Elderly Rheumatoid Arthritis Patients Research Articles

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.

Cytokines in gingival crevicular fluid in elderly rheumatoid arthritis patients in a population-based cross-sectional study: RANTES was associated with periodontitis.

ObjectiveWe studied cytokines in gingival crevicular fluid (GCF) in a cross‐sectional population‐based cohort of rheumatoid arthritis (RA) patients ≥61 years of age with and without a diagnosis of periodontitis.Background dataEarlier studies on cytokines in GCF in RA patients have not given clear results.MethodsIn a population‐based cross‐sectional study of patients ≥61 years of age, 233 RA patients were identified. 132 (57%) dentate RA patients participated. All participants received rheumatological and dental examinations, and had a panoramic radiograph taken. GCF was sampled on each patient. Interleukins 1‐β (IL‐1β), IL‐4, IL‐6, IL‐10, IL‐17A, tumor necrosis factor alpha (TNF‐α), interferon gamma (IFN‐γ), and chemokines RANTES/CCL5, eotaxin and monocyte chemoattractant protein (MCP‐1) were analyzed in GCF. These cytokines were stratified for periodontitis, age, gender, body mass index (BMI), smoking, and anti‐cyclic citrullinated protein (anti‐CCP) status. Binary logistic regression analyses with periodontitis as outcome were performed adjusting for the above mentioned confounding factors including anti‐rheumatic medication, disease duration and the cytokine in question.ResultsPeriodontitis was diagnosed in 80/132 (61%) of study participants. The 110 RA patients not participating were older, had a higher mean erythrocyte sedimentation rate (ESR), had a higher mean DAS28ESR (Disease Activity Score 28 using ESR) and were less often on biologic treatment. Only RANTES was associated with periodontitis (p = .049, OR 1.001, 95% CI 1.000–1.002) in the binary logistic regression analyses.ConclusionIn this population‐based elderly RA cohort, neither pro‐inflammatory nor anti‐inflammatory cytokines in GCF were clearly associated with a diagnosis of periodontitis.

Association between Malnutrition and Quality of Life in Elderly Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a progressive articular disease. In addition to damaging the joints, it may cause multiple organ complications, and considerably impair the patient’s functioning. Elderly patients with RA report pain, fatigue, mood disorders, sleep disorders and insomnia, accompanied by weakness, poor appetite, and weight loss. All these factors combined have an adverse effect on the patient’s perceived quality of life (QoL). Due to the chronic nature of RA and the high risk of malnutrition in this patient group, the present study investigated QoL, activities of daily living, and frailty syndrome severity in relation to MNA (Mini Nutritional Assessment) questionnaire scores among elderly RA patients. The study included 98 patients (aged over 60) diagnosed with RA per the ARA (American Rheumatism Association) criteria. The following standardized instruments were used: WHOQoL-BREF for QoL, the Edmonton Frail Scale for frailty syndrome severity, MNA for nutritional status assessment, and MMSE (Mini-Mental State Examination) to assess any cognitive impairment. Medical data were obtained from hospital records. Patients with a different nutritional status differed significantly in terms of limitations in activities of daily living (ADL) and instrumental activities of daily living (IADL). Higher levels of malnutrition were associated with greater limitations in activity. An adverse impact of lower body weight on cognitive function was also observed (dementia was identified in 33.33% of malnourished patients vs. 1.79% in patients with a normal body weight). Likewise, frailty was more common in malnourished patients (mild frailty syndrome in 33.3%, moderate in 16.67%, and severe in 16.67%). Malnourished patients had significantly lower QoL scores in all WHOQoL-BREF questionnaire domains than those with a normal body weight, and multiple-factor analysis for the impact of selected variables on QoL in each domain demonstrated that frailty was a significant independent determinant of poorer QoL in all domains: perceived quality of life (β = −0.069), perceived health (β = −0.172), physical domain (β = −0.425), psychological domain (β = −0.432), social domain (β = −0.415), environmental domain (β = −0.317). Malnutrition was a significant independent determinant of QoL in the “perceived health” domain (β = −0.08). In addition, regression analysis demonstrated the positive impact of male sex on QoL scores in the psychological (β = 1.414) and environmental domains (β = 1.123). Malnourished patients have a lower QoL than those with a normal body weight. Malnutrition adversely affects daily functioning, cognitive function, and the severity of frailty syndrome. Frailty syndrome is a significant independent determinant of poorer QoL in all WHOQoL BREF domains.

Muscle wasting, a neglected complication associated with physical dysfunction in elderly patients with rheumatoid arthritis: a cross-sectional observational study

Objective: Little is known about muscle wasting in elderly patients with rheumatoid arthritis (RA). We examined muscle characteristics and their clinical significance in this group. Method: Consecutive RA patients were recruited and clinical data were collected. Muscle mass and distribution were assessed using bioelectric impedance analysis. Myopenia was defined as an appendicular skeletal muscle mass index (ASMI) ≤ 7.0 kg/m2 (men) and ≤ 5.7 kg/m2 (women). Results: Among the 643 RA patients recruited, 165 (25.7%) were elderly patients (age ≥ 60 years) with a mean age of 65.1 ± 4.5 years. Compared with young patients (age < 60 years), elderly RA patients had significantly higher Disease Activity Score based on 28-joint count–C-reactive protein (DAS28-CRP) (median 3.4 vs 3.2), Health Assessment Questionnaire Disability Index (HAQ-DI) (0.38 vs 0.13), and modified total Sharp score (mTSS) (16 vs 9), and a higher proportion of myopenia (54.5% vs 41.4%; all p < 0.01). Elderly RA patients with myopenia (n = 90, 14.0%) had significantly higher DAS28-CRP (3.6 vs 3.0), HAQ-DI (0.50 vs 0.12), and mTSS (21 vs 7) than young RA patients without myopenia (n = 280, 43.5%; all p < 0.0083). Multivariate logistic and linear regression analyses showed that myopenia, high HAQ-DI, active smoking, hypertension, diabetes, and coronary atherosclerotic heart disease were the main relevant characteristics of elderly RA patients. Age positively correlated with HAQ-DI, and ASMI negatively correlated with HAQ-DI (both p < 0.01). Further mediation analysis showed that ASMI partially mediated the association between age and HAQ-DI. Conclusion: Our data reveal that half of elderly RA patients manifest myopenia which aggravates physical dysfunction as a mediator of age. Myopenia, a neglected complication in elderly RA patients, should be recognized and further investigated.

MiRNAs and rheumatoid arthritis: new update in expression pattern and pathogenicity

Rheumatoid arthritis (RA) is a polygenic autoimmune disease characterized by systemic inflammation and disability of joints. Early diagnosis and treatment could prevent diseases in RA patients from becoming severe. miRNAs are small, non-coding RNA that regulate the post-transcriptional level of gene expression. miRNAs play important roles in gene expression and pathogenicity of autoimmune diseasesas well as RA. Properly using miRNAs regulation potential and detecting different expression patterns andtheir functions could facilitate and manage effective therapeuticinterventions in RA patients. Herein, we discuss miRNAs as a therapeutic agent in RA patients.

Drug Survival of Biologic Therapy in Elderly Patients With Rheumatoid Arthritis Compared With Nonelderly Patients: Results From the Korean College of Rheumatology Biologics Registry.

Although the proportion of elderly patients with rheumatoid arthritis (RA) is increasing, the persistency of biologic therapy in elderly patients requires additional investigation. This study evaluated the drug survival of biologic therapy and associated factors in elderly compared with nonelderly patients. This longitudinal observational study included RA patients who were enrolled in the Korean College of Rheumatology Biologics Registry (NCT01965132, started from January 1, 2013) between 2013 and 2015. We compared the retention rate of biologic therapy between elderly (age ≥70 years) and nonelderly (age <70 years) patients, and investigated the causes and predictors of biologic withdrawal in both groups. Of 682 patients, 122 were aged 70 years or older. The retention rate of biologic therapy at 24 months was 57.8% and 46.5% in nonelderly and elderly patients, respectively (p = 0.027). Biologic withdrawal due to adverse events and inefficacy within 24 months was not significantly different between the 2 groups, although adverse events were more common in elderly patients (20.6% vs 12.8%, p = 0.360). Drug withdrawal due to patient refusal was more common in elderly patients (9.8% vs 1.8%, p < 0.001). In elderly patients, biologic withdrawal was associated with current smoking and older age at disease onset, whereas the use of tumor necrosis factor inhibitors, nonuse of methotrexate, and combination of corticosteroid were important in nonelderly patients. Elderly RA patients are more likely to discontinue biologic agents within 24 months. To increase the retention rate of biologic therapy, rheumatologists should consider patient characteristics before and during biologic therapy.

Features and Outcomes of Elderly Rheumatoid Arthritis: Does the Age of Onset Matter? A Comparative Study From a Single Center in China.

IntroductionThe aim of this work is to investigate the clinical and radiological characteristics of elderly rheumatoid arthritis and compare the outcomes between the two subgroups, elderly- and young-onset rheumatoid arthritis (EORA and YORA, respectively).MethodsWe conducted a retrospective case-control study on the elderly rheumatoid arthritis patients in our medical center. EORA was defined as the patient whose onset age was above 60.ResultsA total of 142 elderly rheumatoid arthritis patients were admitted, with 79 patients in EORA and 63 in YORA group. Inflammatory parameters including C-reactive protein, D-dimer, serum ferritin, and platelet count levels were all higher in the EORA group than those in YORA. EORA patients showed a higher score of health assessment questionnaire's disability index (p = 0.01) and patient global health assessment (p = 0.049), but a lower status of modified total sharp score (p = 0.001). Bivariate logistic regression analysis revealed that elderly onset of the disease (OR 2.30, 95% CI [1.45–3.77]), age (OR 2.04, 95% CI [1.22–3.41]), high disease activity (OR 1.90, 95% CI [1.17–3.32]), and red blood cell distribution width (OR 1.81, 95% CI [1.03–3.19]) were independent prognostic factors of disability. Age (OR 0.25, 95% CI [0.07–0.91]), disease duration (OR 2.73, 95% CI [0.97–7.70]), and co-morbid diabetes mellitus (OR 118.10, 95% CI [3. 50–3985.57]) independently contributed to radiographic joint damage in the elderly population. EORA patients showed increased death incidents and worse prognosis than YORA. Cox regression analysis reveals that comorbid hypertension (HR 12.02, 95% CI [1.08–133.54]), interstitial lung disease (ILD) (HR 85.04, 95% CI [4.11–1759.19]), and compressive fracture (HR 85.04, 95% CI [4.11–1759.19]) are independent predictors of mortality, and that ILD (HR 50.21, 95% CI [5.56–335.33]) and pulmonary hypertension (HR 25.37, 95% CI [3.03–265.81]) are independent predictors of no disease remission in the EORA patients.ConclusionsThe distinct features of EORA patients make EORA a unique entity different from “classic rheumatoid arthritis”. EORA patients develop an upgraded systemic inflammatory status, more declined life quality, and worse prognosis than the elderly YORA. Better control of the comorbidities like ILD and diabetes mellitus may benefit the management of elderly rheumatoid arthritis. Further investigation regarding the pathogenesis and therapeutic strategies of EORA is urgently warranted.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-020-00267-8.

Medicare expenditures for conventional and biologic disease modifying agents commonly used for treatment of rheumatoid arthritis

BackgroundBiologic disease modifying agents (bDMARDs) are an integral part of rheumatoid arthritis treatment guidelines but are associated with significant cost in the US. We present the trends in total spending and unit cost of conventional DMARDs (cDMARDs) as compared to bDMARDs in Medicare program. MethodsWe used the Medicare drug spending data for the year 2012–2017 covering all part B (fee-for-service) and part D drugs. Total spending was calculated by summing spending across various drug formulations and unit drug cost by dividing total spending by number of doses dispensed. We present the 6-year trends in total spending, total beneficiary count and unit costs of each of the commonly used cDMARDs and bDMARDs. ResultsBetween 2012 and 2017, the total spending on the cDMARDs increased 5-folds from $98 million to $579 million; this was fraction of total spending on bDMARDs which increased from $4.3 to $10.0 billion. This increase was driven largely by unit costs of drug rather than number of beneficiaries. There was a 6-fold increase in the unit cost of generic hydroxychloroquine followed by methotrexate and leflunomide. Amongst bDMARDs, adalimumab and etanercept unit cost increased by 2-folds. The increase was less pronounced for office-administered products. ConclusionsDespite the availability of several generic cDMARDs over decades, there were steep increases in the unit cost of these agents to “keep pace” with the increases in bDMARDs. As the number of elderly rheumatoid arthritis patients increases, policy interventions might be required to reduce the spending on both biologics and conventional DMARDs.

Clinical effectiveness of iguratimod based on real-world data of patients with rheumatoid arthritis.

Iguratimod (IGU) is a conventional synthetic disease-modifying drug that has been approved based on its additive effects with methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). The objective of the study is to establish the effectiveness of IGU with versus IGU without MTX irrespective of whether MTX is well tolerated or not by the patients. Disease activity scores in 177 RA patients treated using IGU were retrospectively evaluated at baseline and after 4, 12, and 24weeks, and adverse events (AEs) were noted. IGU reduced the disease activity parameters, disease activity score (DAS)-ESR, DAS-CRP, the simplified disease activity index (SDAI), and clinical disease activity index (CDAI) in the concomitant MTX and non-MTX, female and male, and young and elderly patient groups after 24weeks. Multivariate analysis demonstrated that IGU was more effective with concomitant MTX and in elderly and male patients. Severe AEs were observed only in the elderly group: two cases of pneumonia, 1 of pneumocystis pneumonia, 1 of heart failure, and 1 of salivary gland adenoma. IGU is effective for RA, especially with concomitant MTX, and in elderly and male patients. Key Points • Iguratimod is effective for RA, especially with concomitant MTX, and in elderly and male patients. • Since all serious adverse events were in the elderly group in this study, sufficient monitoring for adverse events, especially for elderly RA patients, is needed during iguratimod therapy.

THU0166 HOW EFFECTIVE AND SAFE ARE BIOLOGIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS IN ELDERLY AND VERY ELDERLY PATIENTS WITH RHEUMATOID ARTHRITIS?

Background: The proportion of elderly patients is increasing in the rheumatoid arthritis (RA) population. However, data on drug effectiveness and safety in these patients is scarce. Objectives: To assess effectiveness and safety of biologic Disease-Modifying Antirheumatic Drugs (bDMARD) in elderly and very elderly RA patients. Methods: Prospective cohort-study of RA patients registered at Reuma.pt starting a 1st bDMARD. Treatment persistence, EULAR response at 6 and 12 months, and adverse events (AE) were compared between adults ( Results: 2401 patients were included, of which 379 were elderly and 83 very elderly. Elderly and very elderly had higher disease activity at baseline and more comorbidities. Elderly patients started bDMARD later in the course of RA (table 1). Crude and adjusted bDMARD treatment persistence was similar in the 3 groups (p=0.07, Graph). At 6/12 months, EULAR response was achieved by 81.6%/83.3%, 75.2%/68.5% and 82.6%/84.2% of adults, elderly and very elderly, respectively (table 2). Except for a lower response rate at 12 months in the elderly group, the EULAR response was comparable in the 3 groups. The same results were observed after adjustment for baseline characteristics, namely the chance of achieving EULAR response was not different in adults and very elderly (OR 0.78, 95% CI 0.19 to 3.2). Also, the variation of DAS, CDAI and SDAI at 6 months and 12 months were comparable in the 3 groups. AE were reported in 21%/22.5%/22.9% of adult/elderly/very elderly patients, respectively. The rate of AE per 100 patient-years was lower in adults when compared to elderly and very elderly (6.4, 13.5 and 14.7, respectively) (table 2). Also the rate of severe AE (SAE) was higher in very elderly (4.29 per 100 patient-years) when comparing to adults and elderly (1.03 and 1.94 respectively). Conclusion: The persistence on 1st bDMARD was similar in adults, elderly and very elderly RA patients. Though older patients have more comorbidities and more active disease at baseline, treatment with biologics was effective and with an acceptable safety profile. However, it is important to take into account the higher risk of AE and SAE in older patients. In conclusion, this study supports the use of bDMARD treatment in elderly and very elderly RA patients. Graph – Persistence in bDMARD Disclosure of Interests: Raquel Freitas: None declared, Nathalie Madeira: None declared, Bruno Miguel Fernandes: None declared, Flavio Costa: None declared, Mariana Santiago: None declared, Agna Neto: None declared, Soraia Azevedo: None declared, Joao Madruga Dias: None declared, Maura Couto: None declared, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Luis Cunha Miranda: None declared, Joaquim Polido-Pereira: None declared, Joao Eurico Fonseca: None declared, Maria Jose Santos Speakers bureau: Novartis and Pfizer

Incident diabetes associated with hydroxychloroquine, methotrexate, biologics and glucocorticoids in rheumatoid arthritis: A systematic review and meta-analysis

ObjectivesTo evaluate the impact of disease-modifying antirheumatic drugs on the risk of developing diabetes in rheumatoid arthritis (RA) patients without diabetes. MethodsElectronic database searches of PubMed, EMBASE and Cochrane Library plus a hand search of conference proceedings were performed from inception to October 2019. The studies assessing the association between diabetes and antirheumatic agents in RA patients in cohort or case-control design were included. Data were pooled using fixed-effects or random-effects meta-analysis according to I2 and pooled hazard ratios (HRs), and 95% confidence intervals (CIs) were used as summary statistic. ResultsA total of 15 studies involving 552,019 patients with RA (11 for hydroxychloroquine, 7 for methotrexate, 6 for tumor necrosis factor inhibitors [TNFi], and 8 for glucocorticoids) were included. In pooled analysis, a reduced risk of diabetes was reported with hydroxychloroquine (meta-HR 0.61, 95% CI 0.56–0.66), methotrexate (meta-HR 0.81, 95% CI 0.75–0.87), TNFi (meta-HR 0.63, 95% CI 0.55–0.71), while glucocorticoids was associated with an increased risk of developing diabetes in a dose-dependent manner (Any dose: meta-HR 1.46, 95% CI 1.39–1.53; <10 mg/day prednisolone or equivalent: meta-HR 1.30, 95% CI 1.13–1.51; ≥10 mg/day prednisolone or equivalent: meta-HR 2.25, 95% CI 1.88–2.70). ConclusionsHydroxychloroquine, methotrexate and TNFi were associated with decreased risk of diabetes, and glucocorticoids with increased risk in RA patients. These important findings may aid clinical decision-making in the management of RA. Large, prospective, well-designed studies are needed in the RA patients with high-risk diabetes.

Rheumatoid arthritis in the elderly: Characteristics and treatment considerations.

The elderly rheumatoid arthritis (RA) population consists of both elderly-onset RA that manifests after the age of 60 and individuals diagnosed with RA early in life who age naturally to become members of this group. The elderly RA population is expanding due to both increased life expectancy and an increased incidence of elderly onset RA. Elderly onset RA seems to have a characteristic clinical pattern and perhaps biological profile different to that of early onset RA. The management of RA in elderly patients can be challenging, as robust treat-to-target approaches must be balanced against the adverse events due to increased comorbidities in old age. This produces a tendency to prefer less aggressive treatment in elderly RA patients in clinical practice. Despite the concerns about adverse events, there is limited evidence on the best way to approach RA in this population, as elderly patients are often not well presented in the clinical trials. Herein, we review the literature to assess the efficacy and safety of RA therapies in this age group. We then suggest a tailored approach that can be adopted in clinical practice, based on the disease severity and risk profiles of elderly RA patients.

高齢関節リウマチ患者へのチーム医療の試み～高齢者総合的機能評価簡易版（CGA7）の有効性～

高齢関節リウマチ患者へのチーム医療の試み～高齢者総合的機能評価簡易版（CGA7）の有効性～

Assessment of renal involvement in an Iraqi cohort of rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is an autoimmune chronic systemic inflammatory disease involves synovial joints but may involve extra-articular organ as well. Objectives: to determine the prevalence of indicators of renal involvement in patients with RA with implications of impact of related drugs on the kidney. Materials and Methods: This cross-sectional study was conducted from May 1, 2019, to November 1, 2019, in the Outpatient Rheumatology Clinic of Hawler teaching hospital, Erbil, Iraq. One hundred and seventy-six patients with seropositive RA were enrolled, other 13 were dropped because of missing data. Participant's characteristics and data regarding drug history were collected. Body mass index (BMI), erythrocyte sedimentation rate (ESR), and serum creatinine were measured; renal function was assessed from the estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula. Urine examined for proteinuria, microscopic hematuria, and noninfectious leucocyturia. When eGFR 0.5). Conclusions: Renal disorder is common in RA patients. Regular monitoring of renal involvement by using eGFR and urinary dipstick is crucial, especially in the elderly obese RA patients with a long duration of the disease and proteinuria. Early identification of renal disease can facilitate the early intervention and achieve the better management of RA patients.

Clinical Characteristics of Frailty in Japanese Rheumatoid Arthritis Patients

ObjectiveThe relationship between clinical characteristics and frailty was investigated in rheumatoid arthritis (RA) patients >40 years old.MethodsRA patients followed for >1 year were interviewed and diagnosed as frail according to a 5-item frailty score index: (1) weight loss >2 kg within 6 months (WL); (2) slower gait speed (GS); (3) exercise less than once per week (EX); (4) decline in short-term memory (SM); and (5) general fatigue in the past 2 weeks (GF). The relationship between frailty status and background parameters was evaluated.ResultsAmong 739 subjects, frail patients comprised 221, pre-frail patients comprised 203, and robust comprised 315. The most common symptom in the Frailty group was GS, followed by SM, GF, EX, and WL, whereas the most common symptom in the Pre-frailty group was GS followed by SM, GF, WL, and EX. Frailty was significantly correlated with aging. Elderly onset rheumatoid arthritis, disease activity, serum C-reactive protein concentration, degree of joint deformity, activities in daily living (ADL), dementia treated, and glucocorticoid steroid administration demonstrated significant correlations with frailty status, although all factors also demonstrated significant correlation with aging. In addition, the EuroQol score (EQ5D) was significantly correlated with both aging and frailty.ConclusionThe results suggest that a remission state for disease activity, ADL, and dementia is correlated with frailty. The most common and primary symptom is GS. Elderly RA patients require careful attention for symptoms of frailty, which may damage the EQ5D score, specifically, the quality of life for RA patients.

Hand Grip Strength in Elderly Rheumatoid Arthritis Patients

Aim: Previous studies have shown that rheumatoid arthritis and aging are independent risk factors for decreased hand grip strength. However, little is known about how coexisting rheumatoid arthritis would affect the reduced hand grip strength in the elderly population. Therefore, the aims of this study were to compare the hand grip strength of elderly female rheumatoid arthritis patients with controls and to investigate the factors associated with hand grip strength in the patients with rheumatoid arthritis.Material and Methods: This cross-sectional study included 45 elderly women with rheumatoid arthritis and 43 age-matched controls. All subjects were provided with self-reported questionnaires measuring physical disability, anxiety and depression, sleep quality, cognitive impairment, and fatigue severity. Hand grip strength was measured with hand dynamometer. The disease activity was assessed by the Disease Activity Score.Results: There were no significant differences in values of age, body mass index, physical disability, anxiety and depression, sleep quality, cognitive impairment, fatigue severity, and grip strength between the groups. Disease period, physical disability, and disease activity were variables which showed statistically significant negative correlation with grip strength in rheumatoid arthritis patients. In further linear regression analysis, it is found that only long disease duration was associated with decreased grip strength.Conclusion: Rheumatoid arthritis does not seem to significantly affect aging-related muscle strength loss. Disease duration was found to be the only independent factor associated with hand grip strength in elderly rheumatoid arthritis patients.

Validity of adopting a Health Assessment Questionnaire Disability Index less than 0.5 as a target in elderly rheumatoid arthritis patients

The effect of age on the Health Assessment Questionnaire Disability Index (HAQ-DI) scores of rheumatoid arthritis (RA) patients and the validity of adopting HAQ-DI < 0.5 as the target for functional remission and comprehensive disease control (CDC) under a treat-to-target (T2T) treatment strategy were investigated. A total of 441 RA patients with > 3-year treatment under T2T were evaluated. The relationships between the HAQ-DI score at follow-up (HAQ) and 28-joint Disease Activity Score with C-reactive protein, Sharp/van der Heijde Score, age at follow-up, and HAQ-DI at baseline were statistically evaluated with best subset regression analysis in groups separated according to age and the EULAR response. CDC status was evaluated with a chi-square test. The HAQ score significantly correlated with all indices in the group ≥ 65years old (G-O) and in the group with good or moderate EULAR responses (p < 0.01). No significant correlation was observed in the group < 65years old (G-Y) or in the group with no EULAR response. The CDC ratio was not significantly different between the age groups, whereas the HAQ failure ratio was significantly greater in G-O than in G-Y (p < 0.01). No significant difference was found between the EULAR response groups. The HAQ score is influenced by age in patients > 65years. T2T is appropriate for attaining good disease activity control but does not always lead to functional remission in these patients. The HAQ score < 0.5 is not an appropriate target for functional remission according to the CDC criteria for elderly patients.Key Points• ADL in elderly RA patient aged ≥ 65years declines corresponding to his/her aging.• Functional remission for elderly RA patients is not the same as that for young RA patients.• The HAQ score < 0.5 in elderly RA patient is not an appropriate target for CDC.

Drug tolerability and reasons for discontinuation of seven biologics in elderly patients with rheumatoid arthritis -The ANSWER cohort study.

BackgroundThe aim of this study is to evaluate the retention rates and reasons for discontinuation for seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of elderly patients (65 years of age or older) with rheumatoid arthritis (RA).MethodsThis multi-center, retrospective study assessed 1,098 treatment courses of 661 patients with bDMARDs from 2009 to 2018 (females, 80.7%; baseline age, 71.7 years; disease duration 10.5 years; rheumatoid factor positivity 81.3%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate, 4.6; concomitant prednisolone dose 2.8 mg/day (45.6%) and methotrexate dose 4.4 mg/week (56.4%); and 60.2% patients were bio-naïve). Treatment courses included abatacept (ABT; n = 272), tocilizumab (TCZ; n = 234), etanercept (ETN; n = 184), golimumab (GLM; n = 159), infliximab (IFX; n = 101), adalimumab (ADA; n = 97), and certolizumab pegol (CZP; n = 51). Drug retention rates and discontinuation reasons were estimated at 36 months using the Kaplan-Meier method and adjusted for potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX, starting date and switched number of bDMARDs) by Cox proportional hazards modeling.ResultsA total of 51.2% of treatment courses were stopped, with 25.1% stopping due to lack of effectiveness, 11.8% due to toxic adverse events, 9.7% due to non-toxic reasons, and 4.6% due to remission. Drug retention rates for each discontinuation reason were as follows; lack of effectiveness [from 55.4% (ETN) to 81.6% (ABT); with significant differences between groups (Cox P<0.001)], toxic adverse events [from 79.3% (IFX) to 95.4% (ABT), Cox P = 0.043], and remission [from 94.2% (TCZ) to 100.0% (CZP), Cox P = 0.58]. Finally, overall retention rates excluding non-toxic reasons and remission for discontinuation ranged from 50.0% (ETN) to 78.1% (ABT) (Cox P<0.001).ConclusionsABT showed lowest discontinuation rate by lack of effectiveness and by toxic adverse events, which lead to highest overall retention rates (excluding non-toxic reasons and remission) among seven bDMARDs in adjusted model of elderly RA patients.