tbuckley/cabot-search huggingface dataset:
POS1077 DISTINGUISHING THE DRYNESS DUE TO FIBROMYALGIA SYNDROME FROM SJÖGREN’S SYNDROME MIGHT BE DIFFICULT WITHOUT IMMUNOLOGICAL TESTS AND HISTOPATHOLOGICAL EVALUATION
Authors: S. Akar, İ. Kurut Aysin, E. Otman, A. Özkan, Ö. Yoğurtçu, H. Kocaayan, D. Solmaz
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The frequency of symptoms related to connective tissue diseases such as dry eye and mouth and Raynaud's phenomenon (RP) in patients with Fibromyalgia Syndrome (FMS) has been reported to be higher in comparison with the healthy population. Additionally, the coexistence of Sjögren's Syndrome (SjS) with FMS might be higher compared to other connective tissue diseases. <h3>Objectives:</h3> In the present study, we aimed to compare the frequency of symptoms and signs that could be related to SjS and to determine whether there are distinguishing characteristics between FMS and SjS patients. <h3>Methods:</h3> 492 patients were referred to a tertiary referral centre to investigate connective tissue disease and underwent minor salivary gland biopsy, and 77 patients diagnosed with FMS, according to treating physicians, were included in the present analysis. One hundred forty-six patients were classified as SjS according to ACR/EULAR 2012 or 2016 criteria (127 [87%] primary SjS; 19 [13.9%] secondary SjS). 25 patients with coexistence of SjS and FMS were excluded. We used t-tests for parametric and Mann Whitney U test for non-parametric analysis to compare between groups. Multivariate logistic regression analysis was performed for the differentiation of two disease groups. The most relevant variables were included in the model, and the backward method was used. A p-value of &lt;0.05 was considered statistically significant. <h3>Results:</h3> When we compared SjS and FMS patients, the female gender was significantly higher in the FMS group (98.7% vs 91.1%; p: 0.038). The mean age was similar. Although arthralgia was more common in FMS patients (90.8% vs 74.5%; p: 0.004), arthritis was higher in SjS patients (22,2% vs 10,5%; p: 0.032). No difference was found between the two groups in terms of morning stiffness and the presence of RP. FMS and SjS patients complained of dry mouth and eyes at similar rates. Schirmer's test positivity was significantly higher SjS patients (72.2% vs 51.9%; p: 0.011), however a significant proportion of FMS patients had Schirmer's test positivity. Tear break-up time (tBUT) was similar in both groups. As expected, immunological tests were much less common in FMS patients compared to SjS patients (p&lt;0.001) (Table 1). Further analysis showed that Schimer, RF and SS-A test negativities were the most important diagnostic differential tools for FMS (Table 2). <h3>Conclusion:</h3> Besides subjective complaints of dryness, objective signs of dry eye are highly frequent in FMS patients compared to SjS, and the need for immunological tests still exists to differentiate a significant proportion of FMS patients with a positive dryness test. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
POS1359 PNEUMOCYSTIS PNEUMONIA IN PATIENTS WITH RHEUMATOID ARTHRITIS-AICHI PREFECTURE DPC DATA
Authors: R. Sato, T. Imaizumi, K. Terabe, J. Hasegawa, S. Asai, S. Imagama
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> While the treatment of rheumatoid arthritis (RA) has made great progress, pulmonary infection is a complication that should always be kept in mind. Pneumocystis pneumonia (PCP) in RA progresses rapidly, and early diagnosis and treatment of PCP are reported to be essential for the prevention of severe disease(1)(2). It is important to understand the actual status of existing pulmonary diseases, treatment details, and epidemiological background from the viewpoint of prevention and early diagnosis of RA-PCP(2)(3). <h3>Objectives:</h3> To understand the actual situation and risk factor of PCP in RA patients. <h3>Methods:</h3> The study was designed as a nested case-control (PCP case:control 1:20) study using DPC data from Aichi prefecture, Japan, from 2015 to 2022, including patients with PCP (n=151) among RA probable cases (n=14190). Conditional logistic regression analysis was used to examine the incidence of RA-PCP and factors associated with the development of RA-PCP. <h3>Results:</h3> The background of patients with PCP was male (38%), and the mean age at admission was 70±13 years. The incidence of PCP was 1.4% in the cumulative 8-year data of DPC hospitals in Aichi Prefecture. Univariate analysis of the Control group (n=2989) and PCP group (n=151) adjusted for age and sex showed significant differences in MTX and b/tsDMARDs as factors associated with RA-PCP incidence(Table 1). Multivariate analysis showed that COPD (OR=1.65, 95% confidence interval 1.02-2.68,P=0.043),PSL10mg/day≤(OR=1.67,95% confidence interval 1.06-2.63,P=0.026),MTX(OR=5.45,95% confidence interval 3.67-8.09,P&lt;0.001) and tsDMARDs (OR=2.67,95% confidence interval 1.05-6.75,P=0.038) were factors associated with the development of PCP. In addition, administration of PCP prophylaxis significantly reduced the risk of developing PCP (OR=0.41,95% confidence interval 0.2-0.82,P=0.012)(Table 2). <h3>Conclusion:</h3> In this study, COPD and RA drug use were factors associated with the development of PCP. In particular, the use of MTX, tsDMARDs, and PSLs of 10 mg/day or more was a significant risk factor for the development of PCP. <h3>REFERENCES:</h3> [1] Shunsuke Mori, Mineharu Sugimoto,et.al. Pneumocystis jirovecii infection: an emerging threat to patients with rheumatoid arthritis. Rheumatology 2012;51:2120-2130 [2] Amine Ghembaza, Mathieu Vautier, Patrice Cacoub,et.al. Risk Factors and Prevention of Pneumocystis jirovecii Pneumonia in Patients With Autoimmune and Inflammatory Diseases. CHEST 2020; 158(6):2323-2332 [3] Takayuki Katsuyama, Kazuyoshi Saito,et.al. Prophylaxis for Pneumocystis pneumonia in patients with rheumatoid arthritis treated with biologics, based on risk factors found in a retrospective study. Arthritis Research &amp; Therapy 2014, 16:R43 <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
Cardiovascular adverse events in patients with cancer treated with chimeric antigen receptor (CAR) T-cell therapy: A meta-analysis of both controlled and single-arm clinical trials.
Authors: Phyo Thazin Myint, Monika Kulasekaran, Muhammad Yasir, Mohammed Saleh, Cherian Verghese
Journal: Journal of Clinical Oncology (2024)

e19006 Background: Chimeric antigen receptor (CAR-T) Chimeric antigen receptor (CAR) T-cell therapy presents a promising avenue in the treatment of hematological malignancies. However, the application of CAR-T cell therapy comes with a range of adverse effects, some of which are not fully understood yet. While previous research has primarily focused on immune effector cell-associated neurotoxicity (ICANs) and cytokine release syndrome (CRS), the cardiovascular safety profile of CAR-T cell therapy remains less defined. This meta-analysis assesses the incidence of cardiovascular (CV) events associated with CAR-T therapy, thereby providing critical insights into these events and guiding clinical decision-making. Methods: We conducted a Pubmed search of clinical trials evaluating the effect of CAR-T cell therapy in cancer patients with cardiovascular adverse events. For phase III trials, a quantitative assessment of Grade 3 or higher CV events was performed using the Review Manager (Rev-Man) Version 5.4 (The Cochrane Collaboration, 2020) and the results were reported as Odd Ratio (OR) with 95% Confidence Interval (CI). A fixed effect model was used. For phase I/II trials, the event rates were calculated for all-grade as well as grade 3 and higher CV adverse events. Results: A total of four Phase III clinical trials with 1345 patients were included for the comparison analysis. Among those trials, two involved multiple myeloma patients, and two involved large B cell lymphoma patients. The age range across trials was 20-83 years with a male-to-female ratio of 1.5:1. The analysis revealed that there was no statistically significant difference in Grade 3 or higher CV events between the CAR-T cell therapy and control (standard of care) groups: OR with 95% CI was 1.44 (0.73,2.82) (p=0.29). Grade 3 and above CV adverse event rates were 3.4% for the CAR-T and 2.1% for the control groups. Notably, there were two CV deaths in the CAR-T group and one CV death in the control group. Additionally, a total of 41 single-arm, Phase I/II clinical trials with 1479 participants were analyzed. Seven studies included solid cancers such as metastatic pancreatic cancer, biliary tract cancer and melanoma. The age range was 17-86 yr and male/female ratio was 1.5:1. Total all-grade CV adverse event rate was 21.83% and total grade 3 and above CV adverse event rate was 8.82%. There were eight CV deaths. Conclusions: There were significantly more CV adverse events reported in Phase I/II trials when compared to those reported in Phase III trials. This indicates that CV adverse events are important consequences of CAR-T cell therapy but are likely underreported in the Phase III clinical trials. Increased awareness and more standardized evaluation of CV adverse events of CAR-T is needed in the future clinical trials.
POS1051 GLUCOCORTICOID-FREE REMISSION IN PATIENTS WITH SLE IN THE ERA OF BIOLOGICS: IMMUNE COMPLEX DISEASE IS LIKELY TO BENEFIT FROM CURRENT MEDICATIONS
Authors: H. Oiwa, T. Suga, Y. Hosokawa, K. Araki
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> In addition to various immunosuppressive agents, belimumab and anifrolumab became available in Japan. <h3>Objectives:</h3> We aimed to investigate glucocorticoid-free clinical remission in a single-centre retrospective cohort in October 2023. <h3>Methods:</h3> Our cohort included patients with SLE who needed to start or increase glucocorticoids for disease activity and were followed up for more than one year. We investigated the rate of achievement of clinical remission off corticosteroids (CR off C), defined as no clinical score on the SLEDAI-2K without glucocorticoids [1], whereas the achievement of CR on C (clinical SLEDAI=0, allowing the use of prednisolone (PSL) 5 mg plus other immunosuppressive drugs, HCQ, and biologic agents) and complete remission (CR, SLEDAI=0, not allowing the use of immunosuppressive drugs and serological activities) was also evaluated. We also determined baseline predictors of CR off C, medications used when CR off C was achieved, and flare rates following CR off C. <h3>Results:</h3> Out of the 60 patients followed for an average of 5.4 (±2.6) years, 17 (28.3%) achieved CR off C in 3.6 (±1.2) years after enrolment. Use of belimumab and anifrolumab accounted for eight (47.1%) of the achievers. Among the baseline data, male sex, recent enrolment, high glucocorticoid dose, and detection of immune complex (IC) significantly predicted CR off C, while lupus nephritis (LN) and a low C3 level were likely predictors, albeit insignificantly. In the multivariate analysis, IC detection was the only predictor of CR off C. Clinical flares were observed in 5.9% of the patients during a median 1.2 years after achievement of CR off C. <h3>Conclusion:</h3> In the era of biologics, CR off C was achieved in 28.3% of the patient cohort requiring the start or increase of glucocorticoids for disease activity, with a relatively low rate of flares, suggesting that glucocorticoid-free clinical remission is an achievable target in SLE. IC disease, represented by male sex or nephritis, is likely to benefit from currently available medications. <h3>REFERENCES:</h3> [1] Zen M, Iaccarino L, Gatto M, et al. Prolonged remission in Caucasian patients with SLE: prevalence and outcomes. Ann Rheum Dis 2015;74:2117-2222. <h3>Acknowledgements:</h3> The authors would like to thank the medical staff in our hospital and all participants of this study. <h3>Disclosure of Interests:</h3> Hiroshi Oiwa I have received speaking fees from GSK, Astra-Zeneca, Asahi-kasei, Astellas, Taisho, Eisai, Pfizer, Eli Lilly, Abbvie, Ayumi, Chugai, and Boehringer Ingelheim., Takeshi Suga: None declared, Yohei Hosokawa: None declared, Kei Araki: None declared.
Real-world Bruton tyrosine kinase inhibitor (BTKi) treatment patterns and outcomes among patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in US community oncology practices.
Authors: Jing-Zhou Hou, Simon Blanc, Gregory A. Maglinte, Anupama Vasudevan, Anna Rui, Mike Gart, Hoa Pham, Lindsay Aton, Brandon Wang, Rushir J. Choksi
Journal: Journal of Clinical Oncology (2024)

e19020 Background: BTKi therapies are standard of care for CLL/SLL, with acalabrutinib (acala) and zanubrutinib (zanu) having improved safety profiles vs ibrutinib (ibru). This study assessed real-world clinical characteristics, treatment patterns, and adverse events (AEs) among BTKi-treated patients with CLL/SLL. Methods: This is a retrospective observational study, updated with 5 months of additional data from a previous analysis. Adults in the US community oncology setting initiated BTKi treatment between Jan 1, 2020, and Jul 31, 2023, and were followed to Oct 31, 2023. De-identified structured electronic health records were analyzed from the Integra Connect-PrecisionQ real-world database. Cardiovascular (CV) AEs (based on ICD codes), time to treatment discontinuation (TTD), and time to next treatment (TTNT) were reported. Results: A total of 3064 patients initiated BTKi therapies during the index period (1L n=2815; 2L+ n=249). Median age (range) was 72 years (33-90) in 1L and 72 years (42-89) in 2L+. There were 63.1% and 65.5% males in 1L and 2L+, respectively. In 1L, 49.3% of patients were treated with ibru, 43.4% with acala, and 7.2% with zanu. Similar trends were observed for 2L+. More patients experienced CV AEs among those who received 1L ibru vs acala or zanu; 12.1%, 7.6%, and 7.3% at month 6 ( P&lt;0.05) and 14.6%, 9.4%, and 8.5% at month 9 ( P&lt;0.05). With longer follow-up, there was a trend for a more favorable CV safety profile for zanu. Of patients treated with 1L ibru, 12.7% discontinued ibru and switched to acala or zanu. Median TTD in 1L was shorter for ibru than acala or zanu (Table). The associated probability of remaining on treatment was higher with zanu vs ibru or acala at months 6 and 12 (Table). Median TTNT was not reached for zanu, while it was 30.2 months for ibru and 35.8 months for acala. Conclusions: While zanu had relatively smaller sample size and shorter follow-up, this study demonstrated better real-world safety and efficacy outcomes for acala and zanu vs ibru. Additional research is needed to explain and validate observed differences favoring zanu over acala. [Table: see text]
POS0163 SOCIOECONOMIC STATUS AND ITS RELATIONSHIP WITH THE SEVERITY OF THE COURSE OF RHEUMATOID ARTHRITIS: A LARGE LONGITUDINAL STUDY
Authors: V. A. C. Vliegenthart, S. J. H. Khidir, B. M. Boxma-de Klerk, A. H. M. Van der Helm – van Mil
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The relationship between low socioeconomic status (SES) and rheumatoid arthritis (RA) severity is described in varying degrees in the literature. Studies with a long follow-up are limited and the relationship with the long-term outcomes as sustained DMARD-free remission (SDFR) is unknown. <h3>Objectives:</h3> To study the association between SES, and SES-related factors, with the disease activity score (DAS), and the chance of achieving SDFR. <h3>Methods:</h3> 789 RA-patients from the Leiden Early Arthritis Clinic (included between 2008-2022) were studied. Patients received DAS-steered treatment. SES was assessed by educational attainment, categorized as low (no/primary education), intermediate (secondary education) or high (college/university). DAS44 was measured at baseline, 4 and 12 months. SDFR was studied during median 6 (4-8) years follow-up and was defined as the sustained absence (≥ 1 year) of synovitis after discontinuing DMARDs. Mediation analysis was performed to evaluate if the association of SES with DAS was mediated by patient delay, BMI, smoking or work -related physical strain (blue/white collar occupation). <h3>Results:</h3> Patients with low educational attainment were older, had a higher BMI, more often had a blue-collar job, and smoked more frequently. Additionally, they had a higher DAS44 (β=0.34,95%CI=0.14-0.54,p=0.007). The DAS-components VAS general health and TJC did not differ between SES-groups, but the low SES-group more often had an increased ESR and more swollen joints (59% vs. 48%,p&lt;0.001 and 6 vs. 5,p=0.023, respectively). The higher DAS at RA-presentation was not mediated by patient delay, smoking, BMI or work-related physical strain. Across three consecutive visits, differences in DAS between SES-groups decreased and disappeared after one year (Figure 1A). Additionally, patients with a low SES had a similar chance of achieving SDFR (HR=1.0, 95%CI=0.7-1.5, p=0.998; Figure 1B). <h3>Conclusion:</h3> RA-patients with a low SES presented with higher inflammation scores at diagnosis. This was not explained by common SES-related factors. Nevertheless, treat-to-target strategy resulted in a comparable disease severity. These data emphasize the relevance of SES and standardized treatment in RA. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>
Preliminary results of a first-in-human study on ESG206, a novel anti-BAFF-R monoclonal antibody, in relapsed or refractory B-cell malignancies.
Authors: Yuqin Song, Ningjing Lin, Hui Liu, Qing Zhou, Xiaoyan Xing
Journal: Journal of Clinical Oncology (2024)

e19000 Background: B-cell-Activating Factor-Receptor (BAFF-R), predominantly expressed on the surface of the mature B cells, including malignant B cells, serves as an attractive therapeutic target for the diseases where CD19 or CD20-targeted therapies encounter challenges, such as loss of therapeutic targets or development of resistance. No BAFF-R targeting agent has been approved yet for clinical use to date. ESG206, a recombinant humanized anti-BAFF-R monoclonal antibody modified by glycoengineering for enhanced ADCC effects, is being developed as a treatment for relapsed or refractory (R/R) B-cell malignancies. Preclinical investigations have successfully validated the antitumor effects of ESG206 across a spectrum of malignant B cell disease models, including lymphoma xenografts which were resistant to Rituximab, and Ibrutinib. This report provides preliminary clinical safety, PK, PD, and efficacy results from an FIH study of ESG206 in patients with R/R B-cell malignancies. Methods: This Phase I, open-label, multicenter dose-escalation study enrolled patients with R/R B-cell malignancies resistant to standard therapy. Dose escalation utilized accelerated titration (1 mg/kg) and Bayesian Optimal Interval design (3, 6, and 9 mg/kg). ESG206 was administered intravenously every 2 weeks, with a 4-week cycle, until disease progression or intolerable toxicity. DLT was assessed in the first 28 days. Safety was evaluated per CTCAE 5.0. Tumor assessments every 8 weeks, and peripheral CD20-positive B cell counts as a PD marker were evaluated. Results: As of Jan 30 th , 2024, data cut-off date, 6 pts (3 follicular lymphoma (FL), 3 diffuse large B-cell lymphoma (DLBCL)) were enrolled, with a median age of 56 years, 83.3% female; median 2 prior lines of therapy (range 1-3). No DLTs were observed up to 6 mg/kg Q2W. Treatment-related adverse events (TRAEs) included anemia (n=2), decreased white blood cell count (n=1), hyperlipidemia (n=1, grade 2), elevated bilirubin (n=1), diarrhea (n=1), infusion reactions (n=1, grade 2), upper respiratory infections (n=1, grade 2), etc. No grade≥3 TRAEs occurred. Among 6 evaluable patients, 1 FL patient (3 mg/kg Q2W) and 1 DLBCL patient (3 mg/kg Q2W) achieved partial response. After 2 cycles of treatment, there was a 39.5% size reduction in the brain lesions of an FL patient who had intracranial metastases in baseline, suggesting that ESG206 may have a therapeutic effect on brain metastases. A significant decrease in the peripheral CD20+B cells was observed at both 1 and 3 mg/kg Q2W dose levels. ESG206 exposure increased with dose escalation across the 1–3 mg/kg dose range. Conclusions: Preliminary data indicates ESG206 is well-tolerated with promising efficacy signals in R/R B-cell malignancies. These encouraging results warrant continued clinical evaluation as the Phase I study progresses. Clinical trial information: NCT05263739 .
OP0061 JIA AND WORK LOSS IN YOUNG ADULTHOOD: NATIONWIDE COHORT STUDY
Authors: G. Bruze, H. Miller, J. Askling, M. Neovius
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Patients diagnosed with JIA during the last two decades have had access to considerably better drug treatments than previous cohorts. The level of work loss in young adulthood for the current generation of patients has not been described in large cohorts using objective measures of the outcome. <h3>Objectives:</h3> To compare trajectories of work loss in individuals with JIA versus age-sex-matched comparators from the general population. <h3>Methods:</h3> Patients with JIA (n=4749; 63.4% women) were identified in the Swedish National Patient Register (2001-2017) and individually matched to up to 5 general population comparators on birthyear, sex, and residence county (n=23,758). Compensated sick leave and disability pension data, including sick leave spells longer than 14 days, were retrieved from the Social Insurance Agency from age 18y. Mean differences were estimated using linear regression with adjustment for parental education. <h3>Results:</h3> Patients with JIA had higher mean annual work loss than their matched general population comparators during all years between 18-30 years of age (Figure 1). At age 20y, patients with JIA had a mean 24 days of work loss annually compared with 12 among comparators (adjusted mean difference 12 days, 95%CI 10-14). The corresponding work loss at age 25y was 31 vs 16 days (adjusted mean difference 15 days, 95%CI 12-18) and at age 30y, 34 vs 20 days (adjusted mean difference 14 days, 95%CI 8-19). The distribution of work loss was heavily skewed with 75% of patients with JIA and 85% of general population comparators not having any compensated work loss days at age 25y, while about 5% vs 1% had 6 months or more of compensated work loss at that age (P&lt;0.001; Figure 2). <h3>Conclusion:</h3> JIA is associated with about twice as high annual work loss in young adulthood compared to the general population, driven by a minority of patients with extensive work loss. Until age 30y, more than 75% of patients with JIA had no work loss compensation for spells longer than 14 days in a given year. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Gustaf Bruze Agreements between Karolinska Institutet (with JA as PI) and Abbvie, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, mainly for the national safety monitoring of rheumatology immunomodulators in Sweden (ARTIS)., Heather Miller: None declared, Johan Askling Agreements between Karolinska Institutet (with JA as PI) and Abbvie, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, mainly for the national safety monitoring of rheumatology immunomodulators in Sweden (ARTIS)., Martin Neovius Agreements between Karolinska Institutet (with JA as PI) and Abbvie, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, mainly for the national safety monitoring of rheumatology immunomodulators in Sweden (ARTIS).