Therapy In Rheumatoid Arthritis Patients Research Articles

Ultrasound Is a Better Target Than Clinical Disease Activity Scores in Rheumatoid Arthritis

The assessment of joint inflammation is essential for diagnosing and monitoring response to therapies in patients affected by inflammatory arthropathies like rheumatoid arthritis (RA). For this, the use of musculoskeletal ultrasonography (US) with the power Doppler (PD) method has increased in the past decade. Also, US is known to detect B-mode synovitis and synovial Doppler activity in RA patients treated with either synthetic or biologic disease-modifying anti-rheumatic drugs. The US-detected synovitis has a predictive value in relation to radiographic damage progression and disease flare-up or relapse. Assessment by US ranges from wrist and hand joints to a comprehensive examination of 44 joints. Ultrasonographic (US) assessment has been shown to be useful in the management of RA and for monitoring the disease course. The application of US is helpful in such evaluations and is a complementary tool for classic methods used to detect RA, such as clinical evaluation and radiography, particularly when the MCP, PIP, and MTP joints are considered. Evidence has confirmed that GS and PD evaluation demonstrates a correlation between disease activity and degree of inflammation of synovial tissue. Moreover, US can be used for evaluating response to biological drugs. Naredo et al. have found a significant improvement in US parameters in RA patients undergoing therapy with a TNF blocking agent. Thus, US evaluation may be a valid method for monitoring response to biological therapy in RA patients. Finally, 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.

Role of LncRNA-AF085935, IL-10 and IL-17 in Rheumatoid Arthritis Patients With Chronic Hepatitis C.

BackgroundThe current study aimed at testing the effect of corticosteroid therapy on serum levels of interleukin-10 (IL-10) and IL-17 as well as lncRNA-AF085935 in patients of rheumatoid arthritis (RA) associated with hepatitis C virus (HCV) and evaluating the usefulness of using these parameters to predict the therapeutic efficacy of steroids in these patients.MethodsThirty healthy control subjects and 65 chronic HCV patients with RA were included in our study. Patients were subjected to clinical examination, abdominal ultrasound, and liver biopsy and received 6-methyl-prednisolone (PDN) 16 mg/day for 48 weeks. Blood samples were collected from all subjects and serum was separated to assess IL-10 and IL-17 by ELISA and HCV RNA and lncRNA-AF085935 by qRT-PCR.ResultsOur study revealed that there were significant increases in serum levels of IL-10, IL-17 and lncRNA-AF085935 in RA patients associated with HCV compared with healthy control subjects. Also there were significant increases in serum levels of IL-10 and HCV RNA and a significant decrease in serum level of IL-17 in patients after corticosteroid therapy, while lncRNA-AF085935 is not significantly changed.ConclusionLncRNA-AF085935 might be a useful candidate biomarker for the early detection of RA associated with HCV, providing potential new strategies for early screening and therapy of these patients. IL-17 is a non-invasive prognostic marker to predict the efficacy of corticosteroid therapy in RA patients associated with chronic hepatitis C.

ATIC missense variant affects response to methotrexate treatment in rheumatoid arthritis patients.

The study was aimed at investigation of several gene variants of folate pathway enzymes for their potential association with methotrexate (MTX) treatment response in patients with rheumatoid arthritis. Four hundred and twenty two Caucasian patients were classified as good or poor responders, and subsequently genotyped for common SNPs in DHFR, FPGS and ATIC genes. No significant differences were observed in case of DHFR and FGPS SNPs. As for ATIC rs2372536 (Thr116Ser), GG minor genotype was significantly associated with good response to MTX (OR: 2.40; 95% CI: 1.30-4.42; p = 0.005), which was confirmed by multivariate analysis. The results of the study suggest that ATIC missense rs2372536 SNP may influence response to MTX therapy in rheumatoid arthritis patients.

The evaluation of sleep quality and response to anti-tumor necrosis factor α therapy in rheumatoid arthritis patients.

Poor sleep quality (SQ) is increasingly recognized as giving rise to decreased quality of life, and raising pain perception. Our aim is to evaluate the SQ in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor alpha (anti-TNF-α) therapy. This was a prospective observational and open-label study of RA patients. A total of 35 patients with RA were enrolled in this study. Of the 35 patients, 22 had high disease activity (DA), and 13 were in remission. High DA group was initiated an anti TNF-α therapy. Clinical and objective parameters of SQ were assessed by using the Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG). The total PSQI score and the frequency of poor SQ were high in 60% of the RA patients. The median PSQI score was significantly higher in the high DA group than in the remission group (P=0.026). Following an anti-TNF-α therapy initiation, significant improvements were observed in the high DA group by PSQI test (P=0.012). However, no statistically significant difference was found by PSG (P>0.05). Although an improvement in DA with anti-TNF-alpha therapy did not provide an amelioration in laboratory parameters, we found a significant improvement in SQ by subjective PSQI test. These findings may support that sleep disorders in RA are likely to be associated with a complex pathophysiology.

Associations between PTPRC rs10919563 A/G and FCGR2A R131H polymorphisms and responsiveness to TNF blockers in rheumatoid arthritis: a meta-analysis.

We aimed to investigate whether the PTPRC rs10919563 A/G and Fc gamma receptor 2A (FCGR2A) R131H polymorphisms can predict the response to anti-TNF therapy in rheumatoid arthritis (RA) patients. We conducted a meta-analysis of studies on the association between the PTPRC rs10919563 A/G or the FCGR2A R131H polymorphism and responsiveness to anti-TNF therapy in RA patients. Eighteen studies (twelve on PTPRC and six on FCGR2A) from eight articles involving 3058 patients were considered in this meta-analysis. The meta-analysis showed a significant association between the PTPRC rs10919563 A allele and response to TNF-α blockers in RA. The OR of the PTPRC A allele was significantly lower in responders (OR=0.584, 95% CI=0.409-0.835, P=0.003). Meta-analysis revealed no association between the FCGR2A HH+HR genotype and responsiveness to TNF blockers in all study subjects (OR=0.762, 95% CI=0.543-1.068, P=0.115). However, stratification by TNF inhibitor type showed that the FCGR2A HH+HR genotype was associated with responsiveness to adalimumab (OR=0.591, 95% CI=0.369-0.947, P=0.029), but not infliximab and etanercept (OR=0.929, 95% CI=0.354-2.440, P=0.881; OR=0.804, 95% CI=0.293-2.207, P=0.673). The PTPRC rs10919563 A allele shows a poor response to anti-TNF therapy, and the FCGR2A HH+HR genotype shows a poor response to adalimumab for RA. Genotyping for these polymorphisms may be useful for predicting the response to TNF-α blockers with respect to personalized medicine.

Tocilizumab and pregnancy: Four cases of pregnancy in young women with rheumatoid arthritis refractory to anti-TNF biologics with exposure to tocilizumab

Objectives: To investigate the use of tocilizumab (TCZ) in pregnant patients with active rheumatoid arthritis (RA) refractory to anti-tumour necrosis factor (TNF) agents.Methods: We retrospectively analysed the medical records of pregnant women with active RA treated between July 2008 and January 2015 by the Division of Maternal Medicine at our hospital. Inclusion criteria for this case series included active RA refractory to anti-TNF agents and exposure to TCZ at the time of conception.Results: Our review of 28 patient hospital records identified four patients who met the inclusion criteria. All four patients had active synovitis before starting treatment with TCZ. Successful TCZ therapy allowed them to plan to become pregnant. When pregnancy was confirmed, TCZ was terminated as soon as possible in all patients. Three patients delivered full-term infants without any adverse outcomes. One patient had a partial molar pregnancy and miscarried during gestational week 11. Two patients remained in clinical remission with low-dose prednisolone (PSL) or no treatment for RA during pregnancy.Conclusions: TCZ may be a good alternative therapy for RA patients with symptoms that are hard to control with TNF blockers who desire to bear children.

Autoantibodies in inflammatory arthritis.

Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides.

Management of interstitial lung disease and infectious pulmonary complications associated with antirheumatic drug therapy for rheumatoid arthritis patients

Management of interstitial lung disease and infectious pulmonary complications associated with antirheumatic drug therapy for rheumatoid arthritis patients

Delays in Initiation of Disease-Modifying Therapy in Rheumatoid Arthritis Patients: Data from a US-Based Registry.

IntroductionThe goal of this study was to evaluate how frequently rheumatoid arthritis (RA) therapy is instituted promptly and to describe the characteristics of patients who are not treated early upon diagnosis.MethodsThe percentage of patients who at the time of enrollment in the Corrona registry were not receiving any RA-directed therapy was evaluated and their characteristics were summarized. The time to subsequent initiation of any RA-directed therapy was also estimated.ResultsAmong 35,485 patients enrolled in Corrona, 34,735 (97.9%) were on appropriate therapy for RA and 750 (2.1%) had no history of any RA-directed therapy at time of enrollment. Among patients without any history of RA-directed therapy, the overall disease duration was 5.5 ± 9.0 years, with only 50.7% of patients having early disease (duration ≤1 year). Patients with no history of directed RA therapy did not have lower disease activity at enrollment compared with those receiving therapy. Clinical Disease Activity Index (CDAI) was 18.3 ± 15.0; 34% of patients had high and 27.6% moderate disease activity by CDAI. Patients were followed for a median (95% CI) time of 29.5 months (24.6–33.8). During the follow-up period, 372 out of 750 (49.6%) patients initiated RA-directed therapy. The median time to initiation of any RA-directed therapy was 12.1 months (95% CI 9.3–14.8).ConclusionIn this registry analysis, approximately 98% of patients were on appropriate RA therapy for their RA. However, a minority of patients with RA did not have a history of receiving disease-modifying therapy within a mean of approximately 5 years of RA onset and approximately 50% of them did not initiate any therapy within 12 months of registry follow-up. This delay in therapy did not appear to be related to a better controlled, or lower, RA disease activity state at the time of enrollment in the registry.FundingCorrona, LLC.Electronic supplementary materialThe online version of this article (doi:10.1007/s40744-015-0019-6) contains supplementary material, which is available to authorized users.

Concepts in monitoring the treatment in rheumatoid arthritis- the role of musculoskeletal ultrasound. Part I: synovitis.

Rheumatoid arthritis (RA) is an incurable chronic inflammatory disease associated with significant functional impairment and disability, linked to inflammatory and structural articular and peri-articular damage. Structural damage occurs rapidly in RA if inflammation is not efficiently suppressed. Identification of patients with high risk to develop RA followed by an early application of efficient medications and standard 'treat to target' recommendations allow a better management aiming remission. Over the last 15 years musculoskeletal ultrasound (MSUS) has proved to detect subclinical inflammatory lesions; thus, targeting therapy to imaging delivered information may provide superior outcomes and a more rapid response to therapy detection in comparison with clinical examination alone. This review provides an insight into the importance of MSUS in quantifying disease activity and monitoring of therapies in RA patients.

Epstein-Barr virus in peripheral blood is associated with response to rituximab therapy in rheumatoid arthritis patients.

Autoreactive B cells infected by Epstein-Barr virus (EBV) are suspected to be involved in the etiology of various human chronic autoimmune diseases. This motivated us to study the relationship between peripheral blood EBV load at baseline and treatment response to B cell-depleting therapy in rheumatoid arthritis (RA) patients. Thirty-five RA patients who started treatment with rituximab (RTX) in a routine clinical setting were assessed for baseline disease activity using disease activity score using 28 joint counts (DAS28) (erythrocyte sedimentation rate [ESR]). Treatment response was evaluated 3-7 months after RTX. EBV load in baseline whole blood (WB) samples was determined using quantitative PCR. EBV DNA was detected in 16/35 (46 %) of the WB samples. In these 16 EBV-positive patients, the median viral load was 3.15 (2.68-4.00) log copies/ml. Good/moderate European League Against Rheumatism (EULAR) response was observed in 16/16 of the EBV DNA-positive vs 13/19 EBV DNA-negative patients, p = 0.022. Significant response (DAS28 change >1.2) was observed in 14/16 of the EBV DNA-positive vs 10/19 EBV DNA-negative patients, p = 0.035. The decline in DAS28 after RTX was 2.10 (1.03-4. 78) in the EBV DNA-positive vs 1.47 (-0.7-4.70) in the EBV DNA-negative patients, p = 0.13. EBV load at baseline significantly correlated with change in DAS28 after RTX (τB = -0.261, p = 0.042). Our results suggest that the presence of EBV genome in WB could serve as a predictive marker to RTX therapy in RA.

Antidrug antibodies against TNF-blocking agents: correlations between disease activity, hypersensitivity reactions, and different classes of immunoglobulins.

Although anti-TNF drugs have changed the clinical course of rheumatoid arthritis (RA), survival rates and resistance-to-therapy data confirm that about 30% of RA patients fail to respond. The aim of this study was to evaluate the correlations between the development of antidrug antibodies, specific IgG4 antibodies against TNF inhibitors, and resistance to therapy in RA patients. This retrospective study involved 129 patients with established RA naïve to biological agents (98 females and 32 males, mean age 56.7±12.3 years, disease duration 6.3±1.2 years, baseline Disease Activity Score [DAS]-28 3.2–5.6) who received treatment with anti-TNF agents after the failure of conventional disease-modifying antirheumatic drugs (32 received infliximab [IFX], 58 etanercept [ETN], and 39 adalimumab [ADA]). After 6 months of treatment, the patients were classified as being in remission (DAS28 <2.6), having low disease activity (LDA; DAS28 2.6–3.2), or not responding (NR: DAS28 >3.2). The patients were also tested for serum antidrug antibodies and IgG4 antibodies against TNF inhibitors. After 24 weeks of treatment, 38% of the ETN-treated patients and 28% of those treated with ADA had injection-site reactions; the rate of systemic reactions in the IFX group was 25%. The differences among the three groups were not statistically significant (P=0.382; ETN versus ADA P=0.319). The percentages of patients with adverse events stratified by drug response were: LDA 8% and NR 18% in the ADA group; in remission 3%, LDA 22%, and NR 10% in the ETN group; and LDA 6% and NR 16% in the IFX group (P=0.051). The percentages of patients with antidrug antibodies were: ADA 33.3%, ETN 11.5%, and IFX 10.3% (P=0.025; ADA versus ETN P=0.015). The percentages of patients with IgG4 antibodies were: ADA 6%, ETN 13%, and IFX 26% (P=0.017; ADA versus ETN P=0.437). Associations between antidrug antibodies, specific IgG4 antibodies, and adverse reactions were not significant for any of the three drugs. IgG4 levels were higher in the ADA group than in the other two groups, and higher in the patients with worse DAS28 (NR) and in those experiencing adverse events. These data suggest a possible association between IgG4 levels and worse DAS28 (r2=5.8%, P=0.011). The presence of specific IgG4 antibodies against TNF blockers in patients with RA might affect the drugs’ activity. Patients with injection-site reactions and IgG4 against ETN may show a decreased response.

Evaluation of tocilizumab therapy in patients with rheumatoid arthritis based on FDG-PET/CT.

BackgroundPositron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) can detect the presence of synovitis in rheumatoid arthritis (RA) patients. The aim of this study was to investigate whether the findings of FDG-PET matched the conventional assessments of the disease activity score (DAS) 28, DAS28-CRP, simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in RA patients receiving tocilizumab (TCZ) therapy.MethodsSeventeen RA patients treated with TCZ were assessed. FDG-PET was performed at baseline and three and six months after the initiation of TCZ therapy. The maximum SUV (SUVmax) of the bilateral shoulder, elbow, wrist, hip, knee and ankle joints were added together (total SUV) and were used to assess the degree of FDG uptake as a representative parameter. The correlations between the ΔSUV and the difference in the clinical parameters at baseline and at each observation period, and the differences in each clinical parameters, were assessed.ResultsThe ΔSUV, the differences in the total SUV at baseline and at three/six months after starting treatment positively correlated with the ΔDAS28 (r = 0.615 p = 0.009/ r = 0.775 p < 0.001), ΔDAS28-CRP (r = 0.696, p = 0.002/ r = 0.828, p < 0.001), ΔSDAI (r = 0.652, p = 0.005/ r = 0.686, p = 0.002) and ΔCDAI (r = 0.662, p = 0.004/ r = 0.711, p = 0.001) for each period. The total SUV was significantly decreased at three and six months after the initiation of TCZ (p < 0.05).ConclusionsA reduction in the FDG uptake was observed at three and six months after the initiation of TCZ therapy. The disease activity estimated on FDG-PET/CT matched the conventional parameters following the TCZ therapy in RA patients.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-393) contains supplementary material, which is available to authorized users.

Assessing the likelihood of new-onset inflammatory bowel disease following tumor necrosis factor-alpha inhibitor therapy for rheumatoid arthritis and juvenile rheumatoid arthritis.

The association between inhibition of tumor necrosis factor-alpha (TNF-α) in patients with rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and the onset of inflammatory bowel disease (IBD) is unclear. We sought to evaluate this association by analyzing adverse events (AEs) reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) with a standardized scoring tool for drug-induced AEs. A search of the FAERS for RA or JRA (January 2003-December 2011) reported with adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab was performed. This dataset was then queried for cases indicating IBD. Full-length reports were accessed using the Freedom of Information Act and organized by age, sex, concomitant medications, co-morbidities, type of TNF-α inhibitor used, and diagnosis/treatment details. The Naranjo score was used to determine whether the drug-induced AEs were definite, probable, possible, or doubtful. There were 158 cases of IBD after TNF-α inhibitor exposure in RA or JRA patients. Use of the Naranjo score revealed that, in a majority of the cases (71.5 %), TNF-α inhibitor exposure was considered a 'possible' cause. A majority of the 'probable cases' in JRA were reported with etanercept (40 patients, 90.91 %). There were no 'definite' cases of anti-TNF-induced IBD. After applying the Naranjo scale, a weak association between new-onset IBD and TNF-α inhibitor therapy in RA patients and a moderately strong association especially with etanercept exposure in JRA patients was observed. However, causality cannot be determined due to limitations of the FAERS and the Naranjo score.

Effect of Methotrexate, Anti–Tumor Necrosis Factor α, and Rituximab on the Immune Response to Influenza and Pneumococcal Vaccines in Patients With Rheumatoid Arthritis: A Systematic Review and Meta‐Analysis

To assess the current literature on the impact of rheumatoid arthritis (RA) treatments on the humoral response to pneumococcal and influenza vaccines. We systematically searched the literature for studies evaluating the immune response to vaccines in RA patients receiving methotrexate (MTX) and/or biologic agents. The efficacy of vaccination, assessed by the response rate based on increased antibody titers before and 3-6 weeks after vaccination, was extracted by one investigator and verified by another. In total, 12 studies were included. RA patients mainly received MTX, anti-tumor necrosis factor α (anti-TNFα), or rituximab (RTX). Influenza vaccination response was reduced for RTX (43 patients; pooled odds ratio [OR] 0.44 [95% confidence interval (95% CI) 0.17-1.12] for H1N1, OR 0.11 [95% CI 0.04-0.31] for H3N2, and OR 0.29 [95% CI 0.10-0.81] for B) but not for anti-TNFα (308 patients; OR 0.93 [95% CI 0.36-2.37] for H1N1, OR 0.79 [95% CI 0.34-1.83] for H3N2, and OR 0.79 [95% CI 0.37-1.70] for B). For MTX, results differed depending on the method of analysis (222 patients; OR 0.35 [95% CI 0.18-0.66] for at least 2 strains, ORs were close to 1.0 in the single strain analysis). Pneumococcal vaccination response was reduced for 139 patients receiving MTX compared with controls (OR 0.33 [95% CI 0.20-0.54] for serotype 6B and OR 0.58 [95% CI 0.36-0.94] for 23F) but not for anti-TNFα (258 patients; OR 0.96 [95% CI 0.57-1.59] for 6B and OR 1.20 [95% CI 0.57-2.54] for 23F). For RTX, the response was reduced (88 patients; OR 0.25 [95% CI 0.11-0.58] for 6B and OR 0.21 [95% CI 0.04-1.05] for 23F). MTX decreases humoral response to pneumococcal vaccination and may impair response to influenza vaccination. The immune response to both vaccines is reduced with RTX but not with anti-TNFα therapy in RA patients.

AB0246 Study of the Antibody Titer by Influenza Vaccination in Rheumatoid Arthritis Patients Treated with Biological Agents -Examination of Multiple Dose-

BackgroundBiologic agents might suppress the immune response to influenza vaccines, but, the report is limited to the number of papers.ObjectivesThe aim is the study to compare antibody titers change after...

FRI0253 Biological Drug Therapy Prioritization Protocol as A Tool to Improve the Cost-Effectiveness Usage of Biological Drugs in Rheumatoid Arthritis Patients

BackgroundUntil 2010 the cost of biological treatments in Rheumatoid Arthritis (RA) was increased annually by 15% in our hospital. Due this situation, in 1st January 2011, a Hospital Biological Drug...

THU0161 Increase in Circulating TH17 Cells during Anti-TNF Therapy in Rheumatoid Arthritis Patients is Associated with Improvement in Joint Inflammation

BackgroundAnti-TNFα agents have revolutionised treatment of rheumatoid arthritis (RA), although a significant proportion of patients respond inadequately. Studies in murine and human arthritis have paradoxically shown that anti-TNF treatment can...

AB0416 Bone Mineral Density and Bone Turnover Changes during Anti-TNFα Therapy in Rheumatoid Arthritis Patients

BackgroundIt is well-known that patients with chronic inflammatory diseases have more bone loss and a higher risk of fractures compared to general population. The causes of bone loss in inflammatory...

FRI0238 Changes in Ultrasonographic Vascularity upon Initiation of Adalimumab Combination Therapy in Rheumatoid Arthritis Patients with Inadequate Response to Methotrexate

BackgroundControl of disease activity in patients with rheumatoid arthritis (RA) has become achievable using synthetic and biologic disease modifying anti-rheumatic drugs, both as monotherapy or in combination. However, residual inflammatory...