Browse

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

ID PMID Title PublicationDate abstract
12915157 Impact of imaging in established rheumatoid arthritis. 2003 Oct Joint damage visualized on radiographs is still the hallmark of rheumatoid arthritis. With increasing duration of disease, there is an increasing relationship between joint damage and functional status. There are also other imaging techniques such as magnetic resonance imaging and ultrasound. The role of these techniques in clinical trials and clinical practice is discussed. Structural damage is an important measure of outcome for showing aspects of disease modification resulting from antirheumatic therapy. Recommendations are presented on how the results could be reported in an optimal way to ensure the correct presentation of data and comparability of the results. Joint damage is a clear sign of severe disease. More data become available that joint damage is related to several aspects of outcome, such as functional status, work disability and mortality. The significance and clinical implication of a certain magnitude of change in the modified Sharp score is discussed.
15248205 The relationship between disease activity and radiologic progression in patients with rheu 2004 Jul OBJECTIVE: Radiologic progression in rheumatoid arthritis (RA) is considered the consequence of persistent inflammatory activity. To determine whether a change in disease activity is related to a change in radiologic progression in individual patients, we investigated the longitudinal relationship between inflammatory disease activity and subsequent radiologic progression. METHODS: The databases of the University Medical Center Nijmegen (UMCN) cohort and the Maastricht Combination Therapy in RA (COBRA) followup study cohort were analyzed. The UMCN cohort included 185 patients with early RA who were followed up for up to 9 years. Patients were assessed every 3 months for disease activity and every 3 years for radiologic damage. The COBRA cohort included 152 patients with early RA who were followed up for up to 6 years. Patients were assessed at least every year for disease activity and every 12 months for radiologic damage. Disease activity was assessed with the Disease Activity Score (DAS) (original DAS in the UMCN cohort, DAS28 in the COBRA cohort). Radiologic damage was measured by the Sharp/van der Heijde score in both cohorts. Data were analyzed with longitudinal regression analysis (generalized estimating equations [GEE]), using autoregression for longitudinal associations and radiologic damage as the dependent variable. Time, time(2) baseline predictors for radiologic progression and their interactions with time, as well as DAS/DAS28 (actual values or interval means and interval SDs of the means) were subsequently modeled as explanatory variables. RESULTS: Data analyzed by GEE showed a decrease in radiologic progression over time (regression coefficient for time(2) -1.0 [95% confidence interval -1.4, -0.6] in the UMCN cohort and -0.4 [95% confidence interval -0.8, 0.0] in the COBRA cohort). After adjustment for time effects and baseline predictors of radiologic progression and their interactions with time, a positive longitudinal relationship was indicated by autoregressive GEE between the mean interval DAS and radiologic progression in the UMCN cohort (regression coefficient 5.4 [95% confidence interval 2.1, 8.6]), and between the DAS28 and radiologic progression in the COBRA cohort (regression coefficient 1.4 [95% confidence interval 0.8, 2.0]). In the UMCN cohort, the SD of the mean interval DAS was independently longitudinally related to the radiologic progression over the same periods (regression coefficient 20.2 [95% confidence interval 7.2, 33.3]). In both cohorts, the longitudinal relationships between (fluctuations in) disease activity and radiologic progression were found selectively in rheumatoid factor (RF)-positive patients. CONCLUSION: Radiologic progression is not linear in individual patients. Fluctuations in disease activity are directly related to changes in radiologic progression, which supports the hypothesis that disease activity causes radiologic damage. This relationship might only exist in RF-positive patients.
14611116 Hemopoietic stem cell transplantation in refractory rheumatoid arthritis is not a contrain 2003 Sep Hemopoietic stem cell transplantation (HCST) is an experimental therapy that may produce prolonged remissions in patients with rheumatoid arthritis (RA) resistant to other treatments. Prosthetic articular replacement is often required in severe long-lasting disease. There is a well-founded concern regarding the feasibility and safety of reconstructive surgery after HSCT and as yet no published data on the subject. We report a patient with RA of 9 years' duration resistant to conventional treatments plus femoral head necrosis, who underwent prosthetic hip replacement with no post-surgical complications one year after HSCT, with a sustained response.
15724930 [Antibodies to cyclic citrullinized peptide in rheumatoid arthritis]. 2004 AIM: To estimate a diagnostic value of antibodies to cyclic citrullinized peptide (CCP) in rheumatoid arthritis (RA). MATERIAL AND METHODS: The study was made of 85 RA patients. Of them, 48 patients had early RA, i.e. of 8 month and less duration. The control group consisted of 35 patients with non-differentiated arthritis (NDA) and 8 healthy donors. Concentrations of CCP antibodies, rheumatoid factor (RF) IgM and RF IgA were measured with enzyme immunoassay (EIA). RESULTS: The level of CCP antibodies in RA patients (76.3 +/- 43.8; median 100.0 U/ml) was significantly higher than in NDA patients (25.1 +/- 43.9; median 0.8 U/ml; p < 0.05) or in donors (0.38 +/- 0.36; median 0.2 U/ml; p < 0.05). A correlation was found between the CCP antibodies level and that of RF IgM (chi2 = 15.4; p = 0.001) and RF IgA (chi2 = 10.3; p = 0.001). Sensitivity (82%) and specificity (90%) of CCP antibodies in RA diagnosis was higher than these parameters for RF IgM and IgA (78%, 86% and 72%, 83%, respectively). Simultaneous tests for CCP antibodies, RF IgM and RF IgA led to a 93% specificity. CCP antibodies were detected in 50% patients seronegative by RF IgM and in 62% patients seronegative by IgA. Detection of CCP antibodies was closely associated with early RA (chi2 = 30.8; p = 0.0001). CONCLUSION: The EIA for CCP antibodies is a sensitive and specific serological test for early RA diagnosis.
12795625 The role of opioid analgesics in rheumatoid disease in the elderly population. 2003 Adequate pain therapy is an important aspect in the treatment of the elderly patient with rheumatoid disease. Problems with traditional NSAIDs include potentially serious gastrointestinal, cardiovascular and renal adverse effects, especially in the elderly. In addition, the selective cyclo-oxygenase-2 inhibitors have been associated with renal and cardiovascular adverse effects which may limit their use in the elderly with renal or cardiovascular disease. Opioids provide a treatment option for the management of pain in elderly patients with rheumatoid disease in whom pain control under standard management is poor; however, various therapeutic difficulties are encountered in the heterogeneous elderly population (increased risk of adverse effects, multimorbidity, and polypharmacy). Lower initial opioid dosage, prolonged dosage intervals and slower dosage titrations are advisable because of altered pharmacokinetics and pharmacodynamics. Kidney function should be tightly monitored and a timely use of laxatives is to be encouraged. Randomised clinical studies of opioids in musculoskeletal pain (e.g. osteoarthritis) have increasingly extended the scientific basis for their use. However, no randomised controlled clinical trials have examined the efficacy and the benefit/risk ratio of opioids in rheumatoid arthritis. Opioids also demonstrate an analgesic effect following local peripheral application. This opens the way to new therapeutic options in the future through the development of systemic peripherally selective opioids without CNS adverse effects.
15293093 Bone status in rheumatoid arthritis assessed at peripheral sites by three different quanti 2004 Aug Rheumatoid arthritis (RA) is characterized by periarticular and generalized loss of bone mass. Quantitative ultrasound (QUS) has been introduced as a method for the assessment of bone status and fracture risk. In this cross-sectional study bone status was assessed by QUS at different peripheral sites in 27 women with RA (mean disease duration 15 years) and in 36 healthy women matched for age, height and weight. Speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz) and stiffness of the calcaneus were assessed by a Lunar Achilles device. Amplitude-dependent SOS (Ad-SOS, m/s) of the second to fifth phalanx was measured by a DBM Sonic 1200, and SOS of the distal forearm and third phalanx was measured by a Omnisense multisite scanner. Bone mass (g/cm2 or g) of the hip, spine, distal forearm and total body was measured by dual-energy X-ray absorptiometry. QUS values were significantly reduced in RA at most sites ( p<0.005-0.001), but between-group differences were small, and large overlaps between the groups were noticed. After correction for bone mass, the observed differences remained statistically significant for the calcaneus and distal radius ( p<0.05). Independent associations between ultrasound measures and markers of disease activity were not demonstrated. In conclusion, bone status as assessed by QUS was compromised in RA, but whether ultrasound transmission may serve as a marker of disease progression and fracture risk in the individual patient remains to be clarified in prospective studies.
14605650 A comparison of static and dynamic wrist splints using electromyography in individuals wit 2003 Oct This study compared strength, dexterity, and the muscle activation of individuals with rheumatoid arthritis (RA) when different splints were worn. Five persons with RA were observed in four splint conditions (none, static, hinged, spiral) during grip, pinch, and dexterity tests by recording muscle activity of eight muscles in the upper extremity using electromyography (EMG). Statistically significant differences were found in clinical tests when hinged (p<0.001) and spiral splints (p=0.02) were worn. Grip strength decreased when hinged splints were worn, whereas two-point pinch increased and dexterity improved on the Nine-Hole Peg Test with the spiral splint. Although no significant EMG differences were found during different splint conditions, wrist muscles were recruited more for grip, and shoulder muscles were used most during pinch and dexterity tests. Individuals with RA who wore splints had decreased grip when wearing hinged splints, but improved pinch and dexterity were found when the spiral splint was worn. Increased use of proximal shoulder muscles was observed during pinch and dexterity tests with and without splints.
12492249 Aerobic and neuromuscular performance capacity of physically active females with early or 2002 OBJECTIVE: To examine aerobic capacity and neuromuscular performance in physically active females with early or long-term rheumatoid arthritis (RA) and healthy women. METHODS: Twenty-three RA-patients (12 early RA patients (ERA). 11 long-term RA (LRA) and 12 healthy controls (HC) performed maximal aerobic oxygen uptake (VO2max), muscle force production. walking and jump tests. RESULTS: The VO2max ranged between 23-27 ml x kg(-1) min(-1) and did not differ between the groups. Isometric grip strength was 25% (p = 0.017) and bilateral leg extension strength 19% (p = 0.031) lower in LRA patients compared to ERA. In LRA the explosive force (p = 0.023) and relaxation times (p = 0.025-0.032) of bilateral leg extension and vertical squat jump (p = 0.015) did not reach the level of HC or ERA. The trunk muscle forces did not differ between the groups. CONCLUSIONS: The physically active females even with LRA could maintain their aerobic fitness comparable to that of age matched healthy subjects. However, the neuromuscular profile suggests that especially explosive strength characteristics of the leg extensors cannot be maintained at the normal level with habitual physical activities.
15061673 Recurrent Mycobacterium xenopi infection in a patient with rheumatoid arthritis receiving 2004 A case of recurrent Mycobacterium xenopi infection presenting as Pott's disease in a patient receiving etanercept for severe rheumatoid arthritis is described. A 49-y-old Caucasian male had received a total of 11 months of anti-mycobacterial therapy for hip infection acquired 15 months earlier; he presented with progressive back pain, which was diagnosed as Pott's disease. He had been treated with etanercept in addition to his prior immunosuppressive agents after the diagnosis of hip infection.
15027757 Detection of anti-Proteus antibodies in sera of patients with rheumatoid arthritis. 2003 Jan This study was carried out to determine increased level of antibodies to certain bacteria in rheumatoid arthritis (RA) patients. Fifty RA patients and 25 each of those suffering from osteoarthritis (OA) and healthy controls were tested for antibodies to somatic ('O) and flagellar ('H') antigens of Proteus mirabilis, Escherichia coli, and for antibodies to 'O' antigen of Klebsiella pneumoniae by standard tube agglutination method. Anti-Proteus antibodies against 'O' and 'H' antigens could be demonstrated in 70% and 64% RA cases respectively, and were statistically significant. Antibodies could be demonstrated against E. coli 'O' and 'H' antigens in 86% and 92% RA cases respectively, and were statistically significant. Against K. pneumoniae 'O' antigen, no antibody could be demonstrated in any of RA and OA cases, and healthy controls. Of the 50 RA patients, 30 had raised CRP levels. Antibodies against P. mirabilis and E. coli antigens appeared to be independent from CRP. Thus a specific elevation in the immune response to P. mirabilis and E. coli has been demonstrated in patients with RA from India.
11981325 Novel pathways that regulate tumor necrosis factor-alpha production in rheumatoid arthriti 2002 May Clinical intervention studies have clearly shown the benefit in suppressing tumor necrosis factor-alpha (TNF-alpha) rheumatoid arthritis (RA). In consequence, considerable interest has arisen in those pathways that in turn regulate TNF-alpha production, because they may offer further possible therapeutic targets. Several candidate pathways are currently being investigated. They include T cell/macrophage interactions mediated primarily through cell-cell membrane contact; novel cytokine activities; microbial-derived products, in particular bacterial deoxyribonucleic acid sequences; autoreactive T cells, and immunoglobulins. At the subcellular level, there is further interest in targeting signaling and mRNA processing and cytokine cleavage pathways required for optimal TNF-alpha production. The key recent observations in these areas, particularly in the extracellular compartment, are reviewed.
12794816 Clinical responses to tumor necrosis factor alpha antagonists do not show a bimodal distri 2003 Jun OBJECTIVE: To study the distribution of clinical responses to treatment with the tumor necrosis factor alpha (TNFalpha) antagonists etanercept and infliximab, and in particular, to determine whether there is a biologically meaningful distinction between responders and nonresponders. METHODS: Among patients in the Stockholm TNFalpha Followup Registry, we analyzed the clinical responses to etanercept and infliximab, using the American College of Rheumatology (ACR) core set of outcome measures. For each parameter, the absolute change (value at baseline - current value) and the percentage change ([absolute change]/[value at baseline] x 100) from baseline were calculated. The results were plotted as histograms and inspected visually, and the distributions were statistically compared with computer-generated normal distributions. RESULTS: Absolute and relative changes in outcomes on the ACR core set of measures in 406 patients receiving etanercept or infliximab were studied. All but a few of these analyses yielded normal or somewhat skewed distributions. The statistical analyses did not detect any non-normal distributions, and visually, the distributions did not appear to be bimodal. CONCLUSION: The clinical response to TNFalpha blockade displays a normal or skewed, but not bimodal, distribution. The frequently encountered perception that a clear distinction can be made between responders and nonresponders is not borne out. These relatively straightforward findings imply that the biologic mechanisms determining responsiveness to TNFalpha blockade are multifactorial and may also have important implications for regulatory guidelines pertaining to treatment with these biologic agents.
15319231 Decreased prolactin response to hypoglycaemia in patients with rheumatoid arthritis: corre 2005 Mar OBJECTIVE: To compare basal and stimulated prolactin levels between patients with rheumatoid arthritis and healthy controls, and to assess the effects of antirheumatic treatment on prolactin concentrations. METHODS: Serum prolactin was assessed under basal conditions and during an insulin tolerance test (ITT) in 20 patients with recently diagnosed active rheumatoid arthritis and 20 age and sex matched controls. The patients were reassessed after two weeks' treatment with naproxen and after six months' additional treatment with either sulfasalazine or methotrexate. Disease activity was assessed by the disease activity score (DAS). RESULTS: Basal levels of prolactin were not significantly different between patients with rheumatoid arthritis and controls. Prolactin responses to hypoglycaemia were less in untreated rheumatoid patients than in controls. DAS scores correlated negatively with the area under the curve (AUC) for prolactin concentrations during the ITT. Treatment with naproxen for two weeks did not influence either basal or stimulated prolactin levels. After six months of antirheumatic treatment, prolactin responses to hypoglycaemia increased significantly to levels observed in controls. At the same time point, DAS had improved considerably. The improvement correlated with the increase in AUC of prolactin during the ITT (r = 0.48; p = 0.05). CONCLUSIONS: Patients with active rheumatoid arthritis have a decreased prolactin response to hypoglycaemia induced stress. The response recovers following treatment with antirheumatic drugs.
12877844 Radiologic evaluation of the rheumatoid hand after synovectomy and extensor carpi radialis 2003 Jul PURPOSE: In this study we radiologically evaluated the effects of extensor carpi radialis longus (ECRL) tendon transfer on the stability and deformity of joints of rheumatoid hands in cases with a postoperative period of more than 5 years. METHODS: Synovectomy concomitant with tendon transfer of the ECRL to the extensor carpi ulnaris (Clayton's procedure) was performed in 28 wrists of 23 patients with rheumatoid arthritis. The follow-up period was 8.8 +/- 2.8 years. Pre- and postoperative x-rays were reviewed and measured. Follow-up evaluation included Steinbrocker's classification of the radiocarpal joints, Larsen's grade of the third metacarpophalangeal (MCP) joint, radial angulation of the wrist, ulnar translocation of the carpus, and ulnar drift of the fingers. RESULTS: Nineteen of 28 wrists (68%) were ankylosed (radius-proximal carpal row fusion or radiolunate limited fusion). Radial angulation of the wrist was reduced from 131 degrees +/- 8.8 degrees before surgery to 121 degrees +/- 7.9 degrees after surgery. Dislocation and ulnar translocation of the carpus (UTC) were prevented by surgery (UTC: 1.05 +/- 0.10 before and 1.07 +/- 0.09 after surgery). The mean ulnar drift of the fingers was maintained at the preoperative level (UDF: 14 degrees +/- 5.7 degrees before and 14 degrees +/- 12.9 degrees after surgery). The incidence of alteration (increase and decrease) of UDF of more than 5 degrees between pre- and postoperative evaluation was significantly higher in the group with worsening of Larsen grade of MCP joints than in the group without worsening (with worsening: 7 of 8 MCP joints, without worsening: 8 of 20 MCP joints). CONCLUSIONS: ECRL tendon transfer (Clayton's procedure) provided effective stabilization at more than 5 years (mean, 8.8 y) after surgery. In addition, this method may help to prevent ulnar drift of the fingers if combined with correction of local factors at the MCP joints.
12453315 Effects of disease modifying agents and dietary intervention on insulin resistance and dys 2002 Patients with rheumatoid arthritis (RA) experience excess cardiovascular disease (CVD). We investigated the effects of disease-modifying antirheumatic drugs (DMARD) and dietary intervention on CVD risk in inflammatory arthritis. Twenty-two patients (17 women; 15 with RA and seven with spondyloarthropathy) who were insulin resistant (n = 20), as determined by the Homeostasis Model Assessment, and/or were dyslipidemic (n = 11) were identified. During the third month after initiation of DMARD therapy, body weight, C-reactive protein (CRP), insulin resistance, and lipids were re-evaluated. Results are expressed as median (interquartile range). DMARD therapy together with dietary intervention was associated with weight loss of 4 kg (0-6.5 kg), a decrease in CRP of 14% (6-36%; P < 0.006), and a reduction in insulin resistance of 36% (26-61%; P < 0.006). Diet compliers (n = 15) experienced decreases of 10% (0-20%) and 3% (0-9%) in total and low-density lipoprotein cholesterol, respectively, as compared with increases of 9% (6-20%; P < 0.05) and 3% (0-9%; P < 0.05) in diet noncompliers. Patients on methotrexate (n = 14) experienced a reduction in CRP of 27 mg/l (6-83 mg/l), as compared with a decrease of 10 mg/l (3.4-13 mg/l; P = 0.04) in patients not on methotrexate. Improved cardiovascular risk with DMARD therapy includes a reduction in insulin resistance. Methotrexate use in RA may improve CVD risk through a marked suppression of the acute phase response. Dietary intervention prevented the increase in total and low-density lipoprotein cholesterol upon acute phase response suppression.
11974488 [Health economics research in the area of chronic polyarthritis]. 2002 Feb Costs of illness are of major economic relevance in rheumatoid arthritis (RA) as in other chronic diseases. Overall costs of 15,000 Euro/year: 10,000 Euro indirect costs, and 5000 Euro direct costs are estimated, respectively. A further detailed analysis of direct costs underlines that inpatient care (50%) is the most prominent cost driver. Medication costs are also evaluated in detail since they are expected to gain importance with the introduction of the more expensive biologicals. While annual costs for regular disease modifying drugs (DMARDs) vary from 160 to 5000 Euro per patient, costs for the new biologicals amount up to 20,000 Euro (100-125% of the current estimated overall costs). For a comparison of different therapeutic strategies, costs are related to effectiveness in cost-effectiveness analyses. Based on present clinical trials, the ratios of medication costs and response according to the ACR 20-criteria of various DMARDs and biologicals are compared. The most cost-effective medication is sulfasalzine, followed by methotrexate, and leflunomide. Combining etanercept and methotrexate is preferable to methotrexate monotherapy and the combination of infliximab and methotrexate. This review shows that important economic issues in RA have already been addressed by applying cost-of-illness analyses and cost-effectiveness analyses. However, the knowledge about cost-effective therapeutic options is still scarce. Thus, primary data will have to be obtained using standardized approaches. These economic findings can be taken into account in the development of disease-management recommendations for RA-therapy.
16019592 Effects of stress on inflammatory autoimmune disease: destructive or protective? 2004 Dec We have summarised evidence in the literature for modulatory effects of stress on inflammatory autoimmune disease. We find that overall there is strong evidence for such an interrelationship. Apparent discrepancies between groups and studies are probably due to differences in experimental design, whether longitudinal or retrospective. Other important variables are the specific effects of different types of stress and the intensity and timing of the stressor relative to onset of inflammation. We conclude that there is much of benefit to be learned from scientific study of stress, such as harnessing and rationalising of stressful experiences through self-expression in patients, or the identification of novel anti-inflammatory compounds activated by stress.
11796409 Carriers of the aspartylglucosaminuria genetic mutation and chronic arthritis. 2002 Feb OBJECTIVE: To ascertain whether being a carrier of an autosomal recessive disease, aspartylglucosaminuria (AGU), predisposes to chronic arthritis, as does AGU disease. METHODS: A group of 173 unrelated patients with rheumatoid arthritis (RA) but with no family members with AGU each gave a blood sample for AGUFin major mutation DNA analysis. A group of 131 AGU carriers who were parents of patients with AGU completed a questionnaire on joint symptoms and gave a blood sample for rheumatoid factor (RF) analysis. Eight RF positive parents with prolonged joint symptoms had a rheumatological evaluation. RESULTS: Six patients (1/28) with RA were carriers of the AGUFin major mutation, whereas the carrier frequency among Finns in general is 1/50 to 1/85. Three AGU carriers had chronic arthritis (2.3%), and 17 (13%) were RF positive; the respective percentages among Finns in general are 1.4% and 5%. CONCLUSION: As for AGU disease, carrier status may also predispose to chronic arthritis.
12748655 Evolving concepts of rheumatoid arthritis. 2003 May 15 Rheumatoid arthritis is the most common inflammatory arthritis and is a major cause of disability. It existed in early Native American populations several thousand years ago but might not have appeared in Europe until the 17th century. Early theories on the pathogenesis of rheumatoid arthritis focused on autoantibodies and immune complexes. T-cell-mediated antigen-specific responses, T-cell-independent cytokine networks, and aggressive tumour-like behaviour of rheumatoid synovium have also been implicated. More recently, the contribution of autoantibodies has returned to the forefront. Based on the pathogenic mechanisms, specific therapeutic interventions can be designed to suppress synovial inflammation and joint destruction in rheumatoid arthritis.
15180124 Correlation between upper limb functional ability and structural hand impairment in an ear 2004 Jun OBJECTIVE: To explore the relationship in individuals with early rheumatoid arthritis (RA) between self-report upper limb function, therapist-assessed upper limb function and therapist-assessed measures of structural impairment (handgrip, active hand motion and metacarpophalangeal (MCP) joint ulnar deviation). DESIGN: Thirty-six patients with early RA were recruited across seven outpatient occupational therapy departments. OUTCOME MEASURES: Upper limb functional activity and ability was measured using the Disability of the Arm, Shoulder and Hand (DASH) questionnaire and the Grip Ability Test (GAT). Upper limb impairment was assessed by bilateral power handgrip using the MIE Digital Grip Analyser, goniometry measures of bilateral metacarpophalangeal (MCP) joint ulnar deviation and bilateral active motion of the wrist. RESULTS: Strong correlations (> 0.7) were seen between the self-report DASH questionnaire and the therapist-rated GAT assessment. Bilateral power handgrips were also strongly correlated with both functional assessments. Dominant ulnar deviation at the MCP joints demonstrated a weak correlation (0.3-0.4) with both self-report and therapist-rated functional ability and a weak to moderate. (0.1-0.5) correlation on the nondominant side. CONCLUSION: In this early RA population handgrip strength is an accurate indicator of upper limb ability. Ulnar deviation at the MCP joints shows only a weak to moderate association with upper limb functional activity and ability. Although the DASH and the GAT were strongly correlated, the DASH was a more discriminating measure than the GAT in assessing upper limb ability in this sample population.