Rheumatoid Arthritis Cohort Research Articles

P137 First-line tumour necrosis factor inhibitor (TNFi) treatment is associated with high multi-criteria remission early on compared to treat-to-target in a treatment naïve RA cohort

Abstract Background/Aims In rheumatoid arthritis (RA) disease assessment, SDAI and Boolean remission criteria are known to be more stringent in comparison to DAS28-ESR. Comparing remission rates across multiple assessment indices provides a more comprehensive evaluation of disease control. In an early RA trial cohort, we aimed to investigate stringent and multi-criteria remission (MCR) rates and evaluate their proportional change in response to treatment. Methods The ‘VEDERA’ trial randomised 120 treatment-naïve, new-onset RA patients to first-line etanercept+methotrexate (ETN+MTX) or methotrexate treat-to-target (MTX-TT) with escalation to ETN+MTX if not in DAS28-ESR remission at week24. Clinical assessments were completed at baseline, weeks12/24/48 (protocolised phase) up to week96 (standard-of-care). Remission cut-points included: DAS28-ESR ≤2.6, SDAI ≤3.3 and Boolean score for individual components≤1. MCR was defined as patients who were in DAS28-ESR, SDAI and Boolean remission concurrently. Descriptive analyses were undertaken to address the above aims. Results Overall, at week12, 26%(31/120) were in SDAI and 13%(16/120) in Boolean remission. This increased to 41%(49/120) and 23%(28/120) respectively by week48. In the ETN+MTX group at week12, 30%(18/60) were in SDAI and 17%(10/60) in Boolean remission. This increased to 43% (26/60) and 32%(19/60) respectively by week48. Stringent remission rates were lower in MTX-TT compared to ETN+MTX and significantly different for Boolean at week48 (15% vs 32%, odds ratio 2.6, 95% confidence interval 1.1 to 6.5, nominal p < 0.05) (Table 1). Of those in remission by the three different criteria, 36%(14/39) were in MCR at week12, with a greater proportion in ETN+MTX group [42%(10/24) compared to 27%(4/15) in MTX-TT]. MCR remained unchanged up to week48 but improved with treatment by week 96 to 45%(27/60). MCR rates did not converge between the 2 treatment groups at week 96 (ETN+MTX 55%; MTX-TT 38%). Conclusion First-line ETN+MTX is associated with higher rates of stringent remission from week 12 compared to MTX-TT, with improvement gradually over time with both strategies. Significantly higher proportion of patients treated with first line ETN+MTX compared to MTX-TT achieved Boolean and MCR. Early TNFi treatment associates with more complete and better cumulative disease activity profile. Patients not meeting MCR early following treat-to-target approach should be considered for more aggressive treatment strategies. Disclosure R. Shukla: None. D. Plant: None. P. Emery: None. M.H. Buch: None.

P114 Exploring micro-RNA content of circulating extracellular vesicles as biomarkers in early rheumatoid arthritis

Abstract Background/Aims Early diagnosis and prompt and effective intervention for people with immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis (RA) improves outcomes. Non-invasive biomarkers that reflect unique aspects of underlying biology could facilitate this. Extracellular vesicles (EVs) released by many cell types are abundantly present in body fluids where they contribute to intercellular signalling by transferring cargo including microRNAs (miRs) - themselves implicated in disease pathogenesis. We investigated whether serum EV miR expression (i) discriminates patients with newly presenting, untreated RA from those with an alternative IMID or none, (ii) predicts therapeutic response to first-line methotrexate (MTX) treatment amongst RA patients, or, in the same individuals (iii) exhibit dynamically altered expression in MTX-responders versus non-responders during treatment. Methods Using a validated protocol, serum EVs were isolated from 43 early RA patients. Identically isolated EV were available from sera of 23 newly presenting, untreated polymyalgia rheumatica (PMR, “IMID control”) patients and 12 “non-inflammatory control” patients (NICs) in whom significant inflammatory disease had been excluded. miRs were isolated and subject to NanoString sequencing (798 miRs). Following quality control, DESeq2 was first used to identify miRs uniquely deregulated in RA EVs at baseline. Within the early RA cohort, a baseline comparison between individuals who subsequently achieved clinical remission after 6 months treatment with MTX (DAS28-CRP<2.4 without having required systemic steroids in preceding 2 months) and those that did not, was also undertaken by partial least squared-discriminant analysis (PLS-DA) with 5-fold cross validation. Linear modelling was used to assess differences in dynamic EV miR expression between responders and non-responders. Multiple test correction was applied (false discovery rate; FDR). Results A signature of 28 miRs uniquely differentially expressed between early RA patients and NICs (i.e. not also between PMR and NICs) was identified, which was robust to MTC after correction for age and sex. Amongst those upregulated in RA were miR-337-3p, whose predicted target proteins include Jak2 and STAT3, and miR-144-3p, recently shown to mediate the expression of pro-inflammatory cytokines and chemokines by macrophages. Whilst EV miRs differentially expressed at baseline between RA patients who subsequently achieved early MTX-induced remission and those who did not were not robust to MTC, PLS-DA indicated their predictive potential. Finally, several miRs whose change in expression over the course of treatment differed significantly between responders and non-responders; namely miR-548ar-3p, miR-212-3p, miR-188-5p, miR-410-3p, and miR-338-5p amongst others, may offer insight into the mechanism of MTX’s therapeutic action. Conclusion Serum EV miRs are a possible source of clinically valuable biomarkers that may shed light on pathophysiology and/or mechanisms of MTX efficacy. Our findings highlight their potential as diagnostic and prognostic tools in early RA. Larger studies and validation in independent cohorts are warranted to pursue this potential, alongside mechanistic evaluation. Disclosure D. Maunder: None. P.M. Brown: None. B. Barron-Millar: None. D. Lendrem: None. N. Naamane: None. J. Macdonald: None. X. Wang: None. A.E. Anderson: None. A.W. Morgan: None. S.L. Mackie: Consultancies; Roche/Chugai, Sanofi, AbbVie and AstraZeneca. Honoraria; Pfizer, Vifor and UCB. Grants/research support; Vifor. R. Crossland: None. A.G. Pratt: Consultancies; Inflection Biosciences.

P124 Rheumatoid Arthritis with Normal CRP: an Underappreciated, Persistent Phenotype: Equally at Risk of Severe Disease

Abstract Background/Aims A subset of seropositive rheumatoid arthritis (RA) with normal CRP levels during ultrasound-proven flairs was previously identified. They experienced worse outcomes, with delays in initiation of conventional DMARDs, more joint damage and higher disease activity scores, with an increased likelihood of needing biologic therapy. The aims were to longitudinally assess this group over 5 years - to determine the persistence of the phenotype and establish if differences in outcome were sustained; and to estimate the prevalence of this phenotype among the wider seropositive RA cohort at UCLH. Methods The initial study described two groups: those with high CRP during flare (hCRP) and those with normal CRP during flare (nCRP). The electronic health records of the initial cohort were interrogated. CRP measurements at 1-, 2- and 5-years post recruitment were collated. Clinical notes were examined to determine if episodes of raised CRP were due to RA activity, or alternative causes. Because of its CRP lowering properties, patients on Tocilizumab were excluded from this analysis. To screen for the nCRP phenotype in the larger population, DAS-28-CRP results were analysed from the 312 most recently reviewed patients in the UCLH seropositive RA database (data extracted 8th October 2019). The clinic letter from the time of the CRP value was examined, and patients were defined as having active disease if DAS-28 > 4.5. Results Patients classified as nCRP at initial recruitment continued to have lower CRP (nCRP group median 1.1, maximum 6.4, hCRP group median 4, maximum 55.2, P = 0.0117). 1 patient originally classified as nCRP had a result >5 at 5 years (6.4). Among the original cohort, at 5 years, patients originally defined as nCRP were more likely to require a biologic (76.67%) than hCRP (44.4%) (P = 0.0324). There was no significant difference in DAS-28 scores between groups at 5 years (hCRP median 3.2, nCRP median 2.9 P = 0.8775) . Patients with nCRP phenotype were as likely to have erosive disease as those in the hCRP cohort (hCRP 66.67%, nCRP 56.52%, P = 0.7356). Among the larger sample of 312 patients, 28 had CRP levels < 5 and DAS-28 >4.5. Of these, on longitudinal analysis of CRP at the time of clinic visits, 16/28 never mounted a CRP in response to active arthritis - likely the most representative of the nCRP patients from the original ultrasound cohort. These data suggest the nCRP phenotype represents at least 5% of the seropositive rheumatoid arthritis cohort at UCLH. Conclusion The subgroup of patients exhibiting normal CRP levels during disease flair maintain this phenotype over time. They remain more likely to require biologic treatment, while having equivalent DAS-28 scores and risk of damage to hCRP patients. Their presence as a significant minority of the wider population has implications for clinical care and resource use. Disclosure M. Hutchinson: None. B. Sethi: None. G. Sritharan: None. B. Greenaway: None. E. Jury: None. J. Manson: None.

E070 How well is the mental health of rheumatoid arthritis patients assessed in the routine rheumatology clinic?

Abstract Background/Aims All patients with rheumatoid arthritis (RA) should have an annual review appointment (NG100). This should involve monitoring for the development of co-morbidities including depression and offer psychological interventions where appropriate. The current literature suggests that the prevalence of depression in RA patients is as high as 38.8% and is associated with poorer disease outcomes. We undertook a retrospective record review of our RA cohort to assess adherence to the NICE RA guidance, including mental health monitoring specifically. Methods 340 patients were selected using convenience sampling from the total population of 3400. The letters 12 months prior to an identified appointment in January 2019 were reviewed looking at: age, gender, DAS28 score, other long-term conditions, whether mental health was discussed that year, and who initiated the conversation. Data was collected, reviewed, and analysed by HC, JE and AA. Results The mean age was 65.9 (SD = 12.3), the female to male ratio was 2.3:1 (70% female), the median DAS28 score was 2.94 (IQR=2.01), and the median VAS score was 40.0 (IQR=63.5). 73.2% (n = 249/340) had at least one other documented co-morbidity, 12.1% (n = 41/340) had a documented chronic pain syndrome, 3.5% (n = 12/340) had a documented mental health diagnosis. 7.9% (n = 27/340) of patients discussed mental health at their appointment; this increased to 58.3% (n = 7/12) of the patients with a known mental health diagnosis. Mental health discussions were initiated by the clinician 18.5% (n = 5/27) of the time, and by the patient 81.5% (n = 22/27) of the time. Of the 5 patients who were asked directly about their mental health: 100% (n = 5/5) were female, the mean age was 63.8, the median DAS28 and VAS scores were lower than the overall cohort at 2.56 (IQR=0.93) and 28.5 (IQR=15.3) respectively. Of the 22 patients who initiated a discussion about their mental health: 72.7% (n = 16/22) were female, the mean age was 62.3, the median DAS28 and VAS scores were higher than the overall cohort at 3.55 (IQR=2.45) and 60.0 (IQR=51.3) respectively. Of the 27 patients who had a mental health discussion: 76.0% (n = 19/27) had another documented co-morbidity, 22.2% (n = 6/27) had a documented chronic pain syndrome, and 25.9% (n = 7/27) had a mental health diagnosis. Conclusion Mental health problems may be under-recognised amongst our patients; this may reflect lack of documentation or limited routine screening. The majority of conversations about mental health appear to be initiated by patients. Patients with lower disease activity appear to be more likely to have mental health discussions. The study is limited by small numbers, and further research in this area would be beneficial. Disclosure H. Cooney: None. J. Ellis: None. B. Mulhearn: None. A. Allard: None.

Relationship between Chinese Herbal Medicine Use and Risk of Sjögren's Syndrome in Patients with Rheumatoid Arthritis: A Retrospective, Population-Based, Nested Case-Control Study.

Background and Objectives: Sjögren's Syndrome (SS) is a common extra-articular feature among subjects with rheumatoid arthritis (RA). While Chinese herbal medicine (CHM) has been used to treat symptoms of RA for many years, few studies have examined its efficacy in guarding against the SS onset. This study aimed to compare risk of SS for RA patients with and without use of CHM. Materials and Methods: Data obtained for this nested case-control study were retrieved from Taiwanese nationwide insurance database from 2000-2013. Cases with SS claims were defined and matched to two randomly selected controls without SS from the recruited RA cohorts. Risk of SS in relation to CHM use was estimated by fitting multiple conditional logistic regression. Results: Patients aged between 20 and 80 years were included and 916 patients with incident SS were matched to 1832 non-SS controls by age, sex and index year. Among them, 28.1% and 48.4% cases ever received CHM therapy, respectively. After adjusting for baseline characteristics, CHM use was found to be related to a lower risk of SS among them (adjusted odds ratio = 0.40, 95% confidence interval: 0.34-0.47). A dose-dependent, reverse association, was further detected between the cumulative duration of CHM use and SS risk. Those receiving CHM therapy for more than 730 days showed a significantly reduced risk of SS by 83%. Conclusions: Findings of this study indicated that the add-on CHM formula, as part of RA care, may be a beneficial treatment for prevention against the incident SS.

Trends in Incidence of Chronic Heart Failure in Patients With Rheumatoid Arthritis: A Population-Based Study Validating Different Heart Failure Definitions.

To assess trends in the incidence of heart failure (HF) in patients with incident rheumatoid arthritis (RA) from 1980 to 2009 and to compare different HF definitions in RA. The study population comprised Olmsted County, Minnesota residents with incident RA (age ≥ 18 yrs, 1987 American College of Rheumatology criteria met in 1980-2009). All subjects were followed until death, migration, or April 30, 2019. Incident HF events were defined as follows: (1) meeting the Framingham criteria for HF, (2) diagnosis of HF (outpatient or inpatient) by a physician, or (3) International Classification of Diseases, 9th revision (ICD-9), or ICD, 10th revision (ICD-10), codes for HF. Patients with HF prior to the RA incidence/index date were excluded. Cox proportional hazards models were used to compare incident HF events by decade, adjusting for age, sex, and cardiovascular risk factors. HF definitions 2 and 3 were compared to the Framingham criteria. The study included 905 patients with RA (mean age 55.9 years; 68.6% female; median follow-up 13.4 years). The 10-year cumulative incidence of HF events by any chart-reviewed method in the RA cohort in the 1980s was 11.66% (95% CI 7.86-17.29), in the 1990s it was 12.64% (95% CI 9.31-17.17), and in the 2000s it was 7.67% (95% CI 5.36-10.97). The incidence of HF did not change across the decades of RA incidence using any of the HF definitions. Physician diagnosis of HF and ICD-9/10 code-based definitions of HF performed well compared to the Framingham criteria, showing moderate to high sensitivity and specificity. The incidence of HF in patients with incident RA in the 2000s vs the 1980s was not statistically significantly different. Physician diagnosis of HF and ICD-9/10 codes for HF performed well against the Framingham criteria.

The Third Dose of BNT162b2 COVID-19 Vaccine Does Not “Boost” Disease Flares and Adverse Events in Patients with Rheumatoid Arthritis

Data on the risk of adverse events (AEs) and disease flares in autoimmune rheumatic diseases (ARDs) after the third dose of COVID-19 vaccine are scarce. The aim of this multicenter, prospective study is to analyze the clinical and immunological safety of BNT162b2 vaccine in a cohort of rheumatoid arthritis (RA) patients followed-up from the first vaccine cycle to the third dose. The vaccine showed an overall good safety profile with no patient reporting serious AEs, and a low percentage of total AEs at both doses (40/78 (51.3%) and 13/47 (27.7%) patients after the second and third dose, respectively (p < 0.002). Flares were observed in 10.3% of patients after the end of the vaccination cycle and 12.8% after the third dose. Being vaccinated for influenza was inversely associated with the onset of AEs after the second dose, at both univariable (p = 0.013) and multivariable analysis (p = 0.027). This result could allow identification of a predictive factor of vaccine tolerance, if confirmed in larger patient populations. A higher disease activity at baseline was not associated with a higher incidence of AEs or disease flares. Effectiveness was excellent after the second dose, with only 1/78 (1.3%) mild breakthrough infection (BI) and worsened after the third dose, with 9/47 (19.2%) BI (p < 0.002), as a probable expression of the higher capacity of the Omicron variants to escape vaccine recognition.

Pre-treatment calprotectin (MRP8/14) provides no added value to testing CRP alone in terms of predicting response to TNF inhibitors in rheumatoid arthritis in a post hoc analysis

ObjectivesThe inflammatory protein calprotectin (MRP8/14) has been identified as a promising biomarker of treatment response in rheumatoid arthritis (RA). Our aim was to test MRP8/14 as a biomarker of response...

Autoantibodies against complement factor B in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder affecting the joints. Many patients carry anti-citrullinated protein autoantibodies (ACPA). Overactivation of the complement system seems to be part of the pathogenesis of RA, and autoantibodies against the pathway initiators C1q and MBL, and the regulator of the complement alternative pathway, factor H (FH), were previously reported. Our aim was to analyze the presence and role of autoantibodies against complement proteins in a Hungarian RA cohort. To this end, serum samples of 97 ACPA-positive RA patients and 117 healthy controls were analyzed for autoantibodies against FH, factor B (FB), C3b, C3-convertase (C3bBbP), C1q, MBL and factor I. In this cohort, we did not detect any patient with FH autoantibodies but detected C1q autoantibodies in four patients, MBL autoantibodies in two patients and FB autoantibodies in five patients. Since the latter autoantibodies were previously reported in patients with kidney diseases but not in RA, we set out to further characterize such FB autoantibodies. The isotypes of the analyzed autoantibodies were IgG2, IgG3, IgGκ, IgGλ and their binding site was localized in the Bb part of FB. We detected in vivo formed FB-autoanti-FB complexes by Western blot. The effect of the autoantibodies on the formation, activity and FH-mediated decay of the C3 convertase in solid phase convertase assays was determined. In order to investigate the effect of the autoantibodies on complement functions, hemolysis assays and fluid phase complement activation assays were performed. The autoantibodies partially inhibited the complement-mediated hemolysis of rabbit red blood cells, inhibited the activity of the solid phase C3-convertase and C3 and C5b-9 deposition on complement activating surfaces. In summary, in ACPA-positive RA patients we identified FB autoantibodies. The characterized FB autoantibodies did not enhance complement activation, rather, they had inhibitory effect on complement. These results support the involvement of the complement system in the pathomechanism of RA and raise the possibility that protective autoantibodies may be generated in some patients against the alternative pathway C3 convertase. However, further analyses are needed to assess the exact role of such autoantibodies.

Unincreased mortality of patients with early rheumatoid arthritis compared to the general population in the past 17 years: Analyses from the IORRA cohort.

The aim of this article is to investigate the mortality rate of patients with early rheumatoid arthritis (RA) over the past 17 years. Japanese patients with early RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort from 2001 to 2012 were classified into Groups A (2001-06) and B (2007-12). The standardized mortality ratio (SMR) and 5-year survival rate were calculated. Groups A and B had 1609 and 1608 patients, of which 167 and 178 patients were lost during follow-up and 47 and 45 deaths were confirmed, respectively. The SMR (95% confidence intervals) for Groups A and B were 0.81 (0.59-1.08) and 0.78 (0.57-1.04), respectively, with the condition that all untraceable patients were alive. Assuming that the mortality rate of untraceable patients was twice as high as that of the general population, the SMR was 0.90 (0.68-1.19) for Group A and 0.92 (0.68-1.23) for Group B. The 5-year survival rates were 96.9% and 97.0% for Groups A and B, respectively. The 5-year mortality of patients with early RA has been comparable to that of the general Japanese population. The 5-year survival rate has been stable over the past 17 years.

Racial and Ethnic Differences in a Biochemical Marker of Rheumatoid Arthritis Disease Activity.

Racial and ethnic disparities in rheumatoid arthritis (RA) disease activity measures have been documented. We compared racial and ethnic differences in disease activity using multiple composite measures, including an objective measure, the multi-biochemical disease activity (MBDA) score. Data are derived from the University of California, San Francisco RA Cohort, a longitudinal observational cohort. Participants with at least one MBDA measure and self-reported race and ethnicity were included. Multivariable linear regression evaluated the association between race and ethnicity groups and mean MBDA score, adjusting for potential confounders, including symptom duration and medication use. Sensitivity analyses substituted the Clinical Disease Activity Index (CDAI) and the Disease Activity Score-28 joints with erythrocyte sedimentation rate (DAS28-ESR) for the MBDA in multivariable models. We included 267 participants (86% female, mean age 52.7 ± 13.3 years). The majority were Latinx (n=137; 51%), followed by Asian (n=91; 34%). After adjustment, Latinx participants had the highest mean MBDA score (40.6± 2.1) compared with White participants at (32.8± 6.7). Black participants had the second highest mean MBDA score, followed by Asian participants (36.3± 5.3, 36.0± 2.7, respectively), although neither were significantly different from White participants. The trends observed for the CDAI and DAS28-ESR were similar to those for the MBDA. We found significantly higher disease activity measured by the MBDA and DAS28-ESR in Latinx participants compared with White participants. We also found significantly higher disease activity in Asian participants compared with White participants with the DAS28-ESR. Our findings, although limited by the small number of White participants in the referent group, suggest that RA disease activity measures may be influenced by external factors that have differential impacts by racial and ethnic group.

Incidence of Herpes Zoster in Patients With Rheumatoid Arthritis in the United States: A Retrospective Cohort Study.

To estimate the incidence of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) compared with the general population in the USA. This retrospective, longitudinal cohort study used data from an administrative claims database containing both commercial and Medicare Advantage Part D data, with a data period from October 2015 to February 2020. Patients were aged ≥ 18 years and divided into 2 cohorts: patients with RA and patients without RA. Diagnosis and procedure codes were used to identify HZ cases and calculate incidence rates (IRs) of HZ in the 2 cohorts. Data were stratified by age group (ie, 18-49, 18-29, 30-39, 40-49, 50-64, and ≥ 65 yrs) and RA therapy type. IR ratios (IRRs), adjusted by cohort baseline characteristics, were estimated using generalized linear models to compare the incidence of HZ between cohorts. The overall IR of HZ was higher in the RA cohort (21.5 per 1000 person-years [PY]; N = 67,650) than in the non-RA cohort (7.6 per 1000 PY; N = 11,401,743). The highest IRs in both cohorts were observed in the age group of ≥ 65 yrs (23.4 and 11.4 per 1000 PY in the RA cohort and non-RA cohort, respectively). The overall adjusted IRR of HZ was 1.93 (95% CI 1.87-1.99, P < 0.001) for the RA cohort compared with the non-RA cohort. In the RA cohort, the highest IRs by medication class were observed in patients using corticosteroids and those using Janus kinase inhibitors. These results highlight the increased incidence of HZ in patients with RA.

Sleep Disorders Among Individuals With Rheumatoid Arthritis.

Self-reported sleep problems are common in rheumatoid arthritis (RA), with potential negative health implications, yet relatively little research has focused on sleep in RA. We examined the prevalence of obstructive sleep apnea (OSA) risk, restless legs syndrome (RLS) symptoms, and short sleep (SS) in a large RA cohort (n=4,200) and factors associated with each. Data are from FORWARD, The National Databank for Rheumatic Diseases. Validated screening measures assessed OSA risk and RLS symptoms. SS was based on self-reported average sleep time (<6 hours). The Medical Outcomes Study Sleep Problems Index I measured self-reported sleep quality. Multivariable logistic regression models identified independent predictors of sleep disorders and sleep quality and the independent association of OSA risk, RLS symptoms, and SS with self-reported poor sleep quality. Twenty-one percent (n=899) had OSA diagnosis or risk, 30% (n=1,272) had RLS symptoms or diagnosis, and 43% (n=1,737) reported SS, and RA disease activity was associated with each sleep disorder. Abatacept use was associated with lower odds of RLS and SS. Use of conventional disease-modifying antirheumatic drugs or abatacept was less frequent in the SS group. No medications were associated with OSA in multivariable analyses. Both RLS and SS was associated with worse perceived sleep quality. Almost two-thirds met criteria for at least one sleep disorder. RA disease activity and pain were significantly associated with each sleep condition. Additional research is needed to identify the causal pathway between sleep disorders and RA disease activity and pain and the long-term consequences of sleep disorders in RA.

Changes in physical function over time in rheumatoid arthritis patients: A cohort study.

Self-reported disability is potentially influenced by many factors in patients with rheumatoid arthritis (RA). In this sense, we evaluated the association between self-reported disability and (1) clinical features, (2) muscle strength and (3) physical performance over time among patients with RA from two distinct patient cohorts. Two independent prospective RA cohorts were analyzed. The Health Assessment Questionnaire (HAQ), Disease Activity Score in 28 Joints (DAS28), handgrip test, chair stand test, timed-up-and-go (TUG) test and Short Physical Performance Battery (SPPB) were performed at baseline and in follow-up. T test for independent samples, Mann-Whitney U test, Spearman correlation coefficients and linear regression with generalized estimating equations were performed to assess associations between individual constructs at baseline and over time. A total of 205 total RA patients were included [North American Cohort (n = 115); Brazilian Cohort (n = 90)]. At enrollment, Brazilian men had better HAQ than North American men (p<0.001). Brazilian patients overall had lower muscle strength than North American patients (p<0.05). HAQ was associated with DAS28, handgrip test, chair stand test, TUG and SPPB (p<0.001) in both cohorts. Worsening of the DAS28 and chair stand test were each associated with worsening in HAQ in longitudinal analysis over time. Worsening of handgrip was also associated in with worsening HAQ in both cohorts (p<0.05). A worse TUG test was associated with worsening in HAQ in Brazilian cohort (p<0.05) and a worse SPPB was associated with worsening in HAQ in North American cohort (p<0.05). Greater disability measured by HAQ is closely associated with disease activity, pain, muscle strength, and physical performance among RA. Worsening in self-reported disability correlate with worsening clinical factors including objectively-observed physical function.

Patterns and factors associated with pneumococcal vaccination in a prospective cohort of 1,697 patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) are at increased risk for serious infections. Pneumococcal vaccination is among the most important preventive measures, however, vaccine uptake is suboptimal. We explored the rate and factors associated with pneumococcal vaccination in a contemporary RA cohort. Multi-center, prospective, RA cohort study in Greece. Patient and disease characteristics and influenza and pneumococcal vaccinations were documented at baseline and 3 years later. One thousand six hundred and ninety-seven patients were included and 34.5% had already received at least one pneumococcal vaccine at baseline. Among 1,111 non-vaccinated patients, 40.1% received pneumococcal vaccination during follow-up, increasing the vaccine coverage to 60.8%. By multivariate analysis, positive predictors for pneumococcal vaccination included prescription of influenza vaccine (OR = 33.35, 95% CI: 18.58-59.85), history of cancer (OR = 2.35, 95% CI: 1.09-5.06), bDMARD use (OR = 1.85, 95% CI: 1.29-2.65), seropositivity (OR = 1.47, 95% CI: 1.05-2.05), and high disease activity (DAS28-ESR, OR = 1.33, 95% CI: 1.17-1.51). Male sex (OR = 0.65, 95% CI: 0.43-0.99) was a negative predictor for pneumococcal vaccination during follow-up. Despite increasing rates of pneumococcal vaccine coverage, 40% of RA patients remain unvaccinated. Severe disease, bDMARD use, comorbidities, and more importantly flu vaccination were the most significant factors associated with pneumococcal vaccination, emphasizing the currently unmet need for cultivating a "vaccination culture" in RA patients.

Factors Associated With Household Work Limitations in Mexican Patients With Rheumatoid Arthritis: The Impact of the Disease on Women's Life.

Little attention has been given to the impact of rheumatoid arthritis (RA) on domestic work, which remains the domain of women, particularly in the Latin American region. The study identified factors associated with RA-related household work limitations (HOWL) in Mexican for women with long-standing disease. This cross-sectional study was performed between September 2020 and April 2022, in patients from the recent-onset RA cohort (initiated in 2004). At study entry, patients had standard rheumatic assessments and were administered the HOWL questionnaire, a survey to assess family responsibilities, household work characteristics, and the patient's economic dependency, and the family APGAR index to assess family function. Multiple logistic regression analysis identified variables associated with RA-related HOWL. Data from 114 female RA patients were analyzed. Overall, at cohort entry, patients were middle-aged (median, 37.5 years), with 12 years of education, and the minority (n = 42 [39.3%]) were married or living together. Patients were representative of typical patients with recent-onset disease and had significant disease activity. At study entry, the patients had 12 (7-16) years of disease duration, and their disease was under control. The median (interquartile range) HOLW-Q score was 0.67 (0-3.33), and 33 patients (28.9%) had RA-related HOWL. Receiving financial support for family living expenses, requiring assistance for activities of daily living, and DAS28 (Disease Activity Score, 28 joints evaluated) were associated with RA-related HOWL; meanwhile, a better Short-Form 36 score at disease onset was protective. Domestic work in Mexican RA women might be impacted by social determinants, health-related quality of life at disease onset, and current disease activity status.

Sleep quality and predictors of optimal sleep in patients with rheumatoid arthritis: data from a recent-onset cohort.

Sleep disorders are part of the symptomatology of rheumatoid arthritis (RA) patients and are related to disease characteristics and comorbidities. The study describes sleep quality among RA patients and identifies predictors of optimal sleep. Patients whose data were analysed were identified from the recent-onset RA cohort initiated in 2004. In 2010, the Medical Outcome Study Sleep Scale (MOS-SS) was incorporated into the patients' assessments. Up to December 2019, the cohort comprised 187 patients with at least one MOS-SS application (in 78 patients at cohort entry) and six months of outcomes behaviour (cumulative) previous to the MOS-SS application: DAS28-ESR, pain-VAS, fatigue, HAQ-DI, SF-36, treatment (corticosteroids, DMARDs/patient and adherence), Charlson score, and major depressive episodes. A trained data abstractor retrospectively reviewed their charts. Multiple logistic regression analysis estimated odds ratios (95% confidence interval) to define baseline and cumulative variables predictive of optimal sleep (dichotomised variable derived from the quantity of sleep dimension of the MOS-SS). At the first MOS-SS application, patients were primarily middle-aged women with short disease duration and low disease activity. They scored higher on the "snoring" and "sleep non-adequacy" MOS-SS dimensions. There were 96 patients (51.3%) with optimal sleep. Lower baseline BMI, better baseline fatigue score, longer follow-up at the clinic, and better SF-36 physical summary score were predictors of optimal sleep (mental summary score also remained in the model when switched to the physical summary score). Optimal sleep is achieved by half of the RA patients and predicted by BMI, patient-reported outcomes, and follow-up.

The Utility of the Central Sensitivity Score as a Predictor of Disease Activity in a Cohort of Stable Rheumatoid Arthritis

Objective: To assess the impact of central sensitisation as measured by the ‘Central Sensitivity Score’ on rheumatoid arthritis disease activity change. Methods: This was a prospective cohort study of rheumatoid arthritis patients receiving routine clinical care. At baseline, participants had assessment of rheumatoid arthritis disease activity from a 3-variable Disease Activity Score with 28 Joint Count Erythrocyte Sedimentation Rate, symptoms of central sensitisation (from central sensitivity score, the numerical score derived from the 2016 American College of Rheumatology Fibromyalgia diagnostic criteria), demographic and clinical variables. A follow up 3-variable Disease Activity Score with 28 Joint Count Erythrocyte Sedimentation Rate was collected on the next routine clinic appointment (median 3 months). The association of central sensitivity score and change in rheumatoid arthritis disease activity was assessed using a multivariate linear regression analysis. Results: Data were obtained from 82 participants. The median baseline 3-variable Disease Activity Score with 28 Joint Count Erythrocyte Sedimentation Rate across the cohort was 2.44. On multivariate linear regression a higher baseline central sensitivity score independently predicted improvement in 3-variable Disease Activity Score with 28 Joint Count Erythrocyte Sedimentation Rate (regression coefficient=-0.02, 95% CI [-0.08 to -0.01]). A higher C-Reactive Protein was also an independent predictor of improvement in 3-variable Disease Activity Score with 28 Joint Count Erythrocyte Sedimentation Rate (regression coefficient -0.02, 95% CI [-0.04 to 0.01]). Exposure to a higher number of biologics predicted worsening in 3-variable Disease Activity Score with 28 Joint Count Erythrocyte Sedimentation Rate (regression coefficient=0.28, 95% CI [0.08 to 0.48]). Conclusion: In this closely monitored cohort with relatively well controlled disease, a higher baseline central sensitivity score was predictive of a small but not clinically meaningful change in objective rheumatoid arthritis disease activity.

Identification and Development of Synovial B-Cell-Related Genes Diagnostic Signature for Rheumatoid Arthritis.

The aim of the study was to investigate the landscape of B-cell-related gene expression profiling in rheumatoid arthritis (RA) synovium and explore the biological and clinical significance of these genes in RA. Expression profiling of synovial biopsies from subjects with 152 RA patients, 22 osteoarthritis (OA) patients, and 28 healthy controls was downloaded from the Gene Expression Omnibus database. Single-sample gene set enrichment analysis (ssGSEA) was performed to evaluate the abundance of infiltrated immune cells, and the results were validated using immunohistochemical staining. GSEA was employed to decipher differences in B-cell-related biological pathways. B-cell-related differential expression genes (BRDEGs) were screened, and BRDEGs-based model was developed by machine learning algorithms and evaluated by an external validation set and clinical RA cohort, then biological functions were further analyzed. High levels of immune cell infiltration and B-cell-related pathway activation were revealed in RA synovium. BRDEGs were screened, and three key molecular markers consisting of FAS, GPR183, and TFRC were identified. The diagnosis model was established, and these gene markers have good discriminative ability for RA. Molecular pathological evaluation confirmed RA patients with high-risk scores presented higher levels of B-cell activation and RA characteristics. In addition, a competitive endogenous RNA network was established to elucidate the molecular mechanisms of the posttranscriptional network. We described the B-cell-related molecular landscape of RA synovium and constructed a molecular diagnostic model in RA. The three genes FAS, GPR183, and TFRC may be potential targets for clinical diagnosis and immunoregulatory therapy of RA.

Erosion-free rheumatoid arthritis: clinical and conceptional implications—a BARFOT study

BackgroundBone erosions may appear early or later during rheumatoid arthritis (RA), causing joint damage and functional impairment. However, in some patients erosions do not occur, even after several years of disease. This study evaluates the prevalence, clinical relevance and possible predictors of erosion-free RA.MethodsSix hundred and eight patients from an early RA cohort (BARFOT) having radiographs of hands and feet at inclusion and after 1, 2, 5 and 8 years were studied. Clinical and functional assessments were performed on all these time-points.ResultsIn all, 144 patients (24%) did not develop erosions up to 8 years follow-up (Never erosive group), while 464 patients (76%) had erosions on one or more assessments (Ever erosive group). At diagnosis, the patients in the Never erosive group were significantly younger, satisfied fewer ACR criteria, and were less frequently RF- and/or anti-CCP- positive compared with those in the Ever erosive group. The Never erosive patients had consistently more tender joints, lower erythrocyte sedimentation rate (ESR) and, from two years and onwards, fewer swollen joints. Absence of rheumatoid factor (RF) and/or anti-CCP were strong independent predictors for erosion-free disease. The erosion-free patients were less frequently treated with DMARDs and/or prednisolone.ConclusionsOne-quarter of the patients was erosion-free during eight years in this early RA cohort. Erosion-free patients had a less severe disease course as to disease activity and were more often seronegative compared with those with erosive disease. The results suggest that non-erosive RA represents a milder form of RA.