkers in Atopic Dermatitis.

Atopic dermatitis (AD) is a persistent inflammatory skin condition that impacts individuals of various age groups, including both children and adults. Its pathophysiology involves allergens penetrating a disrupted epidermal barrier, triggering the dermal cells to produce pro-inflammatory cytokines and eliciting a T-cell-mediated immune response. Notably, interleukins (ILs), particularly interleukin 4 (IL-4) and interleukin 13 (IL-13), play a key role in AD pathogenesis. Therapies directed at inflammatory mechanisms, including Dupilumab, have demonstrated notable effectiveness in enhancing skin lesions, alleviating subjective symptoms, and improving the overall quality of life for individuals with AD. Despite therapeutic advances, assessing AD severity remains challenging. The commonly used tools, such as the SCORAD and DLQI scores, rely on subjective patient responses. Paraclinically, the search for universal biomarkers continues, with efforts to identify reliable indicators reflecting disease severity and treatment response. Various biomarkers, including Th2-related chemokines and cytokines, have been explored, but none have gained universal recognition for routine clinical use. This study aims to investigate the dynamics of the plasma levels of IL-4 and IL-13 during Dupilumab treatment and establish correlations between these ILs and disease severity, as measured using the SCORAD and DLQI scores. The ultimate endpoint is to determine whether IL-4 and IL-13 can serve as reliable biomarkers, assessing their correlation with patient-reported feelings and disease activity and potentially influencing their inclusion or exclusion as diagnostic elements in routine clinical practice.

Long-term safety and effectiveness of canakinumab in patients with monogenic autoinflammatory diseases: results from the interim analysis of the RELIANCE registry

ObjectiveInterim analysis of the RELIANCE registry, an on-going, non-interventional, open-label, multicentre, prospective study evaluating the long-term safety, dosing regimens and effectiveness of canakinumab in patients with cryopyrin-associated periodic syndromes (CAPS),...

Development of a novel clinimetric tool: PAtient Reported Disease Activity Index in Rheumatoid Arthritis (PARDAI-RA) by PANLAR, for the assessment of patients living with rheumatoid arthritis.

Clinical experience has shown that a single measure is not sufficient to assess disease activity in rheumatoid arthritis (RA). Various clinimetric tools are necessary to address the many clinical situations that can arise. In order to develop a comprehensive measurement tool, the Pan American League of Associations for Rheumatology searched for the most frequent measures of disease activity applied in RA by means of a semi-systematic review of the available literature. We found that the most frequently reported measures of disease activity were the 28-joint Disease Activity Score, C-reactive protein, and the erythrocyte sedimentation rate, followed by patient-reported measures of pain and stiffness and many other composite indices and patient-reported outcome measures. The most frequent physician-reported sign of disease was the swollen joint count, and the most frequently self-reported feature was the increase in disease activity or flares. In this article, we present a new clinimetric tool developed based on expert consensus and on data retrieved from our search. Disease activity can be better assessed by combining various data sources, such as clinical, laboratory, and self-reported outcomes. These variables were included in our novel clinimetric tool. Key Points • The goal of treatment of RA is to achieve the best possible control of inflammation, or even remission; therefore, disease management should include systematic and regular evaluation of inflammation and health status. • Clinimetric tools evaluate a series of variables (e.g., symptoms, functional capacity, disease severity, quality of life, disease progression) and can reveal substantial prognostic and therapeutic differences between patients. • Our clinimetric tool, which is based on a combination of data (e.g., clinical variables, laboratory results, PROMs), can play a relevant role in patient assessment and care.

P258 Correlation between patient-reported disease activity, physician’s global assessment and quality of life in Inflammatory Bowel Disease

Abstract Background As a chronic disease, patients’ perspectives on their disease status and quality of life is an essential part of inflammatory bowel disease (IBD) management. Patient reported outcomes should be the standard of measure for signs and symptoms evaluation. We aimed to evaluate the correlation between patients’ self-assessment of disease activity, activity scores and the physician’s global assessment. Methods A unicentric cross-sectional study was conducted. The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) was administered to consecutively evaluated IBD patients in the outpatient setting. Additionally, a pilot questionnaire containing items related to disease activity was also applied to both the patients and the attending physician. Disease activity was categorized as remission, mild, moderate, or severe. Remission was defined as Harvey Bradshaw Index (HBI) ≤ 4 for Crohn's disease or Mayo Clinic Subscore (MCS) ≤ 2 for ulcerative colitis. Correlations between patient's perspective on disease activity, attending physician’s global assessment, activity scores and patient's quality of life were assessed using Spearman’s rank correlation coefficient. Results A total of 105 patients were included (female: 52%; mean age: 44±15 years), of whom 68% had Crohn's disease. 71% percent of patients were receiving biological therapy (table 1). A quarter of the patients (n=27) perceived their disease to be in remission, of whom 56% were indeed in deep remission and 19% in endoscopic remission (table 1). A statistically significant positive correlation was observed between patient self-assessment and HBI scores (mean=2.5±6.5 points, r=0.400, p=0.001) and MCS scores (mean=3.4±4.0 points, r=0.574, p&amp;lt;0.001). Among patients who did not consider themselves in remission, 42% rated the activity of their disease as mild, 23% as moderate, and 9% as severe. The attending physician assessed 26% with mild disease, 22% with moderate disease, and 18% with severe disease (table 1). There was a statistically significant positive correlation between patient and physician assessments (r=0.374; p&amp;lt;0.001). The mean score on the SIBDQ was 28±11 points (table 1), and a statistically significant positive correlation was found between patient self-assessment of disease activity and the SIBDQ (r=0.508, p&amp;lt;0.001). Conclusion These observational data suggest a weak correlation between patient-reported disease activity and the physician’s global assessment. Divergent perceptions of disease activity between patients and physicians may compromise patient-engagement. Furthermore, the moderate correlation observed with overall quality of life supports the importance of alignment patients and physicians to improve the quality of care provided.

Relationships of Work Productivity and Activity Impairment With Patient-Reported Outcomes in Ankylosing Spondylitis: Results From Two Trials.

We examined the relationships of work productivity and activity impairment with key patient-reported outcomes (PROs) assessing pain, disease activity, and health-related quality of life (HRQoL) in patients with ankylosing spondylitis (AS). This post hoc analysis pooled available data from baseline to end of the double-blind phase of phase 2 and 3 placebo-controlled tofacitinib trials in patients with active AS. A repeated-measures longitudinal model assessed the relationships (linear or nonlinear) between Work Productivity and Activity Impairment questionnaire in Spondyloarthritis (WPAI:SpA) domains (absenteeism, activity impairment, presenteeism, and productivity loss) as outcomes and key PROs (total back pain, nocturnal spinal pain, Patient Global Assessment of Disease Activity, AS Quality of Life, EuroQol 5-Dimension 3-Level [EQ-5D-3L], and EQ-5D Visual Analog Scale [EQ-5D-VAS]) as predictors. Data from 330 to 475 patients were available, depending on the analysis. Relationships between WPAI:SpA domains and PROs were approximately linear. The worst PRO scores were associated with a decline in patients' work capacity (measured by activity impairment, presenteeism, and productivity loss [>65%]); the best scores were associated with improvements in WPAI:SpA domains (8%-23%). Incremental PRO improvements were associated with improvement of activity impairment, presenteeism, and productivity loss. Relationships between absenteeism and PROs were the weakest, owing to absenteeism being low in the study population. Evidence of linear relationships between work productivity and activity impairment with patient-reported pain, disease activity, and HRQoL was observed. Interventions to control pain and disease activity and improve HRQoL are therefore likely to improve work productivity and reduce activity impairment in patients with AS.

Higher levels of physical activity are associated with less evasive coping, better physical function and quality of life in patients with axial spondyloarthritis.

To evaluate daily physical activity (PA) in relation to psychosocial factors, such as anxiety, depression and different types of coping strategies, as well as patient- and disease-related factors in patients with axial spondyloarthritis (axSpA). Consecutive outpatients from the Groningen Leeuwarden AxSpA (GLAS) cohort completed the modified Short Questionnaire to assess health-enhancing PA (mSQUASH), Hospital Anxiety and Depression Scale (HADS) and Coping with Rheumatic Stressors (CORS) questionnaires, as well as standardized patient- and disease-related assessments. Univariable and multivariable linear regression analyses and comparison of lowest and highest PA tertiles were performed to explore associations between the HADS, CORS, patient- and disease-related factors and PA. In total, 84 axSpA patients were included; 60% male, mean age 49 (SD ±14) years, median symptom duration 20 (25th-75th percentiles: 12-31) years, mean ASDAS 2.1 (±1.0). Higher PA levels were significantly associated with better scores on patient-reported disease activity (BASDAI), physical function (BASFI) and quality of life (ASQoL). Furthermore, higher levels of PA were associated with less impact of axSpA on wellbeing and lower HADS depression scores. In the multivariable linear regression model, less use of the coping strategy 'decreasing activities' (β: -376.4; p 0.003) and lower BMI (β:-235.5; p: 0.030) were independently associated with higher level of PA. Comparison of patients from the lowest and highest PA tertiles showed results similar to those found in the regression analyses. In this cohort of axSpA patients, higher levels of daily PA were associated with better patient-reported outcomes and lower depression scores. Additionally, the passive coping strategy "decreasing activities" and lifestyle factor BMI were independently associated with PA. Besides anti-inflammatory treatment, coping strategies and lifestyle should be taken into account in the management of individual axSpA patients. Incorporating these aspects into patient education could increase patient awareness and self-efficacy. In the future, longitudinal studies are needed to better understand the complex relationship between patient-, disease- and psychosocial factors associated with daily PA.

The Comorbidity of Patient-Reported Crohn's Disease Activity and Depression: The Role of Health Behavior Mediators.

Longitudinal research reveals a unidirectional relationship between a nonsomatic symptom of depression, a negative view of the self, and later reported Crohn's disease (CD) activity. We evaluated whether health behaviors mediated this association using a longitudinal design. We studied 3304 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, a symptom-specific index of depression, and measures of physical activity, smoking, and sleep quality. Crohn's disease status and the cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We specified single-mediator and multiple-mediator models to elucidate the depression-disease activity relationship. Among 2395 females and 909 males, we found a significant mediation effect for activity level (P < .001) after adjusting for age, sex, and body mass index. There was no evidence that sleep quality and smoking are significant single mediators. When we considered multiple mediation models, smoking and less activity partially mediate the depression-CD association. Smoking and lower levels of physical activity are potential mediators of the unidirectional association between a nonsomatic symptom of depression-a negative view of the self-and patient-reported CD activity. Evaluating and treating specific symptoms of depression may reduce the frequency of CD exacerbations.

Impact of disease outcomes on the Assessment of SpondyloArthritis International Society Health Index (ASAS HI): a Bayesian network analysis of the DESIR cohort

ObjectiveThe objective of this study is to build a structural model visualising and quantifying the interrelationships of different disease outcomes with the Assessment of SpondyloArthritis International Society Health Index (ASAS...

A Real-World Effectiveness Study Using a Mobile Application to Evaluate Early Outcomes with Upadacitinib in Rheumatoid Arthritis.

The impact of upadacitinib on rheumatoid arthritis (RA) symptoms was evaluated during the first 12weeks of treatment via patient-reported outcomes (PROs) using a mobile health application (app). Participating rheumatologists from the CorEvitas RA Registry (prospective, observational cohort) recruited patients with RA initiating upadacitinib treatment. A modified version of the ArthritisPower® app was used to collect PROs, including the Routine Assessment of Patient Index Data 3 (RAPID3), duration of morning joint stiffness, and the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue 7a Short Form at baseline and weeks 1-4, 8, and 12. RAPID3 responses over time were assessed using Kaplan-Meier estimation to determine the proportion of patients achieving disease activity improvement and minimal clinically important difference (MCID). Results were analyzed for all patients initiating upadacitinib and a subsample of TNF inhibitor (TNFi)-experienced patients with moderate to severe disease at baseline. A total of 103 patients with RA initiating upadacitinib (62.1% TNFi-experienced) were included. At week 12, 53 patients (51.4%) completed the study and provided PRO data via the app. Among all patients, improvements in RAPID3, pain, morning stiffness, and fatigue were observed at week 1 and were maintained or further improved through week 12. At week 12, 37.5% of patients achieved RAPID3 low disease activity. Starting at week 1, improvements in RAPID3 disease activity category (19.4% of patients) and achievement of MCID (16.3%) were reported, with nearly 50% of patients achieving these outcomes by week 4 (RAPID3 category: 48.8%; MCID: 49.2%) and 60% by week 12 (RAPID3 category: 59.6%; MCID: 59.8%). TNFi-experienced patients generally reported similar outcomes. Patient-reported medication convenience and compliance were generally high. In this real-world cohort of patients with RA, treatment with upadacitinib was associated with early and significant improvement in RAPID3, pain, morning stiffness, and fatigue regardless of prior TNFi experience. Clinically meaningful improvement in RAPID3 patient-reported disease activity was observed as early as week 1, with continued improvement reported through week 12.

Early life stress (ELS) promotes B cell expansion and aortic pathology in a mouse model of systemic lupus erythematosus (SLE)

SLE is an autoimmune disease that primarily affects young women and is associated with high rates of cardiovascular disease (CVD). Exposure to ELS (adversity in childhood such as verbal and physical abuse and/or familial dysfunction) is an independent risk factor for CVD and SLE. ELS heightens the risk of developing SLE and SLE patient-reported disease activity, however the underlying mechanism is unclear. We previously showed in a mouse model of ELS, maternal separation with early weaning (MSEW), that mice with pristane-induced SLE develop autoantibodies and increased aortic stiffness earlier in disease progression compared to normally reared (NR) SLE mice. We hypothesized that disease acceleration in MSEW+SLE mice compared to NR+SLE mice is associated with an expansion of B-cells and aortic structural changes. The pristane-induced model of SLE uses an intraperitoneal injection (i.p.) to induce SLE-like symptoms in female mice. The MSEW protocol separates pups from the dam 4h/day (postnatal, PD 2 to 5) and 8h/day (PD 6 to 16) with weaning at PD17. NR litters are weaned at PD21. At 6-8 weeks of age, female mice were randomly assigned to control (CON) or SLE groups: CON received an i.p. PBS injection, while NR+SLE and MSEW+SLE received an i.p. pristane injection. Spleen and thymus were weighed and collected for B-cell subset analysis with flow cytometry and aorta were dissected for histological assessments. At 4 months-post pristane, spleen weights did not differ between groups, however, we observed that MSEW+SLE mice had significantly larger thymus/body weight (BW) compared to CON and NR+SLE mice (p=0.0004 F=7.5 n=4). At 7 months post-pristane or PBS injection, MSEW+SLE mice and NR+SLE mice had significantly higher splenic weights/BW compared to CON mice (p=0.03 F=4.36, n=6) as expected. Using flow cytometry, we found increased thymic %age of CD19+ B-cells in both NR+SLE and MSEW+SLE compared to CON (p&lt;0.0001 F=57.33, n=8,4,4), whereas we found similar %age of CD19+ B-cells in the aorta or spleen of mice in all groups. MSEW+SLE mice had increased germinal center B-cells compared to CON (CON: 0.77%, NR+SLE: 6.0%, MSEW+SLE 7.4%, p=0.008 F=7.08 n=8,4,4) while NR+SLE mice had increased plasma cells compared to CON (CON: 0.08%, NR+SLE: 1.3%, MSEW+SLE 0.68%, p=0.015 F=5.92 n=8,4,4). At 7 months post-pristane, MSEW+SLE mice had significantly greater aortic wall thickness (um) compared to NR+SLE and NR+CON mice (p=0.008 F=11.99, n=3,3,3), however, aortic collagen content (picrosirius red) was similar. These data suggest a difference in B-cell subset expansion and aortic structural changes may contribute to the MSEW driven acceleration of disease activity. Understanding how ELS accelerates autoimmunity and CVD risk is crucial to preventing worsened outcomes in vulnerable populations of individuals exposed to ELS with SLE. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparing Patient-Reported Outcomes Among Anti-TNF-Experienced Patients with Crohn's Disease Initiating Vedolizumab Versus Ustekinumab.

Primary and secondary non-response to anti-tumor necrosis factor (TNF) therapy is common in patients with Crohn's disease (CD), yet limited research has compared the effectiveness of subsequent biological therapy. We sought to compare the effectiveness of vedolizumab and ustekinumab in anti-TNF-experienced patients with CD, focusing on patient-prioritized patient-reported outcomes (PROs). We conducted a prospective, internet-based cohort study nested within IBD Partners. We identified anti-TNF-experienced patients initiating with CD vedolizumab or ustekinumab and analyzed PROs reported approximately 6months later (minimum 4months, maximum 10months). Co-primary outcomes were Patient-Reported Outcome Measurement Information System (PROMIS) domains of Fatigue and Pain Interference. Secondary outcomes included patient-reported short Crohn's disease activity index (sCDAI), treatment persistence, and corticosteroid use. Inverse probability of treatment weighting (IPTW) was used to control for a number of potential confounders and incorporated into linear and logistic regression models for continuous and categorical outcomes, respectively. Overall, 141 vedolizumab and 219 ustekinumab initiators were included in our analysis. After adjustment, we found no differences between treatment groups in our primary outcomes of Pain Interference or Fatigue or the secondary outcome of sCDAI. However, vedolizumab was associated with lower treatment persistence (OR 0.4, 95% CI 0.2-0.6) and higher corticosteroid use at follow-up assessment (OR 1.7, 95% CI 1.1-2.6). Among anti-TNF experienced patients with CD, Pain Interference or Fatigue was not significantly different 4-10months after starting ustekinumab or vedolizumab. However, reduced steroid use and increased persistence suggest superiority of ustekinumab for non-PRO outcomes.

E086 Comparing ankylosing spondylitis disease activity during the COVID-19 pandemic using patient-reported outcome measures with face-to-face clinical evaluation of disease scores pre-pandemic

Abstract Background/Aims During the COVID-19 pandemic, asynchronous consultations were introduced for patients with ankylosing spondylitis (AS). To assess disease activity in the absence of face-to-face clinical review and blood testing, patients submitted patient-reported outcome measures (PROMs) via electronic survey forms which were subsequently triaged by clinicians. We compared pre-pandemic clinician-reported scores with intra-pandemic self-reported scores and assessed clinical outcomes including allocation of follow-up and further management/treatment escalation. Methods Clinician-reported scores were obtained in-person pre-pandemic (defined as 01/01/2019-01/03/2020). Self-reported BASDAI scores were submitted by patients via electronic forms sent out during-pandemic (defined as 01/12/2020-31/03/22). The responses were stored and analysed in a secure database. These scores are analogous to disease activity scores completed by clinicians during outpatient appointments. Score comparison was performed using Wilcoxon Sign Rank testing. We used the need for a follow-up within 3 months as target for those with severe disease. Data analysis was performed in Microsoft Excel and R (version 4.2.1). Results We noted a significantly higher overall level of patient-reported disease activity during the pandemic. In the total cohort of AS patients, the median BASDAI Score collected during-pandemic increased from 5.30 (n = 124, range 0-10) compared to 2.80 pre-pandemic (n = 590, range 0-12) (p &amp;lt; 0.001). The proportion of patients with severe/active disease (defined as BASDAI &amp;gt;4) increased from 36% pre- to 65% during pandemic. In a smaller cohort of 34 patients for whom we had both pre- and during-pandemic scores, all patient parameters worsened during the pandemic. Notably, median BASDAI increased from 2.65 to 5.62 (p &amp;lt; 0.0001). Patients with severe AS increased from 10 (29.4%) to 21 (61.8%) intra-pandemic. Follow-up data was available for 12/21 patients with severe AS during-pandemic. 7/12 patients (58%) received a follow-up appointment within one month; 11/12 (91%) were seen within three months. On subsequent clinician assessment, only 7 (58%) of patients with self-reported severe AS were felt to have active disease; treatment was escalated for 3 patients. Conclusion There was a significantly higher reported level of AS disease activity during the COVID-19 pandemic, with 62 % of patients qualifying for biologic therapy (BASDAI &amp;gt;4). In a focussed sample, 91% of patients with new severe disease during-pandemic were followed up within the target of 3 months. The BASDAI score is independent from clinical examination and inflammatory markers, and therefore self-reported score should reliably reflect a patient’s perception of disease activity. Further work is required to determine the reason for the increased disease activity observed during pandemic, and for the disparity between clinician impression and score results. Disclosure D.A. Kurzeja: None. K. Song: None. M. Mirza: None. M. Ashraf: None. L. James: None. A. Verdiyeva: None. R. Luqmani: None.

Impact of the COVID-19 pandemic on patients with rheumatoid arthritis: data from the Ontario Best Practices Research Initiative (OBRI).

The coronavirus disease 2019 (COVID-19) pandemic created challenges for patients with RA. We examined the potential impact of the pandemic on patient-reported outcomes (PROs), disease activity and medication profiles, comparing the periods pre-pandemic and during the pandemic. Patients enrolled in the Ontario Best Practices Research Initiative were included if they had at least one visit to a physician or study interviewer within 12 months before and after the start of pandemic-related closures in Ontario (15 March 2020). Baseline characteristics, disease activity, PROs [i.e. health assessment questionnaire disability index, RA disease activity index (RADAI), European quality of life five-dimension questionnaire], medication use and changes were included. Student's paired two-sample t-tests and McNamar's tests were performed for continuous and categorical variables between time periods. The sample for analysis consisted of 1508 patients, with a mean (s.d.) age of 62.7(12.5) years, and 79% were female. Despite decreases in the number of in-person visits during the pandemic, there was no significant negative impact on disease activity or PRO scores. The DASs in both periods remained low, with either no clinically significant differences or slight improvement. Scores for mental, social and physical health were either stable or improved. There were statistically significant decreases in conventional synthetic DMARD use (P < 0.0001) and increased Janus kinase inhibitor usage (P = 0.0002). Biologic DMARD use remained stable throughout the pandemic. In this cohort, disease activity and PROs of RA patients remained stable during the COVID-19 pandemic. The longer-term outcomes of the pandemic warrant investigation.

Evaluation of the LFA-REAL clinician-reported outcome (ClinRO) and patient-reported outcome (PRO): prespecified analysis of the phase III ustekinumab trial in patients with SLE

ObjectiveThe Lupus Foundation of America Rapid Evaluation of Activity in Lupus (LFA-REAL) system is a novel and simple SLE disease activity instrument, consisting of a tandem clinician-reported (ClinRO) and patient-reported...

Perceived Stress and Prediction of Worse Disease Activity and Symptoms in a Multiracial, Multiethnic Systemic Lupus Erythematosus Cohort.

Studies have suggested a potential link between traumatic experiences, psychological stress, and autoimmunity, but the impact of stress on disease activity and symptom severity in systemic lupus erythematosus (SLE) remains unclear. The present study was undertaken to examine whether increases in perceived stress independently associate with worse SLE disease outcomes over 3 years of follow-up. Participants were drawn from the California Lupus Epidemiology Study (CLUES). Stress was measured annually using the 4-item Perceived Stress Scale (PSS). Participants with increases of ≥0.5 SD in PSS score were defined as having an increase in stress. Four outcomes were measured at the year 3 follow-up visit: physician-assessed disease activity (Systemic Lupus Erythematosus Disease Activity Index); patient-reported disease activity (Systemic Lupus Activity Questionnaire); pain (Patient-Reported Outcomes Measurement Information System [PROMIS] pain interference scale); and fatigue (PROMIS fatigue scale). Multivariable linear regression evaluated longitudinal associations of increase in stress with all 4 outcomes while controlling for potential confounders. The sample (n=260) was 91% female, 36% Asian, 30% White, 22% Hispanic, and 11% African American; the mean ± SD age was 46 ± 14 years. In adjusted longitudinal analyses, increase in stress was independently associated with greater physician-assessed disease activity (P=0.015), greater self-reported disease activity (P < 0.001), more pain (P=0.019), and more fatigue (P < 0.001). In a racially diverse sample of individuals with SLE, those who experienced an increase in stress had significantly worse disease activity and greater symptom burden at follow-up compared to those with stress levels that remained stable or declined. Findings underscore the need for interventions to bolster stress resilience and support effective coping strategies among individuals living with lupus.

The association of trauma with self-reported flares and disease activity in systemic lupus erythematosus (SLE).

Trauma has been linked to incident SLE, but its relationship with SLE disease activity is unknown. This analysis examines associations between trauma exposures and patient-reported SLE disease activity and flares. Data were from the California Lupus Epidemiology Study (CLUES). Flares were self-reported as any flare and, of those, flares accompanied by medical care (hospitalization or physician contact). The Systemic Lupus Activity Questionnaire (SLAQ) assessed disease activity. The Brief Trauma Questionnaire (BTQ) assessed all historical trauma exposures. The Adverse Childhood Experiences (ACEs) questionnaire was available for a subset. Multivariable regression analyses (n = 252) examined whether trauma exposure was associated with flares or SLAQ controlling for age, sex, poverty, race/ethnicity, comorbidities, perceived stress, disease duration and self-reported disease damage. Excluding exposure to serious illness, 63.4% reported ≥1 trauma exposure. Any traumatic event, excluding illness, doubled the odds of a flare [OR 2.27 (95% CI 1.24, 4.17)] and was associated with significantly higher SLAQ scores [β 2.31 (0.86, 3.76)]. Adjusted odds of any flare and flare with medical care were significantly elevated for those with both BTQ and ACE exposures [5.91 (2.21, 15.82) and 4.69 (1.56, 14.07), respectively]. SLAQ scores were also higher for those with both exposures [β 5.22 (3.00, 7.44)]. In this cohort, those with a history of trauma reported more flares and greater disease activity. Identifying mechanisms of associations between trauma and disease activity and flares, as well as interventions to mitigate the effects of trauma exposures is critical, given the high rates of trauma exposures.