Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
27996221 The practice of physical activity and cryotherapy in rheumatoid arthritis: systematic revi 2017 Oct INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune, chronic and inflammatory disease, which the affected patients present a higher cardiovascular mortality rate. Physical activities have been identified as the most important strategy to prevent cardiovascular diseases. However, the articular damage and the chronic pain caused by RA challenges its regular practice. Moreover, persons with RA tend to avoid PA due to the fear of exacerbating the inflammatory potential and pain. One alternative to avoid the collateral effects of the PA could be the cryotherapy. Therefore, this study aimed to review studies focused on the use of both PA and cryotherapy in RA patients and to identify evidences that both therapies could be combined in order to optimize the symptomatic treatment. EVIDENCE ACQUISITION: Four databases (MEDLINE, CINAHL, Elsevier and PEDro) were searched to identify publications regarding RA patients, PA and cryotherapy intervention by the terms and operators (rheumatoid arthritis AND exercise OR physical activity OR activity OR training OR reconditioning OR cryotherapy OR cold OR immersion). The selected studies should at least present one measure of the aerobic capacity, disease activity or pain relief. Among 19 studies with RA patients identified, only 4 studies used PA combined with cryotherapy. The other 13 studies used physical activities and 2 studies used cryotherapy intervention. EVIDENCE SYNTHESIS: The results of the physical activities combined with cryotherapy studies showed an improvement in the disease activity and pain relief, however without details of the physical activities intervention and an aerobic capacity. Among the physical activities studies, evidence was found suggesting that aerobic exercises and multiactivity exercises with high intensity are the more effective for improve the aerobic capacity. CONCLUSIONS: Even if few studies on cryotherapy were found, there are enough evidences in the literature that demonstrate the benefits of this intervention on pain relief and disease activity. In summary, neither study found associated physical activities to improve aerobic capacity with cryotherapy to improve disease activity and pain relief. This may be an innovative therapeutic strategy to improve the aerobic capacity in arthritis patients and consequently reduce their cardiovascular risk while minimizing pain and disease activity.
27329782 RAACFDb: Rheumatoid arthritis ayurvedic classical formulations database. 2017 Feb 2 ETHNOPHARMACOLOGICAL RELEVANCE: In the past years, the treatment of rheumatoid arthritis (RA) has undergone remarkable changes in all therapeutic modes. The present newfangled care in clinical research is to determine and to pick a new track for better treatment options for RA. Recent ethnopharmacological investigations revealed that traditional herbal remedies are the most preferred modality of complementary and alternative medicine (CAM). However, several ayurvedic modes of treatments and formulations for RA are not much studied and documented from Indian traditional system of medicine. Therefore, this directed us to develop an integrated database, RAACFDb (acronym: Rheumatoid Arthritis Ayurvedic Classical Formulations Database) by consolidating data from the repository of Vedic Samhita - The Ayurveda to retrieve the available formulations information easily. MATERIALS AND METHODS: Literature data was gathered using several search engines and from ayurvedic practitioners for loading information in the database. In order to represent the collected information about classical ayurvedic formulations, an integrated database is constructed and implemented on a MySQL and PHP back-end. RESULTS: The database is supported by describing all the ayurvedic classical formulations for the treatment rheumatoid arthritis. It includes composition, usage, plant parts used, active ingredients present in the composition and their structures. CONCLUSION: The prime objective is to locate ayurvedic formulations proven to be quite successful and highly effective among the patients with reduced side effects. The database (freely available at www.beta.vit.ac.in/raacfdb/index.html) hopefully enables easy access for clinical researchers and students to discover novel leads with reduced side effects.
29202486 Vitamin D status in patients with rheumatoid arthritis: a correlation analysis with diseas 2017 OBJECTIVES: Recent epidemiological studies suggested an association between a poor vitamin D [25(OH)D] status, inflammatory mediators, and rheumatoid arthritis (RA). We have recently proposed that pro-inflammatory interleukin 6 (IL-6) may represent a good marker for disease activity of RA. The aim of this study was to investigate the relationship between serum 25(OH)D levels and disease activity, joint damage, as well as serum IL-6 levels in a Polish RA population. MATERIALS AND METHODS: Serum 25(OH)D levels were measured in 35 female RA patients and 38 age- and gender-matched healthy controls. Statistical correlations between 25(OH)D levels and the disease activity score 28 (DAS 28), joint damage based on the Steinbrocker criteria, as well as serum IL-6 levels were performed. RESULTS: There was no statistically significant difference between levels of 25(OH)D in RA (16.89±8.57 ng/ml) and healthy controls (14.12±7.51 ng/ml), and the vitamin D deficiency (<20 ng/ml) was found in 71.43% of RA patients and 73.68 % of healthy controls. While vitamin D status did not correlate with DAS 28 (r=0.265, p=0.149) and joint damage based on the Steinbrocker criteria (r=0.367, p=0.065), a positive correlation between 25(OH)D and IL-6 (r=0.537, p=0.002) was observed in RA. CONCLUSION: Although further studies on a larger group of patients will be needed to confirm the data presented here, it seems that hypovitaminosis D is common in the RA patients and middle-aged non-RA healthy women in the Polish population. 25(OH)D levels were similar in the RA patients and age- and gender-matched healthy controls, and were not associated with joint damage and disease activity in patients.
29128424 The use of synthetic peptides for detection of anti-citrullinated protein antibodies in rh 2018 Mar Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology. A characteristic feature of RA is the presence of anti-citrullinated protein antibodies (ACPA). Since ACPAs are highly specific for RA and are often present before the onset of RA symptoms, they have become valuable diagnostic and prognostic. As a result, several assays for detection of ACPAs exist, which vary in sensitivity and specificity. In this study, we analyzed the reactivity of RA sera to selected peptides by solid-phase immunoassays in order to develop an ACPA assay with improved sensitivity and specificity. ACPA levels were determined with respect to sensitivity and specificity in 332 serum samples using the newly developed peptide panel, which was compared to the commercial assays CCPlus (Eurodiagnostica) and CCP3.1 (Inova Diagnostics). A primary panel (peptides 814, 33062 and 33156) was identified, which obtained a sensitivity of 71%, while the complete peptide panel reacted with 79% of RA sera screened. Total specificities of 89% and 80% were obtained for the primary peptide panel and the complete peptide panel. Sensitivities for the commercial assays ranged between 71% and 76% and specificities between 88% and 90%. These findings indicate that the generated peptide panel is optimal for ACPA detection and able to compete with commercial available assays. Collectively, this study may contribute to characterize autoimmunity towards citrullinated proteins and to the development of new and improved diagnostic assays for detection of ACPA and determination of RA.
28545499 Pre-silencing of genes involved in the electron transport chain (ETC) pathway is associate 2017 May 25 BACKGROUND: In the current context of personalized medicine, one of the major challenges in the management of rheumatoid arthritis (RA) is to identify biomarkers that predict drug responsiveness. From the European APPRAISE trial, our main objective was to identify a gene expression profile associated with responsiveness to abatacept (ABA) + methotrexate (MTX) and to understand the involvement of this signature in the pathophysiology of RA. METHODS: Whole human genome microarrays (4 × 44 K) were performed from a first subset of 36 patients with RA. Data validation by quantitative reverse-transcription (qRT)-PCR was performed from a second independent subset of 32 patients with RA. Gene Ontology and WikiPathways database allowed us to highlight the specific biological mechanisms involved in predicting response to ABA/MTX. RESULTS: From the first subset of 36 patients with RA, a combination including 87 transcripts allowed almost perfect separation between responders and non-responders to ABA/MTX. Next, the second subset of patients 32 with RA allowed validation by qRT-PCR of a minimal signature with only four genes. This latter signature categorized 81% of patients with RA with 75% sensitivity, 85% specificity and 85% negative predictive value. This combination showed a significant enrichment of genes involved in electron transport chain (ETC) pathways. Seven transcripts from ETC pathways (NDUFA6, NDUFA4, UQCRQ, ATP5J, COX7A2, COX7B, COX6A1) were significantly downregulated in responders versus non-responders to ABA/MTX. Moreover, dysregulation of these genes was independent of inflammation and was specific to ABA response. CONCLUSION: Pre-silencing of ETC genes is associated with future response to ABA/MTX and might be a crucial key to susceptibility to ABA response.
27903508 The patient perspective on absence of disease activity in rheumatoid arthritis: a survey t 2017 May BACKGROUND: Guidelines suggest treatment in rheumatoid arthritis (RA) to target remission, in close consultation with the patient. Our recent qualitative study of the patients' perspective on remission in RA identified 26 domains. The current study aimed to identify a short list of the most important aspects to inform future research. METHODS: Patients with RA from the Netherlands, the UK, Austria, Denmark, France and the USA completed a survey that contained all domains identified in our qualitative study. They rated domains for importance ('not important', 'important' or 'essential' to characterise a period of remission) and if important or essential, whether this domain needs to be 'less', 'almost gone' or 'gone' to reflect remission. Respondents were also asked to determine their personal top 3 most important/essential domains. Frequency of specific domains in the top 3 was calculated, and domains were sorted on the percentage of patients that evaluated a particular domain as 'essential'. RESULTS: Of 274 respondents, 75% were female, mean (SD) age 57(13) years, disease duration 12(9) years. The top 3 were as follows: pain (67%), fatigue (33%) and independence (19%); domains most frequently rated as 'essential' were as follows: pain (60%), being mobile (52%), physical function (51%), being independent (47%) and fatigue (41%). Pain needed to be less (13%), almost gone (42%) or gone (45%) to reflect remission. Similar patterns were seen for fatigue, independence, mobility and physical functioning. CONCLUSION: Patients identified pain, fatigue and independence as the most important domains of RA disease activity that need to be improved to reflect remission.
27992958 Impaired Akt Phosphorylation in Monocytes of Patients with Rheumatoid Arthritis. 2017 Feb It has been proposed that the Akt kinase pathway provides a regulatory mechanism to limit the inflammatory response. We examined the activation of Akt upon lipopolysaccharide (LPS) challenge in monocytes of patients with rheumatoid arthritis (RA) and correlated it with disease activity. Twelve subjects with recent-onset, DMARD-naïve RA, thirteen patients with chronic, DMARD therapy-non-responding RA and 27 healthy volunteers provided whole blood samples for phosphospecific flow cytometric measurement of unstimulated and LPS-stimulated Akt phosphorylation at serine 473 in monocytes, determined in relative fluorescence units (RFU). Activation capability, that is responsiveness of monocytes, was determined as the difference between stimulated and unstimulated samples and compared between groups using Mann-Whitney test. CRP and ESR, swollen and tender joint counts, patients' global assessment of disease activity, DAS28 score and plasma IL-6 determined by ELISA were correlated with Akt activation using Spearman method. Median (interquartile range) Akt activation capability was significantly lower in DMARD-naïve (379 RFU [285, 432], P = 0.016) and even lower in DMARD-non-responding RA (258 RFU [213, 338], P < 0.001), compared to healthy controls (505 RFU[408, 639]) and showed a negative correlation with swollen joint count (r = -0.48, CI -0.78 to -0.05, P = 0.014), CRP (r = -0.42, CI -0.80 to -0.02, P = 0.039) and plasma IL-6 levels (r = -0.44, CI -0.65 to -0.17, P = 0.001). In conclusion, Akt activation capability of monocytes is low in early untreated RA and even lower in chronic, DMARD-non-responding RA, suggesting a role for Akt pathway in the pathogenesis of RA.
28134327 IL-32 promoter SNP rs4786370 predisposes to modified lipoprotein profiles in patients with 2017 Jan 30 Patients with rheumatoid arthritis (RA) are at higher risk of developing cardiovascular diseases (CVD). Interleukin (IL)-32 has previously been shown to be involved in the pathogenesis of RA and might be linked to the development of atherosclerosis. However, the exact mechanism linking IL-32 to CVD still needs to be elucidated. The influence of a functional genetic variant of IL-32 on lipid profiles and CVD risk was therefore studied in whole blood from individuals from the NBS cohort and RA patients from 2 independent cohorts. Lipid profiles were matched to the specific IL-32 genotypes. Allelic distribution was similar in all three groups. Interestingly, significantly higher levels of high density lipoprotein cholesterol (HDLc) were observed in individuals from the NBS cohort and RA patients from the Nijmegen cohort homozygous for the C allele (p = 0.0141 and p = 0.0314 respectively). In contrast, the CC-genotype was associated with elevated low density lipoprotein cholesterol (LDLc) and total cholesterol (TC) in individuals at higher risk for CVD (plaque positive) (p = 0.0396; p = 0.0363 respectively). Our study shows a functional effect of a promoter single-nucleotide polymorphism (SNP) in IL32 on lipid profiles in RA patients and individuals, suggesting a possible protective role of this SNP against CVD.
28243760 Switching profiles in a population-based cohort of rheumatoid arthritis receiving biologic 2017 May Despite improved quality of care for rheumatoid arthritis (RA) patients, many still experience treatment failure with a biologic agent and eventually switch to another biologic agent. We investigated patterns of biologic treatment and reasons for switching biologics in patients with RA. Patients with RA who had started on a biologic agent or had switched to another biologic agent were identified from the prospective observational Korean nationwide Biologics (KOBIO) registry. The KOBIO registry contained 1184 patients with RA at the time of initiation or switching of biologic agents. Patients were categorized according to the chronological order of the introduction of biologic agents, and reasons for switching biologics were also evaluated. Of the 1184 patients with RA, 801 started with their first biologic agent, 228 were first-time switchers, and 89 were second-time or more switchers. Second-time or more switchers had lower rheumatoid factor and anti-CCP positivity, and higher disease activity scores at the time of enrollment than the other groups. Among these patients, tocilizumab was the most commonly prescribed biologic agent, followed by adalimumab and etanercept. The most common reason for switching biologics was inefficacy, followed by adverse events, including infusion reactions, infections, and skin eruptions. Furthermore, the proportion of inefficacy, as a reason for switching, was significantly higher with respect to switching between biologics with different mechanisms of action than between biologics with similar mechanisms. In this registry, we showed diverse prescribing patterns and differing baseline profiles based on the chronological order of biologic agents.
28464477 Smoking Behavior Changes in the Early Rheumatoid Arthritis Period and Risk of Mortality Du 2018 Jan OBJECTIVE: To investigate whether rheumatoid arthritis (RA) diagnosis influences smoking behavior changes and whether these changes were associated with mortality. METHODS: We identified an incident RA cohort in the Nurses' Health Study (NHS; 1976-2012). Behavioral data were collected through biennial questionnaires. We created a comparison cohort, matching RA cases to women without RA by age and calendar year at the index date of RA diagnosis. To investigate smoking behavior changes in the early RA period, sustained cessation was defined as permanently quitting within 4 years of the RA/index date. We used Cox regression to obtain hazard ratios (HRs) for mortality, comparing sustained smoking cessation to continued smoking. RESULTS: Among 121,700 women in the NHS, we identified 938 with incident RA matched to 8,951 non-RA comparators. Among current smokers, 40.0% with RA permanently quit smoking in the early RA period, compared to 36.1% of comparators (odds ratio for sustained cessation 1.18 [95% confidence interval (95% CI) 0.88, 1.58]). There were 313 deaths (33.4%) in the RA cohort and 2,042 (22.8%) among comparators. Compared to continued smoking, sustained cessation was associated with similarly decreased mortality in both the RA (HR 0.58 [95% CI 0.33, 1.01]) and comparison (HR 0.47 [95% CI 0.39, 0.58]) cohorts. Women with RA had higher mortality for >5 post-RA pack-years (HR 3.67 [95% CI 2.80, 4.81]) than comparators with >5 post-index pack-years (HR 1.88 [95% CI 1.62, 2.17]; P < 0.001 for interaction; reference: ever-smoker non-RA women with 0 post-index pack-years). CONCLUSION: Sustained smoking cessation within 4 years of RA diagnosis reduced mortality risk, with a similar effect observed among non-RA comparators. Smoking >5 pack-years after RA diagnosis significantly increased mortality beyond the risk of non-RA comparators.
28336519 Anticollagen type II antibodies are associated with an acute onset rheumatoid arthritis ph 2017 Sep OBJECTIVE: Antifibrillar collagen type II (anti-CII) antibody-positive patients with rheumatoid arthritis (RA) have early but not late signs of increased inflammation and joint erosions. We wanted to replicate this in a large RA cohort, and to relate to human leukocyte antigen (HLA)-DRB1* alleles. METHODS: Anti-CII and anti-cyclic citrullinated peptide (CCP)2 were measured at baseline in 773 patients with RA from the Swedish Epidemiological Investigation in Rheumatoid Arthritis (EIRA) study with clinical follow-up data from the Swedish Rheumatology Quality Register (SRQ) registry, and 1476 with HLA-DRB1* information. Comparisons were done concerning C reactive protein (CRP), erythrocyte sedimentation rate (ESR), tender joint count (TJC), swollen joint count (SJC), Disease Activity Score encompassing 28 joints based on ESR (DAS28), DAS28CRP, pain-Visual Analogue Scale (VAS), global-VAS and Health Assessment Questionnaire Score (HAQ) at eight occasions during 5 years, and association with HLA-DRB1* alleles. RESULTS: Anti-CII associated with elevated CRP, ESR, SJC, DAS28 and DAS28CRP at diagnosis and up to 6 months, whereas anti-CCP2 associated with SJC and DAS28 from 6 months to 5 years, but not earlier. The anti-CII-associated phenotype was strong, and predominated in anti-CII/anti-CCP2 double-positive patients. Anti-CII was associated with improvements in CRP, ESR, SJC, TJC and DAS28, whereas anti-CCP2 was associated with deteriorations in SJC and DAS28 over time. Anti-CII-positive patients achieved European League Against Rheumatism good or moderate response more often than negative patients. Anti-CII was positively associated with HLA-DRB1*01 and HLA-DRB1*03, with significant interaction, and double-positive individuals had >14 times higher mean anti-CII levels than HLA double negatives. Whereas smoking was associated with elevated anti-CCP2 levels, smokers had lower anti-CII levels. CONCLUSIONS: Anti-CII seropositive RA represents a distinct phenotype, in many respects representing the converse to the clinical, genetic and smoking associations described for anticitrullinated protein peptide autoantibodies. Although not diagnostically useful, early anti-CII determinations predict favourable inflammatory outcome in RA.
27783235 Welfare costs in patients with rheumatoid arthritis and their partners compared with match 2017 Mar Rheumatoid arthritis (RA) is a chronic autoimmune disease with significant morbidity, mortality, and costs for the individual patient and for society. The purpose of this study was to examine welfare costs in patients with RA including their partners before and after initial diagnosis. Data were collected from population-based registers in the period from 1998 to 2009. A total of 25,547 Danish patients with a diagnosis of RA and 15,660 of their partners were identified and compared with 101,755 randomly selected age- and gender-matched controls and 62,681 control partners. The direct and indirect costs were calculated for patients and their partners and compared to matched controls. These included inpatient and outpatient treatment, medication, income from employment and social transfer payments. Patients with RA had statistically significantly more inpatient and outpatient costs than control subjects, i.e., treatment (€346 vs. €211), hospitalization (€1261 vs. €778), and medication use (€654 vs. €393). The costs associated with the patients were present 11 years before diagnosis of RA (€1592) compared with control subjects (€1172). Furthermore, income from employment was lower for patients (€14,023) than for control subjects (€17,196). Being a partner to a patient with RA was associated with high total welfare costs. This register-based study shows that RA has significant welfare costs for patients, their partners, and society. The differences in total health costs exist up to 11 years before the diagnosis of RA is established.
28597306 Maintenance of remission with combination etanercept-DMARD therapy versus DMARDs alone in 2017 Sep In this transglobal, randomized, double-blind, placebo-controlled, treat-to-target study, the maintenance of efficacy was compared between biologic-and biologic-free-disease-modifying antirheumatic drug (DMARD) combination regimens after low disease activity (LDA) was achieved with biologic DMARD induction therapy. Patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy received open-label etanercept 50 mg subcutaneously once weekly plus methotrexate with or without other conventional synthetic (cs) DMARDs for 24 weeks. Patients achieving LDA [disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) <3.2] at week 24 were randomized to receive etanercept-methotrexate combination therapy or placebo-methotrexate combination therapy, with or without other csDMARDs, for 28 weeks. In the open-label period, 72% of patients achieved DAS28-ESR LDA at week 24. Patients enrolled in the double-blind period had long-standing rheumatoid arthritis and high disease activity at baseline (mean duration, 8.1 years; DAS28-ESR, 6.4). In the etanercept and placebo combination groups, 44% versus 17% achieved DAS28-ESR LDA and 34 versus 13% achieved DAS28-ESR remission at week 52 (p < 0.001). Adverse events were reported in 37 and 43%, serious adverse events in 0 and 4%, and serious infections in 0 and 2% in these groups, respectively, in the double-blind period. After induction of response with etanercept combination therapy following a treat-to-target approach in patients with long-standing rheumatoid arthritis and high disease activity at baseline, the etanercept combination regimen was significantly more effective in maintaining LDA and remission than a biologic-free regimen. ClinicalTrials.gov identifier. NCT01578850.
28968793 52-week results of the phase 3 randomized study comparing SB4 with reference etanercept in 2017 Dec 1 OBJECTIVE: To compare the 52-week efficacy and safety of SB4 [an etanercept biosimilar] with reference etanercept (ETN) in patients with active RA. METHODS: In a phase 3, randomized, double-blind, multicentre study, patients with moderate to severe RA despite MTX treatment were randomized to receive 50 mg/week of s.c. SB4 or ETN up to week 52. Efficacy assessments included ACR response rates, 28-joint DAS, Simplified and Clinical Disease Activity Indices and changes in the modified total Sharp score (mTSS). Safety and immunogenicity were also evaluated. RESULTS: A total of 596 patients were randomized to receive either SB4 (n = 299) or ETN (n = 297) and 505 (84.7%) patients completed 52 weeks of the study. At week 52, the ACR20 response rates in the per-protocol set were comparable between SB4 (80.8%) and ETN (81.5%). All efficacy results were comparable between the two groups and they were maintained up to week 52. Radiographic progression was also comparable and the change from baseline in the mTSS was 0.45 for SB4 and 0.74 for ETN. The safety profile of SB4 was similar to that of ETN and the incidence of anti-drug antibody development up to week 52 was 1.0 and 13.2% in the SB4 and ETN groups, respectively. CONCLUSION: Efficacy including radiographic progression was comparable between SB4 and ETN up to week 52. SB4 was well tolerated and had a similar safety profile to that of ETN. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01895309, EudraCT 2012-005026-30.
27796445 Biologic therapies and bone loss in rheumatoid arthritis. 2017 Feb INTRODUCTION: Rheumatoid arthritis (RA) is a common systemic autoimmune disease of unknown cause, characterized by a chronic, symmetric, and progressive inflammatory polyarthritis. One of the most deleterious effects induced by the chronic inflammation of RA is bone loss. During the last 15 years, the better knowledge of the cytokine network involved in RA allowed the development of potent inhibitors of the inflammatory process classified as biological DMARDs. These new drugs are very effective in the inhibition of inflammation, but there are only few studies regarding their role in bone protection. The principal aim of this review was to show the evidence of the principal biologic therapies and bone loss in RA, focusing on their effects on bone mineral density, bone turnover markers, and fragility fractures. METHODS: Using the PICOST methodology, two coauthors (PC, LM-S) conducted the search using the following MESH terms: rheumatoid arthritis, osteoporosis, clinical trials, TNF- antagonists, infliximab, adalimumab, etanercept, certolizumab, golimumab, IL-6 antagonists, IL-1 antagonists, abatacept, tocilizumab, rituximab, bone mineral density, bone markers, and fractures. The search was conducted electronically and manually from the following databases: Medline and Science Direct. The search period included articles from 2003 to 2015. The selection included only original adult human research written in English. Titles were retrieved and the same two authors independently selected the relevant studies for a full text. The retrieved selected studies were also reviewed completing the search for relevant articles. The first search included 904 titles from which 253 titles were selected. The agreement on the selection among researchers resulted in a Kappa statistic of 0.95 (p < 0.000). Only 248 abstracts evaluated were included in the acronym PICOST. The final selection included only 28 studies, derived from the systematic search. Additionally, a manual search in the bibliography of the selected articles was made and included into the text and into the section of "small molecules of new agents." CONCLUSION: Treatment with biologic drugs is associated with the decrease in bone loss. Studies with anti-TNF blocking agents show preservation or increase in spine and hip BMD and also a better profile of bone markers. Most of these studies were performed with infliximab. Only three epidemiological studies analyzed the effect on fractures after anti-TNF blocking agent's treatment. IL-6 blocking agents also showed improvement in localized bone loss not seen with anti-TNF agents. There are a few studies with rituximab and abatacept. Although several studies reported favorable actions of biologic therapies on bone protection, there are still unmet needs for studies regarding their actions on the risk of bone fractures.
28710354 Ssu72 attenuates autoimmune arthritis via targeting of STAT3 signaling and Th17 activation 2017 Jul 14 Signal transducer and activator of transcription 3 (STAT3) orchestrates the differentiation of several cell types, including interleukin-17 (IL-17)-releasing Th17 cells. Dysregulation of Th17 cells results in chronic inflammatory responses. Ssu72 is a C-terminal domain phosphatase required for transcriptional regulation. However, the mechanism by which Ssu72 affects STAT3 activation and Th17 cell differentiation is unclear. Here, we found that Ssu72 overexpression suppresses STAT3 activation and Th17 cell responses in vitro. A systemic infusion of Ssu72 attenuates experimental autoimmune arthritis by reducing STAT3 activity and the differentiation of Th17 cells. It also reduces joint destruction, serum immunoglobulin concentrations and osteoclastogenesis but increases the number of marginal zone B cells and B10 cells. These effects are associated with reduced p-STAT3 levels and the suppression of Th17 cell formation in vivo. Based on these data, Ssu72 is related to STAT3 activation and the inflammatory response; and Ssu72 overexpression in T-cell-mediated immunity has potential utility for the treatment of autoimmune arthritis.
27864689 Epstein-Barr virus infection and gene promoter hypermethylation in rheumatoid arthritis pa 2017 Feb We analyzed CpG-island hypermethylation status in 12 genes of paraffin-embedded tissues from 38 rheumatoid arthritis (RA) patients with methotrexate (MTX)-associated large B cell lymphoproliferative disorder (BLPD), 11 RA patients with non-MTX-associated BLPD (non-MTX-BLPD), 22 controls with diffuse large B cell lymphoma (DLBCL), and 10 controls with Epstein-Barr virus (EBV)(+) DLBCL. Among them, tumor cells from EBV(+) MTX-BLPD patients and control EBV(+) DLBCL patients had significantly lower median incidence of CpG island methylator phenotype (CIMP) than those from non-MTX-BLPD and control DLBCL groups (2.3 and 1.7 vs. 4.3 and 4.4; P < 0.01 for each). In the MTX-BLPD group, EBV(+) patients showed lower median CIMP than EBV(-) patients (2.3 vs. 3.2); they also had significantly lower hypermethylation incidence in four apoptosis-related genes, especially death-associated protein kinase (14 vs. 55 %), higher incidence of massive tumor necrosis (86 vs. 27 %), and lower BCL2 protein expression (19 vs. 86 %) than did the control DLBCL group (P < 0.01 for all). In all clinical stages, EBV(+) MTX-BLPD patients had better prognoses than the EBV(-) MTX-BLPD (P = 0.011), non-MTX-BLPD (P = 0.002), and control DLBCL groups (P = 0.015). MTX-BLPD patients without hypermethylated RAS-associated domain family-1A (RASSF1A) or O (6) -methyl guanine-DNA methyltransferase (MGMT) had significantly better prognosis than those with hypermethylation of those genes (P = 0.033). We conclude that in RA patients with MTX-BLPD, EBV infection is associated with a lower incidence of CIMP, apoptosis-related gene hypermethylation, and BCL2 expression, which can induce tumor regression by MTX withdrawal and lead to better prognoses.
28875320 [Low back pain in rheumatoid arthritis]. 2017 Dec Low back pain (LBP) in patients with rheumatoid arthritis (RA) has so far been of little concern in clinical investigations. The main focus of scientific publications on spinal problems in RA was the cervical spine. In a recent study, we could demonstrate that LBP in RA patients leads to a significantly higher degree of disability and depression as well as to a reduction in quality of life compared to RA patients without LBP. If there is a specific reason for the additional symptom of LBP, such as spinal stenosis or segmental instability, surgical treatment may be indicated to improve disability and quality of life. For a successful outcome of spinal surgery it is important to address the specific aspects of RA patients, such as poor bone quality and the immunosuppressive effect of antirheumatic drug treatment. Whenever possible, minimally invasive surgical techniques should be used and the immunosuppressive medication should be stopped before surgery.
27852695 Anti-inflammatory treatment improves high-density lipoprotein function in rheumatoid arthr 2017 May OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased cardiovascular risk. Recent studies suggest that high-density lipoprotein (HDL) may lose its protective vascular phenotype in inflammatory conditions. However, the effects of common anti-inflammatory treatments on HDL function are not yet known. METHODS: We compared the function of HDL in 18 patients with RA and 18 matched healthy controls. Subsequently, patients were randomised to (methotrexate+infliximab (M+I) (5 mg/kg)) or methotrexate+placebo (M+P) infusions for 54 weeks. At week 54 and thereafter, all patients received infliximab therapy until completion of the trial (110 weeks), enabling assessment of the impact of 1 year of infliximab therapy in all patients. HDL functional properties were assessed at baseline, 54 weeks and 110 weeks by measuring the impact on endothelial nitric oxide (NO) bioavailability and superoxide production (SO), paraoxonase activity (PON-1) and cholesterol efflux. RESULTS: All HDL vascular assays were impaired in patients compared with controls. After 54 weeks, NO in response to HDL was significantly greater in patients who received M+I compared with those who received M+P. Endothelial SO in response to HDL was reduced in both groups, but PON-1 and cholesterol efflux remained unchanged. All vascular measures improved compared with baseline after ≥1 infliximab therapy in the analysis at 110 weeks. No significant trend was noted for cholesterol efflux. CONCLUSIONS: HDL function can be improved with anti-inflammatory treatment in patients with RA. The M+I combination was superior to the M+P alone, suggesting that the tumour necrosis factor-α pathway may have a role in HDL vascular properties.
27258623 Should tumour necrosis factor antagonist safety information be applied from patients with 2017 Mar BACKGROUND: Information on the safety of tumour necrosis factor (TNF) antagonists frequently arises from their use in rheumatic diseases, their first approved indications, and is later applied to psoriasis. Whether the risk of biological therapy is similar in psoriasis and rheumatoid arthritis has been considered a priority research question. OBJECTIVES: To compare the safety profile of anti-TNF drugs in patients with rheumatoid arthritis and psoriasis. METHODS: We compared two prospective safety cohorts of patients with rheumatoid arthritis and psoriasis that share methods (BIOBADASER and BIOBADADERM). RESULTS: There were 1248 serious or mortal adverse events in 16 230 person-years of follow-up in the rheumatoid arthritis cohort (3171 patients), and 124 in the 2760 person-years of follow-up of the psoriasis cohort (946 patients). Serious and mortal adverse events were less common in patients with psoriasis than in rheumatoid arthritis (incidence rate ratio of serious adverse events in psoriasis/rheumatoid arthritis: 0·6, 95% confidence interval 0·5-0·7). This risk remained after adjustment for sex, age, treatment, disease, hypertension, diabetes, hypercholesterolaemia and simultaneous therapy with methotrexate (hazard ratio 0·54, 95% confidence interval 0·47-0·61), and after excluding patients receiving corticosteroids. Patients with rheumatoid arthritis showed a higher rate of infections, cardiac disorders, respiratory disorders and infusion-related reactions, whereas patients with psoriasis had more skin and subcutaneous tissue disorders and hepatobiliary disorders. CONCLUSIONS: Patients with rheumatoid arthritis clinical practice have almost double the risk of serious adverse events compared with patients with psoriasis, with a different pattern of adverse events. Safety data from rheumatoid arthritis should not be fully extrapolated to psoriasis. These differences are likely to apply to other immune-mediated inflammatory diseases.