Cohort Of Rheumatoid Arthritis Patients Research Articles

E022 Audit on the baricitinib dose in elderly and patients with chronic kidney disease among a cohort of rheumatoid arthritis patients

Abstract Background/Aims Baricitinib use among elderly patients and in patients with chronic kidney disease needs modification of the dose. Baricitinib dose should be reduced to 2mg daily in patients who are 75 years or older given the associated increased risks in this age group. Additionally, baricitinib should be avoided in patients with creatinine clearance of less than 30 ml/min and dose needs to be reduced in patients with a creatinine clearance between 30-60 ml/min because it is primarily renally excreted drug. Methods All the blueteq requests for baricitinib at University Hospitals Coventry and Warwickshire, from 05/07/2021 to 05/07/2023 were evaluated. There were 128 patients who have been on baricitinib during this period. Twenty patients out of this, were 75 years or above. The baricitinib dose in patients above the age of 75 and in patients with chronic kidney disease was assessed by using NICE guidance on the use of baricitinib in patients with rheumatoid arthritis and the BNF as the audit standards respectively. Results Of the 20 patients who were 75 years and above, 13 patients were still on baricitinib. Ten patients were on a dose of 2mg daily which is in keeping with NICE guidance while 3 patients were still receiving a dose of 4mg daily. Seven patients were started on baricitinib after 75 years and 4 of them were started on 4mg daily which is not keeping with NICE guidance. Of the 128 patients, none of them had a creatinine clearance less than <30 ml/min while there were 16 patients who had received baricitinib (at some point) with a creatinine clearance of 30-60 ml/min. Of them, 14 patients were at some point on 4mg daily dose of Baricitinib which is not in keeping with guidance. Of those 14 patients, 6 patients were still receiving a dose of 4mg daily. Conclusion In conclusion, it appears that we have not completely adhered to standard criteria laid down by NICE guidelines and in the BNF. This presentation aims to raise awareness among rheumatologists regarding these guidelines. Also, changing the format of the prescription to include the age and renal functions would prompt the prescriber to amend the dose accordingly. The use of baricitinib may reduce in the future due to concerns of increased cardiovascular disease. However, there is a group of patients who are already on baricitinib and will want to continue, despite these concerns, given the significant improvements in disease control. Disclosure C. Rosa: None. J. Joseph: None. G. Kasavkar: None.

Predictors of serious infections in rheumatoid arthritis—a prospective Brazilian cohort

BackgroundInfections increase mortality and morbidity and often limit immunosuppressive treatment in rheumatoid arthritis patients.ObjectiveTo analyze the occurrence of serious infections and the associated factors in a cohort of rheumatoid arthritis patients under real-life conditions.MethodsWe analyzed data from the REAL, a prospective observational study, that evaluated Brazilian RA patients, with clinical and laboratory data collected over a year. Univariate and multivariate analyses were performed from the adjustment of the logistic regression model Generalized Estimating Equations (GEE), with the primary outcome being the occurrence of serious infection, defined as need for hospitalization or use of intravenous antibiotics for its treatment.Results841 patients were included with an average follow-up time of 11.2 months (SD 2.4). Eighty-nine serious infections occurred, corresponding to 13 infections per 100 patient-years. Pulmonary fibrosis, chronic kidney disease (CKD) and central nervous system disease increased the chances of serious infection by 3.2 times (95% CI: 1.5–6.9), 3.6 times (95% CI: 1.2–10.4) and 2.4 times (95% CI: 1.2–5.0), respectively. The use of corticosteroids in moderate doses increased the chances by 5.4 times (95% CI: 2.3–12.4), and for each increase of 1 unit in the health assessment questionnaire (HAQ), the chance increased 60% (95% CI: 20–120%).ConclusionThe use of corticosteroids at moderate doses increased the risk of serious infection in RA patients. Reduced functionality assessed by the HAQ and comorbidities were other important factors associated with serious infection in this cohort.

Incidence and risk factors of major cardiovascular events in rheumatoid arthritis and psoriatic arthritis: A population-based cohort study

ObjectiveTo evaluate the incidence and risk factors of major adverse cardiovascular events (MACE) in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. MethodsA population-based retrospective cohort of RA and PsA patients was identified in a citywide database. All patients recruited from Jan 2006 to Dec 2015 were followed until the end of 2018. The outcome was the occurrence of a first MACE. Covariates of interest included traditional cardiovascular (CV) risk factors, inflammatory markers and pharmacotherapies. The independent predictors of MACE were identified by the time-dependent cox proportional hazard models. ResultsA total of 13,905 patients (12,233 RA and 1,672 PsA) were recruited. After a total of 119,571 patient-years of follow-up, 934 (6.7%) patients developed a first MACE. RA and PsA patients had similar adjusted incidence (incidence rate ratio 0.96, 95 % CI 0.75–1.22, p = 0.767). After adjusting for traditional CV risk factors, the time-varying erythrocyte sedimentation (ESR) rate and C-reactive protein (CRP) levels, and the use of glucocorticoids were independently associated with higher risk of MACE in both the RA and PsA cohorts. In RA, the use of methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs) were associated with fewer MACE. The use of biologic disease modifying anti-rheumatic drugs was not associated with MACE in both RA and PsA. ConclusionThe incidence of MACE was similar in RA and PsA. Systemic inflammation and glucocorticoid use independently increased the risk of MACE in inflammatory arthritis, while methotrexate and NSAIDs use were protective against the development of MACE in RA.

Retinal microvascular alterations in patients with active rheumatoid arthritis without cardiovascular risk factors: the potential effects of T cell co-stimulation blockade.

The evaluation of microvascular alterations might provide clinically useful information for patients with an increased cardiovascular (CV) risk, such as those with rheumatoid arthritis (RA), being the small artery remodeling the earliest form of target organ damage in primary CV diseases, such as arterial hypertension. The evaluation of retinal arterioles is a non-invasive technique aimed to identify an early microvascular damage, represented by the increase of the wall-to-lumen ratio (WLR) index. Abatacept (ABA), a T-cell co-stimulator blocker, is used to treat RA. A CV protective action was hypothesized for its peculiar mechanism of action in the modulation of T-cells, potentially involved in the pathogenesis of CV comorbidity. The study aimed to non-invasively investigate morphological characteristics of retinal arterioles in a cohort of RA patients treated with ABA. Seventeen RA patients [median (25th-75thpercentile) age = 58 (48-64) years, baseline 28-joint Disease Activity Score DAS28-C-reactive protein (DAS28-CRP) = 4.4 (3.9-4.6), body mass index (BMI) = 24.2 (23.4-26) kg/m2, rheumatoid factor positive:52.9%, anti-citrullinated peptide autoantibodies positive:76.5%] without known CV risk factors (arterial hypertension, diabetes, hypercholesterolemia, previous CV events, smoking) were evaluated by the adaptive optics imaging system of retinal arterioles before and every 6 months of therapy with ABA (T0, T6 and T12). Office blood pressure evaluation, 24-h ambulatory blood pressure monitoring and tissue-doppler echocardiography were also performed. A progressive significant reduction of the WLR of retinal arterioles was observed [T0 = 0.28 (0.25-0.30), T6 = 0.27 (0.24-0.31), T12 = 0.23 (0.23-0.26); p T0 vs. T6 = 0.414; p T6 vs. T12 = 0.02; p T0 vs. T12 = 0.009], without significant variations in other parameters. The T0-T12 reduction of WLR was correlated with that of DAS28-CRP (r:0.789; p = 0.005). Moreover, a significant reduction of diastolic office blood pressure and a trend for reduction of daily pressure measured by ambulatory monitoring were observed. In a cohort of RA patients without known CV risk factors, a reduction of retinal microvascular alterations was demonstrated after treatment for 12 months with ABA, in parallel with the reduction of disease activity. These results might suggest the possibility of microvascular abnormalities regression induced by the immune system modulation.

The impact of folate pathway variants on the outcome of methotrexate therapy in rheumatoid arthritis patients.

There are currently no validated criteria that entirely explain or predict response to methotrexate (MTX) treatment in rheumatoid arthritis (RA). We tried to identify the connection between three variants (RFC1 G80A (rs1051266), TYMS 2R/3R (rs34743033), and ATIC C347G (rs2372536)) in the folate pathway of MTX metabolism and the response to MTX monotherapy in a cohort of RA cases. A prospective study on 100 RA patients on MTX monotherapy was performed. Disease activity was measured at the start of treatment and 6months after treatment with MTX. The patients were then split into two groups: those who responded to the treatment and those who did not. The molecular genetic study for the RFC1 (G80A) variant was employed via the PCR-restriction fragment length polymorphism (PCR-RFLP) technique, the ATIC (C347G) variant was performed using TaqMan allelic discrimination real-time PCR, and the tandem repeat sequences of TYMS (2R/3R) were amplified by conventional PCR and detected by agarose gel electrophoresis. The genotype distribution of RFC-1 (G80A) showed significant variations among non-responders and responders in the recessive genetic model. A significant difference was found in TYMS (2R/3R) in the dominant and heterozygous genetic models. However, ATIC (C347G) genotype frequency did not exhibit substantial link with drug response in all genetic models. Furthermore, the genotype and allele rates of the analyzed variants did not show any significant association with adverse events in all genetic models. The 80AA genotype of RFC-1 G80A and the 2R/3R or 3R/3R genotypes of TYMS 2R/3R are more vulnerable to the good consequences of MTX therapy. Key Points • Current recommendations support the gold standard role of MTX as a first-line monotherapy for RA patients. However, up to 40% of RA patients do not respond or exhibit partial response to MTX. • Persistent disease activity due to treatment unresponsiveness will affect the long-term outcomes in RA patients. • We aimed, through molecular genetic study, to identify the connection between three variants in the folate pathway of MTX metabolism and the response to methotrexate monotherapy in a cohort of RA patients.

Associations of galectin-3 levels with measures of vascular disease in patients with rheumatoid arthritis

ObjectivesGalectin-3 is a beta-galactoside-binding lectin and is a marker of cardiovascular disease (CVD) in the general population. It may also play a role in joint inflammation. We asked whether serum galectin-3 is a useful marker of subclinical vascular disease in patients with rheumatoid arthritis (RA). MethodsRA patients without clinical CVD underwent assessment of coronary artery calcium (CAC) score, aortic inflammation (using 18Fluorodeoxyglucose positron emission-computed tomography [FDG PET/CT]), and myocardial flow reserve (MFR). Aorta FDG uptake was measured as standardized uptake values (SUV). Generalized linear models were constructed to explore the associations of galectin-3 levels with CAC score, aortic SUV, and MFR. ResultsA total of 124 RA patients (mean age 57; 82 % women, 45 % Hispanic; median RA duration 6.8 years; 75 % seropositive; median CDAI 16; 33 % on prednisone; 89 % on DMARDs; median CAC score 0; median aorta SUV 2.59; mean MFR 2.86; median galectin-3 level 8.54 ng/mL) were analyzed. In univariable analysis, higher galectin-3 levels were associated with higher aortic SUV (p = 0.007) but CAC score and MFR were not. In multivariable analysis, higher galectin-3 level remained significantly associated with higher aortic SUV (ß Coefficient=0.1786, p value=0.002). ConclusionIn our cohort of RA patients without clinical CVD, higher serum galectin-3 levels were independently associated with higher levels of aortic inflammation, but not CAC score or MFR. This suggests that galectin-3 may be a biomarker for an inflammatory and potentially reversible stage, but not a later (calcified) stage, of atherosclerosis in patients with RA.

Analysis of survival rate and persistence predictors of baricitinib in real-world data from a large cohort of rheumatoid arthritis patients

ObjectivesThe persistence in therapy of rheumatoid arthritis drugs and particularly bDMARD is a limiting factor for their long-term use. The randomized controlled trials (RCTs) may not reflect real-world contexts due to strict inclusion and exclusion criteria. Baricitinib, which targets both JAK1 and JAK2, has been used in Italy for several years. The aim of this multi-center study is to assess the real world persistence on therapy of baricitinib in RA patients and to identify predictive factors of baricitinib's survival rate. MethodsThis is a retrospective, multicentric, Italian, longitudinal study. All patients were enrolled according to the following criteria: a) age ≥ 18 years old; b) diagnosed with RA according 2010 ACR/EULAR classification criteria; c) treated with baricitinib. In order to describe baricitinib clinical efficacy, the survival rate was evaluated by The Kaplan–Meier curve. Then, predictive factors of drug retention rate were assessed by performing the Cox analysis, identifying which risk factors influenced treatment persistence. ResultsOverall, we included 478 patients treated with baricitinib. Among them, 380 (79.5%) were females. Baricitinib's survival rate was 94.6% at 6 months, 87.9% at 12 months, 81.7% at 24 months and 53.4% at 48 months. The Cox analysis regression showed that a higher bDMARDs/tsDMARD line of therapy seems to be a negative prognostic factor for the drug retention rate (HR 1.26 CI 95% 1.07–1.49, p = 0.006. ConclusionReal-life study confirms baricitinib effectiveness up to 4 years, but previous treatment with bDMARDs was a negative prognostic factor for its survival rate.

External validation of a multi-biomarker-based score for predicting risk of cardiovascular disease in patients with rheumatoid arthritis.

A multi-biomarker disease activity (MBDA)-based cardiovascular disease (CVD) risk score was developed and internally validated in a Medicare cohort to predict 3-year risk for myocardial infarction (MI), stroke or CVD death in patients with rheumatoid arthritis (RA). It combines the MBDA score, leptin, MMP-3, TNF-R1, age and four clinical variables. We are now externally validating it in a younger RA cohort. Claims data from a private aggregator were linked to MBDA test data to create a cohort of RA patients ≥18 years old. A univariable Cox proportional hazards regression model was fit using the MBDA-based CVD risk score as sole predictor of time-to-a-CVD event (hospitalized MI or stroke). Hazard ratio (HR) estimate was determined for all patients and for clinically relevant subgroups. A multivariable Cox model evaluated whether the MBDA-based CVD risk score adds predictive information to clinical data. 49,028 RA patients (340 CVD events) were studied. Mean age was 52.3 years; 18.3% were male. HR for predicting 3-year risk of a CVD event by the MBDA-based CVD risk score in the full cohort was 3.99 (95% CI: 3.51-4.49, p = 5.0×10-95). HR were also significant for subgroups based on age, comorbidities, disease activity, and drug use. In a multivariable model, the MBDA-based CVD risk score added significant information to hypertension, diabetes, tobacco use, history of CVD, age, sex and CRP (HR = 2.27, p = 1.7×10-7). The MBDA-based CVD risk score has been externally validated in an RA cohort that is younger than and independent of the Medicare cohort that was used for development and internal validation.

Flare and change in disease activity among patients with stable rheumatoid arthritis following coronavirus disease 2019 vaccination: a prospective Chinese cohort study.

Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA). A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups. A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment (P = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred. COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.

FRI544 Serological Profile In Rheumatoid Arthritis And Its Interplay With Autoimmune Thyroid Diseases

Abstract Disclosure: T. Kolitz: None. S. Kivity: None. I. Tessler: None. Y. Marcus-Perlman: None. E. Izkhakov: None. I. Yaish: None. Y. Greenman: None. Objective: Autoimmune thyroid diseases (AITD) are the most common organ-specific autoimmune disorders, with an estimated prevalence of 5%. AITD encompass the clinical scope of Hashimoto’s thyroiditis (HT) and Graves’s disease (GD). Rheumatoid arthritis (RA) is a relatively common non-organ-specific autoimmune disease with an estimated global prevalence of 0.5-1%. Numerous studies have investigated the association of thyroid disorders and RA in various populations, but results were inconsistent. This study is aimed to assess the rate of AITD in RA patients and to further investigate these rates in subgroups of patients with seronegative RA, seropositive RA and dual-positive RA antibodies [i.e., positive anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF)]. Methods: We used a big-data platform (MDClone Ltd., Israel) to create a cohort of RA patients with and without coexistent AITD. The cohort included 1316 patients who were treated in the Tel Aviv Sourasky Medical Center for any diagnosis between January 2008 and December 2022. Results: There were 340 men (25.8%) and 976 (74.2%) women in the cohort. The mean age at time of initial coding of RA diagnosis in our referral center was 62.5±15 years. AITD was found in 15.5% of the entire RA cohort. Hypothyroidism was the most common thyroid-associated diagnosis (in 95.8% of patients with RA and AITD). When RA patients were further sub-classified to seronegative, seropositive, and dual-positive RA, the rates of AITD were 11.8%, 17.6% and 25%, respectively (p=0.007). AITD rates in seropositive women and men were 20.6% and 8%, respectively (p<0.001). In the RA-seronegative subgroup, the rate of AITD was 15.6% in women and 2.7% in men (p<0.001). The mortality rates in RA-seronegative patients, RA-seronegative patients with AITD, RA-seropositive patients and RA-seropositive patients with AITD were 5.5%, 8.3%, 21.6% and 29.5%, respectively (p=0.05). Conclusion: Our findings suggest that the prevalence of AITD in patients with RA is associated with the specific serological profile, with highest rates in RA patients who are positive for both anti-CCP and RF. Randomized prospective studies are required to explore any cause-and-effect correlation and to delineate the impact of AITD on RA outcome and mortality rates. Presentation: Friday, June 16, 2023

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan-Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8-91.5%) at month 12, 78.8% (95% CI: 78.8-85.2%) at month 24, 63.8% (95% CI: 55.1-73.8%) at month 36, and 59.9% (95% CI: 55.1-73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Preferred Mode of Therapy Among Patients in Rheumatoid Arthritis Saudi Database: A Cross-Sectional Study.

Current knowledge of patients' preferences for rheumatoid arthritis (RA) treatment is limited. Our goal was to determine the most favorable mode of therapy and the reasons behind choosing each route among RA patients in the Rheumatoid Arthritis Saudi Database (RASD). In this cross-sectional, nationwide, qualitative study, we conducted interviews with 308 RA patients to assess their preferred mode of therapy (oral, subcutaneous (SC) injection, or intravenous (IV) infusion) and to determine the reasons behind their choice. The determining factors behind patients' preferred mode of therapy were evaluated using a 10-point allocation system (1 = least important, 10 = most important). We interviewed 308 RA patients (83.4% females, mean age, 48 years). Among all administration modes, the oral route was identified as the most preferred mode among our patients, with a percentage of 73.3%, followed by SC injection and IV infusion at 19.5% and 7.3%, respectively. Ease of drug administration was the most reported reason for patients who chose the oral route over the injection route (63.2%). Difficulty remembering to take the drug and finding it hard to swallow the pills were the highest-scored reasons for avoiding the oral route (24.9%). Our study demonstrates and emphasizes the importance of shared decision-making between patients and their physicians. The oral route of therapy is, by far, the most preferred mode among our cohort of RA patients.

Increased risk of herpes zoster with tofacitinib treatment in Korean patients with rheumatoid arthritis: a single-center prospective study

We aimed to determine the risk of herpes zoster (HZ) in Korean rheumatoid arthritis (RA) patients on tofacitinib compared with tumor necrosis factor inhibitor (TNFi) treatment. From the prospective cohorts of RA patients who started tofacitinib or TNFi in an academic referral hospital in Korea, patients who started tofacitinib between March 2017 and May 2021 and those who started TNFi between July 2011 and May 2021 were included. Baseline characteristics of tofacitinib and TNFi users were balanced through inverse probability of treatment weighting (IPTW) using the propensity score including age, disease activity of RA and medication use. The incidence rate of HZ in each group and incidence rate ratio (IRR) were calculated. A total of 912 patients were included: 200 tofacitinib and 712 TNFi users. There were 20 cases of HZ among tofacitinib users and 36 among TNFi users during observation period of 331.4 person-years (PYs) and 1950.7 PYs, respectively. In IPTW analysis with a balanced sample, IRR of HZ was 8.33 (95% confidence interval 3.05–22.76). Tofacitinib use increased the risk of HZ compared with TNFi in Korean patients with RA, but the rate of serious HZ or permanent discontinuation of tofacitinib due to HZ event was low.

MMP-13, VEGF, and Disease Activity in a Cohort of Rheumatoid Arthritis Patients

Identifying certain serum biomarkers associated with the degree of rheumatoid arthritis (RA) activity can provide us with a more accurate view of the evolution, prognosis, and future quality of life for these patients. Our aim was to analyze the presence and clinical use of matrix metalloproteinase-13 (MMP-13), along with vascular endothelial growth factor (VEGF) and well-known cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) for patients with RA. We also wanted to identify the possible correlations between MMP-13 and these serological markers, as well as their relationship with disease activity indices, quality of life, and ultrasonographic evaluation. For this purpose, we analyzed serum samples of 34 RA patients and 12 controls. In order to assess serum concentrations for MMP-13, VEGF, TNF-α, and IL-6, we used the enzyme-linked immunosorbent assay (ELISA) technique. Our results concluded that higher levels of MMP-13, VEGF, TNF-α, and IL-6 were present in the serum of RA patients compared to controls, with statistical significance. We furthermore identified moderately positive correlations between VEGF, MMP-13, and disease activity indices, as well as with the ultrasound findings. We also observed that VEGF had the best accuracy (97.80%), for differentiating patients with moderate disease activity. According to the data obtained in our study, that although MMP-13, TNF-α and C-reactive protein (CRP) have the same sensitivity (55.56%), MMP-13 has a better specificity (86.67%) in the diagnosis of patients with DAS28(4v) CRP values corresponding to moderate disease activity. Thus, MMP-13 can be used as a biomarker that can differentiate patients with moderate or low disease activity. VEGF and MMP-13 can be used as additional parameters, along with TNF-α and IL-6, that can provide the clinician a better picture of the inflammatory process, disease activity, and structural damage in patients with RA. Our data can certainly constitute a start point for future research and extended studies with multicenter involvement, to support the selection of individualized and accurate therapeutic management strategies for our patients.

Time Trends in Glucocorticoid Use in Rheumatoid Arthritis During the Biologics Era: 1999-2018

ObjectivesTo examine time trends in glucocorticoid (GC) use among patients diagnosed with rheumatoid arthritis (RA) during the biologic era. MethodsA population-based inception cohort of RA patients diagnosed during 1999 – 2018 was followed longitudinally through their medical records until death, migration or 12/31/2020. All patients fulfilled 1987 American College of Rheumatology classification criteria for RA. GC start and stop dates were collected along with dosages in prednisone equivalents. The cumulative incidence of GC initiation and discontinuation adjusted for the competing risk of death was estimated. Cox models adjusted for age and sex were used to compare trends between time periods. ResultsThe study population included 399 patients (71% female) diagnosed in 1999 – 2008 and 430 patients (67% female) diagnosed in 2009 – 2018. GC use was initiated within 6 months of meeting RA criteria in 67% of patients in 1999-2008 and 71% of patients in 2009-2018, corresponding to a 29% increase in hazard for initiation of GC in 2009-2018 (adjusted hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.09-1.53). Among GC users, similar rates of GC discontinuation within 6 months after GC initiation were observed in patients with RA incidence in 1999 – 2008 and 2009 – 2018 (39.1% versus 42.9%, respectively), with no significant association in adjusted Cox models (HR: 1.11; 95% CI: 0.93-1.31). ConclusionMore patients are initiating GCs early in their disease course now compared to previously. The rates of GC discontinuation were similar, despite the availability of biologics.

Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis.

This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints. We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n=2,110), Swedish age- and sex-matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE). Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98-100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19-26%) of early RA patients seronegative for anti-cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE. A multiplex immunoassay with peptides from disease-related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.

P142 Cytomegalovirus seropositivity is associated with an increased frequency of highly differentiated T effector memory cells re-expressing CD45RA (Temra) and persistent disease refractory to anti-TNF therapy in rheumatoid arthritis

Abstract Background/Aims The role of highly differentiated T effector memory re-expressing CD45RA (Temra) in rheumatoid arthritis (RA) is unclear, including whether they can be used as a marker of persistent disease activity. Our aim was to investigate whether peripheral blood Temra frequency can be used to identify RA patients with active disease refractory to anti-TNF therapy. As cytomegalovirus (CMV) has been reported to be associated with the expansion of Temra as well as implicated in RA pathogenesis, we also explored the relationship between serum CMV immunoglobulin (IgG) status, Temra, and remission status. Methods A cross-sectional cohort of RA patients on anti-TNF therapy were recruited. Patients were stratified based on remission status. Remission was defined as no recorded DAS28-CRP≥2.4, no swollen joints, no C-reactive protein (CRP) >5mg/L, and on a stable DMARD dose and no reported disease flare/loss of remission in the last 6 months before recruitment. Patients on abatacept or on conventional DMARDs only were recruited as comparison groups. Peripheral blood mononuclear cells (PBMC) were analysed by flow cytometry. Serum CMV IgG was analysed by ELISA. Two-tailed Mann-Whitney U test or unpaired t-test were used to obtain unadjusted values, analysis of variance (ANOVA) of log-transformed data to obtain age-adjusted values, Spearman’s rank correlation to compare correlation between two variables, Fisher’s exact test to compare proportions. Results Thirty-six anti-TNF, 12 abatacept, and 16 patients on conventional synthetic DMARDs (csDMARDs) only were recruited. A higher proportion of CD4 and CD8 Temra (age-adjusted p = 0.004 and p = 0.0007 respectively) was observed in RA patients on anti-TNF with persistent disease compared to those in remission. This difference in Temra frequency was not observed in patients treated with csDMARDs only or abatacept. CD4 and CD8 Temra frequency correlated positively with CMV IgG levels (Spearman r = 0.8987, p < 0.0001 and Spearman r = 0.7211, p < 0.0001 respectively). There was a strikingly high proportion of anti-TNF patients with persistent disease who were CMV seropositive compared to anti-TNF patients in remission (93% versus 42%, Fisher’s exact test, p = 0.009). This difference was less marked and not significant in the other treatment groups. Conclusion The increased CMV seropositivity and Temra frequency in the context of persistent disease only in anti-TNF treated patients may provide a causal link between Temra and RA pathogenesis refractory to anti-TNF treatment. Disclosure S. Yeoh: Grants/research support; S.A.Y. has received funding for research from Versus Arthritis, Royal College of Physicians, Rosetrees Trust, University College London Hospitals NIHR BRC and UCLH charities. J. Kimpton: None. M. Shipa: Grants/research support; M.S. has received funding for research from Versus Arthritis and GSK. E. Hawkins: None. A. Akbar: Grants/research support; A.A. has received funding for research from the Medical Research Council and the Leo Skin Foundation (Denmark). M. Ehrenstein: None.

P118 Baseline Characteristics of and Early Outcomes in the First 200 Patients With Rheumatoid arthritis Treated With Filgotinib in a Prospective Observational Study

Abstract Background/Aims Filgotinib (FIL) is a preferential Janus kinase 1 inhibitor, approved in Europe for the treatment of Rheumatoid arthritis (RA). A phase 4 European study of FIL (FILOSOPHY; NCT04871919) in patients with RA is ongoing. We report baseline characteristics and 1-month efficacy data from the first 200 patients. Methods The prospective, observational study will enroll approximately 1500 patients aged ≥18 years with moderate-severe active RA, prescribed FIL for the first time in accordance with the product label. We report baseline demographics, disease characteristics, comorbidities, prior treatments, reasons for starting FIL, and mean change from baseline (CFB) in pain severity (measured using a 10-cm visual analog scale [VAS]) and Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue score (range 0-52) via electronic PRO data collection at Week 1 and Month 1, and mean CFB in Clinical Disease Activity Index (CDAI; range 0-76) score at Month 1. The proportion of patients with clinically meaningful CFB in FACIT-fatigue (increase of ≥ 4) and VAS pain (reduction of ≥ 10) from Week 1 to Month 1 was reported. Patients included in analysis were enrolled May 2021-February 2022. Results 206 patients were enrolled from Germany (n = 134), UK (n = 40), Netherlands (n = 27), Belgium (n = 4), and Italy (n = 1); nearly 75% were female, mean (standard deviation [SD]) age 56.8 (10.6) years, and mean (SD) RA duration 10.0 (9.5) years. Approximately 40% of treated patients had comorbidities, most common: hypertension (28.3%), dyslipidemia (9.1%), type 2 diabetes mellitus (5.3%). FIL was started due to inadequate response (43.3%), loss of response (40.6%), or intolerance (non-allergic) to previous treatment (5.9%), or for other reasons (10.2%). Of treated patients, 167 (89.3%) received FIL 200 mg and 20 (10.7%) received FIL 100 mg (study drug information was pending for 19 patients). FIL monotherapy was taken by 55.6% of patients (19.3% with glucocorticoids), while 37.4% received FIL in combination with MTX (13.4% with glucocorticoids). Mean (SD) and median (range) daily dose of oral glucocorticoids at baseline was 7.5 (6.0) mg and 5.0 (1.0-30.0) mg. At Week 1 and Month 1, respectively, mean (SD) CFB in FACIT-fatigue score was 3.7 (6.9) and 6.8 (8.6), and mean (SD) CFB in VAS pain score was -11.9 (18.0) and -22.2 (27.8). At Month 1, mean (SD) CFB in CDAI score was -13.7 (17.1). Conclusion These are the first international real-world data to be reported from a cohort of RA patients treated with FIL. At baseline, patients generally had moderate disease activity. Initial interim data indicate rapid improvements in disease measures with FIL treatment (given as combination therapy or monotherapy, with/without glucocorticoids), which could be observed as early as Week 1 for VAS pain and FACIT-fatigue scores. Long-term follow-up is needed to further evaluate effectiveness and safety. Disclosure J. Galloway: Other; AbbVie, AstraZeneca, Biogen, Celgene, Galapagos, Gilead, Janssen, Medicago, Lilly, Novartis, Novavax, Pfizer, Roche, UCB. K. Bevers: None. P. Verschueren: Other; AbbVie, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Pfizer, Roularta, Sidekick Health. R. Caporali: Other; AbbVie, Celltrion, Fresenius-Kabi, Galapagos, Janssen, Pfizer, Roche, UCB, Eli Lilly, Gilead, Sanofi. S. Romero Yuste: Other; Pfizer, Lilly, AbbVie, Biogen, Sanofi. J. Avouac: Other; Galapagos, AbbVie, Lilly, Pfizer, Bristol Myers Squibb, Novartis, Fresenius-Kabi, Sanofi, Sandoz, Nordic Pharma, Biogen, Medac, Janssen, Roche-Chugai. E. Gvozdenovic: Other; Galapagos. K. Harris: Other; Galapagos. M. Zignani: Other; Galapagos. G. Burmester: Other; AbbVie, Galapagos, Lilly, MSD, Pfizer, Roche, UCB, Janssen, Gilead Sciences, Inc.

P146 Pragmatic Biologic Tapering Combining Clinical and Ultrasound Assessment in Patients with Rheumatoid Arthritis in Routine Clinical Practice - Predictors of Failure from a Regional Centre in UK

Abstract Background/Aims Tapering biologic therapies in patients with rheumatoid arthritis (RA) is evolving. Our primary objective was to combine clinical and ultrasound assessment in selecting patients with RA for tapering biologic therapies. The secondary objectives were to identify predictors for failure and cost savings. Methods RA patients on biologics in sustained clinical remission (defined as DAS 28 < 2.6) in the previous year and imaging remission (defined as Power Doppler US of small joints of hands not significant) were included. The patients were seen in a multidisciplinary clinic with an advanced pharmacy practitioner between April 2019 and March 2022. They were advised to lengthen the interval of their biologics gradually and were followed quarterly till September 2022. Failure was defined as reverting to previous regime at any point during follow up. Independent predictors of failure were identified with Cox multiple regression analysis SPSS v29.0 (IBM 2022). Results Biologics were tapered in 184 patients including 129 on anti-cytokine therapy (abatacept 13, adalimumab 35, certolizumab 31, etanercept 18, golimumab 8, infliximab 4, tocilizumab 20) and 55 on rituximab. The mean age of the cohort was 63.8±11.7 years and there were 72.3% females. The mean duration of RA was 15.2 ± 7.9 years and baseline DAS28 before taper was 1.93±1.04 years. Concomitant DMARDs were used in 53.8%. Anti-cytokine therapy:Over 287.9 patient-years follow up (mean follow up duration: 26.8 ± 14.1 months), taper failure occurred in 36 (27.9%) patients in a mean time of 12.0 ± 8.1 months. There was no statistically significant difference in failure rate between different agents. A 50% dose reduction could be achieved in 65 (50.4%) patients with the mean time to achieve it of 10.4 ±9.1 months. Thirteen (10.1%) patients stopped biologics completely. Current smoking [HR:3.67 95%CI:1.50-9.00, p:0.04] and higher DAS28 at initiation of taper [HR:1.93 95%CI:1.11-3.36, p:0.020] were predictive of taper failure. All but 3 of the 36 patients who failed taper, responded on reverting to their previous treatment regime. Anti B-cell therapy:The 55 patients on Rituximab were tapered to a lower dose or had their interval lengthened. Over 98.6 patient-years follow up (mean follow up: 21.5 ± 11.3 months). Mean dose reduction achieved was 62.2 ± 19.9 %. Mean interval between RTX infusions was 12.9 ± 6.4 months. We have managed to save nearly £800,000 over the 3 years with tapering of biologics in this cohort of RA patients compared to the standard dose. Conclusion Successful tapering of biologic therapies in patients with rheumatoid arthritis is feasible and safe in majority of patients who are in clinical and imaging remission. Current smoking and baseline high DAS28 predicted taper failure for anti-cytokine biologics. This can be safely managed by reverting to the original dosing in most patients. Disclosure H. Muhammed VK: None. A. Yau: None. G. Hirsch: None. T. Sheeran: None. S. Venkatachalam: None.

P140 Janus Kinase Inhibitors in Rheumatoid Arthritis Patients: Real-World Experience from a Regional Centre in UK

Abstract Background/Aims Tofacitinib and baricitinib were the first orally available, targeted synthetic Janus kinase (JAK) inhibitors approved for the treatment of rheumatoid arthritis (RA) in the UK. Evidence suggests that JAK inhibitors are as efficacious as biological DMARDs in the treatment of RA. Their safety profile has been demonstrated in long term extension studies and RCTs. However, real-world, long-term data remains as important in bridging the gap between controlled studies and routine practice. We report our initial real-world experience of a cohort of RA patients commenced on JAKi before the SARS-CoV-2 pandemic within a regional centre in the UK. Methods All patients commenced on JAKi for the treatment of RA between February 2018 and March 2020 were identified from our in-house database. Data was retrospectively collected from clinical notes and electronic health records from February 2018 up until April 2022. This included patient demographics, disease duration, serological status, concurrent csDMARD usage, history of bDMARD exposure, duration of use and reason for discontinuation of the drug if appropriate. DAS-28 scores were recorded at baseline and quarterly. SPSS (version 22.0) was used for data analysis. Results One hundred thirty patients were treated with JAK inhibitors (Tofacitinib 22%, Baricitinib 78%); 80% female, mean (S.D.) age 61.5 (12.3) years. 92 (70.8%) patients were seropositive. 70 (53.8%) patients were on concurrent csDMARDs and 23 (17.7%) on concurrent steroids. The mean number of previous bDMARDs was 1.8 ± 1.7; 41 (31.5%) were bDMARD naive. The mean baseline DAS-28 ESR (S.D.) score was 5.96 (0.96). There were significant differences in mean DAS-28 ESR scores (compared with baseline) of 1.54, 1.96, 2.41, 2.33 and 1.80 at 3, 6, 12, 18 and 24 months respectively (p < 0.0001). Mean DAS-28 ESR scores were not statistically significant between bDMARD naïve patients and those that had previously received bDMARDs. Overall JAKi retention rate was 66.9% with a mean follow up duration of 27.4±13.1 months. Persistence was 88.5%, 76.9%, 73.2% and 68.5% at 6, 12, 18, and 24 months, respectively. Of the 38 patients who stopped JAK inhibitors, 11 stopped due to inefficacy (6, primary inefficacy). 3 patients were lost to follow-up and 6 deceased. Cause of death was sepsis (2), venous thromboembolism (1) and unknown (3). 18 patients stopped because of adverse events (AEs). The most common AEs were recurrent infections (11), gastrointestinal side effects (9), lymphopenia (7), thromboembolic events (6) and herpes zoster (5). In total 6 (4.1%) patients had thromboembolic events which included pulmonary embolism (4) and deep vein thrombosis (1) and central retinal artery thrombosis (1). Conclusion JAK inhibitors in this real-world population of RA patients were effective in reducing disease activity and patients had high persistence rates. Recurrent infections, herpes zoster and thrombo-embolism remain adverse events of concern. Disclosure A. Ajibade: None. A. Hawarden: None. A. Leong: None. G. Hirsch: None. T. Adizie: None. S. Venkatachalam: None.