Control Of Rheumatoid Arthritis Disease Activity Research Articles

A study of carotid intima media thickness in patients with rheumatoid arthritis and its correlation with acute phase reactants and disease activity

Introduction: There is increased risk of cardiovascular morbidity and mortality in patients of rheumatoid arthritis (RA) due to accelerated atherosclerosis. In this study we measured Carotid artery intima media thickness (CIMT) as a surrogate marker for subclinical atherosclerosis in RA patients without pre-existing cardiovascular disease. This study also analyzed the correlation between CIMT, disease duration, Simplified Disease Activity Index (SDAI) and acute phase reactants. Methods: A cross-sectional study was conducted on 90 patients divided into two groups of 45 patients of RA and another 45 control subjects. Subjects with RA and age and sex matched healthy controls were included in the study without pre-existing CV risk factors. Complete clinical evaluation, hematological and biochemical profile done. ESR, CRP and platelet count were used as markers of acute phase reactants. All the RA patients included in the study were evaluated for their disease activity using Simplified Disease Activity Index (SDAI). All the subjects including the controls evaluated for carotid intima media thickness by using carotid ultrasonography. CIMT measured in common carotid artery bilaterally by examining throughout common carotid artery up to 2 cm proximal to bifurcation. CIMT measurement taken at the site of greatest thickness. All measurements taken in diastole, measured in phase when lumen diameter is at its smallest and IMT at its largest. Mean value of 6 readings (3 from each side) taken as final CIMT for evaluation. B mode (linear probe) USG was used to determine carotid IMT. Results: 45 cases and similar control subjects included in the study with mean age (SD) as 45.07 (14.81) years. We found female preponderance with 37 females out of 45 cases. Mean (SD) disease duration in male subjects was 5.38(2.40) years while in females was 5.09 (2.78) years. CRP was found to be significantly increased in cases group with mean (SD) of 5.75(8.85) mg/dl. ESR significantly raised to 35.22(13.55) mm/hour in cases group compared to control group where it was 16.16(5.71) mm/hr. Mean (SD) platelets (x10³/mm³) were 229.24(69.80) in cases while controls had 290.33(83.85), so platelets correlation with disease could not be established. CIMT was significantly raised in cases group. Mean (SD) CIMT in cases was 0.95(1.06) mm whereas in control group it was 0.60(0.16) mm with p value of 0.002. Moderate positive correlation was found between CIMT (mm) and SDAI and this correlation was statistically significant with p=0.001. For every 1 unit increase in CIMT, the SDAI increases by 2.92 units. A strong positive correlation between CIMT (mm) and Disease Duration (Years), and this correlation was statistically significant (rho = 0.9, p = <0.001). For every 1 unit increase in CIMT (mm), the Disease Duration (Years) increases by 1.26 units. Conversely, for every 1 unit increase in Disease Duration (Years), the CIMT (mm) increases by 0.19 units. Conclusion: A strong correlation was observed between CIMT and disease duration in rheumatoid arthritis. Hence, CIMT can be a useful surrogate marker for detecting atherosclerosis in patients with RA. In view of the relation to duration of disease, established RA patients should regularly be screened to identify the evidence of atherosclerosis and manage it earlier. Prevention of cardiovascular disease in RA requires an integrated approach encompassing cardiovascular risk factors screening and management, effective and sustained control of RA disease activity, high index of suspicion and prompt investigation of suspected cardiac disease.

The Impact of Early Optimization of Infliximab Blood Concentrations >1 μg/mL on Therapeutic Effectiveness in Rheumatoid Arthritis

Infliximab is a human-murine chimeric monoclonal IgG antibody against tumor necrosis factor that is used in combination with methotrexate for the treatment of moderate to severe rheumatoid arthritis (RA). The trough concentration of serum infliximab required to control disease activity in RA is ≥1 μg/mL, and we investigated whether this trough concentration can predict the effectiveness of RA treatment. We retrospectively analyzed the cases of 76 patients with RA. The REMICHECK Q® (REMIQ) is a kit that can check for serum infliximab concentrations. Infliximab concentrations >1 μg/mL at 14 weeks after an initial infliximab induction is considered REMIQ-positive, otherwise considered REMIQ-negative. Here, we determined the retention rates and investigated the clinical and serologic features of REMIQ-positive and REMIQ-negative patients. At 14 weeks, significantly more of the REMIQ-positive patients (n = 46) were responders compared to the non-responders (n = 30). The retention rate at 54 weeks was also significantly higher in the REMIQ-positive group versus the negative group. After 14 weeks, more patients in the REMIQ-negative group were considered inadequate responders, and their infliximab doses were escalated. At baseline, the REMIQ-positive group had significantly lower C-reactive protein (CRP) levels compared to the negative group. Cox regression analysis with multiple variables showed that the positivity of REMIQ (hazard ratio [HR] 2.10 and 95% confidence interval [CI]: 1.55-5.71) at baseline was associated with the achievement of low disease activity. The positivities of rheumatoid factor and anti-CCP antibody at baseline were associated with the achievement of remission with infliximab treatment (HR 0.44, 95% CI: 0.09-0.82 and HR 0.35, 95% CI: 0.04-0.48, respectively). The results of this study suggest that the control of RA disease activity may be facilitated by using the REMIQ kit at 14 weeks to check whether it is necessary to increase a patient's infliximab dose to ensure a therapeutic blood concentration that will help the patient achieve low disease activity.

Locomotive syndrome in rheumatoid arthritis patients during the COVID-19 pandemic.

This study aimed to longitudinally evaluate the development of locomotive syndrome (LS) in rheumatoid arthritis (RA) patients during the COVID-19 pandemic using the 25-question Geriatric Locomotive Function Scale (GLFS-25). Subjects were 286 RA patients (female, 70.6%; mean age, 64.2 years) who had GLFS-25 and Clinical Disease Activity Index (CDAI) data available for a 1-year period during the COVID-19 pandemic and who did not have LS at baseline. Associations between subject characteristics and development of LS were determined using logistic regression analysis. Among the 286 patients, 38 (13.3%, LS group) developed LS at 1 year after baseline. In the LS group, scores of the GLFS-25 categories "GLFS-5" and "Social activities" were significantly increased at 1 year relative to baseline. GLFS-5 is a quick 5-item version of the GLFS-25, including questions regarding the difficulty of going up and down stairs, walking briskly, distance able to walk without rest, difficulty carrying objects weighing 2 kg, and ability to carry out load-bearing tasks and housework. A significant correlation was also observed between changes in "Social activities" and that of "GLFS-5." Multivariable logistic regression analysis revealed that the development of LS was significantly associated with BMI (OR: 1.11 [95% confidence interval (CI): 1.00-1.22]) and CDAI (OR: 1.08 [95%CI: 1.00-1.16]) at baseline. Adequate exercise and tight control of RA disease activity are important for preventing the development of LS in view of restrictions on going out imposed during the COVID-19 pandemic. GLFS-5 is useful for evaluating the physical function of RA patients.

Risk factors for low back pain increase in rheumatoid arthritis: Analysis of a 7-year follow-up study.

Several studies have demonstrated that low back pain (LBP) is related to disease activity in patients with rheumatoid arthritis (RA). However, there is no longitudinal research. This study aimed to determine the impacts and risk factors for LBP increase in RA in a longitudinal cohort study. The study evaluated 113 patients with RA who completed the secondary survey. LBP increase was defined as ≥1 standard deviation of mean change in visual analogue scale (VAS) between the baseline and secondary surveys. The impacts of LBP increase on quality of life (QOL) and psychological status were evaluated. Risk factors were assessed among patient demographic characteristics and radiological changes. Mean change in VAS for LBP was -0.8 ± 30.4 mm during a mean 7-year follow-up. LBP increase was defined as ≥30-mm increase in VAS for LBP. Patients with LBP increase had significantly lower QOL and worse mental status than patients without it. Poor control of RA was identified as an independent risk factor for LBP increase (odds ratio, 9.82, p = .001). Patients with poor control of RA were likely to experience LBP increase in the long term. Control of RA disease activity is important for control of LBP, QOL, and mental status.

Disease activity affects the recurrent deformities of the lesser toes after resection arthroplasty for rheumatoid forefoot deformity

Objectives The purpose of this study was to clarify the effect of disease activity on recurrent deformities after resection arthroplasty for forefoot deformities in patients with rheumatoid arthritis (RA). Methods This study included 83 feet in 58 patients with RA who underwent resection arthroplasty of all metatarsal heads, with a minimum follow-up of 2 years. The patients’ demographic characteristics, preoperative radiographic findings, and RA disease activity evaluated using the 28-joint disease activity score based on the erythrocyte sedimentation rate (determined preoperatively and at the final follow-up) were compared between feet with and without postoperative recurrent deformities of the toes. Recurrent deformities were assessed separately for the hallux and lesser toes. Results Recurrence in the hallux and lesser toes occurred in 23 feet (27.7%) and 13 feet (15.7%), respectively. With respect to recurrent hallux deformity, only the preoperative severity of hallux deformity was associated with recurrence. On the other hand, postoperative deformity of the lesser toes was positively associated with disease activity alone and not with other preoperative factors. Conclusion Postoperative control of RA disease activity was associated with recurrent deformity of the lesser toes but not that of the hallux after resection arthroplasty of all metatarsals for rheumatoid forefoot deformities.

Relationship between disease activity of rheumatoid arthritis and development of locomotive syndrome: A five-year longitudinal cohort study

Objective This study aimed to longitudinally evaluate the association between rheumatoid arthritis (RA) and locomotive syndrome (LS) in RA patients using the 25-question Geriatric Locomotive Function Scale (GLFS-25). Methods Subjects were 58 RA patients (female, 48 (82.8%); mean age, 60.9 ± 10.9 years) who had GLFS-25 scores available for five consecutive years and who did not have LS at baseline (i.e. GLFS-25 < 16 points). Associations between DAS28-CRP and the development of LS were determined using linear regression analysis and receiver operating characteristic (ROC) curve analysis. Results Subjects were divided into the LS group (n = 15, GLFS-25 ≥ 16 points) and non-LS group (n = 43, GLFS-25 < 16 points) based on GLFS-25 scores at the 5th year of the study period. In the LS group, DAS28-CRP worsened every year. The linear regression model adjusted for age and sex revealed that ΔGLFS-25 increased by 3.80 (95% confidence interval: 1.81–5.79) each time ΔDAS28-CRP increased by 1 (p<.001). Among patients in remission (DAS28-CRP < 2.3), 13.5% had LS. ROC curve analysis yielded a five-year mean DAS28-CRP of 1.99 (sensitivity, 86.7%; specificity, 62.8%) as the cut-off point for the development of LS. Conclusion Tight control of RA disease activity for deeper remission may be needed to prevent the development of LS.

Chronic Opioid Use in Rheumatoid Arthritis: Prevalence and Predictors.

The opioid epidemic is a major public health concern. However, little is known about opioid use among rheumatoid arthritis (RA) patients. We undertook this study to examine trends in chronic opioid use in RA patients in 2002-2015 and to identify clinical predictors. RA patients were identified from the Corrona registry. Opioid use was ascertained from surveys obtained at clinical visits as often as every 3 months. Chronic opioid use was defined as any opioid use reported during ≥2 consecutive study visits. Annual prevalence of chronic opioid use was calculated using data from 33,739 RA patients with information on opioid use from ≥2 visits. Among the 26,288 individuals who were not taking opioids at baseline, Cox proportional hazards models identified associations between patient characteristics and incident chronic opioid use. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated. Chronic opioid use increased from 7.4% in 2002 to 16.9% in 2015. Severe pain (HR 2.53 [95% CI 2.19-2.92]) and antidepressant use (HR 1.79 [95% CI 1.64-1.92]) were associated with an increased risk of chronic opioid use. High disease activity (HR 1.55 [95% CI 1.30-1.84]) and a high level of disability (HR 1.45 [95% CI 1.27-1.65]) were also associated with chronic opioid use, whereas Asian ethnicity (HR 0.49 [95% CI 0.36-0.68]) was associated with a decreased risk of chronic opioid use. Among RA patients, chronic opioid use doubled from 2002 to 2015. Pain and antidepressant use were the strongest predictors of chronic opioid use. To curb the rise in chronic opioid use, strategies for stringent control of RA disease activity and management of pain and depression should be research priorities.

Ischemic heart disease and rheumatoid arthritis: Do inflammatory cytokines have a role?

BackgroundThe increase in Rheumatoid arthritis (RA) associated mortality is predominantly due to accelerated coronary artery and cerebrovascular atherosclerosis with increased risk of ischemic heart disease about 50% in RA patients compared to controls. ObjectiveTo study the pathogenesis of ischemic heart disease in RA, role of inflammatory cytokine interplay, disease activity and rheumatoid factor positivity. MethodsEighty RA patients and 44 healthy controls were included. All subjects were younger than 45years for females and 55years for males with exclusion of all traditional risk factors for atherosclerosis. Interleukin (IL) 1, 6 and 18 were assessed in all subjects. RA patients fulfilled ACR/EULAR 2010 criteria and were subjected to Dobutaminestress-echocardiography, diseases activity assessed by DAS-28, X-ray hands for Larsen score and function assessment by HAQ. ResultsRA patients had significantly higher serum IL 1, 6 and 18 than controls (p=0.00 in all). Thirty four (42.5%) patients had hypertensive reaction on Dobutamine-stress-echocardiography, four of them had ischemic change, and 46 (57.5%) had normal reaction. All patients with hypertensive reaction had positive RF (p=0.00), 10 had DAS-28>5.1, 20 had DAS-28 from 3.2 to5.1 and 4 were in remission (p=0.001). CRP was higher in patients with hypertensive reaction (p=0.003) while serum levels of IL1, 6 and 18 showed no significant difference. In all patients, serum levels of IL1, 6 and 18 showed significant positive correlation with VAS, HAQ and DAS-28 (p<0.001 in all). Only IL18 showed significant positive correlation with X-ray score in all patients. ConclusionDisease activity and RF positivity play an important risk factor for ischemic heart disease in RA. Serum levels of IL1, 6 and 18 did not help much in detecting patients at risk of ischemic heart disease. Better control of RA disease activity with early remission helps in preventing cardiac complications. More studies on larger number of patients are needed for better understanding of mechanism of ischemic heart disease in RA.

Appearance of hindfoot valgus deformity and recurrence of hallux valgus in the very early period after hallux valgus surgery in a poorly controlled rheumatoid arthritis case: A case report

Control of rheumatoid arthritis (RA) disease activity is an important factor related to the development of hallux valgus (HV) deformity. Furthermore, if valgus hindfoot remains and/or appears after HV surgery, the affected foot is at risk of recurrence of HV deformity. We experienced a case suggesting the possibility that hindfoot valgus deformity appeared after HV surgery because of poor control of RA disease activity, and the HV deformity recurred in the very early period after surgery.

Rheumatoid Arthritis Pharmacotherapies: Do They Have Anti-Atherosclerotic Activity?

Rheumatoid arthritis (RA) is associated with a heightened risk of cardiovascular disease (CVD) events, presumably related to a greater burden of atherosclerosis, as well as atherosclerotic plaques that tend to be inflamed and rupture prone. Many of the inflammatory pathways underlying the pathobiology of RA are also recognized contributors to atherosclerosis. Immunomodulation is the mainstay for RA therapy, and a variety of biologic and non-biologic pharmacotherapies are used either singly or in combination to control articular and systemic inflammation and prevent joint destruction. Almost all of these agents have theoretical potential to favorably affect atherogenesis and atherothrombosis, but mechanisms by which they exert effects have been incompletely studied, to date. However, whether clinical control of RA disease activity is associated with a reduction in CVD events regardless of agent used or whether the potency of anti-atherogenic effects varies between disease-modifying anti-rheumatic drugs (DMARDs) is an area of current interest in RA research. More broadly, RA immunotherapies are currently being tested in high-CVD-risk patients in proof-of-concept clinical trials that could alter the paradigm for CVD treatment and prevention in the general population. In this review, we will summarize the current evidence ascribing atheroprotective effects to RA pharmacotherapies.

Identification of Independent Predictive Factors for Atherosclerosis in Rheumatoid Arthritis: Based on KARRA Cohort Study

Objective. This study sought to investigate independent predictive factors for subclinical atherosclerosis in Korean patients with rheumatoid arthritis (RA). Methods. We used high-resolution B-mode ultrasonography to measure the carotid artery intima-media thickness (IMT) and carotid plaque in 367 patients with RA. Detailed information on the demographic characteristics, cardiovascular (CV) risk factors, and RA disease characteristics were collected on all subjects. The relationship of the carotid artery IMT and carotid plaque to relevant clinical and laboratory variables were examined. Results. Old age and male sex had the most significant association with increased IMT and presence of plaque than other factors. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and mKHAQ (Korean version of modified health assessment questionnaire) were significantly associated with both increased IMT and presence of plaque after univariate analysis adjusting for age and sex. A multivariable logistic regression analysis revealed that ESR and TJC68 were independent factors associated with the presence of plaque (p<0.001 and p=0.019, respectively). There was a significant linear correlation between the number of plaques and ESR (p<0.001 and R =0.07). Conclusion. Our results indicated that markers of systemic inflammation contributed significantly to subclinical atherosclerosis in patients with RA. We emphasize the need for aggressive control of RA disease activity in patients who persistently demonstrate highly elevated ESR levels.

Efficacy of total joint arthroplasty in patients with established rheumatoid arthritis: improved longitudinal effects on disease activity but not on health-related quality of life

Though excellent clinical results have been reported for total joint arthroplasty (TJA) in rheumatoid arthritis (RA) patients, the longitudinal effects of TJA on pain, physical function, and health-related quality of life in RA patients remain unknown. This study aimed to assess changes in disease activity and health-related quality of life after TJA in patients with established RA. We analyzed the effect of total knee arthroplasty (TKA) and total hip arthroplasty (THA) on RA disease activity in an observational cohort of RA patients. Of the registered RA patients, 333 TKA and 77 THA patients were followed for 5 years after surgery. RA disease activity and health-related quality of life were measured using the Disease Activity Score 28 (DAS28) and a Japanese version of the Stanford health assessment questionnaire (J-HAQ). The mean DAS28 in TKA patients decreased from 4.66 (preoperatively) to 4.02 (3 years postoperatively) and to 3.94 (5 years postoperatively); the mean DAS28 in THA patients decreased from 4.41 (preoperatively) to 3.99 (3 years postoperatively) and to 3.92 (5 years postoperatively). The mean J-HAQ for TKA remained essentially unchanged, ranging from 1.48 (preoperatively) to 1.45 (3 years postoperatively) and to 1.47 (5 years postoperatively); the mean J-HAQ for THA also remained unchanged, ranging from 1.74 (preoperatively) to 1.74 (3 years postoperatively) and to 1.73 (5 years postoperatively). Of the total J-HAQ score, the lower limb score improved while the upper limb score worsened. Although TKA and THA improve clinical outcomes in damaged knees and hips and have a positive secondary systemic effect on RA disease activity, they have not had a continuously good effect on the measures of health-related quality of life. We conclude that tight control of RA disease activity is indicated for those patients with TKA and/or THA.

Efficacy of total joint arthroplasty in patients with established rheumatoid arthritis: improved longitudinal effects on disease activity but not on health-related quality of life

Though excellent clinical results have been reported for total joint arthroplasty (TJA) in rheumatoid arthritis (RA) patients, the longitudinal effects of TJA on pain, physical function, and health-related quality of life in RA patients remain unknown. This study aimed to assess changes in disease activity and health-related quality of life after TJA in patients with established RA. We analyzed the effect of total knee arthroplasty (TKA) and total hip arthroplasty (THA) on RA disease activity in an observational cohort of RA patients. Of the registered RA patients, 333 TKA and 77 THA patients were followed for 5years after surgery. RA disease activity and health-related quality of life were measured using the Disease Activity Score 28 (DAS28) and a Japanese version of the Stanford health assessment questionnaire (J-HAQ). The mean DAS28 in TKA patients decreased from 4.66 (preoperatively) to 4.02 (3years postoperatively) and to 3.94 (5years postoperatively); the mean DAS28 in THA patients decreased from 4.41 (preoperatively) to 3.99 (3years postoperatively) and to 3.92 (5years postoperatively). The mean J-HAQ for TKA remained essentially unchanged, ranging from 1.48 (preoperatively) to 1.45 (3years postoperatively) and to 1.47 (5years postoperatively); the mean J-HAQ for THA also remained unchanged, ranging from 1.74 (preoperatively) to 1.74 (3years postoperatively) and to 1.73 (5years postoperatively). Of the total J-HAQ score, the lower limb score improved while the upper limb score worsened. Although TKA and THA improve clinical outcomes in damaged knees and hips and have a positive secondary systemic effect on RA disease activity, they have not had a continuously good effect on the measures of health-related quality of life. We conclude that tight control of RA disease activity is indicated for those patients with TKA and/or THA.

Rheumatoid arthritis and heart disease: the chicken and the egg?

Rheumatoid arthritis and heart disease: the chicken and the egg?

Targeting cardiovascular risk in rheumatoid arthritis: a dual role for statins

Rheumatoid arthritis (RA) is a prototypical immune-mediated inflammatory disease that is characterized by increased cardiovascular morbidity and mortality, independent of the traditional risk factors for cardiovascular disease. The chronic inflammatory state--a hallmark of RA--is considered to be a driving force for accelerated atherogenesis. Consequently, aggressive control of RA disease activity is thought to be instrumental for cardiovascular risk reduction. Currently, statin-mediated reduction of LDL-cholesterol levels is considered to be the cornerstone of cardiovascular disease prevention. In addition to their lipid-lowering capabilities, statins exert immunomodulatory effects, which could be of dual benefit in the treatment of RA. Guidelines on the reduction of cardiovascular risk in patients with RA are lacking, however, largely owing to the absence of data from randomized controlled trials. This Review focuses on the pathophysiology of cardiovascular events in RA, as well as the need to adjust cardiovascular risk engines to better-accommodate the impact of chronic inflammatory disease over and above the established risk factors to predict cardiovascular risk in patients with RA.

Statin therapy for targeting cardiovascular risk in rheumatoid arthritis

Rheumatoid arthritis (RA), a prototypical immune-mediated inflammatory disease, is now definitely recognized to increase cardiovascular morbidity and mortality, irrespective of established classical risk factors. The chronic inflammatory state, a hallmark of RA, is increasingly considered to be a driving force for accelerated atherogenesis. Consequently, aggressive control of RA disease activity has been suggested to be instrumental for cardiovascular risk reduction. Currently, statins are the cornerstone of cardiovascular risk-reducing strategies. Apart from their lipid-lowering capacity, statins also exert immune-modulatory effects, which therefore may be of dual benefit in RA patients. Yet guidelines for optimal cardiovascular risk reduction in patients with RA are lacking, largely owing to the absence of randomized, clinical trial data. In this review, we focus on the pathophysiology and observational evidence of cardiovascular risk in RA, as well as the need to adjust currently employed cardiovascula...