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ID PMID Title PublicationDate abstract
24913966 Rheumatoid arthritis-associated interstitial lung disease: lung inflammation evaluated wit 2015 Jan OBJECTIVE: To describe the association between rheumatoid arthritis disease activity (RA) and interstitial lung damage (inflammation and fibrosis), in a group of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: A retrospective study of RA patients with interstitial lung disease (restrictive pattern in lung function tests and evidence of interstitial lung disease in high resolution computed tomography (HRCT)). Patients were evaluated to exclude other causes of pulmonary disease. RA disease activity was measured with the CDAI index. Interstitial lung inflammation and fibrosis were determined by Kazerooni scale. We compared Kazerooni ground-glass score with the nearest CDAI score to HRCT date scan of the first medical evaluation at our institution. In nine patients, we compared the first ground-glass score with a second one after treatment with DMARDs and corticosteroids. Spearman's rank correlation coefficient was used to evaluate association between RA disease activity and the Kazerooni ground-glass and fibrosis scores. RESULTS: Thirty-four patients were included. A positive correlation between CDAI and ground-glass scores was found (rs=0.3767, P<0.028). Fibrosis and CDAI scores were not associated (rs=-0.0747, P<0.6745). After treatment, a downward tendency in the ground-glass score was observed (median [IQR]): (2.33 [2,3] vs. 2 [1.33-2.16]), P<0.056, along with a lesser CDAI score (27 [8-43] vs. 9 [5-12]), P<0.063. CONCLUSION: There is a correlation between RA disease activity and ground-glass appearance in the HRCT of RA-ILD patients. These results suggest a positive association between RA disease activity and lung inflammation in RA-ILD.
28712248 One Stage Bilateral Knee And Hip Arthroplasties In 42 Years Old Female. 2016 Jul Knee and hip joint replacement surgeries are the mainstay of treatment in patients having grade 3 or grade 4 arthritis either due to degenerative process, rheumatoid disease or due to some other disease process. The main aims of these surgeries are to decrease the morbidity, early rehabilitation and decrease management costs of such patients. We report the first case in which bilateral total knee and total hip replacement surgery were done in single anaesthesia in 42 years old female patient suffering from Rheumatoid Arthritis.
25224416 Psychological distress over time in early rheumatoid arthritis: results from a longitudina 2015 Mar OBJECTIVE: RA is a chronic disease with frequent psychological co-morbidities, of which depression and anxiety are two common manifestations. We aimed to identify predictive factors of psychological distress in a large prospective cohort of very early RA patients. METHODS: ESPOIR (Etude et Suivi des Polyarthrites Indifférenciées Récentes) is a multicentre, longitudinal and prospective cohort study of patients with early arthritis (<6 months disease duration). The study sample comprised 641 patients with very early RA according to the 2010 ACR/European League Against Rheumatism RA criteria from the ESPOIR cohort. Psychological distress was assessed over 3 years by the five-item Mental Health Inventory questionnaire at various time points (baseline, 6, 12, 18, 24 and 36 months). Logistic regression with a generalized estimating equation model was used to analyse the association of disease variables and risk of psychological distress. RESULTS: At baseline, 46.9% of RA patients were screened as positive for psychological distress. Over 3 years, psychological distress decreased significantly, with a prevalence of 25.8% at 36 months. The HAQ Disability Index (HAQ-DI) score was the most important factor predicting psychological distress over 3 years [odds ratio 2.10 (95% CI 1.41, 3.14)-3.59 (2.29, 5.63)]. Baseline biological and radiological variables and treatment regimens were not associated with distress. CONCLUSION: Psychological distress in very early RA is frequent and the HAQ-DI score is a predictor of depression and anxiety in these patients. A psychological evaluation in patients with early RA is important for further individual psychiatric diagnosis and management.
25738587 Is ultrasound a better target than clinical disease activity scores in rheumatoid arthriti 2015 OBJECTIVES: Our goal is to study the correlations among gray-scale seven-joint ultrasound score (GS-US7), power Doppler seven-joint ultrasound score (PD-US7), disease activity score-28 joints (DAS28), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in patients with and without fibromyalgia (FM). METHODS: A matched case-control study included all patients consecutively seen in the Rheumatoid Arthritis (RA) Clinic. Participants were allocated into one of two groups: RA with FM and RA without FM. Ultrasound (US) and clinical scoring were blinded for the presence of FM. Medians and proportions were compared by Mann-Whitney's test and McNemar's test, respectively. Spearman's rank correlation coefficients (rs) were calculated among clinical and US scores and differences were tested by r-to-z transformation test. RESULTS: Seventy-two women were included, out of 247 RA patients, mostly white, with median (IQR) age of 57.5 (49.3-66.8) years, with RA symptoms for 13.0 (6.0-19.0) years and FM symptoms for 6.0 (2.0-15.0) years. Disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs and prednisone use was comparable between groups. Objective activity parameters were not different between groups. RA patients with FM had greater DAS28, SDAI and CDAI but similar GS-US7 and PD-US7. GS-US7 correlated with DAS28, SDAI and CDAI in patients with and without FM (rs = 0.36-0.57), while PD-US7 correlated with clinical scores only in patients without FM (rs = 0.35-0.38). CONCLUSION: To our knowledge, this is the first study to demonstrate that ultrasound synovitis scores are not affected by FM in RA patients. PD-US7 performed better than GS-US7 in long-standing RA patients with DAS28, SDAI or CDAI allegedly overestimated due to FM. Since sonographic synovitis predicts erosion better than swollen joint count, C-reactive protein and erythrocyte sedimentation rate, US should be considered a promising treatment target in RA patients with FM.
26523023 Association of Body Mass Index Categories with Disease Activity and Radiographic Joint Dam 2015 Dec OBJECTIVE: Obesity and overweight are increasing conditions. Adipose tissue with proinflammatory properties could be involved in rheumatoid arthritis (RA) activity and radiographic progression. This study aims to investigate the influence of overweight and obesity on RA activity and severity. METHODS: We conducted a systematic review and metaanalysis to assess the association of body mass index (BMI) categories with the Disease Activity Score in 28 joints (DAS28), functional disability [Health Assessment Questionnaire (HAQ)], and radiographic joint damage in patients with RA. We searched Medline through PubMed, EMBASE, and the Cochrane Database of Systematic Reviews for all studies assessing DAS28, HAQ, or/and radiographic damage according to predefined BMI groups. RESULTS: Among the 737 citations retrieved, 58 articles met the inclusion criteria and 7 were included in the metaanalysis. DAS28 was higher in obese (BMI > 30 kg/m(2)) than non-obese (BMI ≤ 30 kg/m(2)) patients (mean difference 0.14, 95% CI 0.01-0.27, p = 0.04, I(2) = 0%). HAQ score was also higher among obese patients (mean difference 0.10, 95% CI 0.01-0.19, p = 0.03, I(2) = 0%). Radiographic joint damage was negatively associated with obesity (standardized mean difference -0.15, 95% CI -0.29 to -0.02, p = 0.03, I(2) = 38%). CONCLUSION: Obesity in RA is associated with increased DAS28 and HAQ score and with lower radiographic joint damage. These associations mainly result from an increase of subjective components of the DAS28 (total joint count and global health assessment) in obese patients. Conflicting results were reported concerning inflammation markers (C-reactive protein and erythrocyte sedimentation rate).
27383913 Macrophage heterogeneity in the context of rheumatoid arthritis. 2016 Aug Macrophages are very important in the pathogenesis of rheumatoid arthritis (RA). The increase in the number of sublining macrophages in the synovium is an early hallmark of active rheumatic disease, and high numbers of macrophages are a prominent feature of inflammatory lesions. The degree of synovial macrophage infiltration correlates with the degree of joint erosion, and depletion of these macrophages from inflamed tissue has a profound therapeutic benefit. Research has now uncovered an unexpectedly high level of heterogeneity in macrophage origin and function, and has emphasized the role of environmental factors in their functional specialization. Although the heterogeneous populations of macrophages in RA have not been fully characterized, preliminary results in mouse models of arthritis have contributed to our understanding of the phenotype and ontogeny of synovial macrophages, and to deciphering the properties of monocyte-derived infiltrating and tissue-resident macrophages. Elucidating the molecular mechanisms that drive polarization of macrophages towards proinflammatory or anti-inflammatory phenotypes could lead to identification of signalling pathways that inform future therapeutic strategies.
25867229 Severe pes planovalgus successfully treated in a patient with mutilating rheumatoid arthri 2017 Nov We report the case of a 56-year-old female with mutilating rheumatoid arthritis, who developed severe pes planovalgus. The foot was successfully reconstructed through a combination of osteotomies, including medial displacement of the talus accompanied by resection of the medial malleolus. This maneuver enabled a ∼1-cm medial displacement of the hindfoot while minimizing the adverse effect on forefoot rotation.
27599513 The gene therapy of collagen-induced arthritis in rats by intramuscular administration of 2016 Jul Wistar rats with collagen-induced arthritis were intramuscularly injected with the recombinant plasmid pcDNA/sTNF-BD encoding the sequence of the TNF-binding protein domain of variola virus CrmB protein (VARV sTNF-BD) or the pcDNA3.1 vector. Quantitative analysis showed that the histopathological changes in the hind-limb joints of rats were most severe in the animals injected with pcDNA3.1 and much less severe in the group of rats injected with pcDNA/sTNF-BD, which indicates that gene therapy of rheumatoid arthritis is promising in the case of local administration of plasmids governing the synthesis of VARV immunomodulatory proteins.
26697770 Evaluating and mitigating fracture risk in established rheumatoid arthritis. 2015 Aug Patients with rheumatoid arthritis are predisposed to systemic bone loss, and they are at an increased risk of fractures. Although there are similarities in the patient demographics between rheumatoid arthritis patients and the general population of osteoporosis patients, there are factors, particularly the use of glucocorticoids, which are specific to rheumatoid arthritis. These factors can lead to an increased risk of bone loss and fracture. Given that fractures are often very debilitating, especially in elderly patients, it is of paramount importance for the practicing rheumatologist to be aware of ways to reduce the risk of fracture in patients with rheumatoid arthritis. This review discusses currently available modalities for fracture risk assessment as well as pharmacologic and lifestyle interventions available to treat and prevent bone loss in rheumatoid arthritis patients.
26951253 The Roles of Cigarette Smoking and the Lung in the Transitions Between Phases of Preclinic 2016 Mar While the etiology of rheumatoid arthritis (RA) remains to be fully elucidated, recent research has advanced the understanding of RA pathogenesis to the point where clinical trials for RA prevention are underway. The current paradigm for RA pathogenesis is that individuals progress through distinct preclinical phases prior to the onset of clinically apparent RA. These preclinical RA phases consist of genetic risk, local inflammation, presence of RA-related autoantibodies, asymptomatic systemic inflammation, and early non-specific symptoms prior to clinical seropositive RA. Epidemiologic studies have been important in forming hypotheses related to the biology occurring in preclinical RA. Specifically, studies associating cigarette smoking with overall RA risk as well as transitions between phases of preclinical RA were vital in helping to establish the lung as a potential important initiating site in the pathogenesis of seropositive RA. Herein, we review the epidemiology associating smoking with transitions in preclinical phases of RA as well as the recent literature supporting the lung as a critical site in RA pathogenesis.
26362159 Clinical validation of surface-enhanced Raman scattering-based immunoassays in the early d 2015 Nov We assessed the clinical feasibility of conducting immunoassays based on surface-enhanced Raman scattering (SERS) in the early diagnosis of rheumatoid arthritis (RA). An autoantibody against citrullinated peptide (anti-CCP) was used as a biomarker, magnetic beads conjugated with CCP were used as substrates, and the SERS nanotags were comprised of anti-human IgG-conjugated hollow gold nanospheres (HGNs). We were able to determine the anti-CCP serum levels successfully by observing the distinctive Raman intensities corresponding to the SERS nanotags. At high concentrations of anti-CCP (>25 U/mL), the results obtained from the SERS assay confirmed those obtained via an ELISA-based assay. Nevertheless, quantitation via our SERS-based assay is significantly more accurate at low concentrations (<25 U/mL). In this study, we compared the results of an anti-CCP assay of 74 clinical blood samples obtained from the SERS-based assay to that of a commercial ELISA kit. The results of the anti-CCP-positive group (n = 31, >25 U/mL) revealed a good correlation between the ELISA and SERS-based assays. However, in the anti-CCP-negative group (n = 43, <25 U/mL), the SERS-based assay was shown to be more reproducible. Accordingly, we suggest that SERS-based assays are novel and potentially useful tools in the early diagnosis of RA.
25251857 Mediterranean diet and incidence of rheumatoid arthritis in women. 2015 May OBJECTIVE: We examined the association between a Mediterranean dietary pattern, as measured by the Alternate Mediterranean Diet Score (aMed), and risk of incident rheumatoid arthritis (RA) in US women. METHODS: We prospectively followed 83,245 participants from the Nurses' Health Study (NHS; 1980-2008) and 91,393 participants from NHS II (1991-2009) who were initially free of baseline connective tissue diseases. Dietary information was obtained via validated food frequency questionnaires at baseline and approximately every 4 years during followup. The aMed score was calculated according to the consumption status of 9 food components using cumulative average value. Time-varying Cox proportional hazards models were used to calculate hazard ratios (HRs) for RA, seropositive RA, and seronegative RA after adjustment for potential confounding factors. Results from 2 cohorts were pooled by an inverse variance-weighted, fixed-effects model. RESULTS: During 3,511,050 person-years of followup, 913 incident cases of RA were documented in the 2 cohorts. After adjustment for several lifestyle and dietary variables, in both cohorts greater adherence to Mediterranean dietary pattern was not significantly associated with altered risk of RA. The pooled HR for women in the highest quartile of the aMed score was 0.98 (95% confidence interval 0.80-1.20) compared with those in the bottom quartile. Similar nonsignificant results were observed for both seropositive and seronegative RA. We did not find significant associations between each individual food component (except for alcohol) of the aMed score and risk of incident RA. CONCLUSION: We did not find a significant association between a Mediterranean dietary pattern and the risk of RA in women.
27172513 The influence of lifestyle habits on quality of life in patients with established rheumato 2016 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, inflammatory, and systemic disease with symptoms that limit activities and affect quality of life. RA is associated with an increased risk of developing comorbidities, some of which are also known to be associated with lifestyle habits such as physical activity, diet, smoking, and alcohol. There has been an augmented focus on the implementation and maintenance of healthy lifestyle habits even for patients with RA in the past decade, but little is known about the link between patients' experiences of lifestyle habits and quality of life. The aim of the study was thus to describe and explore how patients with established RA experience the influence of lifestyle habits on quality of life. METHODS: The study had a descriptive and explorative design, based on qualitative content analysis. Strategic sampling was used in order to achieve variations in experiences. Twenty-two patients with RA (14 women and 8 men) from 30 to 84 years old, with a disease duration ranging from 8 to 23 years, were interviewed. RESULTS: The analysis of the influence of lifestyle habits on quality of life resulted in the theme balancing between ideality and reality. Three categories emerged about how lifestyle habits influenced quality of life by limitations (including insufficiency and adaptation), self-regulation (including guilt and motivation), and companionship (including belonging and pleasure). CONCLUSIONS: Quality of life for patients with established RA was influenced by the balance between ideality and reality in the lifestyle habits: physical activity, diet, smoking, and alcohol. This is important new knowledge for health professionals when discussing lifestyle habits with RA patients.
25890172 Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-respons 2015 Mar 29 INTRODUCTION: The evidence from published studies on the association between obesity and rheumatoid arthritis has been contradictory. To clarify the association between obesity and rheumatoid arthritis, we conducted a systematic review and dose-response meta-analysis to assess the relationship between body mass index and rheumatoid arthritis risk. METHODS: A systematic literature search of PubMed and Embase (up to 12 July 2014) was performed to identify all eligible published reports. The pooled relative risk results with corresponding 95% confidence intervals of rheumatoid arthritis development were estimated using a random-effects model. RESULTS: Eleven eligible related citations fulfilled the inclusion criteria and were included in the study. Compared with individuals with a body mass index under 30, obese individuals showed an association with a significantly increased risk of rheumatoid arthritis (relative risk = 1.25, 95% confidence interval: 1.07 to 1.45, P heterogeneity <0.01, I(2) = 63%). Compared to normal weight subjects, the pooled relative risks for rheumatoid arthritis were 1.31 (1.12 to 1.53) and 1.15 (1.03 to 1.29) for the categories of obese and overweight, respectively. In the dose-response analysis, there was evidence of a nonlinear association (P nonlinear = 0.005) and the estimated summary relative risk for a 5-unit increment was 1.03 (95% confidence interval: 1.01 to 1.05, P heterogeneity = 0.001, I(2) = 70.0%). CONCLUSIONS: An increase in body mass index can contribute to a higher risk for rheumatoid arthritis development. However, the finding also highlights the need for research on the association between body mass index and rheumatoid arthritis risk with adjustment for more confounding factors.
25143522 How much does Disease Activity Score in 28 joints ESR and CRP calculations underestimate d 2015 Jun OBJECTIVES: Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) is used instead of erythrocyte sedimentation rate (DAS28-ESR) to assess rheumatoid arthritis disease activity; however, values for remission and low disease activity (LDA) for DAS28-CRP have not been validated. American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) guidelines suggest remission should be calculated by Simplified Disease Activity Index (SDAI) rather than DAS28-ESR. We examined values of remission and LDA of DAS28-CRP that correspond to the respective cut-off points for DAS28-ESR and SDAI from five clinical trials. METHODS: DAS28-CRP cut-offs that best correspond to DAS28-ESR remission <2.6 and LDA ≤3.2 were obtained by cumulative distribution plots, receiver operating curves and maximum concordance and averaged for each approach, treatment group and study. Level of agreement between DAS28-CRP and DAS28-ESR remission and LDA cut-offs was compared against each other and versus SDAI remission ≤3.3 and LDA ≤11. RESULTS: Percentage of patients who achieved remission and LDA by DAS28-ESR cut-offs was greater for DAS28-CRP versus DAS28-ESR regardless of patient population or treatment group. Discordance between CRP and ESR cut-offs ranged from 4%-26% and 8%-23% for remission and LDA, respectively, and 19%-40% and 6%-11% for DAS28-CRP versus SDAI, respectively. Estimated (range) remission and LDA thresholds were 2.4 (2.2-2.6) and 2.9 (2.6-3.3), 1.9 (1.6-2.2) and 3.1 (3.1-3.3) and 2.2 (1.1-2.9) and 3.6 (3.4-4.0) for DAS28-CRP versus DAS28-ESR, DAS28-CRP versus SDAI and DAS28-ESR versus SDAI, respectively. CONCLUSIONS: DAS28-CRP underestimates disease activity when using cut-off points validated for DAS28-ESR; therefore, DAS28-ESR cut-off values should not be applied to DAS28-CRP. Although DAS28-CRP and DAS28-ESR cut-offs for LDA ≤3.2 correspond to SDAI LDA, neither corresponds well to SDAI remission.
27811914 Update on the genetic architecture of rheumatoid arthritis. 2017 Jan Human genetic studies into rheumatoid arthritis (RA) have uncovered more than 100 genetic loci associated with susceptibility to RA and have refined the RA-association model for HLA variants. The majority of RA-risk variants are highly shared across multiple ancestral populations and are located in noncoding elements that might have allele-specific regulatory effects in relevant tissues. Emerging multi-omics data, high-density genotype data and bioinformatic approaches are enabling researchers to use RA-risk variants to identify functionally relevant cell types and biological pathways that are involved in impaired immune processes and disease phenotypes. This Review summarizes reported RA-risk loci and the latest insights from human genetic studies into RA pathogenesis, including how genetic data has helped to identify currently available drugs that could be repurposed for patients with RA and the role of genetics in guiding the development of new drugs.
25496404 Predictive value of bone destruction and duration of clinical remission for subclinical sy 2015 Jul OBJECTIVES: Treatment for rheumatoid arthritis (RA) should aim to achieve full remission. The aim of this study was to investigate predictors of persistent subclinical synovitis and whether longer clinical remission is effective in reducing subclinical synovitis. METHODS: Forty-four RA patients who achieved DAS28ESR clinical remission for at least 3 months were enrolled in this study and underwent ultrasound examination of 22 joints (bilateral proximal interphalangeal joints, metacarpophalangeal joints, and wrists); bilateral hand X-ray; and blood examination. The severity of synovial effusion, synovial hypertrophy, and blood flow were semi-quantitatively graded from 0 to 3 using gray-scale (GS) and power Doppler (PD) modes. RESULTS: Among patients with DAS28ESR-defined clinical remission, 59.1% (26/44) demonstrated residual synovitis (≥ PD1) in at least one joint. Genant-modified total Sharp score (TSS) demonstrated the highest statistical difference between patients with and without residual subclinical synovitis (p = 0.0057), and full remission was only observed in patients with low TSS. A nonsignificant trend for decreased residual synovitis with longer sustained clinical remission was also observed (p = 0.724). CONCLUSION: Residual synovitis can persist during clinical remission, particularly in patients with progressive bone destruction. Early treatment and longer sustained clinical remission prior to bone destruction are critical for full remission.
26910492 The Association Between Rheumatoid Arthritis and Adverse Postoperative Outcomes: A Retrosp 2016 Jun BACKGROUND: Patients with rheumatoid arthritis have a high overall incidence of mortality, primarily because of cardiovascular complications. Thus, we tested the primary hypothesis that rheumatoid arthritis is independently associated with increased postoperative cardiovascular complications. Second, we determined whether rheumatoid arthritis is associated with increased thromboembolic complications, microcirculatory complications, and mortality. METHODS: We obtained censuses of 2009 to 2010 inpatient hospital discharge data across 7 states (Arizona, California, Florida, Iowa, Maryland, Michigan, and New Jersey). Rheumatoid arthritis was identified using the present-on-admission diagnosis code 714.0. Each rheumatoid arthritis discharge that had surgery was propensity matched to a control discharge. Multivariable logistic regression was used to compare matched rheumatoid arthritis and control patients on risk of in-hospital cardiovascular complications. RESULTS: Among 5.5 million qualifying discharges, the matching procedure yielded successful 66,886 matched pairs. One thousand ninety-five (1.64%) of the matched rheumatoid arthritis discharges and 1006 (1.50%) of the matched controls had in-hospital cardiovascular complications. The adjusted odds ratio (99% confidence interval) was estimated at 1.08 (0.96-1.21; P = 0.08). There were no significant differences in the odds of in-hospital thromboembolic complications (1.03 [0.93-1.15]; P = 0.42), in-hospital microcirculatory complications (0.94 [0.86-1.01]; P = 0.03), or in-hospital mortality (1.11 [0.98-1.25]; P = 0.04). CONCLUSIONS: Rheumatoid arthritis was not associated with an increased risk for postoperative cardiovascular complications.
26505439 Differential expression of COX-2 in osteoarthritis and rheumatoid arthritis. 2015 Oct 21 In this study, we investigated the differential expression profiles of cyclooxygenase-2 (COX-2) mRNA and proteins in osteoarthritis (OA) and rheumatoid arthritis (RA) patients to elucidate the role of COX-2 expression in the pathogenesis and development of these diseases and to provide novel drug targets for treating arthritis. A total of 60 patients who received arthroscopic surgeries for treating OA (N = 30) or RA (N = 30) were examined. Fifteen normal synovial tissue samples were included as the control group. Fibroblastic synovial cells in all samples were cultured in vitro and COX-2 mRNA, protein expression levels, and COX-2 levels were detected in synovial fluids by real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay methods, respectively. The mRNA level of COX-2 was significantly elevated in synovial cells from OA and RA patients compared to that in control samples (P < 0.05). COX-2 mRNA level was significantly higher in synovial cells from OA patients than in those from RA patients (P < 0.05). Consistent results were obtained for COX-2 protein expression levels from patients' synovial samples. In synovial fluids, OA (P < 0.05), but not RA (P > 0.05), patients showed significantly higher COX-2 levels compared to the control group. Elevated synovial COX-2 expression facilitates the pathogenesis of OA and RA, and thus this index reflects the condition of these 2 diseases.
26995880 [Optimal Treatment for Rheumatoid Arthritis with Companion Diagnostics]. 2015 Nov The medical strategy for rheumatoid arthritis (RA) has markedly advanced in recent years. The introduction of biologics in addition to methotrexate, an anchor drug, has made it possible to not only suppress pain and inflammation (clinical remission), but also inhibit joint destruction (structural remission), leading to cure from the disease. Since the condition and pathology are heterogeneous among individual patients, optimal treatment for each patient based on the use of companion diagnostics is desired (precision medicine). ACPA is important to diagnose RA, but also to assess the prognosis. ACPA is also a part of companion diagnostics for preclinical RA because it has been found to be positive before the onset. Treatment should be performed under consideration of the disease state such as activity, prognosis regarding joint destruction, and complications. It is also important to clarify the patient characteristics, such as responsiveness to the drugs and risk of adverse effects. Biomarkers, such as proteomics and pharmacogenomics, have been reported as companion diagnostics for optimal treatment of RA. RA is a multifactorial disorder with clinically heterogeneous features. Gene-environment interaction is closely involved in the production of ACPA, and then secondary stimuli to joints may lead to symptoms of RA. Joint injury, emotional stress, and infections often trigger the onset of RA. It is possible to cure RA, achieving complete remission, by early aggressive treatment and returning to the pre-clinical state with environmental improvement. [Review]