Elderly Rheumatoid Arthritis Patients Research Articles

Risk Factors Associated with Adverse Events Leading to Methotrexate Withdrawal in Elderly Rheumatoid Arthritis Patients: A Retrospective Cohort Study.

Background: Rheumatoid arthritis (RA) in elderly population represents a challenge for physicians in terms of therapeutic management. Methotrexate (MTX) is the first-line treatment among conventional synthetic-disease-modifying anti-rheumatic drugs (cs-DMARDs); however, it is often associated with adverse events (AEs). Therefore, the objective of this study was to identify the incidence and risk factors of MTX discontinuation due to AEs in elderly patients with RA in a long-term retrospective cohort study. Methods: Clinical sheets from elderly RA patients taking MTX from an outpatient rheumatology consult in a university centre were reviewed. To assess MTX persistence, we used Kaplan-Meir curves and Cox regression models to identify the risk of withdrawing MTX due to adverse events. Results: In total, 198 elderly RA patients who reported using MTX were included. Of them, the rates of definitive suspension of MTX due to AEs were 23.0% at 5 years, 35.6% at 10 years and 51.7% at 15 years. The main organs and system involved were gastrointestinal (15.7%) and mucocutaneous (3.0%). Factors associated with withdrawing MTX due to AEs were MTX dose ≥ 15 mg/wk (adjusted HR: 2.46, 95% CI: 1.22-4.96, p = 0.012); instead, the folic acid supplementation was protective for withdrawal (adjusted HR: 0.28, 95% CI: 0.16-0.49, p < 0.001). Conclusions: Higher doses of MTX increase the risk of withdrawals in elderly RA, while folic acid supplementation reduces the risk. Therefore, physicians working in therapeutic management for elderly patients using MTX must focus on using lower MTX doses together with the concomitant prescription of folic acid.

Retention rate of biologic and targeted synthetic anti-rheumatic drugs in elderly rheumatoid arthritis patients: data from GISEA registry.

An increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old. RA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected. A total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi (p = 0.02), JAKi (p < 0.001), and anti-IL6R (p < 0.001), and for TNFi vs. JAKi (p = 0.013). We described, in a real-life setting, elderly RA patients treated with a biologic or a ts-DMARD in Italy. Loss of efficacy was the main cause of discontinuation, and the DMARD safety profile suggests that age does not contraindicate their use. Our study reinforced that the control of disease activity is mandatory.

MANAGEMENT OF RHEUMATOID ARTHRITIS IN ELDERLY PATIENTS

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by polyarthritis, progresses with joint damage, and may involve extra-articular tissue. Although RA can develop at any age, its prevalence increases with age. The number of elderly RA patients is gradually increasing due to both the increase in the frequency of late-onset (age 65 and over) RA (LORA) patients and the increased life expectancy. RA is characterized by inappropriately accelerated immune aging that occurs in the early period and is independent of disease duration. Aging can affect both the onset and the clinical phenotype of RA. Moreover, one of the most challenging issues for specialists is the treatment of RA in elderly patients. Targeted treatment of RA in elderly patients is inadequate or not optimally administered due to patients’ pre-existing comorbidities, polypharmacy, physicians’ concerns about possible drug side effects, and the lack of specific treatment guidelines for elderly RA patients. Elderly RA patients have been rarely and sometimes not even included in randomized controlled trials due to both age and comorbidities. Nevertheless, evidence for the safety and efficacy of specific RA treatments in the elderly population is gradually increasing. In elderly patients with RA, disease activity, all the comorbidities of the patient, and possible side effects of the drugs should be taken into consideration when making treatment decisions, and the treatment target should be individualized. In this review, the epidemiology of elderly RA patients, their comorbidities, briefly immune aging in RA, and the medical treatment approach in elderly RA will be discussed in light of studies.

Vetiver Root Oil Therapy's Effectiveness in Reducing Pain in Elderly Patients with Rheumatoid Arthritis ?

Rheumatoid arthritis is an autoimmune joint inflammation. This illness mainly affects those over 55. Many studies have examined the therapeutic advantages of perfume root oil, a processed product, for pain relief. Ginger compresses and warm water have been studied as treatments. This study evaluated the pain reported by Lansia Garut Griya Service Unit residents before and after scented root oil therapy and its effectiveness in treating pain. The study included 13 RA patients, 10 of whom met the inclusion criteria. The study found that 60% (n=6) of men and 40% (n=4) of women had rheumatoid arthritis. (RA). Before the intervention, 70% (n=7) had moderate pain and 30% (n=3) had severe pain. H0's Wilcoxon test result can be rejected because the p-value is 0.005, below the 0.05 standard of significance. It can be concluded that pre- and post-test pain scale measurements differ. These data imply that aromatic root oil therapy reduces pain in elderly rheumatoid arthritis patients.

The dichotomy of glucocorticosteroid treatment in immune-inflammatory rheumatic diseases: an evidence-based perspective and insights from clinical practice.

Glucocorticosteroids (GCs) are the most used anti-inflammatory and immunosuppressive drugs due to their effectiveness in managing pain and disease modification in many immune-inflammatory rheumatic diseases (IRDs). However, their use is limited because of adverse effects (AEs). The authors analyzed recent studies, including randomized controlled trials (RCTs), observational, translational studies and systematic reviews, providing an in-depth viewpoint on the benefits and drawbacks of GC use in rheumatology. Glucocorticosteroids are essential in managing life-threatening autoimmune diseases and a cornerstone in many IRDs given their swift onset of action, necessary in flares. Several RCTs and meta-analyses have demonstrated that when administered over a long time and on a low-dose basis, GC can slow the radiographic progression in early rheumatoid arthritis (RA) patients by at least 50%, satisfying the conventional definition of a disease-modifying anti-rheumatic drug (DMARD). In the context of RA treatment, the use of modified-release prednisone formulations at night may offer the option of respecting circadian rhythms of both inflammatory response and HPA activation, thereby enabling low-dose GC administration to mitigate nocturnal inflammation and prolonged morning fatigue and joint stiffness. Long-term GC use should be individualized based on patient characteristics and minimized due to their potential AEs. Their chronic use, especially at medium/high dosages, might cause irreversible organ damage due to the burden of metabolic systemic effects and increased risk of infections. Many international guidelines recommend tapering/withdrawal of GCs in sustained remission. Treat-to-target (T2T) strategies are critical in setting targets for disease activity and reducing/discontinuing GCs once control is achieved. Glucocorticosteroids' use in treating IRDs should be judicious, focused on minimizing use, tapering and discontinuing treatment, when possible, to improve long-term safety. Glucocorticosteroids remain part of many therapeutic regimens, particularly at low doses, and elderly RA patients, especially with associated chronic comorbidities, may benefit from long-term low-dose GC treatment. A personalized GC therapy is essential for optimal long-term outcomes.

The genes expression status of inflammatory determinants following the oral administration of Mannuronic acid in patients with rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is a progressive multifactorial inflammatory disorder. According to numerous evidence, pro-inflammatory markers such as TNF-a, IL-6, IL-22, MYD88 and TLR2 play a substantial role in the pathogenesis and persistence of this disease. B-D-Mannuronic acid (M2000) is a new immunosuppressive drug whose therapeutic effects have been approved in several clinical trials and the results of the phase III clinical trial of this drug in RA patients were potent and efficient. Therefore, the present investigation was designed to evaluate its anti-inflammatory effects on the expression of mentioned factors in RA patients. Material and methods: This research was carried out on 12 healthy individuals and 12 patients with RA and M2000 was administered to the patients orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected from the patients before and after treatment with M2000 to investigate the gene expression levels of TNF-a, IL-6, IL-22, MYD88 and TLR2 molecules in them using Real-time PCR. Results: This study data represented a higher gene expression in all target molecules in the RA patients in comparison to the healthy individuals. Furthermore, the outcomes showed that after 12 weeks of therapy with M2000, the gene expression levels of inflammatory factors TNF-a, IL-6, IL-22, MYD88 and TLR2 decreased significantly in treated patients compared to before therapy. The gene expression results were following the clinical and paraclinical assessments. Conclusion: In conclusion, M2000 as a newly approved anti-inflammatory and immunosuppressive drug, can be proposed as a therapeutic agent in RA patients.

Tocilizumab as a first line biologic agent in rheumatoid arthritis patients with inadequate response to disease-modifying anti-rheumatic drugs: real life experience from the TReasure Registry.

To evaluate the retention rate, treatment response and safety of tocilizumab (TCZ) as first-line biologic treatment in rheumatoid arthritis (RA) patients with inadequate response to disease-modifying anti-rheumatic drugs (DMARD-IR). The TReasure Registry is a multicentre, web-based registry of RA and spondyloarthritis patients across Turkey. DMARD-IR RA patients who received TCZ as first-line biologic treatment were included in this registry for efficacy and safety. Demographic and clinical data, treatments, and adverse events were collected. Drug retention rate was estimated using Kaplan-Meier analysis. Among 642 RA patients who ever used TCZ, 258 DMARD-IR RA patients (male/female: 18.2%/81.8%, mean age, 54.41 years) received TCZ as first-line biologic. The median disease duration was 97 (range, 60-179) months and the median TCZ treatment duration was 15 (range, 6-28) months. At the 6th and 12th months of TCZ treatment, the decrease in disease activity scores from baseline was significant. The Kaplan-Meier analysis revealed the retention rate of TCZ at the 12th, 24th, 36th, and 60th months as 81.1%, 73.8%, 66.2%, and 63.6%, respectively. Fifty-seven (22%) patients discontinued TCZ; the main reason being primary or secondary inefficacy (n=29). Over 80% drug retention rate at 12th month of TCZ treatment in this real-world study was concordant with previously conducted TCZ clinical studies. Significant reductions not only in the disease activity score-28 but also in the simplified disease activity index (SDAI) and clinical disease activity index (CDAI) scores, along with health assessment questionnaire (HAQ) scores, supported the impact of TCZ in RA management with a good safety profile.

The effect of disease-modifying antirheumatic drugs on sleep and quality of life in older patients with rheumatoid arthritis.

The sleep quality is worse in rheumatoid arthritis (RA) patients than in healthy controls and it is more difficult to achieve a satisfactory quality of life after treatment with age. Our aim is to assess the quality of life and sleep in elderly onset RA patients and to analyze the effect of disease-modifying agents on sleep and quality of life. Thirty-four older patients with RA patients and 30 healthy controls are included in the study. Sleep quality was evaluated with the Pittsburg sleep quality index and quality of life with Short Form-36. Parametric/non-parametric tests and Spearman/Pearson correlation analysis were applied for the data according to the distribution. While the rate of poor sleep quality before treatment was 67.6%, the rate was 26.5% after treatment. There was a statistically significant difference before and after treatment in terms of subjective sleep quality, sleep latency, sleep duration, sleep efficiency, and scores for sleep disturbance. The mean steroid dose and Disease Activity Score-28 were higher in patients with poor sleep quality than in patients with good sleep quality. Patients with poor sleep quality had lower mean physical function, pain, general health, social function, emotional role difficulties, and energy/vitality values than patients with good sleep quality. Both sleep and quality of life improved after treatment in older patients with RA patients. In older patients, it should be regularly evaluated in terms of sleep and quality of life and appropriate treatment should be provided.

Factors associated with impaired physical function in elderly rheumatoid arthritis patients who had achieved low disease activity.

We aimed to investigate factors associated with impaired physical function [defined as Health Assessment Questionnaire Disability Index (HAQ-DI) >0.5] of old-old (aged 75-84 years) patients with rheumatoid arthritis. Data from 15,185 rheumatoid arthritis patients in the National Database of Rheumatic Disease in Japan were extracted from 2017 to 2018. We enrolled 3708 patients aged 55-84 years in Simplified Disease Activity Index (SDAI) ≤11 and Steinbrocker Stage I/II. Factors associated with HAQ-DI >0.5 were analysed by multivariable logistic regression. About half of the old-old patients received methotrexate, which was lower than middle-aged (55-64 years) and young-old patients (65-74 years). The proportion of glucocorticoids in the old-old patients was highest among the three groups, and biological disease-modifying antirheumatic drugs were similarly used. The prevalence of HAQ-DI >0.5 was significantly higher in old-old patients with low disease activity than in those with remission. The same was true in the middle-aged and young-old patients. Multivariable analysis showed age, higher SDAI, glucocorticoid use, and methotrexate nonuse were significantly associated with HAQ-DI >0.5 in the old-old patients. Achieving SDAI remission was an ideal goal for old-old patients in terms of physical function. Glucocorticoids and a low proportion of methotrexate use may influence the physical function of old-old patients.

Severe Periodontitis Is a Major Contributory Factor to Unmet Dental Healthcare Needs among Rheumatoid Arthritis Patients in Hong Kong.

This study aimed to examine the frequency and predictive factors of adverse oral and dental outcomes in patients with rheumatoid arthritis (RA) with the goal to address their unmet dental healthcare needs in the metropolitan city of Hong Kong. 238 RA patients followed up at local public hospitals were recruited in this cross-sectional study. A full dental examination was performed. Data were compared with the retrospective data collected from age-matched control groups in the community conducted in a territory-wide oral health survey in 2011. Predictive factors for severe periodontitis including various demographic and disease-specific factors were examined by multiple logistic regression analysis. Loose teeth and gum bleeding were frequent dental complaints. Only 85.0% of RA patients had >20 natural teeth. Total edentulism was observed in 3.8% of patients, which was higher among adult (22-64 years) and elderly (>65 years old) RA patients than their respective age-matched community control groups. RA patients had a higher decayed, missing, and filled tooth score. Adult RA patients had a 5.3-fold increase in risk of severe periodontitis than their community counterparts. The plaque index was the main predisposing factor for severe periodontitis (odds ratio 17.5, p=0.001), which was worse among the 22-34 age group of patients. More RA patients required tooth extraction compared to dental filling for their community controls. Severe periodontitis is a major cause of unmet dental healthcare needs among RA patients in Hong Kong. It is recommended that dental care plans for RA patients be commenced early among newly diagnosed patients.

Anxiety, Distress, and Depression in Elderly Rheumatoid Arthritis Patients.

Evaluation of anxiety, distress, and depression in elderly (≥65 years old) patients with RA. 114 patients from the cities of Patras, Arta and Ioannina (all located in Western Greece) were included. Demographics and medical information regarding RA were recorded, including disease duration, medication, previous treatments, disease activity measures, comorbidities etc. Patients answered the State-Trait Anxiety Inventory (STAI), General Health Questionnaire-28 (GHQ28) and Health Assessment Questionnaire -Disability Index (HAQ-DI) questionnaires, for evaluation of anxiety, general health and functional ability, respectively. Statistical analysis was made by using STATA. 88 women (78.07%) and 25 men (21.93%) with median age 70 years and median disease duration 10 years were studied. Female patients, with longer disease duration and higher disease activity, had statistically significant higher levels of anxiety, worse general health and decreased functional ability. A strongly significant association was found between the levels of anxiety and distress, with disease activity and functional inability. Levels of anxiety and distress are strongly associated with disease activity and functional inability in elderly patients with RA. Women with longer disease have higher levels of anxiety and distress. Controlling disease activity is of upmost importance for improvement of anxiety and distress and functional ability. Larger studies are needed for evaluation of anxiety and distress in elderly patients with RA.

Persistence and Safety of Golimumab in Elderly Patients with Rheumatoid Arthritis and Renal Dysfunction in a Real-World Setting.

The efficacy and safety of golimumab in elderly patients with renal dysfunction are not well evaluated due to the exclusion criteria of clinical trials. To assess the persistence and safety of golimumab in elderly rheumatoid arthritis patients with renal dysfunction. In this retrospective observational study, we used Japan's nationwide electronic medical records and claims database to identify patients aged 65years and older who were newly prescribed golimumab for rheumatoid arthritis between July 2011 and June 2018. Patients were divided into three groups according to estimated glomerular filtration rate (eGFR; high, ≥ 90; moderate, ≥ 60, < 90; low, ≥ 30, < 60), and the persistence of golimumab and adverse events were compared between the groups. A total of 423 patients met the eligibility criteria. At 6 months, the persistence rates of golimumab were 62.4%, 63.7% and 67.0% in the high, moderate and low eGFR groups, respectively. In Cox proportional hazards regression analysis, baseline eGFR was not associated with golimumab persistence or adverse events, but concomitant methotrexate and low baseline C-reactive protein (CRP) were associated with longer golimumab persistence. Reduced renal function was not associated with continuation of golimumab or incidence of adverse events, suggesting that the persistence of golimumab therapy in patients with rheumatoid arthritis is independent of the baseline level of renal function. On the other hand, concomitant use of methotrexate and low baseline CRP levels were suggested as factors that may affect the persistence of golimumab treatment.

Medical ozone arrests oxidative damage progression and regulates vasoactive mediator levels in elderly patients (60-70years) with oxidative etiology diseases.

Medical ozone reestablishes cellular redox balance so that it may be a valid therapeutic approach in the prevention and management of age-related diseases with oxidative etiology in older people. The aim of this study is to evaluate oxidative stress and some vasoactive substances in elderly (60-70years) rheumatoid arthritis patients with diabetes and hypertension, as well as another group with bronchial asthma patients in order to demonstrate the beneficial effects of medical ozone in the prevention and therapy of age-related diseases in these age groups. A randomized clinical study with 45 older patients (60-70years) was performed. Group I (n = 15) with rheumatoid arthritis + diabetes and hypertension received no ozone treatment, and group II (n = 30) was treated with medical ozone. This group was divided into two subgroups (n = 15 each), group IIa: the same as group I + medical ozone and group IIb: bronchial asthma patients. Indicators of RA in I and IIa groups were evaluated. Redox balance was assessed through defense and injury biomarkers. Thromboxane A2 (TXA2) and prostacyclin levels were assessed in group IIb patients. Medical ozone arrested oxidative injury progression in the Ia group and decreased thromboxane levels and the TXA2/6-keto PGF1α ratio in the IIb group. Medical ozone arrested the progression of oxidative damage and modulated those endogenous mechanisms that promote a suitable redox status and TXA2/PGI2 balance. These results suggest that medical ozone may become a standard approach in the prevention and management of age-related oxidative diseases in elderly people.

Geriatric syndromes among patients with rheumatoid arthritis: A comparison between young and elderly patients

In the general geriatric population, Geriatric syndromes (GSs) predict greater likelihood of hospitalization, increased health care use and cost. The present study aimed to compare GSs among young and elderly patients with rheumatoid arthritis (RA). In a cross-sectional study a total of 98 participants, including 65 elderly (≥60 years) and 33 young adult patients (<60 years) with RA who referred to the geriatric and rheumatologic clinic were enrolled. Patients were categorized into three groups (healthy elderly, n=27; elderly with RA, n=38; and young people with RA, n=33). GSs were assessed using mini-mental state exam (MMSE), five-item geriatric depression scale-15 (GDS-15), mini nutritional assessment (MNA), and asking patients about history of falls in the past year. The RA activity in patients was assessed using disease activity for rheumatoid arthritis score-28 (DAS-28) scale, serum ESR (mm/h) level. There was a statistically significant differences in terms of DAS-28 (2.23±1.01 vs. 0.64±0.97, P=0.025) and ESR (28.10±6.64 vs. 23.09±7.65 mm/h, P=0.042) between healthy elderly and RA elderly patients. Elderly patients with RA were significantly more prone to have cognitive impairment (P=0.002), fall (P=0.005), malnutrition (P<0.001), urinary incontinence (P<0.001), and functional disability (P=0.021) compared to healthy elderlies and young RA patients. The results of binary logistic regression revealed that in elderly RA patients, higher DAS-28 score [odds ratio (OR) = 1.96; 95% CI 1.03, 3.84; P=0.041] was an independent risk factors for the GSs. The prevalence of some features of GSs were higher in the elderly RA patients than healthy elderly and young RA patients.

Association between Rheumatoid Arthritis Disease Activity and Risk of Ovarian Malignancy in Middle-Aged and Elderly Women.

Objective To investigate the risk of ovarian malignancy in middle-aged and elderly women with rheumatoid arthritis (RA) and its correlation with disease activity. Methods 219 middle-aged and elderly (age ≥ 40) female RA patients who were treated at the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from August 2019 to September 2020 were selected. Their general information such as age and medical history was collected. RA disease activity-related indicators include rheumatoid factor (RF), anticyclic citrullinated peptide antibody (ACPA), ESR, CRP, and ovarian malignancy risk-related indicators including alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), CA125, CA199, and human epididymis protein 4 (HE4) were detected. According to Risk of Ovarian Malignancy Algorithm (ROMA), they were divided into a low-risk group (ROMA-low, premenopausal: ROMA ≤ 11.4%, postmenopausal: ROMA ≤ 29.9%) and a high-risk group (ROMA-high, premenopausal: ROMA > 11.4%, postmenopausal: ROMA > 29.9%) for ovarian malignancy. Meanwhile, according to the DAS28-ESR, they were divided into the general disease activity group (DAS28-ESR ≤ 5.1) and the high disease activity group (DAS28-ESR > 5.1). SPSS 25.0 software was used to compare the differences among groups and to analyze the correlation between ovarian malignancy risk and RA disease activity. Results Compared with the ROMA-low group, the levels of RF, ACCP, CDAI, SDAI, DAS28-ESR, and DAS28-CRP in the ROMA-high group were significantly increased (P < 0.05). HE4 and ROMA in the high disease activity group were significantly higher than general disease activity group (P < 0.05). Spearman correlation analysis showed that age (r = 0.472), RF (r = 0.221), ACPA (r = 0.156), CDAI (r = 0.226), SDAI (r = 0.221), DAS28-ESR (r = 0.254), DAS28-CRP (r = 0.208), medications (r = 0.189), and CA199 (r = 0.250) were correlated with ROMA (P < 0.05). Multivariate regression analysis showed that ESR (OR = 1.11), SDAI (OR = 1.02), DAS28-ESR (OR = 1.33), DAS28-CRP (OR = 1.26), and CA199 (OR = 1.03) were independent risk factors for high risk of ovarian malignancy (P < 0.05). Subgroup analysis showed that CA199 is an effect modification factor for DAS28-ESR (P < 0.05). Conclusion The risk of ovarian malignancy is significantly increased in middle-aged and elderly women with high disease activity with rheumatoid arthritis. In clinical, full attention should be paid to the risk of ovarian malignancy in this population. Screening in time, especially in patients with increased DAS28-ESR and CA199 at the same time, is needed.

Comparison between Young and Elderly Onsetof Rheumatoid Arthritis in a Romanian Cohort

Rheumatoid arthritis (RA) is a chronic inflammatory disease that predominantly affects middle-aged adults in the third to fifth decades of life, but can also occur at any age. Significant differences were observed between patients with the diagnose of the disease under the age of 65 years – young- onset of RA (YORA) and those with the onset over the age of 65 years -elderly-onset of RA (EORA). The literature has shown that patients in the EORA group, in comparison to the young, have more severe onset, shorter duration of morning stiffness, lower frequency of sero- positivity and a more important biological inflammatory syndrome. Objective: Describe and compare the clinical characteristics, laboratory features, functional status, therapeutic approach and disease progression in elderly-onset and young-onset rheumatoid arthritis (RA) patients. Materials and methods: This retrospective, transversal study included 102 patients diagnosed with rheumatoid arthritis according to the ACR / EULAR criteria and who had at least 3 visits to our clinic, the last one during 2019-2020. Depending on the age at disease onset, we divided them into 2 groups- EORA and YORA and analyzed them comparing the clinical, laboratory and treatment data obtained at diagnosis. Subsequently we studied the evolution of the disease activity and the therapy efficiency at 6 months of follow-up and at the last hospitalization for each group. Results: The percentage of women is similar and predominant in both groups, YORA and EORA (68.3% and 71.8%). YORA was associated with a longer disease length and a prolonged symptom duration prior to the diagnosis in comparison to EORA (p&lt;0.001 and P=0.002). Extra-articular manifestations were more frequent in elderly onset RA patients at diagnosis, especially the presence of rheumatoid nodules (46.2% vs 22.2%. p=0.011) and weight loss (82.1% vs 34.9%, p&lt;0.001). Anemia was statistically associated with the EORA group (p=0.037). Analyzing the radiological findings, there was a greater number of patients who showed erosions (48.7%) and geodes (28.2%) in EORA, than in YORA group (33.3% and 19.0%). The prevalence of specific auto-antibodies positivity as anti-CCP was higher in YORA (76.2% vs 53.8%, p=0.019), as well as the positivity of Rheumatoid factor (RF) (84.1% vs 61.5%, p=0.010). The majority of patients began treatment with synthetic DMARD monotherapy, 54.0% of YORA and 64.1% of EORA. Methotrexate was the main drug administrated in both groups (61.5% in EORA and 54.0% in YORA, p-value= 0.602). Other medications, such as Sulfasalazine and Leflunomide, were less preferred in the two groups. Biologic therapy was preferred in younger patients than in those with RA at 65 years of age or over (69.8% vs 35.9%, p=0.001). Disease activity measured with DAS28(CRP) score was similar between the two groups at baseline, but significantly lower for YORA patients measured at the last hospitalization (p=0.020), treat to target (low disease activity and remission) being achieved in 53% of cases in the YORA group versus 23% of EORA patients (p=0.002). Conclusions: The definite diagnosis of RA was delayed in YORA patients in comparison to EORA patients and the extra-articular manifestations of the disease were more frequently found in the EORA group. Seropositivity was statistically significantly associated with the YORA group. Anemia was predominant in patients with disease onset over 65 years old. Both groups underwent DMARDs therapy in the early stages of the disease, but biologic therapy was more often administered in younger patients. Disease activity at diagnosis was similar in both groups, but in dynamic, the treat to target endpoint was achieved more frequent in YORA population.

Treatment of rheumatoid arthritis and its outcomes in an aging society: a single-center cohort study in Japan from 2011 to 2020

BackgroundWe conducted a single-center cohort study of rheumatoid arthritis (RA) patients from 2011 to 2020 to understand their real world treatment and outcomes, especially changes in physical function and quality of life (QOL) in elderly patients, including those aged ≥ 80 years.MethodsFor RA patients attending our outpatient clinic, we annually recorded tender and swollen joint counts, laboratory findings, therapeutic drugs, and scores from the Japanese Health Assessment Questionnaire and EuroQoL-5 Dimensions questionnaire. We examined changes in treatment and outcomes over time, by age group, in patients enrolled over a 10-year period, from 2011 to 2020.ResultsOne thousand eight hundred thirty RA patients were enrolled and data were recorded once a year, and a total of 9299 patient records were evaluated. The average age of patients increased by 3.7 years during the study period; the patients aged rapidly. Intensive pharmacological treatment was more frequent in younger patients. Disease activity, physical function, and QOL showed improvement in all age groups over the study period. Physical function and QOL showed greater changes with aging, compared with disease activity. This may be due to the effects of accumulated RA damage, disability due to aging, and depression.ConclusionsIntensive pharmacological treatment contributes to not only control of disease activity but also the improvement of physical activity and QOL, even in elderly patients. Relieving age-related physical impairment and depression may improve the QOL of very elderly RA patients.

Chronic inflammation-induced senescence impairs immunomodulatory properties of synovial fluid mesenchymal stem cells in rheumatoid arthritis

BackgroundAlthough the immunomodulatory properties of mesenchymal stem cells (MSCs) have been highlighted as a new therapy for autoimmune diseases, including rheumatoid arthritis (RA), the disease-specific characteristics of MSCs derived from elderly RA patients are not well understood.MethodsWe established MSCs derived from synovial fluid (SF) from age-matched early (average duration of the disease: 1.7 years) and long-standing (average duration of the disease: 13.8 years) RA patients (E-/L-SF-MSCs) and then analyzed the MSC characteristics such as stemness, proliferation, cellular senescence, in vitro differentiation, and in vivo immunomodulatory properties.ResultsThe presence of MSC populations in the SF from RA patients was identified. We found that L-SF-MSCs exhibited impaired proliferation, intensified cellular senescence, reduced immunomodulatory properties, and attenuated anti-arthritic capacity in an RA animal model. In particular, E-SF-MSCs demonstrated cellular senescence progression and attenuated immunomodulatory properties similar to those of L-SF-MSC in an RA joint-mimetic milieu due to hypoxia and pro-inflammatory cytokine exposure. Due to a long-term exposure to the chronic inflammatory milieu, cellular senescence, attenuated immunomodulatory properties, and the loss of anti-arthritic potentials were more often identified in SF-MSCs in a long-term RA than early RA.ConclusionWe conclude that a chronic RA inflammatory milieu affects the MSC potential. Therefore, this work addresses the importance of understanding MSC characteristics during disease states prior to their application in patients.Graphical abstract

Sustained Long-Term Retention Rates of Abatacept in Combination with Conventional Synthetic Disease-Modifying Antirheumatic Drugs in Elderly Patients with Rheumatoid Arthritis.

Background and Objectives: Treatment for elderly (aged ≥75 years) patients with rheumatoid arthritis (RA) is important because they usually have several complications and organ dysfunction and are more susceptible to drug-related adverse events. Abatacept (ABT) treatment is relatively safe in elderly RA patients; however, the real-world data of efficacy and long-term retention of ABT is sparse in such patients. This study aimed to investigate the clinical efficacy and long-term retention rates of ABT in elderly Japanese RA patients. Materials and Methods: This 10-year retrospective observational cohort study was performed in two centers in Fukushima, Japan. We reviewed the clinical features of elderly RA patients who received ABT and investigated the differences in retention rates with concomitant administration of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Results: The clinical characteristics of younger (<75 years old, 39 cases) and elderly (≥75 years old, 20 cases) RA patients were generally similar. Although the efficacy was also similar, the concomitant administration of csDMARDs with ABT differed between the two groups. Younger patients significantly decreased methotrexate (MTX) administration than elderly patients (p < 0.01), and elderly patients significantly received tacrolimus (TAC) (p < 0.01) or salazosulfapyridine (SASP; p = 0.01) than younger patients. The overall retention and infection-free survival rates were similar between the two groups. Conclusion: Elderly RA patients showed sustained retention rates compared to younger RA patients. TAC and SASP can help to maintain sustained retention rates in elderly RA patients.

Scoring Model to Predict a Low Disease Activity in Elderly Rheumatoid Arthritis Patients Initially Treated with Biological Disease-modifying Antirheumatic Drugs.

Objective We aimed to develop a scoring model to predict a low disease activity (LDA) in elderly rheumatoid arthritis (RA) patients initially treated with biological disease-modifying antirheumatic drugs (bDMARDs). Methods This retrospective cohort study included 82 elderly RA patients who initially received bDMARDs. The outcome was an LDA after bDMARDs initiation. We developed a predictive formula for an LDA using a multivariate analysis, the accuracy of which was assessed by the area under the curve (AUC) of the receiver operating characteristic curves; the scoring model was developed using the formula. For each factor, approximate odds ratios were scored as an integer, divided into three groups based on the distribution of these scores. In addition, the scoring model accuracy was assessed. Results The mean age was 73.5±6.0 years old, and 86.6% were women. An LDA was achieved in 43 patients (52.4%). The predictive formula for an LDA was prepared using six factors selected for the multivariable analysis: the neutrophil-to-lymphocyte ratio (NLR), anemia, the 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR), serum level of matrix metalloproteinase-3 (MMP-3), diabetes mellitus (DM), and rheumatoid factor (RF). The AUC for the formula was 0.829 (95% confidence interval, 0.729-0.930). The odds ratios of the six factors were scored (DAS28-ESR and serum MMP-3=1 point, NLR, anemia, DM, and RF=2 points) and divided into three groups (≤4, 5-7, and ≥8). The high-score group (≥8) achieved a positive predictive value of 83%. Conclusion The scoring model accurately predicted an LDA in elderly RA patients initially treated with bDMARDs.