Mean Rheumatoid Arthritis Research Articles

Yoga as a complementary therapy for rheumatoid arthritis: a case-based review.

Rheumatoid arthritis (RA) presents patients with chronic pain and functional limitations due to its autoimmune nature. Despite symptomatic and pharmaceutical interventions, many patients experience inadequate relief, prompting exploration into non-pharmacological approaches such as yoga. This study aims to evaluate the effectiveness of yoga as an adjunctive therapy for RA by examining clinical data from patients experiencing chronic pain and limitations. This study analyzed several clinical cases at the Shymkent City Regional Clinical Hospital. Ten RA patients, irrespective of various demographic factors, were enrolled. Parameters including pain intensity, inflammation activity, systolic blood pressure, joint function, and morning stiffness were assessed to gauge the impact of yoga. The findings demonstrated notable positive changes following a three-month yoga program. These changes encompassed enhanced joint health, reduced pain severity, and decreased disease activity. Particularly noteworthy was the reduction in morning stiffness by an average of 31min, alongside a decrease in the average pain index from 80mm to 41.5mm. The mean RA activity level decreased from 5.8 to 4.7. Furthermore, mean systolic blood pressure decreased by 15.5 mmHg, and mean cholesterol levels decreased from 5.3 mmol/L to 4.8 mmol/L. These results underscore the potential significance of yoga as a supplementary intervention for RA. Yoga practice may enhance patients' quality of life and alleviate disease symptoms. Nevertheless, the study's limited sample size necessitates caution, and further research is warranted to validate these findings.

The Association of Anti-CCP Positivity with Extra-Articular Manifestations in Patients with Rheumatoid Arthritis

Rheumatoid Arthritis (RA) is an autoimmune inflammatory disorder that primarily affects the joints. Objective: To examine association between anti-cyclic citrullinated peptide and extra-articular manifestation of Rheumatoid arthritis. Methods: It was a descriptive cross-sectional study in the Department of Rheumatology outpatient Khyber Teaching Hospital in Peshawar from 13th April 2023 to 13th September 2023. A descriptive cross-sectional study was conducted on 100 patients diagnosed with rheumatoid arthritis according to ACR/EULAR 2010 criteria at the Rheumatology outpatient department of Khyber teaching hospital in Peshawar from 13th April 2023 to 13th September 2023. Sampling technique was non probability consecutive. Statistical analysis was performed using SPSS version 23.0. Results: Our study involved 100 patients diagnosed with rheumatoid arthritis. Majority of the patients were female (90%) with overall mean age was 42.3 ± 10.06 years. The average duration of the disease was 5.9 years, with a mean RA disease activity score of 2.8. Extra-articular manifestations were observed in 84% of the patients, encompassing various symptoms such as anemia, subcutaneous nodules, episcleritis, and interstitial lung disease. Most patients (94%) tested positive for Rheumatoid Arthritis Factor, while 84% tested positive for anti-CCP antibodies. Our analysis revealed significant associations between the presence of extra-articular manifestations and factors such gender distribution, disease activity score and anti-CCP antibody positivity while no significance was noted for factors such as age, Rheumatoid Arthritis Factor and duration of disease. Conclusions: Our study concludes that anti-CCP was positively associated with the presence of extra-articular manifestation of Rheumatoid Arthritis.

Associations Between Rheumatoid Arthritis Clinical Factors and Synovial Cell Types and States.

Recent studies have uncovered diverse cell types and states in the rheumatoid arthritis (RA) synovium; however, limited data exist correlating these findings with patient-level clinical information. Using the largest cohort to date with clinical and multicell data, we determined associations between RA clinical factors with cell types and states in the RA synovium. The Accelerated Medicines Partnership Rheumatoid Arthritis study recruited patients with active RA who were not receiving disease-modifying antirheumatic drugs (DMARDs) or who had an inadequate response to methotrexate (MTX) or tumor necrosis factor inhibitors. RA clinical factors were systematically collected. Biopsies were performed on an inflamed joint, and tissue were disaggregated and processed with a cellular indexing of transcriptomes and epitopes sequencing pipeline from which the following cell type percentages and cell type abundance phenotypes (CTAPs) were derived: endothelial, fibroblast, and myeloid (EFM); fibroblasts; myeloid; T and B cells; T cells and fibroblasts (TF); and T and myeloid cells. Correlations were measured between RA clinical factors, cell type percentage, and CTAPs. We studied 72 patients (mean age 57 years, 75% women, 83% seropositive, mean RA duration 6.6 years, mean Disease Activity Score-28 C-reactive Protein 3 [DAS28-CRP3] score 4.8). Higher DAS28-CRP3 correlated with a higher T cell percentage (P < 0.01). Those receiving MTX and not a biologic DMARD (bDMARD) had a higher percentage of B cells versus those receiving no DMARDs (P < 0.01). Most of those receiving bDMARDs were categorized as EFM (57%), whereas none were TF. No significant difference was observed across CTAPs for age, sex, RA disease duration, or DAS28-CRP3. In this comprehensive screen of clinical factors, we observed differential associations between DMARDs and cell phenotypes, suggesting that RA therapies, more than other clinical factors, may impact cell type/state in the synovium and ultimately influence response to subsequent therapies.

Safety and Effectiveness of Baricitinib in Chinese Patients with Moderate-to-Severe Rheumatoid Arthritis: 24-Week Results from a Post-Marketing Safety Study.

Baricitinib, a JAK1/JAK2 inhibitor, is approved for treatment of moderate-to-severe rheumatoid arthritis (RA) in China. This single-arm, prospective, multi-center, post-marketing safety study (PMSS) evaluated the safety and effectiveness of baricitinib in Chinese patients. This study included adult patients with moderate-to-severe active RA who received baricitinib over periods of approximately 12 and 24 weeks. The primary endpoint was safety, defined as week 12 adverse event (AE)/serious AE incidence. Secondary endpoints were week 24 safety and effectiveness (disease activity score with 28 joints/C-reactive protein [DAS28-CRP] and simplified/Clinical Disease Activity Index [SDAI/CDAI]). Safety analyses included 667 patients (female, 82.3%; mean age, 53.3years; mean RA duration, 86.9months); 106/667 (15.9%) were 65-74years old and 19/667 (2.8%) were ≥ 75years old; 87.0% received baricitinib 2mg QD. Total exposure was 262.1 patient-years (PY). At week 12, AEs had occurred in 214 (32.1%; exposure-adjusted incidence rate [EAIR], 172.5 per 100PY) patients (serious AEs: 22 [3.3%; EAIR, 15.0]). At week 24, AEs had occurred in 250 (37.5%; EAIR, 125.9) patients (serious AEs: 28 [4.2%; EAIR, 10.9]). Two patients (0.3%) died (of pneumonia and unknown cause); EAIR for death, 0.77. Serious infection occurred in 1.2% of patients (EAIR, 3.1). Hepatotoxicity occurred in 3.4% of patients (EAIR, 9.0). No patients met potential Hy's law laboratory criteria (alanine/aspartate aminotransferases ≥ 3 × upper limit of normal (ULN) and total bilirubin ≥ 2 × ULN). Malignancy occurred in one patient. No patients experienced venous thromboembolism (VTE) or major adverse cardiovascular events (MACE). At week 24, 52.4%, 27.5%, and 27.6% of patients achieved remission per DAS28-CRP, SDAI, and CDAI, respectively. This PMSS investigated the safety and effectiveness of baricitinib in clinical practice in China. No VTE/MACE or new safety signals were reported and there was promising effectiveness, supporting the use of baricitinib in Chinese patients with moderate-to-severe active RA. EU PAS Register: EUPAS34213.

Systematic Literature Review of Real-World Evidence on Baricitinib for the Treatment of Rheumatoid Arthritis.

Baricitinib, an orally available small-molecule inhibitor of Janus kinase (JAK)1 and JAK2, is indicated to treat active moderate-to-severe rheumatoid arthritis (RA). This systematic review described the real-world clinical characteristics of baricitinib-treated patients with RA, prescription patterns, effectiveness, drug persistence, patient-reported outcomes (PROs; physical function, pain, health-related quality of life [HRQoL]), patient global assessment (PGA), and safety of baricitinib. A PRISMA systematic review of real-world studies was conducted to identify relevant literature published between January 2016 and September 2022 using MEDLINE®, EMBASE®, and evidence-based medicine review databases. Websites or online repositories of the American College of Rheumatology and the European Alliance of Associations for Rheumatology were searched manually to include relevant abstracts from conferences held between January 2016 and November 2022. A total of 11,472 records were identified by searching online databases. Seventy studies were included in the study, of which 40 were abstracts. Most patients were older (51-71 years), female, and with mean RA duration of 4-19 years. Baricitinib was mostly used after the failure of one or more bDMARDs, and 4 mg dosing was prevalent in patients with RA (range 22-100%). Clinical effectiveness of baricitinib was reported in real-world settings regardless of prior biologic/targeted synthetic disease-modifying antirheumatic drug (DMARD) use and concomitant conventional synthetic DMARD use. Achievement of Clinical Disease Activity Index (CDAI) remission was reported in 8.7-60% of patients at week 12 and CDAI low disease activity (LDA) in 20.2-81.6% at week 24. The proportion of patients attaining Simple Disease Activity Index (SDAI) remission was reported in 12% at week 4 to 45.4% at 24 weeks. Drug persistence was high, similar, or equal to anti-tumor necrosis factor drugs. No new safety signals were identified. Baricitinib demonstrated effectiveness in the real-world setting with a consistent safety profile observed in clinical studies. Better persistence rates for baricitinib compared to bDMARDs with improvement in PROs were reported, although baricitinib-treated patients had RA with poor prognostic characteristics.

Periodontal health status, Porphyromonas gingivalis and anti-cyclic citrullinated peptide antibodies among rheumatoid arthritis patients

Porphyromonas gingivalis (P. gingivalis) is the primary periodontal pathogen involved in protein citrullination, which triggers the production of anti-cyclic citrullinated peptide (anti-CCP) antibodies, exacerbating rheumatoid arthritis (RA). This study aims to evaluate the amount of P. gingivalis and its association with anti-CCP antibodies in RA patients with periodontitis. This cross-sectional study involves 100 RA patients with a mean age of 52.36 (SD 13.90) years. Smokers and patients with other uncontrolled systemic diseases were excluded. Disease Activity Score-28 (DAS-28) was used to determine RA disease severity. Periodontal parameters were examined to determine periodontal status. Subsequently, plaque samples were collected from the subgingival periodontal pocket for assessment of P. gingivalis bacterial load using the loop-mediated isothermal amplification method. Blood samples (5 ml) were obtained from all participants to analyse anti-CCP antibody levels. Data was analysed by using SPSS version 24.0. Most participants were female (85.0%) and had low RA disease severity (62%). The mean RA disease duration was 7.77 (SD 6.3) years, with a mean DAS-28 of 3.17 (SD 1.0). Forty-seven per cent of participants had periodontitis, but all periodontal parameters were not associated with RA disease activity (P = 0.38). P. gingivalis bacterial load ranged from 10 to 109 copies/μl. Fifty-five per cent of the collected samples showed positive anti-CCP antibody levels, but no significant association was observed with the P. gingivalis bacterial load (P = 0.58). Considering the study's limitations, although periodontitis is prevalent among RA patients, there is a lack of association between P. gingivalis bacterial load and anti-CCP antibody levels, which should be investigated further.

Management of patients with rheumatoid arthritis in real clinical practice: Switching from interleukin 6 receptor inhibitors to interleukin 6 inhibitor (olokizumab)

Aim. Switching to another biologic with the same mode of action provides greater opportunity for long-term management of patients with rheumatoid arthritis (RA). In clinical practice, especially in the context of the COVID-19 pandemic, such switching occurred for non-medical reasons as well. However, there is no information about switching from interleukin 6 (IL-6) receptor (R) inhibitor to direct IL-6 inhibitor. Objective – to assess the efficacy and safety of therapy in RA patients, after switching from IL-6R inhibitors (tocilizumab (TOC), sarilumab (SAR)) to olokizumab (OKZ) for reasons not related to the loss of their efficacy or adverse events. Material and methods. In this retrospective cohort study efficacy parameters and routine biochemical data were analyzed using descriptive statistics – mean values with standard deviation for continuous parameters and absolute and relative frequency for binary variables. Adverse events (AE) were reported according to patient’s files. The statistical significance and changes of the analyzed variables by visits were determined using paired t-test. Fisher’s exact test or chi-square test was used to compare the proportion of patients with improvement/no change and of patients with worsening. All tests were 2-sided, and p&lt;0.050 was considered statistically significant. As this was an observational study, the statistical criteria have not been pre-specified. Results. We analyzed results obtained during 5 visits (2 visits before switching, switching visit and 2 visits after switching) in 110 RA patients who switched to OKZ 64 mg every 4 weeks subcutaneously (SC). Most patients (79.1%) were women, and 70% of patients were both positive by rheumatoid factor and antibodies to cyclic citrullinated peptide. Mean RA duration was 11 [6; 16] years, previous treatment duration was 44 [27; 62] months and mean interval before switching to OKZ was 35 [31; 68] days. This relatively long interval led to an increase in DAS28-ESR (Disease Activity Score 28 with determination of erythrocyte sedimentation rate) from 2.4 [1.9; 3.0] to 2.6 [2.1; 3.5] and DAS28-CRP (DAS28 with determination of C-reactive protein level) from 2.8 [2.0; 3.3] to 2.9 [2.2; 4.0] (the trends were similar in patients who received combined therapy and monotherapy). After switching, all of RA symptoms and indexes have been improved compared with the switching visit (some of them were significantly better even compared with stable therapy period e. g. DAS28-CRP was 2.4 [2.0; 3.1] in the overall group and 2.4 [2.1; 2.7] in the monotherapy group). AEs were registered in only 7 (6.4%) patients, of which 1 (0.9%) case (an exacerbation of herpes infection) was considered as serious. The most frequent AEs were arthralgia and mild transient leukopenia (2 patients each). There were no deaths. Conclusion. OKZ effectively maintained remission/low activity of RA after switching in both regimens: as add-on to disease modifying anti-rheumatic drugs and as monotherapy, and did not cause any additional safety concerns. The optimal results were reported when intervals before switching to OKZ were closer to those indicated in the instructions for IL-6R inhibitors.

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.

Effectiveness and safety profile of tofacitinib and baricitinib in rheumatoid arthritis patients: results from a 24-month real-life prospective study in Southern-Italy.

The primary objectives of the study were to evaluate the efficacy and safety of tofacitinib and baricitinib up to 24 months of follow-up in patients with rheumatoid arthritis (RA) treated in Southern Italy. Patients' data, activity index, and clinimetric scores were collected at baseline (T0), six (T6), twelve (T12), and twenty-four (T24) months following treatment initiation. At six, twelve, and twenty-four months, adverse events and treatment cessation were also recorded. Sixty-eight patients (mean age: 62.2±10.9 years; mean RA duration: 15±9.6 years) were enrolled over a period of 12 weeks. At baseline, twenty-four patients (35.3%) were treated with tofacitinib, and forty-four patients (64.7%) were treated with baricitinib. The baseline mean disease activity was moderate as measured by DAS28- ESR (5.0±1.0), DAS 28 CRP (4.69±0.94), and SDAI (26.87±10.73) score. Before beginning JAKinhibs therapy, thirty-two patients (61.8%) were taking bDMARDs, while the remaining thirty-six (38.2%) were bDMARDs-naïve. The 24-month retention rate for JAKinhibs was 91.1%. Six months after beginning treatment with JAKinhibs, a statistically significant improvement was observed in all evaluated activity indices and clinimetric scores. Improvement was confirmed during the 12- and 24-month follow-up evaluations. The positive correlation between baseline-T6 SDAI delta and discontinuation of JAKinhibs (p=0.02) suggests that RA worsening in the first six months may be a predictor of therapy withdrawal. Patients with RA responded favorably to tofacitinib and baricitinib in this prospective, real-world study from a single center in Southern Italy. Efficacy was observed despite an underlying persistent and treatment-resistant disease.

A national, multicenter, secondary data use study evaluating efficacy and retention of first-line biologic treatment with tocilizumab in patients with rheumatoid arthritis in real-life setting: results from TURKBIO registry

Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody that targets the IL-6 receptor. TCZ found to be efficacious and has a good tolerated safety profile in rheumatoid arthritis (RA) patients. The aim of this study was to describe the disease activity and retention rate in Turkish RA patients who were prescribed TCZ as first-line biologic treatment in a real-world setting. Secondary data obtained from adult RA patients’ files was used in a multicenter and retrospective context. Clinical Disease Activity Index (CDAI), Disease Activity Score in 28 joints with ESR (DAS28-ESR), and retention rates of TCZ were evaluated at related time points. 130 patients (87.7% female) with a mean age of 53 years (SD; 15.0) were included in the study. Mean RA duration was 14 years and median duration of follow-up was 18.5 months. Number of patients with ongoing TCZ treatment at 6, 12, and 24 months were 121 (93%), 85 (65%), and 46 (35%), respectively. Remission rates at 6, 12, and 24 months per CDAI (< 2.8) and DAS28-ESR (< 2.6) scores were 61.5, 44.6, 30%, and 54.6, 40.8, 27.7%, respectively. Both CDAI and DAS28-ESR scores significantly improved at 6, 12 and 24 months (p < 0.001 for both). At 24 months, 23 patients (17.6%) discontinued TCZ, of whom majority (17/23) were due to unsatisfactory response. Retention rates of TCZ at 6, 12, and 24 months were 93, 84.3, and 72.2%, respectively. In this real-world study, TCZ as a first-line biologic therapy was found to be efficacious and showing high retention rates. These real-world study results are in line with previous randomized studies.

Abstract 11968: Association Between Reduction in Inflammation and Change in Cardiovascular Risk: Results From the Liira Study

Background: Coronary microvascular disease (CMD) is associated with increased cardiovascular (CV) risk in rheumatoid arthritis (RA). Studies suggest that higher RA disease activity is associated with a higher degree of CMD, as measured by coronary flow reserve (CFR). However, it is not known whether reducing inflammation results in improvement in CMD or other CV correlates. The objective of this study was to determine the association between reducing inflammation with changes in CV risk. Methods: The Lipids, Inflammation and CV risk in RA (LiiRA) study recruited RA patients age ≥18 yrs with active RA about to initiate a TNFi as part of clinical care. All subjects underwent a stress myocardial perfusion PET scan to quantify CFR at baseline and after 24 weeks. A lower CFR in the absence of obstructive CAD is indicative of CMD, CFR&lt; 2.5 defined CMD. Inflammatory markers and hs-cTnT were performed at baseline and 24 weeks. Primary and secondary outcomes was change in CFR and hs-cTnT, respectively, and tested by Spearman correlations. Results: A total of 66 subjects completed the study, 80% female, mean RA duration 7.7 yrs. Baseline estimated ASCVD risk was 5.6%, yet 47% had evidence of CMD. We observed a significant reduction in all inflammatory markers between baseline and follow-up, along with improvements in RA disease activity; however, no change in the mean CFR or hs-cTnT was observed. A reduction in hsCRP and IL-1beta was associated with a reduction in hs-cTnT. A non-significant trend for correlation of reduced IL-1beta with higher CFR was observed among subjects with CMD at baseline (Figure). Conclusion: There was a high prevalence of CMD at baseline, but CFR did not significantly improve. Reducing inflammation was correlated with improvements in measures of CV risk, mainly in the subset of patients with detectable hs-cTnT, particularly via the IL-1beta pathway. These data suggest that hs-cTnT may be a useful marker when considering targeting inflammation to reduce CV risk in RA.

Anti-SARS-CoV-2 Spike Antibody Titers and Neutralizing Antibodies in Vaccinated Rheumatoid Arthritis Patients.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A serological test is used to assess the efficacy of vaccination. It has been reported that anti-SARS-CoV-2 spike (S) and neutralizing antibody (Ab) levels are lower following vaccination in patients with rheumatic disease. Here, we investigated anti-SARS-CoV-2 S and neutralizing Abs in vaccinated rheumatoid arthritis (RA) patients in Japan. Anti-SARS-CoV-2 S and neutralizing Abs were quantified in 101 RA patients and 117 controls. Anti-SARS-CoV-2 S Ab levels were lower in RA patients than both earlier after vaccination in controls (mean RA 324.1 ± 591.8 SDM vs. control 1216.6 ± 854.4 [U/mL], p < 0.0001) and later after vaccination (324.1 ± 591.8 vs. 582.0 ± 415.6 [U/mL], p = 0.0002). The interval between vaccination of the RA patients and serum collection was longer than for controls early after vaccination (142.1 ± 31.6 vs. 98.3 ± 11.2 [days], p < 0.0001), but shorter than the later sample from the controls (142.1 ± 31.6 vs. 257.3 ± 11.2 [days], p < 0.0001). Importantly, anti-SARS-CoV-2 neutralizing Ab titers in RA patients were higher than in either early or later control samples (10.7 ± 4.9 vs. 8.6 ± 6.6 [%], p = 0.0072, and 10.7 ± 4.9 vs. 3.1 ± 3.7 [%], p < 0.0001, respectively). Anti-SARS-CoV-2 S Ab titers in vaccinated RA patients were lower than in controls, but they were influenced by other clinical manifestations. Anti-SARS-CoV-2 neutralizing Ab levels were independently increased in RA.

Real-world evidence of the effectiveness and safety of generic tofacitinib in rheumatoid arthritis patients: a retrospective, single-centre analysis from Western India.

Generic tofacitinib has been available in India for more than a year and is widely used in rheumatoid arthritis (RA) therapy. There is scarce real-world data on its effectiveness and safety from India, especially given infection endemicity. We retrospectively analysed records (demographic and clinical information, haematology and biochemistry, adverse events) of patients prescribed generic tofacitinib from a single centre in Mumbai, India. Disease activity was calculated using the disease activity score-28 and erythrocyte sedimentation rate (DAS28-ESR) and other tools, and we used paired T-tests for significant response. We defined clinical tofacitinib failure as a composite outcome, including clinician’s decision to change to an alternative disease-modifying anti-rheumatic drug (DMARD) or flare after self-withdrawal. We performed logistic regression and survival analysis for determinants of clinical failure. We reviewed records of 102 patients (92 female; median age: 53 years) with mean RA duration of 146 months. Thirteen had prior treatment with innovator tofacitinib. There was significant improvement in disease activity parameters at a mean duration of 186 days. No serious adverse events were reported; 4 patients had tuberculosis and 19 patients had mild COVID-19 while on treatment. Clinical failure was seen in 25 patients, and mean time to failure on survival analysis was 357 days. No baseline characteristic predicted clinical failure. Generic tofacitinib showed good effectiveness and a tolerable adverse effect profile, despite tuberculosis endemicity and COVID-19. Setting up registries would be valuable in gaining more data on generic tofacitinib.Key Points• There is scarce data from India regarding the use of tofacitinib in rheumatoid arthritis, despite widespread use.• In this retrospective analysis of 102 patients at a single centre, we found tofacitinib monotherapy was efficacious and tolerable.• Tuberculosis was detected in four and nineteen patients had mild covid.

Usability Study of PF-06410293, an Adalimumab Biosimilar, by Prefilled Pen: Open-Label, Single-Arm, Sub-Study of a Phase 3 Trial in Patients with Rheumatoid Arthritis.

IntroductionThe aim of this sub-study was to evaluate injection success of patients with rheumatoid arthritis (RA) and their caregivers administering the adalimumab (ADL) biosimilar, PF-06410293 (ADL-PF: adalimumab-afzb; Abrilada®/Amsparity®/Xilbrilada®) by prefilled pen (PFP) during the open-label treatment period in year two (weeks 52–78) of a phase 3 multinational, double-blind, clinical study (NCT02480153) comparing ADL-PF and reference ADL (Humira®) sourced from the EU.MethodsThis sub-study included adult patients with active RA not adequately controlled by methotrexate. Patients received subcutaneous ADL-PF 40 mg by prefilled syringe (PFS) at weeks 52 and 54, then six biweekly doses (weeks 56–66) of ADL-PF 40 mg each via a single-use PFP device. Training was given on first injection at week 56; all injections were given by patients/caregivers. The primary endpoint was delivery system success rate (DSSR): the percentage of participants (i.e., actual PFP user) achieving delivery success for each of the six attempted PFP injections. Injection success was recorded by the observer (Observer Assessment Tool) and participant (Participant Assessment Tool).ResultsIn total, 50 patients with no experience self-injecting with an autoinjector/injection pen were included (74.0% female; mean age at screening, 54.9 years; mean RA duration, 8.0 years). Of these, 49 (98.0%) completed the sub-study and 46 (92.0%) received all six PFP injections. Overall DSSR (n = 294 injections) across visits was 100% (95% CI 92.0–100.0%). Complete injection was confirmed following inspection of 292 used and returned PFPs. A total of 47/49 (95.9%) participants who completed the sub-study elected to continue study treatment using PFP injections, rather than switching back to the PFS.ConclusionsAll actual PFP users could safely and effectively administer ADL-PF by PFP at each visit, and nearly all participants who completed the sub-study elected to continue study treatment using PFP injections.Trial registrationClinicalTrials.gov identifier: NCT02480153; EudraCT number: 2014-000352-29.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00439-8.

Quality of Life and Depression in Rheumatoid Arthritis Patients Treated with Biologics - A Single Centre Experience.

IntroductionPatients with rheumatoid arthritis (RA) often experience depression, which has a very negative impact on the assessment of the quality of life (QoL). However, there are not many studies that assess the relationship between depression and QoL in RA patients. The aim of the study was to assess the level of QoL and determine the mutual relationship between anxiety and depression levels and QoL in patients treated for RA.Material and MethodsThe study included 101 patients (aged:52.4±16.97), who met the established criteria for a diagnosis of RA and treatment with a biological agent. Only standardized tools were used to examine the patients: WHO-QoL, HADS and the VAS scale.ResultsThe mean RA duration in the group studied was 13.54±9.51 years and the disease activity score was 4.8±0.8. The mean QoL perception score was 3.48± 0.8. Nearly 40% of the respondents could not clearly determine their QoL, perceiving it as neither poor nor good, and 10% believed their QoL is poor or very poor. The correlation analysis revealed that anxiety is significantly and negatively associated with QoL in the psychological domain (r = −0.472, p < 0.001) and social domain (r = −0.298, p = 0.023) and depression is significantly and negatively associated with QoL in the psychological domain (r = −0.322, p = 0.01) and physical health domain (r = −0.209, p = 0.04). In the multiple linear regression model, depression was an independent negative predictor affecting the following domains: perception of QoL and perception of health, and physical health.ConclusionRA patients treated with biologics present a low level of health perception and an average level of QoL perception. Depression and anxiety negatively correlate with QoL domains: the higher the anxiety and depression levels, the poorer the QoL in the psychological and social relationships domains. Depression is an independent determinant of decreased QoL.

Low cumulative disease activity is associated with higher bone mineral density in a majority Latinx and Asian US rheumatoid arthritis cohort

ObjectivePrior studies have found conflicting results when evaluating the association between rheumatoid arthritis (RA) disease activity and bone mineral density (BMD). Whether or not cumulative RA disease activity is associated with BMD remains unanswered. MethodsData were from the University of California San Francisco RA Cohort from years 2006–2018. Those with BMD measures and at least two study visits prior to BMD measure were included in the study. The association between low cumulative disease activity, as measured by DAS28ESR, with the primary outcome of femoral neck BMD was assessed using multivariable linear regression. Sensitivity analyses were performed substituting CDAI for the disease activity measure as well as total hip and lumbar spine BMD as outcomes. Results161 participants with RA were studied. The cohort was 62.4 ± 10.2 years old and 88% female. Hispanic/Latino (N = 73, 45%) and Asian (N = 59, 37%) were the most common racial/ethnic groups in our cohort. Mean RA duration was 10.5 ± 7.3 years and 83% were ACPA positive. Low disease activity was independently associated with higher femoral neck BMD compared to the moderate/high disease activity group (β= 0.071 [95%CI: 0.021 to 0.122], p = 0.020). The relationship between low cumulative disease activity was similar when CDAI and other BMD sites were substituted in the multivariable models. ConclusionLow cumulative disease activity as measured by DAS28ESR was associated with higher femoral neck BMD, independent of traditional osteoporosis risk factors (e.g., age, sex, BMI) in a unique RA cohort. Results were similar when evaluating cumulative low CDAI and other BMD sites.

Circulating Biomarkers and Cardiac Structure and Function in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) increases the risk for abnormalities of the cardiac structure and function, which may lead to heart failure (HF). Studying the association between circulating biomarkers and echocardiographic parameters is important to screen patients with RA with a higher risk of cardiac dysfunction.Aim: To study the association between circulating biomarkers and echocardiographic parameters in patients with RA.Methods: Echocardiography was performed in 355 patients with RA from RA Porto cohort and the associations between echocardiographic characteristics and 94 circulating biomarkers were assessed. These associations were also assessed in the Metabolic Road to Diastolic Heart Failure (MEDIA-DHF) [392 patients with HF with preserved ejection fraction (HFpEF)] and the Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux (STANISLAS) (1,672 healthy population) cohorts.Results: In the RA Porto cohort, mean age was 58 ± 13 years, 23% were males and mean RA duration was 12 ± 10 years. After adjustment and multiple testing correction, left ventricular mass index (LVMi), left atrial volume index (LAVi), and E/e′ were independently associated with biomarkers reflecting inflammation [i.e., bone morphogenetic protein 9 (BMP9), pentraxin-related protein 3 (PTX3), tumor necrosis factor receptor superfamily member 11a (TNFRSF11A)], extracellular matrix remodeling [i.e., placental growth factor (PGF)], congestion [i.e., N-terminal pro-brain natriuretic peptide (NT-proBNP), adrenomedullin (ADM)], and myocardial injury (e.g., troponin). Greater LVMi [hazard ratio (HR) (95% CI) per 1 g/m2 = 1.03 (1.02–1.04), p < 0.001], LAVi [HR (95% CI) per 1 ml/m2 = 1.03 (1.01–1.06), p < 0.001], and E/e′ [HR (95% CI) per 1 = 1.08 (1.04–1.13), p < 0.001] were associated with higher rates of cardiovascular events. These associations were externally replicated in patients with HFpEF and asymptomatic individuals.Conclusion: Circulating biomarkers reflecting inflammation, extracellular matrix remodeling, congestion, and myocardial injury were associated with underlying alterations of cardiac structure and function. Biomarkers might be used for the screening of cardiac alterations in patients with RA.

AB0229 A NATIONAL, MULTICENTER, SECONDARY DATA USE STUDY EVALUATING EFFICACY AND RETENTION OF FIRST-LINE BIOLOGIC TREATMENT WITH TOCILIZUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS IN REAL-LIFE SETTING FROM TURKBIO REGISTRY

Background:Tocilizumab (TCZ) is a human anti-interleukin (IL)-6 receptor antibody approved in Turkey for the treatment of rheumatoid arthritis (RA).Objectives:In this study our purpose was to describe the disease activity, quality of life (QoL), and retention rate in RA patients who were prescribed TCZ as first-line biologic treatment in a real-world setting.Methods:Anonymized patient registry of TURKBIO was used based in a national, multicenter, and retrospective context. We conducted a search in the registry between years 2013 and 2020 and included adult RA patients who were prescribed with TCZ as their first-line biologic treatment with a post-TCZ follow-up of at least 6 months. CDAI, DAS28-(ESR), and HAQ-DI scores in 6, 12, and 24 months were obtained. Pairwise comparison was carried out for survey scores across baseline and timepoints. Subgroup analysis for route of TCZ administration was performed. EULAR response criteria were used for response evaluation. Retention of TCZ was evaluated by Kaplan-Meier analysis.Results:Overall,130 patients with a mean RA duration of14 years were included in the study. 87.7% of the patients were female and mean age was53 (SD; 15.0). Median duration of follow-up was 18.5 months. Majority (90.8%) of patients were given tocilizumab via intravenous route at baseline. Number of patients with ongoing TCZ treatment and follow-up at 6, 12, and 24 months were 121 (93%), 85 (65%), and 46 (35%), respectively. Remission rates at 6, 12, and 24 months per CDAI (&lt;2.8) and DAS28-(ESR) (&lt;2.6) scores were 61.5%, 44.6%, 30%, and 54.6%, 40.8%, 27.7%, respectively. CDAI, DAS28-(ESR) and HAQ-DI survey scores significantly improved at 6, 12 and 26 months, respectively (p&lt;0.001) (Table 1) in both IV and SC TCZ subgroups. At 6, 12 and 24months 74.8%, 82.5% and 86.4% of patients achieved a EULAR good response respectively. Twenty-three patients (17.6%) discontinued TCZ at 24 months. Of these, 19 patients discontinued due to unsatisfactory response. Retention rates of TCZ at 6, 12, and 24 months were 93%, 84.3%, and 72.2%, respectively (Figure 1).Conclusion:TCZ as a first-line biologic treatment was found to be clinically effective in this real-world study with a high retention rate. These results are in line with the results gathered from previous TCZ controlled and real-life studies in which TCZ was found clinically safe and effective.

POS0095 DEVELOPPING A SCORE TO PREDICT PRECLINICAL INTERSTITIAL LUNG DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS – A CROSS-SECTIONAL STUDY FROM THE ESPOIR COHORT

Background:Interstitial lung disease (ILD) is an extra-articular manifestation of rheumatoid arthritis (RA) detected in 20% to 60% of patients with RA on high-resolution computed-tomography (HRCT) chest scan and is clinically significant in near 10%. Despite a high morbi-mortality rate, a definite strategy for preclinical ILD screening in patients with RA remains to be determined. To date, several factors have been reported to increase the risk of RA-ILD occurrence (i.e. older age at RA onset, ACPA positivity, male sex, RA disease activity, the MUC5B rs35705950 promoter variant...). However, none of these risk factors has been validated in a prospective cohort of patients with RA. The ESPOIR prospective cohort includes patients aged 18 to 70 years with recent arthritis (less than 6 months) and a definite or probable diagnosis of RA.Objectives:To identify in the ESPOIR cohort factors associated with ILD after at least 10 years of RA duration in order to develop a predictive score to identify patients with preclinical RA-ILD.Methods:An ILD detection by chest HRCT scan was systematically offered to every patient with definite RA after at least 10 years-follow-up. Chest HRCT scans were centrally reviewed by an experienced radiologist. Potential predictors of ILD were prospectively collected from baseline to the date of the HRCT scan, and all included patients were genotyped for MUC5B rs35705950. To take into account repeated measures, trajectories were determined for disease activity, C reactive protein, smoking, treatment exposure (i.e. prednisone, methotrexate [MTX] and biological disease modifying anti-rheumatic drugs [bDMARDs]). A logistic model was used to identify independent predictors for the occurrence of ILD on HRCT scans. Confidence intervals were estimated using sampling methods. A predictive score for preclinical ILD occurrence was developed based on the identified predictors.Results:163 RA patients according to 2010 ACR/EULAR classification criteria, none of whom had pulmonary symptoms, were investigated with a chest HRCT scan (128 women (78.5%), mean RA duration 13.7 ± 1.1 years, age at inclusion 47.6 y/o ± 10.4, mean disease activity score [DAS]-28 during follow up was 3.1 ± 1.0). ILD was detected in 31 patients (19.0%). The MUC5B rs35705950 minor allele frequency (MAF) was 22.2% and 10.0% in the RA-ILD and RA-noILD populations, respectively (OR univariate=2.6 CI95% [1.2-5.5], P=0.01). After logistic regression, independent predictors for preclinical RA-ILD were male sex (OR=3.9 CI95% [1.4-11.4]), older age at RA onset (OR=1.1 per year CI95% [1.0-1.2]), mean DAS-28 score during the follow-up (OR=2.0 CI95% [1.2-3.4]) and MUC5B rs35705950 T risk allele (OR=3.7 CI95% [1.4-10.4]) (Figure 1). No influence of the use of RA-related drugs (prednisone, MTX or bDMARDs) was identified as risk factor. The logistic model could predict preclinical ILD occurrence after 13 years of RA duration with an AUC=0.82 CI95% (0.72-0.91). A predictive score for preclinical RA-ILD based on the 4 identified predictive risk factors was developed (Sensitivity 80%, Specificity 56%).Figure 1.Factors independently associated with preclinical ILD after 13 years of RA durationConclusion:In this cross-sectional study of the prospective ESPOIR cohort, we identified clinical and genetic predictors for ILD after 13 years of RA duration. We developed a predictive score that could improve risk stratification for preclinical RA-ILD and help physicians identify patients with RA in whom a HRCT scan should be performed.Disclosure of Interests:Pierre-Antoine Juge Consultant of: BMS, Benjamin Granger: None declared, Marie-Pierre Debray: None declared, Esther Ebstein: None declared, Fabienne Louis Sidney: None declared, Joanna KEDRA: None declared, Raphael Borie: None declared, Arnaud Constantin Consultant of: Bristol-Meyers Squibb, Chugai, Roche, Abbvie, MSD, Pfizer, and UCB, Bernard Combe Consultant of: Abbvie, Bristol-Meyers Squibb, Lilly, MSD, Janssen, Pfizer, Roche, Chigai, and Sanofi, Grant/research support from: Abbvie, Bristol-Meyers Squibb, Lilly, MSD, Janssen, Pfizer, Roche, Chugai, and Sanofi, René-Marc Flipo Consultant of: Bristol-Meyers Squibb, Roche, Chugai, Abbvie, and Pfizer, Grant/research support from: Roche, Chugai, Abbvie, and Pfizer, Xavier Mariette Consultant of: Bristol-Meyers Squibb, GSK, Janssen, Pfizer, and UCB, Olivier VITTECOQ Consultant of: Bristol Myers Squibb, Roche, Chugai, MSD, Novartis, Pfizer, Abbvie, and Lilly, Alain Saraux Consultant of: Roche, Chugai, and Bristol-Meyers Squibb, Grant/research support from: Roche, Chugai, and Bristol-Meyers Squibb, Guillermo CARVAJAL ALEGRIA: None declared, Jean Sibilia Consultant of: Roche, Chugai, Bristol-Meyers Squibb, UCB, GSK, LFB, Actelion, Pfizer, MSD, Novartis, Amgen, Hospira, AbbVie, Sandoz, Gilead, Lilly, Sanofi, Janssen, and Mylan, Francis Berenbaum Consultant of: Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Elli Lilly, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica, 4P Pharma, Caroline Kannengiesser: None declared, Catherine Boileau: None declared, Bruno Crestani Consultant of: Boehringer Ingelheim, Roche, Sanofi, Apellis, Astra-Zeneca, Grant/research support from: MedImmune, Boehringer Ingelheim, Bruno Fautrel Consultant of: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, SOBI, UCB, Grant/research support from: AbbVie, MSD, Pfizer, Philippe Dieudé: None declared

AB0061 ALTERATIONS OF XANTHINE OXIDOREDUCTASE ACTIVITY IN RED BLOOD CELLS AFTER GLUCOCORTICOID TREATMENT IN RHEUMATOID ARTHRITIS

Background:According to modern concepts, rheumatoid arthritis (RA) refers to severe autoimmune rheumatic diseases. The activation of free radical oxidation processes is essential in the development of this disease [1]. Xanthine oxidoreductase is a significant reactive oxygen species source [2]. Despite the great advances in the treatment of rheumatoid arthritis (RA) associated with the introduction of innovative drugs and especially the improvement of the strategy for their use into clinical practice, glucocorticoids still remain an important component of RA pharmacotherapy in actual clinical practice.Objectives:to evaluate the changes in activities of xanthine oxidoreductase interconvertible forms (xanthine oxidase, ЕС 1.17.3.2 and xanthine dehydrogenase, ЕС 1.17.1.4) in lysed red blood cells of RA patients in relation with glucocorticoid treatment.Methods:47 RA patients with verified RA and 30 healthy controls were enrolled in the study. The diagnosis was verified using the 2010 ACR/EULAR criteria 2010. All patients have moderate DAS28 scores. RA patients were randomized into 2 groups comparable in gender, age and the principal clinical manifestations. Methylprednisolone (Metipred, Orion Corp.), average dose 30 mg/day, and betamethasone (Diprospan, Schering-Plough), single dose7 mg, were administered intramuscularly in the respective groups. Хanthine oxidase (XO) and xanthine dehydrogenase (XDG) activities were measured in lysed red blood cells by spectrophotometric method as previously described [3]. The changes of these enzymes activities were studied in RA patients before and after the injection of glucocorticoids. Statistical comparison tests were selected in according to common guidelines, differences were considered significant when p&lt;0.05. Central tendencies were expressed as means±SEM.Results:Mean age of patients in methylprednisolone group was 41.8±1.05 years, and mean RA duration (± SEM) was 7.9±0.21 years. Mean age of patients in diprospan group was 40.9±1.07 years, and mean RA duration was 8.0±0.33 years. Significant decreases of XO activity and increase of XDG activity were observed in lysed red blood cells of RA patients just after the injection of each glucocorticoid drug. Changes of the enzymatic activities in lysed red blood cells were more pronounced in methylprednisolone group. However enzymatic activity did not reach the level of healthy controls. As described previously, decreased XO activity and increased XDG activity were observed in plasma of RA patients just after the injection of the average therapeutic doses of glucocorticoids, as well as in lysed lymphocytes just after the injection of methylprednisolone [4].Conclusion:Treatment with methylprednisolone and betamethasone can affect the balance of XO/XDG activity and increase the antioxidant potential of the blood. This effect can exert beneficial influence on autoimmune inflammation in RA.