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ID PMID Title PublicationDate abstract
11906961 2-Chloroadenosine but not adenosine induces apoptosis in rheumatoid fibroblasts independen 2002 Mar 1. The apoptotic effect of adenosine and its analogues was studied in fibroblast-like synoviocytes derived from rheumatoid arthritis patients (RA-FLSs). Evoked cell death was quantitatively examined by assessing DNA fragmentation using an enzyme-liked immunosorbent assay and by measuring phosphatidylserine exposure through flow cytometric analysis of annexin V binding. 2. Exposing cells for 24 h to 2-chloroadenosine (2-CADO), a nonspecific, adenosine deaminase (ADA)-resistant, adenosine receptor (AdoR) agonist, induced DNA fragmentation, and thus apoptosis, in RA-FLSs at concentrations > or =50 microM. By contrast, incubation with adenosine for up to 72 h did not evoke DNA fragmentation, even in the presence of ADA inhibitor coformycin and nucleoside transporter inhibitor nitrobenzylmercaptopurin (NBMPR). Transcription of all four AdoR isoforms was detected in RA-FLSs; nevertheless selective AdoR agonists similarly failed to induce DNA fragmentation. 3. DNA fragmentation evoked by 2-CADO was inhibited by NBMPR and by 5'-iodotubercidin, an adenosine kinase inhibitor, but not by xanthine amine congener, an A(1) and A(2) receptor antagonist, or by selective AdoR antagonists. 4. The nonspecific caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone abolished the apoptotic effect of 2-CADO. 5. These results suggest that 2-CADO induces apoptosis in RA-FLSs independently of AdoR-mediated signalling. Instead, 2-CADO, but not adenosine, is taken up into RA-FLSs via human equilibrative nucleoside transporter-1, where it is phosphorylated by adenosine kinase. The resultant phospho-2-CADO induces DNA fragmentation by activating a caspase pathway.
12875993 FcgammaRI up-regulation induced by local adenoviral-mediated interferon-gamma production a 2003 Aug Using various FcgammaR-deficient mice, we have obtained suggestive evidence that FcgammaRI on macrophages is responsible for severe cartilage destruction during arthritis mediated by immune complexes (ICs). This role of FcgammaRI is pronounced in the presence of activated Th1 cells and a likely Th1 cell-derived cytokine mediating up-regulation of FcgammaRI expression is interferon (IFN)-gamma. We now investigated whether local overexpression of IFN-gamma using an adenoviral vector is able to elevate cartilage destruction during experimental immune complex-mediated arthritis (ICA) and to what extent this process is FcgammaRI-mediated. IFN-gamma overexpression during ICA had no significant effect on the total cell mass infiltrating the knee joint. However, a higher percentage of macrophages expressing markers for a proinflammatory phenotype was found and these macrophages were situated in close proximity of the cartilage surface. Interestingly, cartilage destruction as studied by matrix metalloproteinase (MMP)-mediated proteoglycan damage (VDIPEN expression), chondrocyte death, and erosion was significantly increased. This effect of IFN-gamma was only found in the presence of ICs, as IFN-gamma overexpression during zymosan-induced arthritis, which is not IC-dependent, did not lead to severe cartilage destruction. These results imply a crucial role for ICs and the IgG-binding receptors in the aggravation of cartilage damage by IFN-gamma. Local overexpression of IFN-gamma induced increased FcgammaRI mRNA levels in synovium. To study whether this up-regulation of FcgammaRI mediates aggravation of cartilage destruction, ICA was raised in FcgammaRI(-/-) and their wild-type controls. IFN-gamma resulted in elevated VDIPEN expression, which was still present in FcgammaRI(-/-). Of great interest, chondrocyte death remained low in FcgammaRI(-/-). These results indicate that IFN-gamma overexpression deteriorates cartilage destruction in the presence of ICs and that FcgammaRI is crucial in the development of chondrocyte death.
15570635 Low dose methotrexate in the first trimester of pregnancy: results of a French collaborati 2004 Dec OBJECTIVE: To assess the risk of major malformations in pregnant women with chronic inflammatory disorders treated with low dose methotrexate (MTX) during the first trimester of pregnancy. Secondary outcomes included the rate of miscarriage, birth weight, and gestational age at delivery. METHODS: Data from the French network of 31 pharmacovigilance centers and 2 teratology information services were analyzed. The outcome of pregnancy was prospectively assessed in women exposed during the first trimester of pregnancy. Data on maternal history and drug exposure were collected at the initial inquiry, and on the outcome of pregnancy at followup. RESULTS: Twenty-eight cases were available for analysis. MTX exposure ended before 8 weeks of gestation in 26 patients. Miscarriages occurred in 4 patients and 5 had elective termination of pregnancy. There were 19 live births, among whom 3 were premature. Birth weights in full-term children were within the expected range. One child exposed until 8.5 weeks of gestation had only minor anomalies (metatarsus varus and eyelid angioma). CONCLUSION: Although no definitive conclusion can be drawn, our results and the analysis of the literature support the conclusion that no strong teratogenic risk is associated with low dose MTX provided that the drug is discontinued as early as possible in pregnant women.
12510371 [Secondary amyloidosis in patients with rheumatoid arthritis(RA)]. 2002 Dec The amyloidoses are a group of protein deposition diseases in which amyloid proteins composed of insoluble fibrils are deposited in various organs. Most cases of the secondary amyloidosis(AA amyloidosis) in which amyloid A(AA) protein is deposited followed by uncontrolled, long term RA(duration 7 to 10 years). It has been revealed that the multi-organ dysfunction associated with AA amyloidosis causes the deterioration of RA prognosis. Since the mechanism of amyloid protein deposition is still unknown, the diagnosis of AA amyloidosis is difficult and there is no fundamental therapy for it; there are only supportive therapies for the malfunction of involved organs.
12102483 Adenoviral-mediated gene transfer to the synovial tissue. 2002 May In various animal models gene transfer to the synovial tissue has been shown after intraarticular injection of adenoviral vectors. Safety of the transfer of therapeutic genes to the synovial tissue depends on multiple factors, including the mode of administration, the vector and the gene used, and the immune system of the host. In this article, data on the biodistribution and induction of inflammation after the intraarticular administration of adenoviral vectors are summarized and discussed. The ultimate goal of gene therapy will be the injection of a vector that has a specific target cell. Such a goal will require major improvements in the currently available delivery systems or the development of novel vectors. In this article new strategies are proposed in which gene transfer efficiency to the synovial tissue increases, whereas simultaneously the effect of neutralization of the adenoviral vector by the synovial fluid is circumvented.
12519388 Dipeptidyl peptidase IV on activated T cells as a target molecule for therapy of rheumatoi 2003 Jan The extracellular domain of the T cell co-stimulatory molecule CD26 possesses dipeptidyl peptidase IV (DP IV) enzyme activity. Activated T cells are known to increase expression of cell surface DP IV and some specific inhibitors of this enzyme have been reported to suppress T cell function. Previously we have identified a DP IV inhibitor, designated TMC-2, found in culture supernatant of Aspergillus oryzae. Administration of TMC-2 to rats with adjuvant arthritis caused marked suppression of paw swelling. To elucidate the mechanism of TMC-2 antiarthritic activity, we have studied its effects on T cell function. Here we show that TMC-2 inhibited DP IV activity of CD26 immunoprecipitated from T cell lysates, and also inhibited proliferative responses of T cells to specific antigen or anti-CD3 antibody. Suppression of IL-2 production was demonstrated at both the mRNA and protein levels. TMC-2 did not alter the PTPase activity of pure CD45, but when this molecule was co-precipitated from T cell lysates together with associated CD26, its PTPase was virtually completely abolished by TMC-2. These results suggest that modulation of CD45 PTPase activity might be responsible for functional suppression of T cells by TMC-2. Because the effects of TMC-2 on T cells were reversible and it was not toxic at the concentrations used, TMC-2 may be a candidate novel therapeutic agent for rheumatoid arthritis.
15355529 Ethical issues in participatory action research. 2004 Sep The purpose of this article is to describe the ethical issues arising out of participatory action research (PAR), on the basis of both an empirical study and the research literature, and to discuss how to deal with these issues. The data consist of the experiences and results of three phases of PAR relating to orthopaedic patients with rheumatoid arthritis (RA) and the analysis of 20 articles on the ethics of action research. As a result, the following ethical issues and the ways to treat them were discussed: informed consent, confidentiality and anonymity, protecting an individual from harm, the role of the researcher, the location of 'power' in PAR, and the ownership of the research. The flexibility of PAR in use and its main features are also related to the decisions made and actions taken in response to ethical issues. It is particularly important in PAR to proceed according to the participants, and to involve them from the beginning of the process, in order to insure the equal balance of power between participants and researcher.
12913928 Description of stable pain in rheumatoid arthritis: a 6 year study. 2003 Aug OBJECTIVE: To study pain quality and variability in patients with rheumatoid arthritis (RA). METHODS: Pain, disease activity, and functional status were assessed 3 times over 6 years in an initial cohort of 120 clinic patients with chronic pain from RA. A pain visual analog scale and the McGill Pain Questionnaire (MPQ) were used to record pain intensity and quality. RA disease activity and function were measured. RESULTS: There was no statistically significant difference in any measure over the 3 assessments. RA pain intensity was moderate. The MPQ showed that sensory components of the pain were described in terms of pressure and constriction. Pain related affect was described with adjectives suggesting positive psychological adaptation to pain. CONCLUSION: The results indicate a general profile of no change in pain sensation, affect, and emotional quality in clinic monitored patients with ongoing RA and ongoing, moderate levels of disease activity and function. The MPQ provides qualitative detail to patient's report of pain severity that could be a useful addition to longterm documentation of RA outcome. Regular MPQ documentation of current pain in outpatients could indicate whether any significant change in pain levels is reflected in altered word selection that reflects physiological or psychological change, and could assist clinicians to select the most appropriate form of therapy for RA pain.
12236622 Preventing joint damage as the best measure of biologic drug therapy. 2002 Sep Joint damage occurs progressively in patients with rheumatoid arthritis (RA), leading to functional decline and disability. The proinflammatory cytokines interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are thought to play a key role in promoting cartilage and bone erosion in the rheumatoid joint. In randomized clinical trials, inhibitors of these cytokines significantly slowed the rate of progressive joint damage as assessed by radiographic techniques. The IL-1 receptor antagonist anakinra significantly reduced erosions, joint space narrowing, and total joint damage when a modified Sharp score was used to evaluate serial hand radiographs. The maximum benefit of anakinra on joint space narrowing was achieved within the first 24 weeks and was maintained during continued treatment, whereas the slowing of erosions by anakinra increased with continued treatment beyond 24 weeks. In terms of TNF-alpha inhibition, infliximab significantly reduced joint damage in patients with long-standing RA, when used in combination with methotrexate (MTX), whereas etanercept significantly reduced erosions relative to MTX in patients with early stage disease. Comparisons among the cytokine inhibitors are made problematic by differences in the designs, patient populations, and outcome measures of these trials. Nevertheless, these studies demonstrate that IL-1 or TNF-alpha inhibition effectively suppresses the pathophysiological mechanisms associated with cartilage degradation and bone erosion, resulting in a slowing of further radiographic progression.
12375310 Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune 2002 Oct OBJECTIVE: The 20S proteasome plays a leading immunologic role in the cytosolic generation of MHC class I restricted antigens, and it represents an abundant antigen in several autoimmune diseases. To investigate the effects of autoimmune inflammatory and perioperative traumatic cellular damage, we determined qualitative and quantitative properties of released proteasomes (circulating proteasomes, cProteasomes) from serum samples of patients with a variety of autoimmune diseases. METHODS: cProteasomes were analyzed from serum samples of 314 patients with several systemic and organ-specific autoimmune diseases and 85 healthy controls. The concentrations of cProteasomes were determined by sandwich ELISA using a monoclonal and a polyclonal proteasome-specific antibody. Followup analyses were performed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) as well as in patients with myasthenia gravis undergoing thoracoscopic thymectomy. RESULTS: Strongly increased levels of cProteasomes (> 1000 ng/ml) were detected in samples obtained from patients with autoimmune myositis, SLE, primary Sjögren's syndrome, RA, and autoimmune hepatitis. Significant differences were observed in the mean values of cProteasomes comparing systemic with organ-specific autoimmune diseases. Followup analyses revealed a close correlation of cProteasome with the autoimmune process as well as cellular damage. Moreover, cProteasomes were isolated in intact and native as well as in degraded or dissociated forms from the serum samples. The immuno-subunit LMP7 was found to be incorporated in the circulating protease complex. CONCLUSION: Levels of cProteasomes are markedly elevated in patients with systemic autoimmune diseases, apparently correlating with disease activity. The cProteasomes represent novel sensitive markers of the autoimmune inflammatory processes and/or reflect the magnitude of cellular damage.
14507509 Total wrist arthroplasty in patients with rheumatoid arthritis. 2003 Sep PURPOSE: After very good midterm results with an uncemented total wrist arthroplasty we evaluated the long-term outcome in a retrospective study. METHODS: Forty uncemented anatomic physiologic (APH, Implant-Service Vertreibs-GmbH, Hamburg, Germany) wrist prosthesis implantations performed in 40 patients were reviewed. The mean follow-up period was 52 months (range, 24-73 mo) and the following parameters were examined: radiographs, grip strength, range of motion, and patient's satisfaction. RESULTS: After a good short-term outcome the results deteriorated with time. The following complications occurred: 2 infections, 3 implant failures, 2 prosthesis migrations, and 33 loosenings/dislocations. All patients (39 of 40) underwent revision surgery, and severe titanium wear in the soft tissues was found intraoperatively in all cases. It became clear that even in a non-weight-bearing joint such as the wrist, titanium alloy may wear and result in tissue metallosis when used as a bearing surface of the implant. As a salvage procedure the prosthesis was removed and an arthrodesis was performed in all patients. CONCLUSIONS: Because of the deterioration of the results including an unacceptable revision rate we currently do not consider the anatomic physiologic wrist prosthesis to be a suitable implant in patients with rheumatoid arthritis.
12625216 Biological response modifiers in the management of rheumatoid arthritis. 2003 Feb 15 The management of rheumatoid arthritis (RA) with biological response modifiers (BRMs) is reviewed. RA, an autoimmune disorder affecting 1-2% of the world's population, is characterized by inflammation of synovial tissues, joint swelling, stiffness, and pain that may progress to joint erosion. There is strong evidence that inflammatory mediators, such as tissue necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), play a critical role in the pathogenesis of this disorder. IL-1-receptor antagonist (IL-1Ra) is produced in healthy subjects and helps to protect against the adverse effects associated with IL-1 overexpression. Administration of IL-1Ra or similar agents may reduce the effects of IL-1 and ameliorate inflammatory conditions. Traditional treatment of RA has been based on symptomatic management with non-steroidal antiinflammatory drugs, disease-modifying antirheumatic drugs, and corticosteroids, each of which has substantial drawbacks in terms of effectiveness or adverse effects. Newer therapeutic strategies for blocking the biological effects of inflammatory cytokines include antibodies directed against TNF (e.g., infliximab), soluble receptors (e.g., etanercept) and receptor antagonists to IL-1 (anakinra) [corrected]. Clinical trials indicate that these BRMs may be more effective than traditional agents because they are able to alter joint remodeling in addition to attenuating symptoms. Anti-TNF therapies may be associated with increased risk for infections, sepsis, tuberculosis reactivation, demyelination disorders, and blood dyscrasias; anakinra appears to be safer. Combination therapy with BRMs may be more appropriate for RA than monotherapy. The role of BRMs in the treatment of RA will evolve as investigators learn more about the drugs and the disorder.
12509618 Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis. 2003 Jan OBJECTIVE: Expression and activation of matrix metalloproteinases such as MMP-3 (stromelysin-1) and MMP-1 (collagenase-1) are increased in patients with rheumatoid arthritis (RA). Previous negative reports of their value as predictors of joint damage may be due to the lack of a large longitudinal study of early RA patients. This study evaluated their use in assessing early untreated patients with RA and predicting subsequent joint damage. METHODS: Ninety-eight patients with early untreated RA of less than 12 months duration and 20 normal controls had baseline serum samples tested with a double-antibody enzyme-linked immunosorbent assay for each of MMP-1 and MMP-3. The subsequent changes in Larsen score (DeltaLarsen) and Health Assessment Questionnaire (DeltaHAQ) over the first 12 months were recorded. RESULTS: Baseline serum levels of MMP-3 and MMP-1 correlated significantly with baseline C-reactive protein (CRP) (r=0.42 and 0.49, P<0.001), DeltaHAQ (r=0.32 and 0.30, P<0.01) and DeltaLarsen (r=0.23 and 0.32, P<0.05) respectively. Analysis of the group of patients with a normal CRP at presentation (n=21) showed correlation of the baseline MMP-3 and MMP-1 with the presence of erosive disease during the first 12 months (r=0.52 and 0.65 respectively, P<0.05). Logistic regression analysis, in the patients who were non-erosive at presentation, showed that the strongest correlation with progression in Larsen score was the baseline MMP-3 level (r=0.30, P=0.01). CONCLUSIONS: Baseline serum MMP-1 and MMP-3 levels correlate with disease activity and predict functional and radiographic outcome in early untreated RA. They may have a particular value in predicting the progression of erosive disease in patients who are not erosive at presentation.
12610802 A randomized double blind, placebo controlled trial of topical Tripterygium wilfordii in r 2003 Mar OBJECTIVE: To assess the efficacy of topical Tripterygium wilfordii (TW), a Chinese herbal therapy, in rheumatoid arthritis (RA). METHODS: A 6 week randomized double blind placebo controlled study of 61 patients with RA meeting American College of Rheumatology (ACR) criteria was conducted in China. The primary outcome was a modified ACR-20 response rate, analyzed by logistic regression analysis. RESULTS: The modified ACR-20 response rate differed significantly (topical TW 58% vs placebo 20%; p = 0.002). There was an 8.1-fold (95% CI 1.9-35.4) increase in the modified ACR-20 response for the TW compared to the placebo group, adjusted for age and erythrocyte sedimentation rate. CONCLUSION: Topical TW appears efficacious for the treatment of RA, but larger studies are needed.
15255803 Leflunomide in active rheumatoid arthritis: a prospective study in daily practice. 2004 Aug AIMS: We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. METHODS: In this prospective case series study, a standard dataset was collected from outpatient medical records, including patient and disease characteristics, data on leflunomide use and adverse drug reactions. RESULTS: During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow-up duration was 317 (11-911) days. Sixty-five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow-up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS(28)) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12-month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS(28) response criteria. CONCLUSIONS: In the setting of care-as-usual rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within 1 year of starting leflunomide treatment, mainly because of adverse drug reactions.
12401535 Estimating the cost-effectiveness of 54 weeks of infliximab for rheumatoid arthritis. 2002 Oct 1 PURPOSE: To estimate the cost-effectiveness of infliximab plus methotrexate for active, refractory rheumatoid arthritis. METHODS: We projected the 54-week results from a randomized controlled trial of infliximab into lifetime economic and clinical outcomes using a Markov computer simulation model. Direct and indirect costs, quality of life, and disability estimates were based on trial results; Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) database outcomes; and published data. Results were discounted using the standard 3% rate. Because most well-accepted medical therapies have cost-effectiveness ratios below $50,000 to $100,000 per quality-adjusted life-year (QALY) gained, results below this range were considered to be "cost-effective." RESULTS: At 3 mg/kg, each infliximab infusion would cost $1393. When compared with methotrexate alone, 54 weeks of infliximab plus methotrexate decreased the likelihood of having advanced disability from 23% to 11% at the end of 54 weeks, which projected to a lifetime marginal cost-effectiveness ratio of $30,500 per discounted QALY gained, considering only direct medical costs. When applying a societal perspective and including indirect or productivity costs, the marginal cost-effectiveness ratio for infliximab was $9100 per discounted QALY gained. The results remained relatively unchanged with variation of model estimates over a broad range of values. CONCLUSIONS: Infliximab plus methotrexate for 54 weeks for rheumatoid arthritis should be cost-effective with its clinical benefit providing good value for the drug cost, especially when including productivity losses. Although infliximab beyond 54 weeks will likely be cost-effective, the economic and clinical benefit remains uncertain and will depend on long-term results of clinical trials.
12966591 Proinflammatory role of fractalkine (CX3CL1) in rheumatoid arthritis. 2003 Sep OBJECTIVE: Fractalkine (CX3CL1) represents the sole member of the so-called CX3C chemokines. In rheumatoid arthritis (RA), functional studies suggest a role for this chemokine in monocyte chemotaxis and angiogenesis in the rheumatoid synovium. We analyzed the expression of fractalkine within different T cell subsets of the peripheral blood and expression of its receptor CX3CR1 within the rheumatoid synovium to further characterize its pathogenic role in RA. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 17 patients with RA and analyzed by flow cytometry in comparison to healthy blood donors. To identify the T helper cell cytokine profile of fractalkine-expressing cells, flow cytometric analysis of PBMC was performed after stimulation with PMA and ionomycin. Expression of fractalkine and its receptor was characterized in RA synovium by immunohistochemistry and laser capture microdissection microscopy. RESULTS: Flow cytometric analysis of fractalkine-expressing T cell subsets revealed a low proportion of fractalkine-expressing CD4+ and CD8+ T cells in both RA patients and controls. In addition, fractalkine was predominantly expressed in CD4+ T cells with a Th1-type cytokine expression profile. In RA synovium, fractalkine was detected in synovial macrophages, dendritic cells, endothelial cells, and a small proportion of T cells. The fractalkine receptor CX3CR1 was found in synovial macrophages, dendritic cells, and T cells as well as in synovial fibroblasts. Fractalkine stimulation of cultured synovial fibroblasts resulted in a marked upregulation of matrix metalloproteinase-2 (MMP-2) production. CONCLUSION: The results suggest that fractalkine may represent a Th1-type chemokine. Upregulation of MMP-2 production in synovial fibroblasts upon fractalkine stimulation in vitro supports the hypothesis of a proinflammatory role of this chemokine in RA.
12563698 Pain extent and diagnosis: development and validation of the regional pain scale in 12,799 2003 Feb OBJECTIVE: To develop and validate a pain scale that measures the extent of body pain. METHODS: A total of 12,799 patients with rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia (FM) completed a mailed survey regarding the location and intensity of their pain in 38 articular and nonarticular regions. The data were analyzed using item response theory (IRT) by nonparametric Mokken analysis followed by Rasch analysis. The resultant scale was examined for its association with clinical severity variables and its ability to distinguish patients diagnosed with and without FM. RESULTS: The resultant 19 item regional pain scale (RPS) was composed primarily of nonarticular regions. The scale had strong scalability as measured by the Mokken H statistic (H = 0.52), and satisfied the Mokken monotonicity and double monotonicity criteria. The RPS also fit the Rasch model and had satisfactory reliability and separation statistics. Of all clinical variables assessed by survey, the RPS best identified patients diagnosed with FM. In addition, the scale correlated with measures of clinical severity, regardless of diagnosis, and predicted measures of utilization. CONCLUSION: The RPS is a valid scale of pain extent. It can be useful to identify patients with FM or can be used to develop a new definition of FM, even among patients with concomitant illnesses such as RA and OA. In addition, it is a measure of pain extent that is disease independent, and works as well in RA and OA as in FM to identify patients with increased severity and resource utilization.
12172953 Pain pressure threshold values in ankylosing spondylitis. 2002 Aug Rheumatic patients experience persistent and disabling pain. We aimed to investigate the pain pressure threshold (PPT) values in ankylosing spondylitis (AS) patients compared to rheumatoid arthritis (RA) patients and healthy subjects. The relationship between lumbar and thoracal Schober, chin-to-chest distance, occiput-to-wall distance, finger-to-floor distance, chest expansion, and pain scores were also evaluated in an AS group. Our study group consisted of 17 AS patients, 20 RA patients, and 21 healthy volunteers. Eighteen tender points accepted by the American College of Rheumatism (ACR) for fibromyalgia syndrome evaluation in 1990 and three control points were evaluated with Fischer's tissue compliance meter, which can also be used as an algometer. Fourteen paravertebral points were evaluated, and mean values of paravertebral myalgic scores were recorded in the AS group. Our data indicate that AS patients do not have lower PPT with respect to healthy individuals, whereas RA patients have significantly lower PPT. A significant correlation was obtained between finger-to-floor distance and paravertebral myalgic score for AS. We conclude that AS does not have a widespread pain nature as RA.
15150428 The impact of new biologicals in the treatment of rheumatoid arthritis. 2004 Jun The past decade has seen a shift in the paradigm for RA management. DMARDs have been introduced at earlier stages of disease in an effort to slow or stop radiographic disease progression before irreversible joint damage, work disability, functional decline and other adverse outcomes are seen. Although often effective, DMARDs have been limited in treatment durability over the long term due to side-effects and declining efficacy. Combination regimens, often involving weekly methotrexate as the anchor drug, have been used increasingly to overcome the limitations of DMARD monotherapy. The advent of biological therapies that specifically target key proinflammatory cytokines, believed to be important in disease pathogenesis, provides several new treatment options. In controlled clinical trials, the IL-1 blocker anakinra (r-metHuIL-1ra) significantly reduced the clinical signs and symptoms of RA when used alone or in combination with weekly methotrexate. The TNF inhibitors etanercept, infliximab and adalimumab have shown similar efficacy; indeed, higher response rates for clinical and radiological parameters have been seen with the TNF blockers. Importantly, each of these biological response modifiers significantly reduced radiographic disease progression in 6- to 12-month studies, and some radiographic data extend to 24 months. Despite these promising findings, it remains to be determined whether slowing radiographic progression will translate into significant improvements in long-term outcomes.