Development of a health care utilisation data-based index for rheumatoid arthritis severity: a preliminary study

Introduction

Health care utilisation ('claims') databases contain information about millions of patients and are an important source of information for a variety of study types. However, they typically do not contain information about disease severity. The goal of the present study was to develop a health care claims index for rheumatoid arthritis (RA) severity using a previously developed medical records-based index for RA severity (RA medical records-based index of severity [RARBIS]).

Methods

The study population consisted of 120 patients from the Veteran's Administration (VA) Health System. We previously demonstrated the construct validity of the RARBIS and established its convergent validity with the Disease Activity Score (DAS28). Potential claims-based indicators were entered into a linear regression model as independent variables and the RARBIS as the dependent variable. The claims-based index for RA severity (CIRAS) was created using the coefficients from models with the highest coefficient of determination (R²) values selected by automated modelling procedures. To compare our claims-based index with our medical records-based index, we examined the correlation between the CIRAS and the RARBIS using Spearman non-parametric tests.

Results

The forward selection models yielded the highest model R² for both the RARBIS with medications (R² = 0.31) and the RARBIS without medications (R² = 0.26). Components of the CIRAS included tests for inflammatory markers, number of chemistry panels and platelet counts ordered, rheumatoid factor, the number of rehabilitation and rheumatology visits, and Felty's syndrome diagnosis. The CIRAS demonstrated moderate correlations with the RARBIS with medication and the RARBIS without medication sub-scales.

Conclusion

We developed the CIRAS that showed moderate correlations with a previously validated records-based index of severity. The CIRAS may serve as a potentially important tool in adjusting for RA severity in pharmacoepidemiology studies of RA treatment and complications using health care utilisation data.     

An external validation study reporting poor correlation between the claims-based index for rheumatoid arthritis severity and the disease activity score

IntroductionWe conducted an external validation study to examine the correlation of a previously published claims-based index for rheumatoid arthritis severity (CIRAS) with disease activity score in 28 joints calculated by using C-reactive protein (DAS28-CRP) and the multi-dimensional health assessment questionnaire (MD-HAQ) physical function score.MethodsPatients enrolled in the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) and Medicare were identified and their data from these two sources were linked. For each patient, DAS28-CRP measurement and MD-HAQ physical function scores were extracted from BRASS, and CIRAS was calculated from Medicare claims for the period of 365 days prior to the DAS28-CRP measurement. Pearson correlation coefficient between CIRAS and DAS28-CRP as well as MD-HAQ physical function scores were calculated. Furthermore, we considered several additional pharmacy and medical claims-derived variables as predictors for DAS28-CRP in a multivariable linear regression model in order to assess improvement in the performance of the original CIRAS algorithm.ResultsIn total, 315 patients with enrollment in both BRASS and Medicare were included in this study. The majority (81%) of the cohort was female, and the mean age was 70 years. The correlation between CIRAS and DAS28-CRP was low (Pearson correlation coefficient = 0.07, P = 0.24). The correlation between the calculated CIRAS and MD-HAQ physical function scores was also found to be low (Pearson correlation coefficient = 0.08, P = 0.17). The linear regression model containing additional claims-derived variables yielded model R² of 0.23, suggesting limited ability of this model to explain variation in DAS28-CRP.ConclusionsIn a cohort of Medicare-enrolled patients with established RA, CIRAS showed low correlation with DAS28-CRP as well as MD-HAQ physical function scores. Claims-based algorithms for disease activity should be rigorously tested in distinct populations in order to establish their generalizability before widespread adoption.     

Clinical and functional remission: even though biologics are superior to conventional DMARDs overall success rates remain low – results from RABBIT, the German biologics register

We investigated the frequency of remission according to the disease activity score (DAS28) definition, modified American Rheumatology Association (ARA) criteria, and the frequency of an achievement of a functional status above defined thresholds ('functional remission', 'physical independence') in rheumatoid arthritis (RA) patients treated with either biologics or conventional DMARDs. We used the data of a prospective cohort study, the German biologics register RABBIT (German acronym for Rheumatoid Arthritis – Observation of Biologic Therapy) to investigate the outcomes in RA patients with two or more DMARD failures who received new treatment with biologics (BIOL; n = 818) or a conventional DMARD (n = 265). Logistic regression analysis was applied to adjust for differences in baseline risks. Taking risk indicators such as previous DMARD failures or baseline clinical status into account, we found that biologics doubled the chance of remission compared to conventional DMARD therapies (DAS28 remission, adjusted odds ratio (OR) 1.95 (95% confidenece interval (CI) 1.2–3.2)); ARA remission, OR 2.05 (95% CI 1.2–3.5)). High remission rates (DAS28 remission, 30.6%; ARA remission, 16.9%) were observed in BIOL patients with a moderate disease activity (DAS28, 3.2 to 5.1) at the start of treatment. These rates decreased to 8.5% in patients with DAS28 > 6. Sustained remission at 6 and 12 months was achieved in <10% of the patients. Severely disabled patients (≤50% of full function) receiving biologic therapies were significantly more likely to achieve a status indicating physical independence (≥67% of full function) than controls (OR 3.88 (95% CI 1.7–8.8)). 'Functional remission' (≥83% of full function) was more often achieved in BIOL than in controls (OR 2.18 (95% CI 1.04–4.6)). In conclusion, our study shows that biologics increase the chance to achieve clinical remission and a status of functional remission or at least physical independence. However, temporary or even sustained remission remain ambitious aims, which are achieved in a minority of patients only.     

Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score

Introduction  

Frequent assessments of rheumatoid arthritis (RA) disease activity allow timely adaptation of therapy, which is essential in preventing disease progression. However, values of acute phase reactants (APRs) are needed to calculate current composite activity indices, such as the Disease Activity Score (DAS)28, the DAS28-CRP (i.e. the DAS28 using C-reactive protein instead of erythrocyte sedimentation rate) and the Simplified Disease Activity Index (SDAI). We hypothesized that APRs make limited contribution to the SDAI, and that an SDAI-modification eliminating APRs – termed the Clinical Disease Activity Index (CDAI; i.e. the sum of tender and swollen joint counts [28 joints] and patient and physician global assessments [in cm]) – would have comparable validity in clinical cohorts.     

Sustained rheumatoid arthritis remission is uncommon in clinical practice

Introduction

Remission is an important goal of therapy in rheumatoid arthritis (RA), but data on duration of remission are lacking. Our objective was to describe the duration of remission in RA, assessed by different criteria.

Methods

We evaluated patients from the Brigham and Women''s Rheumatoid Arthritis Sequential Study (BRASS) not in remission at baseline with at least 2 years of follow-up. Remission was assessed according to the Disease Activity Score 28-C-reactive protein (DAS28-CRP4), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) scores, and the recently proposed American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria for remission. Analyses were performed by using Kaplan-Meier survival curves.

Results

We identified 871 subjects with ≥2 years of follow-up. Of these subjects, 394 were in remission at one or more time-points and not in remission at baseline, according to at least one of the following criteria: DAS28-CRP < 2.6 (n = 309), DAS28-CRP < 2.3 (n = 275), SDAI (n = 168), CDAI (n = 170), and 2010 ACR/EULAR (n = 158). The median age for the 394 subjects at entrance to BRASS was 56 years; median disease duration was 8 years; 81% were female patients; and 72% were seropositive. Survival analysis performed separately for each remission criterion demonstrated that < 50% of subjects remained in remission 1 year later. Median remission survival time was 1 year. Kaplan-Meier curves of the various remission criteria did not significantly differ (P = 0.29 according to the log-rank test).

Conclusions

This study shows that in clinical practice, a minority of RA patients are in sustained remission.     

A Pilot Study on Zinc Levels in Patients with Rheumatoid Arthritis

The aim of the study was to evaluate zinc levels in three biological compartments (serum, erythrocytes and hair) in patients with rheumatoid arthritis (RA) as compared to healthy individuals. Zinc levels in serum, erythrocytes and hair (in 74 patients with RA and 30 healthy individuals) were assessed by atomic absorption spectroscopy. The mean hair zinc content was significantly lower in RA patients as compared to healthy individuals (p < 0.001). Moreover, a positive correlation was observed in the RA patient group between the erythrocyte zinc levels and the prednisone dose (r _s = 0.48, p < 0.05), and a negative correlation was found in this population between the serum zinc levels and disease duration (r _s = −0.42, p < 0.0006). In conclusion, it seems that hair may be a useful complementary study material for evaluating “zinc status” in rheumatoid arthritis patients.     

A cross-sectional study of pain sensitivity,disease-activity assessment,mental health,and fibromyalgia status in rheumatoid arthritis

IntroductionPain remains the most important problem for people with rheumatoid arthritis (RA). Active inflammatory disease contributes to pain, but pain due to non-inflammatory mechanisms can confound the assessment of disease activity. We hypothesize that augmented pain processing, fibromyalgic features, poorer mental health, and patient-reported 28-joint disease activity score (DAS28) components are associated in RA.MethodsIn total, 50 people with stable, long-standing RA recruited from a rheumatology outpatient clinic were assessed for pain-pressure thresholds (PPTs) at three separate sites (knee, tibia, and sternum), DAS28, fibromyalgia, and mental health status. Multivariable analysis was performed to assess the association between PPT and DAS28 components, DAS28-P (the proportion of DAS28 derived from the patient-reported components of visual analogue score and tender joint count), or fibromyalgia status.ResultsMore-sensitive PPTs at sites over or distant from joints were each associated with greater reported pain, higher patient-reported DAS28 components, and poorer mental health. A high proportion of participants (48%) satisfied classification criteria for fibromyalgia, and fibromyalgia classification or characteristics were each associated with more sensitive PPTs, higher patient-reported DAS28 components, and poorer mental health.ConclusionsWidespread sensitivity to pressure-induced pain, a high prevalence of fibromyalgic features, higher patient-reported DAS28 components, and poorer mental health are all linked in established RA. The increased sensitivity at nonjoint sites (sternum and anterior tibia), as well as over joints, indicates that central mechanisms may contribute to pain sensitivity in RA. The contribution of patient-reported components to high DAS28 should inform decisions on disease-modifying or pain-management approaches in the treatment of RA when inflammation may be well controlled.     

A<Subscript>2A</Subscript> and A<Subscript>3</Subscript> adenosine receptor expression in rheumatoid arthritis: upregulation,inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release

Introduction  

The reduction of the inflammatory status represents one of the most important targets in rheumatoid arthritis (RA). A central role of A_2A and A₃ adenosine receptors (ARs) in mechanisms of inflammation has been reported in different pathologies. The primary aim of this study was to investigate the A_2A and A₃ARs and their involvement in RA progression measured by Disease Activity Score in 28 or 44 joints (DAS28 or DAS).     

No evidence of major effects in several Toll-like receptor gene polymorphisms in rheumatoid arthritis

Introduction  

The objective was to study the potential genetic contribution of Toll-like receptor (TLR) genes in rheumatoid arthritis (RA). TLRs bind to pathogen-associated molecular patterns, and TLR genes influence both proinflammatory cytokine production and autoimmune responses. Host–pathogen interactions are involved in RA physiopathology.     

Metabolic responses to change in disease activity during tumor necrosis factor inhibition in patients with rheumatoid arthritis

Assessment of disease activity in patients with rheumatoid arthritis (RA) is of importance in the evaluation of treatment. The most important measure of disease activity is the Disease Activity Score counted in 28 joints (DAS28). In this study, we evaluated whether metabolic profiling could complement current measures of disease activity. Fifty-six patients, in two separate studies, were followed for two years after commencing anti-TNF therapy. DAS28 was assessed, and metabolic profiles were recorded at defined time points. Correlations between metabolic profile and DAS28 scores were analyzed using multivariate statistics. The metabolic responses to lowering DAS28 scores varied in different patients but could predict DAS28 scores at the individual and subgroup level models. The erythrocyte sedimentation rate (ESR) component in DAS28 was most correlated to the metabolite data, pointing to inflammation as the primary effect driving metabolic profile changes. Patients with RA had differing metabolic response to changes in DAS28 following anti-TNF therapy. This suggests that discovery of new metabolic biomarkers for disease activity will derive from studies at the individual and subgroup level. Increased inflammation, measured as ESR, was the main common effect seen in metabolic profiles from periods associated with high DAS28.     

Association between occupational exposure to mineral oil and rheumatoid arthritis: results from the Swedish EIRA case–control study

The aim of the present study was to investigate the association between exposure to mineral oil and the risk of developing rheumatoid arthritis (RA), and in addition to perform a separate analysis on the major subphenotypes for the disease; namely, rheumatoid factor (RF)-positive RA, RF-negative RA, anticitrulline-positive RA and anticitrulline-negative RA, respectively. A population-based case–control study of incident cases of RA was performed among the population aged 18–70 years in a defined area of Sweden during May 1996–December 2003. A case was defined as an individual from the study base who for the first time received a diagnosis of RA according to the American College of Rheumatology criteria of 1987. Controls were randomly selected from the study base with consideration taken for age, gender and residential area. Cases (n = 1,419) and controls (n = 1,674) answered an extensive questionnaire regarding lifestyle factors and occupational exposures, including different types of mineral oils. Sera from cases and controls were investigated for RF and anticitrulline antibodies.     

Anti-citrullinated antibodies, radiological joint damages and their correlations with disease activity score (DAS28)

Determination of anti-citrullinated peptides (anti-CCP) specificity as a predictor of joint erosive changes, correlation between their serum level and radiological damages as well as disease activity score (DAS28). A trial has been conducted on a 211 patient sample fulfilling ACR criteria for rheumatoid arthritis (RA). There was assigned anti-CCP serum level, disease activity score by the formula for DAS28(3)-CRP and assessed radiological changes degree after Steinbrocker score. In 132 patient (62.559%) the serum anti-CCP concentration was positive for RA. Specificity of the test was 100% and sensitivity 65% (Z = 0.731, p = 0.465). There is a medium intensity correlation between variables representing anti-CCP and Steinbrocker score. Pearson's coefficient was 0.479 and Spearman's rank correlation coefficient was 0.614, i.e. statistically significant (p = 0.000). There is no statistically significant correlation between variables representing anti-CCP and DAS28(3)-CRP Anti-CCP are good RA predictor and their concentration correlate with radiological damages degree.     

Forefoot disease activity in rheumatoid arthritis patients in remission: results of a cohort study

Introduction  

The aim of our study was to investigate the presence of disease activity in the metatarsophalangeal (MTP) joints of the forefoot in rheumatoid arthritis (RA) patients in remission according to the Disease Activity Score based on 28 joints (DAS28) remission criterion.     

A promoter haplotype of the interleukin-18 gene is associated with juvenile idiopathic arthritis in the Japanese population

Recently, we reported that genetic polymorphisms within the human IL18 gene were associated with disease susceptibility to adult-onset Still's disease (AOSD), which is characterized by extraordinarily high serum levels of IL-18. Because high serum IL-18 induction has also been observed in the systemic type of juvenile idiopathic arthritis (JIA), we investigated whether similar genetic skewing is present in this disease. Three haplotypes, S01, S02, and S03, composed of 13 genetic polymorphisms covering two distinct promoter regions, were determined for 33 JIA patients, including 17 with systemic JIA, 10 with polyarthritis, and 6 with oligoarthritis. Haplotypes were also analyzed for 28 AOSD patients, 164 rheumatoid arthritis (RA) patients, 102 patients with collagen diseases, and 173 healthy control subjects. The frequency of individuals carrying a diplotype configuration (a combination of two haplotypes) of S01/S01 was significantly higher in the JIA patients, including all subgroups, than in the healthy controls (P = 0.0045, Fischer exact probability test; odds ratio (OR) = 3.55, 95% confidence interval (CI) = 1.55–8.14). In patients with systemic JIA, its frequency did not differ statistically from that of normal controls. Nevertheless, it is possible that haplotype S01 is associated with the phenotype of high IL-18 production in systemic JIA because the patients carrying S01/S01 showed significantly higher serum IL-18 levels compared with patients with other diplotype configurations (P = 0.017, Mann-Whitney U test). We confirmed that the frequency of the diplotype configuration of S01/S01 was significantly higher in AOSD patients than in healthy control subjects (P = 0.011, OR = 3.45, 95% CI = 1.42–8.36). Furthermore, the RA patients were also more predisposed to have S01/S01 (P = 0.018, OR = 2.00, 95% CI = 1.14–3.50) than the healthy control subjects, whereas the patients with collagen diseases did not. In summary, the diplotype configuration of S01/S01 was associated with susceptibility to JIA as well as AOSD and RA, and linked to significantly higher IL-18 production in systemic JIA. Possession of the diplotype configuration of S01/S01 would be one of the genetic risk factors for susceptibility to arthritis in the Japanese population.     

Plasma concentrations of amino acid and nicotinamide metabolites in rheumatoid arthritis – potential biomarkers of disease activity and drug treatment

This study aimed to evaluate changes in plasma amino acid and nicotinamide metabolites concentrations in rheumatoid arthritis (RA) in a search for potential biomarkers of the disease activity and the effect treatment. Analysis of plasma metabolite patterns with liquid chromatography/mass spectrometry revealed specific changes in RA as well as correlations with clinical parameters. Combined concentration parameter calculated as [aspartic acid]?+?[threonine]?+?[tryptophan]???[histidine]???[phenylalanine] offered the strongest correlation (p?<?0.001) with pain joint count, swollen joint count and DAS 28. Such analysis of amino acid and related metabolite pattern offers potential for diagnosis as well as for monitoring disease progression and therapy in RA.     

Adherence to a treat-to-target strategy in early rheumatoid arthritis: results of the DREAM remission induction cohort

Introduction

Clinical trials have demonstrated that treatment-to-target (T2T) is effective in achieving remission in early rheumatoid arthritis (RA). However, the concept of T2T has not been fully implemented yet and the question is whether a T2T strategy is feasible in daily clinical practice. The objective of the study was to evaluate the adherence to a T2T strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6) in early RA in daily practice. The recommendations regarding T2T included regular assessment of the DAS28 and advice regarding DAS28-driven treatment adjustments.

Methods

A medical chart review was performed among a random sample of 100 RA patients of the DREAM remission induction cohort. At all scheduled visits, it was determined whether the clinical decisions were compliant to the T2T recommendations.

Results

The 100 patients contributed to a total of 1,115 visits. The DAS28 was available in 97.9% (1,092/1,115) of the visits, of which the DAS28 was assessed at a frequency of at least every three months in 88.3% (964/1,092). Adherence to the treatment advice was observed in 69.3% (757/1,092) of the visits. In case of non-adherence when remission was present (19.5%, 108/553), most frequently medication was tapered off or discontinued when it should have been continued (7.2%, 40/553) or treatment was continued when it should have been tapered off or discontinued (6.2%, 34/553). In case of non-adherence when remission was absent (42.1%, 227/539), most frequently medication was not intensified when an intensification step should have been taken (34.9%, 188/539). The main reason for non-adherence was discordance between disease activity status according to the rheumatologist and DAS28.

Conclusions

The recommendations regarding T2T were successfully implemented and high adherence was observed. This demonstrates that a T2T strategy is feasible in RA in daily clinical practice.     

Abatacept with methotrexate versus other biologic agents in treatment of patients with active rheumatoid arthritis despite methotrexate: a network meta-analysis

Introduction  

The goal of this study was to compare the efficacy in terms of Health Assessment Questionnaire change from baseline (HAQ CFB), 50% improvement in American College of Rheumatology criterion (ACR-50) and Disease Activity Score in 28 joints (DAS28) defined remission (< 2.6) between abatacept and other biologic disease modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX-IR).     

Protein,iron, and meat consumption and risk for rheumatoid arthritis: a prospective cohort study

A recent prospective study showed that higher consumption of red meat and total protein was associated with increased risk for inflammatory polyarthritis. We therefore prospectively examined the relationship between diet (in particular, protein, iron, and corresponding food sources) and incident rheumatoid arthritis (RA) among 82,063 women in the Nurses' Health Study. From 1980 to 2002, 546 incident cases of RA were confirmed by a connective tissue disease screening questionnaire and medical record review for American College of Rheumatology criteria for RA. Diet was assessed at baseline in 1980 and five additional times during follow up. We conducted Cox proportional hazards analyses to calculate the rate ratio of RA associated with intakes of protein (total, animal, and vegetable) and iron (total, dietary, from supplements, and heme iron) and their primary food sources, adjusting for age, smoking, body mass index, and reproductive factors. The multivariate models revealed no association between RA and any measure of protein or iron intake. In comparisons of highest with lowest quintiles of intake, the rate ratio for total protein was 1.17 (95% confidence interval 0.89–1.54; P for trend = 0.11) and for total iron it was 1.04 (95% confidence interval 0.77–1.41; P for trend = 0.82). Red meat, poultry, and fish were also not associated with RA risk. We were unable to confirm that there is an association between protein or meat and risk for RA in this large female cohort. Iron was also not associated with RA in this cohort.     

类风湿关节炎患者血脂水平与疾病活动度的相关性研究

目的:观察类风湿关节炎(RA)患者血脂的变化,以及血脂水平与疾病活动度之间的相关性。方法:对71例RA患者和77例正常对照的血脂水平进行回顾性分析,并对RA患者的血脂水平与其疾病活动度进行相关性分析。结果:RA患者的血清总胆固醇(TC)、甘油三酯(TG)水平均高于正常对照组(P0.01),高密度脂蛋白(HDL)水平降低(P0.01)。DAS28评分与TC(r=0.49,P0.01)、TG(r=0.38,P0.01)和LDL(r=0.55,P0.01)呈正相关,与HDL呈负相关(r=-0.57,P0.01),血沉与TC(r=0.26,P=0.03)、TG(r=0.28,P=0.02)呈正相关,C反应蛋白与TC(r=0.65,P0.01)、TG(r=0.30,P=0.01)和LDL(r=0.39,P0.01)均呈正相关。结论:RA患者存在血脂水平异常,且与疾病活动度相关。对血脂进行干预可能改善RA患者的长期预后。