Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
17531512 Polyethylene insert exchange for wear after total shoulder arthroplasty. 2007 Sep Virtually no information is available in the literature to guide clinical decision-making in regard to modular polyethylene exchange with metal-backed glenoid components in total shoulder arthroplasty for the indication of polyethylene wear. This level IV study reports our experience with exchange of the modular polyethylene glenoid component during revision total shoulder arthroplasty. We retrospectively identified 12 shoulders in 11 patients who underwent exchange of the modular polyethylene glenoid component during revision arthroplasty. The primary reason for revision arthroplasty with polyethylene exchange was wear-through or displacement of the polyethylene portion of the glenoid component, but rotator cuff tearing and instability often coexisted. The average follow-up from time of revision to latest evaluation or repeat revision arthroplasty was 68 months. Preoperative pain was a mean of 4.5 (range, 4-5), and postoperative pain was a mean of 2.6 (range, 1-5). Preoperative average active forward elevation was 93 degrees, and external rotation was 51 degrees. Postoperative active forward elevation was 89 degrees, and external rotation was 64 degrees. Average patient satisfaction was rated as the same. According to the modified Neer rating system, 4 shoulders (33%) had a satisfactory result, and 8 (62%) had an unsatisfactory result. Polyethylene exchange of glenoid component after total shoulder arthroplasty can be an effective treatment option in patients who do not have coexistent rotator cuff tear or instability. For most, instability, rotator cuff tear, and glenoid wear occur together, and this is a challenging problem to treat successfully.
18846409 Isolated polyethylene exchange versus acetabular revision for polyethylene wear. 2009 Jan Polyethylene wear and osteolysis are not uncommon in THA mid- and long-term. In asymptomatic patients the dilemma faced by the orthopaedic surgeon is whether to revise the cup and risk damage to the supporting columns and even pelvic discontinuity or to perform isolated polyethylene exchange and risk a high rate of postoperative recurrent instability and dislocation that will necessitate further surgery. We retrospectively reviewed 62 patients (67 hips) who underwent revision arthroplasty for polywear and osteolysis. Thirty-six hips had isolated polyethylene exchange, while 31 had full acetabular revision. The minimum followup was 2 years (mean, 2.8 years; range, 2-5 years). Three of 36 hips with a retained cup grafted through the cup holes failed within 5 years due to acetabular loosening. One of 31 hips with full revision underwent re-revision for aseptic cup loosening at 5 months postoperatively. Although we do not recommend prophylactic revision of all cups for polywear and osteolysis, the patient may be warned of the possibility of an approximate 10% failure rate when retaining the acetabular component. We do, however, advocate cup extraction in the following situations: damage to the locking mechanism, erosion of the femoral head through the liner and into the cup damaging the metal, and a malpositioned component that may jeopardize the stability of the revision. LEVEL OF EVIDENCE: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
19066890 Total knee replacement in the fixed valgus deformity using a lateral approach: role of the 2009 Dec The purpose of this work was to document eleven years of experience in knee replacement for fixed knee valgus through a lateral approach with special emphasis on the balancing procedures. At a mean follow-up of seven years, only one revision for sepsis was required in this series of 63 knee replacements. The mean knee score improved from 37 (range 20-45) to 91 (range 65-100) at the last review (p < 0.01) while the function score increased from 29.5 (range 0-50) to 78.7 (range 10-100) (p = 0.01). The mean mechanical axis (HKA) was 14.7 degrees of valgus preoperatively and 1 degrees of valgus postoperatively. After the iliotibial band was automatically released in the approach, only four of 63 knees required additional release for tightness in extension. These results underline the appeal of the lateral approach with the automatic release of the iliotibial band. If required, additional ligament release is recommended step-by-step after bone section to avoid postoperative instability.
17266078 Barriers in the management of glucocorticoid-induced osteoporosis. 2007 Feb 15 OBJECTIVE: To determine present practice for the management of glucocorticoid-induced osteoporosis (GIOP) in veterans; to characterize provider knowledge, beliefs, and practice behaviors regarding management of GIOP; and to identify potential barriers and interventions in the management of GIOP. METHODS: To characterize current management of GIOP in an academic veterans administration medical center, we conducted a retrospective chart review of 100 patients who were prescribed a 90-day supply of prednisone. To assess clinicians' knowledge of GIOP clinical guidelines and perceptions of GIOP management, primary care clinicians and subspecialists completed a questionnaire and participated in focus groups. RESULTS: Chart review revealed that only 32 of 100 patients receiving long-term glucocorticoid treatment underwent bone mineral density testing, and only 32 patients were prescribed the recommended calcium supplements. Of the 23 providers who completed the questionnaire and participated in the focus groups, 4 correctly identified both the dose and duration of glucocorticoid use at which GIOP prevention measures should be instituted. Common GIOP management barriers cited by participants were lack of knowledge, having limited time during the clinic visit to address all problems, patient nonadherence, and system problems. The most commonly mentioned potential interventions were the use of computerized clinical reminders and patient education. CONCLUSION: Clinicians frequently do not follow recommended guidelines for the management of GIOP. Improving the management of GIOP will likely require a fundamental redesigning of care processes for this disorder in order to overcome provider, patient-related, and system barriers.
17360386 Modification of nuclear PML protein by SUMO-1 regulates Fas-induced apoptosis in rheumatoi 2007 Mar 20 The small ubiquitin-like modifier (SUMO)-1 is an important posttranslational regulator of different signaling pathways and involved in the formation of promyelocytic leukemia (PML) protein nuclear bodies (NBs). Overexpression of SUMO-1 has been associated with alterations in apoptosis, but the underlying mechanisms and their relevance for human diseases are not clear. Here, we show that the increased expression of SUMO-1 in rheumatoid arthritis (RA) synovial fibroblasts (SFs) contributes to the resistance of these cells against Fas-induced apoptosis through increased SUMOylation of nuclear PML protein and increased recruitment of the transcriptional repressor DAXX to PML NBs. We also show that the nuclear SUMO-protease SENP1, which is found at lower levels in RA SFs, can revert the apoptosis-inhibiting effects of SUMO-1 by releasing DAXX from PML NBs. Our findings indicate that in RA SFs overexpression of SENP1 can alter the SUMO-1-mediated recruitment of DAXX to PML NBs, thus influencing the proapoptotic effects of DAXX. Accumulation of DAXX in PML NBs by SUMO-1 may, therefore, contribute to the pathogenesis of inflammatory disorders.
17631740 Complication rates of 127 surgical procedures performed in rheumatic patients receiving tu 2007 May OBJECTIVE: Tumor necrosis factor (TNF) blockers have been reported to increase the risk of infections, thrombosis, and delayed healing. However, there is little data on the risk of complications after surgery in rheumatic patients receiving TNF blockers. The aim of this study was to assess the complication rate after surgery in such patients, to assess the effect of interrupting TNF blocker therapy, and to identify other potential predictors of complications. METHODS: This was a systematic, retrospective monocenter study of all patients treated with TNF blockers and who underwent surgery. Complications were recorded and complication rates were compared based on the type of surgery and the timing of the discontinuation of TNF blockers before surgery (above 2 or 5 half-lives). The complication rates were compared with those reported in the literature (orthopaedic procedures in RA patients: 7%, abdominal surgery: 13%). RESULTS: Between 1997 and 2004, 770 patients were treated with TNF blockers of whom 92 underwent surgery (127 surgical procedures). The most frequent underlying disease was rheumatoid arthritis (77%). Most of the surgical procedures were orthopaedic (85%). The complication rates for orthopaedic procedures and for abdominal procedures were 13% and 43%, respectively. The infection rate after orthopaedic procedures was 6.5%. Interrupting therapy before surgery did not significantly decrease the postoperative complication risk. There were no independent factors predicting complications. CONCLUSION: In daily practice the complication rate after surgery is high in patients treated with TNF blockers. Discontinuing TNF therapy before surgery should be considered, although this study did not clearly demonstrate its role.
19080985 [Introduction to biological drugs]. 2008 Jul Biological therapies have revolutionized the treatment of chronic systemic diseases in which the immune system disorders form a part of the disease mechanism. In these diseases, the patients follow different drug treatments for long periods of time that causes serious adverse reactions and often obtain unsatisfactory efficacy results. Due to the research conducted in the last 10 years, biological drugs have been introduced into the treatment that are aimed against specific targets, such as inflammatory and immunopathological responses that give rise to tissue injury. The new biological therapies have improved the currently available treatments due to greater efficacy, fast action and greater tolerability. The present work aims to provide a global and up-dated view on the biological agents used most in the usual clinical practice and their importance in the management of the chronic immunologically based inflammatory diseases.
18508588 The modulatory capacity of interleukin-21 in the pathogenesis of autoimmune disease. 2008 May 1 In this review, we discuss recent progress from studies on the biology of IL-21 and the role of this cytokine in the pathogenesis of autoimmunity. Recent studies have demonstrated that IL-21 plays an important and non-redundant role in a number of autoimmune animal models indicating that IL-21 could be a common modulator of the adaptive immune response towards self-tissue constituents in diseases such as systemic lupus erythematosus, models of rheumatoid arthritis, multiple sclerosis and type-1 diabetes. Also, the studies on the production of IL-21 in human autoimmune diseases and its behaviour on human cells in vitro are revealing the potential of IL-21 to exacerbate cellular processes that determine the course of autoimmune diseases.
19061612 Erythema elevatum diutinum. 2008 Oct 15 A 64-year-old woman presented with a one-and-one-half year history of an enlarging, red-brown, firm plaque on the left thigh, with numerous, scattered, indurated, hyperpigmented patches on the lower extremities. Histopathologic examination of the largest plaque confirmed the diagnosis of erythema elevatum diutinum, which is a rare form of leukocytoclastic vasculitis that is associated with many disease entities, which include human immunodeficiency virus infection, malignant conditions, hematologic abnormalities, chronic infection, and autoimmune and connective-tissue disorders. The treatment of choice is dapsone; however, several other treatment modalities have been reported to be of benefit.
16698443 How NKG2D ligands trigger autoimmunity? 2006 Mar The function of NK and CD8 T cells in the elimination of infected, transformed, or stressed cells occurs together with tolerance to self, a property that is essential to prevent autoimmunity. Inappropriate expression of NK receptor ligands, leading to activation of autoreactive effector cells, might therefore trigger or exacerbate autoimmunity. We review here some recent data on the activating receptor NKG2D and its MIC ligand, which are indicative of their detrimental roles in some autoimmune disorders.
17392348 Imbalance in distribution of functional autologous regulatory T cells in rheumatoid arthri 2007 Sep OBJECTIVES: Regulatory T cells (Tregs) exert their anti-inflammatory activity predominantly by cell contact-dependent mechanisms. A study was undertaken to investigate the regulatory capacity of autologous peripheral blood Tregs in contact with synovial tissue cell cultures, and to evaluate their presence in peripheral blood, synovial tissue and synovial fluid of patients with rheumatoid arthritis (RA). METHODS: 44 patients with RA and 5 with osteoarthritis were included in the study. The frequency of interferon (IFN)gamma-secreting cells was quantified in synovial tissue cell cultures, CD3-depleted synovial tissue cell cultures, synovial tissue cultures co-cultured with autologous CD4+ and with CD4+CD25+ peripheral blood T cells by ELISPOT. Total CD3+, Th1 polarised and Tregs were quantified by real-time PCR for CD3epsilon, T-bet and FoxP3 mRNA, and by immunohistochemistry for FoxP3 protein. RESULTS: RA synovial tissue cell cultures exhibited spontaneous expression of IFNgamma which was abrogated by depletion of CD3+ T cells and specifically reduced by co-culture with autologous peripheral blood Treg. The presence of Treg in RA synovitis was indicated by FoxP3 mRNA expression and confirmed by immunohistochemistry. The amount of FoxP3 transcripts, however, was lower in the synovial membrane than in peripheral blood or synovial fluid. The T-bet/FoxP3 ratio correlated with both a higher grade of synovial tissue lymphocyte infiltration and higher disease activity. CONCLUSION: This study has shown, for the first time in human RA, the efficacy of autologous Tregs in reducing the inflammatory activity of synovial tissue cell cultures ex vivo, while in the synovium FoxP3+ Tregs of patients with RA are reduced compared with peripheral blood and synovial fluid. This local imbalance of Th1 and Treg may be responsible for repeated rheumatic flares and thus will be of interest as a target for future treatments.
16806997 The cleavage of biglycan by aggrecanases. 2006 Nov OBJECTIVE: Aggrecanase-1 [a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4] and aggrecanase-2 (ADAMTS-5) have been named for their ability to degrade the proteoglycan aggrecan. While this may be the preferred substrate for these enzymes, they are also able to degrade other proteins. The aim of this work was to determine whether the aggrecanases could degrade biglycan and decorin. METHODS: Biglycan, decorin and aggrecan were purified from human and bovine cartilage and subjected to degradation by recombinant aggrecanase-1 or aggrecanase-2. In vitro degradation was assessed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) and immunoblotting, and the cleavage site in biglycan was determined by N-terminal amino acid sequencing. SDS/PAGE and immunoblotting were also used to assess in situ degradation in both normal and arthritic human articular cartilage. RESULTS: Both aggrecanase-1 and aggrecanase-2 are able to cleave bovine and human biglycan at a site within their central leucine-rich repeat regions. Cleavage occurs at an asparagine-cysteine bond within the fifth leucine-rich repeat. In contrast, the closely related proteoglycan decorin is not a substrate for the aggrecanases. Analysis of human articular cartilage from osteoarthritic (OA) and rheumatoid arthritic (RA) joints showed that a biglycan degradation product of equivalent size is present in the extracellular matrix. No equivalent degradation product was, however, detectable in normal adult human articular cartilage. CONCLUSION: Biglycan, which is structurally unrelated to aggrecan, can act as a substrate for aggrecanase-1 and aggrecanase-2, and these proteinases may account for at least part of the biglycan degradation that is present in arthritic cartilage.
18703528 IgG1 and IgG4 are the predominant subclasses among auto-antibodies against two citrullinat 2008 Oct OBJECTIVE: Antibody subclasses reflect specific immunological processes and may be indicative of the underlying pathological pattern in an autoimmune disease like RA. We therefore quantified anti-cyclic citrullinated peptides (CCP) and anti- citrullinated vimentin (MCV) IgG subclass titres in RA patients and compared them with the respective titres of antibodies directed against the varicella zoster virus (VZV) and to total serum titres. METHODS: Sera of 77 patients fulfilling the ACR criteria for RA were collected. An IgG subclass-specific ELISA system was then established and combined with commercially available MCV, CCP and VZV pre-coated microtitre plates. RESULTS: Even though IgG1 is the predominant subclass among antibodies against CCP and MCV in RA patients, IgG4 is second with respect to titres and frequencies. This increase in IgG4 among RA-specific antibodies is independent of disease duration and does not reflect a general skewing of the immune response in these patients as overall serum titres and antibodies directed against VZV show a normal distribution of IgG1, IgG2, IgG3 and IgG4. CONCLUSION: Elevated IgG4 titres are specific for auto-antibodies against citrullinated antigens in RA and are indicative of a Th2-biased environment during the generation of auto-reactive plasma cells. We discuss here an indirect role for IgG4 auto-antibodies in hindering the elimination of auto-reactive B and plasma cells and thus driving the autoimmune process.
18584044 Increased responsiveness to toll-like receptor 4 stimulation in peripheral blood mononucle 2008 BACKGROUND: Cell signaling via Toll-like receptors (TLRs) leads to synovial inflammation in rheumatoid arthritis (RA). We aimed to assess effects of TLR2 and TLR4 stimulation on proinflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from patients with recent-onset RA, osteoarthrosis (OA), and healthy control (HC). METHODS: PBMCs were stimulated with LPS, biglycan and cytokine mix. Cytokines were analyzed in supernatants with ELISA. Expression of toll-like receptors mRNA in leukocytes was analyzed using real-time qPCR. RESULTS: PBMCs from RA patients spontaneously produced less IL-6 and TNFalpha than cells from OA and HC subjects. LPS increased cytokines' production in all groups. In RA patients increase was dramatic (30 to 48-fold and 17 to 31-fold, for respective cytokines) compared to moderate (2 to 8-fold) in other groups. LPS induced 15-HETE generation in PBMCs from RA (mean 251%) and OA patients (mean 43%), although only in OA group, the increase was significant. TLR2 and TLR4 gene expressions decreased in response to cytokine mix, while LPS enhanced TLR2 expression in HC and depressed TLR4 expression in OA patients. CONCLUSION: PBMCs from recent-onset RA patients are overresponsive to stimulation with bacterial lipopolysaccharide. TLR expression is differentially regulated in healthy and arthritic subjects.
17618693 Investigation of the functional characteristics of antibodies to therapeutic anti-human tu 2007 Aug 15 Humanized antibody-based treatment modalities represent an active area of investigation. Included in these strategies are passive administrations of monoclonal antibodies, which recognize tumor necrosis factor alpha (TNF-alpha). However, several problems associated with these types of treatment strategies have been reported in the literature. We attempted to address the issue related to unresponsiveness to infliximab that might be induced by anti-idiotype response to the passively administered humanized monoclonal antibody. The characteristics and functional importance of antibodies to infliximab (ATI) were investigated in human sera. We studied the binding characteristics of ATI to infliximab, TNF-alpha Receptor-I (RI, p55) and Receptor-II (RII, p75). In addition, cytotoxicity effect on L929 cells and blocking effects on the binding of TNF-alpha with infliximab and etanercept were also analyzed. On the basis of the results obtained from the experiments, it seems that the target epitope for ATI is related with somewhere else not residing in the region capable of generating "mirror image". The results presented indicate that ATI does not mimic the functional characteristics of TNF-alpha. However, ATI inhibited the binding properties of infliximab to TNF-alpha.
17437169 Inositol 1,4,5-trisphosphate receptors are autoantibody target antigens in patients with S 2007 IP(3)R2 and IP(3)R3 double knock-out mice present with exocrine dysfunctions such as secretion deficits of saliva and pancreatic juice. Therefore, we investigated whether the presence of antibodies to IP(3)Rs could be found in patients with Sjögren's syndrome, and the location of the epitopes. Subjects included 35 primary Sjögren's syndrome, 39 secondary Sjögren's syndrome, 144 rheumatoid arthritis, and 96 other connective tissue disease patients. As controls, 33 healthy subjects were included. Immunoblot was conducted using recombinant proteins IP(3)R1, IP(3)R2, and IP(3)R3 made from full-length cDNA, and core, T604, and EL for epitope mapping. Antibodies to IP(3)R1 in sera from patients with primary Sjögren's syndrome, secondary Sjögren's syndrome, and rheumatoid arthritis were found to be positive in 17 of 35 (48.6%), 13 of 39 (33%), and 34 of 124 (27.4%) cases, respectively. These frequencies were significantly higher than the 1 of 33 (3.0%) found in normal healthy subjects. The frequency of anti-IP(3)R2 antibodies in rheumatoid arthritis was found to be higher than those found in Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Anti-IP(3)R2 antibodies found in rheumatoid arthritis primarily recognized residues 578-2171 of the internal coupling and regulatory domain. On the other hand, anti-IP(3)R1 found in Sjögren's syndrome recognized residues 224-604 of the core protein IP(3)R1. Anti-IP(3)R1 antibodies were present in 48.6% of primary Sjögren's syndrome and in 3.0% of normal healthy subjects. Anti-IP(3)R2 antibodies were detected most frequently in rheumatoid arthritis. Locations of the antigenic epitopes were found to differ among the disease conditions.
17585753 Acridone-based inhibitors of inosine 5'-monophosphate dehydrogenase: discovery and SAR lea 2007 Jul 26 Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5'-monophosphate to xanthosine-5'-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.
18304941 Treatment response to a second or third TNF-inhibitor in RA: results from the South Swedis 2008 Apr OBJECTIVES: To study treatment response rates of RA patients undergoing second- and third-line anti-TNF therapy and to identify baseline predictors of response to second-line treatment. METHODS: RA patients monitored in a prospective, observational study, having switched anti-TNF therapy once (first-time switchers, n = 337) or twice (second-time switchers, n = 36)--i.e. following failures with one antibody- and one receptor-type agent--between March 1999 and December 2006, were studied. Treatment responses at 3 months were assessed by the ACR and European League Against Rheumatism (EULAR) response criteria. Predictive potentials for response to second-line treatment of demographics, baseline disease activity measures, disease and treatment characteristics were analysed using logistic regression. RESULTS: ACR20 response was met by 51% of first-time and 35% of second-time switchers. Corresponding ACR50 rates were 27 and 18%; EULAR overall rates (EULAR good or moderate response) 71 and 58%; EULAR good rates 25 and 9% and 28-joint disease activity score (DAS28) remission rates 16 and 6%. Identified baseline predictors of response to second-line treatment were lower age and HAQ scores, elevated DAS28 values and having ceased the former anti-TNF treatment due to adverse events rather than inefficacy. No variable was predictive for all examined response criteria. CONCLUSIONS: Response rates of first-time anti-TNF switchers are somewhat below those of anti-TNF naïve RA patients, while the markedly inferior response rates of second-time switchers suggest other therapeutic options to be considered in this situation. Identified baseline predictors of response may be useful indicators to second-line anti-TNF therapy, but vary depending on the response criteria set studied.
17328715 The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantatio 2007 Apr Uncommitted (naive) murine CD4+ T helper cells (Thp) can be induced to differentiate towards T helper 1 (Th1), Th2, Th17 and regulatory (Treg) phenotypes according to the local cytokine milieu. This can be demonstrated most readily both in vitro and in vivo in murine CD4+ T cells. The presence of interleukin (IL)-12 [signalling through signal transduction and activator of transcription (STAT)-4] skews towards Th1, IL-4 (signalling through STAT-6) towards Th2, transforming growth factor (TGF)-beta towards Treg and IL-6 and TGF-beta towards Th17. The committed cells are characterized by expression of specific transcription factors, T-bet for Th1, GATA-3 for Th2, forkhead box P3 (FoxP3) for Tregs and RORgammat for Th17 cells. Recently, it has been demonstrated that the skewing of murine Thp towards Th17 and Treg is mutually exclusive. Although human Thp can also be skewed towards Th1 and Th2 phenotypes there is as yet no direct evidence for the existence of discrete Th17 cells in humans nor of mutually antagonistic development of Th17 cells and Tregs. There is considerable evidence, however, both in humans and in mice for the importance of interferon (IFN)-gamma and IL-17 in the development and progression of inflammatory and autoimmune diseases (AD). Unexpectedly, some models of autoimmunity thought traditionally to be solely Th1-dependent have been demonstrated subsequently to have a non-redundant requirement for Th17 cells, notably experimental allergic encephalomyelitis and collagen-induced arthritis. In contrast, Tregs have anti-inflammatory properties and can cause quiescence of autoimmune diseases and prolongation of transplant function. As a result, it can be proposed that skewing of responses towards Th17 or Th1 and away from Treg may be responsible for the development and/or progression of AD or acute transplant rejection in humans. Blocking critical cytokines in vivo, notably IL-6, may result in a shift from a Th17 towards a regulatory phenotype and induce quiescence of AD or prevent transplant rejection. In this paper we review Th17/IL-17 and Treg biology and expand on this hypothesis.
16507128 Switching TNF antagonists in patients with chronic arthritis: an observational study of 48 2006 The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34-0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97-2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13-4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications.