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ID PMID Title PublicationDate abstract
21304506 Pharmacogenetics: Anti-TNF therapy in RA--towards personalized medicine? 2011 Mar A substantial proportion of patients with rheumatoid arthritis do not respond to tumor necrosis factor blocking therapy. Results of a large genome-wide association study demonstrate evidence of novel genetic factors that determine response to treatment, which could provide a basis for individualizing therapy.
21827002 [Detecting anti-cyclic citrullinated peptide antibody in patients with connective tissue d 2011 May OBJECTIVE: To determine the clinical significance of anti-cyclic citrullinated peptide antibody (anti CCP) in mixed connective tissue diseases (MCTD). METHODS: Enzyme linked immunosorbent assay was performed to detect anti-CCP in 57 patients with MCTD, 78 with rheumatoid arthritis (RA), 64 with systemic lupus erythematosus (SLE), 56 with polymyositis/dermatomyositis (PM/DM), 53 with Sjögren syndrome (SS) and with 33 systemic sclerosis (SSc). The association between anti-CCP and clinical features of MCTD was analysed. RESULTS: Anti-CCP was detected in 87.5% RA cases, 15.8% MCTD cases, 57.1% MCTD with RA cases, 14.1% SLE cases, 15.2% PM/DM cases, 18.9% SS cases and 9.1% SSc cases. Patients with RA (or MCTD with RA) were more likely to be anti-CCP positive than those without RA (P < 0.05). The MCTD patients with positive anti-CCP had higher prevalence of RA and SS related manifestations than those MCTD patients with negative anti-CCP (P < 0.05). The MCTD patients with RA had higher prevalence of RA-related symptoms, diffuse sclerosis and positive anti-CCP than those MCTD patients without RA (P < 0.01). Significant deviation of disease spectrum was found in the MCTD patients with RA compared with the anti-CCP positive MCTD patients without RA. CONCLUSION: High titer of anti-CCP in combination with RA, SLE and SSc manifestations in MCTD patients can be an indicator of erosive arthritis.
21556737 The role of Raf kinase inhibitor protein in rheumatoid fibroblast-like synoviocytes invasi 2012 Apr Fibroblast-like synoviocytes (FLS) play an important role in the pathogenesis of rheumatoid arthritis. Raf kinase inhibitor protein (RKIP) negatively regulates the Raf/MEK/ERK and NF-κB pathway. The role of RKIP in rheumatoid FLS is unknown. The purpose of the present study was to investigate the function of RKIP in rheumatoid FLS. Rheumatoid FLS were transfected with either RKIP-expressing plasmids or RKIP small interfering RNA (siRNA). RKIP protein was detected in rheumatoid synovial tissue (ST) and FLS. RKIP overexpression significantly decreased IL-6 mRNA expression in TNF-α-stimulated rheumatoid FLS. RKIP overexpression also showed a decreased trend in IL-8, MMP-1, and MMP-3 mRNA expression in TNF-α-stimulated rheumatoid FLS. RKIP silencing resulted in significantly increased MMP-1 and MMP-3 mRNA expression in TNF-α-stimulated rheumatoid FLS. RKIP silencing also increased IL-6 and IL-8 mRNA expression in TNF-α-stimulated rheumatoid FLS, but this increase did not reach statistical significance. TNF-α-induced ERK and NF-κB activation was suppressed in FLS with RKIP overexpression. RKIP silencing resulted in a significantly higher invasion index in TNF-α-stimulated rheumatoid FLS compared to controls. These results suggest that RKIP might be a potential therapeutic target for rheumatoid arthritis.
21844139 Influence of Janus kinase inhibition on interleukin 6-mediated induction of acute-phase se 2011 Nov OBJECTIVE: Inhibition of intracellular signal transduction is considered to be a therapeutic target for chronic inflammation. The new Janus kinase (JAK)3 inhibitor CP690,550 has shown efficacy in the treatment of rheumatoid arthritis (RA). We investigated the influence of JAK/STAT inhibition using CP690,550 on the induction of acute-phase serum amyloid A (SAA), which is triggered by interleukin 6 (IL-6) stimulation in rheumatoid fibroblast-like synoviocytes (RA-FLS). METHODS: IL-6-stimulated gene expression of the acute-phase serum amyloid A genes (A-SAA; encoded by SAA1+SAA2) and SAA4 was analyzed by reverse transcriptase-polymerase chain reaction. The intracellular signaling pathway mediating the effects of CP690,550 on IL-6-stimulated JAK/STAT activation was assessed by measuring the phosphorylation levels using Western blots. RESULTS: IL-6 trans-signaling induced A-SAA messenger RNA (mRNA) expression in RA-FLS. By contrast IL-6 stimulation did not affect SAA4 mRNA expression, which is expressed constitutively in RA-FLS. IL-6 stimulation elicited rapid phosphorylation of JAK2 and STAT3, which was blunted by CP690,550. CP690,550 abrogated IL-6-mediated A-SAA mRNA expression in RA-FLS. Similarly, CP690,550 inhibited IL-6-mediated A-SAA mRNA expression in human hepatocytes. CONCLUSION: Our data indicated that CP690,550 blocked IL-6-induced JAK2/STAT3 activation, as well as the induction of A-SAA. Inhibition of IL-6-mediated proinflammatory signaling pathways by CP690,550 may represent a new antiinflammatory therapeutic strategy for RA and AA amyloidosis.
21789616 Osteomalacia caused by tumors in facies cranii mimicking rheumatoid arthritis. 2012 Aug Tumor-induced osteomalacia (TIO) is an extremely rare metabolic bone disease and the occult offending tumor arising in facies cranii is even more uncommon. In this report, we described 2 middle-aged females with TIO caused by the tumor in facies cranii, which had ever been misdiagnosed as rheumatoid arthritis. Case 1 was present with diffuse bone pain and muscle weakness for 4 years, as well as esotropia in the right eye for 1 month. Case 2 was present with progressive bone pain in low back and hip for 2 years. Biochemical studies both showed persistent hypophosphatemia and urinary over wasting phosphate. Radiological examinations revealed the infiltrative mass in right apex partis petrosae ossis temporalis in case 1, and the soft mass in left nasal cavity and ethmoid sinuses in case 2, respectively. The offending tumors were resected completely in case 2, however, incompletely in case 1. Pathology examination revealed mixed connective tissue variant phosphaturic mesenchymal tumors. In conclusion, TIO should be presumed in patients presenting with unexplained persistent hypophosphatemia osteomalacia, also a thorough detection for tumor in facies cranii should be performed.
22066553 High rate of complications and radiographic loosening of the biaxial total wrist arthropla 2011 Dec BACKGROUND AND PURPOSE: The third generation of total wrist arthroplasty (TWA) was designed to solve the early loosening problem, but there have been few long-term follow-ups. We present the outcome of the biaxial total wrist prosthesis (no longer available) after 5-8 years of follow-up. PATIENTS AND METHODS: 40 biaxial wrist prostheses were implanted uncemented in 36 patients with rheumatoid arthritis. 32 wrists were followed clinically and radiographically. 7 prostheses had been revised at median 21 (8-71) months; 1 patient died from an unrelated cause. Mean follow-up of the remaining 32 wrists was 6 (5-8) years. Kaplan-Meier survival analysis was performed with revision defined as failure. RESULTS: Survival after 7 years was 81% (95% CI: 64-91). There were 31 complications. 22 wrists showed radiographic loosening. Range of motion improved, except for pronation. The mean DASH score improved and the median postoperative pain score (from 0 to 10) was 0 (0-6) at rest and 0 (0-7) during activity. INTERPRETATION: One quarter of the prostheses had been revised and radiographic loosening had occurred in two thirds of the cases. Radiographic and clinical follow-up is therefore necessary for patients with this implant.
22460410 Profile of users of anticytokines offered by the health care system in the state of Paranà 2012 Mar INTRODUCTION: The Brazilian Unified Health Care System (SUS) offers treatment for patients with RA through federal funding (Ministry of Health) and state co-financing. The Clinical Protocol and Therapeutic Guidelines for the treatment of rheumatoid arthritis describe the therapeutic regimen for the disease, including the anticytokines adalimumab, etanercept or infliximab. OBJECTIVES: The aim of this study was to evaluate the profile of registered users of those anticytokines, biologics registered in the Information System of the Pharmaceutical Assistance Specialized Division, managed by the Paraná State Drug Center. METHODS: A cross-sectional study regarding data from March 2010 was conducted. Based on dispensation data, information regarding the following variables were collected: age; gender; regional health care centers; International Classification of Diseases (ICD); and drug dispensed. In addition, the monthly cost with anticytokines for the SUS was calculated. RESULTS: In the state of Paraná, 923 patients on anticytokines were identified, 40%, 44% and 16% of whom receiving adalimumab, etanercept and infliximab, respectively. This generated a monthly cost of R$3,403,195.59. Regarding the ICD, the distribution of patients was as follows: 55% had ICD M05.8; 27%, ICD M06.0; 9%, ICD M6.8; 8%, ICD M5.0; and 1% had other ICDs related to the disease. The regional health care centers of the state of Paraná with the largest number of patients on anticytokines were in the following municipalities: Ponta Grossa; Cornélio Procópio; Londrina; Cianorte; Maringá; Irati; and Campo Mourão. CONCLUSION: This study assessed the distribution and profile of users of anticytokines for the rheumatoid arthritis treatment covered by the SUS in the state of Paraná, in March 2010.
22549135 Synergy between adiponectin and interleukin-1β on the expression of interleukin-6, interl 2012 Jul 31 To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1β regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1β, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E(2) (PGE(2)), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1β to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1β each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1β did not synergistically support the degradation of IκB-α or the nuclear translocation of NF-κB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-κB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1β may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.
22226402 International cohort study of 73 anti-Ku-positive patients: association of p70/p80 anti-Ku 2012 Jan 6 INTRODUCTION: An international cohort study of 73 anti-Ku-positive patients with different connective tissue diseases was conducted to differentiate the anti-Ku-positive populations of patients based on their autoantibody profile and clinical signs/symptoms and to establish possible correlations between antibodies against Ku p70 and Ku p80 with autoimmune diseases. METHODS: Sera of anti-Ku-positive patients were collected from six European centers and were all secondarily tested (in the reference center); 73 were confirmed as positive. Anti-Ku antibodies were detected with counter-immunoelectrophoresis (CIE), line immunoassay (LIA), and immunoblot analyses. All clinical and laboratory data were follow-up cumulative data, except for anti-Ku antibodies. Statistical analyses were performed by using R (V 2.12.1). The Fisher Exact test was used to evaluate the association between anti-Ku antibodies and diagnosis, gender, clinical signs, and other observed antibodies. The P values were adjusted for multiple testing. Separation of disease populations based on the presence of antibodies and clinical signs was investigated by principal-components analysis, which was performed by using thr// R's prcomp function with standard parameters. RESULTS: A 16% higher prevalence of anti-Ku p70 was found over anti-Ku p80 antibodies. In 41 (57%) patients, a combination of both was detected. Five (7%) patients, who were CIE and/or LIA anti-Ku positive, were negative for both subsets, as detected with the immunoblot; 31% of the patients had undifferentiated connective tissue disease (UCTD); 29% had systemic sclerosis (SSc); 18% had systemic lupus erythematosus (SLE); 11% had rheumatoid arthritis; 7% had polymyositis; and 3% had Sjögren syndrome. CONCLUSIONS: A significant positive association was found between female patients with anti-Ku p70 and joint/bone features, and a significant negative association was found between female patients with anti-Ku p80 only and joint/bone features (P = 0.05, respectively). By using the first and the third components of the principal-component analysis (PCA) with 29 parameters evaluated, we observed that the anti-Ku-positive population of UCTD patients had overlapping parameters, especially with SLE, as opposed to SSc, which could be helpful in delineating UCTD patients.
22257601 An incidental finding? Pneumatosis intestinalis after minor trauma. 2013 Feb BACKGROUND: Pneumatosis intestinalis (PI) refers to the identification of air within the wall of the gastrointestinal tract. This finding often marks serious underlying pathology, which can be potentially surgical in nature. However, this process may also occur within a benign context, for example, in patients who are chronically immunosuppressed. The prevalence of benign PI may be greater than previously anticipated, because its discovery is facilitated by the increasingly widespread use of computed tomography (CT) scanning. OBJECTIVES: We will illustrate how widespread use of CT scanning after trauma leads to incidental findings, some of which are difficult to distinguish from acute pathologic findings. We will also discuss the differential diagnosis for PI and the associated clinical significance. CASE REPORT: A female patient with two autoimmune disorders requiring immunosuppression presented after minor trauma. Her clinical stability and benign examination led us to refrain from ordering a full radiographic evaluation, including an abdominal CT scan. She was safely discharged; however, per CT several days later, the incidental finding was made of PI with free intraperitoneal air. These findings after trauma commonly prompt an exploratory laparotomy. However, given her persistent stability, we attributed this to immunosuppression rather than to recent trauma. CONCLUSION: The indications for ordering CT scans after minor trauma must be carefully considered, and incidental findings must be interpreted in the context of the overall clinical scenario.
21833687 The expression and distribution of immunomodulatory proteins B7-H1, B7-DC, B7-H3, and B7-H 2012 Feb CD28/B7 signals have been shown to have the capacity to regulate T cell activation and participate in regulating the development of rheumatoid arthritis (RA). However, the expression and anatomical distribution of some members of the B7 superfamily including B7-H1, B7-DC, B7-H3 and B7-H4 in RA synovium is still unclear. We analyzed the expression of these molecules in synovial tissues from RA patients. Immunohistochemistry showed that all of these molecules were observed in synovium. On the cellular level, all of them were found on cell membrane and in cytoplasma. The expression of B7-DC and B7-H3 was major on capillaries, synovicytes and infiltrated inflammatory cells in the lining layer, while B7-H1 and B7-H4 were detected in some inflammatory cells residing in the sublining and lining layer. Fluorescent dual staining indicated that all these molecules were principally associated with CD31(+) endothelial cells and CD68(+) macrophages. In addition, B7-H1 and B7-H3 were also observed on CD3(+) T cells (including CD4(+) and CD8(+) T cells). Interestingly, B7-H1/B7-H4, B7-H3/B7-DC were co-expressed on the same cells. The characteristic expression and distribution of these molecules in synovium indicated that they probably have different effects during the progress of RA, and a clear understanding of their functional roles may further elucidate the pathogenesis of this disease.
23264338 Risk of mortality in patients with psoriatic arthritis, rheumatoid arthritis and psoriasis 2014 Jan BACKGROUND: There are conflicting reports in the literature of the mortality risk among patients with psoriatic arthritis (PsA). The objective of this study was to examine the risk of mortality in patients with PsA compared with matched controls, patients with psoriasis and those with rheumatoid arthritis (RA). METHODS: A longitudinal cohort study was performed in a large UK medical record database, The Health Improvement Network, among patients with PsA, rheumatoid arthritis (RA) or psoriasis with data from 1994 to 2010. Unexposed controls were matched on practice and start date within the practice for each patient with PsA. Cox proportional hazards models were used to calculate the relative hazards for death. RESULTS: Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=82 258) were identified; 1 442 357 person-years were observed during which 21 825 deaths occurred. Compared with population controls, patients with PsA did not have an increased risk of mortality after adjusting for age and sex (disease-modifying antirheumatic drug (DMARD) users: HR 0.94, 95% CI 0.80 to 1.10; DMARD non-users: HR 1.06, 95% CI 0.94 to 1.19) whereas patients with RA had increased mortality (DMARD users: HR 1.59, 95% CI 1.52 to 1.66; DMARD non-users: HR 1.54, 95% CI 1.47 to 1.60). Patients with psoriasis who had not been prescribed a DMARD had a small increased risk of mortality (HR 1.08, 95% CI 1.04 to 1.12) while those who had been prescribed a DMARD, indicating severe psoriasis, were at increased risk (HR 1.75, 95% CI 1.56 to 1.95). CONCLUSIONS: Patients with RA and psoriasis have increased mortality compared with the general population but patients with PsA do not have a significantly increased risk of mortality.
22440160 Chloroquine keratopathy of rheumatoid arthritis patients detected by in vivo confocal micr 2012 Apr AIM: To investigate microscopic changes in corneal morphology in chloroquine (CQ)-treated patients without corneal abnormalities being diagnosable by slit lamp microscopy. METHODS: Thirty-six eyes of 36 patients with rheumatoid arthritis (RA) were divided into two groups: group 1 included 26 patients receiving chloroquine therapy; group 2 included the other 10 patients, not receiving chloroquine therapy. The control group included 15 healthy subjects. Best spectacle-corrected visual acuity (BSCVA), intraocular pressure (IOP) and slit lamp microscopy and in vivo confocal microscopy examinations were performed on all subjects. RESULTS: In group 1, hyperreflective abnormal particles were found in different layers of the cornea in 19 (75%) of 26 eyes by confocal microscopy. The deposits were present within the superficial epithelium (14/19), basal epithelium (8/19) and anterior stroma (5/19). In both RA groups, more beaded and tortuous fibers were seen in the sub-basal corneal nerve bundles, and the sub-epithelial and stromal nerves had much more branches, than did normal controls. The anterior keratocyte density in group 1 was lower than in group 2 (P < 0.05) and the number of sub-basal nerves was larger than in group 2 (P < 0.05). Cumulative dosage had a statistically significant correlation with anterior keratocyte density, the number of sub-basal nerves and the density of abnormal particles. CONCLUSION: Corneal microdeposits are an important manifestation of chloroquine-induced keratopathy. Corneal stroma cell density and corneal nerve number and morphology changes are also useful for detecting early chloroquine-induced keratopathy. This would be proved in our future longitudinal studies.
23001847 PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial-mesenchymal t 2013 Jan Migration and invasion of fibroblast-like synoviocytes (FLSs) are critical in the pathogenesis of rheumatoid arthritis (RA). Hypoxic conditions are present in RA joints, and hypoxia has been extensively studied in angiogenesis and inflammation. However, its effect on the migration and invasion of RA-FLSs remains unknown. In this study, we observed that RA-FLSs exposed to hypoxic conditions experienced epithelial-mesenchymal transition (EMT), with increased cell migration and invasion. We demonstrated that hypoxia-induced EMT was accompanied by increased hypoxia-inducible factor (HIF)-1α expression and activation of Akt. After knockdown or inhibition of HIF-1α in hypoxia by small interfering RNA or genistein (Gen) treatment, the EMT transformation and invasion ability of FLSs were regained. HIF-1α could be blocked by phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, indicating that HIF-1α activation was regulated by the PI3K/Akt pathway. Administration of LY294002 (20 mg/kg, intra-peritoneally) twice weekly and Gen (25 mg/kg, by gavage) daily for 3 weeks from day 20 after primary immunization in a collagen-induced arthritis rat model, markedly alleviated the clinical signs, radiology progression, synovial hyperplasia, and inflammatory cells infiltration of joints. Thus, results of this study suggest that activation of the PI3K/Akt/HIF-1α pathway plays a pivotal role in mediating hypoxia-induced EMT transformation and invasion of RA-FLSs under hypoxia.
21946459 Effects of anti-tumor necrosis factor agents for familial mediterranean fever patients wit 2011 Oct BACKGROUND: Effectiveness of anti-tumor necrosis factor (anti-TNF) agents in colchicine-resistant familial Mediterranean fever (FMF) patients has attracted attention in recent years. OBJECTIVE: We analyzed the effect of anti-TNF agents on clinical findings of colchicine-resistant FMF patients with chronic arthritis and/or sacroiliitis. METHODS: Data from 10 FMF patients (5 male and 5 female patients: mean age, 30.1 [SD, 8.5] years) with chronic arthritis and/or sacroiliitis who were on anti-TNF agents are reviewed. Frequency of FMF attacks before and after treatment with anti-TNF agents was recorded from hospital files. The effects of the anti-TNF treatment were determined by using the number of tender and/or swollen joints, serum acute phase reactant levels, and Bath Ankylosing Spondylitis Disease Activity Index scores. Change in urine protein loss was also evaluated in patients with amyloidosis. In 6 patients, FMF attacks had been considered to be unresponsive to colchicine, and 4 patients were partial responders before treatment with anti-TNF agents. RESULTS: Mean attack frequency of the patients in the 3 months' period before anti-TNF agent treatment was 3.8 (SD, 3.1). After anti-TNF treatment, in 3 patients, FMF attack frequency decreased, and in the remaining 7 patients, no attack occurred. Serum acute phase reactant levels were decreased significantly at 3 and 6 months after anti-TNF treatment (P < 0.05 for all). After anti-TNF treatment Bath Ankylosing Spondylitis Disease Activity Index scores were also decreased significantly (6.2 [SD], 1.7 vs. 2.1 [SD], 1.7; P = 0.012). In all 3 patients with amyloidosis, urine protein loss decreased without any increase in serum creatinine levels. CONCLUSION: Anti-TNF treatment can have beneficial effects for controlling FMF attacks in FMF patients with chronic arthritis and/or sacroiliitis.
21501791 Linked total elbow arthroplasty. 2011 May This article provides an overview of the current state of linked total elbow arthroplasty. Discussed are the general indications for using a linked implant and currently available implants. Disease-specific indications, contraindications, surgical technique, and rehabilitation are discussed. The overall results and disease-specific results, as well as complications after a linked elbow arthroplasty, are reviewed.
22168788 Adalimumab, etanercept, and infliximab utilization patterns and drug costs among rheumatoi 2012 OBJECTIVES: To evaluate the utilization patterns of the anti-tumor necrosis factor (anti-TNF) agents Humira (adalimumab), Enbrel (etanercept), and Remicade (infliximab) in patients with rheumatoid arthritis (RA) and compare medication costs during the first year of treatment. (Humira is a registered trademark of Abbott Laboratories, IL; Enbrel is a registered trademark of Immunex Corporation, CA; and Remicade is a registered trademark of Janssen Biotech, Inc., PA). METHODS: This retrospective analysis of medical and pharmacy claims included patients who were aged ≥18 years, had ≥2 RA diagnosis codes, and had ≥365 days of persistence with the index anti-TNF. Patients excluded had claims for anti-TNF agents within 6 months before the index date. Refill patterns for adalimumab and etanercept, number of infliximab infusions, time between infusions, and dose per infusion were analyzed for 12 months. Direct anti-TNF medication costs were compared among anti-TNFs for the initial treatment year. RESULTS: Infliximab-treated patients (n = 457) were significantly older than adalimumab- (n = 337) or etanercept-treated patients (n = 902). Time between refills was longer than recommended for 28% and 30% of adalimumab and etanercept refill periods, respectively. Potential cumulative time without therapy was 33 days for adalimumab and 43 days for etanercept. Statistically significant differences in mean per-patient anti-TNF medication costs for the first year were reported for adalimumab, etanercept, and infliximab ($14,991, $13,361, and $18,139, respectively; p < 0.0001); however, a cost assessment using labeled dosing of the anti-TNF agents with optimal treatment compliance yielded comparable annual medication costs. LIMITATIONS: This analysis only evaluated utilization patterns for selected anti-TNF agents and was not inclusive of other medications that patients may have been using for RA. Absolute patient adherence could not be assessed due to lack of information on how patients were self-administering adalimumab and etanercept or if samples of the agents were made available. CONCLUSIONS: This study identified gaps in patients' refills compared with prescriber recommendations. The infliximab-treated group had infusion patterns consistent with prescribing information. Potential clinical and economic implications of dose attenuation with adalimumab and etanercept should be explored further.
22344576 Certolizumab pegol plus MTX administered every 4 weeks is effective in patients with RA wh 2012 Jul OBJECTIVE: Certolizumab pegol (CZP) is known to be effective as monotherapy at a dosage of 400  mg every 4 weeks in patients with active RA who have failed DMARDs. The aim of this study was to investigate every 4-week CZP in addition to continued MTX therapy in patients with an inadequate response to MTX alone. METHODS: Patients with active RA with inadequate response to MTX, on background MTX, were randomized to double-blind treatment with CZP 400  mg or placebo every 4 weeks for 24 weeks (NCT00544154). The primary efficacy end-point was the ACR 20% improvement criteria (ACR20) response rate at Week 24. Other end-points included ACR50 and ACR70 response rates, ACR core components, 28-joint DAS (ESR) with three variables (DAS28-3) and health-related quality-of-life outcomes in addition to safety. RESULTS: Of 247 randomized patients, 126 received CZP and 121 received placebo, in addition to MTX. ACR20 response rates were 45.9 vs 22.9%, respectively [P < 0.001 analysed by the Cochran-Mantel-Haenszel (CMH) method], with improvements being apparent from Week 1. Statistically significant improvements over placebo were seen with CZP for ACR50, ACR core components, DAS28-3 and physical functioning. Rates of treatment-related adverse events were similar between groups (25.0 vs 27.7%), and there were no deaths or serious opportunistic infections. CONCLUSION: CZP 400  mg every 4 weeks plus MTX demonstrated a favourable risk-benefit profile with rapid onset of action in RA patients with an inadequate response to an earlier MTX therapy.
23044076 Successful treatment of pemphigus with biweekly 1-g infusions of rituximab: a retrospectiv 2013 Mar BACKGROUND: Rituximab is increasingly being appreciated as a remarkably effective treatment for pemphigus, mostly concomitantly with other immunosuppressive medications. The majority of studies have used a single cycle of rituximab with the same dosage as approved for the treatment of lymphomas, ie, 375 mg/m(2) weekly × 4 weeks. Rituximab is also approved for the treatment of rheumatoid arthritis, with a different dosing regimen: 1000 mg × 2, days 1 and 15. OBJECTIVE: We aimed to assess the clinical response of patients with pemphigus to a single cycle of rituximab at the dosage used in rheumatoid arthritis. We also evaluated the response to repeated cycles of rituximab. METHODS: A total of 47 patients with pemphigus who were treated with rituximab at a dosage of 1000 mg × 2, days 1 and 15, most with concurrent immunosuppressive medications, were retrospectively studied. RESULTS: Remission rates after the first treatment cycle reached 76%. Repeating the treatment further increased the remission rates to 91%. There was a 22% relapse rate at a median time of 8 months, but 75% of relapsing patients achieved remission again with additional cycles. The side-effect profile was similar to previous reports, except for an immediate postinfusion pemphigus exacerbation in 4 patients. LIMITATIONS: This was a retrospective study with a limited follow-up period. CONCLUSION: The rheumatoid arthritis dosage of rituximab was efficacious and well tolerated in patients with pemphigus. Patients who fail to achieve remission after 1 cycle or patients who relapse seem to benefit from repeated rituximab cycles.
21794814 [How does one manage patients with rheumatoid arthritis and positive serology to hepatitis 2011 May Chronic viral infections in rheumatic patients are a diagnostic and therapeutic challenge. Some of the disease-modifying antirheumatic drugs (DMARD) commonly used in rheumatoid arthritis, such as methotrexate and leflunomide, are hepatotoxic. With biological therapy, which is now widely used in patients refractory to these and other DMARD, some cases of reactivation of hepatitis B, even fulminant cases, have been reported, especially when employing TNF antagonists and rituximab, so their use must be carefully assessed and usually accompanied by antiviral therapy. However, there have not been reports of reactivation of hepatitis C after immunosuppressive therapy. In patients with HIV infection, administration of immunosuppressive therapy carries a high risk of opportunistic infections, although the new highly active antiviral therapy allows the use of some drugs in selected cases.