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ID PMID Title PublicationDate abstract
19854855 Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. 2010 Jan RA is a chronic, debilitating disease in which articular inflammation and joint destruction are accompanied by systemic manifestations including anaemia, fatigue and osteoporosis. IL-6 is expressed abundantly in the SF of RA patients and is thought to mediate many of the local and systemic effects of this disease. Unlike a number of other cytokines, IL-6 can activate cells through both membrane-bound (IL-6R) and soluble receptors (sIL-6R), thus widening the number of cell types responsive to this cytokine. Indeed, trans-signalling, where IL-6 binds to the sIL-6R, homodimerizes with glycoprotein 130 subunits and induces signal transduction, has been found to play a key role in acute and chronic inflammation. Elevated levels of IL-6 and sIL-6R in the SF of RA patients can increase the risk of joint destruction and, at the joint level, IL-6/sIL-6R can stimulate pannus development through increased VEGF expression and increase bone resorption as a result of osteoclastogenesis. Systemic effects of IL-6, albeit through conventional or trans-signalling, include regulation of acute-phase protein synthesis, as well as hepcidin production and stimulation of the hypothalamo-pituitary-adrenal axis, the latter two actions potentially leading to anaemia and fatigue, respectively. This review aims to provide an insight into the biological effects of IL-6 in RA, examining how IL-6 can induce the articular and systemic effects of this disease.
20660877 Plantar shear stress distribution in patients with rheumatoid arthritis: relevance to foot 2010 Jul BACKGROUND: Rheumatoid arthritis is an autoimmune disease that causes chronic, progressive joint inflammation; it commonly affects the joints of the feet. Biomechanical alterations and daily pain in the foot are the common outcomes of the disease. Earlier studies focusing on plantar pressure in such patients reported increased vertical loading along with peak pressure-pain associations. However, footwear designed according to the pressure profiles did not relieve symptoms effectively. We examined plantar shear and pressure distribution in patients with rheumatoid arthritis and compared the findings with those of controls, and we investigated a potential relationship between foot pain and local shear stresses. METHODS: A custom-built platform was used to collect plantar pressure and shear stress data from nine patients with rheumatoid arthritis and 14 control participants. Seven patients reported the presence of pain under their feet. Pressure-time and shear-time integral values were also calculated. RESULTS: Peak pressure, pressure-time integral, resultant shear-time integral, and mediolateral shear stress magnitudes were higher in the complication group (P < .05). An association between peak shear-time integral and maximum pain locations was observed. CONCLUSIONS: Increased mediolateral shear stresses under the rheumatoid foot might be attributable to gait instability in such patients. A correlation between the locations of maximum shear-time integral and pain indicate the clinical significance of plantar shear in patients with rheumatoid arthritis.
20594896 Indications of glucocorticoids in early arthritis and rheumatoid arthritis: recommendation 2010 Dec OBJECTIVE: To develop clinical practice guidelines about the indications of glucocorticoid therapy in early arthritis and established rheumatoid arthritis, based on previously published data and on the opinions of rheumatology experts. METHODS: We used a three-step procedure. (a) A scientific committee used a Delphi procedure to select three questions about glucocorticoid indications: what is the role for glucocorticoid therapy in early arthritis? What is the role for long-term glucocorticoid therapy in established rheumatoid arthritis? What is the role for systemic glucocorticoid therapy in flares of rheumatoid arthritis? (b) Evidence providing answers to the three questions was sought in Pubmed, Embase, Cochrane, and abstracts from the annual meetings of the ACR and EULAR. (c) Based on this evidence, recommendations were developed and validated by a panel of experts. The strength of each recommendation was determined based on the level of the underlying evidence. The level of agreement among experts regarding each recommendation was measured. RESULTS: The literature search retrieved 2851 publications, of which 36 were selected based on the titles and abstracts then on the full-length articles. These 36 studies were presented to the experts as a basis for discussion. Six recommendations rated A to D were developed and validated by the experts. They dealt with the appropriateness of low- or moderate-dose glucocorticoid therapy for a limited period in early polyarthritis after advice from a specialist and in the event of active disease, in combination with disease-modifying antirheumatic drug (DMARD) therapy; the appropriateness of low-dose glucocorticoid therapy (no more than 0.1mg/kg/day) in RA if needed to achieve symptom control; and the appropriateness of oral glucocorticoid therapy (no more than 0.5mg/kg/day) for 1 to 2 weeks in polyarticular flares of RA. CONCLUSION: The six recommendations for everyday practice presented here should help to standardize and to optimize clinical practice, thereby improving the management of patients with early arthritis or RA.
19431082 CP-690550, a JAK3 inhibitor as an immunosuppressant for the treatment of rheumatoid arthri 2009 May Pfizer Inc is developing the novel JAK3 inhibitor CP-690550 for the potential prevention of transplant rejection and treatment of autoimmune diseases, such as rheumatoid arthritis (RA) and psoriasis. The benefits of currently available immunosuppressive drugs are countered by numerous side effects, caused mainly by the ubiquitous distribution of the target molecules of these treatments. CP-690550 is expected to overcome these limitations by selectively targeting JAK3, which is expressed generally only in immune cells and is only bound by gamma-chain-bearing cytokine receptors involved in the JAK/STAT signaling pathway. CP-690550 exhibited potent immunosuppressive activity in preclinical models of RA and organ transplant rejection. Phase I and II clinical trials demonstrated the efficacy and safety of CP-690550 in preventing transplant rejection and alleviating the symptoms of RA and psoriasis. At the time of publication, CP-690550 was in phase II/III trials in patients with RA, phase II trials in patients with psoriasis, ulcerative colitis and Crohn's disease, and transplant recipients, and a phase I/II trial for dry eye disease (xerophthalmia). Thus, the preclinical and clinical data strongly support the use of CP-690550 to produce sufficient immunosuppression to prevent organ transplant rejection and to treat autoimmune diseases; CP-690550 could herald the beginning of a new generation of safe and effective immunosuppressive therapies.
19775924 Long-term effects of therapeutic education for patients with rheumatoid arthritis. 2009 Dec INTRODUCTION: The objective of this study was to assess the effects of an educational program on the course of rheumatoid arthritis (RA) after 3 years. METHODS: From December 2002 to December 2003, 39 RA patients participated in a 3-day education program delivered to groups of four or five patients. Effects of the program were evaluated after 3 years in 33 patients, comparatively to baseline, based on the following variables: knowledge of RA (self-questionnaire), disease activity (DAS 28), functional impairment (health assessment questionnaire [HAQ]) and quality of life (arthritis impact measurement scale 2 [AIMS2], short-form). We also compared patient knowledge in the educational program participants and in 38 controls with RA. Direct questions were used to evaluate the program after 3 years. RESULTS: Patient knowledge 3 years after the education program was significantly improved compared to baseline (P<0.0001) and was significantly better than in the controls (P<0.0001). Disease activity was significantly lower in the education group after 3 years than at baseline (DAS28, 3.1 vs. 3.8, P<0.005). Neither the HAQ nor the AIMS2 scores changed significantly after 3 years compared to baseline. The replies to the direct questions indicated a very high level of overall satisfaction with the educational program. CONCLUSION: An educational program tailored to patient needs can produce lasting improvements in knowledge of the disease and may help to control the activity of RA. These results warrant the development of education programs for patients with chronic inflammatory joint disease.
20196860 Diagnostic value of anti-cyclic citrullinated peptides and association with HLA-DRB1 share 2010 INTRODUCTION: The purpose of this study was to examine the diagnostic performance of autoantibodies against citrullinated peptides/proteins (ACPA) and to determine the prevalence of HLA-DRB1 shared epitope alleles (SE) in African patients with rheumatoid arthritis (RA). METHODS: Serum levels of anti-cyclic citrullinated peptides antibodies (anti-CCP2, anti-CCP3), IgM and IgA rheumatoid factors (RF) were measured by enzyme-linked immunosorbent assay in the serum of 56 consecutive RA patients regularly followed in the Rheumatology Unit of the School of Medicine, University of Yaoundé, Yaoundé, Cameroon. Genotyping of HLA-DRB1 alleles was performed by polymerase chain reaction and hybridization with sequence-specific oligonucleotide probes on microbeads arrays. Fifty-one patients with other inflammatory rheumatic diseases and 50 healthy individuals were included as controls. RESULTS: An anti-CCP2 assay showed the best diagnosis sensitivity (82%) and specificity (98%) with high positive predictive (PPV) (96%) and negative predictive values (NPV) (91%). Thirty percent of RA patients were carrying at least one copy of the HLA-DRB1 shared epitope (SE) compared to 10% and 14% of patients with other inflammatory rheumatic diseases and healthy individuals, respectively. The presence of the SE was associated with the production of ACPA. CONCLUSIONS: Anti-CCP2 antibodies are useful markers of RA in African patients. In this cohort, the prevalence of the SE is higher in RA patients than in controls but lower than that reported in patient cohorts of European ancestry. The discrepancy between the high prevalence of ACPA-positive patients and the relatively low number of SE-positive cases suggest that, in addition to SE, other genetic factors control the development of ACPA in African RA patients.
19300372 Oral bisphosphonates-associated osteonecrosis in rheumatoid arthritis. 2009 Jun 1 Adverse effects associated with the use of bisphosphonates are infrequent and consist of pyrexia, renal function impairment, and hypocalcemia. Bisphosphonates-associated osteonecrosis of the jaws is an uncommon but potentially serious complication of intravenous bisphosphonate therapy in cancer patients. The degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as alendronate, is uncertain and warrants careful monitoring. Oral bisphosphonates-associated osteonecrosis can occur in patients with rheumatoid arthritis. We report a case of mandibular osteonecrosis in a patient who received alendronate for 3.8 years. The pathology improved after bisphosphonate therapy discontinuation and sequestrectomy. To our knowledge there are only three cases published in the literature relating bisphosphonates-associated osteonecrosis of the jaws in patients with rheumatoid arthritis. All the cases published, including our case, have reported association between methotrexate, prednisone and alendronate sodium (Fosamax) therapy. Corticosteroid therapy and dental surgery could increase the risk of developing bisphosphonates-associated osteonecrosis of the jaws in these patients.
19273455 Gonadal hormones in men with rheumatoid arthritis--from onset through 2 years. 2009 May OBJECTIVE: To evaluate changes over a 2-year course in the hypothalamic-pituitary-gonadal (HPG) axis in men with early rheumatoid arthritis (RA) from start of treatment with disease modifying antirheumatic drugs. METHODS: Forty-one men with early RA and with joint symptoms less than 1 year were studied. Mean age at inclusion was 53 years and mean disease duration 6 months. They were followed prospectively for 2 years for disease activity [Disease Activity Score 28 (DAS28)], physical impairment (Health Assessment Questionnaire), total serum testosterone, non-sex hormone-binding globulin-bound testosterone, and luteinizing hormone (LH). A group of 131 healthy, medicine-free men served as controls for baseline hormone concentrations. RESULTS: The men with RA already had mean testosterone levels lower than controls early in the disease course. Patients older than 50 years also had significantly lower LH levels compared with controls, consistent with mild hypogonadotropic hypogonadism. In patients who responded to treatment at the 2-year followup the testosterone levels increased significantly. A decrease in DAS28 during the 2 years correlated significantly with increased testosterone levels (r(s) = -0.46, p = 0.006). LH levels were low and stable and did not correlate with disease activity. CONCLUSION: In early RA, current inflammation seemed to affect the HPG axis, mainly at the gonadal rather than the hypothalamic-pituitary level. Prospective studies are indicated to determine if low HPG activity may be a cause rather than a consequence of a chronic inflammatory state.
20688263 Fish oil supplementation increases the cyclooxygenase inhibitory activity of paracetamol i 2010 Jun OBJECTIVE: To examine interactions between fish oil and paracetamol for inhibition of prostaglandin synthesis in patients with rheumatoid arthritis (RA). METHODS: Patients from an early RA clinic who were treated with a standardized combination DMARD regimen were enrolled. They were advised to consume an anti-inflammatory dose of fish oil containing the n-3 fatty acid, eicosapentaenoic acid (EPA), or a comparator oil. High EPA and Low EPA groups were defined by blood EPA levels >3.5% or <2%, respectively, of plasma phospholipid fatty acids. Participants provided a blood sample before, and 1h after ingestion of 1g paracetamol. The blood was incubated in different ways to allow measurement of COX-2 generated prostaglandin E(2) (PGE(2)) and COX-1 generated thromboxane A(2) (TXA(2)). RESULTS: Paracetamol suppressed the eicosanoid measures of COX-1 and COX-2 activities and the suppression was greater in the High EPA group. The results indicate that the combination of fish oil and paracetamol suppresses PGE(2) synthesis by an amount equivalent to that from maximum therapeutic doses of NSAIDs. CONCLUSION: Paracetamol is recommended for first-line use ahead of NSAIDs for symptom relief in RA or OA. Combining paracetamol with fish oil will enhance suppression of nociceptive PGE(2) synthesis and thereby may provide additive symptomatic benefits.
19365268 Clinical value of blocking IL-6 receptor. 2009 May PURPOSE OF REVIEW: Interleukin-6 (IL-6) is a multifunctional cytokine that regulates inflammatory response and immune reaction. Overproduction of IL-6 is pathologically involved in inflammatory autoimmune diseases such as rheumatoid arthritis (RA) and juvenile idiopathic arthritis, and therefore, blocking IL-6 activity is one of therapeutic options for these diseases. Tocilizumab is a humanized anti-IL-6 receptor (IL-6R) antibody and inhibits IL-6 activity. There is now accumulating evidence that tocilizumab is therapeutically effective for patients with RA and other inflammatory autoimmune diseases. This article reviews the clinical value of blocking IL-6R. RECENT FINDINGS: Tocilizumab, as monotherapy and in combination with methotrexate, has been shown to be effective for RA patients with insufficient efficacy to methotrexate or other disease-modifying antirheumatic drugs. These findings of tocilizumab have been expanded to patients refractory to tumor necrosis factor inhibitors. Tocilizumab also retards the progression of structural joint damage. Furthermore, a 5-year long-term safety and efficacy has been shown. Tocilizumab is also a promising therapeutic option for other rheumatic diseases such as systemic-onset juvenile idiopathic arthritis, adult-onset Still's disease, and Takayasu arteritis. SUMMARY: Blocking IL-6R with tocilizumab represents a promising new treatment for RA and other inflammatory diseases. Large registry data will warrant the safety profile of tocilizumab.
20593110 Thrombin generation in rheumatoid arthritis: dependence on plasma factor composition. 2010 Aug Growing evidence indicates that rheumatoid arthritis (RA) is associated with an increased risk for thromboembolic cardiovascular events. We investigated thrombin generation profiles in RA patients and their dependence on plasma factor/inhibitor composition. Plasma factor (F) compositions (II, V, VII, VIII, IX, X), antithrombin and free tissue factor pathway inhibitor (TFPI) from 46 consecutive RA patients with no cardiovascular events (39 female, 7 male, aged 57 [range, 23-75] years; DAS28 [Disease Activity Score] 5.2 +/- 1.1) were compared with those obtained in age- and sex-matched apparently healthy controls. Using each individual's plasma coagulation protein composition, tissue factor-initiated thrombin generation was assessed both computationally and empirically. RA patients had higher fibrinogen (4.18 [IQR 1.09] vs. 2.56 [0.41] g/l, p<0.0001), FVIII (226 +/- 40 vs. 113 +/- 15%, p<0.001), PC (107 [16] vs. 100 [14]%, p<0.001), and free TFPI levels (22.3 [2.2] vs. 14.7 [2.1] ng/ml, p<0.001). DAS28, but not age, RA duration, or C-reactive protein, was associated with FV, FVIII, FIX, FX, antithrombin, and free TFPI (r from 0.27 to 0.48, p<0.05). Intergroup comparison of computational thrombin generation profiles showed that in RA patients, maximum thrombin levels (p=0.01) and the rate of thrombin formation (p<0.0001) were higher, whereas the initiation phase of thrombin generation (p<0.0001) and the time to maximum thrombin levels (p<0.0001) were longer. Empirical reconstructions of the populations reproduced the thrombin generation profiles generated by the computational model. Simulations of thrombin formation suggest that blood plasma composition, i.e. a marked increase in FVIII, somewhat counterbalanced by free TFPI, contributes to the prothrombotic phenotype in RA patients.
19342689 Bruton's tyrosine kinase is involved in miR-346-related regulation of IL-18 release by lip 2009 Apr 15 MicroRNAs (miRNAs) have emerged as key players in the regulation of expression of target mRNAs expression. They have been associated with diverse biological processes, and recent studies have demonstrated that miRNAs play a role in inflammatory responses. We reported previously that LPS-activated fibroblast-like synoviocytes (FLS) isolated from rheumatoid arthritis (RA) patients express IL-18 mRNA but they do not release IL-18. Based on the observation that this inhibition was due to a rapid degradation of IL-18 mRNA, our group has conducted a study to identify miRNAs that could play a role in the "antiinflammatory" response of LPS-activated RA FLS. LPS challenge modulated the expression of 63 miRNAs as assessed by microarray analysis. Fifteen miRNAs were up-regulated, including miR-346, for which overexpression upon LPS treatment was validated by quantitative RT-PCR. We then transfected FLS with an antisense oligonucleotide targeting miR-346 and found that, in these conditions, IL-18 release could be measured upon LPS activation of FLS. Moreover, we also demonstrated that miR-346 indirectly regulated IL-18 release by indirectly inhibiting LPS-induced Bruton's tyrosine kinase expression in LPS-activated RA FLS. These findings suggest that miRNAs function as regulators that help to fine-tune the inflammatory response in RA.
20941938 [Proposal for biologic drugs therapy in rheumatoid arthritis]. 2010 Rheumatoid arthritis is a chronic, inflammatory disease with the prevalence about 1%. Rheumatoid arthritis is characterized with synovitis, often evolve erosions of the joints, pain and functional deficit. Etiology is unknown, but the development of such autoimmune disease is due to genetic and environmental factors. Most of the patients with diagnosis of rheumatoid arthritis use nonbiologic disease modifying antirheumatic drugs. Advances in the undersstanding of the disease process have led to the development of biological agents to treat rheumatoid arthritis. With the use of biologic agents we wish to evolve the goal of therapy from that of symptomatiic relief to clinical remission. Biologic drugs have documented, fast and continuous efficacy with generaly well accepted safety profile. On behalf of Croatian Society for Rheumatology we propose recommendations for the biologic therapy in rheumatoid arthritis.
20035901 Development and validation of gene therapies in autoimmune diseases: Epidemiology to anima 2010 Mar Recent advancement in immunology, molecular biology, and bioinformatics has yielded extensive information on the pathophysiological mechanisms of autoimmunity, which has greatly facilitated the identification of potential therapeutic targets and the development of gene therapy in the treatment of autoimmune disease. Preclinical studies were carried out in animal models. This phenomenon is well illustrated in two prototypic animal models of autoimmune disease: the autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) and collagen-induced arthritis (CIA) model in rheumatoid arthritis (RA). Here we discuss the current data on the development and validation of gene therapy in autoimmunity in these two models. The success in preclinical animal model studies provides the proof-of-concept of gene therapy for potential future applications in the treatment of autoimmune diseases. Furthermore, the identification of risk factors from epidemiological studies reveals further potential therapeutic targets to be examined in animal models.
19877044 Altered skeletal expression of sclerostin and its link to radiographic progression in anky 2009 Nov OBJECTIVE: Osteocytes are considered to be sensors of bone damage and regulators of bone mass by specifically expressing sclerostin, an inhibitor of bone formation. The contribution of osteocytes in regulating local bone remodeling in arthritis is unknown. The aim of this study was to investigate the role of osteocytes as contributors to bone remodeling in ankylosing spondylitis (AS). METHODS: Sclerostin expression and osteocyte death were assessed by immunohistochemistry in joints derived from patients with AS, patients with rheumatoid arthritis (RA), and patients with osteoarthritis (OA), as well as from control subjects. In addition, the serum level of sclerostin was assessed by enzyme-linked immunosorbent assay in healthy subjects and patients with AS; this assessment included the longitudinal correlation of sclerostin serum levels and radiographic progression in the spine of patients with AS. RESULTS: Sclerostin expression was confined exclusively to osteocytes. Whereas the majority of osteocytes in healthy individuals and patients with RA were sclerostin positive, expression was significantly reduced in patients with OA and was virtually absent in patients with AS. Moreover, serum levels of sclerostin were significantly lower in patients with AS than in healthy individuals. Importantly, low serum sclerostin levels in patients with AS were significantly associated with the formation of new syndesmophytes (P = 0.007). CONCLUSION: Sclerostin expression is impaired in patients with AS, suggesting a specific alteration of osteocyte function in this disease. A low serum level of sclerostin in the setting of AS is linked to increased structural damage, emphasizing the role of sclerostin in the suppression of bone formation.
19413909 Enhanced reactivity to pain in patients with rheumatoid arthritis. 2009 INTRODUCTION: Maladaptive physiological responses to stress appear to play a role in chronic inflammatory diseases such as rheumatoid arthritis (RA). However, relatively little stress research in RA patients has involved the study of pain, the most commonly reported and most impairing stressor in RA. In the present study, we compared psychophysical and physiological responses to standardized noxious stimulation in 19 RA patients and 21 healthy controls. METHODS: Participants underwent a single psychophysical testing session in which responses to a variety of painful stimuli were recorded, and blood samples were taken at multiple time points to evaluate the reactivity of cortisol, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) to the experience of acute pain. RESULTS: The findings suggest that RA patients display a fairly general hyperalgesia to mechanical and thermal stimuli across several body sites. In addition, while serum cortisol levels did not differ at baseline or following pain testing in patients relative to controls, the RA patients tended to show elevations in serum IL-6 and demonstrated enhanced pain-reactivity of serum levels of TNF-alpha compared with the healthy controls (P < 0.05). CONCLUSIONS: These findings highlight the importance of pain as a stressor in RA patients and add to a small body of literature documenting amplified responses to pain in RA. Future studies of the pathophysiology of RA would benefit from the consideration of acute pain levels when comparing RA patients with other groups, and future trials of analgesic interventions in RA patients may benefit from evaluating the effects of such interventions on inflammatory activity.
20552328 Osteoporosis in inflammatory joint diseases. 2011 Feb Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are two inflammatory joint diseases characterized by bone complications including osteoporosis. In RA, periarticular bone loss, bone erosions, and systemic osteoporosis are observed, with an increased risk of fractures. Determinants of fractures are underlying conditions (as RA has a female preponderance and an increased prevalence with age), severity of the disease, and use of glucocorticoids. However, bone loss can occur even in glucocorticoid-naive patients. Prospective data show that the optimal control of inflammation in RA is associated with decrease in structural damage and bone loss. RA illustrates the role of inflammation on bone resorption. In AS, osteoporosis is an early event and vertebral fracture risk is increased. Bone loss is related mainly to inflammation, as the disease can occur in young male adult populations, and glucocorticoids are not used in this disease. However, AS is characterized by progressive stiffness and ankylosis of the spine and illustrates also the potential role of inflammation on local bone formation.
20012960 Report of anti-CCP antibody positive paraneoplastic polyarthritis and review of the litera 2011 Dec A 45-year-old female presented to the rheumatology clinic with complaint of pain and swelling of multiple small joints of the hands and feet. She also complained of cough and shortness of breath onset around the same time. Since her cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor tests were positive, rheumatoid arthritis (RA) was diagnosed and she was started on prednisone with plans for additional disease modifying therapy. Chest X-ray showed a small right pleural effusion. While additional pulmonary evaluation was being planned, a few weeks later she presented with dyspnea, fever and tachycardia. Spiral CT showed pulmonary emboli and increased pleural effusion and patient was started on anticoagulation. A chest tube was placed and exudative pleural effusion was drained. Cytology sample from bronchoscopy raised concerns for adenocarcinoma. Open lung biopsy confirmed moderately differentiated adenocarcinoma. The patient died of lung cancer in the hospital 8 weeks from her diagnosis of RA. We describe a case of paraneoplastic polyarthritis with positive anti-CCP antibody test which has not been reported before. We also review the literature on paraneoplastic arthritis which has been described in association with various other malignancies besides lung cancer.
20529331 Vaccination response to protein and carbohydrate antigens in patients with rheumatoid arth 2010 INTRODUCTION: Rheumatoid arthritis (RA) is frequently complicated with infections. The aim of our study was to evaluate vaccination response in patients with RA after B-cell depletion by using rituximab. METHODS: Influenza (Afluria) and pneumococcal polysaccharides (Pneumo23) vaccines were given 6 months after rituximab (post-RTX group, n=11) or 6 days before rituximab treatment (pre-RTX group; n=8). RA patients never exposed to RTX composed the control group (n=10). Vaccine-specific cellular responses were evaluated on day 6 after vaccination, and vaccine-specific humoral responses, on day 21. RESULTS: On day 6 after vaccination, formation of influenza-specific B cells was lower in post-RTX group as compared with the pre-RTX group and controls (P=0.04). Polysaccharide-specific B cells were found in 27% to 50%, being equally distributed between the groups. On day 21, the impairment of humoral responses was more pronounced with respect to influenza as compared with the pneumococcal vaccine and affected both IgG and light-chain production. Total absence of influenza-specific IgG production was observed in 55% of the post-RTX group. CONCLUSIONS: RTX compromises cellular and humoral vaccine responses in RA patients. However, repeated RTX treatment or previous anti-tumor necrosis factor (anti-TNF) treatment did not accentuate these defects.
20007746 A comparison of fatigue correlates in rheumatoid arthritis and osteoarthritis: disparity i 2010 Feb OBJECTIVES: To investigate correlates of fatigue among individuals with RA and OA, including mood, sleep, disease activity and radiographic damage. METHODS: Fatigue was assessed using the Multidimensional Assessment of Fatigue-Global Fatigue Index (MAF-GFI) in 103 patients with RA and 103 with OA. Sleep disturbance and pain were assessed using a visual analogue scale anxiety and depression using the Hospital Anxiety and Depression scale and disability using the HAQ. In the RA cohort, the disease activity score-28 joint count (DAS-28) and the Van der Heijde modified Sharp score were calculated, and in the OA cohort, the Kellgren-Lawrence score and the WOMAC score calculated. RESULTS: The MAF-GFI scores were higher in the OA cohort (P = 0.02). This was not significant after controlling for disability (P = 0.59). OA participants reported greater pain, disability, depression and sleeplessness than those with RA (all P < 0.01). The strongest correlates of fatigue in the RA cohort were depression (P < 0.001) and anxiety (P < 0.001). There was no significant association with pain (P = 0.43), DAS-28 (P = 0.07), HAQ (P = 0.10) or Sharp score (P = 0.78). In OA, the correlates of fatigue were older age (P = 0.02), sleep disturbance (P = 0.03), depression (P = 0.04), disability (P = 0.04) and lower CRP (P = 0.001). CONCLUSIONS: Fatigue is common and severe in both RA and OA. In RA, fatigue had no significant association with pain, disease activity, disability or erosions, but was associated with depression and anxiety. The disparity in correlates indicates that generalizing the experience of fatigue between OA and RA is not appropriate. Fatigue is an important domain in the assessment of disease impact.