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ID PMID Title PublicationDate abstract
12110143 The paradigm of IL-6: from basic science to medicine. 2002 IL-6 is a pleiotropic cytokine with a wide range of biological activities in immune regulation, hematopoiesis, inflammation, and oncogenesis. Its activities are shared by IL-6-related cytokines such as leukemia inhibitory factor and oncostatin M. The pleiotropy and redundancy of IL-6 functions have been identified by using a unique receptor system comprising two functional proteins: an IL-6 receptor (IL-6R) and gp130, the common signal transducer of cytokines related to IL-6. Signal transduction through gp130 is mediated by two pathways: the JAK-STAT (Janus family tyrosine kinase-signal transducer and activator of transcription) pathway and the Ras mitogen-activated protein kinase pathway. The negative regulators of IL-6 signaling have also been identified, although the physiological roles of the molecules are not yet fully understood. The pathological roles of IL-6 have also been clarified in various disease conditions, such as inflammatory, autoimmune, and malignant diseases. On the basis of the findings, a new therapeutic approach to block the IL-6 signal using humanized anti-IL-6R antibody for rheumatoid arthritis, Castleman's disease, and multiple myeloma has been attempted.
14640907 Pathophysiological roles for IL-18 in inflammatory arthritis. 2003 Dec IL-18 is a unique cytokine with prominently wide spectrum biological actions. Among these, its IFN-gamma/TNF-alpha-inducing activity primarily contributes to the development of various inflammatory diseases including inflammatory arthritis. IL-18 levels correlate with the disease activity of rheumatoid arthritis (RA) and osteoarthritis (OA). IL-18 is spontaneously released from RA synovial cells and OA chondrocytes and seems to participate in the development of the inflammatory and destructive alterations of joints via induction of TNF-alpha, a potent effector molecule. TNF-alpha, in turn, increases IL-18 expression in RA synovial cells. Recent clinical trials have revealed the efficacy of TNF-alpha in RA with a reduction in circulatory IL-18 levels. These may implicate the positive circuit between IL-18 and TNF-alpha for development of RA. As IL-18-deficient mice evade collagen-induced arthritis in a mouse RA model, therapeutics targeting IL-18 may be beneficial against RA/OA. Here, the authors review the possible roles of IL-18 in inflammatory arthritis.
14994384 Tumor necrosis factor-alpha promotes the expression of osteoprotegerin in rheumatoid synov 2004 Mar OBJECTIVE: To clarify the regulation of osteoprotegerin (OPG) expression in rheumatoid synovial fibroblasts by investigating the effect of tumor necrosis factor-alpha (TNF-alpha) and the mechanism of TNF-alpha-induced OPG expression. METHODS: OPG expression was examined by Northern blot hybridization and reverse transcriptase-polymerase chain reaction in synovial fibroblasts from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and subjects with no inflammatory condition. Amounts of OPG in conditioned medium were determined by ELISA. The effect of OPG on TNF-alpha-induced osteoclastogenesis was investigated in primary cultures of RA synovial cells. RESULTS: OPG was highly expressed in RA synovial fibroblasts compared to OA and noninflammatory synovial fibroblasts. Different levels of OPG expression were found among patients with RA. TNF-alpha induced OPG expression in all synovial fibroblasts, even OA and noninflammatory fibroblasts, and expression occurred to a remarkable degree in RA fibroblasts. The OPG expression was upregulated by TNF-alpha in a time- and dose-dependent manner. TNF-alpha-induced OPG expression was inhibited by hymenialdisine, a nuclear factor-kappaB inhibitor, in a dose-dependent manner, and expression was inhibited by soluble TNF receptor/Fc fusion protein I (TNFs-RI/Fc), not by TNFs-RII/Fc. In contrast, TNF-alpha-induced osteoclastogenesis in primary cultures of RA synovial cells was inhibited by the addition of OPG. CONCLUSION: These results suggest that OPG is highly expressed and is upregulated by TNF-alpha in rheumatoid synovial fibroblasts. TNF-alpha-induced OPG expression is mediated predominantly through TNF-RI. Although TNF-alpha is known to stimulate bone destruction, TNF-alpha-induced upregulation of OPG may contribute to self-protection from the bone destruction in RA.
15228617 Does route of administration affect the outcome of TNF antagonist therapy? 2004 The tumor necrosis factor (TNF) antagonists are parenterally administered biologic response modifiers indicated for the management of rheumatoid arthritis. Although infliximab, etanercept, and adalimumab are all members of this class, they differ in route of administration and dosing regimen. In the USA and in Europe, infliximab, in combination with oral methotrexate, is administered intravenously, initially at a dose of 3 mg/kg at weeks 0, 2, and 6, then every 8 weeks thereafter. The US Food and Drug Administration (FDA) has further approved that the dosage can be increased to 10 mg/kg and the doses can be given as often as every 4 weeks to optimize patient outcome (information based on the US package insert dated June 2002). Etanercept and adalimumab are given subcutaneously and can be self-injected. The FDA-approved dose of etanercept is 25 mg twice weekly, and of adalimumab is 40 mg every 2 weeks with methotrexate, or 40 mg alone. Medication adherence, possibly the most important factor in maintaining the benefits of anti-TNF therapy, is influenced by the interaction between the patient and his or her healthcare team, the patient's attitude toward the disease and medication regimen, and the choice of therapy.
12745961 The Canadian Occupational Performance Measure as an outcome measure and team tool in a day 2003 May 20 PURPOSE: To investigate the usefulness of the Canadian Occupational Performance Measure (COPM) in a day treatment programme for clients with rheumatoid arthritis. METHOD: The study was conducted in two parts. In the first part rehabilitation without changes in the programme was performed (n = 16). After that the COPM was introduced to all team members. In part two the COPM was used (n = 40). Clients' experiences of participation in the process were studied via a structured interview 2 - 4 weeks after discharge in both parts. Qualitative interviews were conducted with team members before part one and after completion of part two. RESULTS: Staff expressed that the COPM improved client participation in the rehabilitation process. Goals were formulated distinctly, and focused on activity and performance rather than function. Team conferences were focused on the client's needs. Outcome was considered clear and evident to the client. The changes in client routines demands thorough introduction, support and involvement, and takes time. Involvement and motivation for changing practice were difficult to obtain, this could be a result of a large staff turnover during the data collection period. CONCLUSIONS: The COPM should be seen as an aid to ensuring client participation in the goal formulation process, and facilitating treatment planning and evaluation of outcome.
12784389 All-cause mortality and vascular events among patients with rheumatoid arthritis, osteoart 2003 Jun OBJECTIVE: To compare all-cause mortality rates and the incidence of major vascular events among patients with rheumatoid arthritis (RA), osteoarthritis (OA) without RA, or no arthritis using the UK General Practice Research Database (GPRD) while adjusting for age and sex. Clinic-based studies have found that patients with RA have higher all-cause and cardiovascular (CV) mortality than those without RA, after adjusting for age and sex. Much smaller elevations in risk have been found in the few community-based studies that have addressed this question. METHODS: After excluding patients with a history of myocardial infarction or cerebrovascular events, we followed a retrospective cohort of patients 40 years and older from GPRD practices until the earliest of death, disenrollment, or the occurrence of an incident vascular event. Using Poisson regression we compared age and gender adjusted incidence rates for RA, OA, or no arthritis. RESULTS: Five hundred and ninety-four practices contributed 2.37 million patients (1.11 million men and 1.26 million women) to the analysis. Over a mean duration of followup of almost 5 years, age and gender adjusted all-cause mortality rates were 60 to 70% higher in patients with RA compared to patients with OA and those with no arthritis. For the various vascular endpoints, the age and gender adjusted incidence rates were 30 to 60% higher in patients with RA compared to both patients with OA and those with no arthritis during the study period. The rates in patients with OA and those with no arthritis were essentially the same. CONCLUSION: Compared to patients with OA and those with no arthritis, patients with RA had a higher age and gender adjusted incidence of all-cause mortality and of major vascular events during almost 5 years of followup.
11922200 Pulmonary miliary tuberculosis in a patient with anti-TNF-alpha treatment. 2002 No difference in the number of serious adverse events was reported in previous clinical trials in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) patients treated with TNF-alpha blockade, but a patient died because of disseminated tuberculosis. A tuberculosis reactivation in a patient with IBD and anti-TNF-alpha treatment has been recently reported. Very recently 70 cases of tuberculosis were reported from the FDA Adverse Event Reporting System. We report a case of pulmonary miliary tuberculosis in a RA patient treated with TNF-alpha blockade. The important role of TNF-alpha in defence against tuberculosis and possible mechanisms of anti-TNF-alpha agents impairing tuberculosis immune response are discussed.
12021312 CD8 T cells are required for the formation of ectopic germinal centers in rheumatoid synov 2002 May 20 The assembly of inflammatory lesions in rheumatoid arthritis is highly regulated and typically leads to the formation of lymphoid follicles with germinal center (GC) reactions. We used microdissection of such extranodal follicles to analyze the colonizing T cells. Although the repertoire of follicular T cells was diverse, a subset of T cell receptor (TCR) sequences was detected in multiple independent follicles and not in interfollicular zones, suggesting recognition of a common antigen. Unexpectedly, the majority of shared TCR sequences were from CD8 T cells that were highly enriched in the synovium and present in low numbers in the periphery. To examine their role in extranodal GC reactions, CD8 T cells were depleted in human synovium-SCID mouse chimeras. Depletion of synovial CD8 T cells caused disintegration of the GC-containing follicles. In the absence of CD8 T cells, follicular dendritic cells disappeared, production of lymphotoxin-alpha1beta2 markedly decreased, and immunoglobulin (Ig) secretion ceased. Immunohistochemical studies demonstrated that these CD8 T cells accumulated at the edge of the mantle zone. Besides their unique localization, they were characterized by the production of interferon (IFN)-gamma, lack of the pore-forming enzyme perforin, and expression of CD40 ligand. Perifollicular IFN-gamma+ CD8 T cells were rare in secondary lymphoid tissues but accounted for the majority of IFN-gamma+ cells in synovial infiltrates. We propose that CD8+ T cells regulate the structural integrity and functional activity of GCs in ectopic lymphoid follicles.
14760788 A web-compatible instrument for measuring self-reported disease activity in arthritis. 2004 Feb OBJECTIVE: To describe a Web-based computer health assessment survey for patients with rheumatoid arthritis (RA) and to evaluate the survey in comparison with current paper versions. METHODS: Utilizing data from a study on RA, we compared results from 43 patients attending a university-based clinic who were each given a paper and a demonstration computer version of a patient self-assessment questionnaire including multiple-choice questions from a multi-dimensional Health Assessment Questionnaire (HAQ); visual analog scales (VAS) for pain, fatigue, and global disease severity; and a tender and swollen joint count reporting tool. Patients were given optional followup surveys to determine their opinion of the computer program. RESULTS: High correlations (intraclass correlation coefficient > 0.9) were seen across methods for the 10-item HAQ and psychological distress scores and the VAS scores for pain and global disease severity. Moderate correlation was observed for the self-efficacy scores, the VAS scores for fatigue, and tender joint counts. The data also revealed a small shift in the mean scores for the HAQ and self-efficacy questions, with patients reporting slightly higher scores on the computer instrument. Overall, patient opinions of the uniquely designed joint count tool were good, with 71% of responding patients answering favorably. CONCLUSION: Web-based computer versions of patient self-assessment surveys in RA are comparable to paper versions, and their use in clinics or over the Internet could dramatically facilitate the ability of physicians to monitor patients' health.
12428223 Long-term safety and maintenance of clinical improvement following treatment with anakinra 2002 Nov OBJECTIVE: To demonstrate the long-term efficacy of anakinra, a human recombinant interleukin-1 receptor antagonist, in patients with rheumatoid arthritis (RA), and to assess the long-term safety of anakinra at different daily doses. METHODS: The efficacy and safety of anakinra were previously demonstrated in a double-blind, placebo-controlled, 24-week evaluation in 472 patients with active RA. Of 345 patients who completed the placebo-controlled phase of the study, 309 continued in a 52-week, multicenter, double-blind, parallel-group extension phase of the study. Patients received subcutaneous injections of anakinra (30, 75, or 150 mg) once daily. Efficacy was assessed among the 309 patients for the first 24 weeks of the extension phase (48 weeks total therapy), using the American College of Rheumatology composite score (ACR20), its components, and radiographs of the hands and wrists. Safety was assessed in all 472 patients over the entire 52-week extension phase (76 weeks total exposure). RESULTS: A total of 218 patients completed the extension phase. Of the 91 patients who withdrew prematurely, 46 did so following adverse events, and 26 withdrew because of lack of efficacy. Among patients receiving anakinra who entered the extension phase, the level of improvement was maintained for 48 weeks. The ACR20 response was 51% at week 24 and 46% at week 48, and this effect was consistent across all dose groups. The durability of the response to anakinra was further demonstrated in an evaluation of the sustained ACR20 response, which was similar during the first and second 24-week periods (36% and 42%, respectively). At week 48, ACR50 and ACR70 responses were demonstrated in 18% and 3% of patients, respectively, who continued taking anakinra (all dose groups) and in 20% and 1% of patients, respectively, who were originally receiving placebo and then were randomized to all doses of anakinra. Anakinra was well tolerated for 76 weeks. The only side effects that appeared to be treatment-related were skin reactions at the injection site. There was no evidence of decreased tolerance, an increased number of withdrawals, or an increased incidence of clinical complications associated with extended anakinra therapy. CONCLUSION: The clinical benefits of treatment with daily self-administered subcutaneous injections of anakinra in a cohort of patients with active RA were maintained for up to 48 weeks. Anakinra was well tolerated over 76 weeks. These observations support the long-term use of anakinra for the treatment of patients with RA.
12555187 Decision making in glenohumeral arthroplasty. 2003 Jan Prosthetic replacement arthroplasty for glenohumeral arthritis is a well-developed and well-described technique with good and excellent results. The surgeon is faced with many decisions to make, however, regarding choice of implant, implant fixation, soft tissue management, and options for glenoid resurfacing. In general, when the precise cause of the arthritic condition is identified, the choices become more straightforward. For advanced osteoarthritis of the shoulder joint in an older patient with asymmetric posterior erosion of the glenoid, a total shoulder arthroplasty renders the best relief of pain and improvement in motion. Similarly, for advanced rheumatoid arthritis in patients with an intact rotator cuff, a total shoulder arthroplasty results in the best pain relief. If the rotator cuff is deficient and irreparable, an anatomically sized humeral head replacement is appropriate, taking care to preserve the coracoacromial arch. Acute, nonreducible fractures of the proximal humerus are treated best with a humeral head replacement. Post-traumatic arthropathy of the shoulder joint is treated with arthroplasty, and the decision to resurface the glenoid should take into account the age of the patient and the wear and concentricity of the glenoid. Many options exist for the choice of an implant; biomechanical and anatomic studies suggest that a better technical result can be achieved with a third-generation implant design that has the ability to recreate accurately the proximal anatomy of the humerus.
11838445 The Souter-Strathclyde elbow arthroplasty. A clinical and radiological study of 525 consec 2002 Jan We present the results of 525 primary Souter elbow arthroplasties undertaken in 406 patients between 1982 and 1997. There were 372 women and 34 men with a mean age of 57 years; 119 patients had a bilateral procedure. The elbows were affected by chronic inflammatory disease, usually rheumatoid arthritis, which had been present for a mean of 24.7 years (2 to 70). In about 30% the joints were grossly destroyed with significant loss of bone. In 179 elbows the ulnar components were metal-backed and retentive; in the remaining 346, with better bone stock, non-retentive, all-polyethylene prostheses were used. Because of complications, 108 further operations were required in 82 patients. During the early years the incidence of complications was higher. Dislocation was the indication for 30 further procedures in 26 patients. Thirty patients underwent 33 revision procedures for aseptic loosening, 12 had 29 operations because of deep infection, two for superficial infection, and 14 further operations were done for other reasons. The cumulative rate of success, without aseptic loosening, five and ten years after surgery, was 96% and 85%, respectively.
14657632 Erythema multiforme-like drug eruption with oral involvement after intake of leflunomide. 2003 Leflunomide is an antirheumatic agent of the type of a 'disease-modifying antirheumatic drug'. In rare cases, severe skin reactions up to the extreme expression of toxic epidermal necrolysis have been observed. A female patient with rheumatoid arthritis had been treated with systemic steroids and methotrexate for 2 years. Five weeks prior to admission to our hospital methotrexate was replaced by leflunomide. Three weeks after initiation of leflunomide therapy a progressive generalized erythema with blistering formation occurred accompanied by increase of body temperature, chills and erosive lesions on the lips and oral mucosa. The palmar and plantar surfaces revealed edema, erythema and pulpitis with epidermolysis. On histologic examination necrotic keratinocytes and epidermal spongiosis were observed. After administration of high-dose prednisolone and topical treatment the patient recovered within 14 days. This is one of the few cases of severe drug reaction after intake of leflunomide. Therefore, the indication of this relatively new drug should be considered carefully.
11982957 The effectiveness of intravenous human immunoglobulin treatment after plasmapheresis in re 2002 Apr This study was performed to examine the effects of intravenous human immunoglobulin (IVIG) on the level of serum immunoglobulin G (IgG) and its subclasses after plasmapheresis in patients with autoimmune disorders. Twenty-nine patients with predominantly rheumatoid arthritis were enrolled in this study. The plasmapheresis was performed by the use of double-filtration plasmapheresis (DFPP). Immediately after DFPP, IVIG (2.5 g, 50 ml) was intravenously administered. The treatment with IVIG had almost no effect on subjective and objective symptoms. Immediately after DFPP, the total of serum IgG was decreased by approximately 40%. After 24 h, the total of serum IgG recovered to 16% reduction in IVIG-treated patients whereas it remained at 32% reduction in nontreated patients. The beneficial effect of IVIG was significantly observed in patients who had shown 1,000-1,800 mg/dl IgG in their sera. After DFPP, IgG subclasses were decreased without change in the ratio of subclasses. Twenty percent to 30% of IgG subclasses were supplemented by the treatment with IVIG without change in the ratio of subclasses. These results suggested that the treatment with IVIG at minimal amount was safe and effective to supplement IgG for hypogammaglobulinemia after DFPP.
14980993 Vertebral deformities in rheumatoid arthritis: a comparison with population-based controls 2004 Feb 23 BACKGROUND: Previous studies have shown an increased prevalence of osteoporosis in rheumatoid arthritis (RA), but the extent of osteoporotic fractures is not clarified. The aim of this study was to compare the prevalence of vertebral deformities in a representative, population-based cohort of female patients with RA with that in matched controls, and to examine the relationship between deformities and RA, bone mineral density (BMD), and corticosteroid use. METHODS: Female patients (mean age, 63.0 years; range, 50.7-73.6 years) were recruited from a county register of patients with RA. Population controls were matched for age, sex, and residential area. Participants had thoracolumbar radiographs taken according to a standardized procedure, and BMD was measured at the hip and spine (L2-L4). RESULTS: The overall number of vertebral deformities was substantially higher in the RA group compared with controls (147 vs 51, applying the morphometric criteria), with a highly significant difference between patients and controls regarding the presence of multiple deformities measured morphometrically (11.2% vs 4.8%; odds ratio, 2.60; 95% confidence interval, 1.21-6.04) and moderate or severe deformities measured semiquantitatively (17.3% vs 10.0%; odds ratio, 2.00; 95% confidence interval, 1.11-3.74). In Poisson regression analysis, vertebral deformities were independently associated with RA, BMD, and long-term corticosteroid use. CONCLUSIONS: Vertebral deformities are markedly increased in patients with RA compared with controls, especially regarding severe and multiple deformities. A diagnosis of RA was associated with vertebral deformities independently of BMD and long-term corticosteroid use. These findings have important implications for prevention of established osteoporosis in RA.
15121040 An economic approach to health care. 2004 Apr Economic analyses have the potential to put all of the positive and negative outcomes of an intervention into perspective to aid decision making. The quality of the data upon which the analysis is based has an impact on the resulting quality of the analysis itself. Analysis of cost-effectiveness requires the input of many types of data, and where data are not available, assumptions must be made. There are many instances where the analysis may go wrong, and it is important to remain cognizant of these. The critical parts of the analysis, which have also been identified in quality assessment tools, include the following: design of the study question, sources of probability estimates and cost data, sensitivity analysis, and the interpretation of results. If the readers are able to identify the assumptions of the analysis they are better equipped to judge the validity. We have reviewed economic analyses relating to two hot economic topics in rheumatology. These are the cost-effectiveness of cyclooxygenase-2 (COX-2) inhibitors for 'arthritis' and cost-effectiveness of anti-tumor necrosis factor alpha (anti-TNF) agents for rheumatoid arthritis (RA). The results of the COX-2 analyses vary by review. Some show cost savings, while others calculate a significant cost in order to achieve any change in quality of life. Given the unanswered questions that still exist, it seems reasonable to conclude that COX-2 inhibitors may be cost effective when used in patients at a high risk of GI complications. Unanswered questions remain regarding the concomitant use of low-dose ASA and proton pump inhibitors and how they may affect the results of these economic analyses. The cost-effectiveness of anti-TNF agents has not been explored in as much detail as that of the COX-2 agents. Two studies have presented cost-effectiveness models that include a hypothetical biologic agent. Two economic analyses report on the cost-effectiveness of etanercept compared with traditional disease-modifying anti-rheumatic drugs (DMARDs) in methotrexate-resistant and methotrexate-naïve patients with RA. Both the analyses show that etanercept has a cost-effectiveness ratio of around 40,000 US dollars for every patient who achieves an American College of Rheumatology 20% improvement score (ACR 20) within a 6-month period. A cost-utility analysis was published regarding the use of infliximab in methotrexate resistant RA. It showed a cost-utility ratio of 3400:34,000 Euro per quality adjusted life year (QALY) gained, depending on the country evaluated (Sweden and the UK, respectively). An important finding in all three studies was that indirect costs dominate costs in RA; therefore, they should be included in all future analyses of this disease.
14730603 Continuous enhanced expression of Hsc70 but not Hsp70 in rheumatoid arthritis synovial tis 2004 Jan OBJECTIVE: To investigate the expression of constitutive and inducible members of the Hsp70 protein family in synovial tissue of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: Frozen sections of synovial tissue and isolated synovial adherent cells obtained from 17 RA patients, 5 OA patients, and 1 patient with carpal tunnel syndrome (CTS) were analyzed with specific monoclonal antibodies, by immunohistochemistry, immunocytochemistry, and immunoblotting. RESULTS: Expression of the constitutive chaperone Hsc70 was increased in synovial tissue from 9 of 9 patients with RA, but was faint or undetectable in 3 of 3 samples from patients with OA. In RA samples, cells mainly of the synovial lining stained intensely for Hsc70 as well as for HLA-DR, CD14, and CD68. Also, in vitro-cultured synovial adherent cells from 8 of 9 RA patients overexpressed Hsc70 (specimens from 1 RA patient were used in both the immunochemistry and the in vitro culture studies). On immunoblots of protein extracts, the synovial and HeLa cell molecules appeared identical in size. The inducible chaperone Hsp70 was not detected in samples from any of the same 17 RA patients, except for rare, isolated cells in 3. Samples from 4 of 5 OA patients also were negative for the inducible chaperone Hsp70, and the fifth was very weakly positive. In addition, tissue from 1 patient with CTS was analyzed 10 months before diagnosis of RA. Synovial tissue from this patient showed extreme overexpression of both Hsc70 and Hsp70. CONCLUSION: In RA, synovial lining cells continuously overexpress Hsc70 but not Hsp70. Hsc70 may be up-regulated due to the high activity of these cells in several respects, including antigen processing and presentation.
12787510 How to assess musculoskeletal conditions. Assessment of disease activity. 2003 Jun The concept of disease activity is useful for characterizing chronic rheumatic diseases and their current degree of severity. Disease activity should be clearly differentiated from damage, which is irreversible. A number of requirements must be met in order to make a measure of disease activity acceptable and valid. Methods for measurement have been developed in the areas of biological, radiographic, ultrasound and computerized imaging techniques. Recently, a particular effort has been made to develop questionnaires in the form of complex indices, derived from the observations of physicians, and self-report questionnaires for patients. Such assessments of disease activity are available for most of the chronic inflammatory rheumatic diseases. They are particularly relevant at a time when new biological drug therapy is being developed. Research effort is needed to develop more instruments suitable for use in clinical practice for individual patients.
12846051 Treatment of early RA in clinical practice: a comparative study of two different DMARD/cor 2003 May OBJECTIVES: To study the outcome in clinical practice of first DMARD and/or corticosteroid (CS) treatment in patients with recent onset rheumatoid arthritis (RA). PATIENTS: 245 patients with active RA, not previously treated with DMARDs or CS, were randomised to one of two treatment groups, T1 = 7.5-15 mg of prednisolone (PRE) daily for one to three months followed, if needed, by methotrexate (MTX) in a weekly dose of 5-15 mg in addition to the lowest possible dose of PRE or T2 = sulfasalazine (SAL), supplemented with lowest possible CS dose if needed. METHODS: The EULAR individual response criteria were applied and remission was defined as a final DAS28 < 2.6. Function was assessed by the HAQ and radiographic progression by Larsen scores. A patient who managed to remain on the allocated treatment for two years was described as a "completer". RESULTS: After 2 years of treatment, 70% of the patients in T1 and 63% in T2 were responders (30% and 33% "good responders", respectively). In T1 29% and in T2 19% were in remission. There was a significant functional improvement in both groups but radiographic progression occurred. The mean decrease in HAQ and increase in the Larsen score were similar in the two groups. One-third of the patients were non-completers, 19% from T1 and 47% from T2. Non-completers had, compared with completers, a significantly lower rate of individual response and remission. Completers and non-completers had similar functional improvement and similar radiological progression. CONCLUSIONS: Individual response and remission was reduced in patients who did not complete their first DMARD/CS treatment option. Treatment failures were significantly more frequent in the sulfasalazine plus optional CS than in the CS plus optional methotrexate treatment group.
12730504 Prevalence of Helicobacter pylori in NSAID users with gastric ulcer. 2003 Aug OBJECTIVE: Regarding the interaction of Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs), we cannot accept unanimous conclusions in inducing gastric ulcer. We therefore evaluated the role of Helicobacter pylori and NSAIDs in inducing gastric ulcer. METHODS: Dyspeptic patients receiving NSAIDs underwent endoscopic examination. Gastric ulcer formation and H. pylori status were investigated. Biopsy specimens from the antrum and lower body of the stomach were prepared for the rapid urease test and pathological evaluation. Anti-H. pylori antibody was measured by enzyme-linked immunosorbent assay. RESULTS: Two hundred and twenty-six patients receiving NSAIDs (220 chronic and six on-demand users) underwent gastrofibrescopic examination. There were 110 patients with gastric ulcer and 111 non-ulcer patients with gastritis. The remaining five patients had neither. NSAID users with gastric ulcer showed a low prevalence of H. pylori compared with those without them [55/110 (50.0%) vs 79/111 (71.2%), P < 0.01]. The same tendency was seen when patients receiving low-dose aspirin and those with rheumatoid arthritis were analysed separately [13/29 (44.8%) vs 50/62 (80.6%), P < 0.01, and 11/33 (33.3%) vs 16/26 (61.5%), P < 0.06 with Yates' correction, respectively]. CONCLUSION: Helicobacter pylori infection appeared to be a risk factor for developing gastritis, but we found no evidence that it increases gastric ulcer formation in NSAID users with dyspepsia.