Cohort Of Rheumatoid Arthritis Patients Research Articles

Risk of exacerbation of pulmonary comorbidities in patients with rheumatoid arthritis after initiation of abatacept versus TNF inhibitors: A cohort study

BackgroundBiologic agents may pose a potential risk for exacerbations of pulmonary comorbidities in rheumatoid arthritis (RA) patients. MethodsUsing U.S. Medicare and Truven MarketScan databases, we identified three cohorts of RA patients with interstitial lung disease (ILD), chronic obstructive pulmonary disease (COPD), or asthma who initiated abatacept or a TNF inhibitor (TNFi). The primary outcome was a composite exacerbation of individual pulmonary comorbidities based on inpatient or emergency department (ED) visits due to exacerbation of the given pulmonary comorbidity. To adjust for >60 baseline confounders, we used propensity-score fine stratification (PSS) and weighting. Negative binomial regression model estimated a cohort-specific incidence rate ratio (IRR) and 95% confidence interval (CI) of the primary outcome per database, comparing abatacept versus TNFi. Database-specific IRRs were combined using a random-effects meta-analysis. ResultsWe identified 3,295 ILD, 7,161 COPD, and 5,613 asthma patients with RA who initiated either abatacept or a TNFi. IR of composite exacerbation was high in all three pulmonary cohorts but highest in COPD cohort (3.59-11.80 per 100 person-years in ILD, 20.68-34.97 in COPD, and 4.66-13.78 in asthma). After PSS weighting, the combined IRR (95%CI) in abatacept initiators versus TNFi initiators was 0.44 (0.18-1.09) for ILD exacerbation, 0.91 (0.80-1.03) for COPD exacerbation, and 0.81 (0.54-1.22) for asthma exacerbation. ConclusionAmong patients with RA and pulmonary comorbidities, exacerbations requiring inpatient or ED visits occurred frequently after initiating abatacept or TNFi. Overall, we found no significant difference in the risk of ILD, COPD or asthma exacerbation between abatacept and TNFi initiators, but precision of our estimates is limited.

Exposure to ambient air pollution and autoantibody status in rheumatoid arthritis.

To evaluate the relationship between air pollutant (AP) exposure and rheumatoid arthritis (RA) autoantibody status METHODS: We performed a cross sectional study utilizing enrollment data from participants in the Veterans Affairs rheumatoid arthritis registry. HLA-DRB1 shared epitope (SE), smoking, rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibody (ACPA) status were collected. Mean exposure levels were obtained for AP (NO2, SO2, particulate matter [PM2.5, PM10], and ozone) from air quality monitoring stations at patients' residential zip codes in the year prior to enrollment. Multivariable logistic and ordinary least squares regression models were used to determine independent associations of AP with RA seropositivity and autoantibody concentration. The cohort included 557 veterans (90% male, 76% Caucasian), with mean age of 70 years and mean disease duration of 13 years. The majority were HLA-DRB1 SE, RF, and ACPA positive (73%, 79%, and 76%, respectively). In univariate models, PM2.5 exposure was associated with higher ACPA concentration (p = 0.009). Similarly, in multivariable regression models, PM2.5 exposure was independently associated with higher ACPA concentration (p = 0.037). Current smoking independently predicted RF and ACPA positivity and titers, while HLA-DRB1 SE alleles were associated with RF positivity and ACPA positivity and titers. In an elderly cohort of RA patients, fine particulate matter (PM2.5) exposure independently predicted higher ACPA concentration. Further study of fine particulate matter in the pathogenesis of RA is warranted. Key Points • A study that integrates both genetic and environmental exposure data, relative to RA autoantibody status. • Of different air pollutants measures, exposure to fine particulate matter (PM2.5) appears to be most closely linked to ACPA titers.

Tobacco-Derived Lipopolysaccharide, Not Microbial Translocation, as a Potential Contributor to the Pathogenesis of Rheumatoid Arthritis.

Microbial lipopolysaccharides (LPS) have been implicated in the pathogenesis of rheumatoid arthritis (RA), possibly driving a systemic inflammatory response that may trigger the development and/or exacerbation of the disease. To explore the existence of this mechanism in African RA patients, we have measured systemic levels of LPS and its surrogate, LPS-binding protein (LBP), as well as those of intestinal fatty acid-binding protein (I-FABP), pulmonary surfactant protein D (SP-D), and cotinine in serum to identify possible origins of LPS, as well as associations of these biomarkers with rheumatoid factor (RF) and anticitrullinated peptide (aCCP) autoantibodies and the DAS 28-3 clinical disease severity score. A cohort of 40 disease-modifying antirheumatic drug-naïve, black South African RA patients rated by compound disease scores and 20 healthy subjects and 10 patients with chronic obstructive pulmonary disease (COPD) as controls were included in this study. Levels of the various biomarkers and autoantibodies were measured using a combination of ELISA and immunofluorimetric and immunoturbidometric procedures. LPS levels were lowest in the RA group compared to the healthy controls (p = 0.026) and COPD patients (p = 0.017), while LBP levels were also significantly lower in RA compared to the healthy individuals (p = 0.036). Levels of I-FABP and SP-D were comparable between all three groups. Categorisation of RA patients according to tobacco usage revealed the following significant positive correlations: LBP with C-reactive protein (p = 0.0137); a trend (p = 0.073) towards an association of LBP with the DAS 28-3 disease severity score; RF-IgG antibodies with both LPS and LBP (p = 0.033 and p = 0.041, respectively); aCCP-IgG antibodies with LPS (p = 0.044); and aCCP-IgG with RF-IgM autoantibodies (p = 0.0016). The findings of this study, several of them novel, imply that tobacco products, as opposed to microbial translocation, represent a potential source of LPS in this study cohort of RA patients, again underscoring the risks posed by tobacco usage for the development and severity of RA.

Comparison of Healthcare Utilization and Costs Between RA Patients Receiving Biological and Conventional Synthetic DMARDs: A Nationwide Population-Based Cohort Study in Taiwan.

Background: The therapy with biological disease-modifying anti-rheumatic drugs (bDMARDs) has proven to rapidly reduce articular symptoms/signs, decrease morbidities, and improve health outcome in patients with rheumatoid arthritis (RA) and be cost-effective in Western countries. However, the difference in healthcare utilization and costs between conventional synthetic DMARDs (csDMARDs) and bDMARDs in the treatment of RA patients in Taiwan remains largely unexplored. Methods: Two cohorts of RA patients and their matched controls were identified from the National Health Insurance Research database (NHIRD). The csDMARD cohort comprised of patients who submitted claims during 1997–2003 for cyclosporine≥50 mg/day with concomitant use of ≥2 csDMARDs for ≥28 days (n=1,569), whilst the bDMARD cohort comprised of patients who had ≥1 claim during 2003–2011 for bDMARD (n = 1,530). The per-patient per-year healthcare utilization and costs were estimated by bootstrapping method, with a comparison being undertaken between csDMARD and bDMARD. Results: The incremental number of hospitalization days was reduced from 2.3 days for csDMARD to 0.58 day for bDMARD. When compared to csDMARD-treated patients, the incremental total costs and RA-related medication costs were significantly higher in bDMARD-treated patients (US$9,081 vs. US$2,481; US$8,992 vs. US$1,883). However, the combined incremental healthcare utilization costs and non-RA medication costs were significantly lower in bDMARDs-treated patients compared to csDMARD-treated patients (US$374.7 vs. US$1,156.2). Conclusion: Although total costs increased as a result of introducing biologics in RA treatment, biologics have undoubtedly given rise to the benefits of reduced healthcare utilization. The increase in medication costs from biologics was offset by the lower costs of healthcare utilization. Our findings suggest that the medication costs of biologics may be alleviated by an improvement in clinical outcomes.

Validation and assessment of minimally clinically important difference of the unadjusted Health Assessment Questionnaire in a Danish cohort: uncovering ordinal bias

Objectives: The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a widely used patient-reported outcome for functional disability in rheumatoid arthritis (RA). Minimal clinically important differences (MCIDs) in the HAQ-DI were previously calculated based on device-corrected ordinal HAQ-DI scores, leading to limited generalizability and validity for today’s patients. Our objectives were to examine the internal construct validity of the unadjusted HAQ-DI and to determine an MCID in a cohort of Danish RA patients based on the transformed linear logit scale of the HAQ-DI.Method: The study included 362 RA patients registered in the DANBIO registry. The Rasch model was fitted to HAQ-DI data at baseline and after 3 months’ follow-up. MCID was calculated as the median changes in the original HAQ-DI score and logit HAQ-DI score in those patients who had experienced minimal improvement (15–30 mm on a 0–100 mm Patient Global scale).Results: HAQ-DI data showed acceptable fit to the Rasch model at both time-points, and consistent item ranking across time indicated instrument invariance. Sixty-one patients (16.8%, ~1/6) had an improvement above the MCID on the logit scale but improvement below the MCID on the original scale, while the opposite was not the case for any patients.Conclusions: The Danish unadjusted version of the HAQ-DI showed acceptable internal construct validity. Application of the logit MCID classified an additional one in six patients as having achieved an MCID compared to the MCID calculated on the ordinal scale, which may have potential implications for the powering of future studies.

Genetic and epigenetic alteration of the programmed cell death 1 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease where both genetics and epigenetics are contributing factors. In order to discover genetic and epigenetic associations with RA and its phenotypes, we analysed RNA expression, DNA variations and DNA methylation of programmed cell death 1 (PDCD1) in a cohort of RA patients and healthy controls. RA patients (n=206) and healthy controls (n=234) were included for analysis of PDCD1 expression, PDCD1 polymorphisms and PDCD1 methylation. Differences in continuous variables between groups were compared by applying t tests. Associations between phenotypes and genotypes were evaluated with contingency tables. Sensitivity analyses were conducted to confirm the robustness of results, considering potential confounding factors and different treatment response definitions. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated. Higher expression of PDCD1 was found in RA compared to controls (P<0.001), with similar PDCD1 polymorphisms in RA and controls. rs36084323 decreased inadequate response to conventional synthetic disease-modifying antirheumatic drugs (OR=0.37, 95% CI=0.19-0.72, P=0.003), and rs41386349 increased rheumatoid factor seropositivity (OR=11.89, 95% CI=1.57-89.87, P=0.003). Sensitivity analysis adjusting for further potential confounders and using different treatment response definition indicated similar results. Additionally, DNA methylation change at regulatory region of PDCD1 was detected in RA (P=0.036). Altogether, this was the first study to suggest genetic and epigenetic changes of PDCD1 in RA subsets and RA. Independent prospective cohorts are awaited to address the implications of these genetic and epigenetic changes in disease pathogenesis and phenotypes of RA.

Assessing synovitis in the hands in patients with rheumatoid arthritis by ultrasound: an agreement study exploring the most inflammatory active side from two Norwegian trials

ObjectiveTo assess if the right hand, the dominant hand, or the hand with more clinically swollen joints (SwJ) is per se the most inflamed and exhibits the greatest change during treatment and hence preferred for unilateral scoring of synovitis by ultrasound in rheumatoid arthritis (RA) patients.MethodsUsing data from two previously published Norwegian RA patient cohorts initiating treatment, bilateral metacarpophalangeal joint 1–5, proximal phalangeal joint 2+3, and wrists were evaluated by ultrasound. Using a 0–3 scoring system a grey-scale (GS), power Doppler (PD) and global synovitis score (GLOESS) was calculated for each hand (0–30). For precision, a difference of < ± 3 in sum score was pre-specified as indicating clinically insignificant difference in inflammatory activity for all three scores.ResultsFour hundred thirty-seven RA patients were included. Baseline ultrasound inflammation was statistically significantly higher in hands with more vs fewer SwJ ([mean difference, 95%CI] GS sum score 2.21[1.30 to 3.12], PD sum score 1.70 [0.94 to 2.47] and GLOESS 2.31[1.36 to 3.26]) and also exhibited significantly more change for all sum scores at 3 months follow-up (GS sum score 1.34 [0.60 to 2.08], PD sum score 1.17 [0.44 to 1.91], and GLOESS 1.43 [0.63 to 2.22]). No such differences were found between the dominant and the non-dominant or the right and the left hands at any time points.ConclusionThe hand with clinically more SwJ is statistically more inflammatory active according to GS, Doppler, and GLOESS sum scores, exhibits a change during treatment, and is potentially the best choice for unilateral scoring systems.

A Combined Transcriptomic and Genomic Analysis Identifies a Gene Signature Associated With the Response to Anti-TNF Therapy in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is the most frequent autoimmune disease involving the joints. Although anti-TNF therapies have proven effective in the management of RA, approximately one third of patients do not show a significant clinical response. The objective of this study was to identify new genetic variation associated with the clinical response to anti-TNF therapy in RA.Methods: We performed a sequential multi-omic analysis integrating different sources of molecular information. First, we extracted the RNA from synovial biopsies of 11 RA patients starting anti-TNF therapy to identify gene coexpression modules (GCMs) in the RA synovium. Second, we analyzed the transcriptomic association between each GCM and the clinical response to anti-TNF therapy. The clinical response was determined at week 14 using the EULAR criteria. Third, we analyzed the association between the GCMs and anti-TNF response at the genetic level. For this objective, we used genome-wide data from a cohort of 348 anti-TNF treated patients from Spain. The GCMs that were significantly associated with the anti-TNF response were then tested for validation in an independent cohort of 2,706 anti-TNF treated patients. Finally, the functional implication of the validated GCMs was evaluated via pathway and cell type epigenetic enrichment analyses.Results: A total of 149 GCMs were identified in the RA synovium. From these, 13 GCMs were found to be significantly associated with anti-TNF response (P < 0.05). At the genetic level, we detected two of the 13 GCMs to be significantly associated with the response to adalimumab (P = 0.0015) and infliximab (P = 0.021) in the Spain cohort. Using the independent cohort of RA patients, we replicated the association of the GCM associated with the response to adalimumab (P = 0.0019). The validated module was found to be significantly enriched for genes involved in the nucleotide metabolism (P = 2.41e-5) and epigenetic marks from immune cells, including CD4+ regulatory T cells (P = 0.041).Conclusions: These findings show the existence of a drug-specific genetic basis for anti-TNF response, thereby supporting treatment stratification in the search for response biomarkers in RA.

Factors associated with medication adherence in a longitudinal study of rheumatoid arthritis patients.

Identification of key determinants of medication adherence may assist with designing interventions to improve this important parameter. The aim of the study was to determine the rate and predictors of self-reported medication adherence in patients with rheumatoid arthritis (RA) over one-year follow-up. Socio-demographic, disease, therapy and patient-related factors were obtained from a longitudinal observational cohort of RA patients between May 2014 and June 2016. Medication adherence was measured using self-reported Compliance Questionnaire for Rheumatology (CQR) at baseline, 6 and 12months. Mixed-effects modelling was used to investigate the relationship between adherence and potential predictors. Of 185 patients invited, 110 were included in the study. The median level of adherence was 71%-74% during the study period. Around 27%-30% of patients achieved>80% adherence, while roughly one-fifth reported a CQR score within the lower quartile (CQR<63%). After adjustment for potential confounders, increased age (β=0.19, P=0.010), higher self-efficacy (β=0.89, P=0.039) and higher medication necessity belief (β=1.12, P<0.0001) were associated with better self-reported adherence. We found a moderate level of self-reported adherence over time and significant association with age, self-efficacy and medication necessity belief. The modifiable predictors of adherence found in this study can be used as a potential target for adherence-improving interventions.

Care quality for rheumatoid arthritis patients in Quebec.

The aims of this study were to: (a) measure the proportion of CARTaGENE rheumatoid arthritis (RA) patients fulfilling pre-specified quality indicators (ie disease-modifying antirheumatic drug [DMARD] use, regular follow up, use of folate supplementation, use of vitamin D and calcium, exercise and smoking status); and (b) examine variation in DMARD use with respect to patient age, sex, education and income. A cohort of RA patients was constructed based on the CARTaGENE survey and health administrative database. CARTaGENE is a large, established, population-based study which recruited 19995 participants from four metropolitan regions in Quebec. Six quality indicators (QI) were assessed; four pertained to RA management and treatment received (use of DMARD therapy, annual medical visits, use of folate supplementation with methotrexate therapy, and use of calcium and vitamin D in steroid-exposed patients) and two pertained to lifestyle factors (physical activity and smoking cessation). QI were reported in terms of proportion of patients fulfilling them. Bayesian logistic regression analyses were preformed to investigate potential variation with DMARD use. Our cohort included 142 RA patients. The QI that pertain to RA pharmacotherapy and medical management ranged 60-80%. Regarding the QI focusing on lifestyle factors, 55% of patients reported performing moderate physical activity and only 16.6% reported current smoking. Results from the Bayesian logistic regression showed no definite associations between DMARD use and patient characteristics (age, education, income and sex). Our findings suggest a seemingly modest performance of Quebec's health-care system for RA patients, with respect to these QI.

Multimodal rheumatologic complex treatment of rheumatoid arthritis-amonocentric retrospective analysis

Multimodal rheumatologic complex treatment (MRCT, operation and procedures classification system, OPS code 8‑983) is aspecific concept of acute inpatient care (DRG I97Z) for treatment of patients with rheumatic diseases, degenerative diseases and/or chronic pain syndromes suffering from exacerbated pain and functional impairment. Amonocentric retrospective analysis of the effects of MRCT on pain and functional status in patients with rheumatoid arthritis (RA) was conducted. Atotal of 103 treatment episodes in 75patients with proven RA who received MRCT between 2014 and 2017 were included in the analysis. The changes in pain intensity were evaluated using anumerical rating scale (NRS), the functional limitations as assessed by the Hanover function questionnaire (FFbH) and the health assessment questionnaire (HAQ) and the disease activity (disease activity score of 28joints, DAS28) before and after MRCT episodes. In addition, the patient characteristics and the course of the disease were documented and a univariate analysis of the influence of these factors on the parameters activity and function was performed. In patients with RA, the MRCT resulted in asignificant amelioration of pain (p < 0.0001), asignificant improvement of functional capacity (FFbH p = 0.0013, HAQ p = 0.1396) and asignificant reduction of disease activity (DAS28 p < 0.0001). Different aspects of the disease and its previous course (e. g. disease duration, type and number of previous anti-rheumatic drugs, current medication) did not have asignificant effect on the response. This retrospective monocentric analysis proved the efficacy of MRCT with respect to the inpatient treatment period in alarge cohort of RA patients. This treatment concept not only improved pain and function (FFbH) but also significantly reduced the disease activity.

Immunosuppressive treatment and the risk of diabetes in rheumatoid arthritis.

ObjectiveInflammation and anti-inflammatory treatments might influence the risk of diabetes. The objective of this study was to assess factors associated with incident diabetes in rheumatoid arthritis (RA).MethodsThe study population consisted of RA patients from a multi-center cohort study, Corrona. To assess risk associated with disease modifying antirheumatic drug (DMARD) exposure, we assessed five mutually exclusive DMARD groups. Additionally, we assessed the risk associated with body mass index (BMI, <25, 25–30, >30 kg/m2) and glucocorticoid usage. Incident cases of diabetes were confirmed through adjudication, and Cox regression models were fit to estimate the risk of incident diabetes.ResultsWe identified 21,775 DMARD treatment regimens, the mean (SD) age at the index visit was 58 (13) years, disease duration 10 (10) years, and 30% used oral glucocorticoids at the time. Eighty-four incident cases of diabetes were confirmed within the treatment exposure periods. The hazard ratio (HR, 95% confidence interval) for diabetes was significantly reduced in patients receiving TNF inhibitors, HR 0.35 (0.13, 0.91), compared to patients treated with non-biologic DMARDs other than hydroxychloroquine and methotrexate. Hydroxychloroquine, methotrexate and use of other biologic DMARDs had a numerically reduced risk compared to the same group. Patients prescribed ≥7.5 mg of glucocorticoids had a HR of 2.33 (1.68, 3.22) of incident diabetes compared with patients not prescribed oral glucocorticoids. RA patients with a BMI >30 had a HR of 6.27 (2.97, 13.25) compared to patients with BMI ≤25.ConclusionDMARDs, glucocorticoids and obesity influenced the risk of incident diabetes in a large cohort of RA patients. Monitoring for the occurrence of diabetes should be part of routine RA management with a focus on specific subgroups.

The Use of Rheumatic Disease Comorbidity Index for Predicting Clinical Response and Retention Rate in a Cohort of Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Alpha Inhibitors

Introduction To retrospectively evaluate the impact of comorbidities on treatment choice, 12-month clinical response, and 24-month retention rate in a cohort of patients with rheumatoid arthritis (RA) treated with a first-line tumor necrosis factor alpha inhibitor (TNFi), by using for the first time the Rheumatic Disease Comorbidity Index (RDCI). Methods The study population was extracted from a local registry of RA patients receiving adalimumab or etanercept as first-line biologics between January 2001 and December 2013. The prevalence of comorbidities was computed, and patients were stratified according to RDCI for evaluating the role of comorbidities on TNFi choice, concomitant methotrexate, clinical response (1-year DAS28-ESR remission and low disease activity [LDA] and EULAR good-moderate response), and the 24-month retention rate. Results 346 patients (172 adalimumab and 174 etanercept) were included. A significantly higher EULAR good/moderate response (P = 0.020) and DAS28-ESR remission (P = 0.003) were obtained according to RDCI (0, 1, 2, or ≥3). Lower RDCI (P = 0.022), male sex (P = 0.006), higher baseline DAS28-ESR (P = 0.001), ETN (P < 0.001), and concomitant methotrexate (P = 0.016) were predictors of EULAR good/moderate response. Elevated RDCI was a predictor of discontinuation of biologics (P = 0.036), whereas treatment with etanercept (P < 0.001) and methotrexate (P = 0.007) was associated with a lower risk of TNFi withdrawal. Conclusions Multimorbidity, measured by RDCI, is a negative predictor of TNFi persistence on treatment and of achieving a good clinical response. The use of RDCI may be very useful for identifying patients with RA carrying those comorbid conditions associated with poor prognostic outcomes and for defining new treatment targets in multimorbid RA patients.

Drug survival rates of biological disease-modifying antirheumatic drugs and Janus kinase-inhibitor therapy in 801 rheumatoid arthritis patients: a 14 year-retrospective study from a rheumatology clinic in Japan

Objectives: To assess long-term outcomes for seven biological disease-modifying antirheumatic drugs (bDMARDs) and one Janus kinase (JAK)-inhibitor in rheumatoid arthritis.Methods: We retrospectively analyzed data from 801 rheumatoid arthritis patients visiting our rheumatology clinic between 2003 and 2017. We determined drug survival rates, drug discontinuation, and switching rates in these patients.Results: Among the drugs administered to naïve subjects, the drug-survival rate was highest for tocilizumab, at 77.8% after 6 years, whereas the rates for golimumab, etanercept, abatacept, infliximab, and adalimumab, were 61.5%, 48.9%, 41.6%, 34.5%, and 34.4%, respectively. Switching drugs led to decreased survival rates. The discontinuation rates for all drugs due to adverse events and poor efficacy increased rapidly in the first 2 years and the first 6 months, respectively.Conclusions: This report is a long-term analysis of a large cohort of rheumatoid arthritis patients from a single rheumatology clinic in Japan. We conclude that to maximize the survival rate of antirheumatic drugs, it is important to maintain their effectiveness over long periods of time by appropriate drug choices and optimizing dosage before switching drugs.

Structural Basis of Cross-Reactivity of Anti-Citrullinated Protein Antibodies.

Anti-citrullinated protein antibodies (ACPAs) develop many years before the clinical onset of rheumatoid arthritis (RA). This study was undertaken to address the molecular basis of the specificity and cross-reactivity of ACPAs from patients with RA. Antibodies isolated from RA patients were expressed as monoclonal chimeric antibodies with mouse Fc. These antibodies were characterized for glycosylation using mass spectrometry, and their cross-reactivity was assessed using Biacore and Luminex immunoassays. The crystal structures of the antigen-binding fragment (Fab) of the monoclonal ACPA E4 in complex with 3 different citrullinated peptides were determined using x-ray crystallography. The prevalence of autoantibodies reactive against 3 of the citrullinated peptides that also interacted with E4 was investigated by Luminex immunoassay in 2 Swedish cohorts of RA patients. Analysis of the crystal structures of a monoclonal ACPA from human RA serum in complex with citrullinated peptides revealed key residues of several complementarity-determining regions that recognized the citrulline as well as the neighboring peptide backbone, but with limited contact with the side chains of the peptides. The same citrullinated peptides were recognized by high titers of serum autoantibodies in 2 large cohorts of RA patients. These data show, for the first time, how ACPAs derived from human RA serum recognize citrulline. The specific citrulline recognition and backbone-mediated interactions provide a structural explanation for the promiscuous recognition of citrullinated peptides by RA-specific ACPAs.

Characterisation of Subclinical Myocardial Dysfunction in Rheumatoid Arthritis Patients with Normal LVEF

Background: Rheumatoid arthritis (RA) is a chronic systemic inflammatory condition modulated by pro-inflammatory cytokines. These are believed to have negative inotropic effects at the level of the myocyte. We hypothesise that chronically elevated pro-inflammatory cytokine levels in RA result in subclinical myocardial dysfunction. Myocardial deformation indices are proposed to be a more sensitive marker of cardiac dysfunction compared to left ventricular ejection fraction (LVEF). We aimed to detect subclinical cardiac dysfunction in a cohort of RA patients with normal LVEF. Methods: Consecutive stable RA patients (>1 year disease activity) admitted to our institution and without known cardiovascular disease were compared to age- and gender-matched controls. Patients without comprehensive transthoracic echocardiography (TTE), congenital heart disease, pulmonary disease, valvular heart disease or poor quality images were excluded. Left ventricular size and systolic function were measured according to ASE guidelines. LV mean global longitudinal strain (GLS) was measured offline using vendor-independent software (TomTec Arena, Germany v4.6). Results: Of the 118 RA patients identified, 82 had a comprehensive TTE. 47 were excluded, leaving a cohort of 35 patients (mean age 71.8 ± 15.9, 77% female). There was no significant difference in baseline clinical characteristics or measures of left ventricular size and systolic function between controls and RA patients. However, LV mean GLS (%) was significantly lower in RA patients (−17.18 ± 1.7%) compared with controls (−19.1 ± 2.5%) (p = 0.02). Conclusions: Our results suggest patients with RA have subclinical cardiac dysfunction despite normal LVEF measurements. These patients may benefit from regular cardiac follow-up and early commencement of cardioprotective agents.

Comparative analysis of US real-world dosing patterns and direct infusion-related costs for matched cohorts of rheumatoid arthritis patients treated with infliximab or intravenous golimumab.

PurposeThe objectives of this study were to evaluate and compare treatment patterns and infusion-related health care resource expenditures for rheumatoid arthritis (RA) patients initiating golimumab for intravenous use (GLM-IV) and infliximab (IFX) therapy and to assess cost implications from the commercial perspective.MethodsAdult RA patients with a new episode of GLM-IV or IFX treatment between Janu-ary 1, 2014 and March 31, 2016 were identified from MarketScan databases and evaluated for maintenance infusion intervals and related costs of treatment. IFX and GLM-IV patients were matched 1:1 on index medication treatment duration, gender, payer type, prior biologic use, and post-index methotrexate use. Paid amounts for drugs and associated administration costs were applied to treatment group dosing patterns.ResultsFinal matched treatment groups included 547 GLM-IV and 547 IFX patients (mean age = 55–56 years). Mean (SD) follow-up was 609 (161) days for GLM-IV and 613 (163) days for IFX. Treatment duration was 396 (240) days for GLM-IV and 397 (239) days for IFX. Overall, 80% of GLM-IV and 39% of IFX maintenance infusions were given approximately every 8 weeks; and 6% of GLM-IV and 53% of IFX maintenance infusions occurred more frequently than every 8 weeks (P<0.001). When weighting of the maintenance infusion interval was applied, the mean number of induction plus maintenance infusions during the first year of treatment was estimated at 7.03 for GLM-IV and 9.48 for IFX. From the commercial perspective, drug plus administration costs per infusion were $5,846 for GLM-IV and $5,444 for IFX with total annual cost of therapy for GLM-IV patients costing $10,507 less than that for IFX patients in the first year and $6,774 less than that for IFX patients in subsequent years.ConclusionAnnual GLM-IV drug plus administration costs for commercial health plans were significantly less than IFX in RA patients due to differences in real-world dosing and administration.

Long-term survival of subcutaneous anti-tumor necrosis factor biological drugs administered between 2008 and 2012 in a cohort of rheumatoid arthritis patients.

To compare the survival of subcutaneous anti-tumor necrosis factor (TNF) drugs used between 2008 and 2012 prescribed in accordance with clinical practice. Retrospective, observational study of the patients in our center diagnosed with rheumatoid arthritis (RA). We included patients who had received a subcutaneous anti-TNF agent for at least 6 months. The data were analyzed using the SPSS V17.0 statistical package. Forty-nine RA patients started subcutaneous biological treatment with an anti-TNF agent (32 with etanercept and 17 with adalimumab). The mean age was 45.94 years (75.5% female). The mean disease duration prior to starting anti-TNF administration was 2.67 years. The mean age at the start of treatment was 51.84 years, and the average Disease Activity Score 28 was 4.93. The median survival of the anti-TNF treatment was 8.40 years; the survival of etanercept was the longer of the two. The main reason for discontinuation was secondary failure (90.9%). In routine clinical practice, the survival of subcutaneous anti-TNF treatment was extensive and was independent of whether or not the patients received concomitant immunosuppressive therapy.

The outcome of patients with rheumatoid arthritis: a cross-sectional study

Background: Rheumatoid arthritis (RA) is an autoimmune disorder that affects human joints. The disease also can destroy others body systems, including skin, eyes, lungs, blood vessels, and heart. The aim of the current study was to investigate the effectiveness of RA concerning disease activity and the rate of remission, quality of life, and employment as measured by the disease activity score (DAS 28). Methodology: This cross-sectional study was conducted during the period from October to November 2018. Two RA patient cohorts were created based on the physician-reported DAS28; adequately controlled (DAS28 &amp;#8804; 3.2) and inadequately controlled (DAS28 &amp;gt;3.2). We used descriptive statistics to compare the two groups. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) software (version. 22). A p-value of &amp;#8804;0.05 was considered statistically significant. Results: A quarter (24.5%) of the inadequately controlled cohort were currently in remission less than 70% of those with adequately controlled RA. Also, 31% of the inadequately controlled group had mild RA which was less than those with adequately controlled RA (83.3%; p = 0.001) and fewer patients were found to be with stable disease status (38% vs 65%; p = 0.001). Patients in the inadequately controlled cohort had a lower quality of life, employment (0.49 vs 0.72; p = 0.001), and had higher rates of work impairment(37 vs 18.4; p = 0.04). Conclusion: Inadequately controlled RA patients (DAS28 &amp;gt; 3.2) were in less remission than those with inadequately controlled RA (DAS28 &amp;#8804; 3.2) and there were fewer patients with stable disease status. Patients in the inadequately controlled group had a lower quality of life and employment compared to the adequately controlled cohort who had higher rates of work impairment.

Vitamin D deficiency and pulmonary affection in rheumatoid arthritis

Background Vitamin D appears to play a key role both in the innate and in the adaptive immune system, and the presence of its receptors in different cell types seems to play a role in the pathogenesis of rheumatoid arthritis (RA). Vitamin D deficiency is common and seems to be correlated with the course of RA and outcome of pulmonary disease, which is a major contributor to morbidity and mortality in RA patients. Aim This study aimed to evaluate the prevalence of vitamin D deficiency and its relationship with pulmonary affection in a cohort of Egyptian RA patients. Patients and methods A total of 100 RA patients were enrolled in this study, who underwent a clinical examination, with a focus on articular and extra-articular manifestations including pulmonary manifestations. Assessment of RA disease activity was performed using the disease activity score (DAS)-28 score and serum vitamin D level was measured. Spirometry and diffusion lung capacity for carbon monoxide were performed. Radiographic evaluation, Plain x-ray on hands, chest x-ray and high-resolution computed tomography (HRCT) chest were done. Results Our study included 100 RA patients (40 patients with pulmonary affection and 60 patients without pulmonary affection). DAS-28 and rheumatoid factor titer were increased in RA patients with pulmonary affection. Moreover, vitamin D serum levels were decreased in RA patients with pulmonary affection. Multiple regression analysis showed that older age, disease activity parameters, and decreased vitamin D levels had an independent effect on increasing the HRCT chest total score. Logistic regression analysis showed that the increase in the DAS-28 score and the rheumatoid factor titer and the decrease in the vitamin D levels had an independent effect on increasing the probability of pulmonary affection occurrence. Conclusion Patients with RA-associated interstitial lung disease ‘proved by HRCT and/or diffusion lung capacity for carbon monoxide’ tend to have a high prevalence of vitamin D deficiency and high disease activity; also, lower levels of vitamin D play a significant role in the pathogenesis of RA-interstitial lung disease.