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ID PMID Title PublicationDate abstract
26331692 Biomarker exposure-response relationships as the basis for rational dose selection: Lesson 2016 May An exposure-response model was used to characterize the pharmacokinetic-pharmacodynamic relationship of GW406381, a COX-2 inhibitor, based on data from ex vivo prostaglandin E2 inhibition collected in a phase 1 study in healthy subjects. The final model was then used to simulate a proof-of-concept study and to explore suitable dosing ranges in case of hepatic dysfunction or metabolic induction. Trough concentrations in the range of IC80 to IC95 were used as target therapeutic concentrations. Symptom relief in a subsequent phase 2b study in 400 patients with rheumatoid arthritis receiving GW406381 was then analysed to support the design of a phase 3 study in which doses in the range between 10 to 400 mg were explored. The exercise also allowed the evaluation of correlations between the biomarker and clinical end point. A 2-compartment model described the pharmacokinetics of GW406381, whereas the pharmacodynamics was described by an Imax model. In patients with normal organ function, the predicted median therapeutic dose was between 100 and 150 mg. The time course of symptom relief was fitted by a Weibull model, with an Imax model describing the drug effect. Simulations showed that dose-response discrimination occurred at doses higher than 150 mg, with predicted 60%-80% target engagement in the dose range of 150-400 mg.
27473088 Measuring transaminases in patients with rheumatoid arthritis on weekly methotrexate: does 2016 Dec The change in transaminase levels over a single week during therapy with methotrexate (MTX) has not been investigated or reported to date. In clinical practice, it is common to observe abnormal transaminase levels upon routine blood work for toxicity monitoring. Many have suggested that such lab abnormalities can sometimes be attributed to sampling blood for toxicity monitoring proximately following MTX dosing. The aim of our study was to evaluate changes in transaminase levels (AST/ALT) over 1 week after MTX administration in rheumatoid arthritis (RA) patients. In this small proof of concept study, we evaluated 13 patients with RA taking stable doses of methotrexate and background medications (e.g., NSAIDs and prednisone), but no other disease-modifying anti-rheumatic drugs (DMARDs). All patients were on a stable dose of folic acid. Patients received their usual doses of MTX administered at a specified time, and then sequential blood samples were obtained over the course of 7 days. Peripheral blood was obtained at each time point to measure serum transaminases. We did not observe any significant change in sequential transaminases over 1 week in relationship to MTX administration. It is possible that MTX therapy alone does not lead to significant weekly transaminase variations, contrary to our clinical expectations. The addition of other medications (i.e., NSAIDs) to stable MTX regimen may result in transaminase abnormalities.
28083614 Significance of Polymorphism and Expression of miR-146a and NFkB1 Genetic Variants in Pati 2016 Dec MicroRNA-146a (miR-146a) has been shown to play an important role in the regulation of inflammatory innate immune responses, and found to be differentially expressed in rheumatoid arthritis (RA). Through NF-κB pathway, this molecule is able to stimulate the release of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-17. It has been also suggested that single-nucleotide polymorphisms (SNPs) in miRNA sequences may alter miRNA expression and that miR-146a rs2910164 SNP may contribute to RA development. These observations prompted us to analyze the potential associations between the miR-146a-3p (rs2910164, G > C) and NFkB1 (rs28362491, ins/del ATTG) polymorphisms and miR-146a-5p expression in patients' sera in relation to clinical outcome of the treatment as well as predisposition to RA. Genotyping was performed in 111 patients and 130 healthy individuals while 16 controls and 13 RA patients (before and after three months of therapy with TNF-α inhibitors (TNFi)) were studied for the circulating miR-146a-5p serum expression level. Patients carrying the NFkB1 ins/ins genotype were characterized by worse response to TNFi treatment (p = 0.023). In patients, before TNFi therapy, expression levels of miR-146a-5p were less (0.422 ± 0.171) as compared to those detected after three months of treatment (1.809 ± 0.658, p = 0.033) and observed for healthy controls (5.302 ± 2.112, p = 0.048). Moreover, patients with higher circulating miR-146a-5p levels after three months of TNFi administration were more frequently carrying the rs2910164-C allele (p = 0.032). These results support the hypothesis that miR-146a might be involved in pathogenesis of RA and imply that miR-146a-3p polymorphism may be associated with miR-146a-5p levels in serum after anti-TNF-α treatment.
27372273 iPAD or PADi-'tablets' with therapeutic disease potential? 2016 Aug Over the last five years, a growing body of literature has strengthened the rationale for the involvement of PAD (protein arginine deiminase) enzymes in diverse diseases, through direct roles of citrullination in mechanisms such as neutrophil extracellular trap formation and immune complex formation. The recent development of inhibitors of the PAD family, coupled with the availability of mice genetically deficient in PAD2 or PAD4, has accelerated understanding of the role of these targets in varied disease models. This review surveys the recent literature to confirm the therapeutic potential of PAD inhibitors as a new class of drugs to treat human autoimmune disease.
27817204 Golimumab for the treatment of axial spondyloarthritis. 2017 Jan Anti-TNF drugs have represented an epochal revolution in the treatment of rheumatoid arthritis and spondyloarthritis. In the field of axial spondyloarthritis, golimumab, a fully human monoclonal anti-TNFα administered subcutaneously every 4 weeks, has shown significant efficacy and good safety in patients with ankylosing spondylitis. More recently, it was also indicated as an effective treatment for patients suffering from non-radiographic axial spondyloarthitits. Areas covered: A systematic literature search was completed, using the largest electronic databases (Medline, Embase and Cochrane), with the aim to review all data concerning the administration of golimumab in patients suffering from axial spondyloartritis. Expert opinion: In the 16-week GO-AHEAD study, golimumab was effective in patients with non-radiographic spondyloarthritis with high levels of CRP and/or positive MRI findings, but not in subjects with both negative CRP and MRI. This finding allows for the addressing the of anti-TNF treatment more specifically. Preliminary data concerning an open-label extension of the GO-AHEAD study outlined the high retention-rate of the drug at 52 weeks. The production of antibodies against golimumab is rare and it seems to exert scarce influence on the drug performances. In conclusion, golimumab appears as a very useful and well tolerated anti-TNF agent.
26001728 Thrombin inhibits the anti-myeloperoxidase and ferroxidase functions of ceruloplasmin: rel 2015 Sep Human ceruloplasmin (CP) is a multifunctional copper-binding protein produced in the liver. CP oxidizes Fe(2+) to Fe(3+), decreasing the concentration of Fe(2+) available for generating harmful oxidant species. CP is also a potent inhibitor of leukocyte myeloperoxidase (MPO) (Kd=130nM), a major source of oxidants in vivo. Rheumatoid arthritis (RA) is an inflammatory autoimmune disease affecting flexible joints and characterized by activation of both inflammatory and coagulation processes. Indeed, the levels of CP, MPO, and thrombin are markedly increased in the synovial fluid of RA patients. Here we show that thrombin cleaves CP in vitro at (481)Arg-Ser(482) and (887)Lys-Val(888) bonds, generating a nicked species that retains the native-like fold and the ferroxidase activity of the intact protein, whereas the MPO inhibitory function of CP is abrogated. Analysis of the synovial fluid of 24 RA patients reveals that CP is proteolytically degraded to a variable extent, with a fragmentation pattern similar to that observed with thrombin in vitro, and that proteolysis is blocked by hirudin, a highly potent and specific thrombin inhibitor. Using independent biophysical techniques, we show that thrombin has intrinsic affinity for CP (Kd=60-270nM), independent of proteolysis, and inhibits CP ferroxidase activity (KI=220±20nM). Mapping of thrombin binding sites with specific exosite-directed ligands (i.e., hirugen, fibrinogen γ'-peptide) and thrombin analogues having the exosites variably compromised (i.e., prothrombin, prethrombin-2, βT-thrombin) reveals that the positively charged exosite-II of thrombin binds to the negatively charged upper region of CP, while the protease active site and exosite-I remain accessible. These results suggest that thrombin can exacerbate inflammation in RA by impairing the MPO inhibitory function of CP via proteolysis and by competitively inhibiting CP ferroxidase activity. Notably, local administration of hirudin, a highly potent and specifc thrombin inhibitor, reduces the concentration of active MPO in the synovial fluid of RA patients and has a beneficial effect on the clinical symptoms of the disease.
27572327 A double-blind randomized comparative study of triamcinolone hexacetonide and dexamethason 2016 Dec Intra-articular glucocorticoid (GC) injection has been used for more than half a century in the treatment of refractory synovitis in patients with rheumatoid arthritis (RA). There are limited data about the efficacy of intra-articular injection of various preparations of GCs on inflamed joint. The aim of this study was to compare the efficacy and side effects of intra-articular injection of dexamethasone (DEX) and triamcinolone hexacetonide (TH) in the treatment of knee joint arthritis in RA. In a double-blind randomized clinical trial, 70 patients with RA and knee joint arthritis were recruited to the study. Swelled knee joints were injected with 40 mg TH or 8 mg DEX randomly. The primary outcome measures were reduction of knee joint swelling and pain 1 and 3 weeks after joint injection. The secondary outcome measures were relapse of knee arthritis at 2, 4, and 6 months after injection and side effects of intra-articular injection. Difference in the knee circumferences between DEX and TH groups at weeks 1 and 3 was not significant. The average times of pain reduction after injection were 3.4 ± 2.3 and 2.3 ± 1.8 days in TH and DEX, respectively. There were no differences of knee pain between the two groups. Relapse of knee arthritis was occurred in two (6.7 %) and three (9.4 %) patients in the DEX and TH groups, respectively. Intra-articular injection of DEX like TH causes rapid and long-term reduction of knee pain and swelling in patients with RA and is safe.
26466491 [Preoperative Management of Patients with Collagen Disease and Endocrine Disease]. 2015 Sep Collagen disease and endocrine disease are frequently associated with systemic organ dysfunctions with a high perioperative morbidity and mortality. The aims of pre-operative management of these patients are to evaluate the extent of the disease process, systemic consequences and side effects of drugs therapy for the disease and to stabilize the symptoms so that the risk of surgery and anesthesia may be minimized.
27140405 Tofacitinib in ulcerative colitis. 2016 May Cytokines orchestrate immune and inflammatory responses involved in the pathogenesis of ulcerative colitis (UC). Protein kinases are essential for signal transduction in eukaryotic cells. Janus kinases (JAKs) are a family of protein tyrosine kinases that play a pivotal role in cytokine receptor signaling. Indeed, a major subgroup of cytokines use Type I and II cytokine receptors which signal via the activation of JAKs. Tofacitinib is an oral JAK inhibitor that has been studied in autoimmune pathologies, including UC and rheumatoid arthritis with good overall efficacy and acceptable safety profile. This literature review was performed with the goal of summarizing the knowledge on JAK inhibitors in UC treatment.
25943001 Factors associated with the initiation of biologic disease-modifying antirheumatic drugs i 2015 May BACKGROUND: Rheumatoid arthritis (RA) is a progressive autoimmune disorder of joints that is associated with high health care costs, yet guidance is lacking on how early to initiate biologic disease-modifying antirheumatic drugs (DMARDs), a class of medications that is the major cost driver in RA management. Few studies have examined the factors associated with the transition from nonbiologic DMARDs, the first-line therapy for RA, to biologic DMARDs in RA patients.  OBJECTIVE: To examine patient sociodemographics, medication use patterns, and clinical characteristics associated with initiation of biologic DMARDs.   METHODS: This was a retrospective study using the Texas Medicaid prescription and medical claims database from July 1, 2003-December 31, 2010. Adults (aged 18-63 years) with an RA diagnosis (ICD-9-CM code 714.xx), no nonbiologic DMARD or biologic DMARD use during the 6-month pre-index period, and a minimum of 2 prescription claims for the same nonbiologic DMARD during the post-index period were included in the study. The index date was defined as the date when the first nonbiologic DMARD claim was made. Predictors of initiation of biologic DMARDs were age, gender, race, adherence (proportion of days covered), persistence to nonbiologic DMARDs, comorbidity (Charlson Comorbidity Index [CCI]), pain medication use, glucocorticoid use, and rheumatologist visit. Logistic regression was used to examine the factors associated with the initiation of biologic DMARDs.   RESULTS: A total of 2,714 patients were included. After controlling for patient characteristics, logistic regression showed, that compared with methotrexate (MTX) users, sulfasalazine (SSZ) and hydroxychloroquine (HCQ) users were less likely to initiate biologic DMARDs by 69.0% (OR = 0.310, 95% CI = 0.221-0.434, P  less than  0.0001) and 79.9% (OR = 0.201, 95% CI = 0.152-0.265, P  less than  0.0001), respectively. Nonbiologic DMARD dual therapy users were 39.1% less likely to initiate biologic DMARDs compared with nonbiologic DMARD monotherapy users (OR = 0.609, 95% CI = 0.463-0.803, P = 0.0004). With each year increase in age, patients were 1.6% less likely to start biologic DMARDs (OR = 0.984, 95% CI = 0.975-0.993, P = 0.0006). Compared with glucocorticoid users, glucocorticoid nonusers were 53.8% less likely to start on biologic DMARDs (OR = 0.462, 95% CI = 0.372-0.573, P  less than  0.0001). Patients with CCI scores of ≥ 3 were approximately 1.6 times more likely to initiate biologic DMARDs than those with CCI scores of 1 (OR = 1.618, 95% CI = 1.228-2.132, P = 0.0006).  CONCLUSIONS: Younger age, CCI scores ≥3, glucocorticoid use, MTX users (vs. SSZ and HCQ users), and nonbiologic DMARD monotherapy users (vs. dual therapy users) were significantly associated with higher likelihood to initiate biologic DMARDs. Recognizing these potential factors that drive the initiation of biologic DMARDs in this patient population, health care providers and Texas Medicaid should take measures to achieve optimal therapy for RA patients through thorough RA medication evaluation, well-structured RA monitoring programs, and patient education.
27671822 Boswellic Acids and Their Role in Chronic Inflammatory Diseases. 2016 Boswellic acids, which are pentacyclic triterpenes belong to the active pharmacological compounds of the oleogum resin of different Boswellia species. In the resin, more than 12 different boswellic acids have been identified but only KBA and AKBA received significant pharmacological interest. Biological Activity: In an extract of the resin of Boswellia species multiple factors are responsible for the final outcome of a therapeutic effect, be it synergistic or antagonistic. Moreover, the anti-inflammatory actions of BAs are caused by different mechanisms of action. They include inhibition of leukotriene synthesis and to a less extend prostaglandin synthesis. Furthermore inhibition of the complement system at the level of conversion of C3 into C3(a) and C3(b). A major target of BAs is the immune system. Here, BEs as well as BAs including KBA and AKBA, have been shown to decrease production of proinflammatory cytokines including IL-1, IL-2, IL-6, IFN-γ and TNF-α which finally are directed to destroy tissues such as cartilage, insulin producing cells, bronchial, intestinal and other tissues. NFĸB is considered to be the target of AKBA. The complex actions of BEs and BAs in inflamed areas may be completed by some effects that are localized behind the inflammatory process as such tissue destruction. In this case, in vitro- and animal studies have shown that BAs and BEs suppress proteolytic activity of cathepsin G, human leucocyte elastase, formation of oxygen radicals and lysosomal enzymes. PHARMACOKINETICS: Whereas KBA is absorbed reaching blood levels being close to in vitro IC(50,) AKBA which is more active in in vitro studies than KBA, but undergoes much less absorption than KBA. However, absorption of both is increased more than twice when taken together with a high-fat meal.Clinical Studies There are a variety of chronic inflammatory diseases which respond to treatment with extracts from the resin of Boswellia species. Though, the number of cases is small in related clinical studies, their results are convincing and supported by the preclinical data. These studies include rheumatoid arthritis, osteoarthritis, chronic colitis, ulcerative colitis, collagenous colitis, Crohn's disease and bronchial asthma. It can not be expected that there is cure from these diseases but at least improvement of symptoms in about 60-70 % of the cases. Side Effects The number and severity of side effects is extremely low. The most reported complaints are gastrointestinal symptoms. Allergic reactions are rare. And most authors report, that treatment with BEs is well tolerated and the registered side effects in BE- and placebo groups are similar.
26095743 Infliximab and etanercept have distinct actions but similar effects on cytokine profiles i 2015 Oct OBJECTIVE: Pro-inflammatory cytokines, especially TNFα, play a central role in the pathogenesis of rheumatoid arthritis (RA). The available TNF inhibitors are only slightly different from one another in terms of clinical efficacy, at least at the group level, but their structures and modes of action are not identical. Infliximab (IFX) and etanercept (ETN) differ in their ability to induce antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, and in their ability to bind TNFβ. The purpose of our study was to elucidate the different cytokine pathways through which these two drugs enact their clinical efficacy. METHODS: Serum from 44 RA patients treated with IFX and 24 patients treated with ETN was studied. All patients had been given these biologics at identical dosages and intervals for one year. The concentrations of 11 inflammatory cytokines and their receptors (IL-1β, IL-2, IL-6, IL-6R, IL-8, IL-10, IL-12, TNFα, TNFβ, IFNγ, and GM-CSF) were measured at weeks 0, 22, and 54 using a high-sensitivity electro-chemiluminescence assay. Cytokine profiles were analyzed along with clinical efficacy. RESULTS: IL-6 was significantly decreased in the ETN+MTX and IFX+MTX groups, although not in the ETN-only group; this change was consistent with changes in disease activity. IFNγ was gradually increased only in the non-remission subgroup of the IFX group, and not at all in the ETN group. TNFβ increased after starting IFX regardless of clinical efficacy. CONCLUSION: IL-6 inhibition is a pathway affected by both IFX and ETN. In addition, IFNγ increase is a distinctive feature of the inefficacy of IFX.
27098399 Role of CX3CL1 in Diseases. 2016 Oct Chemokines are a family of small 8-10 kDa inducible cytokines. Initially characterized as chemotactic factors, they are now considered to affect not just cellular recruitment. CX3CL1 is a unique chemokine that can exist in a soluble form, as a chemotactic cytokine, or in a membrane-attached form that acts as a binding molecule. Recently, the effects of CX3CL1 on diseases, such as inflammation and cancer, have been supported and confirmed by numerous publications. However, due to its dual effects, CX3CL1 exerts numerous effects on pathophysiological conditions that have both negative and positive consequences on pathogenesis and outcome. This review article summarizes the important scientific and clinical data that now point to a critical role for CX3CL1 in diseases.
27775461 Effect of a treat-to-target strategy based on methotrexate and intra-articular betamethaso 2017 Sep OBJECTIVES: To investigate whether a treat-to-target strategy based on methotrexate (MTX) and intra-articular (IA) betamethasone suppresses magnetic resonance imaging (MRI)-determined measures of disease activity and reduces joint destruction in early rheumatoid arthritis (eRA) patients, and to investigate whether concomitant cyclosporin A (CyA) provides an additional effect. METHOD: In the 2-year randomized, double-blind, treat-to-target trial CIMESTRA, 160 patients with eRA (< 6 months) were randomized to MTX, intra-articular betamethasone and CyA, or placebo CyA. A total of 129 patients participated in the MRI substudy, and had contrast-enhanced MR images of the non-dominant hand at months 0, 6, 12, and 24. MR images were evaluated for osteitis, synovitis, tenosynovitis, bone erosion, and joint space narrowing (JSN), using validated scoring methods. RESULTS: Significant reductions were seen at 6 months in all inflammatory parameters [synovitis, mean change -1.6 (p < 0.001, Wilcoxon), tenosynovitis, -3.5 (p < 0.001), and osteitis, -1.3 (p < 0.05)] and at 12/24 months in synovitis and tenosynovitis [-1.6/-2.2 and -3.6/-3.8, respectively; all p < 0.001]. MRI signs of inflammation were not fully eliminated, and increases in erosion and JSN scores were observed at 6 months [0.4 (p < 0.01)/0.1 (p < 0.05)], 12 months [0.8 (p < 0.001)/0.3 (p < 0.01)], and 24 months [1.0 (p < 0.001)/0.4 (p < 0.001)]. Clinical measures decreased significantly (p < 0.001) at all time points. There were no consistent statistically significant differences between treatment groups. CONCLUSIONS: In this eRA treat-to-target trial, MTX and intra-articular glucocorticoids markedly reduced, but did not eliminate, MRI osteitis, synovitis, and tenosynovitis. Accordingly, minimal but statistically significant increases in bone erosion and JSN were observed. No additional effect of CyA was demonstrated.
24818633 Intensive combination treatment regimens, including prednisolone, are effective in treatin 2015 Jun BACKGROUND: Recently, we documented the likely non-inferiority of Combinatietherapie Bij Reumatoïde Artritis (COBRA)-light therapy (methotrexate increased to 25 mg/week with initial prednisolone 30 mg/day) compared with the original COBRA therapy (methotrexate 7.5 mg/week, sulfasalazine 2 g/day, with initial prednisolone 60 mg/day) after 26 weeks in patients with early active rheumatoid arthritis (RA). OBJECTIVE: To assess the non-inferiority of COBRA-light versus COBRA after 1 year in terms of disease activity (DAS44), functional outcome (Health Assessment Questionnaire (HAQ)) and radiographic progression (Sharp/van der Heijde score (SHS)), and to assess the effect of adding etanercept. METHODS: An open-label, randomised controlled, non-inferiority trial of 162 patients with active early RA, following a treat-to-target protocol incorporating the addition of etanercept if DAS44 ≥1.6 at weeks 26 or 39. RESULTS: Both groups showed major improvements in DAS44 after 52 weeks: mean (SD) -2.41 (1.2) in the COBRA and -2.02 (1.0) in the COBRA-light group (p=ns). In both groups, functional ability improved and radiological progression of joints was minimal. At least one adverse event was reported in 96% of the patients in both groups. In total, 25 serious adverse events occurred: 9 vs 16 in COBRA and COBRA-light, respectively. Treatment actually instituted was often less intensive than required by the protocol: of the total population, 108 patients (67%) required etanercept (more in the COBRA-light group), but only 67 of these (62%) actually received it. CONCLUSIONS: Intensive COBRA or COBRA-light therapy has major, comparably favourable effects on disease activity, functional ability and radiological outcome after 1 year in patients with early RA. Protocolised addition of etanercept was often not implemented by treating rheumatologists, and patients receiving it appeared to have limited added benefit, probably because of low disease activity levels at its initiation. TRIAL REGISTRATION NUMBER: ISRCTN55552928.
26139109 Protein tyrosine phosphatase nonreceptor type 2: an important regulator of lnterleukin-6 p 2015 Oct OBJECTIVE: To investigate the role of protein tyrosine phosphatase nonreceptor type 2 (PTPN2) in the pathogenesis of rheumatoid arthritis (RA). METHODS: Synovial tissue samples from patients with RA and patients with osteoarthritis (OA) were stained for PTPN2. Synovial fibroblasts were stimulated with tumor necrosis factor (TNF) and interleukin-1β (IL-1β), lipopolysaccharide (LPS), TRAIL, or thapsigargin. The expression of PTPN2 in synovial fibroblasts and peripheral blood mononuclear cells (PBMCs) was analyzed by real-time polymerase chain reaction and Western blotting. Cell death, the release of IL-6 and IL-8, and the induction of autophagy were analyzed after PTPN2 silencing. Methylated DNA immunoprecipitation analysis was used to evaluate DNA methylation-regulated gene expression of PTPN2. RESULTS: PTPN2 was significantly overexpressed in synovial tissue samples from RA patients compared to OA patients. Patients receiving anti-TNF therapy showed significantly reduced staining for PTPN2 compared with patients treated with nonbiologic agents. PTPN2 expression was higher in RA synovial fibroblasts (RASFs) than in OASFs. This differential expression was not regulated by DNA methylation. PTPN2 was further up-regulated after stimulation with TNF, TNF combined with IL-1β, or LPS. There was no significant difference in basal PTPN2 expression in PBMCs from patients with RA, ankylosing spondylitis, or systemic lupus erythematosus or healthy controls. Most interestingly, PTPN2 silencing in RASFs significantly increased the production of the inflammatory cytokine IL-6 but did not affect levels of IL-8. Moreover, functional analysis showed that high PTPN2 levels contributed to the increased apoptosis resistance of RASFs and increased autophagy. CONCLUSION: This is the first study of PTPN2 in RASFs showing that PTPN2 regulates IL-6 production, cell death, and autophagy. Our findings indicate that PTPN2 is linked to the pathogenesis of RA via synovial fibroblasts.
27238195 Osteoarticular manifestations associated with HIV infection. 2017 Jan About 150,000 people are HIV-positive in France, and the number of new cases is estimated at 7000-8000 per year, with no tendency to diminish over time. Admissions of HIV-positive patients have been decreasing, in contrast, since 2008, reflecting the dramatic improvements in quality of life and survival provided by triple antiretroviral regimens. HIV infection is now a chronic disease that exposes patients to the virus and antiretroviral drugs for many years. One consequence has been the emergence of new health conditions in HIV-positive patients, such as tumors, cardiovascular disease, and osteoarticular complications. These epidemiological and clinical changes have made it necessary for rheumatologists to learn about the osteoarticular abnormalities associated with the HIV, which they are likely to encounter at some point during their everyday practice. Osteoporosis is one such abnormality, and this review article starts with a discussion of the literature on this topic. Bone loss is common, chiefly in males. Multiple factors are involved. Studies have demonstrated an increase in the fracture risk and, consequently, recommendations about the screening and treatment of osteoporosis have been issued. The focus of this review article then turns to the other rheumatic manifestations seen in HIV-positive patients, including osteomalacia, avascular necrosis, and inflammatory joint disease. Osteoarticular pain is frequently reported by HIV-positive patients. Identifying the cause is essential to determine the best treatment strategy. Interestingly, immunosuppressant drugs, and even biotherapies, have shown a good safety profile in these immunodeficient patients.
26854217 Point of care testing of phospholipase A2 group IIA for serological diagnosis of rheumatoi 2016 Feb 28 Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care.
25935455 Serum resistin levels in patients with rheumatoid arthritis and systemic lupus erythematos 2015 Oct The purpose of this meta-analysis was to investigate whether serum resistin level was associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by comparing serum resistin levels between RA or SLE patients and normal controls. PubMed and EMBASE databases (up to May 13, 2014) were used to search all related articles. The weighted mean differences (WMDs) with 95 % confidence interval (CI) were calculated using random-effect model analysis. The Cochrane Q test and I(2) statistic were used to test heterogeneity. To assess publication bias, the Egger's test and visual observation of a funnel plot were used. The Newcastle-Ottawa scale was used to assess the study quality. The STATA statistical software (version 11.0) was applied to deal with statistical data. A total of eight studies of RA including 620 patients and 460 healthy controls, and six studies of SLE including 559 patients and 430 healthy controls were finally included in the meta-analysis. The results revealed that the serum resistin levels in RA were significantly higher than those in normal controls (WMD = 0.767 ng/ml, 95 % CI = 0.114-1.419, P = 0.021), but there was no significant difference between SLE patients and normal controls (WMD = 2.771 ng/ml, 95 % CI = -0.521-6.063, P = 0.099). Publication bias was undetected. In conclusion, this meta-analysis indicate that serum resistin level was significantly elevated in RA patients.
27686099 Older age is associated with more MRI-detected inflammation in hand and foot joints. 2016 Dec OBJECTIVES: Although MRI is recommended for diagnostic use in detecting joint inflammation, its value in clinical practice has not been settled. Older symptom-free persons show more MRI-detected inflammation in their hands and feet. Within arthritis patients, a similar effect could be present (a general age effect). The association of age with MRI inflammation could also be enhanced by disease (disease-dependent age effect). Because both effects could have diagnostic consequences, we evaluated the association between age-at-onset and MRI-detected inflammation in early arthritis and RA. METHODS: Unilateral contrast-enhanced MRI of the MCP joint, wrist and MTP joints was performed in 589 newly presenting early arthritis patients, of whom 229 had RA. Bone marrow oedema, synovitis and tenosynovitis were summed, yielding the MRI inflammation score. MRI findings were associated with age and compared with those of 193 (previously reported) symptom-free controls. RESULTS: Early arthritis and RA-patients had, respectively, 2.6 (95% CI: 2.3, 3.0, P < 0.001) and 3.7 times (95% CI: 3.2, 4.3, P < 0.001) higher MRI inflammation scores than controls (adjusted for age). At higher age of onset, early arthritis and RA patients had higher MRI inflammation scores (1.03/year, P < 0.001). A similar effect was observed in controls (1.03/year, P < 0.001). The interaction term age*group (arthritis/RA vs controls) was non-significant (P = 0.80 and P = 0.23), suggesting that the age effect was not disease dependent. At the joint level, older RA patients had more extended MRI inflammation, but the preferential locations were similar. CONCLUSION: Older age is associated with more MRI-detected inflammation, and the effect was similar in arthritis and controls. This age effect should be considered when interpreting hand and foot MRI for diagnostic purposes.