Browse

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

ID PMID Title PublicationDate abstract
16100341 Potential relationship between herpes viruses and rheumatoid arthritis: analysis with quan 2005 Sep OBJECTIVE: To determine whether the human herpes viruses, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6), are detectable in serum and peripheral blood mononuclear cells (PBMCs) of patients with rheumatoid arthritis (RA). METHODS: 133 PBMC samples (61 RA, 72 healthy donors) and 136 serum samples (59 RA, 77 healthy donors) were analysed by quantitative real time polymerase chain reaction for DNA prevalence and viral load of HHV-6, EBV, and CMV. RESULTS: For PBMC samples significant differences were found for EBV in DNA prevalence (56% in RA v 33% in controls, p = 0.009) and viral load (copies/microg DNA 0-592.3 for RA v 0-40.4 for controls, p = 0.001). For serum samples a significant difference was found for HHV-6 DNA prevalence (10% in RA v 0% in controls, p = 0.006) and viral load (copies/microg DNA 0-529.1 for RA v 0 for controls, p = 0.007). CONCLUSIONS: Herpes viruses may have a role in RA, although alternative explanations are possible: (a) defects in cellular immunity in patients with RA may result in a relatively high viral load; (b) patients with RA may be more prone to infection/reactivation. The usefulness of monitoring the DNA viral load in patients with RA is questioned by these data.
15725578 Tumor necrosis factor-alpha -308 promoter polymorphism contributes independently to HLA al 2005 Feb The aim of this study was to determine the frequency and potential relevance of the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha) in the severity of rheumatoid arthritis (RA) in Mexicans. HLA-DR and polymorphisms at positions -238 and -308 of TNF-alpha gene were determined in 137 Mexican RA patients (44 with severe and 93 with non-severe RA) as well as in 169 healthy controls (99 were typed for HLA-DR). We observed an increased frequency of HLA-DR4 in severe RA compared to healthy controls (pC=0.02, OR=2.33). TNF polymorphism analysis showed a significant increased frequency of TNF -238 GG genotype in the whole group of RA patients when compared to healthy controls (pC=0.007, OR=4.71). When the analyses were carried out separately in severe and non-severe RA patients, the increased frequency of -238 GG genotype only was observed in patients with non-severe forms of the disease. Analysis of -308 polymorphism showed increased frequency of -308 T2 (A) allele in severe RA when compared to non-severe disease (pC=0.011, OR=3.29) and to healthy controls (pC=0.002, OR=3.97). The data demonstrate that -308 T2 (A) allele is associated with susceptibility to develop severe RA in Mexicans. This association could be independent from HLA-DR alleles and might be used as a prognostic marker for severe RA.
17011587 Monotonicity of interleukin-1 receptor-ligand binding with respect to antagonist in the pr 2007 Feb 7 We consider the interaction between interleukin-1 IL-1, its receptor IL-1RI, the receptor antagonist IL-1Ra and a decoy receptor (or trap) that binds both with the ligand and the antagonist. We study how the interaction between IL-1Ra and the decoy receptor influences the effect of either reagent on reducing the equilibrium concentration of the receptor-ligand complex. We obtain that, given a certain relationship among the equilibrium constants and the total concentrations of solutes, IL-1Ra can reverse the effect of the decoy receptor of decreasing the equilibrium concentration of the receptor-ligand complex. This finding derives from a mathematical result applicable to any reversible chemical reaction system comprising four species arranged in a square such that each species binds its two immediate neighbors. The result gives the monotonicity of the equilibrium concentrations of the complex species as functions of the total concentrations of the simple species.
16370225 5,10-Methylenetetrahydrofolate reductase polymorphisms and pharmacogenetics: a new role of 2005 Nov Knowledge about the role of folate, a water-soluble B vitamin, and single nucleotide polymorphisms (SNPs) in the folate metabolic pathway in human health and disease has been rapidly expanding. Recently, functionally significant SNPs in 5,10-methylenetetrahydrofolate reductase (MTHFR), a critical enzyme for intracellular folate homeostasis and metabolism, have been identified and characterized. An emerging body of in vitro and clinical evidence suggests that these MTHFR SNPs may be an important pharmacogenetic determinant of predicting response to and toxicity of methotrexate and 5-fluorouracil-based cancer and anti-inflammatory treatments because of their well-defined and highly relevant biochemical effects on intracellular folate composition and one-carbon transfer reactions.
16320331 Discovery of new rheumatoid arthritis biomarkers using the surface-enhanced laser desorpti 2005 Dec OBJECTIVE: To identify serum protein biomarkers specific for rheumatoid arthritis (RA), using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology. METHODS: A total of 103 serum samples from patients and healthy controls were analyzed. Thirty-four of the patients had a diagnosis of RA, based on the American College of Rheumatology criteria. The inflammation control group comprised 20 patients with psoriatic arthritis (PsA), 9 with asthma, and 10 with Crohn's disease. The noninflammation control group comprised 14 patients with knee osteoarthritis and 16 healthy control subjects. Serum protein profiles were obtained by SELDI-TOF-MS and compared in order to identify new biomarkers specific for RA. Data were analyzed by a machine learning algorithm called decision tree boosting, according to different preprocessing steps. RESULTS: The most discriminative mass/charge (m/z) values serving as potential biomarkers for RA were identified on arrays for both patients with RA versus controls and patients with RA versus patients with PsA. From among several candidates, the following peaks were highlighted: m/z values of 2,924 (RA versus controls on H4 arrays), 10,832 and 11,632 (RA versus controls on CM10 arrays), 4,824 (RA versus PsA on H4 arrays), and 4,666 (RA versus PsA on CM10 arrays). Positive results of proteomic analysis were associated with positive results of the anti-cyclic citrullinated peptide test. Our observations suggested that the 10,832 peak could represent myeloid-related protein 8. CONCLUSION: SELDI-TOF-MS technology allows rapid analysis of many serum samples, and use of decision tree boosting analysis as the main statistical method allowed us to propose a pattern of protein peaks specific for RA.
16776632 Increased fructosamine in non-diabetic rheumatoid arthritis patients: role of lipid peroxi 2006 Modification of proteins by non-enzymatic glycation is one of the underlying factors known to play a major role in the pathogenesis of many clinical disorders. Glycation of plasma proteins is enhanced by elevated glucose concentrations. However, increased fructosamine has been documented in rheumatoid arthritis patients without any history of diabetes. Collective evidence reveals that malondialdehyde and reduced glutathione can modulate the glycation process. This study was undertaken to unravel the possible association of malondialdehyde and glutathione with fructosamine in rheumatoid arthritis patients. A case-control study was performed on 15 rheumatoid arthritis patients and 15 control subjects. Whole blood glutathione, plasma malondialdehyde, fructosamine and fasting glucose were analyzed in both groups. Partial correlation analysis was performed to predict the independent association of malondialdehyde, glutathione and fasting glucose on fructosamine. In rheumatoid arthritis patients, while fructosamine and malondialdehyde levels were significantly increased, glutathione levels were significantly decreased compared with controls. With partial correlation analysis, fructosamine was found to have a significant positive correlation with malondialdehyde and a negative correlation with glutathione. These data suggest that plasma fructosamine levels are closely associated with malondialdehyde and glutathione in rheumatoid arthritis patients, warranting extra precaution in interpreting fructosamine as a measure of glycemic control in these patients.
16526229 Cytokines in rheumatoid arthritis and osteoarthrosis. 2005 May The aim of this research was to determine the clinical significance of tumor necrosis factor-alpha (TNF-alpha), IL-12, IL-15 and IL-18 in evaluation of the activity of rheumatoid arthritis. Cytokine concentrations in serum samples and synovial fluid were measured by immunoenzymatic methods using kits for human interleukins and the Disease Activity Score 28 in 64 patients with active disease. The control group consisted of 25 subjects with arthritis of the knee and osteoarthrosis. Patients with rheumatoid arthritis have significantly high (p < 0.01) concentrations of examined cytokines in relation to patients with osteoarthritis. By comparing concentrations in 30 patients with high, 14 patients with moderate and 20 patients with mild activity of rheumatoid arthritis, it was established that patients with high degree of disease activity have significantly high (p<0.01; p<0.05) concentrations of examined cytokines in the blood and synovial fluid in relation to patients with moderate and mild disease. We have concluded that cytokine concentrations are good indicators of the degree of rheumatoid arthritis activity. This research is a contribution to understanding the insufficiently known pathogenetic mechanisms of cytokines, especially IL-18, in active disease.
16755805 Handling safety for patients with inflammatory arthritis. 2006 May 23 Moving and handling in the healthcare setting is heavily focused on the safety of healthcare workers and the importance of ensuring training in techniques is up to date. However, careful risk assessment should focus on reduction of injury to patients as much as to healthcare workers. Patients with inflammatory arthritis can be particularly challenging due to the condition and its symptoms.
16583428 What factors account for referral delays for patients with suspected rheumatoid arthritis? 2006 Apr 15 OBJECTIVE: Rheumatoid arthritis (RA) is a common, costly, and disabling disease. Early referral and treatment reduce long-term joint damage and improve functional outcomes. Despite efforts to improve referral, half of patients with RA are not referred in a timely manner. Our objective was to explore the factors influencing the decision of a primary care physician (PCP) to refer or not refer a patient with suspected RA, and to identify modifiable factors influencing timely referral. METHODS: Using qualitative methods and in-depth, face-to-face interviews, we asked Connecticut PCPs to describe the last patient encounter where they suspected RA and the factors influencing referral and nonreferral. Participants represented a range of clinical experience, access to rheumatologists, and practice settings. Sample size was determined by thematic saturation. Transcripts were coded and analyzed using the constant comparative method of qualitative data analysis. RESULTS: We interviewed 19 PCPs, 9 of whom were women. Our analysis identified clinical characteristics, patient preferences, access issues, clinical and administrative leadership, physician confidence and expectations, and interpersonal relationships as important domains influencing the referral decision. These domains interacted to impact timely referral and quality of care. Previously underappreciated factors, such as the magnitude of the effect of physician rapport, appeared to be critical in determining whether or not patients are promptly referred. CONCLUSION: Issues such as physician rapport, as well as clinical and system issues, influence referral for suspected RA. To improve referral for RA, clinical guidelines, medical education, and quality improvement efforts should address all domains influencing the referral decision.
16502118 Risk factors for vertebral fracture in menopausal or postmenopausal Japanese women with rh 2006 The occurrence of vertebral fracture was examined cross-sectionally and longitudinally over a 4-year interval in 117 menopausal and postmenopausal Japanese women with rheumatoid arthritis (RA), whose ages ranged from 50 to 64 years. Patients treated with bisphosphonate were excluded. Vertebral fracture was diagnosed by lateral thoracic and lumbar spine radiography at the start and end of a 4-year period. Bone mineral density (BMD) at L2-L4 according to dual-energy X-ray absorptiometry (DXA), the administration of corticosteroids or methotrexate, and urinary excretion of N-telopeptide of type I collagen (NTx) were also recorded. In the cross-sectional study, the prevalence of vertebral fracture in the initial radiographs of RA patients was 21%, while it was 5% in healthy age-matched controls. Among RA patients treated with corticosteroids, 33% had vertebral fracture, which was a significantly higher prevalence than that in RA patients without steroid administration. In the longitudinal study, vertebral fracture prevalence was also increased in patients more than 60 years old. RA patients having steroid treatment and a BMD/YAM (young adult mean) ratio below 70% had higher risk of vertebral fracture than patients with a BMD/YAM ratio of 70%-80%, which in turn exceeded the risk with a BMD of 80% or more. No adverse effect of low-dose methotrexate on vertebral fracture was found. Urinary NTx was high in RA patients, as reported previously, and did not differ between patients with or without new fracture after 4 years. In conclusion, Japanese RA patients more than 60 years old who were treated with corticosteroid or had a BMD below 80% had high risk of vertebral fracture.
15515123 Serum E-selectin and erythrocyte membrane Na+K+ ATPase levels in patients with rheumatoid 2005 Jul We conducted this study to assess serum soluble E-selectin (sE-selectin) levels and erythrocyte membrane Na(+)K(+) ATPase activity in patients with rheumatoid arthritis (RA) and correlate the levels with disease activity. Levels of sE-selectin were measured in the serum of 20 patients with RA and 20 control subjects by an enzyme-linked immunosorbant assay. Na(+)K(+) ATPase activity was determined by a colorimetric method in RA patients and healthy controls. There were no statistically significant differences between the two groups with respect to demographic data such as age and sex (p > 0.05). The serum levels of sE-selectin, ESR and C-reactive protein (CRP) in RA patients were significantly higher than in healthy controls (p < 0.001). Erythrocyte membrane Na(+)K(+) ATPase activity was significantly lower in the RA group than in the control group (p < 0.001). Correlation analysis revealed significant positive correlations between soluble E-selectin and ESR (r = 0.457; p < 0.05) and CRP (r = 0.682; p < 0.01) levels. There were statistically significant negative correlations between erythrocyte membrane Na(+)K(+) ATPase activity and ESR (r = -0.450; p < 0.05) and CRP (r = -0.446; p < 0.05) levels. Additionally, a significant negative correlations between sE-selectin and Na(+)K(+) ATPase activity was observed (r = -0.80; p < 0.001). These results show that decreases in erythrocyte membrane Na(+)K(+) ATPase activity and increases in sE-selectin are observed in RA, and that increased levels of sE-selectin may also reflect disease status or activity.
16247585 A study on vascular endothelial growth factor and endothelin-1 in patients with extra-arti 2006 May Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with a wide range of extra-articular manifestations. Recent studies emphasise a key inflammatory role of the endothelial cells, either by overexpression of inflammatory mediators or by the proliferation of new blood vessels, in the disease process leading to the systemic organ involvement. To evaluate the relationship between internal organ manifestations and immunological markers of endothelial activation, serum levels of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were determined by an enzyme-linked immunosorbent assay in 64 RA patients and in 32 healthy controls. In comparison with a control group, higher serum concentrations of VEGF and ET-1 (p<0.001) in RA patients were demonstrated. A comparison between both RA groups with (20 patients) and without systemic involvement (44 patients) showed significantly higher concentrations of VEGF (p<0.05) and ET-1 (p<0.01) in the sera of patients with systemic manifestation. Moreover, a significant positive correlation between VEGF and ET-1 (r=0.475, p<0.001) in RA patients was found. A positive correlation between VEGF and Disease Activity Score (DAS) 28 index (r=0.39, p<0.005) as well as erythrocyte sedimentation rate (ESR) (r=0.564, p<0.0001) and C-reactive protein was found. ET-1 serum level correlated significantly with ESR (r=0.326, p<0.05) and DAS 28 index (r=0.307, p<0.05). These results suggest that the elevated serum levels of VEGF and ET-1 are associated with systemic organ involvement in RA patients and may play a key role in the pathogenesis of extra-articular manifestation of the disease.
16641046 Killer cell immunoglobulin-like receptor gene's repertoire in rheumatoid arthritis. 2006 Mar OBJECTIVE: To investigate the role of the killer cell immunoglobulin-like receptor (KIR) gene's repertoire in the pathogenesis of rheumatoid arthritis (RA) in Taiwan. METHODS: KIR genotypes were determined in 122 patients with RA and 96 healthy controls by the sequence-specific primer polymerase chain reaction (SSP-PCR) method. Human leucocyte antigen (HLA)-C genotyping was also performed simultaneously in 72 patients and 66 controls by the SSP-PCR method. RESULTS: The total carriage frequency of KIR 2DS4 regardless of corresponding HLA-Cw4 was significantly increased in RA patients compared with controls [p<0.001, odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.4, Pc<0.01]. The total carriage frequency of KIR 2DL1 regardless of corresponding HLA-C also tended to be increased in RA patients (p<0.02, OR = 2.1, 95% CI = 1.2-3.9, Pc = not significant). The frequency of KIR 2DS4 with corresponding HLA-Cw4 was increased in RA patients in comparison with controls (p = 0.02, OR = 3.2, 95% CI = 1.1-9.4). Moreover, the association of RA with KIR 2DS4 depended on the presence of the corresponding HLA-Cw4. CONCLUSIONS: KIR 2DS4 may be a risk factor for susceptibility to RA in Taiwan.
16628200 MIF: a new cytokine link between rheumatoid arthritis and atherosclerosis. 2006 May Macrophage migration inhibitory factor (MIF) is well established as a key cytokine in immuno-inflammatory diseases such as rheumatoid arthritis. Inflammation is now also recognized as having a crucial role in atherosclerosis, and recent evidence indicates that MIF could also be important in this disease. Here, we review the role of MIF in rheumatoid arthritis and atherosclerosis, discuss the ways in which MIF and its relationship with glucocorticoids could link these diseases, and consider the potential of MIF as a new therapeutic target for small-molecule and antibody-based anti-cytokine drugs.
16269464 Organ messenger ribonucleic acid and plasma proteome changes in the adjuvant-induced arthr 2006 Feb Two receptors [estrogen receptor (ER)alpha and ERbeta] mediate the manifold effects of estrogens throughout the body. Although a clear role has been established for ERalpha in the classical effects of estrogen activity, the physiological role of ERbeta is less well understood. A small-molecule ERbeta selective agonist, ERB-041, has potent antiinflammatory activity in the Lewis rat model of adjuvant-induced arthritis. To characterize the response of target organs and pathways responsible for this antiinflammatory effect, mRNA expression profiling of the spleen, lymph node, and liver was performed, in conjunction with a global analysis of the plasma proteome. We find that the expression of a large number of genes and proteins are altered in the disease model and the majority of these are partially or fully reversed by ERB-041 treatment. Regulated pathways include the acute-phase response, eicosanoid synthesis, fatty acid metabolism, and iron metabolism. In addition, many of the regulated genes and proteins are known to be dysregulated in human rheumatoid arthritis, providing further evidence that the manifestations of the Lewis rat adjuvant-induced arthritis model bear similarity to the human disease.
16870100 Short-term adalimumab therapy improves endo-thelial function in patients with rheumatoid a 2006 May OBJECTIVE: Endothelial dysfunction has been found in patients with rheumatoid arthritis (RA). In this study we aimed to assess whether adalimumab, a fully human monoclonal antibody directed against TNF-alpha, was able to improve endothelial function in RA patients with long-standing disease refractory to infliximab. METHODS: Eight RA patients (7 women; range: 24- 74 years) were studied. They had been treated with the chimeric monoclonal anti-TNF-alpha antibody-infliximab for at least 1 year and were switched to adalimumab therapy because of loss of efficacy following periodical treatment with infliximab. Endothelial dependent (EDV) and independent vasodilatation (EIV) were measured by brachial ultrasonography. Patients were assessed prior to (day 0) and at day 2, and weeks 2 and 12 after the onset of adalimumab therapy. RESULTS: Following adalimumab administration a rapid increase in the percentage (%) of EDV was found in all patients (mean +/- SD: 10.1 +/- 5.1% at day 2 compared to 5.8 +/- 4.1% at day 0). At weeks 2 and 12 the %EDV was also significantly increased compared to day 0. All patients showed decrease in the disease activity score 28 and C-reactive protein levels (P = 0.012). Moreover, at week 12 the atherogenic index was reduced in all patients (P = 0.012). CONCLUSION: Our study confirms that short-term adalimumab therapy yields an active and positive effect on endothelial function in long-standing RA patients with severe disease. This observation emphasizes the potential role of the TNF-alpha blockade in the mechanisms implicated in the development of atherogenesis in RA.
17134501 Effect of infliximab on mRNA expression profiles in synovial tissue of rheumatoid arthriti 2006 We examined the gene expression profiles in arthroscopic biopsies retrieved from 10 rheumatoid arthritis patients before and after anti-TNF treatment with infliximab to investigate whether such profiles can be used to predict responses to the therapy, and to study effects of the therapy on the profiles. Responses to treatment were assessed using European League Against Rheumatism response criteria. Three patients were found to be good responders, five patients to be moderate responders and two patients to be nonresponders. The TNF-alpha status of the biopsies from each of the patients before treatment was also investigated immunohistochemically, and it was detected in biopsies from four of the patients, including all three of the good responders. The gene expression data demonstrate that all patients had unique gene expression signatures, with low intrapatient variability between biopsies. The data also revealed significant differences between the good responding and nonresponding patients (279 differentially expressed genes were detected, with a false discovery rate < 0.025). Among the identified genes we found that MMP-3 was significantly upregulated in good responders (log2 fold change, 2.95) compared with nonresponders, providing further support for the potential of MMP-3 as a marker for good responses to therapy. An even more extensive list of 685 significantly differentially expressed genes was found between patients in whom TNF-alpha was found and nonresponders, indicating that TNF-alpha could be an important biomarker for successful infliximab treatment. Significant differences were also observed between biopsies taken before and after anti-TNF treatment, including 115 differentially expressed genes in the good responding group. Interestingly, the effect was even stronger in the group in which TNF-alpha was immunohistochemically detected before therapy. Here, 1,058 genes were differentially expressed, including many that were novel in this context (for example, CXCL3 and CXCL14). Subsequent Gene Ontology analysis revealed that several 'themes' were significantly over-represented that are known to be affected by anti-TNF treatment in inflammatory tissue; for example, immune response (GO:0006955), cell communication (GO:0007154), signal transduction (GO:0007165) and chemotaxis (GO:0006935). No genes reached statistical significance in the moderately responding or nonresponding groups. In conclusion, this pilot study suggests that further investigation is warranted on the usefulness of gene expression profiling of synovial tissue to predict and monitor the outcome of rheumatoid arthritis therapies.
15899051 Tolerability and adverse events in clinical trials of celecoxib in osteoarthritis and rheu 2005 The objective was to improve understanding of adverse events occurring with celecoxib in the treatment of osteoarthritis and rheumatoid arthritis. Data were extracted from company clinical trial reports of randomised trials of celecoxib in osteoarthritis or rheumatoid arthritis lasting 2 weeks or more. Outcomes were discontinuations (all cause, lack of efficacy, adverse event, gastrointestinal adverse event), endoscopically detected ulcers, gastrointestinal or cardio-renal events, and major changes in haematological parameters. The main comparisons were celecoxib (all doses) versus placebo, paracetamol (acetaminophen) 4,000 mg daily, rofecoxib 25 mg daily, or nonsteroidal anti-inflammatory drugs (NSAIDs) (naproxen, diclofenac, ibuprofen, and loxoprofen). For NSAIDs, celecoxib was compared both at all doses and at licensed doses (200 to 400 mg daily). Thirty-one trials included 39,605 randomised patients. Most patients had osteoarthritis and were women of average age 60 years or above. Most trials lasted 12 weeks or more. Doses of celecoxib were 50 to 800 mg/day. Compared with placebo, celecoxib had fewer discontinuations for any cause or for lack of efficacy, fewer serious adverse events, and less nausea. It had more patients with dyspepsia, diarrhoea, oedema, more adverse events that were gastrointestinal or treatment related, and more patients experiencing an adverse event. There were no differences for hypertension, gastrointestinal tolerability, or discontinuations for adverse events. Compared with paracetamol, celecoxib had fewer discontinuations for any cause, for lack of efficacy, or diarrhoea, but no other differences. Compared with rofecoxib, celecoxib had fewer patients with abdominal pain and oedema, but no other differences. Compared with NSAIDs, celecoxib had fewer symptomatic ulcers and bleeds, endoscopically detected ulcers, and discontinuations for adverse events or gastrointestinal adverse events. Fewer patients had any, or a gastrointestinal, or a treatment-related adverse event, or vomiting, abdominal pain, dyspepsia, or reduced haemoglobin or haematocrit. Discontinuations for lack of efficacy were higher. No differences were found for all-cause discontinuations, serious adverse events, hypertension, diarrhoea, nausea, oedema, myocardial infarction, cardiac failure, or raised creatinine. Company clinical trial reports present much more information than published papers. Adverse event information is clearly presented in company clinical trial reports, which are an ideal source of information for systematic review and meta-analysis.
16235295 Low level laser therapy (Classes I, II and III) for treating rheumatoid arthritis. 2005 Oct 19 BACKGROUND: Rheumatoid arthritis (RA) affects a large proportion of the population. Low Level Laser Therapy (LLLT) was introduced as an alternative non-invasive treatment for RA about ten years ago. LLLT is a light source that generates extremely pure light, of a single wavelength. The effect is not thermal, but rather related to photochemical reactions in the cells. The effectiveness of LLLT for rheumatoid arthritis is still controversial. This review is an update of the original review published in October 1998. OBJECTIVES: To assess the effectiveness of LLLT in the treatment of RA. SEARCH STRATEGY: We initially searched MEDLINE, EMBASE (from 1998), the registries of the Cochrane Musculoskeletal Group and the field of Rehabilitation and Related Therapies as well as the Cochrane Central Register of Controlled Trials (CENTRAL) up to June 2001. This search has now been updated to include articles published up to June 2005. SELECTION CRITERIA: Following an a priori protocol, only randomized controlled trials of LLLT for the treatment of patients with a clinical diagnosis of RA were eligible. Abstracts were excluded unless further data could be obtained from the authors. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, then extracted data and assessed quality using predetermined forms. Heterogeneity was tested using chi-squared. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed, in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI), where the difference between the treated and control groups was weighted by the inverse of the variance. Dichotomous outcomes were analyzed with relative risks. MAIN RESULTS: A total of 222 patients were included in the five placebo-controlled trials, with 130 randomized to laser therapy. Relative to a separate control group, LLLT reduced pain by 1.10 points (95% CI: 1.82, 0.39) on visual analogue scale relative to placebo, reduced morning stiffness duration by 27.5 minutes (95%CI: 2.9 to 52 minutes) and increased tip to palm flexibility by 1.3 cm (95% CI: 0.8 to 1.7). Other outcomes such as functional assessment, range of motion and local swelling did not differ between groups. There were no significant differences between subgroups based on LLLT dosage, wavelength, site of application or treatment length. For RA, relative to a control group using the opposite hand, there was no difference observed between the control and treatment hand for morning stiffness duration, and also no significant improvement in pain relief RR 13.00 (95% CI: 0.79 to 214.06). However, only one study was included as using the contralateral limb as control. . AUTHORS' CONCLUSIONS: LLLT could be considered for short-term treatment for relief of pain and morning stiffness for RA patients, particularly since it has few side-effects. Clinicians and researchers should consistently report the characteristics of the LLLT device and the application techniques used. New trials on LLLT should make use of standardized, validated outcomes. Despite some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected by four important factors: wavelength, treatment duration of LLLT, dosage and site of application over nerves instead of joints. There is clearly a need to investigate the effects of these factors on LLLT effectiveness for RA in randomized controlled clinical trials.
16255017 Infections in patients with rheumatoid arthritis treated with biologic agents. 2005 Nov OBJECTIVE: To estimate the incidence rates of serious and nonserious infections in patients with rheumatoid arthritis (RA) who start treatment with a biologic agent, and to compare these rates with those in patients with RA who receive conventional treatment. METHODS: Patients enrolled in the German biologics register between May 2001 and September 2003 were included. Treating rheumatologists assessed adverse events and serious adverse events. All adverse events and serious adverse events experienced within 12 months after study entry were analyzed. Propensity score methods were applied to estimate which part of a rate increase was likely to be attributable to differences in patient characteristics. RESULTS: Data were available for 512 patients receiving etanercept, 346 patients receiving infliximab, 70 patients receiving anakinra, and 601 control patients treated with disease-modifying antirheumatic drugs. The total number of adverse events per 100 patient-years was 22.6 (95% confidence interval [95% CI] 18.7-27.2) among patients receiving etanercept, 28.3 (95% CI 23.1-34.7) among patients receiving infliximab, and 6.8 (95% CI 5.0-9.4) among controls (P < 0.0001). Significant differences in the rate of serious adverse events were also observed. For patients receiving etanercept, those receiving infliximab, and controls, the total numbers of serious adverse events per 100 patient-years were 6.4 (95% CI 4.5-9.1), 6.2 (95% CI 4.0-9.5), and 2.3 (95% CI 1.3-3.9), respectively (P = 0.0016). After adjusting for differences in the case patient mix, the relative risks of serious adverse events were 2.2 (95% CI 0.9-5.4) for patients receiving etanercept and 2.1 (95% CI 0.8-5.5) for patients receiving infliximab, compared with controls. CONCLUSION: Patients treated with biologic agents have a higher a priori risk of infection. However, our data suggest that this risk is increased by treatment with tumor necrosis factor inhibitors.