Severe Rheumatoid Arthritis Patients Research Articles

Promoter polymorphisms of neuropeptide Y, interleukin-1B and increased IL-1β levels are associated with rheumatoid arthritis susceptibility in South Gujarat population

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint destruction. Interleukin-1B(IL-1β) has been implicated in RA, and neuropeptide Y (NPY) induces the release of pro-inflammatory cytokines including IL1-β, TNF-α and IL-6. Single nucleotide polymorphisms (SNPs) in NPY and IL1B gene may lead to their altered levels leading to RA pathogenesis. Therefore, we aimed to investigate association of NPY rs16147(T > C) SNP, and genotype–phenotype correlation of the IL1B rs16944(C > T) SNP in 302 RA patients and 337 controls by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Both the genotype and allele frequencies for NPY rs16147(T > C)(p = 0.0019 &p = 0.012) and IL1B rs16944(C > T)(p = 0.0024 &p = 0.0014) SNPs differed significantly between RA patients and controls. The odds ratios of 1.23 and 1.47 for NPY rs16147(T > C) and IL1B rs16944(C > T) SNPs respectively, suggest that these SNPs may be genetic risk factor for RA in South Gujarat population. The plasma IL-1β levels(p = 0.0332) and genotype-phenotype correlation of IL1B rs16944(C > T) SNP suggested increased IL-1β levels, particularly in patients with susceptible ‘TT' genotypes(p < 0.0001). Additionally, plasma IL-1β level was significantly increased in severe RA patients (p = 0.0025) and positively correlated with Rheumatoid factor(RF) (r = 0.9240, p < 0.0001), suggesting the role of IL-1β in disease severity. Overall, the study for the first time suggests that NPY rs16147(T > C) and IL1B rs16944(C > T) SNPs may be associated with RA susceptibility in South Gujarat population. Additionally, the IL1B rs16944 susceptible ‘TT' genotype may lead to increased IL-1β levels, thereby contributing to RA pathogenesis and severity.

Assessment of physical functioning in rheumatoid arthritis patients after rituximab therapy using health assessment questionnaire-disability index

The most frequently used instrument for measuring self-reported physical function in rheumatoid arthritis is the health assessment questionnaire – disability index. The objective of this study was to assess the effects of treatment with rituximab on patient-reported outcomes in severe rheumatoid arthritis patients. Rituximab was initiated in RA-diagnosed patients who experienced treatment failure or decreased response on the administration of conventional disease-modifying anti-rheumatic drugs. Treatment response after 1g of rituximab infusion was assessed at &lt;6 months and &gt; 6 months follow-up period using patient-reported outcome measure tools and laboratory investigations. Functional ability was evaluated using a questionnaire and the overall disability index was calculated. It was found that all patients achieved minimum clinically important difference(&gt;0.2) from baseline HAQ value within 6 months of rituximab. Assessment of the functional ability demonstrated that the majority of the patients experienced significant improvement in all domains of HAQ-DI after rituximab administration. Patient global assessment shared a moderate correlation with almost all domains of HAQ-DI. Physical function as measured by HAQ-DI showed clinically meaningful improvement within 1 year of rituximab therapy. It has proven to be a safer and more effective treatment option when compared to conventional disease-modifying antirheumatic drugs and has also helped in achieving better responses at a faster pace.

Biologics initiation in moderate versus severe rheumatoid arthritis: real-world experience from a Canadian registry.

To evaluate the treat-to-target experience, and quality of life measures of moderate and severe rheumatoid arthritis (RA) patients initiating a biologic in a real-world setting of a publicly funded payer system. Biologic naive RA patients who had initiated their first biologic while enrolled in the Ontario Best Practices Research Initiative registry from 2008 to 2020 were selected if they had moderate (DAS28 >3.2 to ≤5.1) or severe (DAS28 >5.1) RA. Remission, LDA, DAS28, HAQ-DI, fatigue, sleep, drug persistence and characteristics associated with remission were assessed at 12 months post biologic initiation. Overall, 838 patients initiated their first biologic, 264 had moderate RA and 219 had severe RA. After 12 months, 44% moderate RA vs. 21% severe RA achieved remission (p<0.0001), and 59% moderate RA vs. 35% severe RA reached LDA (p<0.0001). Mean change (SD) from baseline in DAS28 was 2.2 (1.5) in severe RA vs. 1.4 (1.3) in moderate RA (p<0.0001), in fatigue score was 1.11 (3.2) in severe RA vs. 0.98 (3.2) in moderate RA (p<0.0001). Moderate disease at a biologic initiation was positively associated with remission (p=0.0016). Female gender (p=0.0170), and a higher HAQ-DI score at baseline (p=0.0042) were negatively associated with remission. Biologic persistence was 77% for moderate, and 73% for severe (p=0.2444). Severe RA patients had higher mean score improvements in DAS28, sleep and fatigue. Moderate RA was more likely to reach remission or LDA. Both groups had similar biologic persistence at 12 months. These findings highlight the importance of the treat-to-target approach and its potential underutilisation in the real-world setting.

The Role of IL-37 as an Anti-Inflammatory Biomarker in some Iraqi Rheumatoid Arthritis Patients and Its Correlation with DAS28

Interleukin-37 (IL-37) is a new anti-inflammatory cytokine that inhibits immunological response and inflammation. The purpose of this study is to look into the role of IL-37 and if it correlates with disease activity in some Iraqi RA patients. The scope of the investigation comprised of 76 females with RA who are aged in the range of (45.38 ±1.23 years) and 40 individuals in the control group with age of (46.48 ± 2.02years). When compared to controls, the level of serum IL-37 was shown to be considerably elevated in RA patients. (49.16 ± 3.25pg/ml vs. 32.04 ± 2.22pg/ml; p ≤ 0.05). However, the DAS28 score results showed a non-significant difference between the mild and severe rheumatoid arthritis patients. There was a positive association, statistically significant between the DAS28 score and anti-CCP Abs, RF. A positive correlation between DAS28 and ESR. While non-significantly correlated between DAS28 and CRP, IL-37.

Assessment of real-life patient handling experience of AVT02 administered subcutaneously via autoinjector in patients with moderate to severe active rheumatoid arthritis: an open-label, single-arm clinical trial, then an extension phase of AVT02 administered with a prefilled syringe

ABSTRACT Background This study investigated the ability of patients, naïve to adalimumab treatment and self-injection with an autoinjector (AI), to successfully self-administer AVT02, an adalimumab biosimilar, using a custom, ergonomic AI (Alvotech hf., Reykjavik, Iceland). Research design and methods This was a single-arm, open-label study, consisting of an 8-week active period and 48-week extension phase. Patients with moderate to severe rheumatoid arthritis (RA) self-administered 40 mg AVT02 subcutaneously via AI in the active period, followed by prefilled syringe in the extension phase. The primary endpoint was the percentage of successful self-injections up to Week 8. Usability and robustness of the AI were evaluated in the active period; safety, efficacy, pharmacokinetic and immunogenicity data were assessed throughout the study. Results The AI success rate was 100%. No handling events were noted up to Week 8. Both Ctrough measurements and immunogenicity profile were in line with expectations from previous studies, with no unexpected safety signals. Conclusions This study demonstrated that AVT02-AI can be successfully and reliably used for repeated self-injections of AVT02 by moderate to severe RA patients, despite no previous experience of adalimumab self-administration. The extension phase provides long-term efficacy and safety data for AVT02 in RA. Study identifier NCT04224194

Comparison of treatment of severe rheumatoid arthritis patients with biological agents and JAK-STAT inhibitors. An observational study.

IntroductionTreatment of severe rheumatoid arthritis (RA) is currently based either on biological agents or Janus kinase/signal transducer and activator of transcription inhibitors, most often in combination with methotrexate (MTX).Aim of the studyThe aim of the study was to compare the effectiveness and side effects of bio- logic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (ts) DMARDs treatment.Material and methodsThe analysis included 108 RA patients with active disease treated with MTX 25 mg per week. Eighty patients (group I) were treated with bDMARDs and 28 patients (group II) with JAK-STAT inhibitors. The duration of morning stiffness, pain on Visual Analogue Scale (VAS), 28-joints Disease Activity Score (DAS28) and Simplified Disease Activity Score (SDAI) were assessed. Classical radiographic images of patients’ hands and feet using the Larsen and Dale’s criteria were evaluated. The effects of treatment with bDMARDs and tsDMARDs were analyzed.ResultsAll studied patients presented at least Larsen and Dale’s stage 3 of X-ray changes typical for RA. There were no statistically significant differences in disease duration, ESR, CRP, DAS28 and SDAI values between studied groups. Patients from group II previously used higher numbers of bDMARDs than group I treated with bDMARDs. Low disease activity after treatment was achieved by all patients; therefore patients from group II (treated with tsDMARDs) achieved lower values of patients’ global assessment on VAS.ConclusionsThe results of the present observational study indicated that treatment with JAK inhibitors is very promising. These drugs are not inferior in effectiveness to bDMARDs. It is important to monitor patients for thromboembolic events before and during JAK treatment.

Peptides Bearing Multiple Post-Translational Modifications as Antigenic Targets for Severe Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies that are of paramount importance for the diagnosis and prognosis of the disease and have been implicated in its pathogenesis. Proteins resulting from post-translational modifications (PTMs) are capable of triggering autoimmune responses important for the development of RA. In this work, we investigate serum antibody reactivity in patients with an established RA against a panel of chimeric peptides derived from fibrin and filaggrin proteins and bearing from one to three PTMs (citrullination, carbamylation and acetylation) by home-designed ELISA tests (anti-AMPA autoantibodies). The role of anti-AMPAs as biomarkers linked to the presence of a more severe RA phenotype (erosive disease with radiological structural damage) and to the presence of interstitial lung disease (ILD), a severe extra-articular manifestation in RA patients entailing a high mortality, was also analyzed. In general, the association with the clinical phenotype of RA was confirmed with the different autoantibodies, and especially for IgA and IgM isotypes. The prevalence of severe joint damage was only statistically significant for the IgG isotype when working with the peptide bearing three PTMs. Furthermore, the median titers were significantly higher in patients with RA-ILD, a finding not observed for the IgG isotype when working with the single- and double-modified peptides.

Genetic association of interleukin-4 VNTR polymorphism with susceptibility to rheumatoid arthritis in South Gujarat population

Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease, which causes swelling and severe pain within joints. The variable number tandem repeats (VNTR) polymorphism of interleukin-4 (IL4) gene has been associated with autoimmune diseases including RA. The study investigated the association of IL4 VNTR (IVS3; R1 > R2) polymorphism with RA susceptibility in South Gujarat population of India. Polymerase chain reaction (PCR) method was used for genotyping of IL4 VNTR polymorphism in 302 RA patients and 334 controls and ELISA was used for estimation of plasma IL-4 levels. The genotype and allele frequencies of the polymorphism were significantly differed between RA patients and control population (p < 0.0001), suggesting that IL4 VNTR polymorphism is associated with RA susceptibility in South Gujarat population. The susceptible ‘R2’ allele was prevalent in RA group as compared to the control group (79.4% vs 64.00%; p < 0.0001). Moreover, both the genotype and allele frequencies were significantly differed between severe and mild RA patients (p = 0.0039 & p = 0.0005 respectively). The plasma IL-4 levels (p = 0.0216) and genotype-phenotype correlation revealed significant increased IL-4 levels for R2R2 genotype in RA patients compared to controls (p = 0.0265). The IL-4 levels were significantly higher in R2R2 genotype when compared to R1R1 and R1R2 genotypes in RA patients (p = 0.007 & p = 0.03 respectively). Furthermore, IL-4 levels were significantly increased in severe RA patients compared to mild (p = 0.0293). Both, IL-4 levels and R2R2 genotypes were positively correlated with rheumatoid factor (r = 0.49, p = 0.0009 & r = 0.41, p = 0.035 respectively). Overall, the study for the first time suggests that IL4 VNTR R2 allele may be associated with susceptibility to RA in South Gujarat population and it is likely to play a role in increased IL-4 levels thereby contributing to RA pathogenesis.

Adverse Impact of Rheumatoid Arthritis on Pregnancy Outcomes: A Saudi Arabia Prospective Multicenter Study.

BackgroundRheumatoid arthritis (RA) is associated with adverse pregnancy outcomes and postpartum complications, especially with severe disease activity.ObjectiveThe current study aimed to compare the pregnancy outcomes in patients with RA and healthy controls as well as to assess the impact of disease-related variables, medications and disease activity on pregnancy and neonatal-related outcomes in the Saudi population.MethodsThis prospective multicenter study included pregnant female patients with RA from three tertiary centers in Saudi Arabia. The demographics, disease activity scoring (DAS28-CRP), medication before and during pregnancy, pregnancy-related outcomes, and complications in comparison to age-matched healthy female controls were noted.ResultsA total of 77 pregnant patients with RA and 250 healthy age-matched pregnant controls were included in the study. A total of 67.53% were in remission before conception (DAS28CRP ≤2.6), and 81.8% of pregnancies were planned. Age of conception, preterm labor, neonatal intensive care unit (NICU) admission and low birth weight were statistically significant (p <0.05) and higher in RA patients than in healthy controls. Longer disease duration (p <0.001), and high C-reactive protein and erythrocyte sedimentation rate levels before conception (p ≤0.001) were statistically associated with preterm NICU admission. There was statistically significant association between mild (p = 0.015) or moderate to severe DAS28-CRP (p = 0.001) and RA patients regarding pregnancy outcomes. The classification table obtained from the logistic model showed patients with mild and moderate-severe DAS28-CRP have significantly high chances of having an adverse pregnancy outcome.ConclusionRA has a negative impact on pregnancy-related outcomes. Higher disease activity is considered a major risk; thus, tight disease control should be aimed. Planned pregnancy follow-up is associated with better pregnancy outcomes.

Disease severity affects myocardial functions in patients with treatment-naive early rheumatoid arthritis.

The cross-sectional study aimed to assess myocardial functions using global longitudinal strain (GLS) echocardiography and arrhythmia parameters with treatment naive newly diagnosed rheumatoid arthritis (RA) and no clinical evidence of cardiovascular disease (CVD). Seventy seven newly diagnosed treatment-naive RA patients were enrolled. Disease severity was evaluated according to rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) positivity, and Disease Activity Score 28 C-reactive protein (DAS28 CRP). Myocardial functions were assessed using conventional echocardiography and GLS technique and electrocardiogram parameters cQT and Tp-e/cQT. Twenty three patients had severe disease while 54 patients were non-severe. The Left Ventricle GLS (17.98±1.24 vs 21.29±1.03, P<.001), cQT (428.71±9.05 vs 394.61±17.83, P<.001), Tp-e/cQT (0.19±0.02 vs 0.16±0.01, P<.001) for severe RA patients was reduced compared to RA non-severe patients. Penalized maximum likelihood estimation logistic regression analysis revealed LVGLS as the only significantly independent predictor of severe RA disease (OR 0.70, CI 95% 0.52-0.92, P=.001). Receiver operating characteristic (ROC) curves of the LVGLS was revealed 19.9 as GLS discriminative value with 88.8% positive predictive value for predicting severity. Severe RA risk increases when log-odds value was over 0, corresponds to LVGLS value less than 18 by partial effect plots. RA severity was associated with lower LV systolic myocardial function and increased arrhythmia parameters. Only LVGLS was significantly independent predictor of RA disease severity.

Activation of inflammation and resolution pathways of lipid mediators in synovial fluid from patients with severe rheumatoid arthritis compared with severe osteoarthritis.

BackgroundThe upregulation of the cyclooxygenase and lipoxygenase pathways of arachidonic acid is thought to be involved in the development of rheumatoid arthritis. Recently, the presence of specialized pro-resolving lipid mediators in synovial tissues from patients with osteoarthritis has been reported.ObjectiveTo clarify the quantitative and qualitative changes in lipid mediators in the synovium of severe rheumatoid arthritis patients, we compared the profiles of lipid mediators in synovial fluid obtained from patients with severe rheumatoid arthritis and from those with severe osteoarthritis.MethodsWe enrolled 18 patients with rheumatoid arthritis and 26 patients with osteoarthritis. All the patients had undergone total knee replacement surgery. Synovial fluid samples had been obtained during the surgery. Lipid profiling in the synovial fluid from these patients was performed using liquid chromatography-tandem mass spectrometry/mass spectrometry.ResultsAmong the 150 oxidized fatty acids examined so far, 119 were substantially detected in synovial fluid from the patients. Not only the concentrations of pro-inflammatory lipid mediators such as prostaglandins and leukotrienes, but also those of specialized pro-resolving lipid mediators such as lipoxins, resolvins, and protectin D1 were significantly higher in synovial fluid obtained from rheumatoid arthritis patients than from synovial fluid obtained from osteoarthritis patients.ConclusionThe activation of both inflammation and resolution pathways of lipid mediators might be a fatty acid signature in the synovial fluid of patients with severe rheumatoid arthritis. Inflammatory, anti-inflammatory and pro-resolving mediators in synovial fluid could be good biomarkers for differentiating between severe rheumatoid arthritis and severe osteoarthritis.

Efficacy and safety of an anti-CD20 monoclonal antibody (Reditux™) for the treatment of patients with moderate to severe rheumatoid arthritis following the failure of conventional synthetic disease-modifying anti-rheumatic drugs.

Rituximab (anti-CD20 monoclonal antibody) has shown to improve symptoms in rheumatoid arthritis (RA) patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). An anti-CD20 monoclonal antibody (Reditux™) developed by Dr. Reddy's Laboratories, India, is currently approved for use both in rheumatology and oncology patients. This retrospective report evaluates the efficacy and safety data from the real-world use of Reditux™ over a 6-month period in Indian patients with RA. All consecutive moderate to severe RA patients who failed therapy with at least two DMARDs including methotrexate (MTX) for 6months, TNFα inhibitor naive, and willing to take Reditux™ were included. They were prescribed two doses of 1g Reditux™, at least 15days apart, with continued stable doses of methotrexate. Efficacy and safety after 24weeks relative to baseline was assessed using various health assessment variables. A total of 39 patients (mean age of 46years; 67.5% females) treated with Reditux™ were evaluated. Statistically significant differences were observed in mean changes of DAS28-CRP, DAS28-ESR, SDAI, HAQ and Patient Global Assessment scores from baseline to 24weeks (p < 0.0001 for all). Average steroid use per week also significantly reduced at 24weeks (p = 0.0002). There was no significant gender difference. Mean changes in SDAI, HAQ and Patient Global Assessment scores for patients on steroids were significantly different from those not on steroids (p < 0.05 for all). At 24weeks, 97% of patients achieved ACR20 response demonstrating the efficacy of Reditux™ treatment. The treatment was well tolerated by patients without any clinically relevant serious adverse events over 24weeks. Though limited by number of patients and retrospective in nature, this analysis serves as a real-world evidence of efficacy and safety of Dr. Reddy's rituximab (Reditux™) in the treatment of csDMARD-failed patients with RA over a 6-month period.

RENACER study: Assessment of 12-month efficacy and safety of 168 certolizumab PEGol rheumatoid arthritis-treated patients from a Spanish multicenter national database

Objective: To assess effectiveness and safety of certolizumab PEGol (CZP) in rheumatoid arthritis (RA) patients after 12 months of treatment and to detect predictors of response.Methods: Observational longitudinal prospective study of RA patients from 35 sites in Spain. Variables (baseline, 3- and 12-month assessment): sociodemographics, previous Disease Modifying Anti-Rheumatic Drug (DMARD) and previous Biological Therapies (BT) use; TJC, SJC, ESR, CRP, DAS28, SDAI. Response variables: TJC, SJC, CRP, ESR, and steroids dose reductions, EULAR Moderate/Good Response, SDAI response and remission, DAS28 remission. Safety variables: discontinuation due to side-effects. Descriptive, comparative and Logistic regression analyses were performed.Results: We included 168 patients: 79.2% women, mean age 54.5 years (±13.2 SD), mean disease duration 7.5 years (±7.3 SD). Mean number of prior DMARD: 1.4 (±1.2 SD), mean number of prior BT was 0.8 (±1.1). Mean time on CZP was 9.8 months (±3.4 SD). A total of 71.4% were receiving CZP at 12-month assessment. Baseline predictors of response: lower prior number DMARD; low number prior BT; higher CRP, ESR, TJC, SJC, DAS28 and SDAI (p < 0.05) scores. A 25/46.4% Moderate/Good Response, a 20% SDAI remission, and a 44% DAS28 remission were observed. We observed 48 discontinuations (28.6%), 31 due to partial or complete ineffectiveness, and 17 due to side-effects.Conclusions: CZP showed benefit in severe RA patients, with significant reduction of all effectiveness parameters, despite the high prevalence of previous BT exposure in our series. We found CRP, ESR, prior DMARD/BT number, TJC, SJC, DAS28, and SDAI as baseline predictors of response. CZP was mostly well tolerated.

TNF as a Target of Inflammation in Rheumatoid Arthritis.

Anti-Tumor Necrosis Factor (TNF) agents were the first molecular targeting drugs developed for the treatment of rheumatoid arthritis (RA). Anti-TNF agents improve the clinical picture of severe RA patients, inhibit joint destruction and improve quality of life. In the 15 years since their introduction, they have become the preferred drug therapy for management of RA. The success of anti-TNF agents in the treatment of RA has resulted in the development of many drugs for other inflammatory diseases using the same molecular targeting concept. However, many unresolved issues surround the use of anti-TNF agents, including the risk for infection, primary non-responders, secondary loss of efficacy and pharmacoeconomical issues. This review focuses on the multifaceted impact of anti-TNF agents in the treatment of RA.

AB0464 The Efficacy and Safety of Iguratimod in Rheumatoid Arthritis Patients with Chronic Renal Failure

BackgroundMethotrexate (MTX) is the first line drug in rheumatoid arthritis (RA) patients. However MTX couldn't be treated in RA patients due to renal failure. Iguratimod is a newly-developed disease-modifying antirheumatic...

Impact of Etanercept on Work and Activity Impairment in Employed Moderate to Severe Rheumatoid Arthritis Patients in the United States

To quantify the impact of etanercept on work and activity impairment in employed US patients with moderate to severe rheumatoid arthritis (RA). This prospective, observational, longitudinal study recruited RA patients initiating etanercept (50 mg/week) between January 2009 and March 2010. The Work Productivity and Activity Impairment Questionnaire (WPAI) and domestic productivity questionnaire were administered by telephone interviews at baseline and at 1, 2, 3, and 6 months after etanercept initiation. The human capital approach was used to estimate the costs of work impairment. Changes in WPAI measures were analyzed using Wilcoxon's signed rank test. RA patients (n = 204) initiating etanercept were a mean ± SD age of 46.6 ± 10.9 years and 72% were women. After 6 months, 153 patients continued treatment (continuers) and showed significant decreases in overall work impairment (41.9% at baseline versus 25.2% at 6 months; P < 0.0001), absenteeism (8.4% versus 2.3%; P = 0.0001), presenteeism (38.9% versus 24.3%; P < 0.0001), and activity impairment (55.7% versus 30.9%; P < 0.0001) and a 76.4% reduction in work hours lost weekly due to RA (3.2 versus 0.8; P = 0.0001). The projected 12-month gain in work productivity for continuers was 284.5 hours per patient, equating to $3,233-22,533 depending on annual income level, which partially or completely offset the annual cost of etanercept ($20,190). Domestic productivity improved from 41.5% at baseline to 69.6% at 6 months (P < 0.0001). In US employed moderate to severe RA patients, etanercept led to significant reductions in overall work and activity impairment; the value of increased work productivity partially or completely offset the cost of treatment.

AB0562 A double-blind, placebo-controlled, multicenter trial of tocilizumab in moderate to severe active RA patients with inadequate response to methotrexate in korean population

BackgroundInterleukin-6 (IL-6), a proinflammatory cytokine, is thought to play a major pathological role in rheumatoid arthritis (RA). Tocilizumab is humanized anti IL-6 receptor monoclonal antibody which has been shown to...

AB0320 Tocilizumab improves left ventricular mass and cardiac output in patients with rheumatoid arthritis

BackgroundRheumatologists need to develop primary prevention strategies for cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients. We reported that tocilizumab (TCZ) improved arterial stiffness as well as etanercept and adalimumab....

SAT0083 Abdominal Aortic Calcifications are Associated with Cardiovascular Diseases and Vertebral Fractures in Patients with Rheumatoid Arthritis.

BackgroundCardiovascular disease and osteoporosis are two major causes of morbidity in rheumatoid arthritis (RA) patients. Vertebral fracture assessment (VFA) by dual-energy X ray absorptiometry (DXA) is a validated tool for...

Immunotherapy of Tocilizumab for Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by persistent joint inflammation, systemic inflammation and immunological abnormalities. Because IL-6 plays a major role in the development of these characteristics, IL-6 blockade may reasonably be expected to constitute a novel therapeutic strategy for the treatment of RA. Phase III clinical trials of a humanized anti-human IL-6 receptor monoclonal antibody, tocilizumab, have demonstrated its outstanding clinical efficacy, either as monotherapy or in combination with disease-modifying antirheumatic drugs, for moderate to severe active RA patients. Although tocilizumab is currently recommended as a second-line biologic for RA patients whose response to one or more of TNF inhibitors is inadequate, further clinical studies including head-to-head comparative studies, and clarification of the mechanisms through which tocilizumab exerts its clinical effects are sure to identify RA patients who should be treated with tocilizumab as a first line biologic.