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ID PMID Title PublicationDate abstract
25583377 Survival in rheumatoid arthritis-associated pulmonary arterial hypertension compared with 2015 Apr BACKGROUND AND OBJECTIVE: In this study, we evaluated survival in rheumatoid arthritis-associated pulmonary arterial hypertension (RA-PAH) compared with idiopathic pulmonary arterial hypertension (IPAH) patients, and evaluate differences in disease severity and treatment. METHODS: We conducted a retrospective cohort study of RA-PAH and IPAH at the University Health Network Pulmonary Hypertension Programme, Toronto, Canada. The primary outcome was time to all-cause mortality. We evaluated survival using Kaplan-Meier curves. Using a propensity score-matched cohort, we used Cox proportional hazards models to estimate survival. RESULTS: Screening 1385 patients identified 18 RA-PAH and 155 IPAH patients. RA-PAH patients had an older median age of onset (64.0 vs 53.7 years) and lower baseline mean pulmonary arterial pressure (mPAP) (41 vs 50 mm Hg, P = 0.02). RA-PAH patients tended to have a higher proportion of females (83% vs 70%, relative risk 0.55, 95% confidence interval (CI): 0.19-1.57), lower proportion with baseline World Health Organization functional class III/IV (39% vs 52%), lower median baseline brain natriuretic peptide (58.4 vs 95.0 pg/mL) and longer baseline 6-min walk distance (440 vs 397 m). There were 35 deaths, 2/18 (11%) RA-PAH patients and 33/155 (21%) IPAH patients. The unadjusted 1-year survival was 93% for RA-PAH and 94% for IPAH. In the matched cohort, there were seven deaths: 2/18 (11%) RA-PAH and 5/18 (28%) IPAH patients, hazard ratio 1.53 (95% CI: 0.15-2.84). Separation of survival curves did not achieve statistical significance, log-rank 0.56. CONCLUSIONS: Compared with IPAH patients, RA-PAH patients have an older age of onset and lower baseline mPAP. RA-PAH patients have comparable survival to IPAH patients.
27243383 The Statistical Value of Raw Fluorescence Signal in Luminex xMAP Based Multiplex Immunoass 2016 May 31 Tissue samples (plasma, saliva, serum or urine) from 169 patients classified as either normal or having one of seven possible diseases are analysed across three 96-well plates for the presences of 37 analytes using cytokine inflammation multiplexed immunoassay panels. Censoring for concentration data caused problems for analysis of the low abundant analytes. Using fluorescence analysis over concentration based analysis allowed analysis of these low abundant analytes. Mixed-effects analysis on the resulting fluorescence and concentration responses reveals a combination of censoring and mapping the fluorescence responses to concentration values, through a 5PL curve, changed observed analyte concentrations. Simulation verifies this, by showing a dependence on the mean florescence response and its distribution on the observed analyte concentration levels. Differences from normality, in the fluorescence responses, can lead to differences in concentration estimates and unreliable probabilities for treatment effects. It is seen that when fluorescence responses are normally distributed, probabilities of treatment effects for fluorescence based t-tests has greater statistical power than the same probabilities from concentration based t-tests. We add evidence that the fluorescence response, unlike concentration values, doesn't require censoring and we show with respect to differential analysis on the fluorescence responses that background correction is not required.
27301524 Methotrexate-associated Intravascular Large B-cell Lymphoma in a Patient with Rheumatoid A 2016 Intravascular large B-cell lymphoma (IVLBCL) is a rare and clinically aggressive lymphoma with an unfavorable prognosis. We report the case of a 50-year-old woman who was diagnosed with IVLBCL during treatment with methotrexate (MTX) and biologic agents for rheumatoid arthritis. The symptoms showed partial improvement only after the cessation of both treatments. She subsequently received chemotherapy and achieved a complete remission and has remained free of recurrence for 2 years without any further treatment. We herein describe a rare case of IVLBCL which presented with the features of an MTX-associated lymphoproliferative disorder.
27575590 Cardiovascular adverse events by non-steroidal anti-inflammatory drugs: when the benefits 2016 Nov Therapeutic efficiency of NSAID is handicapped by ongoing discussion of cardiovascular (CV) safety. Areas covered: We update meta-analyses on NSAIDs in patients with and without cardiovascular (CV) diseases and analyse the association between NSAIDs and cardiovascular events in patients with inflammation. We demonstrate the substantial influence of an indication bias and confounding, which falsely increase the CV risk. We demonstrate protective cardiovascular effects of NSAIDs due to their anti-inflammatory activity, in particular in patients with rheumatoid arthritis, osteoarthritis or inflammatory pain. Expert commentary: t-NSAIDs and Coxibes drugs resemble in their observed CV risk which, in contrast, reflects the intrinsic risk of patients with pain and inflammation. The anti-inflammatory NSAIDs reduce the risk of first myocardial infarction in patients with inflammation and elevated CRP. The extended use of NSAIDs is not associated with an increased CV risk in patients with pain and inflammation but with reduction in all-cause mortality.
24810700 Rheumatoid myositis leading to acute lower extremity compartment syndrome: a case-based re 2015 Oct Muscle pain and weakness in a rheumatoid arthritis (RA) patient has a broad differential, and myositis should be considered early in the disease course as serious limb and life-threatening sequelae may occur. A 55-year-old woman with a past medical history of methotrexate-controlled RA presented with right leg pain for 4 days. The patient suffered sensory loss in the right foot and decreased strength in the toes. Lab tests revealed elevated creatine kinase, ESR, and anti-rheumatoid factor antibody titers. CT scan revealed myositis of posterior compartment muscles. Progressive edema, pain, and neuromuscular deficits persisted despite steroid and antibiotic therapy, so the patient was taken for urgent fasciotomy for acute compartment syndrome. The muscle biopsy showed diffuse mononuclear cell infiltration as well as perivascular and perineural involvement consistent with rheumatoid myositis (RM). The patient did well post-op on a prednisone taper. This case underlines the systemic nature of RA and exemplifies the severity of inflammation that may lead to grave consequences such as compartment syndrome. The histopathology is diagnostic when there is evidence of mononuclear cell infiltration; however, this is not entirely specific. Early, aggressive therapy with immunosuppressives is warranted in such patients. RM has not, to our knowledge, been recorded to cause acute compartment syndrome. Clinicians should be aware of this uncommon manifestation of RA keeping the various presentations of rheumatoid disease in mind when faced with these patients.
27936930 Different Contributions of CDKAL1, KIF21B, and LRRK2/MUC19 Polymorphisms to SAPHO Syndrome 2017 Feb OBJECTIVES: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, rheumatoid arthritis (RA), ankylosing spondylitis (AS), and seronegative spondyloarthropathy (SPA) are autoimmune diseases of unknown etiology, which share some clinical manifestations in common. Previous family-based investigations support genetic contributions to the susceptibility of these diseases. The current study evaluated whether three previously reported AS-associated single-nucleotide polymorphisms (SNPs), rs6908425 T>C in CDKAL1, rs11584383 T>C near KIF21B, and rs11175593 C>T near LRRK2/MUC19, have any genetic overlap across multiple autoimmune diseases including SAPHO syndrome, RA, AS, and SPA. MATERIALS AND METHODS: Genomic DNA was obtained from 71 SAPHO, 125 RA, 67 AS, and 35 SPA Han Chinese patients, as well as 104 healthy controls. SNPs were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Genotype and allele frequencies were analyzed using chi-square test. RESULTS: rs6908425 T>C in CDKAL1 was significantly different between SAPHO cases and healthy controls (odds ratios = 2.056, 95% confidence intervals: 1.211-3.490; p = 0.007), but no SNPs were associated with the risk of developing RA, AS, or SPA (p > 0.05). Analysis of genotype distributions showed similar results. A significant difference was only found in the genotype frequency of rs6908425 in SAPHO cases (p = 0.004); no significant differences were detected among patients with RA, AS, and SPA (p > 0.05). CONCLUSIONS: Our results suggest that rs6908425 in CDKAL1 is associated with the risk of developing SAPHO in Han Chinese populations. People who carry the risk allele T of rs6908425 might be more prone to developing SAPHO syndrome.
26166764 miR-573 is a negative regulator in the pathogenesis of rheumatoid arthritis. 2016 Nov Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by abnormal inflammation, angiogenesis, and cartilage destruction. Our previous study demonstrated an increased expression of thioredoxin domain containing 5 (TXNDC5) in the synovial tissues of RA, and its overexpression was implicated in RA pathology. Although TXNDC5 variation is linked to genetic susceptibility to RA, the regulation of its abnormal expression has not been well defined. Here, we show that TXNDC5 is directly targeted by microRNA (miR)-573, and TXNDC5, in turn, mediates the suppressive effect of miR-573 on the invasion of synovial fibroblasts of RA (RASFs). miR-573 overexpression suppressed the expression of interleukin 6 (IL-6) and cyclooxygenase 2 in RASFs, as well as the production of tumor necrosis factor-alpha and interleukin-1 beta by activated THP-1 cells in response to lipopolysaccharide (LPS) stimulation. Moreover, treatment with conditioned medium of RASFs transfected with miR-573 mimic inhibited the angiogenic ability of human umbilical vein endothelial cells (HUVECs). Of note, epidermal growth factor receptor and Toll-like receptor 2 were validated as new direct targets of miR-573, and mediate the regulation of miR-573 on IL-6 production as well as the angiogenesis of HUVECs. In addition, exogenous miR-573 expression suppressed the activation of mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3, and phosphatidylinositol-3 kinase/activate protein kinase B in RASFs in response to LPS. Indeed, MAPK signaling was essential to ensure the function of miR-573. Taken together, our study points toward the protective roles of miR-573 in the pathological process of RA and suggests a potential target in the treatment of RA.
26882526 Reduced DICER1 Expression Bestows Rheumatoid Arthritis Synoviocytes Proinflammatory Proper 2016 Aug OBJECTIVE: While the regulatory role of individual microRNAs (miRNAs) in rheumatoid arthritis (RA) is well established, the role of DICER1 in the pathogenesis of the disease has not yet been investigated. The purpose of this study was to analyze the expression of factors involved in miRNA biogenesis in fibroblast-like synoviocytes (FLS) from RA patients and to monitor the arthritis triggered by K/BxN serum transfer in mice deficient in the Dicer gene (Dicer(d/d) ). METHODS: The expression of genes and precursor miRNAs was quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MicroRNA macroarray profiling was monitored by qRT-PCR. Cytokines were quantified by enzyme-linked immunosorbent assay. Experimental arthritis in mice was achieved by the transfer of serum from K/BxN donors. Apoptosis was quantified using an enzyme-linked immunosorbent assay. RESULTS: We found decreased DICER1 and mature miRNA expression in synovial fibroblasts from RA patients. These cells were hyperresponsive to lipopolysaccharide, as evidenced by their increased interleukin-6 secretion upon stimulation. Experimental serum-transfer arthritis in Dicer(d/d) mice confirmed that an unbalanced biogenesis of miRNAs correlated with an enhanced inflammatory response. Synoviocytes from both RA patients and Dicer(d/d) mice exhibited increased resistance to apoptotic stimuli. CONCLUSION: The findings of this study further substantiate the important role of DICER1 in the maintenance of homeostasis and the regulation of inflammatory responses.
26833303 Usability and Acceptability of the Abatacept Pre-Filled Autoinjector for the Subcutaneous 2016 Feb INTRODUCTION: The purpose of the present study was to determine whether the abatacept autoinjector can be used by the intended population without patterns of preventable use errors, and is acceptable when assessed against key user needs. METHODS: Two independently conducted simulated-use studies, with no active drug administered, quantified use errors and evaluated the abatacept autoinjector and competitor devices on key attributes (comfort, control, ease of use, confidence of dose) and overall acceptability. Autoinjector preference was also assessed. Participants were patients with rheumatoid arthritis, caregivers, and healthcare professionals (HCPs). Participants were informed that a new rheumatoid arthritis autoinjector was being tested but were blinded to the intended drug and sponsor identity. RESULTS: In the formative (pre-validation) study (n = 54), two high-priority use errors occurred, both of which resulted from protocol non-compliance rather than mental confusion or physical limitations. In the summative (validation) study (n = 99), one high-priority use error occurred; this was deemed a simulated-use study artifact as participant behavior was guided by actual experience associated with the feel of drug delivery into the skin rather than by protocol, so no mitigation steps were considered necessary. Across user groups, average scores were consistently high for the pre-defined key attributes. Overall acceptability scores (7-point scale) were significantly higher for the abatacept versus competitor autoinjectors-formative study: patients 6.7 vs 5.2 (P = 0.0001), caregivers 7.0 vs 4.6 (P = 0.0093), HCPs 6.8 vs 5.1 (P = 0.0020); summative study: patients 6.5 vs 5.9 (P = 0.0404), caregivers 6.8 vs 5.8 (P = 0.0047), HCPs 6.8 vs 5.1 (P = 0.0002). The abatacept autoinjector was preferred to competitor devices: patients 85.7% vs 14.3% (P = 0.00002), caregivers 84.2% vs 15.8% (P = 0.00443), HCPs 95.0% vs 5.0% (P = 0.00004). Positive experiences with the abatacept autoinjector were attributed to the rubberized grip, device size, visualization of dose progression, button ergonomics, and ease of use. CONCLUSION: The abatacept autoinjector demonstrated usability without patterns of preventable use errors, and with high acceptability ratings across all key attributes assessed. Preference over competitor autoinjectors was due to device ergonomics, visualization of dose progression, confidence of dose delivery, and overall ease of use. FUNDING: Bristol-Myers Squibb.
26775479 [Treatment of Refractory Rheumatoid Arthritis by Huayu Tongbi Recipe Combined Methotrexate 2015 Nov OBJECTIVE: To evaluate the clinical efficacy and safety of Huayu Tongbi Recipe (HTR) combined methotrexate (MTX) in treating refractory rheumatoid arthritis (RRA). METHODS: Totally 167 RRA patients were assigned to the treatment group (73 cases) and the control group (94 cases) according to different therapeutic methods. Patients in the treatment group were treated with HTR combined MTX, while those in the control group were treated with leflunomide (LEF) combined MTX. Clinical signs and symptoms, RF, CRP, ESR, disease activity score 28 (DAS28), and safety indicators were compared between the two groups before treatment, at week 12 and 24 after treatment. The efficacy and safety indices were also evaluated. RESULTS: At week 12 after treatment the total effective rate was 82.2% (60/73 cases) in the treatment group and 79.8% (75/94 cases) in the control group, showing no statistical difference between the two groups (chi2 = 0.15, P > 0.05). At week 24 after treatment the total effective rate was 78.1% (57/73 cases) in the treatment group and 755% (71/94 cases) in the control group, showing no statistical difference between the two groups (chi2 = 0.15, P > 0.05). There was statistical difference in the total effective rate between week 24 and week 12 in the control group (chi2 = 0.49, P < 0.05). Clinical signs and symptoms, RF, CRP, ESR, and DAS28 were significantly improved in the two groups after 12- and 24-week treatment (P < 0.01). There was no statistical difference in the improvement at week 12 after treatment between the two groups (P > 0.05). There was statistical difference in time of morning stiffness, tender joint numbers, swollen joint numbers, patient global assessment, RF, CRP, and DAS28 at week 24 after treatment between the two groups (P < 0.05). Besides, adverse reactions occurred less in the treatment group than in the control group (P < 0.01). CONCLUSION: The efficacy of HTR combined MTX was equivalent to that of LEF (10 mg per day) combined MTX, but with more stable therapeutic effects and less adverse reactions.
26801332 Body mass index and response to tocilizumab in rheumatoid arthritis: a real life study. 2016 Apr Several studies have suggested that obesity could have a negative effect on response to anti-tumor necrosis factor α (anti-TNFα) in rheumatoid arthritis (RA). Little is known about the impact of body mass index (BMI) on other biologic agents. We aimed to evaluate the effect of BMI on response to tocilizumab (TCZ) in RA. RA patients treated with TCZ were included in this multicenter retrospective study. BMI was calculated at the initiation of treatment. After 6 months of treatment, change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate and C-reactive protein level, and tender and swollen joints were analyzed. The primary endpoint was decrease in DAS28 ≥ 1.2. Secondary outcomes were good response and remission by EULAR criteria. At baseline, among 115 RA patients included, the median (interquartile range) BMI was 25.4 (22.0-28.8) kg/m(2). The number of patients with normal weight, overweight, and obesity was 53 (46 %), 37 (32 %), and 25 (22 %), respectively. Baseline characteristics did not differ between the three subgroups of BMI. The median BMI did not differ between responders and non-responders for DAS28 decrease ≥1.2 (25.7 [22.1-29.9] vs 24.9 [22.0-27.1], P = 0.38), EULAR good response (25.9 [22.8-30.0] vs 25.4 [22.0-28.4], P = 0.61), and remission (25.1 [22.5-28.6] vs 25.4 [22.0-28.9], P = 0.76). BMI did not affect the response to TCZ in RA. If confirmed, these results could be helpful for the selection of a biologic agent in obese RA patients.
26210073 Prescribing Patterns of Intravenous Golimumab for Rheumatoid Arthritis. 2015 Sep PURPOSE: The use of intravenous golimumab (GLM-IV), in combination with methotrexate, was approved by the US Food and Drug Administration in July 2013 for the treatment of moderate to severe, active rheumatoid arthritis (RA). GLM-IV is available in 50-mg vials, and the prescribing information specifies a dosing regimen of 2 mg/kg at 0 and 4 weeks and then every 8 weeks thereafter. The purpose of this study was to examine the patterns of prescribing and administration of GLM-IV, including the demographic, clinical, and utilization characteristics of patients with RA newly treated with GLM-IV. METHODS: Rheumatology practices across the continental United States were solicited for a chart-review study. Inclusion criteria were: (1) diagnosis of RA; (2) current treatment with GLM-IV; (3) age ≥18 years; and (4) lack of pregnancy (in female patients). Physicians were offered a monetary incentive for each eligible chart provided. An electronic case-report form was developed to aid in the chart data extraction and included fields for demographic characteristics, available comorbid diagnoses, prior RA treatments, and doses and dates of GLM-IV administration. FINDINGS: A total of 117 eligible patient charts from 15 rheumatologist practices were reviewed. The patient sample was predominantly female (81.2%), with a mean (SD) age of 55.4 (14.5) years. A total of 55.6% of patients had evidence of biologic treatment before receiving GLM-IV, and 53% had at least 1 comorbid condition. In total, 300 individual GLM-IV infusions from this sample were reviewed. Due to the relatively recent approval of GLM-IV use by the US Food and Drug Administration, the majority of patients in this sample (69.2%) had received only between 2 and 4 infusions at the time of the review. For infusion records with valid dose data, the mean number of administered vials was 3.6 (0.8) (total dose, 180 mg); the majority of patients received a dose consistent with the prescribed dose of 2 mg/kg. Combination therapy with methotrexate was observed in the charts of a minority of patients (27.4%). The mean interval between induction and the first follow-up infusion was 32.9 (11.4) days, with a mean maintenance interval of 56.5 (13.3) days. IMPLICATIONS: This analysis provides an early glimpse of the patterns of prescribing GLM-IV. Overall, patients appeared to have been receiving GLM-IV in accordance with Food and Drug Administration labeling; although the rate of prescribing methotrexate was low, dosages and administration intervals were within the expected ranges.
27564656 Brief Report: Sex Ratio of Offspring Born to Women With Systemic Lupus Erythematosus or Rh 2017 Jan OBJECTIVE: To determine whether the sex ratio among offspring born to women with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) is different from that in the general population. METHODS: Women with a singleton delivery were identified from the Swedish Medical Birth Register (1973-2012) and linked to the National Patient Register (1964-2012) to identify those with prevalent SLE or RA. A sample of general population comparators was identified from the Swedish Total Population Register. We calculated the percentages of males born to women with SLE, women with RA, and women in the general population, as well as the risk ratio (RR) for having a male child among first births and all births. We also examined a history of antiphospholipid syndrome in the SLE population, using International Classification of Disease codes before or at delivery. RESULTS: We identified 661 women with SLE and 1,136 women with RA before their first delivery. There were a total of 1,401 deliveries to women with SLE and a total of 2,674 deliveries to women with RA. Compared with women in the general population, women with SLE and those with RA had a lower risk of having a first-born male (RR 0.92 [95% confidence interval 0.85-1.00] and RR 0.93 [95% confidence interval 0.87-0.99], respectively). Among all births, the percentage of male offspring remained lower than that in the general population, but the difference was not statistically significant for RA. CONCLUSION: The proportion of male offspring born to women with prevalent SLE or RA at delivery was lower than that in the general population, although the difference was small. Chronic inflammation may affect the sex ratio through fetal loss in early gestation.
27692966 Erosive osteoarthritis: A systematic analysis of definitions used in the literature. 2017 Feb BACKGROUND: Erosive osteoarthritis (EOA) is a commonly invoked diagnosis representing an important variant of hand osteoarthritis (OA). There is increasing literature on the prevalence, risk factors, etiology, and management of EOA. METHODS: We systematically reviewed the literature to assess variability in the diagnostic definitions used to define EOA in these studies. RESULTS: We reviewed 336 articles and found 62 articles citing diagnostic definitions for EOA. Radiographic appearance was the most commonly used criterion, but there was little agreement on the details or extent of the radiographic changes. Overall, 56 of the 62 studies included clinical features in the diagnostic definitions, yet these features varied considerably. Exclusion criteria were mentioned in 43 of the studies. CONCLUSION: Based on the widely disparate definitions of EOA, we urge caution in interpretation of this literature, and propose that further understanding of EOA will require consensus on its definition.
27097818 Connective Tissue Disorder-Associated Vasculitis. 2016 Jun Vasculitides secondary to connective tissue diseases are classified under the category of 'vasculitis associated with systemic disease' in the revised International Chapel Hill Consensus Conference (CHCC) nomenclature. These secondary vasculitides may affect any of the small, medium or large vessels and usually portend a poor prognosis. Any organ system can be involved and the presentation would vary depending upon that involvement. Treatment depends upon the type and severity of presentation. In this review, we describe secondary vasculitis associated with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, relapsing polychondritis, systemic sclerosis, Sjogren's syndrome and idiopathic inflammatory myositis, focusing mainly on recent advances in the past 3 years.
26984652 Results of a unicentric series of 15 wrist prosthesis implantations at a 5.2 year follow-u 2016 Mar Our retrospective study aimed to evaluate functional and radiological results of a unicentric series of 17 total wrist prostheses implanted between 2001 and 2011. Nine women and seven men, mean age 59, underwent wrist joint arthroplasty, bilateral in one case. Universal Total Wrist and Remotion prostheses were used and followed-up at a mean of 5.2 years (1.1-10). Fifteen patients were reviewed. Four patients had postoperative complications, three of whom required arthrodesis. The rest obtained satisfactory pain relief. Grip strength nevertheless decreased compared to the contralateral side and mobility was reduced: flexion/extension=33°, ulnar/radial deviation=20°. The Quick DASH score was 29% and PRWE, 26%. Radiological assessment revealed carpal implant loosening in eight patients. Our series confirms the discordance generally observed between patients' subjective satisfaction and mediocre clinical and radiological results over the medium term.
27338778 Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in pa 2017 Feb BACKGROUND: Adalimumab has been used in patients with moderately to severely active rheumatoid arthritis (RA) for over 10 years and has a well-established safety profile across multiple indications. OBJECTIVE: To update adverse events (AEs) of special interest from global adalimumab clinical trials in patients with RA. METHODS: This analysis includes 15 132 patients exposed to adalimumab in global RA clinical trials. AEs of interest included overall infections, laboratory abnormalities and AEs associated with influenza vaccination. Pregnancy outcome data were collected from the Adalimumab Pregnancy Registry. RESULTS: Serious infections and tuberculosis occurred at a rate of 4.7 and 0.3 events/100 patient-years, respectively. Two patients experienced hepatitis B reactivation. No significant laboratory abnormalities were reported with adalimumab-plus-methotrexate compared with placebo-plus-methotrexate. Influenza-related AEs occurred in 5% of vaccinated patients compared with 14% of patients not vaccinated during the study. Relative risk of major birth defects and spontaneous abortions in adalimumab-exposed women were similar between that of unexposed women with RA and healthy women. CONCLUSIONS: This analysis confirms and expands the known safety profile of adalimumab and reports no additional safety risk of laboratory abnormalities, hepatitis B reactivation and pregnancy outcomes, including spontaneous abortions and birth defects. The benefits of influenza vaccination are reinforced. TRIAL REGISTRATION NUMBERS: NCT00195663, NCT00195702, NCT00448383, NCT00049751, NCT00234845, NCT00650390, NCT00235859, NCT00647920, NCT00649545, NCT00647491, NCT00649922, NCT00538902, NCT00420927, NCT00870467, NCT00650156, NCT00647270, NCT01185288, NCT01185301.
25802943 Orthopedic uses of stem cell therapy. 2015 Apr The treatment of musculoskeletal disorders is gaining importance as the population ages. In addition to the complications brought on by prolonged life expectancy, the growing epidemic of obesity is contributing to joint degradation. Cell-based tissue engineering has the potential to advance the current treatment for musculoskeletal disorders. This article reviews the various forms of arthritis and describes stem cell therapy as a promising treatment option.
25896410 Brazilin isolated from Caesalpinia sappan L. inhibits rheumatoid arthritis activity in a t 2015 Apr 22 BACKGROUND: Caesalpinia sappan L. extracts exhibit great therapeutic potential, and have been shown to have analgesic and anti-inflammatory properties. This study aimed to understand the anti-rheumatoid activity of brazilin that was isolated from ethyl acetate extract of C. sappan L. The evaluations were conducted in mice with type-II collagen-induced arthritis (CIA). METHODS: Brazilin was purified via preparative HPLC and identified by mass spectrometry and 1H/13C NMR analysis. DBA/1J mice were divided into four groups (n=10). Three groups of mice received intradermal injections of inducer bovine type-II collagen (BTIIC; 2 mg/ml in 0.05 ml acetic acid) and 0.1 ml of booster complete Freund's adjuvant (CFA). A second injection of BTIIC with booster incomplete Freund's adjuvant (ICFA) was given subsequently after 21 days. On 22nd day, purified brazilin (10 mg/kg body weight) or the disease-modifying anti-rheumatic drug methotrexate (3 mg/kg body weight) was administered intraperitoneally daily or every three days for 21 days, respectively to two groups of mice. At the 42nd day, mice sera were collected, and the levels of pro-inflammatory cytokines and stress enzyme markers in serum were measured using standard immunoassay methods. The microstructure and morphometric analyses of the bones were assessed using high-resolution microfocal computed tomography. RESULTS: Brazilin isolated from C. sappan reduced the arthritis index score and the extent of acute inflammatory paw edema in CIA-mice. The bone mineral density was significantly (p<0.05) lower in only-CIA mice, and appeared to increase commensurate with methotrexate and brazilin administration. Brazilin prevented joint destruction, surface erosion, and enhanced bone formation as revealed by microstructural examinations. Brazilin markedly attenuated mouse CIA and reduced the serum levels of inflammatory cytokines including TNF-α, IL-1β, and IL-6. CONCLUSIONS: Brazilin purified from C. sappan L. shows protective efficacy in CIA mouse, and may be useful to treat chronic inflammatory disorders including rheumatoid arthritis.
26440629 Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti-TNF Respo 2015 OBJECTIVES: To determine whether genetic variation within genes related to the Toll-like receptor, inflammasome and interferon-γ pathways contributes to the differences in treatment response to tumour necrosis factor inhibitors (anti-TNF) in patients with rheumatoid arthritis (RA). METHODS: In a retrospective case-case study, we assessed 23 functional single nucleotide polymorphisms (SNPs) in 15 genes. We included 538 anti-TNF naïve Danish RA patients from the nationwide DANBIO database. Multivariable logistic regression analyses were performed to detect associations (p-value<0.05) between genotypes and European League Against Rheumatism (EULAR) treatment responses. False Discovery Rate corrections for multiple testing (q-value) and stratified analyses were performed to investigate association with individual therapies and IgM-rheumatoid factor (RF) status. RESULTS: Six of twenty successfully genotyped polymorphisms were nominally associated with EULAR treatment response. Three of these were in weak to moderate linkage disequilibrium with polymorphisms previously reported associated with anti-TNF treatment response. TLR5(rs5744174) variant allele carriers (odds ratio(OR) = 1.7(1.1-2.5),p = 0.010,q = 0.46) and TLR1(rs4833095) homozygous variant carriers (OR = 2.8(1.1-7.4),p = 0.037,q = 0.46) had higher odds for a positive treatment response. NLRP3(rs10754558) variant allele carriers (odds ratio(OR) = 0.6(0.4-1.0),p = 0.045,q = 0.46) were more likely to have a negative treatment response. The association in TLR5(rs5744174) remained significant after correction for multiple comparisons among patients negative for RF (OR = 6.2(2.4-16.3),p = 0.0002,q = 0.024). No other association withstood correction for multiple testing. Post hoc analyses showed that change in Patient Global score on a visual analogue scale (VAS) and change in pain VAS were the main factors responsible for the association. CONCLUSIONS: We reproduced previously reported associations between genetic variation in the TLR10/1/6 gene cluster, TLR5, and NLRP3 loci and response to anti-TNF treatment in RA. Changes in VAS pain and patient global scores were the main contributors to the association found for TLR5. Furthermore, we identified other candidate genes that require replication in independent cohorts.