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ID PMID Title PublicationDate abstract
19430960 Implications of long-term conditions for both mental and physical health: comparison of rh 2009 Aug PURPOSE: To investigate whether people with long term conditions, whatever their specific nature, need to be assessed and treated for the full range of mental, physical and social problems. Main question investigated: that rheumatoid arthritis and schizophrenia will be associated with significantly greater impairment across the subscores of the SF36 scale than in reference general population samples. Specific hypothesis tested: while rheumatoid arthritis and schizophrenia will impair both physical and mental functioning, when comparing the two groups there will be a greater difference between the physical component scores than there will be between the mental/emotional component scores of the short form health survey (SF-36). METHODS: Cross sectional comparison of SF-36 subscore profiles of cohorts of: (1) people with rheumatoid arthritis attending specialist Rheumatology outpatient clinics in five London hospitals (n = 446), and (2) people with schizophrenia treated by community psychiatric teams in four sites in Europe (n = 409). RESULTS: Both groups had greater impairments across the whole spectrum of mental and physical problems assessed by the SF-36 than age specific normative data for the general population. The results also support our hypothesis that, comparing the people with rheumatoid arthritis and schizophrenia, we did find that there is a greater discrepancy between the physical scales than there is between the mental/emotional scales of the SF-36. CONCLUSIONS: These findings show that whether the primary long-term condition is presenting as physical or as mental disorder, the practitioner should ensure that the full range of physical, mental and social problems is assessed and treated.
20822712 Lack of association of PTPN22, STAT4 and TRAF1/C5 gene polymorphisms with cardiovascular r 2010 Sep OBJECTIVES: To determine whether the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms may be implicated in the development of cardiovascular (CV) events and subclinical atherosclerosis manifested by the presence of endothelial dysfunction or increased carotid intima-media thickness (IMT) in a series of Spanish patients with rheumatoid arthritis (RA). METHODS: Six hundred and twelve patients fulfilling the 1987 American College of Rheumatology classification criteria for RA, seen at the rheumatology outpatient clinics of Hospital Xeral-Calde, Lugo, and Hospital San Carlos, Madrid, were studied. Patients were genotyped using predesigned TaqMan single nucleotide polymorphism genotyping assays. Moreover, between March and December 2007, a subgroup of unselected RA patients with no history of CV events was studied for the presence of subclinical atherosclerosis by the assessment of the endothelial function (n=126) and the carotid artery IMT (n=110) by ultrasonography studies. RESULTS: No significant differences in the allele or genotype frequencies for the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms between RA patients with or without CV events were found. It was also the case when we analysed the potential influence of the genotypes in the presence of endothelial dysfunction or increased carotid artery IMT of patients with RA. CONCLUSIONS: Our results do not show that the PTPN22, STAT4 and TRAF1/C5 gene polymorphisms may confer a direct risk of CV disease in patients with RA.
20520526 Histopathologic spectrum of psoriasiform skin reactions associated with tumor necrosis fac 2010 Aug Tumor necrosis factor (TNF)-α inhibitors (anti-TNF-α biologic drugs), currently used to treat different autoimmune conditions, may be associated with cutaneous drug reactions. New onset or worsening of psoriasis and psoriasis-like reactions have been reported in these patients. However, not much is known about the different histopathologic patterns of such skin lesions. The aim of this study was to evaluate the pathologic spectrum of clinically papulosquamous to pustular "psoriasiform" lesions in this setting. Sixteen biopsies from 9 patients on anti-TNF-α therapy for rheumatoid arthritis (n = 7), Crohn disease (n = 1), and Behçet disease (n = 1) who developed a "psoriasiform" skin rash during treatment were included in this study. None of the patients had history of psoriasis. Five patients (10 biopsies) showed a psoriasis-like pattern that varied from that seen in guttate lesions (4 biopsies), to well-established plaques (3 biopsies) to pustular psoriasis (3 biopsies). Three patients (4 biopsies) showed an interface/lichenoid dermatitis mimicking lichen planus. Two patients (2 biopsies) showed features of pustular folliculitis. Eosinophils varied from none (2 biopsies) to scattered (7 biopsies) to numerous (7 biopsies). Plasma cells were present in most cases. All pustular lesions had negative cultures. In conclusion, anti-TNF drugs elicit a spectrum of cutaneous reactions that go beyond the classical eosinophilic-rich hypersensitivity reaction and may closely mimic primary dermatitis. In addition to psoriasis-like lesions, lichen planus-like dermatitis and sterile pustular folliculitis should be included in the list of anti-TNF-α-related drug reactions. Because the different histopathologic findings may be subtle, clinical correlation is crucial to make the diagnosis.
20704618 Subclinical coronary artery disease in Asian rheumatoid arthritis patients who were in rem 2010 Aug INTRODUCTION: Rheumatoid arthritis (RA) patients who have active disease with longer disease duration have been reported to have increased risk of cardiovascular events compared to the normal population. OBJECTIVE: The primary aim of our study is to ascertain the prevalence of significant asymptomatic coronary artery disease (CAD) in Asian RA patients who are in remission using multi-detector computed tomography (MDCT). The secondary aims of our study are the usage of pulse wave velocity and the biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-senstivity C-reactive protein (hs-CRP) to detect subclinical atherosclerosis in RA patients. METHODS: We performed a comparative cross-sectional study of 47 RA patients who were in remission with a control group of non-RA patients with a history of atypical chest pain in Sarawak General Hospital from November 2008 to February 2009. All patients underwent 64-slice MDCT, assessment of arterial stiffness using the SphygmoCor test and blood analysis for NT-proBNP and hsCRP. RESULTS: There were 94 patients in our study with a mean age of 50 +/- 8.8 years. The RA and control patients in each group were matched in terms of traditional CV risk factors. Our RA patients had a median disease duration of 3 years (IQR 5.5). MDCT showed evidence of CAD in nine (19.1%) RA patients and three (6.4%) control patients (P = 0.06). There was no significant association between pulse wave velocity (PWV) and presence of CAD in our RA group. There was no significant correlation between PWV with levels of proBNP or hsCRP in our RA patients. CONCLUSIONS: In our current pilot study with the limitation of small sample size, RA was not associated with an increased risk of CAD in our RA patients who were in remission. Larger studies of CAD in Asian RA patients are needed to confirm our current finding.
18723565 Sustained changes in lipid profile and macrophage migration inhibitory factor levels after 2009 Aug BACKGROUND: Macrophage migration inhibitory factor (MIF) has recently emerged as an important cytokine possibly linking rheumatoid arthritis (RA) and atherogenesis. Because atherogenesis is accelerated in RA this study was conducted to investigate whether anti-tumour necrosis factor (TNF) therapy could lead to sustained downregulation of systemic MIF levels and improvement in lipid profiles. METHODS: Fifty RA patients with active disease (disease activity score in 28 joints (DAS28) >or=3.2), who started adalimumab therapy at 40 mg every other week, were included. At baseline, weeks 16 and 52 serum levels of MIF and lipids were assessed. In addition, the DAS28 and serum C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were determined. RESULTS: After 16 weeks of adalimumab therapy, both DAS28 and MIF levels were significantly decreased (p<0.001 and p = 0.020, respectively). This was sustained up to week 52 (p<0.001 and p = 0.012, respectively). CRP levels and ESR were significantly reduced after 16 and 52 weeks of adalimumab therapy (p<0.001). High-density lipoprotein cholesterol levels increased at week 16 (p<0.001), but returned to baseline at week 52. Apolipoprotein (apo) A-I levels increased at week 16 (p<0.001) and remained stable (p = 0.005). This resulted in an improved apo B/A-I ratio. CONCLUSIONS: The results underline the sustained downregulation of MIF as a potential new mechanism by which anti-TNF therapy might reduce vascular inflammation, and as such perhaps cardiovascular morbidity in RA patients. This hypothesis is supported by an improved apo B/A-I ratio as well as reduced CRP levels in these patients.
20973999 Data-driven identification of co-morbidities associated with rheumatoid arthritis in a lar 2010 Oct 25 BACKGROUND: In drug development, it is important to have an understanding of the full spectrum of co-morbidities to be expected in the group of patients with the disease of interest. It is usually a challenge to identify the less common events associated with the target disease, even if these events are severe. The purpose of this study is to identify co-morbidities associated with rheumatoid arthritis (RA) as compared with a control group, using a large health care database. METHODS: Marketscan US claims database was used for this retrospective cohort study. Selected were records of persons aged at least 16 Y with at least two claims for RA, and with active insurance status on June 30, 2007. The control group had at least two claims for eczema/dermatitis. Controls were matched by age, gender and insurance status (Medicare or not). All co-morbidities with an ICD9 diagnostic code were identified in the RA and control groups, during a one-year window. Relative risks (RRs) were calculated. Diagnoses were rank-ordered by magnitude of RR. Codes covering RA and arthropathy were excluded. In order to get stable estimates, rank-ordering was performed for diagnoses occurring in at least 20 persons in the control group. RESULTS: Records were selected of 62,681 persons with RA (mean age was 59.0 Y, with 73.8% female, Medicare-covered 35%). A total of 6,897 different ICD9 diagnostic codes were recorded, with 2,220 codes in at least 20 persons of the control group [listed with Relative Risk]. Apart from joint/bone related conditions, strong associations with RA (RR > 3) were found for Adverse effect medicinal and biological substance not elsewhere classified, Unspecified adverse effect drug properly administered, Idiopathic fibrosing alveolitis, Osteomyelitis, Immune deficiency, Elevated sedimentation rate, Tuberculin test reaction abnormal or positive, Anemia and Cushing syndrome. CONCLUSIONS: Data on a large number (> 60,000) of patients with a diagnosis of RA were used to analyze and to list a large number (> 2,000) of co-morbidities. Rank-ordering of RRs of diagnostic codes is a tool to identify quickly many conditions associated with RA.
20422909 Cardiac autonomic dysfunction in patients with systemic lupus, rheumatoid arthritis and su 2010 Jan INTRODUCTION: The manifestations of autonomic nervous system (ANS) dysfunction in autoimmune diseases have been the subject of many studies. However, the published results pertaining to such research are controversial. Sudden cardiac death due to fatal arrhythmias is frequent in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). OBJECTIVE: To analyse risk predictors of sudden cardiac death related to the degree of autonomic dysfunction. METHODS: We performed cardiovascular ANS assessment in 90 patients in this case-controlled study, including 52 (6 male, 46 female) patients with SLE, 38 (6 male, 32 female) with RA and 41 (23 male, 17 female) healthy subjects. The methodology included a comprehensive ECG analysis (with Schiller software AT-10) of QTc interval, late potentials, short-term heart rate variability (HRV) and nonlinear HRV (Poincare plot) analysis; 24-hour Holter ECG monitoring with ECG QTc interval analysis, HRV analysis; 24-hour blood pressure monitoring with systolic and diastolic blood pressure variability; cardiovascular autonomic reflex tests (according to Ewing). Vagal dysfunction was established by performing 3 tests: Valsalva maneuver, deep breathing test and heart rate response to standing test. Dysfunction of the sympathetic nervous system was examined by applying 2 tests: blood pressure response to standing and handgrip test. RESULTS: In all cardiovascular reflex tests, the frequencies of abnormal results were significantly higher among the patients than among the healthy subjects. Severe autonomic dysfunction was more common in RA. QTc interval was more prolonged in patients with SLE. Both diseases were associated with depressed heart rate variability compared to controls, the reduction being greater in RA patients. In the patients with SLE, autonomic dysfunction is predominantly with higher sympathetic activity while in RA vagal predominance is evident. CONCLUSION: SLE and RA are associated with severe autonomic dysfunction and the presence of significant risk predictors related to the onset of sudden cardiac death.
21182767 Increased frequency of metabolic syndrome among Vietnamese women with early rheumatoid art 2010 INTRODUCTION: Rheumatoid arthritis (RA) is associated with increased morbidity and mortality due to cardiovascular disease, and this occurs early in the disease process. The metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in RA; however, little information is available regarding MetS in early RA. We aimed to identify the prevalence of MetS and to determine the potential factors associated with the presence of MetS in Vietnamese women with early RA. METHODS: A total of 105 consecutive women with early RA (disease duration ≤3 years) and 105 age-matched healthy women were checked for MetS according to six MetS definitions (Joint Consensus, International Diabetes Federation, National Cholesterol Education Program 2004 and 2001, European Group for Study of Insulin Resistance, and World Health Organization). Multivariate logistic regression models were constructed to determine independent predictors of MetS in women with RA. RESULTS: Prevalence of MetS varied from 16.2% to 40.9% according to the definitions used in women with RA, and was higher (P < 0.001) than in healthy controls (from 10.5% to 22.9%). Among individual components of MetS, differences between women with RA and controls were observed for hypertension (P < 0.001), low high density lipoprotein-cholesterol (HDL-C) levels (P < 0.001), and abdominal obesity (P = 0.019). After adjusting for age and physical activity, higher erythrocyte sedimentation rate (ESR) (odds ratios (OR) = 1.516, 95% confidence interval (CI): 1.073 to 3.195, P = 0.042), disease activity score (DAS28) (OR = 1.736, 95% CI: 1.293 to 2.786, P = 0.019), health assessment questionnaire (HAQ) score (OR = 1.583, 95% CI: 1.195 to 2.367, P = 0.035), and less methotrexate use (OR = 0.736, 95% CI: 0.547 to 0.962, P = 0.024) remained significant independent predictors of the presence of MetS in women with RA. CONCLUSIONS: Women with early RA already had higher prevalence of MetS compared with healthy controls. Higher systemic inflammatory marker, disease activity and disability scores, and less methotrexate use were independent predictors associated with the presence of MetS in women with early RA. These findings suggest that physicians should screen for MetS in women with early RA to control its components and therefore reduce their risk of cardiovascular diseases.
20838658 Persistence with statins and onset of rheumatoid arthritis: a population-based cohort stud 2010 Sep 7 BACKGROUND: The beneficial effects of statins in rheumatoid arthritis (RA) have been suggested previously, but it is unclear whether statins may prevent its development. The aim of this retrospective cohort study was to explore whether persistent use of statins is associated with onset of RA. METHODS AND FINDINGS: The computerized medical databases of a large health organization in Israel were used to identify diagnosed RA cases among adults who began statin therapy between 1998 and 2007. Persistence with statins was assessed by calculating the mean proportion of follow-up days covered (PDC) with statins for every study participant. To assess the possible effects of healthy user bias, we also examined the risk of osteoarthritis (OA), a common degenerative joint disease that is unlikely to be affected by use of statins. A total of 211,627 and 193,770 individuals were eligible for the RA and OA cohort analyses, respectively. During the study follow-up period, there were 2,578 incident RA cases (3.07 per 1,000 person-years) and 17,878 incident OA cases (24.34 per 1,000 person-years). The crude incidence density rate of RA among nonpersistent patients (PDC level of <20%) was 51% higher (3.89 per 1,000 person-years) compared to highly persistent patients who were covered with statins for at least 80% of the follow-up period. After adjustment for potential confounders, highly persistent patients had a hazard ratio of 0.58 (95% confidence interval 0.52-0.65) for RA compared with nonpersistent patients. Larger differences were observed in younger patients and in patients initiating treatment with high efficacy statins. In the OA cohort analysis, high persistence with statins was associated only with a modest decrement in risk ratio (hazard ratio = 0.85; 0.81-0.88) compared to nonadherent patients. CONCLUSIONS: The present study demonstrates an association between persistence with statin therapy and reduced risk of developing RA. The relationship between continuation of statin use and OA onset was weak and limited to patients with short-term follow-up.
21160042 Immune complex-mediated cell activation from systemic lupus erythematosus and rheumatoid a 2011 Jan 15 IL-1R-associated kinases (IRAKs) are important mediators of MyD88-dependent signaling by the TLR/IL-1R superfamily and facilitate inflammatory responses. IRAK4 and IRAK1 function as active kinases and as scaffolds for protein-protein interactions. We report that although IRAK1/4 kinase activity is essential for human plasmacytoid dendritic cell (pDC) activation, it is dispensable in B, T, dendritic, and monocytic cells, which is in contrast with an essential active kinase role in comparable mouse cell types. An IRAK1/4 kinase inhibitor abrogated TLR7/9-induced IFN-α responses in both mouse and human pDCs, but other human immune cell populations activated via TLR7/9 or IL-1R were refractory to IRAK4 kinase inhibition. Gene ablation experiments using small interfering RNA demonstrated an essential scaffolding role for IRAK1 and IRAK4 in MyD88-dependent signaling. Finally, we demonstrate that autoimmune patient (systemic lupus erythematosus and rheumatoid arthritis) serum activates both pDC and B cells, but IRAK1/4 kinase inhibition affects only the pDC response, underscoring the differential IRAK1/4 functional requirements in human immune cells. These data reveal important species differences and elaborate cell type requirements for IRAK1/4 kinase activity.
20230188 The clinical efficacy and safety of certolizumab pegol in rheumatoid arthritis. 2010 May IMPORTANCE OF THE FIELD: The treatment of rheumatoid arthritis has changed dramatically over the past 25 years, first with the introduction of methotrexate and then the introduction of biologic therapy. These agents have provided patients with multiple treatment options to try to achieve disease remission. Unfortunately, no one single agent is fully effective in every patient; different patients respond to different therapies, even those with the same mechanism of action, in different ways. Another medication, such as certolizumab pegol, is a welcome addition to our treatment armamentarium of rheumatoid arthritis. AREAS COVERED IN THIS REVIEW: The basis of this review is all the peer-reviewed manuscripts found in PubMed and Medline searches from 1990 to 2009 and abstracts on certolizumab pegol presented at the American College of Rheumatology and European League Against Rheumatism within the past 5 years. WHAT THE READER WILL GAIN: This review should enable the reader to fully understand the benefit:risk ratio of certolizumab pegol in the treatment of rheumatoid arthritis. TAKE HOME MESSAGE: Certolizumab pegol is an effective agent either in combination with methotrexate or as monotherapy in the treatment of rheumatoid arthritis with a safety profile similar to other approved TNF inhibitors.
20370892 A crucial role for tumor necrosis factor receptor 1 in synovial lining cells and the retic 2010 INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that mainly affects synovial joints. Biologics directed against tumor-necrosis-factor (TNF)-alpha are efficacious in the treatment of RA. However, the role of TNF receptor-1 (TNFR1) in mediating the TNFalpha effects in RA has not been elucidated and conflicting data exist in experimental arthritis models. The objective is to investigate the role of TNFR1 in the synovial lining cells (SLC) and the reticuloendothelial system (RES) during experimental arthritis. METHODS: Third generation of adenovirus serotype 5 were either injected locally in the knee joint cavity or systemically by intravenous injection into the retro-orbital venous sinus to specifically target SLC and RES, respectively. Transduction of organs was detected by immunohistochemistry of the eGFP transgene. An adenoviral vector containing a short hairpin (sh) RNA directed against TNFR1 (HpTNFR1) was constructed and functionally evaluated in vitro using a nuclear factor-kappaB (NF-kappaB) reporter assay and in vivo in streptococcal cell wall-induced arthritis (SCW) and collagen-induced arthritis (CIA). Adenoviruses were administered before onset of CIA, and the effect of TNFR1 targeting on the clinical development of arthritis, histology, quantitative polymerase chain reaction (qPCR), cytokine analyses and T-cell assays was evaluated. RESULTS: Systemic delivery of Ad5.CMV-eGFP predominantly transduced the RES in liver and spleen. Local delivery transduced the synovium and not the RES in liver, spleen and draining lymph nodes. In vitro, HpTNFR1 reduced the TNFR1 mRNA expression by three-fold resulting in a 70% reduction of TNFalpha-induced NF-kappaB activation. Local treatment with HpTNFR1 markedly reduced mRNA and protein levels of interleukin (IL)-1beta and IL-6 in SLC during SCW arthritis and ameliorated CIA. Systemic targeting of TNFR1 in RES of liver and spleen by systemic delivery of Ad5 virus encoding for a small hairpin RNA against TNFR1 markedly ameliorated CIA and simultaneously reduced the mRNA expression of IL-1beta, IL-6 and Saa1 (75%), in the liver and that of Th1/2/17-specific transcription factors T-bet, GATA-3 and RORgammaT in the spleen. Flow cytometry confirmed that HpTNFR1 reduced the numbers of interferon (IFN)gamma (Th1)-, IL-4 (Th2)- and IL-17 (Th17)-producing cells in spleen. CONCLUSIONS: TNFR1-mediated signaling in both synovial lining cells and the reticuloendothelial system independently played a major pro-inflammatory and immunoregulatory role in the development of experimental arthritis.
20329616 [Clinical efficacy of Corydalis composite combined with methotrexate in treating rheumatoi 2009 Nov OBJECTIVE: To observe the clinical efficacy and safety of Corydalis composite (CDC) combined with methotrexate (MTX) in treating rheumatoid arthritis (RA). METHODS: Seventy-six RA patients were randomly assigned to 2 groups, 37 in the treated group received the combined therapy, and the 39 received MTX treatment alone, all were treated for 12 weeks. Efficacy of treatment was evaluated adopting the standard of American College of Rheumatology (ACR), taking ACR20 as the chief criterion; ACR50, ACR70 as well as the clinical indexes and items in Health Account Questionnaire (HAQ) as the auxiliary criteria, including joint swelling index, joint tenderness index, holding power, morning stiffness time, resting pain, erythrocyte sedimentation rate (ESR), C-reactive protein. And the adverse reaction was recorded at the same time. RESULTS: After being treated for 4, 8 and 12 weeks, the ACR20 response rate reached 35.14%, 59.46% and 70.27% respectively in patients of the treated group, while that in the control group was 17.95%, 35.90% and 46.15% respectively, significant difference between groups was shown in the outcome of week 8 and 12 (P < 0.05). ACR50 and ACR70 improving rate at all the time points of observation were increased in the treated group, with the ACR50 improving rate at week 12 higher than that in the control group (43.24% vs. 20.51%, P < 0.05). As compared with the control group, the improvements in all the auxiliary criteria were more significant in the treated group (P < 0.05). The incidence of adverse reaction was less in the treated group than in the control group (32.43% vs. 56.41%, P < 0.05), particularly in term of the damage on liver (0 vs. 10.26%, P < 0.05). CONCLUSION: CDC combined with MTX is more effective than MTX alone in treating active RA with less adverse reaction.
19479340 Association of STAT4 polymorphism with rheumatoid arthritis and systemic lupus erythematos 2010 Jan STAT4 is a transcription factor that has been implicated in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Recently, several reports has documented that a STAT4 haplotype is associated with RA, SLE and Sjogren's syndrome. To summarize and review these findings, we conducted a meta-analysis of all relevant reports published before September 2008. Studies on STAT4 rs7574865 single nucleotide polymorphism (SNP) of RA and SLE were identified using PubMed. Meta-analyses were performed for 15,609 patients with RA and 15,793 controls from 14 published studies and for 2,478 patients with SLE and 5,058 controls from 8 published studies. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on random effects models were calculated for all available studies. The overall ORs for the minor T allele of STAT4 rs7574865 SNP were 1.27 (95% CI 1.20-1.34) in RA and 1.57 (95% CI 1.44-1.71) in SLE. Asian controls have significantly higher allele frequency (32%) for the minor T allele of STAT4 rs7574865 SNP than population of European origin (22%), however, there was no significant difference of ORs for RA and SLE by ethnicity. No apparent effect of anti-CCP positivity was found in stratified analysis. The risk of STAT4 genotype for SLE was significantly higher than for RA in populations of European origin and Asian. The results of our meta-analysis demonstrated that STAT4 rs7574865 SNP is significantly associated with RA and SLE. In addition to specific alleles of HLA-DRB1, the minor T allele of STAT4 rs7574865 SNP is a common RA risk factor in populations of European origin and Asian.
20108988 Newer biological agents in rheumatoid arthritis: impact on health-related quality of life 2010 Health-related quality of life (HR-QOL) in patients with rheumatoid arthritis (RA) is significantly impaired as a result of pain, deficits in physical function and fatigue associated with this disease. Decrements in HR-QOL are also associated with an increased probability of no longer working, absence from work due to RA-associated sickness, and reduced productivity while at work or in the home, all of which have consequences for the patient as well as society. HR-QOL and productivity are thus important components in the assessment of outcomes in RA, and assessment of HR-QOL is now recommended in clinical trials that assess the efficacy of new treatments for RA. Measures to assess HR-QOL include the Medical Outcomes Study Short Form 36 (SF-36), EuroQol (EQ-5D) and the Health Utilities Index - Mark 3 (HUI3); these measures not only provide an indication of the clinical (i.e. statistical) efficacy of a treatment, but also provide information on whether this efficacy is truly 'meaningful' from a patient's perspective. These measures have been utilized in clinical trials of biological agents in patients with RA, including tumour necrosis factor inhibitors (etanercept, infliximab, adalimumab, certolizumab pegol and golimumab), the co-stimulatory inhibitor molecule abatacept, the B-cell depletion agent rituximab and the interleukin-6 receptor antagonist tocilizumab, and have demonstrated that these agents can significantly improve HR-QOL. Assessment of work productivity in patients with RA and the impact of treatment is a practical way to measure disability from RA from individual and societal perspectives. As RA affects women three times more frequently than men, there is also a critical need for productivity assessment within the home as well as participation in family/social/leisure activities. Data from recent trials of biological agents demonstrate that these agents can reverse disease-related decrements in productivity and limitations in participation in family, social and leisure activities in patients with active RA. However, despite this recognition, several challenges in the assessment of productivity remain, including standardization of instruments. Development of additional instruments to assess HR-QOL and productivity that are easier to use in daily practice may further improve our ability to monitor the effectiveness of therapies.
20024514 Melanocortin peptide therapy for the treatment of arthritic pathologies. 2009 Dec 16 Arthritic pathologies are a major cause of morbidity within the western world, with rheumatoid arthritis affecting approximately 1% of adults. This review highlights the therapeutic potential of naturally occurring hormones and their peptides, in both arthritic models of disease and patients. The arthritides represent a group of closely related pathologies in which cytokines, joint destruction, and leukocytes play a causal role. Here we discuss the role of naturally occurring pro-opiomelanocortin (POMC)-derived melanocortin peptides (e.g., alpha melanocyte stimulating hormone [alpha-MSH]) and synthetic derivatives in these diseases. Melanocortins exhibit their biological efficacy by modulating proinflammatory cytokines and subsequent leukocyte extravasation. Their biological effects are mediated via seven transmembrane G-protein-coupled receptors, of which five have been cloned, identified, and termed MC1 to MC5. Adrenocorticotrophic hormone represents the parent molecule of the melanocortins; the first 13 amino acids of which (termed alpha-MSH) have been shown to be the most pharmacologically active region of the parent hormone. The melanocortin peptides have been shown to display potent anti-inflammatory effects in both animal models of disease and patients. The potential anti-inflammatory role for endogenous peptides in arthritic pathologies is in its infancy. The ability to inhibit leukocyte migration, release of cytokines, and induction of anti-inflammatory proteins appears to play an important role in affording protection in arthritic injury, and thus may lead to potential therapeutic targets.
20131274 Human single-chain variable fragment that specifically targets arthritic cartilage. 2010 Apr OBJECTIVE: To demonstrate that posttranslational modification of type II collagen (CII) by reactive oxygen species (ROS), which are known to be present in inflamed arthritic joints, can give rise to epitopes specific to damaged cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA) and to establish a proof of concept that antibodies specific to ROS-modified CII can be used to target therapeutics specifically to inflamed arthritic joints. METHODS: We used a semisynthetic phage display human antibody library to raise single-chain variable fragments (scFv) specific to ROS-modified CII. The specificity of anti-ROS-modified CII scFv to damaged arthritic cartilage was assessed in vitro by immunostaining articular cartilage from RA and OA patients and from normal controls. The in vivo targeting potential was tested using mice with antigen-induced arthritis, in which localization of anti-ROS-modified CII scFv in the joints was determined. The therapeutic effect of anti-ROS-modified CII scFv fused to soluble murine tumor necrosis factor receptor II-Fc fusion protein (mTNFRII-Fc) was also investigated. RESULTS: The anti-ROS-modified CII scFv bound to damaged arthritic cartilage from patients with RA and OA but not to normal preserved cartilage. When systemically administered to arthritic mice, the anti-ROS-modified CII accumulated selectively at the inflamed joints. Importantly, when fused to mTNFRII-Fc, it significantly reduced inflammation in arthritic mice, as compared with the effects of mTNFRII-Fc alone or of mTNFRII-Fc fused to an irrelevant scFv. CONCLUSION: Our findings indicate that biologic therapeutics can be targeted specifically to arthritic joints and suggest a new approach for the development of novel treatments of arthritis.
20198405 No differences in outcomes between cemented and uncemented acetabular components after 12- 2010 Mar BACKGROUND: Even though there are multiple studies documenting the outcome of the Charnley low-friction arthroplasty as well as abundant studies on uncemented arthroplasties, there is a dearth of comparative studies of the uncemented acetabular component and a cemented component. In this study we aimed to document the long-term clinical and radiographic outcome as well as component survival in a randomized controlled trial. MATERIALS AND METHODS: Two hundred fifteen patients (240 hips) were randomly allocated to receive a cemented Charnley cup or uncemented Duraloc 1200 cup. All patients received cemented Charnley stems and were evaluated clinically and radiographically after 6 months, and 2, 5, and 10 years. RESULTS: Harris Hip Scores improved from 48.3 [95% confidence interval (CI) 45.0-51.6] to 90.2 [95% CI 87.9-92.6] in the Charnley group and from 49.3 [95% CI 86.9-91.3] in the Duraloc group at 6 months. After 10 years, the Charnley group's Harris Hip Score was 89.8 [95% confidence interval (CI) 87.0-92.6], and the Duraloc group's score was 87.3 (95% CI 84.1-90.6). In the radiographic analysis after 10 years, there was no statistical difference in the prevalence of radiographic signs of loosening. Nine cups were revised in the Charnley group, and five cups were removed in the Duraloc group. The difference was not statistically significant. There was no statistical difference between the cups when aseptic loosening was the end-point, nor in survival analyses. CONCLUSIONS: There is no statistically significant difference in clinical or radiological outcome between the Charnley cup and the Duraloc after 10 years, and no difference in implant survival after 12-14 years. The uncemented Duraloc cup is as good as the cemented Charnley cup after 10 years.
20447957 Current evidence for the management of rheumatoid arthritis with biological disease-modify 2010 Jun OBJECTIVES: To review the evidence for the efficacy and safety of biological agents in patients with rheumatoid arthritis (RA) to provide data to develop treatment recommendations by the European League Against Rheumatism (EULAR) Task Force. METHODS: Medline, Embase and Cochrane databases were searched for relevant articles on infliximab (IFX), etanercept (ETN), adalimumab (ADA), certolizumab-pegol (CZP), golimumab (GLM), anakinra (ANA), abatacept (ABT), rituximab (RTX) and tocilizumab (TCZ) published between 1962 and February 2009; published abstracts from the 2007-2008 American College of Rheumatology (ACR) and EULAR conference were obtained. RESULTS: 87 articles and 40 abstracts were identified. In methotrexate (MTX) naïve patients, biological therapy with IFX, ETN, ADA, GLM or ABT has been shown to improve clinical outcomes (level of evidence 1B). In MTX/other synthetic disease-modifying antirheumatic drug (DMARD) failures all nine biological agents confer benefit (1B), with lower efficacy noted for ANA. RTX, ABT, TCZ and GLM demonstrate efficacy in tumour necrosis factor inhibitor (TNFi) failures (1B). Less evidence exists for switching between IFX, ETN and ADA (3B). Biological and MTX combination therapy is more efficacious than a biological agent alone (1B). A safety review shows no increased malignancy risk compared with conventional DMARDs (3B). TNFi are generally associated with an increased risk of serious bacterial infection, particularly within the first 6 months of treatment initiation; increased tuberculosis (TB) rates with TNFi are highest with the monoclonal antibodies (3B). CONCLUSIONS: There is good evidence for the efficacy of biological agents in patients with RA. Safety data confirm an increased risk of bacterial infection and TB with TNFi compared with conventional DMARDs.
19638454 Methotrexate therapy in rheumatoid arthritis after failure to sulphasalazine: to switch or 2009 Oct OBJECTIVES: MTX, either alone or in combination with SSZ, is effective in the treatment of RA. Trials have shown that, after SSZ failure, the addition of MTX to SSZ is more effective than a switch to MTX. Whether this is also the case in daily practice has not been analysed yet. In this study, we compared the efficacy of a switch to MTX monotherapy with that of the addition of MTX to SSZ in the daily clinical practice of RA patients who had failed SSZ monotherapy in the Nijmegen RA Inception Cohort. METHODS: For this study, 230 patients who failed to SSZ monotherapy were followed for up to 52 weeks. A total of 124 underwent a switch to MTX alone, whereas 106 patients received the combination of MTX and SSZ. The primary outcome measure was the mean change in the disease activity score (DAS28) after 24 weeks. RESULTS: Both treatment groups showed a significant decrease in DAS28 after 24 weeks, which was similar in both groups. Drug survival analysis showed that the chance to stop with a DMARD within 52 weeks was higher in the MTX-SSZ group (P <0.01). CONCLUSIONS: In RA patients who failed to SSZ the clinical efficacy of a switch to MTX monotherapy was similar to that of the addition of MTX, suggesting that in daily clinical practice a switch to MTX is a good option for patients with an inadequate response to SSZ.