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ID PMID Title PublicationDate abstract
29029341 An increased concentration of receptor activator of nuclear factor kappa-B ligand pre-date 2017 Dec 1 OBJECTIVES: RANK ligand (RANKL) is involved in destruction and osteoporosis in RA. In this study, the relationships between RANKL and ACPA, anti-carbamylated protein antibodies (anti-CarP), cytokines and chemokines were analysed in individuals before the onset of RA symptoms, and their associations with radiological findings at disease onset were assessed. METHODS: This was a case-control study performed within the Medical Biobank of Northern Sweden that included 470 pre-symptomatic individuals [334 women and 136 men; mean (s.d.) age 52.3 (9.4) years] using blood samples donated before symptom onset (pre-dating time; 5.0 years) and 96 controls (60 women and 36 men). Plasma was analysed for RANKL (BioVendor, Karasek, Brno, Czech Republic), anti-CCP2 antibodies (Eurodiagnostics, Malmö, Sweden), anti-CarP antibodies (in-house ELISA), ACPA specificities (ISAC-platform, Phadia AB, Uppsala, Sweden) and cytokines/chemokines (Meso Scale Discovery methods, Rockville, MD, USA). Radiographs of hands and feet were graded using the Larsen score. RESULTS: The concentration of RANKL was higher in the pre-symptomatic individuals compared with controls; mean (s.e.m.): 0.50 (0.03) vs 0.22 (0.02) nmol/l (P < 0.001). The concentration increased gradually over time until symptom onset but appeared later than ACPA/RF/anti-CarP antibodies. Positivity for these antibodies yielded higher levels of RANKL compared with seronegativity (P < 0.001). RANKL concentrations were significantly associated with IL-6 and IL-10 concentrations. The combination of positivity for RANKL and anti-CarP antibodies resulted in a higher Larsen score at diagnosis β = 6.18 (95% CI: 0.93, 11.43; P = 0.022). CONCLUSION: RANKL concentrations were increased several years before symptom onset for RA, particularly in ACPA/RF/anti-CarP-positive individuals, all detectable earlier than RANKL. Positivity for RANKL and anti-CarP antibodies yielded the highest Larsen score at disease onset.
28540605 Characteristics of rheumatoid arthritis patients undergoing reverse shoulder arthroplasty. 2018 Feb The risks and complication profile of reverse total shoulder arthroplasty (RSA) in rheumatoid arthritis (RA) patients has yet to be clearly defined as most studies have small cohorts. Using a large inpatient database, the purpose on our study was to determine the overall demographics, hospitalization characteristics, and early complication rates in rheumatoid patients and compared these to rotator-cuff arthropathy patients without RA undergoing RSA. Utilizing United States Nationwide Inpatient Sample from 2010 to 2013, we evaluated a total of 919 RA RSA and compared them to 8097 patients without RA undergoing RSA. The outcomes included demographic characteristics like age, race, sex, Deyo comorbidity score, perioperative complications, and mean length-of-stay. The RA cohort had 81% females versus 60% in the comparison cohort. This cohort was younger (p = 0.006) and had longer hospitalization time (p = 0.001), but the total inpatient costs were not significantly different (p = 0.15). In regards to Deyo index, rheumatoid patients had significantly higher scores (p < 0.001). The inpatient complication rates for infection (p = 0.9), nerve injury (p = 0.9), and instability (p = 0.19) were similar, but the RA cohort had more prosthetic-related (p = 0.001) and greater tuberosity-related (p = 0.008) complications. The mortality rates were also similar (p = 0.625). In RSA for RA patients, surgeons should be mindful of preoperative risk factors and demographic characteristics that may influence their outcomes. Caution should specifically be paid to the possibility of longer hospitalization time and increased incidence of certain complications, including intraoperative fracture, when compared to non-rheumatoid patients. Close collaboration between rheumatologists, surgeons, and primary care physicians is a must for optimizing and managing these patients.
28821984 Nonassociation of homocysteine gene polymorphisms with treatment outcome in South Indian T 2018 Feb The aim of the study was to look for any association of MTR 2756A>G and MTRR 66A>G gene polymorphisms with clinical phenotype, methotrexate (MTX) treatment response, and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). A total of 335 patients with RA were investigated. MTR 2756A>G gene polymorphism was analyzed by PCR-RFLP, and MTRR 66A>G SNP was analyzed by TaqMan 5' nuclease assay. The allele frequencies were compared with HapMap groups. MTR 2756G allele was found to be associated with risk of developing RA. The allele frequencies of MTR 2756A>G and MTRR 66A>G SNPs in controls differed significantly when compared with HapMap groups. Neither of the SNPs influenced the MTX treatment outcome and adverse effects. Neither of the SNPs seems to be associated with MTX treatment outcome and adverse events in South Indian Tamil patients with RA.
28121199 Functional analysis of choline transporters in rheumatoid arthritis synovial fibroblasts. 2017 Nov OBJECTIVES: In this study, we examined the functional characteristics of choline uptake and sought to identify the transporters in rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: The expression of choline transporters was evaluated by quantitative real-time PCR, western blotting, and immunocytochemistry. Time course, Na(+)-dependency, and kinetics of [(3)H]choline uptake were investigated. Effects of cationic drugs on the uptake of [(3)H]choline, cell viability, and caspase-3/7 activity were also examined. Finally, we investigated the influence of choline uptake inhibitor, hemicholinium-3 (HC-3), and choline deficiency on cell viability and caspase-3/7 activity. RESULTS: Choline transporter-like protein 1 (CTL1) and CTL2 mRNA and protein were highly expressed in RASFs and were localized to the plasma membrane. [(3)H]Choline uptake occurred via a Na(+)-independent and pH-dependent transport system. The cells have two different [(3)H]choline transport systems, high- and low-affinity. Various organic cations, HC-3 and choline deficiency inhibited both [(3)H]choline uptake and cell viability, and enhanced the caspase-3/7 activity. The functional inhibition of choline transporters could promote apoptotic cell death. In RASFs, [(3)H]choline uptake was significantly increased compared with that in OASFs without a change in gene expression. CONCLUSIONS: These results suggest that CTL1 (high-affinity) and CTL2 (low-affinity) are highly expressed in RASFs and choline may be transported by a choline/H(+ )antiport system. Identification of this CTL1- and CTL2-mediated choline transport system should provide a potential new target for RA therapy.
27871200 Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis. 2017 Jan Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by focal pathologic bone resorption due to excessive activity of osteoclasts (OC). Receptor activator of nuclear factor kappa B ligand (RANKL) is essential for the proliferation, differentiation, and survival of OC. Denosumab (DMab) is a humanized monoclonal antibody that binds to RANKL with high affinity and blocks its subsequent association with its receptor RANK on the surface of OC precursors. Area covered: The authors review the molecular and cellular mechanisms underlying therapeutic applications of DMab, provide recent highlights on pharmacology, efficacy and safety of DMab, and discuss the potential of DMab as a novel therapeutic option for the treatment of rheumatoid arthritis. Expert opinion: Clinical results suggest that DMab is efficient both in systemic and articular bone loss in RA with limited side effects. Diminished bone erosion activity was also noted in RA patients on corticosteroids and bisphosphonates. Combination of DMab with an anti-TNF agent was not associated with increased infection rates. Collectively, these data indicate that DMab, in combination with methotrexate and possibly other conventional synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs), is an effective, safe and cost-effective option for the treatment of RA.
28216193 Frequency of concomitant fibromyalgia in rheumatic diseases: Monocentric study of 691 pati 2017 Aug OBJECTIVE: Fibromyalgia (FM) is a confounding factor for diagnosing and assessing rheumatic disease activity. This study sought to assess the extent of this syndrome in rheumatism patients at a French rheumatology department. METHOD: This monocentric epidemiological study enrolled all patients consulting due to rheumatoid arthritis (RA), spondyloarthritis (SpA), or connective tissue disease (CTD). FM diagnosis was confirmed or excluded according to the rheumatologist opinion and the 1990 American College of Rheumatology (ACR) criteria. RESULTS: We enrolled 691 patients, including 451 women (65.3%), with a mean age of 55.8 years (18-93). Of the enrolled patients, 325 presented with RA, 298 SpA [59 psoriatic arthritis (PsA), 137 ankylosing spondylitis (AS), 64 non-radiographic SpA (nr-SpA), and 38 peripheral SpA], and 71 CTD. The rheumatologist established FM diagnosis in 97 patients (14%), while 55 (8%) fulfilled the 1990 ACR criteria. The frequency of FM was lower in RA patients (4.9% by 1990 ACR criteria; 7.7% by expert opinion) compared to SpA (11.1% by 1990 ACR, p < 0.05; 17.5% by expert opinion, p < 0.003) and CTD (11.3% by 1990 ACR, non-significant; 28.2% by expert opinion, p < 0.001). In the SpA subgroups, FM was more common in the nr-SpA than in PsA or AS (23.9%, 9.6%, and 6.4%, by 1990 ACR, p = 0.001; 37.3%, 13.5%, and 7.2%, by expert opinion, p < 0.001). CONCLUSION: FM-like symptoms are commonly associated with rheumatic diseases. The frequency of FM is particularly high in non-radiographic axial SpA, thus raising questions about the specificity of the Assessment of SpondyloArthritis International Society (ASAS) classification criteria.
28811351 Content and Construct Validity, Reliability, and Responsiveness of the Rheumatoid Arthriti 2017 Oct OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis (RA) Flare Group was established to develop a reliable way to identify and measure RA flares in randomized controlled trials (RCT). Here, we summarized the development and field testing of the RA Flare Questionnaire (RA-FQ), and the voting results at OMERACT 2016. METHODS: Classic and modern psychometric methods were used to assess reliability, validity, sensitivity, factor structure, scoring, and thresholds. Interviews with patients and clinicians also assessed content validity, utility, and meaningfulness of RA-FQ scores. RESULTS: People with RA in observational trials in Canada (n = 896) and France (n = 138), and an RCT in the Netherlands (n = 178) completed 5 items (11-point numerical rating scale) representing RA Flare core domains. There was moderate to high evidence of reliability, content and construct validity, and responsiveness. Factor analysis supported unidimensionality. Rasch analysis showed acceptable fit to the Rasch model, with items and people covering a broad measurement continuum and evidence of appropriate targeting of items to people, ordered thresholds, minimal differential item functioning by language, sex, or age. A summative score across items is defensible, yielding an interval score (0-50) where higher scores reflect worsening flare. The RA-FQ received endorsement from 88% of attendees that it passed the OMERACT Filter 2.0 "Eyeball Test" for instrument selection. CONCLUSION: The RA-FQ has been developed to identify and measure RA flares. Its review through OMERACT Filter 2.0 shows evidence of reliability, content and construct validity, and responsiveness. These properties merit its further validation as an outcome for clinical trials.
28866645 Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dos 2017 Dec BACKGROUND: Although methotrexate (MTX) is the consensual first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), substantial heterogeneity remains with its prescription and dosage, which are often not optimal. OBJECTIVE: To evaluate the symptomatic and structural impact of optimal MTX dose in patients with early RA in daily clinical practice over 2 years. METHODS: Patients included in the early arthritis ESPOIR cohort who fulfilled the ACR-EULAR (American College of Rheumatology/European League against Rheumatism) criteria for RA and received MTX as a first DMARD were assessed. Optimal MTX dose was defined as ≥10 mg/week during the first 3 months, with escalation to ≥20 mg/week or 0.3 mg/kg/week at 6 months without Disease Activity Score in 28 joints remission. Symptomatic and structural efficacy with and without optimal MTX dose was assessed by generalised logistic regression with adjustment for appropriate variables. RESULTS: Within the first year of follow-up, 314 patients (53%) with RA received MTX as a first DMARD (mean dose 12.2±3.8 mg/week). Only 26.4% (n=76) had optimal MTX dose. After adjustment, optimal versus non-optimal MTX dose was more efficient in achieving ACR-EULAR remission at 1 year (OR 4.28 (95% CI 1.86 to 9.86)) and normal functioning (Health Assessment Questionnaire ≤0.5; OR at 1 year 4.36 (95% CI 2.03 to 9.39)), with no effect on radiological progression. Results were similar during the second year. CONCLUSION: Optimal MTX dose is more efficacious than non-optimal dose for remission and function in early arthritis in daily practice, with no impact on radiological progression over 2 years.
29084618 [Inhibition of the Janus kinase-signal transducer and activator of transcription is a new 2017 Oct 30 Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. The introduction of a new class of disease-modifying anti-rheumatic drugs, which work by inhibiting the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway, has led to new possibilities for achieving remission of RA. Tofacitinib and baricitinib are both JAK/STAT inhibitors, which have shown efficacy in line with anti-tumour necrosis factor treatment. The side effects seem manageable, and up to now only increased risk of herpes zoster has raised consideration. JAK/STAT inhibitors create new possibilities for reaching low disease activity or remission for patients with RA.
28754958 A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent f 2017 Jul 28 Tofacitinib (CP-690550), an oral Janus kinase inhibitor, has shown significant efficacy in the treatment of rheumatoid arthritis through blocking the signaling pathways of pro-inflammatory cytokines. However, recent evidence suggests that long-term tofacitinib treatment is associated with increased risk of infection (e.g. tuberculosis) in patients. In the present study, we illustrate that tofacitinib administration significantly reduced the survival rate of mice given lethal or sub-lethal dose challenge with Candida albicans. This was related to the ability of tofacitinib to reverse TNFα- and IFNγ-enhanced candidacidal activity of murine polymorph nuclear cells (PMNs) and also to suppress chemokine CXCL5 expression and PMN infiltration in the infected tissues of mice. More importantly, tofacitinib significantly antagonized the ability of TNFα, IFNγ and GM-CSF to boost human PMNs in phagocytosis and direct killing of C. albicans in vitro. It also down-regulated reactive oxygen production and neutrophil extracellular trap formation by human PMNs stimulated with yeast-derived β-glucans in the presence of TNFα, IFNγ or GM-CSF. Our data emphasizes a significantly increased risk for opportunistic fungal infection associated long-term tofacitinib treatment in humans, likely through antagonizing the PMN-boosting effect of pro-inflammatory cytokines.
29128828 Quantitative assessment of betamethasone dual-acting formulation in urine of patients with 2018 Feb 5 Quantitative evaluation and assessment of pharmacokinetic parameters of Diprospan(®) (suspension for injection 7mg/mL (2mg+5mg/mL) of betamethasone) were performed in urine samples taken from patients with rheumatoid arthritis or ankylosing spondylitis for 28days after systemic intramuscular administration in routine clinical practice in an open-comparative prospective cohort study. The maximum betamethasone concentration was reached at day 4 of the follow-up; in some cases, β-phase of elimination of the drug was appeared at day 14 or at day 21 of the follow-up. The deferred β-phase elimination was likely a consequence of the physiological characteristics of the patients or of the influence of non-steroidal agents. The half-life of betamethasone was 8.5days. The elimination rate constant was 2.49h-1; the mean clearance was 4.72L/d. The recommended frequency of the drug administration to its complete elimination was estimated up to 48days. Mann-Whitney test showed no significant differences in pharmacokinetic characteristics between male and female subjects. The prolonged elimination phase was observed in patients with deviations in their body mass index, continual treatment by diclofenac and nimesulide or, possibly, after consuming an alcohol. The study was recorded in Clinical Trials open source with identifier NCT03119454.
27851983 Osteopontin inhibition of miR-129-3p enhances IL-17 expression and monocyte migration in r 2017 Feb BACKGROUND: Osteopontin (OPN) is an important proinflammatory cytokine in rheumatoid arthritis (RA). Levels of OPN have been shown to be significantly correlated with interleukin-17 (IL-17) production and expression of Th17 cells in the synovial fluid of RA patients. Here, we investigated the role of OPN in monocyte migration, IL-17 production and osteoblasts. METHODS: OPN and IL-17 expression profiles in osteoarthritis (OA) and RA synovial fluid were determined by enzyme-linked immunosorbent assay (ELISA). The expression of the microRNA, miR-129-3p, in osteoblasts was analyzed by real-time quantitative polymerase chain reaction (qPCR). Immunoreactive proteins were spotted by Western blotting. We used the collagen-induced arthritis (CIA) mouse model to investigate the role of OPN in monocyte migration during RA. RESULTS: OPN and IL-17 expression were higher in RA synovial fluid as compared to OA samples. We also found that OPN promotes IL-17 expression in osteoblasts and thereby enhances monocyte migration via the Syk/PI3K/Akt signaling pathway. miR-129-3p expression was found to be negatively regulated by OPN via the Syk/PI3K/Akt signal cascade. In contrast, lentiviral vectors expressing short hairpin RNA inhibited OPN expression and ameliorated articular swelling, cartilage erosion and monocyte infiltration in the ankle joints of CIA mice. CONCLUSION: To our knowledge, our study is the first to describe how OPN promotes monocyte migration by upregulating IL-17 expression in osteoblasts in RA disease. SIGNIFICANCE: These findings indicate that OPN could serve as a potential therapeutic target for the treatment of RA.
27860244 Role of protein arginine methyltransferase 5 in inflammation and migration of fibroblast-l 2017 Apr To probe the role of protein arginine methyltransferase 5 (PRMT5) in regulating inflammation, cell proliferation, migration and invasion of fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). FLSs were separated from synovial tissues (STs) from patients with RA and osteoarthritis (OA). An inhibitor of PRMT5 (EPZ015666) and short interference RNA (siRNA) against PRMT5 were used to inhibit PRMT5 expression. The standard of protein was measured by Western blot or immunofluorescence. The excretion and genetic expression of inflammatory factors were, respectively, estimated by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). Migration and invasion in vitro were detected by Boyden chamber assay. FLSs proliferation was detected by BrdU incorporation. Increased PRMT5 was discovered in STs and FLSs from patients with RA. In RA FLSs, the level of PRMT5 was up-regulated by stimulation with IL-1β and TNF-α. Inhibition of PRMT5 by EPZ015666 and siRNA-mediated knockdown reduced IL-6 and IL-8 production, and proliferation of RA FLSs. In addition, inhibition of PRMT5 decreased in vitro migration and invasion of RA FLSs. Furthermore, EPZ015666 restrained the phosphorylation of IκB kinaseβ and IκBα, as well as nucleus transsituation of p65 as well as AKT in FLSs. PRMT5 regulated the production of inflammatory factors, cell proliferation, migration and invasion of RA FLS, which was mediated by the NF-κB and AKT pathways. Our data suggested that targeting PRMT5 to prevent synovial inflammation and destruction might be a promising therapy for RA.
28288682 Low disease activity for up to 3 years after adalimumab discontinuation in patients with 2017 Mar 14 BACKGROUND: This study was conducted to evaluate the feasibility of long-term adalimumab (ADA) discontinuation after achievement of low disease activity (LDA) in Japanese patients with early rheumatoid arthritis (RA) and to identify predictors of LDA maintenance. METHODS: In the HOPEFUL-1 study, patients received initial therapy with either ADA plus methotrexate (MTX; intensive therapy) or MTX alone (standard therapy) for 26 weeks, followed by ADA + MTX for 26 weeks. In the HOPEFUL-2 study, patients received ADA + MTX (ADA continuation) or MTX alone (ADA discontinuation) for 52 weeks. HOPEFUL-3 was an observational study that enrolled patients who had completed HOPEFUL-2; these patients were followed for an additional 104 weeks. RESULTS: Of the 172 patients enrolled in the HOPEFUL-3 study, 135 (ADA continuation, n = 61; ADA discontinuation, n = 74) with 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) values at both week 52 (start of HOPEFUL-2) and week 208 (end of HOPEFUL-3) were included in the effectiveness analysis. At week 208, 58 (95.1%) of 61 patients and 59 (79.7%) of 74 patients who continued or discontinued ADA, respectively, had LDA (DAS28-CRP <3.2). Initial intensive therapy was associated with a better outcome than standard therapy in terms of change in modified total Sharp score from week 0 to week 208, which was ≤0.5 (64% vs. 30%). The incidence of adverse events was significantly lower in the ADA discontinuation group than in the ADA continuation group (9.7% vs. 32.9%; p < 0.001). CONCLUSIONS: Approximately 80% of patients who discontinued ADA for 3 years after achieving LDA with ADA + MTX were still in LDA, with a lower incidence of adverse events than patients who continued ADA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01346501. Registered 29 April 2011.
27756166 Kocuria kristinae infection during adalimumab treatment. 2017 Mar A common inhabitant of skin, the Kocuria kristinae of the Micrococcaceae family, has gained attention in recent years because it can induce pathology in humans. Reported is a Kocuria kristinae-caused abdominal abscess in a patient treated for rheumatoid arthritis with adalimumab. The tumor necrosis factor (TNF) inhibitor drugs are known to cause various bacterial, viral, and fungal infections. This is the first known case where an opportunistic infection with Kocuria has presented with an abdominal abscess in an immunocompromised individual who is on long term TNF inhibitors.
28012172 MHC class II alleles associated with Th1 rather than Th17 type immunity drive the onset of 2017 Mar Polymorphisms in the MHC class II (MHCII) genes are strongly associated with rheumatoid arthritis, supporting the importance of autoreactive T helper (Th) cells for the development of this disease. Here, we used pristane-induced arthritis (PIA), induced by the non-antigenic hydrocarbon pristane, to study the impact of different MHCII alleles on T-cell activation and differentiation. In MHCII-congenic rats with disease-promoting MHCII alleles, pristane primarily induced activation of Th1 cells, whereas activated T cells were Th17 biased in rats with protective MHCII alleles. Neutralization of IFN-γ during T-cell activation abrogated the development of disease, suggesting that Th1 immunity is important for disease induction. Neutralization of IL-17, by contrast, suppressed arthritis only when performed in rats with established disease. Adoptive T-cell transfers showed that T cells acquired arthritogenic capacity earlier in strains with a prevailing Th1 response. Moreover, upon pristane injection, these strains exhibited more Ag-primed OX40+ and proliferating T cells of polyclonal origin. These data show that T cells are polarized upon the first encounter with peptide-MHCII complexes in an allele-dependent fashion. In PIA, the polyclonal expansion of autoreactive Th1 cells was necessary for the onset of arthritis, while IL-17 mediated immunity contributed to the progression to chronic disease.
27496347 Basement membranes and autoimmune diseases. 2017 Jan Basement membrane components are targets of autoimmune attack in diverse diseases that destroy kidneys, lungs, skin, mucous membranes, joints, and other organs in man. Epitopes on collagen and laminin, in particular, are targeted by autoantibodies and T cells in anti-glomerular basement membrane glomerulonephritis, Goodpasture's disease, rheumatoid arthritis, post-lung transplant bronchiolitis obliterans syndrome, and multiple autoimmune dermatoses. This review examines major diseases linked to basement membrane autoreactivity, with a focus on investigations in patients and animal models that advance our understanding of disease pathogenesis. Autoimmunity to glomerular basement membrane type IV is discussed in depth as a prototypic organ-specific autoimmune disease yielding novel insights into the complexity of anti-basement membrane immunity and the roles of genetic and environmental susceptibility.
29043892 Tofacitinib in the treatment of active rheumatoid arthritis in adults. 2018 Jan Tofacitinib, a pan Janus kinase inhibitor, has been investigated as monotherapy in patients naive to methotrexate and in methotrexate incomplete responders and in combination with disease-modifying antirheumatic drugs in antirheumatic drug incomplete responders and TNF inhibitor failures in the Phase II and III programs. The clinical trial program demonstrated efficacy and a reasonable safety profile in these disease populations that has led to the approval of tofacitinib 5 mg twice daily orally in many countries. The pharmacology, chemistry, pharmacokinetics, pharmacodynamics, efficacy and safety in the Phase II and III clinical trials, safety in the long-term extension studies and postmarketing safety reports are the focus of this review.
28792167 Study of Carotid Artery Intimomedial Thickness in Patients with Rheumatoid Arthritis and i 2017 Jul INTRODUCTION: RA is a chronic inflammatory state, predisposing for atherosclerosis as it is an immunoinflammatory process. This study focuses on use of Carotid artery intimomedial thickness (CIMT) as a marker for subclinical atherosclerosis. OBJECTIVE: To study the assessment of atherosclerosis by Carotid Intimo-Medial Thickness (CIMT) in patients with rheumatoid arthritis and Correlation of ultrasonographic findings with severity of disease (using DAS-28 score). MATERIAL AND METHODS: A prospective, case-control study involving 50 cases of diagnosed RA cases, and 50 healthy control. Sonological examination of the carotid and the vertebral arteries was done using a L&T SEQUINA color Doppler scanner with a linear band probe of frequency 6.6 to 14 MHz's. RESULTS: This case control study was carried out in 100 subjects (50 cases and 50 controls). Cases comprised of 41 rheumatic women (Mean age 42.08+12.13 yrs) and 9 (mean age 48.4+12.8 years) rheumatic men. Mean CIMT of the study group (0.5996+0.109mm) was significantly greater (p<0.001) than that of control group (0.5290+0.006mm). We observed carotid plaques in 18% subjects of study group compared to 2% in controls (p<0.001). Mean age in the study group was 46.56+12.82 years and that of controls was 46.38+11.69 years (p>0.05). In the study group mean CIMT was significantly increased in RA factor positive patients than in RA factor negative patients. We also calculated the DAS-28 score of the study group subjects and found that 8, 27 and 15 were having Mild, Moderate & severe disease activity respectively. CONCLUSIONS: CIMT has significant correlation with the age, and CIMT increases with age. Mean CIMT was found to be more with RF+(ve) patients indicating acute inflammation also has a role. When compared, the mean CIMT in each DAS sub group the result was found to be statistically insignificant.
27992692 Rheumatoid Arthritis and Risk of Malignant Lymphoma: Is the Risk Still Increased? 2017 Apr OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas with a strong correlation with RA disease severity. Given the changes in RA therapy over recent decades, this study was undertaken to assess whether lymphoma risk remains increased, and if so, to explore risk predictors and lymphoma subtypes. METHODS: We identified 12,656 cases of incident RA in the Swedish Rheumatology Quality Register 1997-2012 and obtained information on therapy and inflammatory activity during the first year after diagnosis. Each patient was matched to 10 population comparator subjects. Through linkage to the Swedish Cancer Register, lymphomas, including subtypes, were identified. We assessed hazard ratios (HRs) using Cox regression. RESULTS: Overall, the HR for lymphoma was increased in RA, to 1.6 (95% confidence interval [95% CI] 1.2-2.1). Taking RA duration into account, risks did not appear to have declined over successive calendar years of RA diagnosis. Neither use of methotrexate the first year after RA diagnosis nor ever use of tumor necrosis factor inhibitors (TNFi) increased lymphoma risk (HR 0.9 [95% CI 0.4-1.9]). Use of oral corticosteroids the first year after RA diagnosis was associated with a reduced risk (HR 0.5 [95% CI 0.3-0.9]). Inflammatory activity during the first year after RA diagnosis did not predict future lymphoma risk. Chronic lymphocytic leukemia occurred less frequently, and Hodgkin's lymphoma occurred more frequently, in RA patients than in the general population. CONCLUSION: The average lymphoma risk in recently diagnosed RA is similar in magnitude to that reported in historical cohorts. Standard antirheumatic treatment including TNFi did not predict future lymphoma risk. Distribution of lymphoma subtypes warrants further investigation.