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ID PMID Title PublicationDate abstract
16700418 [Correlation between different clinical activity and anti CC-P (anti-cyclic citrullinated 2006 Mar TNF-alpha role in RA is confirmed by the improvement on joint inflammation and physical function and by the slowing of radiographic damage induced by TNF-alpha blockers, that also reduce Rheumatoid Factor (RF) and anti-CC-P titres. (1) To evaluate the effects of 3 TNF-alpha blockers on (a) disability (HAQ), disease activity (DAS28), acute phase reactants (ERS, CRP); (b) autoantibodies: IgM RF, anti-CCP abs. (2) To evaluate if anti-CCP abs could be useful for testing the efficacy of anti-TNF-alpha agents in the follow-up of RA patients. 34 patients with RA (25 F, 9 M; mean age: 59.1 +/- 12.1 years, mean disease duration: 9.6 +/- 2.3 years; 23/34 positive for anti-CCP abs, 19/34 for IgM RF) were enrolled: 18 received Etanercept (25 mg twice weekly subcutaneously), 8 received Infliximab (3 mg/kg intravenously every 8 weeks) and 8 Adalimumab (40 mg every 14 days). All the patients were evaluated for the above mentioned parameters at baseline (t0) and after 6 months of therapy (t6). Anti-TNF-alpha agents differently reduced HAQ and DAS28, ERS and CRP, RF and anti-CCP ab titres RA patients whose RF (14) and/or anti-CCP abs (17) titres were significantly lowered at the end of the study, at t6 presented a significant reduction in respect to t0 of VES, PCR, DAS28 and HAQ values (p < 0.05 for all comparison). This effect was not shown in patients in whose RF (5) and/or anti-CCP abs (6) titres were not reduced in respect to baseline. In RA, anti-TNF-alpha agents, especially Etanercept, reduce disability, disease activity and acute phase reactants expecially in patients showing reduction of RF and anti CC-P titres.
16690341 Cardiovascular risk and rheumatoid arthritis: clinical practice guidelines based on publis 2006 Jul OBJECTIVE: To develop clinical practice guidelines for the evaluation and management of cardiovascular risk in patients with rheumatoid arthritis (RA), using the evidence-based approach and expert opinion. METHODS: Recommendations were developed using the evidence-based approach and expert opinion: A scientific committee used a Delphi procedure to select five questions, which formed the basis for developing the recommendations; Evidence providing answers to the five questions was sought in the literature; Based on this evidence, recommendations were developed by a panel of experts. RESULTS: The recommendations were as follows: 1) In patients with RA, attention should be given to the risk of cardiovascular disease, which is responsible for an excess burden of morbidity and mortality; 2) It must be recognized that RA may be an independent cardiovascular risk factor. Persistent inflammation is an additional risk factor; 3) The cardiovascular risk should be evaluated, and modifiable risk factors should be corrected; 4) In patients with RA requiring glucocorticoid therapy, the need for cardiovascular risk minimization is among the reasons that mandate the use of the minimal effective dose; 5) It should be recognized that methotrexate may protect against cardiovascular mortality in patients with RA; 6) It should be recognized that TNFalpha antagonists remain contraindicated in patients with RA and severe heart failure. TNFalpha antagonists do not seem to worsen moderate heart failure and may protect against cardiovascular mortality; 7) AFSSAPS recommendations about LDL-cholesterol objectives should be followed, with active RA being counted as a cardiovascular risk factor; 8) In patients with RA, statin therapy should be considered only when cholesterol levels are elevated despite appropriate dietary treatment; 9) RA per se does not indicate aspirin for primary prevention. When aspirin is used for secondary prevention, it should be recognized that concomitant treatment with nonsteroidal antiinflammatory drugs (NSAIDs) may decrease the antiplatelet effects and increase the gastrointestinal side effects of aspirin therapy.
16958637 Etanercept in severe active rheumatoid arthritis: first Australian experience. 2006 Oct BACKGROUND: Etanercept reduces disease activity in adults with chronic rheumatoid arthritis (RA) who are resistant to other therapies. Medicare Australia Pharmaceutical Benefit Scheme subsidized treatment (since August 2003) restricts etanercept availability to a most drug-resistant RA population. The aim of the study was to assess the efficacy of etanercept in this unique group after 12 months of therapy. METHODS: A prospective study of the first 50 consecutive private practice, adult RA patients whom were commenced on etanercept. The primary efficacy measures included short form 36 scores, Disease Activity Score 28, American College of Rheumatology (ACR) response improvement in per cent and the ACR individual core set components at baseline, 3 and 12 months. Analysis was by intention to treat. RESULTS: There was significant improvement in all mean short form 36 component scores (P < 0.05) and all ACR core set component scores (P < 0.05) comparing 12 months to baseline. The disease activity score 28 also significantly fell from baseline at both 3 and 12 months (P < 0.05). The ACR 20% response significantly improved (P < 0.05) both at baseline to 3 months 92% (81.2, 96.9) and to 12 months 80% (67.0, 88.8). Serious adverse events occurred in 16%. At 12 months 88% completed treatment. CONCLUSION: Etanercept therapy will, by 3 and 12 months, significantly improve the short form 36, disease activity score 28, ACR 20% response and core set components. Our results are similar to international studies using etanercept in efficacy and tolerance despite our cohort being more resistant to preceding drug therapy. Etanercept offers this unique active severe refractory late RA Australian population a new therapeutic option to control their disease.
16465609 Rheumatoid arthritis: a disease of chronic, low-amplitude signals transduced through T cel 2006 Jan Technology has advanced to the stage where it is now possible to identify genes that confer low to moderate risk of developing autoimmune diseases such as rheumatoid arthritis (RA). This has been facilitated by the growing appreciation that these hard to detect genetic signals can only be defined in large cohorts of well characterized patients. In RA, the association between disease susceptibility and genes encoded within the MHC has been known for decades. Recent studies have identified several new candidate genes that provide further insights into the molecular nature of aberrant immune responses in chronic inflammatory diseases. Here, we describe some of these new genes. Based on their known functions we propose that in a subgroup of patients with RA inheritance of allelic variants at distinct loci could lead to dysregulation of adaptive immune responses characterized by chronic, low-amplitude signaling transduced by antigen T cell receptors.
18260176 The risk of hospitalized infection in patients with rheumatoid arthritis. 2008 Mar OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) are at increased risk of hospitalized infection and whether the risk varies by RA treatment. METHODS: A retrospective cohort study was conducted using data from a medical and pharmacy claims managed-care database from 1999 to 2006. A total of 24,530 patients were included in the RA cohort; a random sample of non-RA patients served as a comparison cohort (n = 500,000). Rates of hospitalized infection were compared between the cohorts. A nested case-control analysis was performed within the RA cohort to assess the effect of current RA medication use on hospitalized infection risk. RESULTS: A total of 1,993 patients with RA and 11,977 non-RA patients experienced a hospitalized infection. The rate of first hospitalized infection was higher in the RA cohort [adjusted hazard ratio = 2.03; 95% confidence interval (CI) 1.93-2.13]. In the case-control analysis, the current use of biological disease modifying antirheumatic drugs (DMARD) was associated with slightly increased risk of hospitalized infection [rate ratio (RR) = 1.21; 95% CI 1.02-1.43]. Methotrexate and hydroxychloroquine were associated with decreased risk. Oral corticosteroid use increased risk (RR = 1.92; 95% CI 1.67-2.21), and there was a dose-related effect [< or = 5 mg/day: RR = 1.32 (95% CI 1.06-1.63), 6-10 mg/day: RR = 1.94 (95% CI 1.53-2.46), > 10 mg/day: RR = 2.98 (95% CI 2.41-3.69)]. CONCLUSION: These data confirm that individuals with RA are at increased risk of hospitalized infection compared to those without RA. Oral corticosteroid use was associated with a dose-related increase. Biological DMARD use was associated with slightly elevated risk; however, this may reflect confounding and channeling bias.
17509810 [Radiological characteristics of the lumbar spine in patients with rheumatoid arthritis]. 2007 Oct AIM: The aim of this study was to assess the prevalence and severity of lumbar lesions on radiography of patients with rheumatoid arthritis (RA) and of population controls and to study the correlation between lumbar lesions and RA severity. METHODS: RA patients who met the revised American College of Rheumatology criteria were matched with population controls for age, sex, and the presence (or absence) of low back pain. Thoracolumbar radiographs were read by two observers looking for vertebral fractures, disc space narrowing, endplate erosion, facet joint involvement, and osteophytosis. A severity score was assigned to each lesion. RESULTS: This study included 60 RA patients and 60 controls, matched for sex (54 women and 6 men in each group) and age (mean age was 47.8+/-14 years in the RA group and 48.4+/-14 years in the control group). Prevalence of lumbar lesions was 83% in RA patients and 85% in the control subjects (p=0.8). Vertebral fractures were significantly more frequent in RA patients (p=0.042). In the RA group, disc space narrowing and the severity of endplate erosion were both correlated with higher Larsen grades (p=0.02 and 0.007 respectively), and the severity of endplate erosion was correlated with coxitis (p=0.03). DISCUSSION: In our study, radiological lumbar lesions, except for vertebral fractures, were no more common among RA patients than among population controls. Endplate erosion and vertebral disc destruction were correlated with RA severity scores.
18677577 Ghrelin and obestatin levels in rheumatoid arthritis. 2008 Oct BACKGROUND: Ghrelin is a powerful, endogenous orexigenic peptide. In addition, ghrelin has anti-inflammatory effects, and it has been reported that ghrelin down-regulates pro-inflammatory cytokines, including interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Obestatin appears to decrease food intake and appetite, and its potential role in inflammation is not yet clear. The aims of this study were to assess total and acylated (active) ghrelin and obestatin serum levels and their relations with inflammatory status in rheumatoid arthritis (RA) patients. DESIGN: Fasting blood samples were obtained from 37 patients with RA, 29 patients with Behçet's disease (BD) and 28 healthy controls (HC). Total ghrelin and obestatin levels were measured by radioimmunoassay and acylated ghrelin was quantified by enzyme-linked immunosorbent assay. RESULTS: Patients with RA had lower total ghrelin, but higher obestatin levels than patients with BD (p<0.05 for both), but when compared with HC group differences were not significant. There was no difference across groups in terms of acylated ghrelin. Total ghrelin level was not correlated with any study parameters in the all groups. Obestatin level correlated with erythrocyte sedimentation rate and DAS-28 in the RA group, the level of IL-6 in the BD group, and with the level of TNF-alpha in the HC group (r=0.400, p<0.05; r=0.412, p<0.05, r=0.543, p<0.01 and r=0.528, p<0.05, respectively). CONCLUSIONS: Our results did not show a significant correlation between circulating ghrelin and clinical or laboratory markers of disease activity in RA. Surprisingly, obestatin correlated with some inflammatory markers. So, obestatin seems to be more valuable than ghrelin in the pathogenesis of RA.
17054845 [Risk factor assessment of cardiocerebrovascular diseases in patients with rheumatoid arth 2006 Jul 4 OBJECTIVE: To assess the prevalence of cardiocerebrovascular diseases (CCVDs) in the patients with rheumatoid arthritis (RA) and analyzed the risk factors. METHODS: The clinical data of 568 RA patients hospitalized 1995 - 2005, were analyzed retrospectively. RESULTS: (1) The total prevalence of CCVD was 16.2% (92/568). The prevalence rate of coronary heart disease, cerebrovascular disease, hypertensive heart disease together with coronary heart disease including 2 cases of heart failure, atherogenesis in large and medium-size arteries proved by color Doppler ultrasonic examination, and gangrene of extremities were 53.26% (49/92), 22.83% (21/92), 13.04% (12/92), 6.52% (6/92), and 4.34% (4/92) respectively. (2) Complication of CCVD in RA patients was associated with age, DAS28 disease activity score, number of involved extra-articular organs, platelet count, hyperfibrinogenemia, and C-reactive protein; and was not associated with sex, auto-antibody, hereditary factor, other traditional CCBVD risk factors, and the number of risk factors. (3) The occurrence of CCVD in RA patients was significantly correlated with poor therapeutic response, lack of persistent effective prevention of the traditional risk factors, use of cyclooxygenase (Cox)-2 specific inhibitors, and long-term medication of high-dosage glucocorticoid. CONCLUSION: Activity of the disease of RA, high inflammatory index, extra-articular involvement, poor response to treatment, lack of persistent effective prevention of the traditional risk factors, use of Cox-2 specific inhibitor, and long-term medication of high-dosage glucocorticoid are risk factors of CCVD-co-morbidities in RA pate.
16358366 Etanercept in combination with sulfasalazine, hydroxychloroquine, or gold in the treatment 2006 Feb OBJECTIVE: To prospectively determine the efficacy and safety of etanercept in combination with sulfasalazine (SSZ), hydroxychloroquine (HCQ), and gold in the treatment of rheumatoid arthritis (RA). METHODS: A prospective open-label study enrolled 119 patients with RA who had active disease despite stable therapy with SSZ (n = 50), HCQ (n = 50), or intramuscular gold (n = 19). Primary efficacy endpoints consisted of American College of Rheumatology responses at 24 and 48 weeks. Safety was established at regularly scheduled visits. RESULTS: Patients in each etanercept combination showed significant improvement at both 24 and 48 weeks. Toxicity withdrawals by 48 weeks included gold (n = 1): proteinuria; HCQ (n = 5): septic wrist and bilateral pneumonia, rash, optic neuritis, breast cancer, squamous cancer of the tongue; and SSZ (n = 5): otitis media, elevated liver function indicators, pericarditis, rash, and gastroenteritis. The most common adverse events not requiring discontinuation from the study were injection site reactions (43% of patients) and upper respiratory type infections (34%). CONCLUSION: This study is the first to prospectively evaluate the safety of etanercept in combination with SSZ, HCQ, and gold in patients with RA. Etanercept in combination with SSZ, HCQ, or gold was efficacious and well tolerated, with a discontinuation rate of 9% (11/119) for adverse events at 48 weeks.
18535644 Outpatient follow-up for patients with rheumatoid arthritis in relation to New Zealand Rhe 2008 May 23 AIM: Current treatment for rheumatoid arthritis (RA) involves the use of various disease-modifying anti-rheumatic drugs (DMARDs) and biologic response agents which require ongoing medical supervision. An audit was undertaken to assess the adequacy of outpatient specialist follow-up for supervision of treatment in patients with RA in the Otago region. METHODS: The Rheumatology Service database was used to assess time between follow-up for the penultimate and last visit to rheumatology outpatient clinic for all patients who made at least two visits between 1 October 2001 and 30 September 2006. Other recorded data included demographic information and clinician expectations for the timing of the next outpatient visit. Comparisons were made between actual follow-up intervals, those indicated by specialists and the follow-up intervals recommended by the New Zealand Rheumatology Association Guidelines. Patients were characterised according to four groups specified in the guidelines: Group A: patients newly started on DMARDs; Group B: patients with some change in disease management: Group C: patient stable on potent medications: Group D: patients stable on less severe medication. RESULTS: According to the guidelines only 40% of patients were followed up within the recommended intervals. Groups A and B (76.9% and 70.6% respectively) had a significantly greater proportion of patients with follow-up at variance to guideline recommendations compared to groups C and D (50% and 45.3% respectively) (p<0.001). There were marked discrepancies between the guideline recommended follow-up intervals and those suggested by the clinicians. Compared with guideline recommendations clinicians advised less frequent follow-up for groups A and B but more frequent for patients in Groups C and D. However, an assessment of the quality of life scores amongst the patients suggested that follow-up was still appropriately targeted to those patients with lower quality of life. CONCLUSION: Discrepancies in follow-up were most marked in the patient groups potentially most at risk of medication-related problems in whom guidelines suggested more intensive monitoring. Additional strategies to promote guideline-based follow-up arrangements may be indicated. Further work should examine the relationships between guideline recommended, physician intended and actual follow-up among rheumatology patients in other regions in order to assess whether modifications should occur to clinician behaviour or guideline content.
18180278 The Mal/TIRAP S180L and TLR4 G299D polymorphisms are not associated with susceptibility to 2008 Sep BACKGROUND: Toll-like receptors (TLRs), including TLR4, have been implicated in the pathogenesis of rheumatoid arthritis (RA). Signalling by these receptors involves interactions with intracellular proteins, including the MyD88 adapter-like (Mal) protein. Recently, a polymorphism (Mal S180L) has been described which contributes to susceptibility to common infectious diseases and inhibits proinflammatory cytokine production. A non-synonymous variant in the extracellular domain of TLR4 (G299D) has been shown to interrupt TLR4-mediated signalling, resulting in endotoxin hyporesponsiveness. OBJECTIVE: To investigate the role of TLR4 G299D and Mal S180L variants in RA. METHODS: A total of 964 Caucasians with RA and 965 controls were genotyped. Deviation from Hardy-Weinberg equilibrium was tested for each single nucleotide polymorphism in cases and controls separately using a chi(2) test with a threshold of p<0.05. The odd ratios were calculated with asymptotic 95% confidence intervals, and p values <0.05 were considered significant. Epistasis was assessed using both stratified analysis and the linkage disequilibrium-based statistic. RESULTS: Mal S180L genotypes were similar in cases and controls (OR = 0.9, 95% CI 0.7 to 1.0, p = 0.2). Similarly, no difference for TLR4 G299D genotypes was seen (OR = 1.7, 95% CI 0.3 to 11.1, p = 0.5). No association with either rheumatoid factor or anti-cyclic citrullinated peptide status or with radiological damage was detected. Finally, no evidence of epistasis was detected between Mal S180L and TLR4 G299D and RA susceptibility. CONCLUSIONS: The Mal S180L and TLR4 G299D polymorphisms do not contribute to RA susceptibility or severity either individually or in combination.
16758511 Cost-effectiveness analysis of MTHFR polymorphism screening by polymerase chain reaction i 2006 Jul OBJECTIVE: To determine whether a strategy based on methylenetetrahydrofolate reductase (MTHFR) genotype screening is more cost-effective than the conventional strategy in reducing the risk of methotrexate (MTX)-related toxicity in patients with rheumatoid arthritis (RA). METHODS: We consecutively enrolled 385 patients with RA (355 female, 30 male) who had received MTX and identified toxicity associated with MTHFR C677T genotypes. We designed a hypothetical decision model to compare the genotype-based strategy with the conventional strategy. The time horizon was set as 1 year, and direct medical costs were used. The measured outcomes were the total expected cost, the effectiveness, and the incremental cost-effectiveness ratio. RESULTS: MTHFR genotype distribution revealed 133 patients (34.6%) with 677CC, 193 (50.1%) with 677CT, and 59 (15.3%) with 677TT. A total of 154 patients (40.0%) exhibited MTX-related toxicity. Compared to RA patients with the CC genotype, the odds ratio (95% confidence interval) for risk of toxicity was 3.8 (2.29-6.33) for the CT genotype, and 4.7 (2.40-9.04) for the TT genotype. In the base-case model, the total expected cost and the probability of continuing MTX medication for the conventional and genotype-based strategies were 851,415 Korean won (710 US dollars) and 788,664 Korean won (658 US dollars), and 94.03% and 95.58%, respectively. CONCLUSION: The MTHFR C677T polymorphism may be an important predictor of MTX-related toxicity in patients with RA. The cost-effectiveness analysis suggests that the genotype-based strategy is both less costly and more effective than the conventional strategy for MTX therapy.
19641502 BH3-only proteins in rheumatoid arthritis: potential targets for therapeutic intervention. 2008 Dec Rheumatoid arthritis (RA) is a debilitating disease, resulting in the destruction of bone and cartilage, and in the permanent disfigurement of joints. Although the precise cause of RA is currently unresolved, it has become clear that the damaging effects are a result of the toxic milieu caused by an influx of inflammatory cells and the resulting heightened proinflammatory state within the joint. As the amount of literature suggesting that this preponderance of cells is a result of decreased local apoptosis in the joint continues to increase, in this review, we describe how Bcl-2 family pro-apoptotic BH3-only proteins, particularly Bim and Bid, could act to protect against the development of the disease. We also suggest a role for BH3-mimetic drugs as potential therapeutics in the treatment of RA.
17059600 Gaining insight into the Clinical Practice Guideline development processes: qualitative st 2006 Oct 23 BACKGROUND: The GRADE method represents a new approach to grading the quality of evidence and strength of recommendations in the preparation of Clinical Practice Guidelines (CPG). In the context of a pilot study to assess the implementability of the system in Spain, we considered it relevant to gain an insight into the significance of the perceptions and attitudes expressed by the actual experts participating in the system try-out. METHODS: Qualitative research with an ethnographic approach, through non-participant observation and focus groups within the context of a consensus workshop in which 19 CPG experts participated to evaluate the GRADE proposal using 12 evidence tables taken from hypertension, asthma and arthritis CPGs. The interventions were recorded, under a guarantee of confidentiality. The transcriptions and field notes were analyzed, based on a sociological discourse analysis model, and the provisional findings were re-sent to participants in order to improve their validity. RESULTS: 1) Certain problems over procedure and terminology hindered the acceptance of this new method as a common reference system for the preparation of CPGs. 2) A greater closeness to clinical practice was accompanied by concerns over value judgments and subjectivity, with a demand for greater explicitness in the consensus process. 3) The type of "evidence" on which the guidelines are based, how and by whom the evidence is prepared, and what the role of the different actors should be, all constitute unresolved concerns in the CPG preparation and implementation processes. 4) The grading process is not neutral: professional background, prior experience and the degree of leadership all condition the participants' input and interactions. CONCLUSION: The findings obtained allow the quantitative evaluation to be better interpreted and, in turn, go beyond the particularities of the GRADE method. Adaptation to the complexities of clinical practice, the need for carefully designed multi-disciplinary work and the reflexivity present in the CPG preparation process, all represent lines of debate that are necessary to improve the CPG quality in the Spanish health care sector.
17684748 Partial remission of refractory RA after Adacolumn cytapheresis: a case report. 2008 Jan We report on a female case of rheumatoid arthritis (RA) with hepatitis C virus comorbidity. The patient was treated once weekly over ten consecutive weeks with Adacolumn device. Clinical assessment and HCV-RNA concentration were monitored at weeks-1, 4, 9, 14 and during follow-up over 6 months. At the end of the treatment: the number of tender and swollen joints, patient's global assessment of disease activity (VAS), physician's VAS, C-reactive protein (CRP) decreased, respectively; ACR response was >20. This improvement was maintained for over 2 months. At week 38, the patient was re-treated achieving again an ACR response >20.
17485422 Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (S 2007 Sep OBJECTIVE: To evaluate the ability of tocilizumab (a humanised anti-IL-6 receptor antibody) monotherapy to inhibit progression of structural joint damage in patients with RA. METHODS: In a multi-centre, x ray reader-blinded, randomised, controlled trial, 306 patients with active RA of <5 years' duration were allocated to receive either tocilizumab monotherapy at 8 mg/kg intravenously every 4 weeks or conventional disease-modifying antirheumatic drugs (DMARDs) for 52 weeks. Radiographs of hands and forefeet were scored by the van der Heijde modified Sharp method. RESULTS: Patients had a mean disease duration of 2.3 years and a disease activity score in 28 joints of 6.5 at baseline. Mean total modified Sharp score (TSS) was 29.4, which was very high despite the relatively short disease duration. At week 52, the tocilizumab group showed statistically significantly less radiographic change in TSS (mean 2.3; 95% CI 1.5 to 3.2) than the DMARD group (mean 6.1; 95% CI 4.2 to 8.0; p<0.01). Tocilizumab monotherapy also improved signs and symptoms. The overall incidences of AEs were 89% and 82% (serious AEs: 18% and 13%; serious infections: 7.6% and 4.1%) in the tocilizumab and DMARD groups, respectively. CONCLUSION: Tocilizumab monotherapy was generally well tolerated and provided radiographic benefit in patients with RA.
18397961 Involvement of a disintegrin and a metalloproteinase 8 (ADAM8) in osteoclastogenesis and p 2009 Mar OBJECTIVES: The eventual role of a disintegrin and a metalloproteinase 8 (ADAM8) in osteoclastogenesis was studied in erosive rheumatoid arthritis (RA) and in vitro. METHODS: ADAM8 protein and mRNA expression was measured in RA pannus and synovitis and compared to osteoarthritic (OA) synovial membrane. Human monocytes were isolated and stimulated with proinflammatory cytokines and their ADAM8 expression and surface ADAM8 were measured. Human peripheral blood monocytes and RAW 264.7 mouse monocyte/macrophage cells were stimulated to osteclast like-cells, and their expression of ADAM8 and osteoclastic markers (calcitonin receptor, integrin beta 3, cathepsin K, TRAP) were analysed. Transfection and small interfering RNA (siRNA) were used to assess the role of ADAM8 in formation of polykaryons. RESULTS: Increased numbers of ADAM8 positive cells were shown particularly in the pannus-cartilage/bone junction close or adjoining to TRAP positive multinucleate cells under formation (60 (2)% in pannus, 47 (2)% in synovitis vs 10 (1)% in OA, p<0.001). Human pannus contained high ADAM8 mRNA copy numbers (23 (7) in pannus, 14 (4) in synovitis vs 1.7 (0.3) in OA, p<0.001). Functional studies in vitro disclosed ADAM8 mRNA and protein, which was first converted to a proteolytically active and then to fusion-active form. Gene transfection and siRNA experiments enhanced and inhibited, respectively, expression of osteoclast markers and maturation of multinuclear cells. CONCLUSIONS: ADAM8 may be involved in bone destruction in RA because it is upregulated in RA pannus adjacent to developing erosions and enhances maturation of osteoclast-like cells.
18759292 Remission and rheumatoid arthritis: data on patients receiving usual care in twenty-four c 2008 Sep OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >or=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.
19024266 [Proposal for anti-TNFalpha therapy in adult patients with rheumatoid arthritis]. 2008 Rheumatoid arthritis is a chronic, inflammatory disease with the prevalence about 1%. Rheumatoid arthritis is caracterized with synovitis, erosive changes of the joints, pain and functional deficit. Etiology is unknown. In the pathogenesis of rheumatoid arthritis the key role have proinflammatory citokines, particularly, tumour necrosis factor (TNFalpha). TNFalpha blockers have documented, fast and continuous efficacy with generally well accepted safety profile. Nowdays, TNFalpha antagonists are established drugs in early and late phase of rheumatoid arthritis. Prescription of TNFalpha antagonists is controlled, according local restrictions, regarding high costs of the therapy. On behalf of Croatian Society for Rheumatology we propose recommendations for the TNFalpha antagonist therapy in rheumatoid arthritis.
17478470 Long-term infliximab treatment in rheumatoid arthritis: subsequent outcome of initial resp 2007 Jul OBJECTIVE: Patients may cease therapy with anti-tumour necrosis factor (TNF) agents due to inefficacy at 12 weeks (termed primary non-response) or later. Until now, the extent of this later secondary non-response has not been clearly defined. We followed-up a substantial single-centre cohort to determine kinetics of this secondary loss of response. The licensed dose of 3 mg/kg was used throughout. METHODS: Prospective data collection since anti-TNF therapy introduction in 1999 formed the basis of the analysis. Patients with rheumatoid arthritis who received infliximab as their first biologic agent, with at least 2 yrs follow-up were included. All relevant clinical data to calculate DAS-28 score and EULAR response were collected at 3, 6, 9, 12, 18 and 24 months. Reasons for cessation in those patients achieving a EULAR response at 3 months (secondary failures) were determined. RESULTS: Of a total of 309 patients commenced on infliximab, 290 received this as their first biologic agent.; 195 commenced > or = 2 yrs ago. Efficacy data to identify EULAR responders at 3 months was available in 174 patients. Sixty-seven per cent achieved a 'moderate' or 'good' EULAR response; 25% failed to achieve a response, 8% developed toxicity within the first 12 weeks. Of the primary responders, over 55% subsequently ceased therapy in the first year, the predominant reason was a secondary loss of response; other reasons included high disease activity despite achieving a definable response, toxicity, and intercurrent illness. Subsequent loss of response in the second year was less pronounced. CONCLUSIONS: This study of patients treated in clinical practice with infliximab demonstrated that secondary non-response occurred in around half the patients in the first year. The data highlight the need to continue development of other therapies as well as investigation of the underlying causes of this loss of response.