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ID PMID Title PublicationDate abstract
21711059 Role of spleen tyrosine kinase inhibitors in the management of rheumatoid arthritis. 2011 Jun 18 Spleen tyrosine kinase (Syk) is a cytoplasmic tyrosine kinase involved in signalling in many of the cells that drive immune inflammation. The development of small molecules that inhibit Syk kinase may change the way we treat disorders such as rheumatoid arthritis (RA), as well as a range of other inflammatory diseases. Fostamatinib (R-788) is an orally bioavailable small molecule. It is the prodrug of R406, which is a potent Syk inhibitor. Fostamatinib was developed because it has more favourable physiochemical properties. It is rapidly converted to R406 by intestinal enterocytes. It has been evaluated in experimental models of RA, such as collagen-induced arthritis. In these models, fostamatinib suppressed clinical arthritis, bone erosions, pannus formation and synovitis. A phase II programme with fostamatinib has largely been completed. Three key trials have been published, lasting 12-26 weeks and each enrolling 189-457 patients (875 in total). All these trials involved placebo therapy and patients continued to receive methotrexate in addition to active treatment with fostamatinib. The first dose-ranging trial evaluated three treatment doses in RA patients who had not fully responded to methotrexate therapy. The second trial compared two treatment doses in patients who had not responded to methotrexate therapy. The third trial compared a single treatment dose with placebo in patients who had not responded to biological therapy. The primary outcome measure was the number of patients achieving American College of Rheumatology (ACR) 20% (ACR20) responses. Placebo ACR20 response rates in all three trials were similar (35-38%). All three trials involved one treatment arm receiving fostamatinib 100 mg twice daily; ACR20 responses with this active treatment ranged from 38% to 67%. A meta-analysis of ACR responses in these trials, using responses to the highest dose in each trial for comparisons with placebo therapy in a random effects model, showed a borderline benefit with ACR20 responses. There were more significant differences with ACR50 and ACR70 responses. The reason that this meta-analysis was not more strongly positive is that the third trial, which evaluated patients who had failed to respond to biological treatments, gave negative results. Individual ACR response components, such as changes in swollen joint counts, showed significant differences in the first two trials, but there were no definite treatment benefits in the third trial. Overall, the differences were significant in a meta-analysis of all three trials. The most important adverse reactions were diarrhoea, neutropenia and raised ALT levels, which all showed significant excesses with active treatment compared with placebo. Too few patients have been studied for a definitive safety profile to be known. Overall, the results of the phase II trials were sufficiently encouraging for a phase III programme to be initiated. It will be some years before their definitive results are available.
22190069 Distressed personality is associated with lower psychological well-being and life satisfac 2012 Apr The distressed personality type ("type D personality") has been shown to be associated with low quality of life and higher morbidity and mortality in various patient groups. Because the role of type D personality is unknown in patients with rheumatoid arthritis (RA), the aim of the present study was to investigate the association of type D personality with aspects of quality of life and disease activity in RA patients. In addition, a potential buffering effect by accepting mindfulness was examined. Participants were 147 patients between 22 and 87 years of age. Patients completed relevant questionnaires at home and the disease activity score was determined. After controlling for potentially confounding variables, multivariate analyses of covariance showed an association of type D personality with a lower satisfaction with life (p < 0.001) and a lower psychological well-being (p < 0.001), but not disease activity in RA patients. Although mindfulness was associated with a higher satisfaction with life (p = 0.02) and positive mood (p = 0.01), it did not diminish the unfavourable associations between type D and well-being. In conclusion, although type D personality is related with lower well-being, it does not seem to be associated with disability or disease activity in RA patients.
21702090 Very early improvements in the wrist and hand assessed by power Doppler sonography predict 2011 Oct OBJECTIVE: To investigate the response of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) by ultrasonographic evaluation of changes in the wrist and hand, and to determine whether such assessments during early TCZ treatment predict later clinical outcome. METHODS: Thirty-two RA patients about to receive TCZ treatment were examined by ultrasound at baseline and after 2 weeks using the Outcome Measures in Rheumatology Clinical Trials semiquantitative scoring of 22 joints (both wrists, proximal interphalangeal joints 1-5, and metacarpophalangeal joints 1-5) as well as clinical and laboratory variables, leading to a calculation of composite indexes. The aim was to determine whether methotrexate treatment and clinical, laboratory, and ultrasonographic evaluation after 2 weeks of TCZ treatment predict treatment outcome at 24 weeks, as assessed by the Disease Activity Score in 28 joints (DAS28). RESULTS: Changes of ultrasound scores after 2 weeks were found to be correlated with changes in DAS28 at 24 weeks (r = 0.545-0.622, P < 0.05). The change of sum power Doppler scores after 2 weeks of treatment was identified as the variable most closely correlated with the change in DAS28 at 24 weeks (r = 0.622, P < 0.05). CONCLUSION: The best predictors after 2 weeks of favorable treatment outcome at 24 weeks were improved power Doppler scores. Methotrexate treatment and composite indexes did not predict favorable treatment outcome in this study.
23073206 Do we need guidelines to stop as well as to start biological therapies for rheumatoid arth 2012 Jul After achieving low disease activity or remission, biological therapy might be stopped in rheumatoid arthritis patients, but information on whether and how this should be done is scarce. Successful discontinuation was highly variable since it was described in 0-97% of patients, in studies with different patient populations and follow-up durations between 12 weeks and over 7 years. In most studies, patients were required to have low disease activity or be in clinical remission for at least 6 months before biological therapy was discontinued. Significant joint damage progression in the first year after discontinuation was rare and functional ability was relatively stable in almost all patients in this year. In patients who had a disease flare, retreatment with biological therapy was successful in 70-100%. Mild infusion reactions after retreatment were described in a small number of patients. In conclusion, in the absence of a guideline for stopping biologicals in RA, we present a preliminary proposal that biological therapy can be stopped in many RA-patients after achieving low disease activity or remission for at least 6 months. Adequate monitoring of disease activity is essential, and retreatment appears to be safe and successful in many patients. Future research may further identify when and/or which patients are most likely to discontinue biological treatment successfully.
21360527 Mapping the CRF-urocortins system in human osteoarthritic and rheumatoid synovial fibrobla 2011 Dec In addition to the brain and pituitary gland, the corticotrophin-releasing factor (CRF) system is expressed in peripheral tissues. In this study we characterize the expression of CRF, urocortins (UCN1, UCN2, and UCN3), and their receptors (CRFR1 and CRFR2) in osteoarthritis (OA) and rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Moreover, we analyze the vasoactive intestinal peptide (VIP) effect on the CRF system, as well as its physiological consequences on mediators of inflammatory/destructive processes. CRF and UCNs exhibit differential pattern in OA and RA-FLS. By real-time PCR we detected more expression of CRF and UCN1 in RA, and UCN2 and UCN3 in OA, while the CRFR2 expression was similar. In RA-FLS VIP treatment resulted in a significant decrease of the proinflammatory peptides, CRF and UCN1, and a significant increase of the potential anti-inflammatory agents, UCN3 and CRFR2. Using Western blot assays, we showed that the ratio between phospho-CREB (p-CREB) and c-AMP response element-binding (CREB) is higher in OA and significantly lower in RA-FLS after VIP treatment, with consequences upon cAMP response element in CRF and UCN1 genes. Real-time PCR and EIA proved that VIP significantly inhibits cycloxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in RA-FLS. In all cases, we consider significant data when P < 0.05. These data indicate a role of endogenous CRF, UCNs, and CRFR2 in the OA and RA joint microenvironment. We confirm the anti-inflammatory function of VIP, through the modulation of the expression of CRF system that impacts in a reduction of mediators with inflammatory/destructive functions, supporting its therapeutic potential in rheumatic diseases.
22179929 The expression and anatomical distribution of BTLA and its ligand HVEM in rheumatoid synov 2012 Jun Co-inhibitory signaling from B and T lymphocyte attenuator (BTLA) can suppress lymphocyte activation and maintain peripheral tolerance. However, the expression and anatomical distribution of BTLA and its ligand, herpesvirus entry mediator (HVEM), in rheumatoid arthritis (RA) synovium have not been reported. In this study, we analyzed the expression of HVEM and BTLA in RA synovium by immunohistochemistry, and our results showed that both factors were observed in all four cases of RA samples. At the cellular level, both HVEM and BTLA were found on the cell membrane and in the cytoplasm. Fluorescence dual staining demonstrated that HVEM was chiefly on CD3(+) T cells, CD68(+) macrophages, and to a lesser extent was found on CD31(+) endothelial cells. Similarly, the expression of BTLA was observed on infiltrated CD3(+) T cells and CD68(+) macrophages. The co-expression of HVEM and BTLA with some members of the B7 family in these sections was also analyzed, and the results showed that HVEM antigen was also found on B7-H3(+) capillaries, while it was absent on B7-H1(+), B7-DC(+), B7-H4(+), and Z39Ig(+) cells. Interestingly, BTLA was observed on B7-H1(+), B7-H4(+), and HVEM(+) cells in the synovium. The characteristic expression and distribution of BTLA/HVEM in the synovium indicated that their signaling probably affects the pathogenesis of RA, and a clear understanding of their functional roles may further elucidate the pathogenesis of this disease.
20221607 Meta-analysis: diagnostic value of serum anti-mutated citrullinated vimentin antibodies in 2011 Jun Conventional tests are not always helpful in making a diagnosis of rheumatoid arthritis (RA). This study aimed to comprehensively and quantitatively summarize the evidence on the accuracy of anti-mutated citrullinated vimentin (MCV) assay in the diagnosis of RA. A comprehensive meta-review of data on the accuracy of MCV concentrations in the diagnosis of RA were carried out from 16 published studies. Furthermore, receiver operating characteristic curves were used to summarize the overall test performance. The summary estimates for MCV in the diagnosis of RA were: sensitivity 0.77 [95% confidence interval (CI) 0.75-0.78], specificity 0.89 (95% CI 0.87-0.90), positive likelihood ratio (LR+) 7.24 (95% CI 5.60-9.36), negative likelihood ratio (LR-) 0.28 (95% CI 0.23-0.34) and diagnostic odds ratio 29.66 (95% CI 21.09-41.71). The area under the summary receiver operating characteristic curves was 0.92. Data from meta-analysis suggest the accuracy of MCV assay in the diagnosis of RA is high, but ultimately clinician must consider the results of MCV tests combing with other conventional examinations and the clinical feature.
22850768 Erosive wrist and hand arthritis: is it a rare manifestation of Behçet's disease? 2013 Oct It is believed that arthritis in Behçet's disease is usually non-erosive and non-destructive. We report herein a 72-year-old female who presented with Behçet's disease and an erosive arthritis of the bilateral elbow, wrist, and metacarpophalangeal and proximal interphalangeal joints, radiologically mimicking rheumatoid arthritis.
21401437 The potential risk of infections during (prolonged) rituximab therapy in rheumatoid arthri 2011 Sep INTRODUCTION: Biologicals are a fast expanding group of new drugs and rituximab (RTX) is one of them. Long-term efficacy and safety constantly need addressing as little is known about these factors. In rheumatoid arthritis, RTX it is used for active disease that is not responding to other therapies. Since RTX acts by depleting B-cells, concerns regarding the long-term safety of this drug have been raised. AREAS COVERED: This review covers 10 manuscripts on RTX safety in rheumatoid arthritis published between January 2004 and July 2010. EXPERT OPINION: In present literature RTX appears to be safe for up to five courses. In this review, important drawbacks of current research are discussed. Longer follow-up time is needed to make relevant conclusions on RTX safety with regard to infectious complications. Prolonged RTX therapy causes subsequent B-cell depletion. Eventually, plasma cells disappear, causing hypogammaglobulinemias and subsequent problems in immunity. The formation of new plasma cells is halted due to a lack of B-cells. Attention needs to be focused on the status of immunoglobulins and the role this plays in the occurrence of infections. Until a complete, long-term safety profile of RTX is available, it cannot be considered safe with regard to the incidence of infectious complications.
23095282 Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patient 2012 Nov 20 BACKGROUND: Rheumatoid arthritis (RA) is a systemic inflammatory condition associated with increased cardiovascular risk. This is not fully explained by traditional risk factors, but direct vascular inflammation and aortic stiffening may play a role. We hypothesized that patients with RA exhibit aortic inflammation, which can be reversed with anti-tumor necrosis factor-α therapy and correlates with aortic stiffness reduction. METHODS AND RESULTS: Aortic inflammation was quantified in 17 patients with RA, before and after 8 weeks of anti-tumor necrosis factor-α therapy by using (18)F-fluorodeoxyglucose positron emission tomography with computed tomography coregistration. Concomitantly, 34 patients with stable cardiovascular disease were imaged as positive controls at baseline. Aortic fluorodeoxyglucose target-to-background ratios (TBRs) and aortic pulse wave velocity were assessed. RA patients had higher baseline aortic TBRs in comparison with patients who have cardiovascular disease (2.02±0.22 versus 1.74±0.22, P=0.0001). Following therapy, aortic TBR fell to 1.90±0.29, P=0.03, and the proportion of inflamed aortic slices (defined as TBR >2.0) decreased from 50±33% to 33±27%, P=0.03. Also, TBR in the most diseased segment of the aorta fell from 2.51±0.33 to 2.05±0.29, P<0.0001. Treatment also reduced aortic pulse wave velocity significantly (from 9.09±1.77 to 8.63±1.42 m/s, P=0.04), which correlated with the reduction of aortic TBR (R=0.60, P=0.01). CONCLUSIONS: This study demonstrates that RA patients have increased aortic (18)F-fluorodeoxyglucose uptake in comparison with patients who have stable cardiovascular disease. Anti-tumor necrosis factor-α therapy reduces aortic inflammation in patients with RA, and this effect correlates with the decrease in aortic stiffness. These results suggest that RA patients exhibit a subclinical vasculitis, which provides a mechanism for the increased cardiovascular disease risk seen in RA.
21779896 Anti-CXCL5 therapy ameliorates IL-17-induced arthritis by decreasing joint vascularization 2011 Dec IL-17-induced joint inflammation is associated with increased angiogenesis. However, the mechanism by which IL-17 mediates angiogenesis is undefined. Therefore, the pathologic role of CXCL1 and CXCL5 was investigated in arthritis mediated by local expression of IL-17, employing a neutralizing antibody to each chemokine. Next, endothelial chemotaxis was utilized to examine whether endothelial migration was differentially mediated by CXCL1 and CXCL5. Our results demonstrate that IL-17-mediated disease activity was not affected by anti-CXCL1 treatment alone. In contrast, mice receiving anti-CXCL5 demonstrated significantly reduced clinical signs of arthritis, compared to the mice treated with IgG control. Consistently, while inflammation, synovial lining thickness, bone erosion and vascularization were markedly reduced in both the anti-CXCL5 and combination anti-CXCL1 and 5 treatment groups, mice receiving anti-CXCL1 antibody had clinical scores similar to the control group. In contrast to joint FGF2 and VEGF levels, TNF-α was significantly reduced in mice receiving anti-CXCL5 or combination of anti-CXCL1 and 5 therapies compared to the control group. We found that, like IL-17, CXCL1-induced endothelial migration is mediated through activation of PI3K. In contrast, activation of NF-κB pathway was essential for endothelial chemotaxis induced by CXCL5. Although CXCL1 and CXCL5 can differentially mediate endothelial trafficking, blockade of CXCR2 can inhibit endothelial chemotaxis mediated by either of these chemokines. These results suggest that blockade of CXCL5 can modulate IL-17-induced inflammation in part by reducing joint blood vessel formation through a non-overlapping IL-17 mechanism.
21430660 Disease-drug-drug interaction involving tocilizumab and simvastatin in patients with rheum 2011 May In rheumatoid arthritis (RA), interleukin-6 (IL-6) concentration is elevated, which may cause reduced cytochrome P450 (CYP) activity and increased exposure (peak plasma concentration and area under the plasma concentration-vs.-time curve (AUC)) to certain drugs. Tocilizumab may reverse IL-6-induced suppression of CYP3A4 activity. In this study, exposure to simvastatin was significantly reduced at 1 and 5 weeks after tocilizumab infusion in 12 patients with RA. The mean effect ratio for simvastatin AUC(last) was 43% (90% confidence interval (CI), 34-55%) at 1 week after tocilizumab infusion (day 15) and 61% (90% CI, 47-78%) at 5 weeks after tocilizumab infusion, as compared with baseline (day 1); both ratios were significantly lower than the bioequivalence boundary (80-125%). Mean plasma C-reactive protein (CRP) levels normalized within 1 week after tocilizumab was initiated; the time course of tocilizumab's CRP-reducing effect paralleled that of simvastatin pharmacokinetics. The study findings suggest that caution should be exercised when starting tocilizumab in RA patients who are taking simvastatin.
21699518 Autoimmune diseases in patients with pemphigus and their first-degree relatives. 2011 Jul BACKGROUND: Pemphigus is an autoimmune blistering disease affecting the skin and mucosa, which mostly in anecdotal reports has been associated with several autoimmune diseases. OBJECTIVE: The aim of this study was to assess the frequency of autoimmune diseases in a large group of patients with pemphigus and their first-degree relatives. METHODS: One hundred and ten patients with pemphigus were interviewed for the existence of various autoimmune diseases. Patients' sera were examined for the presence of several autoantibodies. The existence of autoimmune diseases in 969 first-degree relatives of the patients was assessed via questionnaires. RESULTS: Seven of 110 (6.3%) patients with pemphigus had concurrent autoimmune diseases, including four (3.6%) with autoimmune thyroid disease and three (2.7%) with rheumatoid arthritis. Ten of 969 (1.03%) first-degree relatives of patients with pemphigus had autoimmune thyroid disease, three (0.31%) had rheumatoid arthritis, and three (0.31%) had type 1 diabetes mellitus. The patient's group had a statistically significant higher prevalence of thyroid disease and rheumatoid arthritis than their first-degree relatives (P = 0.046 and 0.016 respectively). CONCLUSIONS: Patients with pemphigus seem to have a higher rate of autoimmune thyroid disease and rheumatoid arthritis than both the general population and their own first-degree relatives. Further studies comparing patients with pemphigus with healthy controls are needed to stratify their risk factors for developing other autoimmune diseases and to define guidelines regarding diagnosis and treatment of coexistent autoimmune disorders.
21266445 Inter-observer reliability of ultrasound detection of tendon abnormalities at the wrist an 2011 Jun OBJECTIVE: To assess inter-observer reliability in US detection of tendon inflammatory and structural changes at wrists and ankles in RA patients. METHODS: Fourteen consecutive RA patients underwent bilateral US assessment of the extensor carpi ulnaris (ECUT) and tibialis posterior tendons (TPTs) by two blinded rheumatologists, with different level of experience in musculoskeletal (MS) US. Grey scale and power Doppler (PD) US assessment was focused on detection of tenosynovitis, tenosynovial and intra-tendon PD signal and structural lesions (i.e. tendinosis, tendon erosion, partial or total rupture). RESULTS: The frequency of US findings detected by Investigator 1 was 28.6% for inflammatory changes and 51.8% for structural damage changes while Investigator 2 detected 34 and 53.6% for the corresponding abnormalities. A high overall agreement (82.7%) was found for inflammatory pathology and 89.7% for structural lesions in all tendons. Mean kappa (κ) values for all tendons and pathology was moderate (κ = 0.42), with fair level of agreement for the wrist region (0.27-0.34) and moderate to good values for the ankle region (κ = 0.47-0.62). Subclinical abnormalities were detected in 37.5% of the tendons by Investigator 1 and 28.6% of the tendons by Investigator 2. CONCLUSIONS: MSUS showed high overall agreement and fair to moderate inter-observer κ-values between investigators with different levels of experience in detection of tendon pathology at the wrist and ankle in RA patients. Further standardization of scanning method and pathology definitions may improve MSUS reproducibility.
21666989 Investigation of the association between metabolic syndrome and disease activity in rheuma 2011 Jun 9 Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis. Increased prevalence of metabolic syndrome (MetS) in RA may occur secondary to specific drug treatment and reduced physical activity associated with this condition. However, some recent studies suggest contradictory theories about the association of RA with MetS. This study was designed to evaluate the frequency of MetS in RA patients and the relationship between MetS with RA disease activity and body mass index (BMI). The study was conducted on 120 RA patients and 431 age- and sex-matched apparently healthy controls. A considerable proportion of patients were being treated with prednisolone and/or methotrexate and/or hydroxychloroquine. Disease activity was measured by the 28 joint count of disease activity score-Cerythrocyte sedimentation rate (DAS28ESR). MetS was evaluated according to International Diabetic Federation (IDF) and Adult Treatment Panel III (ATP III) criteria. The prevalence of MetS was significantly higher in the control group (p = 0.005). We did not find any difference in the prevalence of MetS between the patients with DAS < 3.2 and DAS ≥ 3.2. There was no association between the DAS28 score and the presence of MetS components by either definition. Multiple logistic regression analysis showed that the odds of a DAS > 3.2 in patients with BMI between 25 and 30 kg/m2 (OR = 0.1, p = 0.01) and BMI > 30 kg/m2 (OR = 0.3, p = 0.1), in comparison to BMI < 25 kg/m2, was 1/5 and 1/3, respectively. RA was not found to increase the risk of MetS. In addition, disease activity in RA patients was not influenced by the presence of MetS.
22690384 Classification and clinical assessment. 2012 Jun 5 There are at least nine classification criteria for psoriatic arthritis (PsA) that have been proposed and used in clinical studies. With the exception of the ESSG and Bennett rules, all of the other criteria sets have a good performance in identifying PsA patients. As the CASPAR criteria are based on a robust study methodology, they are considered the current reference standard. However, if there seems to be no doubt that they are very good to classify PsA patients (very high specificity), they might be not sensitive enough to diagnose patients with unknown early PsA. The vast clinical heterogeneity of PsA makes its assessment very challenging. Peripheral joint involvement is measured by 78/76 joint counts, spine involvement by the instruments used for ankylosing spondylitis (AS), dactylitis by involved digit count or by the Leeds dactylitis index, enthesitis by the number of affected entheses (several indices available) and psoriasis by the Psoriasis Area and Severity Index (PASI). Peripheral joint damage can be assessed by a modified van der Heijde-Sharp scoring system and axial damage by the methods used for AS or by the Psoriatic Arthritis Spondylitis Radiology Index (PASRI). As in other arthritides, global evaluation of disease activity and severity by patient and physician and assessment of disability and quality of life are widely used. Finally, composite indices that capture several clinical manifestations of PsA have been proposed and a new instrument, the Psoriatic ARthritis Disease Activity Score (PASDAS), is currently being developed.
20020135 Cementless total hip arthroplasty in patients with rheumatoid arthritis using a tapered de 2011 Mar The results of cementless tapered designed femoral stem were studied at a minimum 10-year follow-up in a non-selected, consecutive group of 27 patients (39 hips) with rheumatoid arthritis. Clinical and radiological analyses were performed in 27 hips, 17 patients (mean age at surgery 45 years) after a mean of 12 years. The postoperative Harris hip score was excellent for 14 hips, 9 hips were rated as good and 4 hips were fair or poor. No stem had to be revised for aseptic loosening. Proximal stress shielding was observed in 26 hips (96%); heterotopic ossification was present in 11 hips (41%). Six hips required revision of the acetabular component. With uncemented tapered femoral fixation excellent 12-year results are achieved in patients with rheumatoid arthritis.
22759910 Adalimumab elicits a restricted anti-idiotypic antibody response in autoimmune patients re 2013 Jan OBJECTIVES: Millions of patients worldwide are treated with therapeutic monoclonal antibodies. These biological therapeutics can be immunogenic, resulting in anti-drug antibody formation which leads to loss of response. Fully human biological agents, such as the anti-tumour necrosis factor α (anti-TNFα) antibody adalimumab, are considered to be weakly immunogenic, but anti-adalimumab antibodies (AAA) were recently detected in more than half of treated patients with rheumatoid arthritis (RA) within 28 weeks of treatment. A study was undertaken to determine the mechanism by which AAA lead to loss of response. METHODS: The specificity of the repertoire of AAA was investigated in a cohort of 50 AAA-positive RA patients. Inhibition experiments using TNFα and patient-derived anti-adalimumab monoclonal antibodies were performed. RESULTS: The antibody response against adalimumab is highly restricted: Fab fragments of a single monoclonal antibody specific for the idiotype of adalimumab inhibited 98.65% (25th-75th percentiles: 98.25-99.90) of the total anti-adalimumab reactivity in serum from 50 AAA-positive patients. The anti-adalimumab response was confined to the TNFα binding region of adalimumab, thereby neutralising its therapeutic efficacy. In line with this restricted specificity, small immune complexes were found in the circulation of AAA-forming patients. CONCLUSIONS: The humoral immune response against adalimumab is highly restricted and limited to the idiotype of the therapeutic antibody. All antibodies result in functional neutralisation of the drug, thereby providing a mechanism by which AAA formation leads to clinical non-response.
23086518 Health care quality indicators on the management of rheumatoid arthritis and osteoarthriti 2013 Feb OBJECTIVE: To make an inventory of quality and content of currently available and published sets of health care quality indicators (HCQIs) for RA and OA. METHODS: A systematic review was performed for documents on the development and/or a description of HCQIs for the management of patients with RA and/or OA, using the PubMed, EMBASE, Web of Science, Cochrane and CINAHL databases up to 1 December 2010 and official websites of arthritis organizations. The following data were extracted: general characteristics, contents and quality of developmental process (six aspects related to the definition of target, target group and stakeholders, patient involvement, description of development and test of validity). RESULTS: The search yielded 498 potentially eligible references and two websites, with ultimately six original HCQI sets for RA and/or OA being identified (one for RA and OA, two for OA and three for RA). The number of HCQI ranged from 7 to 27, with the majority being process indicators. No conflicting indicators between the HCQI sets for one condition were seen. Concerning the quality of the developmental process, all six sets lacked patient involvement. CONCLUSION: Only a limited number of HCQI sets for the management of OA and RA are available, mainly including process indicators. The developmental process was methodologically suboptimal in all cases. As improvement of health care quality is an ongoing process, there is a need for development of HCQIs covering different aspects of health care quality (structure, process and outcome) and using appropriate methodology.
21924866 B cells undergo unique compartmentalized redistribution in multiple sclerosis. 2011 Dec Increasing evidence fosters the role of B cells (BC) in multiple sclerosis (MS). The compartmentalized distribution of BC in blood and cerebrospinal fluid (CSF) is incompletely understood. In this study, we analyzed BC-patterns and BC-immunoreactivity at these sites during active and during stable disease and the impact of disease modifying drugs (DMD) on peripheral BC-homeostasis. For this purpose we assessed BC-subsets in blood and CSF from patients with clinically isolated syndrome (CIS), relapsing remitting MS (RRMS), rheumatoid arthritis (RA), and healthy controls (HC) by flow cytometric detection of whole (W-BC), naïve, transitional (TN-BC), class-switched memory (CSM-BC), unswitched memory (USM-BC), double-negative memory (DNM-BC) BC-phenotypes, plasma blasts (PB), and plasma cells (PC). FACS-data were correlated with BC-specific chemotactic activities in CSF, intrathecal CXCL13-levels, and immunoreactivity of peripheral W-BC. Our study revealed that frequencies of systemic CSM-BC/USM-BC became contracted in active CIS/MS while proportions of naive BC, TN-BC and DNM-BC were reciprocally expanded. Moreover, the shifted BC-composition promoted reduced immunoreactivity of W-BC and resolved during remission. Cross-over changes in CSF included privileged accumulation of CSM-BC linked to intrathecal CXCL13-concentrations and expansion of PB/PC. Treatment with interferon-beta and natalizumab evoked distinct though differing redistribution of circulating BC-subsets. We conclude that symptomatic CIS and MS are accompanied by distinctive changes in peripheral and CSF BC-homeostasis. The privileged reciprocal distribution between naïve versus CSM-phenotypes in both compartments together with the marked chemotactic driving force towards BC prompted by CSF supernatants renders it likely that CSF BC are mainly recruited from peripheral blood during active CIS/MS, whereas constantly low percentages of circulating PB/PC and their failure to respond to migratory stimuli favors intrathecal generation of antibody secreting cells. Notably, BC-redistribution closely resembles alterations detectable in systemic autoimmunity associated with active RA and impacts BC-function Together with unique effects of DMDs on BC-homeostasis these findings underline the important role of BC in MS.