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ID PMID Title PublicationDate abstract
30634208 [Effect of Xinfeng Capsule on Improving Pulmonary Function in Rheumatoid Arthritis Patient 2016 Jul OBJECTIVE: To observe the effect of Xinfeng Capsule (XFC) on pulmonary function, peripheral blood B and T lymphocyte attenuator (BTLA), and oxidative stress in rheumatoid arthritis (RA) patients. METHODS: Totally 100 RA patients were assigned to the treatment group and the control group according to random digit table, 50 in each group. Patients in the treatment group took XFC (0. 5 g/pill, 3 pills each time, 3 times per day) , while those in the control group took Leflunomide (LEF) Tablet (0. 1 g/tablet 1, tablet each time, once every evening). The therapeutic course for all was 90 days. Pulmonary functions were detected including forced vital capacity (FVC), forced expiratory volume in one second (FEV1) , peak expiratory flow (PEF), 25% maximal expiratory flow-volume (MEF25), 50% maximal expiratory flow-volume (MEF50), 25% -75% maximal expiratory flow-volume (MEF25 -75). Levels of erythrocyte sedimentation rate (ESR) and high-sensitivity C-reactive protein (hs-CRP) were observed. The disease activity was assessed using disease activity score in 28 joints (DAS28). The ex- pression of BTLA, levels of methane dicarboxylic aldehyde (MDA) , reactive oxygen species (ROS) , superoxide dismutase (SOD) , total antioxidant capacity (TAOC) , and related cytokines (IL-17, TNF-α, IL- 4, IL-35) were also detected. Results Compared with before treatment in the same group, post-treatment FEV1, PEF, MEF25-75, MEF50, and MEF25 were all increased (P <0. 05, P <0. 01) ; ESR, hypersensi- tive C reactive protein (hs-CRP) , and DAS28 were all decreased (P <0. 01) , peripheral blood levels of BTLA +, CD19 +, CD24 +, CD19 + CD24 +, CD24 + BTLA +, SOD, TAOC, IL-4, and IL-35 all increased (P < 0. 01, P <0. 05) ; levels of ROS, MDA, TNF-α, and IL-17 all decreased (P <0. 01 , P <0. 05) in the two groups. Compared with the control group, levels of FVC, MEF25-75, MEF50, and MEF25 all increased (P <0. 05, P <0. 01) , and levels of ESR, hs-CRP, and DAS28 all decreased (P <0. 05, P <0. 01 ) in the treatment group after treatment. Peripheral blood levels of BTLA+ , CD24 +, CD19 + CD24 + , TAOC, and TNF-α all increased (P<0. 05), and levels of CD24 CD19 +, ROS, and MDA all decreased (P<0. 01, P < 0. 05) in the treatment group after treatment. CONCLUSIONS: Decreased pulmonary function and attenua- ted BTLA expression generally exist in RA patients. Besides, its disease activity was closely related with attenuated expression of BTLA and imbalanced oxidative stress. XFC could not only improve joint symptoms of RA patients, but also improve lung function by elevating BTLA expression, attenuating tissue damage from immunological inflammation and oxidative stress.
27668566 Variation in Private Payer Coverage of Rheumatoid Arthritis Drugs. 2016 Oct BACKGROUND: Payers in the United States issue coverage determinations to guide how their enrolled beneficiaries use prescription drugs. Because payers create their own coverage policies, how they cover drugs can vary, which in turn can affect access to care by beneficiaries. OBJECTIVE: To examine how the largest private payers based on membership cover drugs indicated for rheumatoid arthritis and to determine what evidence the payers reported reviewing when formulating their coverage policies. METHODS: Coverage policies issued by the 10 largest private payers that make their policies publicly available were identified for rheumatoid arthritis drugs. Each coverage determination was compared with the drug's corresponding FDA label and categorized according to the following: (a) consistent with the label, (b) more restrictive than the label, (c) less restrictive than the label, or (d) mixed (i.e., more restrictive than the label in one way but less restrictive in another). Each coverage determination was also compared with the American College of Rheumatology (ACR) 2012 treatment recommendations and categorized using the same relative restrictiveness criteria. The policies were then reviewed to identify the evidence that the payers reported reviewing. The identified evidence was divided into the following 6 categories: randomized controlled trials; other clinical studies (e.g., observational studies); health technology assessments; clinical reviews; cost-effectiveness analyses; and clinical guidelines. RESULTS: Sixty-nine percent of coverage determinations were more restrictive than the corresponding FDA label; 15% were consistent; 3% were less restrictive; and 13% were mixed. Thirty-four percent of coverage determinations were consistent with the ACR recommendations, 33% were more restrictive; 17% were less restrictive; and 17% were mixed. Payers most often reported reviewing randomized controlled trials for their coverage policies (an average of 2.3 per policy). The payers reported reviewing an average of 1.4 clinical guidelines, 1.1 clinical reviews, 0.8 other clinical studies, and 0.5 technology assessments per policy. Only 1 payer reported reviewing cost-effectiveness analyses. The evidence base that the payers reported reviewing varied in terms of volume and composition. CONCLUSIONS: Payers most often covered rheumatoid arthritis drugs more restrictively than the corresponding FDA label indication and the ACR treatment recommendations. Payers reported reviewing a varied evidence base in their coverage policies. DISCLOSURES: Funding for this study was provided by Genentech. Chambers has participated in a Sanofi advisory board, unrelated to this study. The authors report no other potential conflicts of interest. Study concept and design were contributed by Chambers. Anderson, Wilkinson, and Chenoweth collected the data, assisted by Chambers, and data interpretation was primarily performed by Chambers, along with Anderson and with assistance from Wilkinson and Chenoweth. The manuscript was written primarily by Chambers, along with Wilkinson and with assistance from Anderson and Chenoweth. Chambers, Chenoweth, Wilkinson, and Anderson revised the manuscript.
26110878 Effects of Tumour Necrosis Factor Antagonists on Insulin Sensitivity/Resistance in Rheumat 2015 OBJECTIVE: Beyond the joints, TNFi (tumour necrosis factor inhibitor) therapy may confer systemic benefits in rheumatoid arthritis (RA). Several studies have investigated the role of TNFi on insulin resistance/sensitivity (IR/IS). This question is of general interest given the emerging evidence linking inflammation and insulin resistance. The main aim of this review was to summarise the published data and to determine the effects of TNFi on IR/IS. METHODS: We searched the PubMed and ISI Web of Knowledge databases for studies which examined the effects of TNFi on IR/IS. The studies were assessed independently by two reviewers according to a pre-specified protocol. The data on Homeostatic Model Assessment for Insulin resistance (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI) were pooled and reported as standard difference in means (SDM) with 95% confidence interval (CI) using a random-effects model. RESULTS: A total of eight studies with 260 subjects met the selection criteria. The duration of the studies was from 8 weeks to 12 months. There was statistically significant reduction in HOMA index in six out of eight studies and four reported significant increment in QUICKI. The pooled analysis revealed significant reduction in HOMA [SDM-0.148, 95%CI[-0.278 to -0.017], p=0.026] and increment in QUICKI [SDM 0.312, 95%CI[0.019 to 0.606], p=0.037] with TNFi. CONCLUSION: There is emerging evidence to support that TNFi therapy improves IS and reduces IR in RA. Further, well conducted trials are needed to determine if such effects translate to lower incidence of diabetes in RA or other autoimmune conditions on biologic therapy.
27234231 STAT4 rs7574865 G/T polymorphism is associated with rheumatoid arthritis and disease activ 2016 Dec Rheumatoid arthritis (RA) is a systemic autoimmune disease in whose etiology genetic factors are known to play an important role. Among the genes associated with RA, STAT4 could be an important factor in conducting helper T cells toward the pro-inflammatory Th1 and Th17 lineages. The aim of this study is to determine the association of the STAT4 polymorphism rs7574865 with RA, disease activity, and anti-cyclic citrullinated peptide (CCP) antibody levels in a Mexican population. Genotyping was carried out using the Taqman® system from Applied Biosystems in 140 patients with RA and 150 healthy subjects. Disease activity was evaluated by a rheumatologist using the DAS28 and Spanish-HAQ-DI instruments. Anti-CCP levels were determined by ELISA. Associations of the genotypes of rs7574865 with DAS28, HAQ, and anti-CCP antibody levels with RA were determined. Findings showed that the GT and TT genotypes and the T allele from rs7574865 were all associated as risk factors for RA, independently of their anti-CCP status. An association with moderate-to-high disease activity (DAS28 ≥ 3.2) was also found. Additionally, patients with the GT or TT genotypes showed lower HAQ values than those who carried the GG genotype. No differences in anti-CCP antibody levels or DAS28 and genotypes were found. This work supports the association of the STAT4 rs7574865 polymorphism with RA and disease activity, but not with anti-CCP antibody levels in a Mexican population.
25605621 Chikungunya viral arthritis in the United States: a mimic of seronegative rheumatoid arthr 2015 May OBJECTIVE: Chikungunya virus (CHIKV) is an arthritogenic mosquito-transmitted alphavirus that spread to the Caribbean in 2013 and to the US in 2014. CHIKV-infected patients develop inflammatory arthritis that can persist for months or years, but little is known about the rheumatologic and immunologic features of CHIKV-related arthritis in humans, particularly as compared to rheumatoid arthritis (RA). The purpose of this study was to describe these features in a group of 10 American travelers who were nearly simultaneously infected while visiting Haiti in June 2014. METHODS: Patient history was obtained and physical examination and laboratory tests were performed. All patients with CHIKV-related arthritis had detectable levels of anti-CHIKV IgG. Using cytometry by time-of-flight (CyTOF), we analyzed peripheral blood mononuclear cells in CHIKV-infected patients, healthy controls, and patients with untreated, active RA. RESULTS: Among 10 CHIKV-infected individuals, 8 developed persistent symmetric polyarthritis that met the American College of Rheumatology/European League Against Rheumatism 2010 criteria for (seronegative) RA. CyTOF analysis revealed that RA and CHIKV-infected patients had greater percentages of activated and effector CD4+ and CD8+ T cells than healthy controls. CONCLUSION: In addition to similar clinical features, patients with CHIKV infection and patients with RA develop very similar peripheral T cell phenotypes. These overlapping clinical and immunologic features highlight a need for rheumatologists to consider CHIKV infection when evaluating patients with new, symmetric polyarthritis.
26454442 Evaluation of radiological methods of assessing cup anteversion in total hip replacement. 2015 Dec STUDY DESIGN: Prospective clinical study. BACK GROUND: In total hip replacement, the placement of the cup is critical as inaccurate placement can cause impingement, accelerated wear and dislocations. The position of the cup is assessed by abduction and anteversion. There are many radiological methods available for this purpose, while the reliability and validity of the methods have not been adequately done. Calculation by CT method is a gold standard. The aim of study was to evaluate the reliability and validity of all the methods. METHODS: In 30 hips of 25 consecutive patients, 13 females and 12 males who underwent primary total hip replacement in our institution, the component version in all the five radiological methods was calculated and compared with CT evaluation of angles. The intra- and interobserver reliabilities were assessed. RESULTS: Average CT measurement was 23.28 for anteversion. Lewinnek, Liaw, Hassan, Widmer and Ritun methods had average deviation of 4.330, 4.390, 4.880, 6.840 and 6.220, respectively. All the radiographic and CT methods had excellent intra- and interobserver reliabilities (C.I. 0.894-0.960 and 0.861-0.953). All the methods except Widmer had a significant validity against CT. CONCLUSION: Plain X-rays (AP) are reliable for measuring cup anteversion. Lewinnek, Liaw, Riten and Hassans methods for calculation of cup anteversion are closer to CT in accuracy (p value >0.05). Widmer method varies significantly (p value <0.05) from CT.
27993828 Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monothera 2017 Jun OBJECTIVES: To evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX). METHODS: In this 24-week phase IIb study, patients with moderately to severely active RA were randomised (1:1:1:1) to receive 50, 100 or 200 mg filgotinib once daily, or placebo, after a ≥4-week washout from MTX. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR)20 response at week 12. RESULTS: Overall, 283 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib at any dose achieved ACR20 responses versus placebo (≥65% vs 29%, p<0.001). For other key end points at week 12 (ACR50, ACR70, ACR-N, Disease Activity Score based on 28 joints and C reactive protein, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index) significant differences from baseline in favour of filgotinib 100 and 200 mg versus placebo were seen; responses were maintained or improved through week 24. Rapid onset of action was observed for most efficacy end points. Dose-dependent increases in haemoglobin were observed. The percentage of patients with treatment-emergent adverse events (TEAE) was similar in the placebo and filgotinib groups (∼40%). Eight patients on filgotinib and one on placebo had a serious TEAE, and four patients, all of whom received filgotinib, experienced a serious infection. No tuberculosis or opportunistic infections were reported. CONCLUSIONS: Over 24 weeks, filgotinib as monotherapy was efficacious in treating the signs and symptoms of active RA, with a rapid onset of action. Filgotinib was generally well tolerated. TRIAL REGISTRATION NUMBER: NCT01894516.
27323772 Antimodified protein antibody response pattern influences the risk for disease relapse in 2017 Feb OBJECTIVE: To perform a detailed analysis of the autoantibody response against post-translationally modified proteins in patients with rheumatoid arthritis (RA) in sustained remission and to explore whether its composition influences the risk for disease relapse when tapering disease modifying antirheumatic drug (DMARD) therapy. METHODS: Immune responses against 10 citrullinated, homocitrullinated/carbamylated and acetylated peptides, as well as unmodified vimentin (control) and cyclic citrullinated peptide 2 (CCP2) were tested in baseline serum samples from 94 patients of the RETRO study. Patients were classified according to the number of autoantibody reactivities (0-1/10, 2-5/10 and >5/10) or specificity groups (citrullination, carbamylation and acetylation; 0-3) and tested for their risk to develop relapses after DMARD tapering. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining the role of autoantibodies in predicting relapse. RESULTS: Patients varied in their antimodified protein antibody response with the extremes from recognition of no (0/10) to all antigens (10/10). Antibodies against citrullinated vimentin (51%), acetylated ornithine (46%) and acetylated lysine (37%) were the most frequently observed subspecificities. Relapse risk significantly (p=0.011) increased from 18% (0-1/10 reactivities) to 34% (2-5/10) and 55% (>5/10). With respect to specificity groups (0-3), relapse risk significantly (p=0.021) increased from 18% (no reactivity) to 28%, 36% and finally to 52% with one, two or three antibody specificity groups, respectively. CONCLUSIONS: The data suggest that the pattern of antimodified protein antibody response determines the risk of disease relapse in patients with RA tapering DMARD therapy. TRIAL REGISTRATION NUMBER: 2009-015740-42; Results.
28167169 Adaptation, reliability and validity testing of a Persian version of the Health Assessment 2017 Jan OBJECTIVE: The aim of the present study was to culturally adapt and evaluate reliability and validity of Health Assessment Questionnaire-Disability Index (HAQ-DI) in Iranian patients with rheumatoid arthritis (RA). SUBJECTS: 234 patients with RA for validation study, Eighty-six participants for reliability study. METHODS: Test-retest relative reliability and internal consistency of Persian version of HAQ-DI were examined by intraclass correlation coefficient (ICC) and Cronbach's alpha, respectively. Additionally, HAQ-DI construct validity (Spearman's correlation) was examined using Persian version of Short-Form 36 Health survey (SF-36), activity and severity parameters. RESULTS: Persian version of HAQ-DI total score showed excellent test-retest reliability (ICC = 0.98) and internal consistency (Cronbach's alpha = 0.95). Spearman's correlations between the total PHAQ-DI score and activity and severity parameters were above 0.55. Correlation between PHAQ-DI and SF-36 Physical Health were higher as compared with SF-36 Mental Health. CONCLUSION: Persian version of HAQ-DI is a reliable and valid culturally-adapted instrument in order to measure functional limitations in Iranian people with RA.
27788229 Characterization of Autoantigens Targeted by Anti-Citrullinated Protein Antibodies In Vivo 2016 Anti-citrullinated protein antibodies (ACPA) have become an integral part of the clinical definition of rheumatoid arthritis, and are hypothesized to be important in the immunopathogenesis of this autoimmune disease. Several citrullinated proteins have been demonstrated to serve as candidate autoantigens for the ACPA, based on in vitro immune reactions between citrullinated peptides/proteins and RA sera. Yet it remains unclear whether the autoantigens identified in vitro are indeed directly and specifically targeted by the ACPA in vivo. Moreover, it is unclear whether ACPA present in RA sera are directed towards the same spectrum of autoantigens as the ACPA present within the synovial compartment. In this study, we isolated ACPA immune complexes from RA synovial fluids (SF) and sera by using immobilized cyclic citrullinated peptides (CCP3) based immune affinity, and characterized the proteins that are directly and specifically associated with them by mass spectrometry. The results demonstrate that four histone proteins are prominent ACPA autoantigens, with the frequency of detection being histone H4 (89%), H2B (63%), H3 (63%), and H2A (58%) in ACPA positive RA SF. We further demonstrate that a histone 4 peptide containing citrulline at position Cit39 was recognized by 100% of ACPA positive RA SF. An adjacent citrulline residue at Cit40 was recognized by 34% of ACPA positive RA SF. An H4 peptide containing Cit39-40 was recognized in the serum of 94% ACPA positive RA, 77% ACPA positive first-degree relatives (FDR) of RA patients, and 2.5% of healthy controls. The Cit39-40 peptide substantially blocked the ACPA reactivity in both SF and serum. Although the spectrum of ACPA we identified was limited to those isolated using immobilized CCP3 peptides, the findings indicate that H4 is a widely recognized RA autoantigen in both the synovial and serum compartments. The identification of this immunodominant ACPA epitope may be valuable in designing approaches to immune tolerance induction in RA.
25708920 Risk of hospitalized infection among rheumatoid arthritis patients concurrently treated wi 2015 Jun OBJECTIVE: Denosumab is a biologic agent used to treat osteoporosis. Its safety profile given concurrently with biologic drugs for rheumatoid arthritis (RA) has not been well studied. We evaluated hospitalized infections among patients treated with biologic agents for RA who initiated denosumab or zoledronic acid (ZA), a parenteral bisphosphonate without known associations with infection. We hypothesized that the rate of hospitalized infection with denosumab would be noninferior to ZA. METHODS: We identified RA patients enrolled in Medicare in 2006-2012 treated with biologic agents who initiated denosumab or ZA. Cox proportional hazards models compared the risk for hospitalized infection, comparing denosumab users to ZA users and adjusting for potentially confounding factors. A noninferiority margin was specified a priori to demonstrate that denosumab had no greater infection risk than ZA if the upper bound of the 95% confidence interval (95% CI) of the hazard ratio (HR) was <1.5. RESULTS: Eligible RA patients receiving biologic agents initiated denosumab (n = 1,354) or ZA (n = 4,460). Characteristics of the denosumab users were as follows: mean ± SD age 73.0 ± 8.9, 98.2% women, with a majority receiving infliximab (35.7%) or abatacept (18.6%). Denosumab users had a higher prevalence of prior infections (11.5% hospitalized and 48.3% outpatient) and infection-related risk factors. The crude rate of hospitalized infections for denosumab (14.9/100 person-years [95% CI 12.2-18.1]) was comparable to that for ZA (13.9/100 person-years [95% CI 12.5-15.4]). After adjustment, the HR of hospitalized infection for denosumab users was noninferior to that for ZA users (HR 0.89 [95% CI 0.69-1.15]). CONCLUSION: The rate of hospitalized infection among RA patients receiving denosumab concurrently with biologic agents for RA was not increased compared to those receiving zoledronate.
26767993 Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumati 2016 Feb BACKGROUND: In the absence of an ideal treatment for chronic pain associated with rheumatic diseases, there is interest in the potential effects of cannabinoid molecules, particularly in the context of global interest in the legalization of herbal cannabis for medicinal use. METHODS: A systematic search until April 2015 was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, www.cannabis-med.org and clinicaltrials.gov for randomized controlled trials with a study duration of at least 2 weeks and at least ten patients per treatment arm with herbal cannabis or pharmaceutical cannabinoid products in fibromyalgia syndrome (FMS), osteoarthritis (OA), chronic spinal pain, and rheumatoid arthritis (RA) pain. Outcomes were reduction of pain, sleep problems, fatigue and limitations of quality of life for efficacy, dropout rates due to adverse events for tolerability, and serious adverse events for safety. The methodology quality of the randomized controlled trials (RCTs) was evaluated by the Cochrane Risk of Bias Tool. RESULTS: Two RCTs of 2 and 4 weeks duration respectively with nabilone, including 71 FMS patients, one 4-week trial with nabilone, including 30 spinal pain patients, and one 5-week study with tetrahydrocannbinol/cannabidiol, including 58 RA patients were included. One inclusion criterion was pain refractory to conventional treatment in three studies. No RCT with OA patients was found. The risk of bias was high for three studies. The findings of a superiority of cannabinoids over controls (placebo, amitriptyline) were not consistent. Cannabinoids were generally well tolerated despite some troublesome side effects and safe during the study duration. CONCLUSIONS: Currently, there is insufficient evidence for recommendation for any cannabinoid preparations for symptom management in patients with chronic pain associated with rheumatic diseases.
24297376 MRP8/14 serum levels as a strong predictor of response to biological treatments in patient 2015 Mar BACKGROUND: One-third of rheumatoid arthritis (RA) patients treated with biological therapy show lack of response. The use of predictive biomarkers to identify responders to treatment may provide guidance in optimising treatment strategies and reduce unnecessary side effects and costs. OBJECTIVE: To test the ability of myeloid-related proteins (MRP)8/14 protein complexes, an endogenous TLR-4 receptor agonist, to predict and monitor response to biologics in RA patients. METHODS: 170 RA patients treated with adalimumab (n=86), infliximab (n=60) or rituximab (n=24) were categorised into clinical responders (n=123) and non-responders (n=47). MRP8/14 serum complexes were measured at baseline, and 4 and 16 weeks after initiation of treatment and related to response outcome. RESULTS: Before initiation of treatment, responders showed significantly higher MRP8/14 protein complex levels compared with non-responders in each prospective cohort (p=0.010, p=0.001 and p<0.001, respectively). Logistic regression analysis showed that having high MRP8/14 baseline levels increased the odds of being a responder by 3.3 up to 55. In responders to adalimumab or infliximab treatment, MRP8/14 levels decreased after 4 weeks of treatment by 46% and 60% and after 16 weeks by 61% and 68%, respectively. In contrast, MRP8/14 levels were stable in non-responders. In patients treated with rituximab, MRP8/14 levels decreased by 59% after 16 weeks in responders and increased by 89% after 16 weeks in non-responders. CONCLUSION: Serum concentrations of MRP8/14 protein complex are a promising biomarker to predict response to biological therapy in active RA patients at baseline and could be used to monitor response to treatment across different mechanisms of action.
25839346 Corneal Biomechanical Properties in Rheumatoid Arthritis. 2015 Nov PURPOSE: To investigate the variations in biomechanical properties of the cornea in rheumatoid arthritis (RA) patients. METHODS: A total of 53 RA patients, and 25 healthy individuals (control group) were enrolled. Rheumatoid arthritis patients were classified as in active phase (group 1; n=24) or in remission phase (group 2; n=29). Corneal biomechanical parameters including corneal hysteresis (CH), corneal resistance factor (CRF), corneal compensated intraocular pressure (IOPcc), and Goldmann-correlated IOP (IOPg) were measured with the Reichert Ocular Response Analyzer. Topographical measurements, including central corneal thickness (CCT), anterior chamber depth, iridocorneal angle, and corneal volume were measured using a Sirius corneal topographer. RESULTS: The mean CH was 9.43±1.17 mm Hg in group 1, 9.42±1.84 mm Hg in group 2, and 10.47±1.68 mm Hg in the control group (P=0.03). The mean IOPcc was 17.85±3.2 mm Hg in group 1, 17.95±3.49 mm Hg in group 2, and 15.36±3.11 mm Hg in the control group (P=0.008). The CH showed a significant positive correlation with CRF (P=0.000, r=0.809) and CCT (P=0.000, r=0.461), and a significant negative correlation with IOPcc (P=0.000, r=-0.469). CONCLUSIONS: Decrease in the mean CH measurements indicates that ultrastructural changes in the cornea may occur in the active phase, and these changes persist in the remission period. In addition, IOPcc is significantly affected by the corneal biomechanical properties. In RA patients, it is important to control the corneal parameters and IOP measurements against the irreversible changes on the optic nerve.
26361944 Validation and relevance of Rheumatoid Arthritis Pain Scale (RAPS) in Indian (Asian) patie 2016 Jan Pain in RA is multifaceted and complex. Measuring instruments are inadequate. Rheumatoid Arthritis Pain Scale (RAPS) (Arthritis Care Res 45:317-323, 2001) was designed to measure pain comprehensively but has been sparsely reported. We decided to validate a suitable version for our community. Post translation (contextual), RAPS was administered (face to face interview) to 172 consenting patients of moderately severe RA (mean pain visual analogue scale (VAS) 5.4 cm) in a cross-sectional study using standard rheumatology case record form. RAPS contained 24 questions (numeric score, anchored at 0 (never) and 6 (always); range 0-144). Fifty-seven cohort patients on supervised rheumatology care were followed for 16 weeks. SPSS (v16) was used for statistical analysis, significant p < 0.05. RAPS showed good face and content validity (consensus). Construct/criterion validity was demonstrated for subclass domains and total RAPS (Cronbach's alpha 0.91, test-retest interclass correlation (Pearson) 0.71). Fair to modest correlation (p < 0.05) was seen with swollen joint count (0.16), Indian health assessment questionnaire (0.23), medical outcome short form (SF), 36 physical score (-0.35), SF 36 mental score (-0.21) and C-reactive protein (0.25), not with pain VAS. Similar results were shown for subclass domains (physiologic, affective, sensory, cognitive), except low alpha for affective. Age, disease duration and SF 36 were significant predictors (linear regression). In factor analysis, RAPS loaded with SF 36. The standardized response mean (0.6) was equal to pain VAS and DAS 28. RAPS was found to be a valid and clinically relevant instrument for measuring pain in Indian patients suffering from RA. It merits more widespread clinical use.
27181115 The efficacy and safety of additional administration of tacrolimus in patients with rheuma 2017 Jan OBJECTIVES: Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown. METHODS: Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8 mg/kg/month] and 2 subcutaneous [324 mg/month] TCZ treatments, methotrexate 6.1 mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI] ≥ 5.8, 18 secondary non-responders) were additionally treated with TAC (1.1 mg/day), and enrolled in this 24-week, prospective study. RESULTS: Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28-CRP) from 3.3 at baseline to 2.1 at week 24 (p < 0.001), CDAI from 17.7 to 7.6 (p < 0.001), and serum matrix metalloproteinase-3 levels from 232.8 to 66.2 ng/ml (p < 0.001). About 15 patients (75%) achieved low disease activity or remission (DAS28-CRP ≤2.7 or CDAI ≤10) at week 24. CONCLUSIONS: Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option.
26782362 Correlation Between the Expression of MicroRNA-301a-3p and the Proportion of Th17 Cells in 2016 Apr Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and subsequent joint destruction. Previous studies have confirmed that Th17 cells play a critical role in the pathogenesis of RA. MicroRNA (miR)-301a-3p is a regulatory factor for Th17 cells differentiation that contributes to the pathogenesis of autoimmune diseases. The purposes of this study were to identify the alteration of Th17 cells and analyze the correlation between the expression of the miR-301a-3p and the proportion of Th17 cells in RA patients. The results showed that the frequency of Th17 cells and the expression of transcription factors (RORγt and STAT3) significantly increased in the peripheral blood mononuclear cells (PBMCs) from RA patients, and the associated proinflammatory cytokines were also upregulated. We also observed that the expression of protein inhibitor of activated STAT3 (PIAS3), the main cellular inhibitor of STAT3, was attenuated in RA patients and negatively correlated with the percentage of Th17 cells in RA. Interestingly, miR-301a-3p, an inhibitor of PIAS3 expression, was overexpressed in the PBMCs from RA patients and positively correlated with the frequency of Th17 cells in patients with RA. Taken together, these data indicated that miR-301a-3p and Th17 cells were augmented in peripheral blood, which may play an important role in the process of RA.
26463248 Biologic Therapy in Immune Mediated Inflammatory Disease: Basic Science and Clinical Conce 2016 During the last decades, the advent of biological therapies has revolutionized the management of several immune-mediated inflammatory disorders, as inflammatory bowel diseases, autoimmune arthritis and psoriasis, which significantly impact both quality of life and health care economics. Biological therapies currently available can be divided into two main categories: the tumor necrosis factor-α antagonists (infliximab, adalimumab, etanercept, golimumab, certolizumab pegol) and interleukin 12/23 monoclonal antibodies (ustekinumab). Biologics, reducing TNFα bioavailability or inhibiting proximal regulators of inflammatory cascade, represent an established therapeutic strategy of inflammatory autoimmune diseases, with remarkable efficacy and a safety profile that is extensively examined and monitored. The biology and the immunological effects of TNFα, IL-12, IL-23 and related signalling pathways are accurately summarized. The dosing regimens, methods of administration, pharmacodynamics profiles, and side effects of the currently licensed TNFα antagonists and IL12/IL23 inhibitor are discussed in detail.
26585362 Expression of allograft inflammatory factor-1 in peripheral blood monocytes and synovial m 2016 Jan OBJECTIVE: Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic protein expressed in various human cells such as monocyte/macrophages and activated T lymphocytes. A recent study showed that AIF-1 is strongly expressed in infiltrating mononuclear cells and synovial fibroblasts in rheumatoid arthritis and that AIF-1 induces the proliferation of cultured synovial cells. In this study we analysed the expression of AIF-1 in peripheral blood monocytes and synovial membranes from patients with rheumatoid arthritis (RA). METHODS: We examined 71 patients with rheumatoid arthritis and 25 control subjects. RESULTS: Using flow cytometry we found significantly increased numbers of circulating AIF-1(+) monocytes in peripheral blood from RA patients compared with controls. Moreover, there were statistically significant positive correlations between AIF-1(+) monocytes, DAS28 and the Sharp erosion score. Immunofluorescence staining showed strong expression of AIF-1 by infiltrating mononuclear cells - predominantly macrophages in RA synovial tissues - compared with tissues derived from joints affected by osteoarthritis. CONCLUSION: The results of this study suggest that AIF-1 may be associated with the pathogenesis of RA and may be a novel cytokine involved in the immunological process underlying RA.
25096983 Segmentation of bones in magnetic resonance images of the wrist. 2015 Apr PURPOSE: Rheumatoid arthritis (RA) is a disease characterized by progressive and irreversible destruction of bones and joints. According to current recommendations, magnetic resonance imaging (MRI) is used to asses three main signs of RA based on manual evaluation of MR images: synovitis, bone edema and bone erosions. The key feature of a future computer-assisted diagnostic system for evaluation RA lesions is accurate segmentation of 15 wrist bones. In the present paper, we focus on developing a wrist bones segmentation framework. METHOD: The segmentation procedure consisted of three stages: segmentation of the distal parts of ulna and radius, segmentation of the proximal parts of metacarpal bones and segmentation of carpal bones. At every stage, markers of bones were determined first, using an atlas-based approach. Then, given markers of bones and a marker of background, a watershed from markers algorithm was applied to find the final segmentation. RESULTS: The MR data for 37 cases were analyzed. The automated segmentation results were compared with gold-standard manual segmentations using a few well-established metrics: area under ROC curve AUC, mean similarity MS and mean absolute distance MAD. The mean (standard deviation) values of AUC, MS and MAD were 0.97 (0.04), 0.93 (0.09) and 1.23 (0.28), respectively. CONCLUSION: The results of the present study demonstrate that automated segmentation of wrist bones is feasible. The proposed algorithm can be the first stage for the detection of early lesions like bone edema or synovitis.