Disease-modifying Antirheumatic Drugs In Rheumatoid Arthritis Research Articles

Association between disease-modifying antirheumatic drugs for rheumatoid arthritis and risk of incident dementia: a systematic review with meta-analysis

BackgroundDysregulation of several inflammatory cytokines including tumour necrosis factor (TNF) in dementia patients has also been identified as a key factor in the pathogenesis of rheumatoid arthritis (RA). We aimed...

Abstract 6 — Are Disease-Modifying Antirheumatic Drugs: for Rheumatoid Arthritis Associated with a Lower Risk of Dementia? A Systematic Review with Meta-Analysis

Background Dysregulation of several inflammatory cytokines including tumor necrosis factor (TNF) in dementia patients has also been identified as a key factor in the pathogenesis of rheumatoid arthritis (RA). We aimed to investigate the association of disease-modifying anti-rheumatic drugs (DMARDs) therapy for RA with risk of incident dementia. Methods Electronic database searches of PubMed, EMBASE and Cochrane Library were performed. Observational studies that assessed the association of dementia with DMARDs in RA were included. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were used as summary statistic. The certainty of evidence using the GRADE system. Results Fourteen studies involving 940,442 patients with RA were included. Pooled RR for developing dementia was 0.76 (95%CI 0.72-0.80) in patients taking biological DMARDs overall versus those taking conventional synthetic DMARDs, with 24% for TNF inhibitors (RR 0.76, 95%CI 0.71-0.82), 24% for non-TNF biologics (RR 0.76, 95%CI 0.70-0.83), separately. There was a significant subgroup effect among different types of TNF inhibitors (RR 0.58, 0.65, 0.80 for etanercept, adalimumab, infliximab, respectively; P-value between groups=0.002). However, compared with nonusers of DMARDs or investigative treatment, no significant effect on dementia incidence was observed in those receiving conventional synthetic DMARDs overall (RR 0.84, 95%CI 0.59-1.20), methotrexate (RR 0.78, 95%CI 0.54-1.12), hydroxychloroquine (RR 0.95, 95%CI 0.63-1.44), except for sulfasalazine (RR 1.27, 95%CI 1.06-1.50). Conclusions Biological DMARDs for RA are associated with decreased dementia risk, while protective effect is not observed in conventional synthetic DMARDs. Controlled clinical trials on TNF inhibitors is necessary to test their neuroprotective potentials.

EPH21 Risk of Incident Cardiovascular Events with Disease-Modifying Antirheumatic Drugs Combinations Among Adult Patients with Rheumatoid Arthritis: A Nested Case-Control Study

Disease-modifying antirheumatic drugs (DMARDs) are the cornerstone of rheumatoid arthritis (RA) treatment. DMARDs targeting inflammation for disease control could reduce cardiovascular (CV) risk; however, each DMARD class with unique mechanistic pathways may have differential CV risk. This study examined the risk of CV disease (CV) associated with DMARDs in RA.

Prevalence, mortality, and treatment of patients with rheumatoid arthritis: A cohort study of the French National Health Data System, 2010-2019.

Rheumatoid arthritis (RA) is a chronic inflammatory disease mostly affecting the joints. Data on the prevalence of RA differ widely, depending on the study and country. Our objectives were to estimate the prevalence of RA in France and the mortality rate, characterise the causes of death, and identify prescribed treatments. This nationwide cohort study was based on data of the French National Health Data System (SNDS) which covers 99% of the French population. All patients identified with RA based on specific ICD-10 codes (M05 and M06, except M06.1) between 2010 and 2019 were included. We identified 385,919 RA cases between 2010 and 2019, 318,243 of which were followed in 2019 (65.8±16.8 years, 72% women). The overall crude prevalence rate in 2019 was 0.47%: 0.66% for women and 0.28% for men. The crude annual mortality rate was 3.1%. The overall standardised mortality ratio (SMR) of RA patients relative to the French general population decreased over time, reaching 1.21 in 2019. Cause-specific mortality was increased in RA patients for cardiovascular (SMR 1.40, 95% confidence interval 1.36-1.43), respiratory system (1.80, 1.73-1.87), digestive system (1.73, 1.59-1.88), and urogenital system (1.73, 1.59-1.88) diseases and infections (1.91, 1.76-2.06). We found no excess mortality due to tumours. The prevalence of treatment with conventional synthetic and biological/targeted synthetic disease-modifying antirheumatic drugs for RA in 2019 was 41.9% (n=133,477) and 18.7% (n=59,409), respectively. Our results may provide a better understanding of RA and its care in France.

Associations between the interleukin-6 rs1800795 G/C and interleukin-6 receptor rs12083537 A/G polymorphisms and response to disease-modifying antirheumatic drugs in rheumatoid arthritis: A meta-analysis

ObjectiveWe aimed to investigate the association between interleukin-6 (IL-6) rs1800795 G/C, IL-6 receptor (IL-6R) rs12083537 A/G, and rs4329505 T/C polymorphisms and responsiveness to disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). MethodsWe searched Medline, Embase, and Web of Science databases. We conducted a meta-analysis of studies on the association between the IL-6 rs1800795 G/C, IL-6R rs12083537 A/G and rs4329505 T/C polymorphisms and responsiveness to DMARDs in RA patients. ResultsFourteen studies from eight published articles involving 982 patients were included in this meta-analysis. The meta-analysis showed a significant association between the IL-6 rs1800795 G allele and response to DMARDs in RA (P = 0.008). Stratification by DMARD class showed that the IL-6 rs1800795 G allele was significantly associated with responsiveness to biological DMARDs (bDMARDs) (P = 0.022), but not conventional synthetic DMARDs (P = 0.145). A significant association was also found between the IL-6 rs1800795 G/C polymorphism and response to DMARDs. The meta-analysis revealed a significant association between the IL-6R rs12083537 A allele and response to tocilizumab in RA patients (P = 0.001). A significant association was also found between the IL-6R rs12083537 AA genotype and response to tocilizumab in RA patients (P = 0.001). However, no association was found between the IL-6R rs4329505 T/C polymorphism and response to tocilizumab. ConclusionsThis meta-analysis revealed associations between treatment response to bDMARDs and the IL-6 rs1800795 G/C polymorphism, and between response to tocilizumab and the IL-6R rs12083537 A/G polymorphism in RA.

Systematic Review and Meta-Analysis on the Effect of Transdermal Preparations of Sinomenium Acutum on Rheumatoid Arthritis

Objective: We evaluated the efficacy and safety of transdermal preparations of Sinomenium acutum (SA) for rheumatoid arthritis (RA). Methods: Randomized controlled trials (RCTs) of SA transdermal preparations for RA were extracted from relevant databases and screened in accordance with the inclusion criteria. The Cochrane System Evaluation Manual (version 5.1.0) was used to assess the quality of the included trials. We used the Cochrane Review Manager (version 5.4) to conduct the meta-analysis. Results: Six trials comprising 436 patients (220 patients in the treatment group and 216 patients in the control group) were analyzed. The meta-analysis indicated that SA transdermal preparations in combination with disease-modifying antirheumatic drugs (DMARDs) enhanced the overall effect (odds ratio [OR] 3.97, 95% confidence interval [CI] [2.25, 7.00], P<0.00001), decreased visual analogue scale (VAS) results (mean difference [MD] –0.64, 95% CI [–1.20, –0.09], P=0.02), decreased laboratory indexes including the erythrocyte sedimentation rate (ESR) (MD –4.36, 95% CI [–5.63, –3.08], P<0.00001) and C-reactive protein (CRP) (MD –3.6, 95% CI [–3.99, –3.21, P<0.00001]), and decreased the Disease Activity Score-28 (DAS28) (MD –0.41, 95% CI [–0.78, –0.03], P=0.03). The results suggest that combination therapy did not shorten the duration of morning stiffness (DMS; standardized MD [SMD] –6.13, 95% CI [–17.33, 5.06], P=0.28) or reduce rheumatoid factor (RF) laboratory indexes (SMD –0.85; 95% CI [–2.19, 0.49], P=0.21). Only one study reported adverse reactions, and thus, it was difficult to determine whether adverse drug reactions in the combination therapy group were significantly different from those in the control group. Conclusion: We found that SA transdermal preparations combined with DMARDs may have greater clinical efficacy than DMARDs for RA. More well-designed and high-quality RCTs are required to verify the findings and determine whether transdermal preparations cause fewer adverse events.

Positive impact on 10-year outcome of the window of opportunity for conventional synthetic DMARDs in rheumatoid arthritis: results from the ESPOIR cohort.

ObjectiveThis study aimed to assess the impact of disease-modifying antirheumatic drugs (DMARDs) on 10-year outcomes in rheumatoid arthritis (RA).MethodsPatients with RA from the ESPOIR cohort with complete data on Disease Activity Score in 28 Joints (DAS28) and Health Assessment Questionnaire (HAQ) at 10 years (n=418) and complete radiographic data at baseline and 10 years (n=343) were included in this study. Outcomes were favourable outcome (FavOut) at 10 years, defined as DAS28 of <2.6 and HAQ score of <0.5 at 10 years, and absence of structural damage progression (AbsSDP) at 10 years, defined as change in Sharp-van der Heijde Score less than the smallest detectable change at 10 years (11.5 points). Three multivariate logistic regression models predicting 10-year outcome were built, considering (1) baseline variables only, (2) baseline variables and DMARD exposure (ever exposed, yes/no) and (3) baseline variables and DMARD exposure as weighted cumulative exposure (WCE) variables.ResultsOverall, 196/418 (46.9%) patients showed FavOut and 252/343 (73.5%) AbsSDP. WCE models had the best predictive performance, with area under the curve=0.80 (95% CI 0.74 to 0.87) for FavOut and 0.87 (95% CI 0.83 to 0.92) for AbsSDP. In the WCE model, the odds of FavOut and AbsSDP were reduced with conventional synthetic disease-modifying antirheumatic drug (csDMARD) initiation at 12 months versus at baseline (OR 0.78, 95% CI 0.65 to 0.94, and OR 0.89, 95% CI 0.76 to 0.98, respectively). Early biologics initiation was not significantly associated with either outcome.ConclusionsWCE models can identify and quantify the long-term benefit of early csDMARD initiation on 10-year functional and structural outcomes in patients with RA.

Pharmacogenetics of Drug Therapies in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that can lead to severe joint damage and is often associated with a high morbidity and disability. Disease-modifying anti-rheumatic drugs (DMARDs) are the mainstay of treatment in RA. DMARDs not only relieve the clinical signs and symptoms of RA but also inhibit the radiographic progression of disease and reduce the effects of chronic systemic inflammation. Since the introduction of biologic DMARDs in the late 1990s, the therapeutic range of options for the management of RA has significantly expanded. However, patients' response to these agents is not uniform with considerable variability in both efficacy and toxicity. There are no reliable means of predicting an individual patient's response to a given DMARD prior to initiation of therapy. In this chapter, the current published literature on the pharmacogenetics of traditional DMARDS and the newer biologic DMARDs in RA is highlighted. Pharmacogenetics may help individualize drug therapy in patients with RA by providing reliable biomarkers to predict medication toxicity and efficacy.

Sweet’s Syndrome in a Patient With Seropositive Rheumatoid Arthritis After Starting Adalimumab: Is Sweet’s Syndrome Related to Rheumatoid Arthritis or Is It the Paradoxical Effect of Adalimumab?

Sweet’s syndrome is a rare acute febrile neutrophilic dermatosis accompanied by fever, neutrophilia, and asymmetrical distribution of tender erythematous skin lesions. The underlying biological pathways responsible for this inflammatory skin disorder are not yet clearly established. However, an association with autoimmune disease, neoplasm, and drugs could be indicative of unusual hypersensitivity involving proinflammatory cytokines. There are several case reports indicating an association between Sweet’s syndrome and rheumatoid arthritis (RA). Proinflammatory cytokines are considered to play a vital role in the pathogenesis of both RA and Sweet’s syndrome. Adalimumab works against proinflammatory cytokines and is considered a disease-modifying antirheumatic drug in RA; it is also reported to be effective in refractory Sweet’s syndrome. While adalimumab has been proven to be beneficial in autoimmune disorders and inflammatory conditions, there are also reports of paradoxical development of Sweet’s syndrome with adalimumab. In this report, we present a case of Sweet’s syndrome in a 74-year-old adult patient with a history of seropositive RA who developed Sweet’s syndrome within two months after the initiation of adalimumab therapy.

Management issues in rheumatoid arthritis-associated interstitial lung disease.

Summarize recent evidence on the identification and management of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Clinical and subclinical interstitial lung disease (ILD) are frequent extra-articular manifestations of rheumatoid arthritis (RA). Better means of identifying and treating RA-ILD are needed to improve the prognosis, with a median survival of only 3-7 years after diagnosis. Several serum biomarkers are currently being evaluated for their ability to detect RA-ILD. Thorough evaluation and multidisciplinary discussion remains the gold standard for establishing the diagnosis of RA-ILD. Management is challenging with most RA disease-modifying antirheumatic drugs (DMARDs) linked to pneumonitis. Methotrexate is typically avoided in clinically significant ILD, although alternative therapies including leflunomide and biologic DMARDs also carry risks in RA-ILD. Antifibrotics appear to slow the progression of ILD, and a large phase II trial exclusively in RA-ILD is underway. In addition, smoking cessation, pulmonary rehabilitation, oxygen therapy, managing comorbidities, and lung transplantation evaluation are vital to improving patient outcomes in RA-ILD. With little high-quality evidence to guide the management of RA-ILD, multidisciplinary teams with expertise in RA-ILD are highly valuable for diagnosing and treating RA-ILD. Clinical and translational research in RA-ILD is needed to fill the many evidence gaps.

Efficacy and safety of combined therapy with synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: Systematic literature review

Objective(1) To systematically and critically review the evidence of combined therapy with synthetic disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) and (2) to design practical recommendations on their use. MethodsA systematic literature review (SLR) was performed with a sensitive bibliographic search strategy in Medline, EMBASE and Cochrane Library. We selected randomised clinical trials that analysed the efficacy and/or safety of (1) combined therapy of synthetic compared with sequential therapy of synthetic DMARD in early RA and (2) combination of methotrexate+leflunomide or triple therapy with synthetic DMARD in established RA refractory to synthetic DMARD. Two reviewers made the first selection by title and abstract and 11 performed the selection after detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. Based on the results, related recommendations were agreed upon in a nominal group meeting. ResultsUltimately, no articles were included in the SLR. The analysis of the reviewed articles demonstrated the effectiveness of the treatment with synthetic DMARD following a “treat to target” strategy in early RA patients, and of combination therapy of synthetic DMARD in established RA refractory to synthetic DMARD. This resulted in 6 recommendations concerning combination therapy with synthetic DMARD. ConclusionsThese recommendations aim to facilitate decision-making with the use of combined therapy with DMARD in RA.

Is cholecalciferol a potential disease-modifying anti-rheumatic drug for the management of rheumatoid arthritis?

Vitamin D is a pleiotropic molecule with a well-characterised immunomodulatory activity in vitro; however, its potential clinical application in autoimmune conditions has yet to be clarified. Several authors have investigated the use of vitamin D as a disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA), obtaining divergent conclusions. This systematic review summarises and critically analyses the findings of papers assessing the impact of vitamin D supplementation on pain relief, disease activity, functional status and flare rate. We conclude that the correction of hypovitaminosis D may have a beneficial effect on pain perception; moreover, the achievement of an adequate plasma vitamin D concentration obtained with high-dose regimens might evoke immunomodulatory activities of vitamin D and favourably impact on disease control. Nevertheless, the current evidence is still not strong enough to support the use of cholecalciferol as a DMARD in RA, and further studies are required to clarify this issue.

A novel function of artesunate on inhibiting migration and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients

IntroductionAnti-malarial drug artesunate can suppress inflammation and prevent cartilage and bone destruction in collagen-induced arthritis model in rats—suggesting it may be a potent drug for rheumatoid arthritis (RA) therapy. We aimed to investigate its effect on the invasive property of fibroblast-like synoviocytes (FLS) from patients with RA.MethodsSynovial tissues were obtained by closed needle biopsy from active RA patients, and FLS were isolated and cultured in vitro. RA-FLS were treated with artesunate at various concentrations, while methotrexate or hydroxychloroquine was employed as comparator drugs. Cell viability, proliferation, cell cycle, apoptosis, migration, invasion, and pseudopodium formation of RA-FLS were assessed by CCK-8 assays, EdU staining, Annexin V-FITC/PI staining, transwell assays, or F-actin staining, respectively. Further, relative changes of expressed proteases were analyzed by Proteome profiler human protease array and verified by quantitative real-time PCR (qPCR), Western blot, and ELISA. The expression of signaling molecules of MAPK, NF-κB, AP-1, and PI3K/Akt pathways were measured by qPCR and Western blot. PDK-1 knockdown by specific inhibitor AR-12 or siRNA transfection was used to verify the pharmacological mechanism of artesunate on RA-FLS.ResultsArtesunate significantly inhibited the migration and invasion of RA-FLS in a dose-dependent manner with or without TNF-α stimulation. The effect was mediated through artesunate inhibition of MMP-2 and MMP-9 production, and pre-treatment with exogenous MMP-9 reversed the inhibitory effect of artesunate on RA-FLS invasion. Artesunate had a stronger inhibitory effect on migration and invasion of RA-FLS as well as greater anti-inflammatory effect than those of hydroxychloroquine. Similar inhibitory effect was detected between artesunate and methotrexate, and synergy was observed when combined. Mechanistically, artesunate significantly inhibited PDK-1 expression as well as Akt and RSK2 phosphorylation—in a similar manner to PDK-1-specific inhibitor AR-12 or PDK-1 knockdown by siRNA transfection. This inhibition results in suppression of RA-FLS migration and invasion as well as decreased MMP-2 and MMP-9 expression.ConclusionsOur study demonstrates artesunate is capable of inhibiting migration and invasion of RA-FLS through suppression of PDK1-induced activation of Akt and RSK2 phosphorylation—suggesting that artesunate may be a potential disease-modifying anti-rheumatic drug for RA.

Systematic review and meta-analysis of the efficacy and safety of leflunomide and methotrexate in the treatment of rheumatoid arthritis

ObjectiveTo assess the efficacy and side effects of methotrexate and leflunomide in patients with rheumatoid arthritis (RA) as the first disease-modifying antirheumatic drug (DMARD). MethodsWe performed a systematic review and meta-analysis of clinical studies that included patients who took methotrexate, leflunomide, placebo or another DMARD for RA treatment. A systematic review yielded 1971 articles from databases; once completely reviewed, 73 trials that completed inclusion criteria were selected. In structured workshops for discussion and assessment of each article, 6 could be meta-analyzed for the primary and secondary outcomes: achievement of American College of Rheumatology (ACR) 20 and its core set components; and change of serum C-reactive protein (CRP) levels, Health Assessment Questionnaire Disability Index (HAQ-Di), liver enzyme aspartate transaminase/alanine transaminase ratio, new gastrointestinal (GI) side effects and infections. ResultsA total of 1984 patients were included: 986 took leflunomide and 998 methotrexate. The probability of achieving ACR 20 had an odds ratio (OR) of 0.88 (95% confidence interval [CI] 0.74, 1.06) with a trend toward favoring methotrexate; reduction of the swollen joint count was greater for methotrexate: mean difference=0.82 (95%CI 0.24, 1.39); tender joint count, physician global assessment, HAQ-Di, and serum CRP levels revealed no significant difference between groups. Increased liver enzymes were more frequent in the leflunomide group, OR=0.38 (95%CI 0.27, 0.53), and new GI complaints were more common with methotrexate (OR=1.44; 95%CI 1.17, 1.79). There was no difference in the incidence of non-severe infections. ConclusionLeflunomide used as the first DMARD in RA seemed to be as efficacious as methotrexate; only the reduction of swollen joint count was more marked for methotrexate. Leflunomide was linked to a greater increase in liver enzymes, but there were fewer GI complaints.

Adherence to Synthetic Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: Results of the OBSERVAR Study

BackgroundTreatment compliance with disease-modifying antirheumatic drugs (DMARD) is essential to achieve the therapeutic goals in rheumatoid arthritis (RA). However, despite the need for good compliance, there is evidence that patients with RA frequently fail to use DMARD for the control of RA. Thus, the main objective of the OBSERVAR study is to evaluate the reasons for the lack of therapeutic adherence to synthetic DMARD in these patients. Patients and methodsA Delphi process involving 18 randomly selected Spanish rheumatologists determined the level of agreement with 66 causes of noncompliance selected from the literature in relation to synthetic DMARD in RA. ResultsThe reasons for noncompliance were consistent in 75.7%, although 3 reasons (4.5%) were highly consistent: (1) not knowing what to do in the case of an adverse event with DMARD; (2) not having undergone adherence screening by health personnel for early detection of “noncompliant patients”; and (3) not having undergone interventions or strategies that improve adherence. ConclusionIn order to improve adherence to RA treatment with synthetic DMARD, the patient should be adequately informed of each new treatment introduced, the patient's compliance profile should be incorporated into the clinical routine and the patient's motivation for therapeutic compliance be reinforced through the methods available to us.

Efficacy and safety of various anti-rheumatic treatments for patients with rheumatoid arthritis: a network meta-analysis.

IntroductionBiologics and traditional disease-modifying anti-rheumatic drugs (DMARDs) are generally used in treating patients with rheumatoid arthritis (RA). Previous studies have presented abundant data and information about the efficacy of such treatments, but the results were incomplete and inconclusive. This network meta-analysis was conducted to compare and assess the efficacy and safety of 15 therapies employing biologics and DMARDs for RA patients.Material and methodsSix outcomes (American College of Rheumatology 20% response rate (ACR20), ACR50, ACR70, remission, adverse events (AEs) and serious adverse events (SAEs)) were used to evaluate the efficacy and safety of different treatments. The node-splitting method was used to assess the inconsistency, and the rank probabilities of the therapies were estimated by surface under the cumulative ranking curve. Besides, Jadad scale was used to evaluate the methodological quality of eligible studies.ResultsA total of 67 randomized controlled trials with 20,898 patients met the inclusion criteria. Most of the therapies presented better performance than conventional DMARDs (cDMARDs) and placebo in ACR20, ACR50 and ACR70. Conversely, the safety of cDMARDs and placebo seemed to be superior in AEs and SAEs. Also, tocilizumab (TCZ) and TCZ + methotrexate (MTX) showed better remission in pain compared to other treatments. Overall, certolizumab pegol (CZP) + MTX and TCZ + MTX had higher probability than the other treatments in efficacy outcomes.ConclusionsWe recommend CZP + MTX as the optimal drug therapy because it has the highest ranking in efficacy outcomes and relatively low risk of adverse events. TCZ + MTX is recommended as an alternative. Abatacept (ABT) and cDMARDs are not recommended due to their low efficacy.

Systematic review and meta-analysis of the efficacy and safety of leflunomide and methotrexate in the treatment of rheumatoid arthritis.

To assess the efficacy and side effects of methotrexate and leflunomide in patients with rheumatoid arthritis (RA) as the first disease-modifying antirheumatic drug (DMARD). We performed a systematic review and meta-analysis of clinical studies that included patients who took methotrexate, leflunomide, placebo or another DMARD for RA treatment. A systematic review yielded 1971 articles from databases; once completely reviewed, 73 trials that completed inclusion criteria were selected. In structured workshops for discussion and assessment of each article, 6 could be meta-analyzed for the primary and secondary outcomes: achievement of American College of Rheumatology (ACR) 20 and its core set components; and change of serum C-reactive protein (CRP) levels, Health Assessment Questionnaire Disability Index (HAQ-Di), liver enzyme aspartate transaminase/alanine transaminase ratio, new gastrointestinal (GI) side effects and infections. A total of 1984 patients were included: 986 took leflunomide and 998 methotrexate. The probability of achieving ACR 20 had an odds ratio (OR) of 0.88 (95% confidence interval [CI] 0.74, 1.06) with a trend toward favoring methotrexate; reduction of the swollen joint count was greater for methotrexate: mean difference=0.82 (95%CI 0.24, 1.39); tender joint count, physician global assessment, HAQ-Di, and serum CRP levels revealed no significant difference between groups. Increased liver enzymes were more frequent in the leflunomide group, OR=0.38 (95%CI 0.27, 0.53), and new GI complaints were more common with methotrexate (OR=1.44; 95%CI 1.17, 1.79). There was no difference in the incidence of non-severe infections. Leflunomide used as the first DMARD in RA seemed to be as efficacious as methotrexate; only the reduction of swollen joint count was more marked for methotrexate. Leflunomide was linked to a greater increase in liver enzymes, but there were fewer GI complaints.

Application of omics in predicting anti-TNF efficacy in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by progressive joint erosion. Tumor necrosis factor (TNF) antagonists are the most widely used biological disease-modifying anti-rheumatic drug in RA. However, there continue to be one third of RA patients who have poor or no response to TNF antagonists. Following consideration of the uncertainty of therapeutic effects and the high price of TNF antagonists, it is worthy to predict the treatment responses before anti-TNF therapy. According to the comparisons between the responders and non-responders to TNF antagonists by omic technologies, such as genomics, transcriptomics, proteomics, and metabolomics, rheumatologists are eager to find significant biomarkers to predict the effect of TNF antagonists in order to optimize the personalized treatment in RA.

Circulating cell free DNA: a marker to predict the therapeutic response for biological DMARDs in rheumatoid arthritis.

To evaluate the correlation between circulating cell-free DNA (ccfDNA) in plasma and clinical disease activities in patients with rheumatoid arthritis (RA). The study group included 30 patients with RA who started biological disease-modifying anti-rheumatic drugs (DMARDs) therapy. The concentration of ccfDNA in plasma was measured by quantitative real-time polymerase chain reaction at baseline to 24 weeks in every 4-week period from 30 patients and 21 healthy individuals. We also evaluated the correlation between ccfDNA and the clinical activity or the therapeutic response for biological DMARDs, using the simplified disease activity index (SDAI), Disease Activity Score of 28 joints (erythrocyte sedimentation rate) and the European League Against Rheumatism (EULAR) response criteria. Synovial fluid samples of knee joints were collected from 13 patients with RA and 12 with osteoarthritis (OA) to measure ccfDNA. The concentration of ccfDNA in RA patients at baseline was higher than healthy controls (P = 0.016). After introducing biological DMARDs, ccfDNA was increased until 8 weeks from the baseline, and decreased after 12 weeks. The average of SDAI was improved in all patients enrolled. At 12 weeks after treatment, 15 patients were good responders to the EULAR response criteria, nine showed moderate response and six showed no response. ccfDNA in good responders was increased until 8 weeks, while those of moderate or no response were not (P = 0.042). In joint fluid of RA patients, ccfDNA was remarkably increased as compared to those from OA (P = 0.00011). After introducing biological DMARDs, increase of ccfDNA at 8 weeks was associated with improvement of disease activities. Compared with biomarkers reported, ccfDNA is able to predict the early therapeutic effects of biological DMARDs in RA patients.

Evaluation of changes in magnetic resonance images following 24 and 52 weeks of treatment of rheumatoid arthritis with infliximab, tocilizumab, or abatacept

Objectives. To compare MRI findings in rheumatoid arthritis (RA) patients treated with biologic disease-modifying anti-rheumatic drugs (DMARDs).Methods. The study subjects were 43 RA patients treated with biologic DMARDs (13 with infliximab, 15 with tocilizumab, and 15 with abatacept). They were evaluated using Simplified Disease Activity Index (SDAI) and low-field extremity MRI at baseline, and at 24 weeks and 52 weeks of treatment.Results. Synovitis scores were significantly lower by 24 weeks in all groups, compared with baseline (P < 0.05). Significant improvement in bone marrow edema (BME) scores were noted from baseline to 24 weeks in infliximab and abatacept groups (P < 0.05), but from 24 weeks to 52 weeks in tocilizumab group (P < 0.01). No significant change was found in erosion score. The synovitis score at baseline correlated significantly with SDAI at 24 weeks (P < 0.05), and the score at 24 weeks correlated significantly with SDAI at 52 weeks (P < 0.05).Conclusions. The results suggest that the inflammatory improvement by infliximab and abatacept may express earlier than those by tocilizumab, despite similar improvement in SDAI. MRI-detected synovitis could be a useful predictor of SDAI at 24 weeks of treatment. The MRI remains the best tool to detect and assess the effects of biologic DMARDs in RA.