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ID PMID Title PublicationDate abstract
17080911 B-lymphocyte activating factor in systemic lupus erythematosus and rheumatoid arthritis in 2006 Overexpression of B-lymphocyte activating factor (BAFF) results in arthritis, glomerulonephritis and autoantibody formation in mice, but its role in human autoimmune disease is less obvious. Serum BAFF levels in patients with systemic lupus erythematosus (SLE) (n=42) and rheumatoid arthritis (RA) (n=60) were related to levels of disease activity, anti-dsDNA Ab, anti-ENA Ab, rheumatoid factor (RF) and anti-CCP Ab. BAFF levels were also followed over time in 19 SLE patients. BAFF levels correlated inversely with age, were higher in SLE than RA (median 2.7 versus 1.4 ng/mL, P < 0.01) and more SLE than RA patients had increased BAFF levels (57% versus 10%, P < or = 0.01). In SLE, BAFF levels correlated with SLEDAI scores but not with anti-dsDNA Ab levels. SLE patients with increased BAFF levels had higher SLEDAI and CRP levels. In RA, BAFF levels correlated weakly with anti-CCP levels (Rs 0.27, P = 0.07), but not with joint counts, ESR, CRP or RF levels. Longitudinal BAFF levels remained unaltered in two thirds of SLE patients and changes in BAFF levels were unrelated to disease flares. These findings suggest that BAFF stimulation of B-cells may contribute to SLE by other mechanisms than autoantibody production.
17603251 Membranous nephropathy associated with the relatively selective cyclooxygenase-2 inhibitor 2007 Renal dysfunction and urinary abnormalities, which are usually related to drug toxicity, secondary amyloidosis, or those which overlap with other autoimmune conditions, are frequently observed in patients with rheumatoid arthritis. This is the first case report of membranous nephropathy in a patient with early-stage rheumatoid arthritis treated with the relatively selective cyclooxygenase-2 inhibitor, etodolac. The present case suggests that any kind of non-steroidal anti-inflammatory drug can cause membranous nephropathy; thus, physicians should be aware of this renal toxicity when prescribing these drugs.
16670337 Interleukin-17 acts independently of TNF-alpha under arthritic conditions. 2006 May 15 The proinflammatory T cell cytokine IL-17 is a potent inducer of other cytokines such as IL-1 and TNF-alpha. The contribution of TNF in IL-17-induced joint inflammation is unclear. In this work we demonstrate using TNF-alpha-deficient mice that TNF-alpha is required in IL-17-induced joint pathology under naive conditions in vivo. However, overexpression of IL-17 aggravated K/BxN serum transfer arthritis to a similar degree in TNF-alpha-deficient mice and their wild-type counterparts, indicating that the TNF dependency of IL-17-induced pathology is lost under arthritic conditions. Also, during the course of the streptococcal cell wall-induced arthritis model, IL-17 was able to enhance inflammation and cartilage damage in the absence of TNF. Additional blocking of IL-1 during IL-17-enhanced streptococcal cell wall-induced arthritis did not reduce joint pathology in TNF-deficient mice, indicating that IL-1 is not responsible for this loss of TNF dependency. These data provide further understanding of the cytokine interplay during inflammation and demonstrate that, despite a strong TNF dependency under naive conditions, IL-17 acts independently of TNF under arthritic conditions.
17443329 Serum leptin in rheumatoid arthritis. 2007 Aug Leptin is a peptide hormone that has an essential role in the regulation of body weight by inhibiting food intake and stimulating energy expenditure. The role of leptin in the modulation of the immune response and inflammation has been regarded as important. In rheumatoid arthritis (RA) patients it was reported that fasting leads to an improvement of clinical and biological measures of disease activity, which was associated with a marked decrease in serum leptin. These features suggest that leptin may also influence the inflammatory mechanisms of arthritis in humans. In this study we assessed serum leptin levels in RA and osteoarthritis (OA) patients and found a correlation between serum leptin level and other markers as well as bone mass density changes, activity of disease, disease duration and the age of the patients. The blood was collected from 30 RA and 30 OA patients who constituted the control group. Serum leptin level was determined using the DRG Leptin ELISA Kit-a solid phase enzyme-linked immunosorbent assay based on the sandwich principle. The serum level of leptin in RA patients ranged from 1.8 to 81.1 ng/ml and median value was 11.2. There was a positive correlation between body mass index (BMI) of RA patients and serum level of leptin (correlation coefficients Spearman's r = 0.81). According to correlation coefficients, serum leptin level is independent of age of RA patients, stage of disease, number of painful and swollen joints, duration of morning stiffness, disease duration as well as value of titre of the Waaler-Rose, disease activity score (DAS 28) value and presence of rheumatoid nodules. There was a negative correlation between serum leptin level and glomerular filtration rate (GFR). No correlation between the serum leptin level and T-score was found. An influence of steroid treatment on the serum leptin level was not shown. The median serum leptin level in OA patients was 9.2 ng/ml. There was a positive correlation between body mass index of OA patients and serum level of leptin (correlation coefficients Spearman's r = 0.57). No correlation was found between serum leptin level and patient's age, duration of disease and value of laboratory data. There were no correlations between serum leptin level and visual analogue pain scale (VAS) for the lower-limb afflicted patients as well as stage of disease according to Kellgren and Lawrence's score in OA patients. There was a negative correlation between serum leptin level and T-score value in OA patients (r = -0.58, P < 0.05). No statistically significant differences were found between serum leptin levels for RA and OA patients.
18544236 Specific adsorption of the autoantibodies from rheumatoid arthritis patient plasma using h 2008 Rheumatoid arthritis is characterized by chronic polyarthritis and destruction of multiple joints. In this study, poly(hydroxyethyl methacrylate-N-methacryloyl-(L-histidine)-methylester) (PHEMAH) beads were used in the removal of pathogenic antibodies from rheumatoid arthritis patient plasma in a packed bed column. PHEMAH beads, in the size range of 80-120 mum, were produced by suspension polymerization. The beads were contacted with blood in an in vitro system. Loss of blood cells and clotting times were followed. PHEMAH beads were characterized by scanning electron microscopy. We found that PHEMAH beads had a spherical shape and porous structure. Loss of cells in the blood contacting with PHEMAH beads was negligible. IgM-antibody adsorption capacity decreased significantly with the increase of the plasma flow-rate. With increasing IgM-antibody concentration, the amount of IgM-antibody adsorbed per unit mass increased and then reached saturation. Maximum IgM-antibody adsorption amount was 69.2 mg/g. IgM-antibody molecules could be repeatedly adsorbed and desorbed without noticeable loss in the IgM-antibody adsorption amount.
17631746 Chronic alcohol consumption as a predisposing factor for multiple tendon ruptures in unusu 2007 May Simultaneous bilateral patellar tendon ruptures are a rare complication of rheumatoid arthritis (RA). Systemic inflammatory diseases (RA, systemic lupus erythematosus (SLE), chronic renal failure, primary and secondary hyperparathyroidism, diabetes mellitus, obesity, sports activity, older age (>50) and drugs (prolonged use of high doses of steroids, local steroid injections and quinolones) are considered as potent predisposing factors for tendon rupture. We report a case of an alcoholic patient with RA and bilateral spontaneous tendon ruptures of the knees. Circumstantial evidence suggest that in this patient, chronic alcohol consumption, a very frequent cause of toxicity to striated and cardiac muscle, contributed to the injury.
17466917 Is steroid resistance related to multidrug resistance-I (MDR-I) in rheumatoid arthritis? 2007 Jun Both healthy ageing and rheumatoid arthritis (RA) are frequently associated with acquired steroid resistance. Here, we investigated the potential involvement of steroid resistance with multidrug resistance (MDR) and explored the impact of pathological ageing on lymphocyte sensitivity to glucocorticoids. Seventy-four RA patients and 26 healthy controls took part in this study. Peripheral blood mononuclear cells were isolated and T-cell sensitivity to glucocorticoids was measured in vitro. The functional activity of P-glycoprotein was analyzed by flow cytometry and ABCB1/MDR-1 gene polymorphisms were assessed in peripheral lymphocytes. Patients and controls had similar sensitivities to glucocorticoids. Only controls presented age-related immunological changes, including reduced T-cell proliferation and relative resistance to corticosterone. Patients had a higher percentage (72%) of lymphocytes actively extruding rhodamine 123 (Rh123(dim)) than controls (60%) in spite of similar P-glycoprotein activity. A higher percentage of Rh123(dim)+ lymphocytes was observed in patients who were more resistant to dexamethasone in vitro. The distribution of ABCB1 genotypes in RA patients did not differ significantly from that in controls and were not associated to steroid sensitiveness or disease activity. These data suggest that peripheral lymphocytes of arthritic patients are fully responsive to GCs in vitro in spite of displaying higher MDR activity.
17405761 Most people over age 50 in the general population do not meet ACR remission criteria or OM 2007 Jun OBJECTIVE: To analyse the proportion of individuals in the general population over age 50 who do not meet American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA) remission, and OMERACT criteria for minimal disease activity (MDA), and to compare results to RA patients. METHODS: A self-report questionnaire was completed by 1400 community control subjects and 1705 RA patients, including the Health Assessment Questionnaire (HAQ), gradual rating scales for pain, fatigue and global health, duration of morning stiffness and painful joints. The prevalence of 4/6 ACR remission criteria and 4/7 OMERACT criteria for MDA was analysed in community control subjects and patients with RA over age 50. RESULTS: For ACR criteria, 76% of control subjects reported painful joints, 37% morning stiffness, 62% pain and 66% fatigue, vs 94, 65, 84 and 84% of patients with RA. MDA criteria were not met by 64% of control subjects for painful joints, 38% for pain, 45% for global health and 18% for HAQ, vs 89, 60, 69 and 52% of RA patients. The four ACR remission criteria were met by only 15% of control subjects over age 50 and 3% of RA patients, and MDA criteria by 28% of controls and 7% of patients. CONCLUSIONS: The majority of community population over age 50 did not meet criteria for remission or MDA in RA. Although a self-report format may differ from results involving an assessor, the current criteria may not be accurate to identify remission or MDA in people with RA who are older than age 50.
16438485 Genetics of rheumatoid arthritis. 2006 Jan Rheumatoid arthritis (RA) is a heterogeneous autoimmune disorder of unknown cause with variable clinical expression. About 70% of patients are women. Genetic factors play an important role and likely account for about 60% of disease susceptibility and expression. The association with the HLA-DRB1 gene is the best understood, although several non-HLA loci have been linked to RA, including the 18q21 region of the TNFRSR11A gene, which encodes the receptor activator of nuclear factor kappaB, important in bone resorption in RA. Genetic factors are also important in the treatment of RA because the activity of enzymes relevant in the metabolism of drugs such as methotrexate and azathioprine, including methylenetetrahydrofolate reductase and thiopurine methyltransferase, are in part genetically determined.
17502356 Bone mineral density in patients with hand osteoarthritis compared to population controls 2007 Dec OBJECTIVES: Several studies have revealed increased bone mineral density (BMD) in patients with knee or hip osteoarthritis, but few studies have addressed this issue in hand osteoarthritis (HOA). The aims of this study were to compare BMD levels and frequency of osteoporosis between female patients with HOA, rheumatoid arthritis (RA) and controls aged 50-70 years, and to explore possible relationships between BMD and disease characteristics in patients with HOA. METHODS: 190 HOA and 194 RA patients were recruited from the respective disease registers in Oslo, and 122 controls were selected from the population register of Oslo. All participants underwent BMD measurements of femoral neck, total hip and lumbar spine (dual-energy x ray absorptiometry), interview, clinical joint examination and completed self-reported questionnaires. RESULTS: Age-, weight- and height-adjusted BMD values were significantly higher in HOA versus RA and controls, the latter only significant for femoral neck and lumbar spine. The frequency of osteoporosis was not significantly different between HOA and controls, but significantly lower in HOA versus RA. Adjusted BMD values did not differ between HOA patients with and without knee OA, and significant associations between BMD levels and symptom duration or disease measures were not observed. CONCLUSION: HOA patients have a higher BMD than population-based controls, and this seems not to be limited to patients with involvement of larger joints. The lack of correlation between BMD and disease duration or severity does not support the hypothesis that higher BMD is a consequence of the disease itself.
18305977 Effect of anti-TNF treatment on body composition and serum adiponectin levels of women wit 2008 Jun The aim of this study was to investigate the effect of anti-tumor necrosis factor alpha (anti-TNF) treatment on body composition and serum adiponectin levels of women with rheumatoid arthritis (RA). Nineteen women with RA starting anti-TNF treatment were included in the study. Disease activity, body composition, lumbar spine bone mineral density (BMD) and serum adiponectin concentrations were measured at baseline and after 1 year of follow-up. No important changes on body composition and lumbar spine BMD were observed, while the serum levels of adiponectin levels increased after 1 year of anti-TNF treatment (p = 0.02). Anti-TNF treatment in women with RA does not have any significant effect on body composition; however, it is associated with increase in adiponectin levels which may ameliorate the systemic inflammatory response state associated with RA.
19035415 Short-term improvement of endothelial function in rituximab-treated rheumatoid arthritis p 2008 Dec 15 OBJECTIVE: Cardiovascular disease is the major cause of excessive mortality in rheumatoid arthritis (RA) and endothelial dysfunction plays a key role in atherosclerosis. The aim of the present study was to assess whether rituximab therapy was able to improve endothelial function in RA patients refractory to tumor necrosis factor alpha (TNFalpha) blockers. METHODS: Six consecutive RA patients (5 women; age range 55-79 years) with active disease refractory to TNFalpha inhibitor therapy were studied. Patients received intravenous rituximab (1 course, consisting of 2 infusions of 1,000 mg each separated by 2 weeks). Flow-mediated endothelium-dependent vasodilatation (FMD%) and endothelium-independent vasodilatation (postnitroglycerin) were measured at day 0 prior to the first rituximab infusion, at week 2 (before the second infusion), and at month 6. RESULTS: At week 2, a dramatic increase in FMD% values was observed in all patients (mean +/- SD 7.02 +/- 2.31%, median 7.29%, range 3.2-9.75%) compared with those observed before the first infusion (mean +/- SD 3.35 +/- 1.58%, median 3.04%, range 1.69-5.89%). In addition, at month 6, FMD% values in all patients (mean +/- SD 7.66 +/- 1.73%, median 7.64%, range 5.61-9.98%) were greater than those found before the first infusion (P = 0.03). The dramatic improvement of FMD% was associated with a significant decrease in C-reactive protein level and Disease Activity Score in 28 joints. CONCLUSION: Our study demonstrates an active effect of rituximab on endothelial function in RA patients refractory to TNFalpha blockers.
18808212 Discontinuation of methotrexate therapy in older patients with newly diagnosed rheumatoid 2008 BACKGROUND: Rheumatoid arthritis (RA) is a potentially devastating form of chronic arthritis. Methotrexate is the cornerstone of drug therapy of the disorder, and may slow or prevent joint damage. Unfortunately, this agent is not without adverse effects. Furthermore, increasing age has been been invoked as a predictor of greater toxicity and drug discontinuation by some, but not all, investigators. OBJECTIVE: To assess the effect of age and other covariates on methotrexate discontinuation in a population-based sample of older patients with newly diagnosed RA. METHODS: We studied the health administrative databases covering residents of the province of Québec, Canada. In these databases, we identified 246 individuals aged>or=65 years with newly diagnosed RA who had been started on methotrexate. We assessed discontinuation of methotrexate therapy using Cox proportional hazards regression models, with potential predictors of discontinuation being age, sex, co-morbidity, methotrexate dose and route (oral vs intramuscular), folic acid coadministration and disease severity. RESULTS: Five patients died or were lost to follow-up in the database at 6 months, and there were ten such patients at 1 year. Six months after the initial prescription of methotrexate therapy, about 80% (n=192) of remaining subjects continued to be prescribed the drug. By 1 year, 161 of 236 (68.2%) subjects continued to be prescribed the drug; by 2 years, only 108 of 217 (49.8%) subjects continued to receive the drug. Increasing age was associated with a greater risk of methotrexate discontinuation. CONCLUSION: Our population-based data indicate that increasing age is associated with a greater tendency for methotrexate discontinuation in patients with newly diagnosed RA. These results emphasize the need to ensure that older patients with RA are provided with effective therapy to minimize the effects of this chronic, potentially disabling disease.
17694261 Impact of rheumatoid arthritis on quality of life. 2007 Quality of life (QOL) of patients affected by various diseases is now recognized as an important outcome variable. Consenting patients with rheumatoid arthritis (American College of Rheumatology criteria) were included in the study. Quality of life was assessed using the World Health Organization Quality of Life assessment, short form (WHOQOL-BREF). Disease activity was assessed by the Disease Activity Score (DAS28) for 3 variables and functional disability by the Health Assessment Questionnaire (HAQ). Extra-articular manifestations (ExRA) were diagnosed clinically. Seventy-five age-matched normal controls and 136 patients (19 males) were included. The mean duration of rheumatoid arthritis (RA) was 9 +/- 5.8 years. The mean DAS28 and HAQ were 4.43 +/- 1.4 and 0.97 +/- 1.6, respectively. At least one ExRA was present in 30 (22.1%) patients. The WHOQOL scores were significantly lower in patients with RA compared to normal controls. Patients and normal controls scored highest in the social relationship domain. There was significant inverse correlation of HAQ with all four domains of WHOQOL. There was significant inverse correlation of DAS28 with the physical health and psychological domains. Patients with ExRA scored significantly lower in the physical health domain of WHOQOL. Multiple regression analysis showed only HAQ to independently affect QOL. Quality of life is compromised in patients with RA. Patients and normal controls scored higher in the social relationship domain. Functional disability is the most important factor affecting QOL in RA.
17673491 A single tumour necrosis factor haplotype influences the response to adalimumab in rheumat 2008 Apr OBJECTIVE: To determine whether tumour necrosis factor (TNF) gene polymorphisms and/or the shared epitope are genetic predictors of the response to adalimumab (ADA) in rheumatoid arthritis (RA). METHODS: This ancillary study to the Research in Active Rheumatoid Arthritis (ReAct) Phase IIIb study included a large cohort of Caucasian patients with RA from France (n = 388) treated with ADA plus methotrexate (MTX) (n = 182), ADA plus any other DMARD (n = 98) or ADA alone (n = 108). The primary outcome was ACR50 at 12 weeks. Patients underwent genotyping for HLA-DRB1 and three TNF gene polymorphisms (-238A/G,-308A/G and-857C/T). Extended haplotypes involving HLA-DRB1 and TNF loci were reconstructed using the PHASE program. RESULTS: A total of 151 patients (40%) had an ACR50 response at week 12. Neither the number of HLA-DRB1 shared epitope copies nor presence of the three TNF polymorphisms tested separately was significantly associated with ACR50 response at week 12. However, haplotype reconstruction of the TNF locus revealed that the GGC haplotype (-238G/-308G/-857C) in a homozygous form (i.e. present in more than half of the patients) was significantly associated with a lower ACR50 response to ADA at 12 weeks (34% vs. 50% in patients without the haplotype) (p = 0.003; pa = 0.015). This effect was more important in the subgroup of patients concomitantly treated with MTX. CONCLUSION: This large pharmacogenetic study provides preliminary data indicating that a single TNF locus haplotype (-238G/-308G/-857C), present on both chromosomes is associated with a lower response to ADA, mainly in patients treated with ADA and MTX.
18392953 Alterations of the CD4(+), CD8 (+) T cell subsets, interleukins-1beta, IL-10, IL-17, tumor 2008 Sep Rheumatoid arthritis is a multisystem disease with underlying immune mechanisms. Osteoarthritis is a debilitating, progressive disease of diarthrodial joints associated with the aging process. Although much is known about the pathogenesis of rheumatoid arthritis and osteoarthritis, our understanding of some immunologic changes remains incomplete. This study tries to examine the numeric changes in the T cell subsets and the alterations in the levels of some cytokines and adhesion molecules in these lesions. To accomplish this goal, peripheral blood and synovial fluid samples were obtained from 24 patients with rheumatoid arthritis, 15 patients with osteoarthritis and six healthy controls. The counts of CD4 (+) and CD8 (+) T lymphocytes were examined using flow cytometry. The levels of some cytokines (TNF-alpha, IL1-beta, IL-10, and IL-17) and a soluble intercellular adhesion molecule-1 (sICAM-1) were measured in the sera and synovial fluids using enzyme linked immunosorbant assay. We found some variations in the counts of T cell subsets, the levels of cytokines and sICAM-1 adhesion molecule between the healthy controls and the patients with arthritis. High levels of IL-1beta, IL-10, IL-17 and TNF-alpha (in the serum and synovial fluid) were observed in arthritis compared to the healthy controls. In rheumatoid arthritis, a high serum level of sICAM-1 was found compared to its level in the synovial fluid. A high CD4(+)/CD8(+) T cell ratio was found in the blood of the patients with rheumatoid arthritis. In rheumatoid arthritis, the cytokine levels correlated positively with some clinicopathologic features. To conclude, the development of rheumatoid arthritis and osteoarthritis is associated with alteration of the levels of some cytokines. The assessment of these immunologic changes may have potential prognostic roles.
16926184 Combination therapy with sulfasalazine and methotrexate is more effective than either drug 2007 Feb BACKGROUND: Optimal use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis is vital if progression of disease is to be reduced. Methotrexate (MTX) and sulfasalazine (SASP) are widely used inexpensive DMARDs, recently often combined despite no firm evidence of benefit from previous studies. AIM: To establish whether a combination of SASP and MTX is superior to either drug alone in patients with rheumatoid arthritis with a suboptimal response to 6 months of SASP. METHODS: A randomised controlled study of step-up DMARD treatment in early rheumatoid arthritis. In phase I, 687 patients received SASP for 6 months. Those with a disease activity score (DAS) > or =2.4 were offered additional treatment in phase II (SASP alone, MTX alone or a combination of the two). The primary outcome measure was change in DAS. RESULTS: At 6 months, 191 (28%) patients had a DAS <2.4, 123 (18%) were eligible but did not wish to enter phase II, 130 (19%) stopped SASP because of reversible adverse events and 165 (24%) entered phase II. DAS at 18 months was significantly lower in those who received combination treatment compared with those who received either SASP or MTX: monotherapy arms did not differ. Improvement in European League Against Rheumatism and American College of Rheumatology 20, 50 and 70 scores favoured combination therapy. CONCLUSIONS: In this "true-to-life" study, an inexpensive combination of DMARDs proved more effective than monotherapy in patients with rheumatoid arthritis with a suboptimal response to SASP. There was no increase in toxicity. These results provide an evidence base for the use of this combination as a component of tight control strategies.
18085596 Measuring fatigue among women with Sjögren's syndrome or rheumatoid arthritis: a comparis 2008 Mar BACKGROUND: Fatigue is common in both Sjögren's syndrome (SS) and rheumatoid arthritis (RA) and can restrict functioning. AIMS: We tested the convergent validity of the Profile of Fatigue (ProF) using the Multidimensional Fatigue Inventory (MFI) in SS and RA. METHODS: The 16-item ProF and the 20-item MFI were completed by 82 White-British women aged 35-79 years (mean 60.4 years). Thirty-four had been diagnosed with SS for a mean of 7.0 years and 48 had been diagnosed with RA for a mean of 14.5 years. The ProF measures four somatic facets of fatigue and two mental facets; the MFI contains one mental and four somatic facets. The structures of the items from both measures were tested by principal component factor analysis using varimax rotation. RESULTS: No significant differences in fatigue were found between the women with SS or RA. Five factors explained a total of 76% of the variance of the MFI; six factors explained 94% of the variance of the ProF. Mental fatigue items from both questionnaires loaded onto separate factors from somatic fatigue items; the two original facets of mental fatigue in the ProF were replicated. The four somatic fatigue facets of the ProF were generally replicated but the somatic facets of the MFI did not replicate as clearly. Equivalent facets correlated well between the two questionnaires (r >or= 0.65). CONCLUSIONS: Both the ProF and the MFI distinguish between somatic and mental fatigue in SS and RA but the ProF appears better at resolving somatic facets of fatigue.
17644538 Long-term effects of infliximab on bone and cartilage turnover markers in patients with rh 2008 Mar BACKGROUND: Rheumatoid arthritis (RA) is associated with systemic bone loss, subchondral bone erosion and cartilage degradation under the control of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNFalpha). Therefore, we tested the hypothesis that administration of infliximab, an anti-TNFalpha drug in the treatment of RA, would modulate systemic and local bone resorption and reduce cartilage degradation. METHODS: We performed a prospective study of a multicentric cohort of 48 women, mean (SD) age 54.2 (12.1) years old, with severe RA for 11.4 (7.8) years, who started infliximab after failure of other disease-modifying antirheumatic drugs. At baseline and 6, 22 and 54 weeks after initiating Infliximab therapy we measured the following biochemical markers: pro-collagen serum type I N-terminal propeptide (PINP), a marker of bone formation; serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), a marker of cathepsin K-mediated bone collagen degradation believed to reflect systemic bone resorption; serum C-terminal cross-linked telopeptide of type I collagen (ICTP), an index of matrix metalloprotease (MMP) mediated type I collagen degradation reflecting preferential joint metabolism; and urinary CTX-II a biochemical markers of cartilage degradation. Total hip and lumbar spine bone mineral density (BMD) was assessed at baseline, and after 6 and 12 months by dual-energy x-ray absorptiometry (DXA). No patient received bisphosphonates while 77% were under oral glucocorticoids. RESULTS: BMD remained stable over 1 year. Serum CTX-I levels rapidly decreased by 19% and 28% at week 6 and week 22, respectively (analysis of variance (ANOVA) p = 0.032) values returning to pre-treatment level at week 54. By contrast, ICTP levels progressively declined with a maximal 25% decrease at week 54 (ANOVA p = 0.028). By contrast, PINP levels remained stable over time, which led to a 30 to 40% improvement in bone remodelling balance, as assessed by the ratios PINP/CTX and PINP/ICTP (p<0.05). There was no significant change of urinary CTX-II in the whole population, but a slight decrease (ANOVA p = 0.041) in those with pre-treatment levels above the upper limit of normal range. CONCLUSIONS: In summary, the improvement in the formation/resorption marker ratio suggests beneficial systemic and local bone effects of infliximab in patients with RA.
16449362 Association between PADI4 and rheumatoid arthritis: a meta-analysis. 2006 Jul OBJECTIVE: Polymorphisms and haplotypes of the peptidylarginine deiminase type 4 gene (PADI4) have been reported to be associated with rheumatoid arthritis (RA) in a Japanese population. However, subsequent replication studies showed conflicting results. The aim of this study was to determine whether meta-analysis would prove the existence of the association. METHODS: PubMed was searched using the term 'PADI4' for articles from the publication of the first study to December 2005. Replication studies that tested the association between PADI4 and RA were reviewed for meta-analysis. The Breslow-Day test for homogeneity across the studies was calculated. The Mantel-Haenszel procedure was used to pool odds ratios (OR) with 95% confidence intervals (CI) to evaluate the association. RESULTS: Six replication studies, one from Japan and five from Europe and North America, fulfilled the selection criteria for inclusion in the meta-analysis. Homogeneity was confirmed across the replication studies. The common OR was 1.14 (95% CI = 1.07-1.21) for allelic distribution. The association was confirmed when only five replication studies in the European descent populations were combined (P = 0.0096, common OR = 1.10). CONCLUSIONS: Our meta-analysis showed a positive association between PADI4 and RA not only in the Japanese population but also in populations of European descent.