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ID PMID Title PublicationDate abstract
18050221 Safety and efficacy of additional courses of rituximab in patients with active rheumatoid 2007 Dec OBJECTIVE: To determine the safety and efficacy of additional courses of rituximab in patients with rheumatoid arthritis (RA). METHODS: An open-label extension analysis of RA patients previously treated with rituximab was conducted. Patients who had participated in any of 3 double-blind trials were eligible for additional courses (2 infusions of 1,000 mg given 2 weeks apart) if they exhibited a swollen joint count and tender joint count of > or =8 with > or =16 weeks elapsing after the previous course. Safety was assessed in patients receiving all or a portion of a rituximab course. Efficacy was assessed 24 weeks after each course, using the American College of Rheumatology 20% criteria for improvement (ACR20), ACR50, ACR70, European League Against Rheumatism (EULAR) response criteria, Disease Activity Score in 28 joints, the disability index of the Health Assessment Questionnaire, and Short Form 36 scores, stratified according to prior tumor necrosis factor (TNF) inhibitor exposure. RESULTS: A total of 1,039 patients received > or =1 course of rituximab. Of these, 570 received 2 courses, 191 received 3 courses, and 40 received 4 courses, for a total of 1,669 patient-years. Irrespective of prior TNF inhibitor exposure, ACR20 responses were comparable at week 24 after course 1 and at week 24 after course 2 (65% versus 72%), as were ACR50 and ACR70 responses. EULAR moderate/good responses were also comparable in course 2 relative to course 1 (88% versus 79%), with EULAR remission occurring in a 2-fold higher proportion of patients after course 2 than after course 1 (13% versus 6%). The most common adverse events, which were mild-to-moderate acute infusion-related events, decreased with each course. The serious infection rate after course 1 (5.1 per 100 patient-years) remained stable through additional courses. The proportion of patients with circulating IgM and IgG levels below the lower limit of normal (LLN) increased with subsequent courses; however, serious infection rates in these patients (5.6 per 100 patient-years in patients with low IgM levels and 4.8 per 100 patient-years in patients with low IgG levels were comparable with those in patients with immunoglobulin levels above the LLN (4.7 per 100 patient-years). Patients with human antichimeric antibody (9.2%) did not exhibit decreasing efficacy or present additional safety concerns. CONCLUSION: These findings indicate that patients treated with repeated courses of rituximab have sustained clinical responses with no new adverse events.
18714591 [Social costs of the most common inflammatory rheumatic diseases in Mexico from the patien 2008 May OBJECTIVE: To estimate the social costs of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and gout from the patient's perspective. METHODS: We carried out a cross-sectional analysis of the cost and resource utilization of 690 RA, AS, and gout patients from 10 medical centers and private facilities in five cities of Mexico. The information was obtained from the baseline of a dynamic cohort. We estimated out-of-pocket expenses, institutional direct costs, and direct medical costs. RESULTS: The mean (SD) annual out-of-pocket expense (USD) was $610.0 ($302.2) for RA, $578.6 ($220.5) for AS, and $245.3 ($124.0) for gout. Figures correspond to 15%, 9.6%, and 2.5% of the family income. They also represented 26.1%, 25.3%, and 24.4% of the total annual cost per RA, AS, and gout patients, respectively. The expected direct institutional patient/year costs were 1,724.2 for RA, $1,710.8 for AS, and $760.7 for gout. The total patient annual costs were $2,334.3 for RA, $2,289.4 for AS, and $1,006.1 for gout. Most out-of-pocket expenses were used to purchase drugs, pay for laboratory tests, imaging studies, and alternative therapies. CONCLUSIONS: From the patient's perspective, the cost of RA, AS, and gout represents 25% of direct medical costs. The cost of RA is higher than that for AS and gout.
17665462 Treatment of older adult patients diagnosed with rheumatoid arthritis: improved but not op 2007 Aug 15 OBJECTIVE: The National Committee on Quality Assurance has determined that all patients with rheumatoid arthritis (RA) should be treated with disease-modifying antirheumatic drugs (DMARDs). Our objective was to determine the rate and predictors of DMARD use in a cohort of elderly patients with RA. METHODS: We analyzed health care utilization data for 5,864 Medicare beneficiaries with RA who also participated in a state-run pharmaceutical benefit program in Pennsylvania. Patients with RA were defined as those with at least 3 diagnoses of RA (International Classification of Diseases, Ninth Revision code 714.xx) at least 1 week apart who were enrolled in these programs for at least 12 months during 1995-2004. Multivariate logistic regression was used to assess predictors of synthetic or biologic DMARD use in the 12 months after cohort entry. RESULTS: Thirty percent of patients filled a DMARD prescription during 12 months of followup. Frequency of DMARD use increased steadily over time: 24% received DMARDs in 1996 compared with 43% in 2003 (P for trend <0.001). Of patients with at least 1 rheumatologist visit, 41% received a DMARD in 1996 compared with 70% in 2003 (P < 0.001). After the introduction of biologic DMARDs in 1998, 6% of all patients with RA received a biologic, including 12% who saw a rheumatologist. Patients ages 75-84 were 52% less likely to receive DMARDs (95% confidence interval [95% CI] 46-58%) and patients ages >or=85 were 74% less likely (95% CI 69-79%) compared with patients ages 65-74. CONCLUSION: In this cohort of patients in the community with full prescription drug coverage, most patients diagnosed with RA did not receive a DMARD during the 12 months after cohort entry. Older patients and those not seeing a rheumatologist were less likely to receive a DMARD and may provide a target for quality improvement interventions.
18203324 Treatment of psoriatic arthritis and rheumatoid arthritis with disease modifying drugs -- 2008 Mar OBJECTIVE: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory diseases of the musculoskeletal system. Although it seems likely that these conditions have a different pathogenesis, the drugs used to treat them are the same. Our study used a cross-sectional clinical database to compare drug use and side-effect profile in these 2 diseases. METHODS: The CASPAR study collected data on 588 patients with PsA and 536 controls, 70% of whom had RA. Data on disease modifying drug treatments used over the whole illness were recorded, together with their outcomes, including adverse events, for RA and PsA. RESULTS: For both diseases methotrexate (MTX) was the most frequently used disease modifying drug (39% of patients with PsA, 30% with RA), with over 70% of patients in both diseases still taking the drug. Other drugs were used with the following frequencies in PsA and RA, respectively: sulfasalazine 22%/13%, gold salts 7%/11%, antimalarial drugs 5%/14%, corticosteroids 10%/17%, and anti-tumor necrosis factor (TNF) drugs 6%/5%. Compared to RA, cyclosporine and anti-TNF agents were less likely to be ineffective in PsA. Compared to RA, subjects with PsA were less likely to be taking MTX and more likely to be taking anti-TNF agents. Hepatotoxicity with MTX was more common in PsA and pulmonary toxicity with MTX was found more often in RA. CONCLUSION: These data provide insight into prescribing patterns of disease modifying drugs in RA and PsA in a large international cohort, together with the differential adverse events of these drugs between these diseases.
16391371 Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype. 2006 Jan 4 BACKGROUND: Some autoimmune and chronic inflammatory disorders are associated with increased risks of non-Hodgkin lymphoma (NHL). Because different NHL subtypes develop at different stages of lymphocyte differentiation, associations of autoimmune and inflammatory disorders with specific NHL subtypes could lead to a better understanding of lymphomagenic mechanisms. METHODS: In a population-based case-control study in Denmark and Sweden, 3055 NHL patients and 3187 matched control subjects were asked about their history of autoimmune and chronic inflammatory disorders, markers of severity, and treatment. Logistic regression with adjustment for study matching factors was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for NHL overall and for NHL subtypes. RESULTS: Risks of all NHL were increased in association with rheumatoid arthritis (OR = 1.5, 95% CI = 1.1 to 1.9), primary Sjögren syndrome (OR = 6.1, 95% CI = 1.4 to 27), systemic lupus erythematosus (OR = 4.6, 95% CI = 1.0 to 22), and celiac disease (OR = 2.1, 95% CI = 1.0 to 4.8). All of these conditions were also associated with diffuse large B-cell lymphoma, and some were associated with marginal zone, lymphoplasmacytic, or T-cell lymphoma. Ever use of nonsteroidal anti-inflammatory drugs, systemic corticosteroids, and selected immunosuppressants was associated with risk of NHL in rheumatoid arthritis patients but not in subjects without rheumatoid arthritis. Also, multivariable adjustment for treatment had little impact on risk estimates. Psoriasis, sarcoidosis, and inflammatory bowel disorders were not associated with increased risk of NHL overall or of any NHL subtype. CONCLUSIONS: Our results confirm the associations between certain autoimmune disorders and risk of NHL and suggest that the associations may not be general but rather mediated through specific NHL subtypes. These NHL subtypes develop during postantigen exposure stages of lymphocyte differentiation, consistent with a role of antigenic drive in autoimmunity-related lymphomagenesis.
18989816 Rearrangement of the JC virus regulatory region sequence in the bone marrow of a patient w 2008 Oct The polyomavirus JC (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy (PML). JCV remains quiescent in kidneys, where it displays a stable archetypal regulatory region (RR). Conversely, rearranged JCV RR, including tandem repeat patterns found in the central nervous system (CNS) of PML patients, have been associated with neurovirulence. The precise site and mechanism of JCV RR transformation is unknown. We present herein a patient with rheumatoid arthritis treated with methotrexate, who developed PML and had a rapid fatal outcome. JCV DNA polymerase chain reaction (PCR) was positive in cerebrospinal fluid (CSF), bone marrow, blood, and urine. Double-immunohistochemical staining demonstrated that 9% of bone marrow CD138(+) plasma cells sustained productive infection by JCV, accounting for 94% of JCV-infected cells. JCV RR analysis revealed archetype and rearranged RR forms in bone marrow, whereas RR with tandem repeat was predominant in blood. These results suggest that the bone marrow may be a potential site of JCV pathogenic transformation. Further studies will be needed to determine the prevalence of JCV in bone marrow of immunosuppressed individuals at risk of PML and characterize the RR and phenotype of these JCV isolates.
17763694 [A fatal case of pulmonary non-tuberculous mycobacteriosis with reactive AA amyloidosis]. 2007 Aug We report a very rare fatal case of reactive AA amyloidosis following pulmonary non-tuberculous mycobacteriosis (PNTM). A 61-year-old woman with a history of PNTM since 1992, whose treatment was difficult because of liver dysfunction and drug eruption caused by antibiotics, had been hospitalized due to recurrent pulmonary bacterial infection. She complained of leg edema in January, 2000, and nephrotic syndrome was diagnosed in February. After diarrhea and abdominal pain appeared in March, she was admitted to our hospital with worsening edema, and dizziness on April 28. Despite treatment, she died on May 5, 2000. Autopsy revealed PNTM and diffuse systemic depositions of amyloid A protein in heart, kidney and gastrointestinal tract. PNTM, often resistance to antibacterial agents, is increasing recently. This case suggests that it is necessary to take care of amyloidosis when various systemic symptoms are observed in chronic inflammatory disease.
16702221 SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum. 2006 Jul 21 CD44-hyaluronan (HA) interaction is involved in diverse physiological and pathological processes. Regulation of interacting avidity is well studied on CD44 but rarely on HA. We discovered a unique covalent modification of HA with a protein, SHAP, that corresponds to the heavy chains of inter-alpha-trypsin inhibitor family molecules circulating in blood. Formation of the SHAP.HA complex is often associated with inflammation, a well known process involving the CD44-HA interaction. We therefore examined the effect of SHAP on the CD44-HA interaction-mediated lymphocyte adhesion. Under both static and flowing conditions, Hut78 cells (CD44-positive) and CD44-transfected Jurkat cells (originally CD44-negative) adhered preferentially to the immobilized SHAP.HA complex than to HA. The enhanced adhesion is exclusively mediated by the CD44-HA interaction, because it was inhibited by HA, but not IalphaI, and was completely abolished by pretreating the cells with anti-CD44 antibodies. SHAP appears to potentiate the interaction by increasing the avidity of HA to CD44 and altering their distribution on cell surfaces. Large amounts of the SHAP.HA complex accumulate in the hyperplastic synovium of rheumatoid arthritis patients. Leukocytes infiltrated to the synovium were strongly positive for HA, SHAP, and CD44 on their surfaces, suggesting a role for the adhesion-enhancing effect of SHAP in pathogenesis.
18446062 IL-17 induces the production of IL-16 in rheumatoid arthritis. 2008 Apr 30 The purpose of this study was to investigate the expression of IL-16 in the rheumatoid synovium and the role of inflammatory cytokines and Toll-like receptor (TLR) ligands in IL-16 production by fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients. Immunohistochemical staining was performed with a monoclonal antibody to IL-16 in synovial tissues from patients with RA and likewise in patients with osteoarthritis (OA). FLS were isolated from RA synovial tissues and stimulated with IL-15, IL-1beta, IFN-gamma, and IL-17. The IL-16 mRNA level was assessed by semiquantitative RT-PCR and real time (RT) PCR and a comparison was made between IL-16 mRNA levels produced by RA-FLS and OA-FLS. Production of IL-16 was identified by a western blot assay, and IL-16 production after stimulation by specific ligands of TLR2 and TLR4 was assessed by RT-PCR. While immunohistochemical staining demonstrated strong expression of IL-16 mRNA in synovial tissues from patients with RA, similar findings were not present in the OA group. Moreover, mRNA expression of IL-16 by RA-FLS increased after treatment with IL-17 but not with IL-15, IL-1beta, and IFN-gamma. Specifically, IL-17 increased IL-16 mRNA level by RA-FLS and peripheral blood mononuclear cells in a dose-dependent manner. However, IL-17 did not stimulate IL-16 production in OA-FLS. Peptidoglycan, a selective TLR2 ligand, also increased production of IL-16 by RA-FLS dose- dependently, whereas LPS, a selective TLR4 ligand, had no such stimulatory effect. The results from our data demonstrate that IL-17 and TLR2 ligands stimulate the production of IL-16 by RA-FLS.
16211336 Successful retreatment with infliximab in patients with prior severe infusion reactions. 2006 Jul Infusion of the antitumor necrosis factor-alpha chimeric monoclonal antibody infliximab can be associated with the development of severe infusion reactions (IR) during retreatment. We present the case of two rheumatoid arthritis patients with a history of severe acute IR to infliximab who subsequently underwent successful infusion using a prophylactic treatment with a combination of H1 and H2 receptor blockers, hydrocortisone, and diphenhydramine.
17384180 Rituximab therapy in patients with resistant rheumatoid arthritis: real-life experience. 2007 Jun OBJECTIVES: Rituximab has recently been shown to be effective in suppressing disease activity in patients with rheumatoid arthritis (RA) who fail anti-TNF therapy. We present our experience of treating patients with long-standing, multi-DMARD and anti-TNF resistant RA with rituximab in 'real-life' setting. METHODS: Patients with RA resistant to more than two anti-TNF drugs and with persistent disease activity (DAS28 > 5.1) were considered for treatment with rituximab (two infusions 1000 mg each, a fortnight apart). DAS28 and HAQ scores were performed at baseline, 3 and 6 months post-treatment. Response to rituximab was defined as per the EULAR response criteria. Re-treatment with a second cycle of rituximab was offered if they had responded to the earlier one but flared. RESULTS: Twenty patients received rituximab. Median disease duration was 16 yrs (range 5-39) and 90% were rheumatoid factor positive. Median number of biologics received pre-treatment was two (range 2-4). Rituximab treatment led to a significant reduction in DAS28 score (P < 0.0001) at 3 months and various other disease parameters. The benefit was sustained at 6 months. Moderate-to-good EULAR response was seen in 85% of patients at 3 months and 60% at 6 months. No significant side effects were observed. 50% of the patients flared and received re-treatment. Interval to re-treatment varied from 6 to 18 months. The majority of the RA patients responded to re-treatment with rituximab and no major side effects were observed. CONCLUSION: Rituximab was effective in controlling disease activity in anti-TNF therapy resistant RA patients in 'real-life' setting. Rituximab was safe with no major side effects. Re-treatment with rituximab was safe and efficacy was maintained.
18050222 Immunohistochemical analysis as a means to predict responsiveness to rituximab treatment. 2007 Dec OBJECTIVE: Anti-CD20-mediated B cell depletion with rituximab is a new and effective therapy for rheumatoid arthritis (RA). Although B cells in peripheral blood (PB) are consistently depleted in all patients, the clinical effects are more heterogeneous, possibly related to differences in the depleting effects of lymphoid or solid tissues. The aim of this study was to investigate B cell depletion in different compartments (PB, bone marrow, and synovium) and determine predictive variables for responsiveness to rituximab therapy. METHODS: Before and 12 weeks after rituximab treatment, samples of PB, bone marrow, and synovium were collected from 25 patients with RA refractory to disease-modifying antirheumatic drugs and tumor necrosis factor-blocking agents. CD19+ and CD20+ B cells in PB and bone marrow were measured by flow cytometric analysis, whereas CD79a+ and cytoplasmic CD20+ B cells in the synovium were stained by immunohistochemistry. The effects of rituximab on serum Ig and autoantibodies were measured by enzyme-linked immunosorbent assay. RESULTS: Rituximab effectively depleted the CD20+ subset of B cells in the PB, bone marrow, and synovium of RA patients. Rituximab significantly reduced autoantibody production (anti-citrullinated protein antibodies [ACPAs] and rheumatoid factor [RF]), in part due to a nonspecific decrease in total Ig production. Importantly, positivity for circulating ACPA IgM, in combination with a high infiltration of CD79a+ B cells in the synovium, but not of CD138+ plasma cells, was a predictor of clinical outcome after rituximab treatment. ACPA IgM titers were independently associated with synovial infiltration of CD20-,CD79a+ B cells, but not with CD138+ plasma cells. CONCLUSION: These data provide novel insights into the mechanisms of CD20-mediated B cell depletion in the lymphoid and solid tissues of RA patients and suggest a pivotal role for ACPA IgM-producing plasmablasts in RA.
16879072 Evaluation of the analytical performance of the advanced method for cardiac troponin I for 2006 BACKGROUND: The determination of cardiac troponins is routinely used for rule in/out, risk stratification, and follow-up of patients with acute coronary artery syndrome. We evaluated the analytical and clinical performance of the advanced immunoassay for troponin I (cTnI) carried out on an AxSYM platform (Abbott Diagnostic Division) and compared these characteristics to those of the previous version of this assay and to cTnI on the Access 2 immunoassay system (Beckman Coulter, Inc.). METHODS: We assayed plasma samples from healthy subjects (n=66) and cardiac patients (n=132) using AxSYM Plus system assays called the old (OLD AxSYM) and advanced TnI (ADV AxSYM) methods and using an Access system. RESULTS: An improvement in analytical sensitivity (detection limit) was observed for the advanced cTnI AxSYM compared to the previous method (0.014 vs. 0.31 microg/L), while the cTnI value for the 10% CV (i.e., functional sensitivity) was 0.41 microg/L for the ADV and 1.9 microg/L for the OLD method. The kinetics of cTnI release was similar, as evaluated in 25 patients with typical acute myocardial infarction (AMI). A close linear relationship was found between the two methods on the AxSYM system (OLD cTnI=7.436+6.858 ADV cTnI; R=0.968, n=214) and with the Access system (OLD AxSYM=7.154+7.9 Access, R=0.876, n=158; ADV AxSYM=0.23+1.209 Access, R=0.927, n=160). However, wide bias was found between the OLD and ADV AxSYM methods (mean difference 118.4 microg/L, p<0.0001), while more similar results were found between the ADV AxSYM and Access methods (mean difference 2.6 microg/L, corresponding to a mean percentage difference of 17%, p<0.0001). In 106 patients with symptomatic rheumatoid arthritis with high rheumatoid factor (RF) concentration, the mean cTnI measured by the ADV AxSYM method was 0.009+/-0.031 mug/L (range 0-0.23 microg/L) with a significant correlation (R=0.316, p=0.001) between cTnI and RF values. Furthermore, in 60 of these serum samples the cTnI concentration was also measured using the Access method; significant correlation with the values found by the ADV AxSYM method was observed (R=0.468, p=0.0002). CONCLUSIONS: The present study indicates that the AxSYM Troponin-I ADV immunoassay shows improved analytical sensitivity compared to the OLD AxSYM method, as well as very similar clinical results to those determined using the Access method.
17056579 Characterization and functional consequences of underexpression of clusterin in rheumatoid 2006 Nov 1 We previously compared by microarray analysis gene expression in rheumatoid arthritis (RA) and osteoarthritis (OA) tissues. Among the set of genes identified as a molecular signature of RA, clusterin (clu) was one of the most differentially expressed. In the present study we sought to assess the expression and the role of CLU (mRNA and protein) in the affected joints and in cultured fibroblast-like synoviocytes (FLS) and to determine its functional role. Quantitative RT-PCR, Northern blot, in situ hybridization, immunohistochemistry, and Western blot were used to specify and quantify the expression of CLU in ex vivo synovial tissue. In synovial tissue, the protein was predominantly expressed by synoviocytes and it was detected in synovial fluids. Both full-length and spliced isoform CLU mRNA levels of expression were lower in RA tissues compared with OA and healthy synovium. In synovium and in cultured FLS, the overexpression of CLU concerned all protein isoforms in OA whereas in RA, the intracellular forms of the protein were barely detectable. Transgenic overexpression of CLU in RA FLS promoted apoptosis within 24 h. We observed that CLU knockdown with small interfering RNA promoted IL-6 and IL-8 production. CLU interacted with phosphorylated IkappaBalpha. Differential expression of CLU by OA and RA FLS appeared to be an intrinsic property of the cells. Expression of intracellular isoforms of CLU is differentially regulated between OA and RA. We propose that in RA joints, high levels of extracellular CLU and low expression of intracellular CLU may enhance NF-kappaB activation and survival of the synoviocytes.
17014006 Reduction of inflammatory biomarker response by abatacept in treatment of rheumatoid arthr 2006 Nov OBJECTIVE: Abatacept, a soluble selective costimulation modulator, selectively modulates T cell activation via the CD80/CD86:CD28 costimulation pathway. Data from a Phase II trial showed efficacy in patients with active rheumatoid arthritis (RA) and inadequate response to methotrexate when treated with abatacept (10 mg/kg or 2 mg/kg). To determine the mechanism of action of abatacept, we analyzed changes in the serum levels of inflammatory biomarkers in the patients enrolled in this trial. RESULTS: Following 12 months' treatment, serum levels of interleukin 6 (IL-6), soluble IL-2 receptor, C-reactive protein, soluble E-selectin, and soluble intercellular adhesion molecule-1 were significantly lower in patients receiving abatacept 10 mg/kg versus placebo. Smaller reductions in tumor necrosis factor-a and rheumatoid factor were also observed in the abatacept 10 mg/kg group compared with the placebo group. Although there was no evidence for efficacy of the 2 mg/kg dose, small reductions in inflammatory biomarkers at this dosage support the biologic effect of this therapy. CONCLUSION: These findings reveal the antiinflammatory and immunomodulatory effects of abatacept in patients with RA, and are consistent with the concept that modulating T cell activation improves clinical signs and symptoms and inhibits the progression of structural damage. These data suggest that selective modulation of the CD80/CD86:CD28 pathway with abatacept may affect several inflammatory cell types and cytokines that are involved in the proinflammatory cascade.
18534522 Risk factors for revision for early dislocation in total hip arthroplasty. 2008 Sep Risk factors were investigated for revision for dislocation in primary total hip arthroplasties (THAs) between September 1, 1999, and December 31, 2004, as reported by the Australian Orthopaedic Association National Joint Replacement Registry. For 65992 primary THAs, the only initial diagnoses with significantly increased relative risk (RR) of revision for dislocation compared to osteoarthritis were fractured neck of femur (RR, 2.03; P < .001), rheumatoid arthritis (RR, 2.01; P < .01), and avascular necrosis (RR, 1.57; P < .05). A total of 58109 primary THAs for osteoarthritis were investigated for effect of age group, sex, and fixation method. There were 428 (0.7%) revisions for dislocation, 369 (0.8%) with a cementless acetabulum, and 59 (0.6%) with cemented acetabulum (RR, 1.59; P < .01). There is a significantly increasing risk of revision for dislocation as head size decreases (P < .001). Cementless acetabula, particularly with smaller heads, have a higher rate of revision for dislocation.
17683577 Improvements in survival of the uncemented Nottingham Total Shoulder prosthesis: a prospec 2007 Aug 4 BACKGROUND: The uncemented Nottingham Total Shoulder Replacement prosthesis system (Nottingham TSR) was developed from the previous BioModular shoulder prosthesis taking into consideration the causes of the initial implant's failure. We investigated the impact of changes in the design of Nottingham TSR prosthesis on its survivorship rate. METHODS: Survivorship analyses of three types of uncemented total shoulder arthroplasty prostheses (BioModular, initial Nottingham TSR and current Nottingham TSR systems with 11, 8 and 4 year survivorship data respectively) were compared. All these prostheses were implanted for the treatment of disabling pain in the shoulder due to primary and secondary osteoarthritis or rheumatoid arthritis. Each type of the prosthesis studied was implanted in consecutive group of patients--90 patients with BioModular system, 103 with the initial Nottingham TSR and 34 patients with the current Nottingham TSR system. The comparison of the annual cumulative survivorship values in the compatible time range between the three groups was done according to the paired t test. RESULTS: The 8-year and 11-year survivorship rates for the initially used modified BioModular uncemented prosthesis were relatively low (75.6% and 71.7% respectively) comparing to the reported survivorship of the conventional cemented implants. The 8-year survivorship for the uncemented Nottingham TSR prosthesis was significantly higher (81.8%), but still not in the desired range of above 90%, that is found in other cemented designs. Glenoid component loosening was the main factor of prosthesis failure in both prostheses and mainly occurred in the first 4 postoperative years. The 4-year survivorship of the currently re-designed Nottingham TSR prosthesis, with hydroxylapatite coating of the glenoid baseplate, was significantly higher, 93.1% as compared to 85.1% of the previous Nottingham TSR. CONCLUSION: The initial Nottingham shoulder prosthesis showed significantly higher survivorship than the BioModular uncemented prosthesis, but lower than expected. Subsequently re-designed Nottingham TSR system presented a high short term survivorship rate that encourages its ongoing use.
16603583 Safety of anti-TNF-alpha therapy in rheumatoid arthritis and spondylarthropathies with con 2006 Oct OBJECTIVE: To assess the safety of anti-tumour necrosis factor (TNF)-alpha therapy in patients with rheumatoid arthritis (RA) or spondylarthropathies (SA) and concurrent chronic hepatitis B or C. METHODS: Records concerning 480 outpatients attending the Rheumatology Department of the University Hospital of Nice (France) for RA or SA were retrospectively reviewed for the duration of disease, treatment, serological status and biological data. RESULTS: Six relevant cases were identified: two of RA with chronic hepatitis B; one of SA with chronic hepatitis B and three of RA with chronic hepatitis C. Five patients had received etanercept and one infliximab; two had been given adalimumab after an unsuccessful trial of etanercept. Patients with concurrent chronic hepatitis B were also given lamivudine. In none of the cases had changes in serum aminotransferases or viral load been reported. CONCLUSION: The use of anti-TNF-alpha therapy (plus lamivudine in the presence of concurrent underlying hepatitis B viral infection) appeared to be safe in that it had no effect on serum aminotransferases and/or viral load. However, repeated monitoring is necessary throughout the treatment period.
17967723 Biological and clinical effects of anti-TNFalpha treatment. 2007 Nov Tumor necrosis factor alpha (TNFalpha) is implicated in the pathogenesis of many chronic inflammatory diseases such as rheumatoid arthritis (RA), psoriasis and psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease, ulcerative colitis and uveitis. The availability of new pharmacological agents (infliximab, etanercept, adalimumab), able to selectively block the TNFalpha, has recently offered new opportunity for the treatment of these diseases. TNFalpha antagonists are different in the mechanism of action and are all effective agents in the treatment of RA and several chronic inflammatory diseases as a large number of controlled clinical trials have shown. Among biological effects of TNFalpha antagonists, the production of autoantibodies has been emphasized. This phenomenon is not correlated with the disease background, since anti-nuclear antibodies (ANA) and anti-double stranded-DNA antibodies (anti-dsDNA) induction is observed in RA as well as in spondyloarthritis (SpA) patients. Nonetheless, recent studies had reported a significant reduction in the serum titre of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (anti-CCP) during anti-TNFalpha therapy. The TNFalpha antagonists represent a significant advance in the therapy of active RA and other chronic inflammatory diseases. However, they have distinct biological, clinical, and pharmacological properties that must be considered when selecting a drug for therapy.
17652100 Association analysis of functional variants of the FcgRIIa and FcgRIIIa genes with type 1 2007 Nov 1 FcgRIIa and FcgRIIIa are potent modulators of the immune system which bind (auto)antibodies and activate immune cells. The FcgRIIa*A519G and FcgRIIIa*A559C functional variants have been associated with several immune-related diseases. We studied FcgRIIa*A519G and FcgRIIIa*A559C SNPs in type 1 diabetes (T1D), celiac disease (CD) and rheumatoid arthritis (RA) patients and controls and included a meta-analysis of all recent studies of FcgRIIIa*A559C and RA. Our cohorts comprised 350 T1D, 519 CD, 639 RA patients and 1359 controls, who were genotyped for FcgRIIa*A519G and FcgRIIIa*A559C variants. Regression and expectation maximization (EM) algorithm-based haplotype analyses were used for the data analysis. We found significant differences in genotype frequencies of FcgRIIa between controls and patients with T1D (P = 0.04), CD (P = 0.000005) and RA (P = 0.04). The FcgRIIa*519GG genotype showed an increased risk for both T1D [odds ratio (OR) = 1.51; 95% confidence interval (95% CI) 1.08-2.12; P = 0.015] and CD (OR = 1.81; 95% CI 1.35-2.37; P = 0.000004), but not for RA. There was no difference in the frequency of FcgRIIIa*A559C genotypes or allelotypes between controls with T1D, CD and RA. We found that FcgRIIa and FcgRIIIa haplotype frequencies differed significantly between controls and patients with T1D (P = 0.05) and with CD (P = 0.00038) but not with RA. Our meta-analysis showed a significant 1.37(95% CI 1.14-1.66)-fold increased risk of RA for the FcgRIIIa*559CC (158VV) genotype (P = 0.001). This is the first report that the FcgRIIa*519GG genotype predisposes to T1D and CD. We confirmed that the FcgRIIIa*559CC genotype is associated with RA. If replicated, our findings would suggest FcgRIIa*519G as a common risk factor for auto-immune diseases. This may have clinical implications with regard to efficacy or safety of antibody-based immuno-modulator therapies.