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ID PMID Title PublicationDate abstract
26252209 The Crosstalk of Pathways Involved in Immune Response Maybe the Shared Molecular Basis of 2015 Rheumatoid arthritis (RA) and Type 2 diabetes (T2D) are both systemic diseases linked with altered immune response, moderate mortality when present together. The treatment for both RA and T2D are not satisfied, partly because of the linkage between them has not yet been appreciated. A comprehensive study for the potential associations between the two disorders is needed. In this study, we used RNA sequencing to explore the differently expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of 10 RA and 10 T2D patients comparing with 10 healthy volunteers (control). We used bioinformatics analysis and the Ingenuity Pathways Analysis (IPA) to predict the commonalities on signaling pathways and molecular networks between those two diseases. 212 DEGs in RA and 114 DEGs in T2D patients were identified compared with healthy controls, respectively. 32 DEGs were shared between the two comparisons. The top 10 shared pathways interacted in cross-talking networks, regulated by 5 shared predicted upstream regulators, leading to the activated immune response were explored, which was considered as partly of the association mechanism of this two disorders. These discoveries would be considered as new understanding on the associations between RA and T2D, and provide novel treatment or prevention strategy.
26314921 In wealthier countries, patients perceive worse impact of the disease although they have l 2016 Apr OBJECTIVES: To investigate patterns in patient-reported and physician-reported disease outcomes in patients with rheumatoid arthritis (RA) from countries with different level of socioeconomic development. METHODS: Data from a cross-sectional multinational study (COMOrbidities in RA) were used. Contribution of socioeconomic welfare (gross domestic product (GDP); low vs high) of country of residence to physician-reported (tender joint count, swollen joint count (SJC), erythrocyte sedimentation rate, disease activity score based on 28 joints assessment (DAS28)-3v based on these three components and physician global assessment) and patient-reported (modified Health Assessment Questionnaire (mHAQ), patient global assessment and fatigue) disease outcomes was explored in linear regressions, adjusting for relevant confounders. RESULTS: In total, 3920 patients with RA from 17 countries (30 to 411 patients per country) were included, with mean age of 56 years (SD13) and 82% women. Mean SJC varied between 6.7 (Morocco) and 0.9 (The Netherlands), mean mHAQ ranged between 0.7 (Taiwan) and 1.5 (The Netherlands). Venezuela had the lowest (1.7) and the Netherlands the highest score on fatigue (5.0). In fully adjusted models, lower GDP was associated with worse physician-reported outcomes (1.85 and 2.84 more swollen and tender joints, respectively, and 1.0 point higher DAS28-3v), but only slightly worse performance-based patient-reported outcome (0.15 higher mHAQ), and with better evaluation-based patient-reported outcomes (0.43 and 0.97 points lower on patient global assessment and fatigue, respectively). CONCLUSIONS: In patients with RA, important differences in physician-reported and patient-reported outcomes across countries were seen, with overall a paradox of worse physician-reported outcomes but better patient-reported outcomes in low-income countries, while results indicate that these outcomes in multinational studies should be interpreted with caution. Research on explanatory factors of this paradox should include non-disease driven cultural factors influencing health.
26786667 Gist and verbatim communication concerning medication risks/benefits. 2016 Jun OBJECTIVES: To describe the information about medication risks/benefits that rheumatologists provide during patient office visits, the gist that patients with rheumatoid arthritis (RA) extract from the information provided, and the relationship between communication and medication satisfaction. METHODS: Data from 169 RA patients were analyzed. Each participant had up to three visits audiotaped. Four RA patients coded the audiotapes using a Gist Coding Scheme and research assistants coded the audiotapes using a Verbatim Coding Scheme. RESULTS: When extracting gist from the information discussed during visits, patient coders distinguished between discussion concerning the possibility of medication side effects versus expression of significant safety concerns. Among patients in the best health, nearly 80% reported being totally satisfied with their medications when the physician communicated the gist that the medication was effective, compared to approximately 50% when this gist was not communicated. CONCLUSION: Study findings underscore the multidimensional nature of medication risk communication and the importance of communication concerning medication effectiveness/need. PRACTICE IMPLICATIONS: Health care providers should ensure that patients understand that medication self-management practices can minimize potential risks. Communicating simple gist messages may increase patient satisfaction, especially messages about benefits for well-managed patients. Optimal communication also requires shared understanding of desired therapeutic outcomes.
25962818 Rheumatoid Arthritis - Anti-TNF. 2015 Aug This review will focus on the recent information and strategies now informing best use of TNF inhibitor therapy in RA. These issues include the role of TNFi therapy in early RA management, anti-drug antibodies in TNFi therapy, updates on safety and optimal dosage regimens in long term management.
26352601 Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Dise 2015 OBJECTIVE: Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested. METHODS: We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and osteoarthritis. Then we detected overlaps of differentially expressed genes across datasets and performed a meta-analysis aiming at identifying common differentially expressed genes that discriminate between pathological cases and normal controls. To further gain insights into the functions of the identified common differentially expressed genes, we conducted gene ontology enrichment analysis and protein-protein interaction analysis. RESULTS: We identified a total of eight differentially expressed genes (TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, PRF1), each associated with at least 3 of the 4 studied rheumatic diseases. Meta-analysis warranted the significance of the eight genes and highlighted the general significance of four genes (CX3CR1, LY96, TLR5, and PRF1). Protein-protein interaction and gene ontology enrichment analyses indicated that the eight genes interact with each other to exert functions related to immune response and immune regulation. CONCLUSION: The findings support that there exist common factors underlying rheumatic diseases. For rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and osteoarthritis diseases, those common factors include TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, and PRF1. In-depth studies on these common factors may provide keys to understanding the pathogenesis and developing intervention strategies for rheumatic diseases.
26245756 A psychometric analysis of outcome measures in peripheral spondyloarthritis. 2016 Jul OBJECTIVES: To assess the discriminatory capacity of various outcome measures and response criteria in patients with peripheral spondyloarthritis (pSpA). METHODS: Data originated from two randomised controlled trials, ABILITY-2 and Tnf Inhibition in PEripheral SpondyloArthritis (TIPES). Continuous outcome measures included patient's global assessment (PGA)/physician's global assessment of disease (PhGA), C-reactive protein (CRP), tender joint counts (TJC)/swollen joint counts (SJC), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Dichotomous response criteria included Peripheral SpondyloArthritis Response Criteria (PSpARC), American College of Rheumatology (ACR), ASDAS and BASDAI response criteria. The capacity to discriminate between adalimumab and placebo groups was assessed by standardised mean differences (SMD) for continuous variables, and Pearson's χ(2) for dichotomous response criteria. RESULTS: Within each trial, the composite indices for axial SpA assessment, ASDAS-CRP (SMD: -0.63 and -0.89 in ABILITY-2 and the TIPES trial, respectively) and BASDAI (SMD: -0.50 and -0.73), and the single-item measures PGA (SMD: -0.47 and -1.12) and PhGA (SMD: -0.64 and -0.87) performed better than other single-item measures, such as CRP (SMD: -0.18 and -0.53), SJC or TJC. In general, the PSpARC and ACR response criteria discriminated better than ASDAS and BASDAI response criteria. CONCLUSIONS: The axial SpA-specific ASDAS-CRP and BASDAI, but also PGA and PhGA, demonstrated good discriminatory ability in patients with pSpA. The pSpA-specific pSpARC response criteria and the rheumatoid arthritis-specific ACR response criteria also discriminated well. To fully capture typical pSpA manifestations, it may be worth developing new pSpA-specific indices with better performance and face validity. TRIAL REGISTRATION NUMBERS: ABILITY-2: NCT01064856; TIPES: EUDRACT 2008-006885-27.
27594565 Frequency of the use of biological treatment of patients with rheumatoid arthritis and ank 2016 Sep 1 BACKGROUND: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic connective tissue diseases. Inadequate treatment of RA and AS results in health failure, disability and premature death. In recent years, development of immunology and genetic engineering techniques has started a new generation of drugs in the treatment of RA and AS, called biologic response modifiers or biologics. It is a very effective therapy of serious RA and AS. In many cases, they represent the only way to improve the quality of life, slowing or even arresting the development of these diseases. According to national statistics, the percentage of patients with rheumatic diseases treated with biologic treatment in Poland is less than 1.5%, and it is much lower than in Western European countries (20%). PURPOSE: The aim of the study was to evaluate the use of biological treatment in Lower Silesia in patients with RA and AS in the years 2006-2015, based on data obtained from the Lower Silesian Branch of the Polish National Health Fund. RESULTS AND CONCLUSIONS: In the last 10 years the frequency of biological treatment of RA or AS in Lower Silesia was estimated as 2.06% of patients (in 2011) to 6.03% of patients (during the first 8 months of 2015). Biological treatment is more often used in Lower Silesia in comparison to national statistics and ranks at a similar level as in other countries of Central and Eastern Europe.
25889955 Angiogenic gene expression and vascular density are reflected in ultrasonographic features 2015 Mar 13 INTRODUCTION: Neovascularization contributes to the development of sustained synovial inflammation in the early stages of Rheumatoid Arthritis. Ultrasound (US) provides an indirect method of assessing synovial blood flow and has been shown to correlate with clinical disease activity in patients with Rheumatoid Arthritis. This study examines the relationship of US determined synovitis with synovial vascularity, angiogenic/lymphangiogenic factors and cellular mediators of inflammation in a cohort of patients with early Rheumatoid Arthritis (RA) patients prior to therapeutic intervention with disease modifying therapy or corticosteroids. METHODS: An ultrasound guided synovial biopsy of the supra-patella pouch was performed in 12 patients with early RA prior to treatment. Clinical, US and biochemical assessments were undertaken prior to the procedure. Ultrasound images and histological samples were obtained from the supra-patella pouch. Histological samples were stained for Factor VIII and a-SMA (a-smooth muscle actin). Using digital imaging analysis a vascular area score was recorded. QT-PCR (quantitative-PCR) of samples provided quantification of angiogenic and lymphangiogenic gene expression and immunohistochemistry stained tissue was scored for macrophage, T cell and B cell infiltration using an existing semi-quantitative score. RESULTS: Power Doppler showed a good correlation with histological vascular area (Spearman r--0.73) and angiogenic factors such as vascular endothelial growth factor-A (VEGF-A), Angiopoietin 2 and Tie-2. In addition, lymphangiogenic factors such as VEGF-C and VEGF-R3 correlated well with US assessment of synovitis. A significant correlation was also found between power Doppler and synovial thickness, pro-inflammatory cytokines and sub-lining macrophage infiltrate. Within the supra-patella pouch there was no significant difference in US findings, gene expression or inflammatory cell infiltrate between any regions of synovium biopsied. CONCLUSION: Ultrasound assessment of synovial tissue faithfully reflects synovial vascularity. Both grey scale and power Doppler synovitis in early RA patients correlate with a pro-angiogenic and lymphangiogenic gene expression profile. In early RA both grey scale and power Doppler synovitis are associated with a pro-inflammatory cellular and cytokine profile providing considerable validity in its use as an objective assessment of synovial inflammation in clinical practice.
25125592 Interferon gene expression signature in rheumatoid arthritis neutrophils correlates with a 2015 Jan OBJECTIVE: The aim of this study was to use whole transcriptome sequencing (RNA-Seq) of RA neutrophils to identify pre-therapy gene expression signatures that correlate with disease activity or response to TNF inhibitor (TNFi) therapy. METHODS: Neutrophils were isolated from the venous blood of RA patients (n = 20) pre-TNFi therapy and from healthy controls (n = 6). RNA was poly(A) selected and sequenced on the Illumina HiSeq 2000 platform. Reads were mapped to the human genome (hg19) using TopHat and differential expression analysis was carried out using edgeR (5% false discovery rate). Signalling pathway analysis was carried out using Ingenuity Pathway Analysis (IPA) software. IFN signalling was confirmed by western blotting for phosphorylated signal transducer and activator of transcription (STAT) proteins. Response to TNFi was measured at 12 weeks using change in the 28-item DAS (DAS28). RESULTS: Pathway analysis with IPA predicted activation of IFN signalling in RA neutrophils, identifying 178 IFN-response genes regulated by IFN-α, IFN-β or IFN-γ (P < 0.01). IPA also predicted activation of STAT1, STAT2 and STAT3 transcription factors in RA neutrophils (P < 0.01), which was confirmed by western blotting. Expression of IFN-response genes was heterogeneous and patients could be categorized as IFN-high or IFN-low. Patients in the IFN-high group achieved a better response to TNFi therapy [ΔDAS28, P = 0.05, odds ratio (OR) 1.4 (95% CI 1.005, 1.950)] than patients in the IFN-low group. The level of expression of IFN-response genes (IFN score) predicted a good response [European League Against Rheumatism (EULAR) criteria] to TNFi using receiver operating characteristic curve analysis (area under the curve 0.76). CONCLUSION: IFN-response genes are significantly up-regulated in RA neutrophils compared with healthy controls. Higher IFN-response gene expression in RA neutrophils correlates with a good response to TNFi therapy.
25609147 The effects of arctigenin on human rheumatoid arthritis fibroblast-like synoviocytes. 2015 Aug CONTEXT: Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) play an important role in the initiation and progression of RA, which are resistant to apoptosis and proliferate in an anchorage-independent manner. OBJECTIVE: The effects of arctigenin on the proliferation and apoptosis of RAFLSs were explored. MATERIALS AND METHODS: Arctigenin (0-160 µM) was used to treat RAFLSs for 48 h. Cell viability and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining. Western blot analysis was performed to detect the changes in apoptosis-related genes. RESULTS AND DISCUSSION: Arctigenin decreased cell viability by 23, 30, and 38% at the dose of 10, 20, and 30 µM, respectively. The half maximal inhibitory concentration (IC50) of arctignein on RAFLSs was about 38 µM. Moreover, 9, 15, and 21% of RAFLSs are induced apoptosis by 10, 20, and 30 µM of arctigenin. The apoptotic response was due to the loss of mitochondrial membrane potential, coupled with the release of cytochrome C into cytoplasm, the up-regulation of pro-apoptotic protein, Bax, and down-regulation of antiapoptotic protein, B cell lymphoma 2 (Bcl-2). The activation of mitochondrial pathway in arctigenin-treated RAFLSs induced the cleavage of caspase-9, caspase-3, and poly (ADP-ribose) polymerase (PARP). Additionally, arctigenin inhibited the nuclear translocation of p65, decreased the degradation of inhibitor of kappa B alpha (IκBα), and attenuated the phosphorylation of Akt. CONCLUSION: Our results reveal that arctigenin inhibits cell proliferation and induces mitochondrial apoptosis of RAFLSs, which is associated with the modulation of NF-κB and Akt signaling pathways.
27123584 The association of hypertension with asymptomatic cardiovascular organ damage in rheumatoi 2016 Oct BACKGROUND: The association of hypertension with asymptomatic cardiovascular organ damage in patients with rheumatoid arthritis (RA) has been little studied by echocardiography. METHODS: Echocardiography was done in 134 RA patients and 102 healthy controls. Left ventricular (LV) geometry was considered abnormal if LV mass index or relative wall thickness was increased. LV diastolic dysfunction was considered present if septal early diastolic tissue velocity <8 cm/s. Systemic arterial compliance (SAC) was assessed from stroke volume index/pulse pressure ratio. RESULTS: The hypertensive RA patients (n = 72) had higher inflammatory activity, older age and more diabetes than the normotensive RA patients (n = 62) (all p < 0.05). Rates of abnormal LV geometry, LV diastolic dysfunction and lower SAC were higher among the hypertensive RA patients (p < 0.05), but similar between normotensive RA patients and controls. Hypertension was associated with a 3-fold higher prevalence both for abnormal LV geometry (odds ratio 2.89 [95% confidence interval 1.09-7.63], p = 0.03) and for diastolic LV dysfunction (odds ratio 2.92 [95% confidence interval 1.14-7.46], p = 0.03) as well as lower SAC (β = 0.31, p = 0.001) independent of age, gender, diabetes and inflammatory activity measured by erythrocyte sedimentation rate. CONCLUSION: The presence of asymptomatic cardiovascular organ damage in RA patients is closely associated with hypertension independent of inflammatory activity.
25992914 Predicted vs. observed radiographic progression in early rheumatoid arthritis (POPeRA): re 2015 OBJECTIVES: The aim of this study was to apply a previously published method for evaluating radiographic progression, namely, predicted vs. observed radiographic progression in early rheumatoid arthritis (POPeRA), to the Swedish pharmacotherapy (SWEFOT) trial. METHOD: In SWEFOT, 487 patients with eRA were given methotrexate (MTX), and non-responders were randomized to group A [triple therapy: MTX+sulfasalazine (SSZ)+hydroxychloroquine (HCQ)] and group B [anti-tumour necrosis factor (anti-TNF) therapy: MTX+infliximab]. Responders continued on MTX. Predicted progression for 343 eligible patients was calculated based on the baseline total Sharp/van der Heijde score (SHS) divided by symptom duration, compared to observed progression at 12 and 24 months. RESULTS: Observed radiographic progression was reduced from predicted by a mean of 50.1% (A), 72.3% (B), and 73.9% (MTX) at 12 months and by 87.2, 89.8, and 87.8% at 24 months, respectively. Among completers, reductions of 56.7% (A) and 76.5% (B) at 12 months and of 91.0% and 96.0% at 24 months, respectively, were observed. At 12 months, there were no significant between-group differences. At 24 months, progression was reduced more in group B than in group A (first quartile difference 8.5% favouring group B) and in MTX [n=316, 89.8% (sd±32.0) vs. 87.2% (±32.2), p=0.021; vs. 87.8% (±27.8), p=0.013, respectively]. CONCLUSIONS: The POPeRA method confirms the original SWEFOT finding in that anti-TNF therapy was statistically marginally superior (2.6%) to triple therapy in preventing radiographic progression at 24 months among initial MTX non-responders. The simulation provided through POPeRA may facilitate comparisons of the relative efficacy of various treatments in preventing radiographic progression.
29932316 [Research progress of JAK-3 kinase and its inhibitors]. 2016 Oct JAK-3, a member of the Janus kinase family, is a protein tyrosine kinase, which plays an important role in the JAK-STAT signaling pathway. Previous studies showed that regulation of JAK-3’s activity plays a crucial role in the treatment of diseases such as rheumatoid arthritis. Many reports have been published with a focus on selective JAK-3 inhibitors, some of which showed excellent JAK-3 selectivity and inhibitory activities. Among the JAK-3 inhibitors reported, tofacitinib has satisfactory therapeutic benefits in the clinical trials, and has been approved for treatment of patients with rheumatoid arthritis. However, some JAK-3 inhibitors exhibited moderate to severe side effects, which need to be controlled by drug improvement. In order to pave the way for improvement of current JAK-3 inhibitors and development of new JAK-3 inhibitors, we provide an outline of the structure of JAK-3 and strategies in development of its inhibitors.
25416711 Relationship between disease activity indices and their individual components and radiogra 2015 Jun OBJECTIVE: The aim of this study was to investigate the relationship between different disease activity indices (DAIs) and their individual components and radiographic progression in patients with RA. METHODS: A systematic literature review until July 2013 was performed by two independent reviewers using the Medline and Embase databases. Longitudinal studies assessing the relationship between DAIs and single instruments and radiographic progression were included. The results were grouped based on the means of measurement (baseline vs time integrated) and analysis (univariable or multivariable). RESULTS: Fifty-seven studies from 1232 hits were included. All published studies that assessed the relationship between any time-integrated DAI including joint count and radiographic progression reached a statistically significant association. Among the single instruments, only swollen joint count and ESR were associated with radiographic progression, while no significant association was found for tender joint count. Data with respect to CRP are conflicting. Data on patient's global health, pain assessment and evaluator's global assessment are limited and do not support a positive association with progression of joint damage. CONCLUSION: Published data indicate that all DAIs that include swollen joints are related to radiographic progression while, of the individual components, only swollen joints and acute phase reactants are associated. Therefore composite DAIs are the optimal tool to monitor disease activity in patients with RA.
25736322 A Comparative Study With In Vitro Ultrasonographic and Histologic Grading of Metatarsal He 2015 Jul BACKGROUND: Ultrasonography is among the valid methods to assess articular cartilage in the foot. This study aimed to evaluate the validity of ultrasonographic grading to assess metatarsal head articular cartilage for rheumatoid forefoot deformity in vivo and to compare the findings with in vitro ultrasonographic and histologic gradings. METHODS: Participants were 15 patients scheduled to undergo resection arthroplasty of the metatarsal heads of the lesser toes because of rheumatoid arthritis of the metatarsophalangeal joints. Ultrasonographic examination was performed in vivo the day before surgery. Specimens of the second to fifth metatarsal heads taken intraoperatively were graded from in vitro ultrasonographic and histologic evaluations. Correlations among in vivo ultrasonographic, in vitro ultrasonographic, and histologic gradings were analyzed. RESULTS: In 46 metatarsal heads, the distribution of grading ranged from grade 1 to 6 for in vivo ultrasonographic examinations and from grade 1 to 4 for histologic examinations. In vivo ultrasonographic grading showed significant correlation to both in vitro ultrasonographic grading (P < .001, R = 0.74) and histologic grading (P < .001, R = 0.67). CONCLUSIONS: The significant correlations between in vivo ultrasonographic and histologic gradings suggest that a semiquantitative in vivo ultrasonographic assessment of forefoot deformity in rheumatoid arthritis may be possible. Ultrasonographic grading may prove useful for pre- and postoperative evaluation of remaining joint function in rheumatoid forefoot deformity. An ultrasonographic grading system for remaining joint surfaces might be helpful in selecting surgical procedures such as joint-sparing osteotomy and metatarsal head resection. LEVEL OF EVIDENCE: Level IV, case series.
27494398 Trend in and predictors for cardiovascular mortality in patients with rheumatoid arthritis 2016 Sep OBJECTIVES: To investigate a) the cardiovascular (CV) mortality in a clinical cohort of patients with established rheumatoid arthritis (RA) in comparison with the general population over 15 years, b) the trend in this CV mortality during the study period, and c) for a broad range of predictors, which baseline variables predict CV mortality. METHODS: In 1997, a sample of 1222 patients was randomly selected from the register of a rheumatology outpatient clinic in Amsterdam. Their CV mortality between 1997 and 2012 was obtained from Statistics Netherlands. The standardised mortality ratio (SMR) for CV mortality was calculated. A linear poisson regression analysis was performed to investigate if there was a trend in SMR over time. A Cox regression analysis was performed to determine which baseline variables predicted CV mortality. RESULTS: Mean age of the population at baseline was 60.4 (SD 15.4) years and 72.6% of the patients were women. Estimated SMR (95% confidence interval) for CV mortality was 1.24 (1.05, 1.43). The SMR decreased with 3% annually (p=0.16). Higher age, higher erythrocyte sedimentation rate, having CV comorbidity and diabetes mellitus (DM) were predictors for CV mortality. CONCLUSIONS: CV mortality among patients with RA in the past 15 years was still higher than in the general population. CV mortality decrease was not statistically significant. As CV mortality in RA is still higher than in the general population, continued attention for CV diseases in RA is important. Both tight control of disease activity and good care for comorbid conditions (CV diseases and DM) are advocated.
27550060 Effectiveness of golimumab for rheumatoid arthritis in patients with an inadequate respons 2017 Mar OBJECTIVES: Several biological disease-modifying antirheumatic drugs (bDMARDs) are currently available for the treatment of rheumatoid arthritis (RA). Increasing evidence indicates that second-line bDMARDs are effective for inadequate responders to first-line bDMARDs. However, all previous studies investigated the use of tumor necrosis factor inhibitors (TNFi) as a first-line bDMARD, while investigated the efficacy of second-line bDMARDs after the use of tocilizumab (TCZ), a non-TNFi, as a first-line bDMARD. Thus, we investigated the efficacy of golimumab (GLM) as a second-line bDMARD after treatment with TCZ as a first-line bDMARD. METHODS: The final study population consisted of 26 patients (inadequate responders to TCZ; TCZ group) with moderate or high disease activity (DAS28-ESR ≥3.2) at week 24 of treatment with TCZ as a first-line bDMARD or whose DAS28-ESR score worsened after starting TCZ treatment. These patients could be followed for another 52 weeks or more after the subsequent switch to GLM treatment. For comparison, 19 patients treated with TNFi as a first-line bDMARD and inadequate response to TNFi (TNFi group) were included. RESULTS: The DAS28-ESR score at week 52 after the start of treatment with GLM improved significantly compared with baseline in the TCZ and TNFi groups. However, the TCZ group showed significantly better improvement. Patients in both groups had significantly improved treatment outcomes according to European League Against Rheumatism response criteria, but there was no statistically significant difference among them. The retention rate at week 52 after the start of treatment with GLM was significantly higher in the TCZ group than in the TNFi group (81% vs. 68%, respectively). In addition, no difference was found in the progression of bone destruction determined by the change in van der Heijde modified total Sharp scoring system scores between groups. CONCLUSIONS: GLM was an effective therapeutic option for inadequate responders to TCZ.
25559062 Prevalence of sexual dysfunction among female patients followed in a Brasília Cohort of e 2015 Mar OBJECTIVE: To determine the prevalence of sexual dysfunction in women diagnosed with early rheumatoid arthritis (RA) (less than one year of symptoms at the time of diagnosis), as well as to evaluate the possible association between sexual dysfunction with AR activity and functional disability. METHODS: Cross-sectional study assessing women diagnosed with early RA, accompanied per protocol in the Brasilia Cohort, Hospital Universitário de Brasília. Demographics, disease activity index (Disease Activity Score 28 - DAS 28) and functional disability questionnaire (Health Assessment Questionnaire - HAQ), were obtained by direct interviews. The Female Sexual Function Index (FSFI) was used, questionnaire which contains 19 items that assess six domains: sexual desire, sexual arousal, vaginal lubrication, orgasm, sexual satisfaction and pain. RESULTS: 68 patients studied, of whom 54 (79.4%) reported sexual activity in the last four weeks. The participants were 49.7±13.7 (mean±SD) years old and the majority were married (61.4%). The mean DAS 28 was 3.6±1.5 and the mean HAQ was 0.7. The prevalence of sexual dysfunction (FSFI ≤26) was 79.6%. There was no association of disease activity or of functional disability with the occurrence of sexual dysfunction in the female patients evaluated. CONCLUSION: The prevalence of sexual dysfunction found in this study was higher than that reported in the literature in healthy women. A knowledge of the extent of the problem is needed to provide adequate therapeutic options for these patients.
26515512 Apigenin, a potent suppressor of dendritic cell maturation and migration, protects against 2016 Jan This study aimed to investigate whether apigenin (API) suppresses arthritis development through the modulation of dendritic cell functions. Bone marrow-derived dendritic cells (BMDCs) were stimulated in vitro with lipopolysaccharide (LPS) and treated with API for 24 hrs; DC functions, including phenotype expressions, cytokine secretion, phagocytosis and chemotaxis, were then investigated. The effects of API on collagen-induced arthritis (CIA) were examined in vivo, and purified DCs from the lymph nodes (LNs) of API-treated CIA mice were analysed for phenotypes and subsets. In in vitro, API efficiently restrained the phenotypic and functional maturation of LPS-stimulated BMDCs while maintaining phagocytotic capabilities. Moreover, API inhibited the chemotactic responses of LPS-stimulated BMDCs, which may be related to the depressive effect on chemokine receptor 4 (CXCR4). In in vivo, API treatment delayed the onset and reduced the severity of arthritis in CIA mice, and diminished secretion of pro-inflammatory cytokines in the serum and supernatants from the LN cells of the CIA mice. Similar to the in vitro findings, the API-treated mice exhibited reduced expression of co-stimulatory molecules and major histocompatibility complex II on DCs. Furthermore, API treatment strongly down-regulated the number of Langerhans cells, but not plasmacytoid DCs (pDCs) in LNs, which may be related to the depressive effect of API on the expression of CXCR4 on DCs of peripheral blood. These data provide new insight into the mechanism of action of API on arthritis and indicate that the inhibition of maturation and migration of DCs by API may contribute to its immunosuppressive effects.
27769592 Defining the optimal biological monotherapy in rheumatoid arthritis: A systematic review a 2017 Jun OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct and indirect comparisons of the treatment effects, while preserving the randomised comparisons within each trial. PROSPERO identifier: CRD42012002800. RESULTS: The analysis comprises 28 trials (8602 patients), including all nine biological agents approved for RA. Eight trials included "DMARD-naïve", and 20 "DMARD-Inadequate responder" (DMARD-IR) patients. All agents except anakinra and infliximab were superior (p < 0.05) to placebo (i.e., no DMARD treatment) with regard to ACR50. Etanercept and rituximab were superior to anakinra (p = 0.018 and p = 0.049, respectively). Tocilizumab was superior to adalimumab (p = 0.0082), anakinra (p = 0.0083), certolizumab (p = 0.037), and golimumab (p = 0.049). No differences among etanercept, tocilizumab, and rituximab were found (p > 0.52). However, because rituximab was evaluated in just 40 patients, our confidence in the estimates is limited. When including only DMARD-IR trials, the same statistical pattern emerged; in addition etanercept and tocilizumab were superior to abatacept. At recommended doses, both etanercept and tocilizumab were superior to adalimumab and certolizumab. No statistically significant differences among biological agents were found with respect to discontinuation due to adverse events (p > 0.068). CONCLUSIONS: Evidence from randomised trials suggests that most biological agents are effective as monotherapy. Although our confidence in the estimates is limited, etanercept or tocilizumab may be the optimal choice for most patients who need treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice.