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ID PMID Title PublicationDate abstract
24334644 A clinical, pathological, and genetic characterization of methotrexate-associated lymphopr 2014 Feb OBJECTIVE: Methotrexate-associated lymphoproliferative disorders (MTX-LPD) often regress spontaneously during MTX withdrawal, but the prognostic factors remain unclear. The aim of our study was to clarify the clinical, histological, and genetic factors that predict outcomes in patients with MTX-LPD. METHODS: Patients with MTX-LPD diagnosed between 2000 and 2012 were analyzed retrospectively regarding their clinical course, site of biopsy, histological typing, Epstein-Barr virus (EBV) in situ hybridization and immunostaining, and HLA type. RESULTS: Twenty-one patients, including 20 with rheumatoid arthritis (RA) and 1 with polymyositis, were analyzed. The mean dose of MTX was 6.1 mg/week and the mean duration of treatment was 71.1 months. Clinically, 5 patients were diagnosed with EBV-positive mucocutaneous ulcer (EBVMCU) and had polymorphic histological findings. The proportion of those patients successfully treated solely by withdrawal of MTX was significantly greater than that of those without EBVMCU (75% vs 7.7%, p = 0.015). The HLA-B15:11 haplotype was more frequent in patients with EBV+ RA with MTX-LPD than in healthy Japanese controls (p = 0.0079, Bonferroni's method). EBV latency classification and HLA typing were not associated with the prognosis of MTX-LPD in our cohort. CONCLUSION: Our data demonstrate that patients in the EBVMCU, a specific clinical subgroup of MTX-LPD, had a better clinical outcome when MTX was withdrawn than did other patients with MTX-LPD.
23838092 Efficacy of treatment intensification with adalimumab, etanercept and infliximab in rheuma 2013 Oct OBJECTIVES: To summarize the empirical evidence regarding the effect of treatment intensification on clinical outcomes in patients with rheumatoid arthritis treated with one of the TNF-α-inhibitors, adalimumab, etanercept or infliximab. METHODS: A systematic search of the bibliographic databases Embase, Medline, Web of Science and Cochrane Central identifying articles concerning treatment with adalimumab, etanercept or infliximab in adult patients with rheumatoid arthritis exposed to dose increase or shortening of dosing intervals was performed. Longitudinal cohorts, both clinical trials and observational studies, were included. ACR and EULAR response criteria and DAS28 were the preferred outcome measures. RESULTS: Out of 1135 records, eleven studies were included in the final evidence synthesis. One article concerned all the three TNF-α-inhibitors, eight used infliximab, one adalimumab and one etanercept. According to GRADE, evidence was weakened in particular by the lack of control groups, and for treatment intensification with adalimumab and etanercept, no conclusions could be drawn. With infliximab, two trials of high quality revealed contradictory results, but six studies described an improved clinical outcome following intensified treatment strategies. Some studies (2/2) also indicated that for infliximab, frequency increase was superior to dose increase. CONCLUSIONS: Available studies indicate that intensifying treatment with infliximab in rheumatoid arthritis patients, preferably by increasing the frequency of drug administration, may lead to improved clinical outcome in some patients, but the evidence is weak. There is an urgent need for prospectively designed cohort studies to be able to draw a final conclusion.
24035192 Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-re 2013 Sep 26 The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient's life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn's disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFβ1 reduces production of proinflammatory cytokines, including TNFα, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses.
23972864 The effects of self-pain management on the intensity of pain and pain management methods i 2013 Sep The aims of this study were to investigate the effects of pain management education on the intensity of pain and frequency of utilization of pain management methods in two groups of patients with arthritis of different pathogenesis and clinical features, and to compare whether a significant difference existed between the two groups. The study was carried out between September 2007 and June 2008 on 30 female patients with gonarthrosis and 30 female patients with rheumatoid arthritis (RA) followed at the rheumatology outpatient clinic of a university hospital. Data on sociodemographic characteristics and those related with the illness were collected using a special survey. Each patient was given information about the features, causes, and treatment of the arthritis and how to cope with pain, emphasizing the importance of pain management methods. The intensity of pain and efficacy of pain management methods were assessed using the McGill Pain Questionnaire and the Pain Management Inventory at baseline and the second and sixth weeks after the education. The SPSS (v15.0) statistical package was used for statistical analysis. After education, significant improvements in pain intensity scores compared with baseline scores were observed in both groups (p < .05), and there was no significant difference between the RA and gonarthrosis groups. Among the various pain management methods, the education program led to significantly more utilization of massaging the painful area, exercising, and using complementary methods to control stress in both groups of patients, and there was no significant difference between the groups. In conclusion, the pain management education given in this study alleviated the intensity of pain and significantly increased the use of some pain management methods in both gonarthrosis and RA cases.
25592093 Cardiovascular autonomic neuropathy in rheumatoid arthritis assessed by cardiovascular aut 2015 Sep OBJECTIVE: In this study, we aimed to evaluate cardiovascular autonomic neuropathy (CAN) in RA patients by cardiovascular autonomic function tests. Because CAN was reported of patients with automimmune rheumatic diseases those may in sudden death or myocardial infarction. METHODS: A total of 44 patients with RA and 44 age- and sex-matched healthy volunteers participated in this cross-sectional study. Assessment of CAN was performed using cardiovascular reflex tests. These five tests were: 1) beat-to-beat heart rate variation during deep breathing; 2) heart rate response to standing up; 3) heart rate response to the Valsalva maneuver; 4) blood pressure response to standing up; and 5) blood pressure response to sustained handgrip. RESULTS: The mean age was 43.15 (SD, 12.18) years (range, 23-68 years) in the RA group, and 38 were women. In beat-to-beat heart rate variation during deep breathing, expiration-to-inspiration ratio was abnormal in 3 cases with RA (6.8%) but in 1 (2.3%) control subject (p=0.3), and maximum minus minimum heart rate was abnormal in 8 patients (18.2%) and in 3 (6.8%) control subjects (p=0.1). 2) In heart rate response to standing up, all patients and controls had normal results. Valsalva ratio was abnormal in 7 RA patients (15.9%) and in 7 control subjects (15.9%). Blood pressure response to standing up was normal in RA patients but abnormal in 1 (2.3%) control subject (p=0.4). Blood pressure response to sustained handgrip was abnormal in 5 RA patients (11.4%) and 2 (4.6%) control subjects (p=0.2). CONCLUSION: Our study failed to show any statistically significant difference between cardiovascular autonomic function tests in RA patients with control subjects by our test done.
25195983 The long-term effects of anti-TNF-α agents on patients with chronic viral hepatitis C and 2015 Jan AIM: To evaluate the long-term effects of anti-tumor necrosis factor-alpha (TNF-α) therapy on patients with chronic hepatitis B and C infections. METHODS: Rheumatoid arthritis, ankylosing spondylitis and Crohn's disease patients administered anti-TNF-α therapy for at least 36 months were retrospectively reviewed for hepatitis B or C serology, liver function tests, viral load, genotype and liver biopsy results, if performed. Nine relevant cases receiving anti-TNF-α were evaluated: six patients had chronic hepatitis C, one had chronic dual hepatitis B and C and two had chronic hepatitis B infection. RESULTS: The patient with dual infection exhibited virologic breakthrough for hepatitis C and required treatment. Two patients with occult hepatitis B infection developed hepatitis B surface antigen (HBsAg) reversion and low-level viremia at the end of the study. CONCLUSION: Long-term use of anti-TNF-α treatments may result in viral replication that requires anti-viral therapy. Before determining the safety of anti-TNF drugs in the treatment of autoimmune diseases in patients with hepatitis C infection, studies with large homogeneous patient groups must be performed, and the exact group of hepatitis C virus infected patients for whom anti-TNF treatment would be deemed safe should be identified. Prior to anti-TNF-α treatment, it seems logical to screen all patients for HBsAg and anti-HB core immunoglobulin G status, especially in endemic regions. These patients must be followed periodically by means of alanine aminotransferase, HBsAg and hepatitis B virus DNA to identify HBsAg reversion and active viral replication that might require anti-viral prophylaxis or treatment.
23528231 Characterization of a new mPGES-1 inhibitor in rat models of inflammation. 2013 Apr Microsomal prostaglandin E synthase (mPGES)-1 inhibition has been proposed as an alternative to cyclooxygenase (COX) inhibition in the treatment of pain and inflammation. This novel approach could potentially mitigate the gastro-intestinal and cardiovascular side effects seen after long-term treatment with traditional non-steroidal anti-inflammatory drugs (NSAIDs) and Coxibs respectively. Several human mPGES-1 inhibitors have been developed in the recent years. However, they were all shown to be considerably less active on rodent mPGES-1, precluding the study of mPGES-1 inhibition in rodent models of inflammation and pain. The aim of this study was to characterize the new mPGES-1 inhibitor compound II, a pyrazolone that has similar potency on rat and human recombinant mPGES-1, in experimental models of inflammation. In cell culture, compound II inhibited PGE2 production in synovial fibroblasts from patients with rheumatoid arthritis (RASF) and in rat peritoneal macrophages. In vivo, compound II was first characterized in the rat air pouch model of inflammation where treatment inhibited intra-pouch PGE2 production. Compound II was also investigated in a rat adjuvant-induced arthritis model where it attenuated both the acute and delayed inflammatory responses. In conclusion, compound II represents a valuable pharmacological tool for the study of mPGES-1 inhibition in rat models.
25541434 Cytokines pre-determined by genetic factors are involved in pathogenesis of Rheumatoid art 2015 Oct Rheumatoid arthritis (RA) is associated with the presence of autoreactive CD4 T cells that produce pro-inflammatory cytokines. The role of genetic factors in the predilection to develop RA is strongly supported by the increased presence of certain HLA class II molecules in patients. The HLA class II genes are highly polymorphic and are critical for generating an immune response to clear infections. Production of Th1 and Th17 response by the CD4 T cells helps to clear infections. HLA-DQ8 is a promiscuous binder and presents many peptides generating immune response and producing a Th17 response. DRB1∗0401 is associated with the production of both IL-17 and IFN-γ. Thus both DR4 and DQ8 can clear infections by producing TH1/Th17 cytokines, but their presence increases the risk of developing RA. Using transgenic mice expressing human HLA genes, we have shown that HLA polymorphism determines the cytokine profile. DRB1∗04 molecules modulate the DQ8-restricted response and determine the outcome of arthritis in mice carrying DR4/DQ8 haplotype. Thus, interaction between DQ and DR molecules determines the cytokine milieu and propensity of the HLA haplotype to predispose to autoimmunity.
24286214 Independent associations of total and high molecular weight adiponectin with cardiometabol 2013 Sep 20 INTRODUCTION: Whether adiponectin levels associate with atherogenesis in RA is uncertain. We examined the independent relationships of total and high molecular weight (HMW) adiponectin concentrations with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with RA. METHODS: We determined total and HMW adiponectin concentrations and those of endothelial activation molecules including soluble E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), in 210 (119 black and 91 white) RA patients. Associations were determined in potential confounder and mediator adjusted mixed regression models. RESULTS: Total and HMW adiponectin concentrations related similarly to metabolic risk factors and endothelial activation. In all patients, total and HMW adiponectin concentrations associated paradoxically with high systolic, diastolic and mean blood pressure (partial R = 0.155 to 0.241, P ≤ 0.03). Ethnic origin did not impact on these relationships (interaction P ≥ 0.09). Total and HMW adiponectin concentrations associated with those of glucose in white and black patients respectively (partial R = -0.304, P = 0.006 and -0.246, P = 0.01). In black but not white participants, total and HMW adiponectin concentrations also related favorably to lipid profiles (partial R = 0.292 to 0.360, P ≤ 0.003 for HDL cholesterol concentrations, -0.269 to -0.299, P ≤ 0.006 for triglyceride concentrations and -0.302 to -0.390, P ≤ 0.002 for total-HDL cholesterol ratio) and the number of metabolic risk factors (partial R = -0.210 to -0.238, P ≤ 0.03). In white but not black patients, total and HMW adiponectin concentrations associated paradoxically with overall endothelial activation as estimated by a standard z-score of endothelial activation molecule concentrations (partial R = 0.262, P = 0.01 and 0.252, P = 0.02); in the respective models, the extent of effect of total and HMW adiponectin concentrations on endothelial activation was larger in white compared to black participants (standardized β (SE) = 0.260 (0.107) versus -0.106 (0.107), P = 0.01 and 0.260 (0.120) versus -0.100 (0.111), P = 0.02). The HMW-total adiponectin ratio related inconsistently to metabolic risk factors and not to endothelial activation. CONCLUSION: In this study, total and HMW adiponectin concentrations associated with increased blood pressure parameters, and in white patients additionally with endothelial activation. The potential mechanism(s) underlying these paradoxical relationships between adiponectin concentrations and cardiovascular risk in RA merit further investigation.
23566735 Does infrapatellar fat pad resection in total knee arthroplasty impair clinical outcome? A 2013 Aug INTRODUCTION: The infrapatellar fat pad (IPFP) is often removed during total knee arthroplasty (TKA). No evidence based guidelines on changes in clinical outcome have yet been described. The aim of this review is to investigate whether regular removal of the IPFP during TKA should be performed. MATERIAL AND METHODS: Seven databases were systematically searched. Clinical studies, in which TKA with IPFP resection was compared with IPFP preservation, were included. Risk of bias was assessed using the Cochrane collaboration tool. Studies reporting anterior knee pain, patellar tendon length, range of motion, patellar vascularisation or functional outcome were included. RESULTS: The indication for TKA varied in the different studies: osteoarthritis (OA), rheumatic arthritis (RA) and multiple indications (OA, RA and osteonecrosis). After IPFP resection: 1. For OA, no differences in function, range of motion, and anterior knee pain were found. 2. In the RA study, there was a trend towards more discomfort and a decrease in function. 3. In OA and RA patients a decrease in patellar tendon length was observed. 4. One study reported no decrease in patellar vascularisation. DISCUSSION: Limitations of this review are the high risk of bias scores of the included studies, the varying outcome measures, follow up, number and type of participants. Randomised clinical trials are required to support or refute the results, contributing to a possible future evidence based guideline on IPFP resection during TKA.
25533796 Cardiorheumatology: cardiac involvement in systemic rheumatic disease. 2015 Mar Autoimmune rheumatic diseases can affect the cardiac vasculature, valves, myocardium, pericardium, and conduction system, leading to a plethora of cardiovascular manifestations that can remain clinically silent or lead to substantial cardiovascular morbidity and mortality. Although the high risk of cardiovascular pathology in patients with autoimmune inflammatory rheumatological diseases is not owing to atherosclerosis alone, this particular condition contributes substantially to cardiovascular morbidity and mortality-the degree of coronary atherosclerosis observed in patients with rheumatic diseases can be as accelerated, diffuse, and extensive as in patients with diabetes mellitus. The high risk of atherosclerosis is not solely attributable to traditional cardiovascular risk factors: dysfunctional immune responses, a hallmark of patients with rheumatic disorders, are thought to cause chronic tissue-destructive inflammation. Prompt recognition of cardiovascular abnormalities is needed for timely and appropriate management, and aggressive control of traditional risk factors remains imperative in patients with rheumatic diseases. Moreover, therapies directed towards inflammatory process are crucial to reduce cardiovascular disease morbidity and mortality. In this Review, we examine the multiple cardiovascular manifestations in patients with rheumatological disorders, their underlying pathophysiology, and available management strategies, with particular emphasis on the vascular aspects of the emerging field of 'cardiorheumatology'.
24550168 Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the ran 2015 Jun OBJECTIVE: CONCERTO was a randomised, double-blind, parallel-armed study of methotrexate (MTX) in combination with adalimumab to assess whether an increasing trend of efficacy and decreased safety exists when increasing MTX dose in patients with early rheumatoid arthritis (RA). METHODS: Early, biologic and MTX-naive RA patients (N=395) were evenly randomised to open-label adalimumab (40 mg every other week) plus weekly blinded 2.5, 5, 10 or 20 mg MTX for 26 weeks. Clinical, radiographic and functional outcomes were analysed using two-sided linear trend tests or one-way analysis of covariance. RESULTS: Statistically significant increasing trends were observed in the proportion of patients achieving the primary endpoint, 28-joint count disease activity score with C reactive protein (DAS28(CRP)) <3.2 (42.9%, 44.0%, 56.6% and 60.2% for 2.5, 5, 10 or 20 mg/week MTX, respectively), DAS28(CRP) <2.6 and American College of Rheumatology 50/70/90 responses with increasing doses of MTX in combination with adalimumab. No statistical differences in minimal clinically important differences in physical function were detected. Statistically significant trends for achieving low disease activity and remission were demonstrated with increasing MTX dose by validated clinical indices; differences comparing 10 and 20 mg MTX were minimal. Adalimumab serum concentrations increased with ascending dose up to 10 mg MTX. More patients experienced infectious adverse events with increasing MTX dose. CONCLUSIONS: Increasing doses of MTX in combination with adalimumab demonstrated a statistically significant trend in improved clinical outcomes that mimicked the adalimumab pharmacokinetic profile. In early RA patients initiating adalimumab combination therapy, efficacy of 10 and 20 mg/week MTX appeared equivalent.
23155222 Individualised aerobic and resistance exercise training improves cardiorespiratory fitness 2013 Nov BACKGROUND AND OBJECTIVES: Low cardiorespiratory fitness (CRF) is a significant predictor of cardiovascular disease (CVD), and interventions aiming at increasing CRF are known to reduce CVD risk. The effects of such interventions on CVD risk have not been studied in patients with rheumatoid arthritis (RA). METHODS: 40 age, gender, body mass index (BMI) and disease duration matched RA patients were allocated to either an exercise (receiving 6 months individualised aerobic and resistance high intensity exercise intervention, three times per week), or control (receiving advice on exercise benefits and lifestyle changes) arm. Participants were assessed at baseline, 3 and 6 months for aerobic capacity (VO2max), individual CVD risk factors (blood pressure, lipids, insulin resistance, body composition), 10-year CVD event probability and RA characteristics (C-reactive protein (CRP), Disease Activity Score 28 (DAS28) and Health Assessment Questionnaire (HAQ)). RESULTS: There were no differences between groups at baseline in any of the assessed variables. VO2max (p=0.001), blood pressure (systolic: p<0.001; diastolic: p=0.003), triglycerides (p=0.030), high density lipoprotein (HDL; p=0.042), total cholesterol:HDL ratio (p=0.005), BMI (p=0.001), body fat (p=0.026), 10-year CVD event probability (p=0.012), CRP (p=0.042), DAS28 (p=0.008) and HAQ (p=0.003) were all significantly improved in the exercise versus the control group. The change in VO2max was the strongest predictor for the observed improvements in all of the assessed CVD risk factors and disease characteristics. CONCLUSIONS: Individualised aerobic and resistance exercise intervention can lead to significantly improved CRF, individual CVD risk factors, composite CVD risk, and disease activity and severity in RA patients.
22962438 Complement receptor type 1 (CR1, CD35) is a potent inhibitor of B-cell functions in rheuma 2013 Jan The involvement of B cells, complement activation and subsequent immune complex deposition has all been implicated in the pathogenesis of rheumatoid arthritis (RA). Although the reduced expression of complement receptor 1 (CR1, CD35) and 2 (CR2, CD21) on the B cells of RA patients has been known for a long time, their exact role in B-cell tolerance and autoimmunity is not yet fully understood. To get a deeper insight into the possible mechanisms, we studied the expression and function of CR1 and CR2 on various subsets of B cells of healthy donors and RA patients at various stages of the disease by FACS analysis, (3)H-thymidine incorporation and ELISA. We found that CD19(+)CD27(-) naive B cells up-regulate the expression of the inhibitory CR1 during differentiation to CD19(+)CD27(+) memory B cells both in healthy donors and in RA patients, whereas the expression of the activatory CR2 is down-regulated. This clearly demonstrates that the expression of these two antagonistic complement receptors is regulated differentially during the development of human B cells, a phenomenon which may influence the maintenance of peripheral B-cell tolerance. Our functional studies show that after clustering CR1 both by its natural ligand and To5 mAb, the inhibitory function of CD35 is maintained in RA patients, despite its significantly reduced expression compared with healthy individuals. Besides blocking B-cell receptor-induced proliferation, CR1 inhibits the differentiation of B cells to plasmablasts and their immunoglobulin production. Since the reduced expression of CR1 in RA patients does not affect its inhibitory function, this receptor might serve as a new target for therapeutical interventions.
24402309 Involvement of histamine 4 receptor in the pathogenesis and progression of rheumatoid arth 2014 Jun Rheumatoid arthritis (RA) is one of the major autoimmune diseases with a global prevalence. Despite significant research into this disease, no drugs with acceptable safety profiles are yet available for its treatment. We investigated the possible anti-arthritic effects of the 4-methylhistamine (4-MeH) histamine 4 receptor (H4R) agonist and the JNJ77777120 (JNJ) H4R antagonist to explore the role of H4R in a mouse model of collagen antibody-induced arthritis (CAIA). Arthritis was induced via intravenous (tail vein) injection of Balb/c mice with a 5-clone cocktail of mAbs against collagen type II, followed by LPS, and the effects of treatment with 4-MeH or JNJ (30 mg kg(-1), i.p, twice daily) for 7 days (prophylactic or therapeutic regimens) were assessed. The results revealed increased paw edema, arthritic scores, joint histological inflammatory damage and matrix metalloproteinase-3 levels and high levels of Th1 pro-inflammatory cytokine mRNA and serum proteins in CAIA mice or following H4R activation via 4-MeH. Additionally, 4-MeH efficiently increased expression levels of NF-κB p65. JNJ-treated mice showed a substantial reduction in all the previously mentioned effects, with a similar trend being observed under prophylactic and therapeutic treatment regimens. The results of the present work indicate that JNJ exhibits significant anti-inflammatory and anti-arthritic activities, demonstrating the clear involvement of H4R antagonism in the pathogenesis and progression of RA.
23722231 Cutaneous papillomavirus infection in patients with rheumatoid arthritis or systemic lupus 2013 Aug Previous studies informed an increased prevalence of cutaneous papillomavirus (cHPV) infection in patients with systemic lupus erythematosus (SLE). The main objective of our study was to evaluate factors associated with cHPV infection in patients with either rheumatoid arthritis (RA) or SLE, and to determine whether SLE itself is an independent risk factor for cHPV infection. We included 670 patients (in consecutive selection) in this cross-sectional study (550 with RA and 120 with SLE). All patients were evaluated by a dermatologist; patients with cHPV infection were selected as cases (63) and the other 607 patients were selected as controls. The prevalence of cHPV infection was increased 2.8-fold in SLE patients (20%) compared with RA patients (7.1%). When comparing cases with controls, bivariate analysis showed statistically significant differences for: age, having SLE, and treatment with mycophenolate mofetil (MMF). When all of the potential risk factors identified using bivariate analysis (age, having SLE, and MMF) were included into a multivariate model, independent risk factors for cHPV infection were: having SLE (odds ratio: 2.16, 95% confidence interval: 1.04-4.48) and MMF therapy (odds ratio: 2.91, 95% confidence interval: 1.18-7.14).
23728826 Electronic monitoring of oral therapies in ethnically diverse and economically disadvantag 2013 Jun OBJECTIVE: To quantify adherence to oral therapies in ethnically diverse and economically disadvantaged patients with rheumatoid arthritis (RA), using electronic medication monitoring, and to evaluate the clinical consequences of low adherence. METHODS: A total of 107 patients with RA enrolled in a 2-year prospective cohort study agreed to have their oral RA drug therapy intake electronically monitored using the Medication Event Monitoring System. Adherence to disease-modifying antirheumatic drugs (DMARDs) and prednisone was determined as the percentage of days (or weeks for methotrexate) on which the patient took the correct dose as prescribed by the physician. Patient outcomes were assessed, including function measured by the modified Health Assessment Questionnaire, disease activity measured by the Disease Activity Score in 28 joints (DAS28), health-related quality of life, and radiographic damage measured using the modified Sharp/van der Heijde scoring method. RESULTS: Adherence to the treatment regimen as determined by the percentage of correct doses was 64% for DMARDs and 70% for prednisone. Patients who had better mental health were statistically more likely to be adherent. Only 23 of the patients (21%) had an average adherence to DMARDs ≥80%. These patients showed significantly better mean DAS28 values across 2 years of followup than those who were less adherent (3.28 versus 4.09; P = 0.02). Radiographic scores were also worse in nonadherent patients at baseline and at 12 months. CONCLUSION: Only one-fifth of RA patients had an overall adherence to DMARDs of at least 80%. Less than two-thirds of the prescribed DMARD doses were correctly taken. Adherent patients had lower disease activity across the 2 years of followup.
25124723 SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity 2014 Nov Methotrexate (MTX) is used for rheumatoid arthritis (RA) treatment showing a wide toxicity profile. This study aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) in genes encoding for MTX transporters with the occurrence of MTX-related toxicity (overall and gastrointestinal). A total of 233 Portuguese RA patients were genotyped for 23 SNPs. Haplotype analyses were performed and a toxicogenetic risk index (TRI) was created for SNPs that revealed to be statistically significant. Regarding MTX overall toxicity, an increased risk was associated to SLC19A1 rs7499 G carriers (p = 0.017), SLC46A1 rs2239907 GG (p = 0.030) and, SLCO1B1 rs4149056 T carriers (p = 0.040) and TT (p = 0.019). TRI revealed that patients with Index 3 were 18-fold more likely to present an adverse drug reaction when compared to those with Index 1 (p = 0.001). For MTX gastrointestinal toxicity, results demonstrated an increased risk associated with SLC19A1 rs7499 G carriers (p = 0.012) and GG (p = 0.045), SLC19A1 rs1051266 G carriers (p = 0.034), SLC19A1 rs2838956 A carriers (p = 0.049) and, SLCO1B1 rs4149056 T carriers (p = 0.042) and TT (p = 0.025). Haplotype analyses showed association between GGAG haplotype for SLC19A1 rs7499, rs1051266, rs2838956 and rs3788200 with MTX gastrointestinal toxicity (p = 0.029). TRI revealed that patients with Index 4 were 9-fold more likely to present a gastrointestinal disorder when compared to those with Index 1 (p = 0.020). This study demonstrated that SLC19A1, SLC46A1 and SLCO1B1 genotypes may help to identify patients with increased risk of MTX-related overall toxicity and that SLC19A1 and SLCO1B1 genotypes, and SLC19A1 haplotypes may help to identify patients with increased risk of MTX-related gastrointestinal toxicity.
25081573 The risk of herpes zoster during biological therapy for psoriasis and other inflammatory c 2014 Jul Recent advances in biological therapies have proved highly effective in treating psoriasis and other inflammatory conditions, including psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease and ankylosing spondylitis. However, adverse effects related to their immunosuppression have been observed, including an increased propensity to viral infections. This review evaluates the evidence of herpes zoster (HZ) risk from biologics based on clinical reports, cohort studies and randomized controlled studies. The risk of HZ associated with these agents remains controversial, especially when comparing their risk with non-biological therapy used to treat the same inflammatory conditions. This review specifically assesses the risk of the TNF inhibitors etanercept, adalimumab and infliximab, as well as interleukin-12/23 inhibitor ustekinumab. We found multiple cohort studies, randomized controlled trials and case reports that suggest infliximab increases risk of HZ, whereas adalimumab, etanercept and ustekinumab HZ risk remain controversial. Nevertheless, HZ vaccination should be considered prior to initiation of biological therapy, particularly infliximab.
23286291 Biologics and the cardiovascular system: a double-edged sword. 2013 Patients with chronic inflammatory diseases such as rheumatoid arthritis have a higher risk of cardiovascular diseases and related mortality compared to the general population. This risk is first due to classical cardiovascular risk factors but also due to systemic inflammation which is independently involved, causing accelerated atherosclerosis, myocardial infarction, cerebrovascular disease and heart failure (HF). Pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 and IL-6 could be major actors on this pathophysiology. Biologics are effective specific treatments in the management of inflammatory rheumatic and systemic diseases. In this review, beneficial and deleterious effects on the heart and vessels of the biologics used in the management of inflammatory arthritis and vasculitides will be discussed, focusing on TNF-alpha, IL-6 and IL-1 blockades, and anti-CD20. Noninflammatory cardiac conditions, such as heart failure, myocardial infarction, and cardiovascular conditions such as atherosclerosis, as well as inflammatory diseases including vasculitides will be discussed.