Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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22069953 | Certolizumab: efficacy and safety profile of a novel pegylated TNF-alpha blocking agent. | 2011 Apr | The treatment of Rheumatoid Arthritis (RA) has changed since the introduction of biological agents. In particular, the anti Tumor Necrosis Factor (TNF)-alpha molecules have been the first group of drugs showing a good efficacy and safety profile. Among these, a new anti TNF-alpha antibody has been recently indicated for the treatment of RA: certolizumab pegol (CZP). In the main clinical trials this new pegylated anti TNF-alpha has shown to be efficacious on clinical, functional and prevention of structural damage in patients with active RA and with inadequate response to traditional disease modifying drugs, including methotrexate. Moreover CZP showed to be well tolerated and most adverse events occurred were mild or moderate. Therefore, results obtained showed that this new molecule can play a role in the treatment of RA. | |
21971513 | Targeting JAK3 in kidney transplantation: current status and future options. | 2011 Dec | PURPOSE OF REVIEW: This review will discuss the mechanism of action and important clinical trial data in renal transplantation for the small molecule Janus kinase (JAK) 3 inhibitor tofacitinib, formerly known as CP-690,550 and tasocitinib. RECENT FINDINGS: JAKs are cytoplasmic tyrosine kinases that participate in the signaling of a broad range of cell surface receptors, particularly members of the cytokine receptor common gamma (cγ) chain family. JAK3 inhibition has immunosuppressive effects and treatment with tofacitinib in clinical trials has demonstrated efficacy in autoimmune disorders such as psoriasis and rheumatoid arthritis. Nonhuman primate models of renal transplantation demonstrated prolonged graft survival with tofacitinib compared with vehicle control. Renal transplant clinical trials in humans have demonstrated tofacitinib to be noninferior to cyclosporine in terms of rejection rates and graft survival. There was also a lower rate of new-onset diabetes after transplant. However, there was a trend toward more infections, including cytomegalovirus and BK virus nephritis. SUMMARY: Tofacitinib may be a promising alternative to calcineurin inhibitors. The optimal therapeutic window is still being determined. | |
21871061 | Gene- or region-based association study via kernel principal component analysis. | 2011 Aug 26 | BACKGROUND: In genetic association study, especially in GWAS, gene- or region-based methods have been more popular to detect the association between multiple SNPs and diseases (or traits). Kernel principal component analysis combined with logistic regression test (KPCA-LRT) has been successfully used in classifying gene expression data. Nevertheless, the purpose of association study is to detect the correlation between genetic variations and disease rather than to classify the sample, and the genomic data is categorical rather than numerical. Recently, although the kernel-based logistic regression model in association study has been proposed by projecting the nonlinear original SNPs data into a linear feature space, it is still impacted by multicolinearity between the projections, which may lead to loss of power. We, therefore, proposed a KPCA-LRT model to avoid the multicolinearity. RESULTS: Simulation results showed that KPCA-LRT was always more powerful than principal component analysis combined with logistic regression test (PCA-LRT) at different sample sizes, different significant levels and different relative risks, especially at the genewide level (1E-5) and lower relative risks (RR = 1.2, 1.3). Application to the four gene regions of rheumatoid arthritis (RA) data from Genetic Analysis Workshop16 (GAW16) indicated that KPCA-LRT had better performance than single-locus test and PCA-LRT. CONCLUSIONS: KPCA-LRT is a valid and powerful gene- or region-based method for the analysis of GWAS data set, especially under lower relative risks and lower significant levels. | |
21834458 | Occupational therapy interventions for chronic diseases: a scoping review. | 2011 Jul | OBJECTIVE: We reviewed the evidence regarding the effectiveness of community occupational therapy interventions, delivered alone or within a multidisciplinary team, in improving occupational outcomes for adults with selected chronic diseases. METHOD: We completed a scoping review of randomized controlled trials published from 1988 through 2008. Studies included participants with heart disease, depression, rheumatoid arthritis, osteoarthritis, chronic obstructive pulmonary disorder, or diabetes. RESULTS: Sixteen studies met the inclusion criteria. Ten studies found significant differences between intervention and control groups for at least one outcome of function in activities of daily living, functional self-efficacy, social or work function, psychological health, general health, or quality of life. Conflicting evidence exists regarding the impact of intervention on physical function and health. CONCLUSION: Occupational therapy can improve occupational outcomes in adults with chronic diseases. Using and building on this evidence, occupational therapists can continue to promote their role in helping to meet this population's needs. | |
21742279 | Tai Chi research review. | 2011 Aug | This review briefly summarizes recent Tai Chi research on physical benefits including balance and muscle strength and psychological benefits including attentiveness, sleep and anxiety. Cardiovascular changes following Tai Chi include decreased heart rate and blood pressure, increased vagal activity and decreased cholesterol. Pain syndromes that have been affected include fibromyalgia, osteoarthritis and rheumatoid arthritis. Autoimmune and immune conditions recently researched and reviewed here include osteoporosis, diabetes and HIV. Methodological problems with this research include the variability in forms (series of postures) used across studies as well as the intensity of the Tai Chi schedule. Further, most of the studies are based on within group changes rather than attention control group comparisons. Nonetheless, significant clinical improvements have been noted. | |
21699506 | Pharmacological modulation of chemokine receptor function. | 2012 Mar | G protein-coupled chemokine receptors and their peptidergic ligands are interesting therapeutic targets due to their involvement in various immune-related diseases, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, chronic obstructive pulmonary disease, HIV-1 infection and cancer. To tackle these diseases, a lot of effort has been focused on discovery and development of small-molecule chemokine receptor antagonists. This has been rewarded by the market approval of two novel chemokine receptor inhibitors, AMD3100 (CXCR4) and Maraviroc (CCR5) for stem cell mobilization and treatment of HIV-1 infection respectively. The recent GPCR crystal structures together with mutagenesis and pharmacological studies have aided in understanding how small-molecule ligands interact with chemokine receptors. Many of these ligands display behaviour deviating from simple competition and do not interact with the chemokine binding site, providing evidence for an allosteric mode of action. This review aims to give an overview of the evidence supporting modulation of this intriguing receptor family by a range of ligands, including small molecules, peptides and antibodies. Moreover, the computer-assisted modelling of chemokine receptor-ligand interactions is discussed in view of GPCR crystal structures. Finally, the implications of concepts such as functional selectivity and chemokine receptor dimerization are considered. | |
21631646 | Medical and non-medical correlates of carpal tunnel syndrome in a Taiwan cohort of one mil | 2012 Jan | BACKGROUND: Carpal tunnel syndrome (CTS), with unclear etiology, is the most common entrapment neuropathy. Its occurrence is related to lots of medical and non-medical conditions with uncertain causality. With a large population, we characterized selected demographical and clinical factors to add more information on CTS-correlated factors and new insight into future CTS prevention. METHODS: A national insurance claim dataset of one million enrollees in Taiwan was used to identify 15 802 patients with CTS and 31 604 randomly selected controls, during a period of 7 years starting 1 January 2000. Statistical association with CTS was determined for five sociodemographic and nine medical factors. RESULTS: Patients were predominantly women (65.6% vs. 47.7% in the control group) and older (40 and above, 62.6% vs. 36.2%). Rheumatoid arthritis was found to be the most significant comorbidity associated with CTS, followed by gout, hypertension, diabetes, obesity, uremia, and acromegaly. For younger group age ≤39, the association of these comorbidities was stronger, and hypothyroidism and vitamin B(6) deficiency were additional comorbidities. Aging appears to reduce the relative impact of the diseases commonly associated with CTS as the possible risk factors. CONCLUSIONS: Identification of the CTS correlates in younger group would be of greater value in timely detection and treatment for these diseases. Correcting these disorders may aid in removing possible causes of CTS. This is the first report on the effect of aging on probable CTS risk factors. How factors associated with aging contribute to the development of CTS remains to be determined. | |
21519269 | How to measure disease activity in axial spondyloarthritis? | 2011 Jul | PURPOSE OF REVIEW: The evaluation of disease activity in axial spondyloarthritis (SpA) is complex and multifactorial. Moreover, patients and physicians have different perspectives of the disease and none of the current single-item or combined indexes adequately unifies both perspectives. Recent efforts have been made to improve disease activity measurement in axial SpA. RECENT FINDINGS: The Assessment of Spondyloarthritis international Society (ASAS) embraced the project of developing a new index for disease activity measurement in axial SpA: the Ankylosing Spondylitis Disease Activity Score (ASDAS). The process closely mimicked the development of the Disease Activity Score in rheumatoid arthritis. Cut-offs for disease activity states and response levels have also been developed. Good performance of ASDAS has been shown in several international datasets, including randomized controlled trials and observational cohorts. SUMMARY: The ASDAS is a well balanced index covering the underlying construct of disease activity and designed to avoid redundancy. It is a feasible and valid measurement instrument with a very good performance compared to existing tools. The ASDAS and its cut-off values may help clinicians and researchers to better assess patients with axial SpA, more reliably determine their disease activity status, the effectiveness of treatments and whether they are providing clinically meaningful improvement. | |
21479340 | Platelets, inflammation and tissue regeneration. | 2011 May | Blood platelets have long been recognised to bring about primary haemostasis with deficiencies in platelet production and function manifesting in bleeding while upregulated function favourises arterial thrombosis. Yet increasing evidence indicates that platelets fulfil a much wider role in health and disease. First, they store and release a wide range of biologically active substances including the panoply of growth factors, chemokines and cytokines released from a-granules. Membrane budding gives rise to microparticles (MPs), another active participant within the blood stream. Platelets are essential for the innate immune response and combat infection (viruses, bacteria, micro-organisms). They help maintain and modulate inflammation and are a major source of pro-inflammatory molecules (e.g. P-selectin, tissue factor, CD40L, metalloproteinases). As well as promoting coagulation, they are active in fibrinolysis; wound healing, angiogenesis and bone formation as well as in maternal tissue and foetal vascular remodelling. Activated platelets and MPs intervene in the propagation of major diseases. They are major players in atherosclerosis and related diseases, pathologies of the central nervous system (Alzheimers disease, multiple sclerosis), cancer and tumour growth. They participate in other tissue-related acquired pathologies such as skin diseases and allergy, rheumatoid arthritis, liver disease; while, paradoxically, autologous platelet-rich plasma and platelet releasate are being used as an aid to promote tissue repair and cellular growth. The above mentioned roles of platelets are now discussed. | |
21457409 | In-hospital rehabilitation after multiple joint procedures of the lower extremities in hae | 2011 Nov | This project aimed to develop guidelines for use during in-hospital rehabilitation after combinations of multiple joint procedures (MJP) of the lower extremities in persons with haemophilia (PWH). MJP are defined as surgical procedures on the ankles, knees and hips, performed in any combination, staged, or during a single session. MJP that we studied included total knee arthroplasty, total hip arthroplasty and ankle arthrodesis. Literature on rheumatoid arthritis demonstrated promising functional results, fewer hospitalization days and days lost from work. However, the complication rate is higher and rehabilitation needs optimal conditions. Since 1995, at the Van Creveldkliniek, 54 PWH have undergone MJP. During the rehabilitation in our hospital performed by experienced physical therapists, regular guidelines seemed useless. Guidelines will guarantee an optimal physical recovery and maximum benefit from this enormous investment. This will lead to an optimal functional capability and optimal quality of life for this elderly group of PWH. There are no existing guidelines for MJP, in haemophilia, revealed through a review of the literature. Therefore, a working group was formed to develop and implement such guidelines and the procedure is explained. The total group of PWH who underwent MJP is described, subdivided into combinations of joints. For these subgroups, the number of days in hospital, complications and profile at discharge, as well as a guideline on the clinical rehabilitation, are given. It contains a general part and a part for each specific subgroup. | |
21419278 | Vitamin D endocrine system and the immune response in rheumatic diseases. | 2011 | Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of autoimmune diseases. The presence of vitamin D receptors (VDRs) in the cells of the immune system and the fact that several of these cells produce the vitamin D hormone suggested that vitamin D could have immunoregulatory properties, and now potent immunomodulatory activities on dendritic cells, Th1 and Th17 cells, as well as B cells have been confirmed. Serum levels of vitamin D have been found to be significantly lower in patients with systemic lupus erythematosus, undifferentiated connective tissue disease, and type-1 diabetes mellitus than in the healthy population. In addition, it was also found that lower levels of vitamin D were associated with higher disease activity in rheumatoid arthritis. Promising clinical results together with evidence for the regulation of multiple immunomodulatory mechanisms by VDR agonists represent a sound basis for further exploration of their potential in the treatment of rheumatic autoimmune disorders. | |
21208657 | Extending pharmacological spectrum of opioids beyond analgesia: multifunctional aspects in | 2011 Jun | Opioids are well known to exert potent central analgesic actions. In recent years, the numerous studies have unfolded the critical role of opioids in the pathophysiology of various diseases as well as in biological phenomenon of therapeutic interest. The endogenous ligands of opioid receptors are derived from three independent genes and their appropriate processing yields the major representative opioid peptides beta-endorphin, met-enkephalin, leu-enkephalin and dynorphin, respectively. These peptides and their derivatives exhibit different affinity and selectivity for the mu-, delta- and kappa-receptors located on the central and the peripheral neurons, neuroendocrine, immune, and mucosal cells and on many other organ systems. The present review article highlights the role of these peptides in central nervous system disorders such as depression, anxiety, epilepsy, and stress; gastrointestinal disorders such as diarrhea, postoperative ileus, ulceration, and irritable bowel syndrome; immune system and related inflammatory disorders such as osteoarthritis and rheumatoid arthritis; and others including respiratory, alcoholism and obesity/binge eating. Furthermore, the key role of opioids in different forms of pre- and post-conditioning including ischemic and pharmacological along with in remote preconditioning has also been described. | |
20929432 | All trans retinoic acid and cancer. | 2011 Jun | All-trans retinoic acid (ATRA) is an active metabolite of vitamin A under the family retinoid. Retinoids, through their cognate nuclear receptors, exert potent effects on cell growth, differentiation and apoptosis, and have significant promise for cancer therapy and chemoprevention. Differentiation therapy with ATRA has marked a major advance and become the first choice drug in the treatment of acute promyelocytic leukemia (APL). Conversions of 13-cis-retinoic acid and 9-cis-retinoic acid to all-trans-retinoic acid is very rapid. Currently, two distinct families of retinoid responsive nuclear receptors have been identified and characterized: retinoic acid receptors (RARs) and retinoid receptors (RXRs), each of which include three isoforms, α,β,and γ. ATRA is being increasingly included in anti-tumour therapeutical schemes for the treatment of various tumoral diseases such as Kaposi's sarcoma, head and neck squamous cell carcinoma, ovarian carcinoma, bladder cancer, neuroblastoma and has shown antiangiogenic effects in several systems, inhibiting proliferation in vascular smooth muscle cells (VSMCs) and anti-inflammatory in rheumatoid arthritis. This review helps to understand in details about the ATRA and its role on cancer and it is predicted that modulating the activity of ATRA will soon provide novel prevention and treatment approaches for the cancer patients. | |
20645294 | An exploration of the prevalence of hypermobility and joint hypermobility syndrome in Oman | 2011 Mar | BACKGROUND AND OBJECTIVES: Joint hypermobility syndrome (JHS) is an inherited disorder of connective tissue. It presents as a condition in which there are neuromusculoskeletal signs and symptoms, including pain, without the inflammatory component of a joint disease such as rheumatoid arthritis. Re-attendance in rheumatology clinics, re-injury and prolonged rehabilitation are also features of JHS. The primary aims of this study were to establish the prevalence of hypermobility and JHS in those attending physiotherapy clinics with neuromusculoskeletal disorders in Oman. METHODS: A cross-sectional case control study design was used. The participant population included Omani women, aged 18-50 years, attending physiotherapy services for musculoskeletal complaints. The comparison population comprised women of a similar age and ethnic origin who were staff at the hospital. The primary outcome measures were the Beighton Score and the Brighton Criteria. RESULTS: A total of 184 subjects were recruited into the study. These consisted of 94 in the participant group and 90 in the comparison group. Hypermobility was recorded in 51% of the participant group and 30% of the comparison group. The number of participants with JHS was 55%, while 21% of the comparison group exhibited features of the JHS phenotype without pain. A significant number of participants with JHS were re-attending for treatment compared with those without JHS. CONCLUSIONS: This study confirms a high prevalence of JHS among subjects with musculoskeletal signs and symptoms and that re-attendance for physiotherapy treatment is more frequent in subjects with JHS than in those without. | |
21666960 | [Hospital hyponutrition]. | 2011 Mar | Identifying hyponutrition is essential at the hospital setting to avoid or minimize the impact on the patients' clinical course and its association with more severe complications, longer hospital staying, and increased mortality, and all of this is associated with increased costs for the institution and the society. The aims of this study were to disbelieve the epidemiology of hospital hyponutrition, the types of hyponutrition, the body response to fasting, the clinical course of the patient with hyponutrition and the consequences of hyponutrition in the different live stages and, thus, we carried out a review on hospital hyponutrition. We found that hyponutrition prevalence is high in the hospital setting, hyponutrition influences genetic, metabolic, and hormonal factors of the human being and leads to harmful effects from the intrauterine fetal development until the adulthood. There are also different types of hyponutrition, the differentiation being important to decide the best therapy. We also found that hyponutrition is related to inflammation. When inflammation is chronic and mild to moderate (such as in organ failure, pancreatic cancer, obesity, rheumatoid or sarcopenic arthritis), the term "hyponutrition-related chronic disease", and when inflammation is acute and severe (severe infection, burns, trauma or head trauma), the preferred term is "hyponutrition-related acute disease or hyponutrition-related lesions". Finally, the patient with hyponutrition has worse clinical course than the patient with an appropriate nutritional status. | |
23252526 | Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. | 2012 Dec 20 | BACKGROUND: Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti-interleukin-1β monoclonal antibody, in two trials. METHODS: In trial 1, we randomly assigned patients, 2 to 19 years of age, with systemic JIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per liter; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), in a double-blind fashion, to a single subcutaneous dose of canakinumab (4 mg per kilogram) or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with canakinumab, patients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with canakinumab or to placebo. The primary outcome was time to flare of systemic JIA. RESULTS: At day 15 in trial 1, more patients in the canakinumab group had an adapted JIA ACR 30 response (36 of 43 [84%], vs. 4 of 41 [10%] in the placebo group; P<0.001). In trial 2, among the 100 patients (of 177 in the open-label phase) who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinumab than among those who were switched to placebo (74% of patients in the canakinumab group had no flare, vs. 25% in the placebo group, according to Kaplan-Meier estimates; hazard ratio, 0.36; P=0.003). The average glucocorticoid dose was reduced from 0.34 to 0.05 mg per kilogram per day, and glucocorticoids were discontinued in 42 of 128 patients (33%). The macrophage activation syndrome occurred in 7 patients; infections were more frequent with canakinumab than with placebo. CONCLUSIONS: These two phase 3 studies show the efficacy of canakinumab in systemic JIA with active systemic features. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT00889863 and NCT00886769.). | |
22162369 | Incidence and risk factors for progressive multifocal leukoencephalopathy among patients w | 2012 Apr | OBJECTIVE: To ascertain the incidence of progressive multifocal leukoencephalopathy (PML) in patients with selected rheumatic diseases, to describe the characteristics of PML cases occurring in this setting, and to evaluate the extent to which such cases occurred in the context of biologic therapies such as rituximab or tumor necrosis factor antagonists. METHODS: We conducted a large population-based study to describe the incidence and risk factors for PML among patients with rheumatoid arthritis, psoriatic arthritis, psoriasis, juvenile idiopathic arthritis, inflammatory bowel disease, and ankylosing spondylitis using national inpatient and outpatient administrative data from the entire Center for Medicare and Medicaid Services from 2000-2009. Suspected PML cases were identified using hospital discharge diagnosis codes. Risk factors for PML were evaluated using outpatient data ≥6 months prior to PML diagnosis. RESULTS: Among 2,030,578 patients with autoimmune diseases of interest, a total of 53 PML cases were identified (2.6 per 100,000 patients). Most PML cases had human immunodeficiency virus (HIV) and/or cancer. Nine PML cases had evidence for biologic use prior to PML hospitalization, of which 3 had neither HIV nor malignancy and were exposed to biologics within 12 (rituximab) or 6 months (all other biologics) prior to PML diagnosis. PML occurred at an estimated incidence of 0.2 per 100,000 patients with autoimmune diseases who did not have HIV or malignancy. CONCLUSION: PML occurs at a very low incidence among patients with rheumatic diseases but can occur even in the absence of HIV or malignancy. | |
22276149 | Cyclin-dependent kinase 9 activity regulates neutrophil spontaneous apoptosis. | 2012 | Neutrophils are the most abundant leukocyte and play a central role in the immune defense against rapidly dividing bacteria. However, they are also the shortest lived cell in the blood with a lifespan in the circulation of 5.4 days. The mechanisms underlying their short lifespan and spontaneous entry into apoptosis are poorly understood. Recently, the broad range cyclin-dependent kinase (CDK) inhibitor R-roscovitine was shown to increase neutrophil apoptosis, implicating CDKs in the regulation of neutrophil lifespan. To determine which CDKs were involved in regulating neutrophil lifespan we first examined CDK expression in human neutrophils and found that only three CDKs: CDK5, CDK7 and CDK9 were expressed in these cells. The use of CDK inhibitors with differing selectivity towards the various CDKs suggested that CDK9 activity regulates neutrophil lifespan. Furthermore CDK9 activity and the expression of its activating partner cyclin T1 both declined as neutrophils aged and entered apoptosis spontaneously. CDK9 is a component of the P-TEFb complex involved in transcriptional regulation and its inhibition will preferentially affect proteins with short half-lives. Treatment of neutrophils with flavopiridol, a potent CDK9 inhibitor, increased apoptosis and caused a rapid decline in the level of the anti-apoptotic protein Mcl-1, whilst Bcl2A was unaffected. We propose that CDK9 activity is a key regulator of neutrophil lifespan, preventing apoptosis by maintaining levels of short lived anti-apoptotic proteins such as Mcl-1. Furthermore, as inappropriate inhibition of neutrophil apoptosis contributes to chronic inflammatory diseases such as Rheumatoid Arthritis, CDK9 represents a novel therapeutic target in such diseases. | |
22076476 | The CIRAS study: a case control study to define the clinical, immunologic, and radiographi | 2012 Jan | Aromatase inhibitors (AIs) are widely prescribed for post-menopausal hormone receptor-positive breast cancer; however, musculoskeletal symptoms limit their tolerability. The purpose of this study was to determine whether joint pain in women receiving AIs is associated with inflammatory arthritis as measured by the disease activity score-28 (DAS-28), and to evaluate association with tenosynovitis on ultrasound. A total of 48 postmenopausal women with stage I-III breast cancer and hand pain were recruited from the Lombardi Comprehensive Cancer Center. Those receiving AIs were cases (n = 25), and those not receiving AIs were controls (n = 23). During a single study visit, subjects underwent blinded rheumatologic evaluation, DAS-28, health assessment questionnaires, autoantibodies, inflammatory markers, hand X-ray, and hand Duplex ultrasound. There were no significant differences between cases and controls in DAS-28, or inflammatory markers. A positive ANA (titer > 1:160) was found in ten patients, four of whom met criteria for autoimmune disease (two with rheumatoid arthritis and two with Sjogren's syndrome, equally distributed among cases and controls). This highlights the importance of considering underlying autoimmune disease in subjects with musculoskeletal complaints. Morning stiffness was more prolonged in women receiving AIs, but this did not reach statistical significance (P = 0.07). Ultrasound evidence of flexor tenosynovitis was common in both groups. Although tenosynovitis was not correlated with AI use (P = 0.26), there was a trend toward an association between tenosynovitis and morning stiffness (P = 0.089). While aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) were more common in subjects receiving AIs, they were not unique to AI users. There was no association between presence of AIMSS features and other chemotherapy or medication exposures. Although the majority of subjects had been using AIs for more than 6 months, this study did not find evidence for inflammatory arthritis in women with hand pain receiving AIs. Further studies are needed to develop a case definition of AIMSS, and to confirm whether these symptoms are attributable to AI use. | |
22078696 | [Duration of treatment with etanercept and motives for discontinuation in a cohort of pati | 2011 Nov | OBJECTIVE: To evaluate the duration of etanercept (ETN) treatment and motives for discontinuation in our local cohort of patients with rheumatic pathology and compare them to the group with other biological treatments. PATIENTS AND METHODS: Prospective observational cohort study. Disease diagnosis, start and end date and motive for discontinuation were recorded. Survival estimation was explored using Kaplan-Meier analysis with remaining patients censored at 1-year, 2-years and 5-years follow-up. RESULTS: Ninety-two (45%) out of 205 patients started ETN treatment. Disease diagnoses recorded were: 48% rheumatoid arthritis, 33% ankylosing spondylitis, 11% psoriatic arthritis, 8% others (juvenile idiopathic arthritis, inflammatory bowel disease related spondylitis, SAPHO syndrome). 52% of patients are still on the drug. The motives for discontinuation were: inefficacy (65%), adverse events (33%) and lack of compliance (2%). Two patients discontinued ETN due to prolonged disease control. Adverse events were: infection (4 patients), post-injection skin reaction (3), uveitis (3), neoplasia (2) and others (3). Using a Kaplan-Meier analysis, at 1-year 64% (CI(95%) 54-74) of patients with ETN treatment had not experienced treatment failure, at 2-years, 59% (48-69) and at 5-years, 43% (30-52). With the rest of biologicals estimated survival was 61% (51-68), 47,5% (40-55) and 23% (10,5-32) respectively. Statistical analysis revealed significant differences (log-rank: P=.024; Breslow: P=.068; Tarone-Ware: P=.040). CONCLUSIONS: In our cohort of patients treated with ETN the estimated survival was better than patients treated with other biological drugs at 1-year, 2-years and 5-years. |