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21534642 Analysis of drug and administrative costs allowed by U.S. Private and public third-party p 2011 May BACKGROUND: Rheumatoid arthritis (RA) is a common chronic condition with substantial morbidity that can now be treated with disease-modifying biologic agents that target tumor necrosis factor (TNF) or related mechanisms. The anti-TNF biologic agents are available in either intravenous (IV) or subcutaneous dose forms. The biologic agents with an indication for rheumatoid arthritis and administered only by IV infusion in medical offices include abatacept, infliximab, and rituximab. Although the literature on RA treatments, their outcomes, and aspects of their costs is substantial, the costs of administration by the IV route have not been directly studied. OBJECTIVE: To assess the detailed costs of administering IV biologic agents for the treatment of RA in relation to the total cost of the medication itself in the United States. METHODS: The sample included all patients with at least 1 medical claim with an ICD-9-CM diagnosis code for RA (codes 714.XX) in any claim field and at least 1 claim for infliximab, abatacept, or rituximab (HCPCS codes J1745, J0129, and J9310, respectively) at any time from January 1, 2006, through December 31, 2008, in a database associated with billing and claims administration for 72 U.S. medical clinics. Costs were determined using the payer allowed payment, which is the total contractual amount that the provider should receive, including the patient cost share. Costs were measured as the average cost per IV administration visit and in relation to the dose of medication billed. The authors verified that an RA diagnosis was present on 100% of infusion claims for the study drugs. RESULTS: Over the study period for claims with dates of service from January 1, 2006, through December 31, 2008, 72 medical clinics had claims for a total of 4,248 unique patients with RA and a total of 33,354 clinic visits in which these patients received at least 1 infusion of 1 of 3 biologic agents (26,586 for infliximab, 4,807 for abatacept, and 1,961 for rituximab). Mean (SD) total payment for all drugs and other cost components was $2,874 ($1,515) per visit, of which IV administration costs were $226 (7.9%); the mean cost of the biologic agent itself was $2,616 (91.0%), and other visit-related services were $33 (1.1%). For individual agents, the total costs of visits were $2,828, $1,827, and $6,076; and the costs of IV administration were $224, $171, and $390, respectively, for infliximab, abatacept, and rituximab. CONCLUSION: For patients who received an IV biologic agent to treat RA, IV administration costs accounted for 7.9% of the total cost of the visit.
22762268 Identification of a novel HLA allele, HLA-DQB1*06:51, in a Japanese rheumatoid arthritis p 2012 Oct A novel HLA allele, HLA-DQB1*06:51, was identified in a Japanese rheumatoid arthritis patient.
22691359 [Expression of the costimulatory molecule BTLA in synovial tissues from rheumatoid arthrit 2012 Jun AIM: To detect the expression of B and T lymphocyte attenuator (BTLA) antigen in synovial tissues from rheumatoid arthritis (RA) patients. METHODS: The expression and distribution of BTLA antigen was analyzed by immunohistochemistry. Moreover, fluorescence double-staining was used to further identify the cell types expressing BTLA. RESULTS: Immunohistochemical analysis revealed that a great deal of BTLA positive cells were found in RA synovium, and fluorescence double-staining further demonstrated that BTLA positive cells were CD3(+); T cells, CD68(+); macrophages, and occasionally CD31(+); endothelial cells. In contrast to other members of B7 superfamily, the expression of BTLA was also found on B7-H1(+);, B7-H4(+); and HVEM(+); cells, while it was absence on B7-DC(+); cells as well as B7-H3(+); cells. CONCLUSION: The expression of BTLA has been observed on the surface of several kinds of cells within synovial tissues of RA patients, which indicates this signal might be involved in the regulation of local T cell activation and the pathogenesis of RA.
22193227 Serum levels of soluble CD26 and CD30 and their clinical significance in patients with rhe 2012 Dec The aim of this study was to assess serum levels and clinical significance of soluble CD26 (sCD26) and soluble CD30 (sCD30) in patients with rheumatoid arthritis (RA). Forty-eight patients with RA and 30 healthy controls were enrolled. Serum sCD26 and sCD30 levels were measured using ELISA. Serum sCD26 levels were significantly lower (P = 0.011), whereas sCD30 levels were higher (P = 0.008) in patients with RA than controls. Serum levels of sCD30 correlated significantly with clinical and laboratory parameters of disease activity like erythrocyte sedimentation rate, C-reactive protein, disease activity scores-28 and health assessment questionnaire score; however, sCD26 levels did not correlate any of these activity parameters. These results suggest that serum sCD30 levels increased and correlated significantly with disease activity, indicating a novel follow-up parameter in RA. Serum levels of sCD26 may be lessen but not related to disease activity in RA.
22247350 Orthopedic surgery among patients with rheumatoid arthritis 1980-2007: a population-based 2012 Mar OBJECTIVE: To describe current trends in arthritis-related joint surgery among a population-based cohort of patients with rheumatoid arthritis (RA) and to examine the influence of joint surgery on mortality. METHODS: A retrospective medical record review was performed of all orthopedic surgeries following diagnosis in cases of adult-onset RA in Olmsted County, Minnesota, USA, in 1980-2007. Surgeries included primary total joint arthroplasty, joint reconstructive procedures (JRP), soft tissue procedures (STP), and revision arthroplasty. Cumulative incidence of surgery was estimated using Kaplan-Meier methods. Time trends, sex differences, and mortality were examined using Cox models with time-dependent covariates for surgery. RESULTS: A total of 189 of 813 patients underwent at least 1 surgical procedure involving joints during followup. The cumulative incidence of any joint surgery at 10 years after RA incidence for the 1980-94 cohort was 27.3% compared to 19.5% for the 1995-2007 cohort (p = 0.08). The greatest reduction was in STP, which decreased from 12.1% in 1980-94 to 6.0% in 1995-2007 at 10 years after RA incidence (p = 0.012). Women had more surgery (cumulative incidence 26.6% at 10 years for women; 20.4% for men; p = 0.049), as did obese patients. JRP were significantly associated with mortality (hazard ratio 2.6; 95% CI 1.8, 3.9; p < 0.001) compared to patients not requiring JRP. CONCLUSION: The rates of joint surgery continue to decrease for patients more recently diagnosed with RA. JRP is associated with increased mortality. These findings may reflect improved treatments for RA as well as continued higher disease burden among some patients.
22337242 Infliximab treatment increases left ventricular ejection fraction in patients with rheumat 2012 Apr OBJECTIVE: To study the influence of anti-tumor necrosis factor-α (TNF-α) treatment on echocardiographic measures and concentrations of endothelin 1 (ET-1), interleukin 6 (IL-6), and amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in a cohort of 23 female patients with rheumatoid arthritis (RA). METHODS: We recruited 23 patients (mean age 51.3 ± 1.55 yrs) with RA resistant to treatment with disease-modifying antirheumatic drugs and average disease duration of 7.1 ± 1.0 years who had been selected to start treatment with the anti-TNF-α antagonist infliximab. Transthoracic echocardiographic examinations were performed before the first infusion and repeated after 1 year of treatment. Data for age, sex, RA disease activity by Disease Activity Score (DAS28) and echocardiographic data, NT-proBNP, IL-6, ET-1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other routine laboratory data were collected before treatment and after 1 year. RESULTS: Twelve months of treatment with infliximab resulted in reduction of RA activity (i.e., reduction of DAS and acute-phase reactants). There was increased left ventricle ejection fraction, from 58.5% before treatment to 63% after. Treatment with infliximab also resulted in significant reduction of ET-1 (1.26 fmol/ml before treatment vs 0.43 fmol/ml after), IL-6 (58.46 pg/ml vs 3.46 pg/ml), and NT-proBNP (43.06 fmol/ml vs 14.78 fmol/ml). These reductions were observed after just 4 months of treatment and remained significant until the termination of the study. CONCLUSION: In patients with RA, treatment with infliximab contributed significantly to increase in left ventricular ejection fraction. Improvement of cardiac function was shown by conventional echocardiography; there was reduction of biochemical markers of heart failure.
22422731 Rituximab or a second anti-tumor necrosis factor therapy for rheumatoid arthritis patients 2012 Aug OBJECTIVE: To compare the effectiveness of rituximab (RTX) or a second anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients who had failed their first anti-TNF and switched to either RTX or a second anti-TNF, in routine clinical practice. METHODS: RA patients were registered with the British Society for Rheumatology Biologics Register. Response to treatment 6 months after switching was assessed using European League Against Rheumatism (EULAR) criteria and improvements in a Health Assessment Questionnaire (HAQ) score (0.22 unit or more). Regression analyses were used to compare EULAR response and improvement in HAQ score between the 2 groups, adjusting for propensity scores. RESULTS: In total, 1,328 patients were included in the analysis of EULAR response, and 937 patients were included in the analysis of HAQ scores. Six months after switching, 54.8% of patients who switched to RTX were EULAR responders compared to 47.3% of those who switched to a second anti-TNF. A total of 38.4% of RTX patients achieved a clinically important improvement in HAQ score compared to 29.6% in anti-TNF patients. After adjustment using propensity scores, patients who switched to RTX were significantly more likely to achieve EULAR response (odds ratio [OR] 1.31; 95% confidence interval [95% CI] 1.02, 1.69) compared to those who switched to an alternative anti-TNF. RTX patients were also significantly more likely to achieve improvements in HAQ score (OR 1.49; 95% CI 1.07, 2.08). CONCLUSION: The results suggest that switching to RTX may be of more benefit than switching to an alternative anti-TNF therapy after failing the first anti-TNF therapy in RA patients.
22942322 Measuring pain and efficacy of pain treatment in inflammatory arthritis: a systematic lite 2012 Sep OBJECTIVE: To systematically review the available literature on measuring pain and the efficacy of pain treatment in inflammatory arthritis (IA), as an evidence base for generating clinical practice recommendations. METHODS: A systematic literature search was performed in Medline, Embase, Cochrane Library, and the American College of Rheumatology/European League Against Rheumatism 2008/2009 meeting abstracts, searching for studies evaluating clinimetric properties of pain measurement tools in IA (convergent validity, internal consistency, retest reliability, responsiveness, feasibility, and standardization). Studies that presented information on these properties were reviewed and their data were integrated into the pool of results available for pain measures in IA. RESULTS: In total, 51 articles were included in the review. Validated information on pain was available for tools covering different facets such as overall pain, anatomically specific pain, or a mixture of both. Data from these studies showed that single pain-related items such as the visual analog scale (VAS), numeric rating scale (NRS), or verbal rating scale (VRS) provide sufficient clinimetric information. Similar results were obtained for the pain subscales of the Arthritis Impact Measurement Scales (AIMS/AIMS2) and the bodily pain subscale of the Medical Outcome Study Short-Form Survey 36. Most clinimetric coefficients showed acceptable results with respect to validity, reliability, and sensitivity to change, while the degree of standardization and feasibility mostly filled at least 2 of 3 predefined criteria. CONCLUSION: A variety of pain measures are available to cover different aspects of pain such as intensity, frequency, or location. Single-item tools such as VAS, NRS, or VRS can be recommended to measure overall pain in clinical practice. If more specific issues need to be addressed, more sophisticated tools should be taken into account.
22527215 [Drug-drug interactions in antirheumatic treatment]. 2012 Apr Clinically relevant drug-drug interactions contribute considerably to potentially dangerous drug side-effects and are frequently the reason for hospitalization. Nevertheless they are often overlooked in daily practice. For most antirheumatic drugs a vast number of interactions have been described but only a minority with clinical relevance. Several potentially important drug interactions exist for non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate, azathioprine, mycophenolate-mofetil and especially for cyclosporin A. Most importantly co-medication with methotrexate and sulfmethoxazole trimethoprim as well as azathioprine and allopurinol carries the risk of severe, sometimes life-threatening consequences. Nevertheless, besides these well-known high-risk combinations in each case of polypharmacy with antirheumatic drugs it is necessary to bear in mind the possibility of drug interactions. As polypharmacy is a common therapeutic practice in older patients with rheumatic diseases, they are at special risk.
21538311 Toward a data-driven evaluation of the 2010 American College of Rheumatology/European Leag 2011 May OBJECTIVE: Recently, new classification criteria for rheumatoid arthritis (RA) have been devised by methodology that used first a quantitative approach (data from databases), then a qualitative approach (consensus; based on paper patients), and finally a common sense-based approach (evaluation of the former phases). Now the individual items that make up these criteria are being evaluated. This study was undertaken to analyze the item "autoantibodies," in particular rheumatoid factor (RF) level. METHODS: Three separate cohorts comprising a total of 972 patients with undifferentiated arthritis were studied for RA development (according to the 1987 American College of Rheumatology criteria) and arthritis persistence. The positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LRs) were compared between different levels of RF and the presence of anti-citrullinated protein antibody (ACPA). A similar comparison was made in 686 RA patients for the rate of joint destruction and achievement of sustained disease-modifying antirheumatic drug-free remission during 7 years of followup. The variation in RF levels obtained by different measurement methods in the same RF-positive sera was explored. RESULTS: Compared to high RF levels, presence of ACPA had a better balance between positive LR and negative LR and between PPV and NPV for RA development. The additive value of ACPA assessment after testing for RF level was higher than vice versa. The association between high RF level and RA severity was not as strong as that between ACPA antibodies and RA severity. The RF level obtained by different methods in the same patients' sera varied considerably. CONCLUSION: Our findings indicate that determination of RF level is subject to large variation; high RF level has limited additive prognostic value compared to ACPA positivity. Thus, omitting RF level and using RF presence, ACPA presence, and ACPA level may improve the 2010 criteria for RA.
21570495 Anti-TNF therapy: safety aspects of taking the risk. 2011 Jul Rheumatoid arthritis (RA) therapy has been revolutionized in recent years following the introduction of three main anti-tumor necrosis factor-alpha inhibitors (anti-TNF) agents, infliximab, adalimumab and etanercept. Evidence in the literature indicates that patients treated with anti-TNF agents are at increased risk for bacterial infections, but it is not clear if this is a result of the treatment or of disease severity. The treatment has been recognized as a clear risk factor for reactivation of latent TB infections. So far, observational studies have not indicated any increased overall risk of cancer in RA patients treated with anti-TNF. The overall risk of lymphoma in these patients does not appear to differ greatly from that recorded among untreated patients, but rather is associated with the degree of disease activity rather than the type of therapy. There is a consensus in the literature that the likelihood of drug survival with infliximab is inferior to both adalimumab and etanercept, mostly due to increased risk of infection or allergic reactions. Due to the lack of head to head studies, there is no agreement as to which agent has the highest rates of treatment response and disease remission.
22098778 Alleviation of rheumatoid arthritis by cell-transducible methotrexate upon transcutaneous 2012 Feb Rheumatoid arthritis (RA) is a systemic autoimmune disease that is initiated and maintained by various inflammatory/immune cells and their cytokines, leading to cartilage degradation and bone erosion. Despite its potent therapeutic efficacy on RA, the oral administration of methotrexate (MTX) provokes serious adverse systemic complications, thus necessitating the local application of MTX. Here, we show that transcutaneous MTX (TC-MTX) can efficiently penetrate joint skin ex vivo and in vivo, and that TC-MTX can significantly improve the various inflammatory symptoms associated with RA. Further, TC-MTX preserved the joint-structures in mice with collagen-induced arthritis (CIA), which was also confirmed by three-dimensional micro-computed tomography scan. TC-MTX markedly decreased the secretion of inflammatory cytokines both in the serum and in inflamed joints of CIA mice. Further, its therapeutic potential is comparable to that of etanercept, a biological agent that block tumor necrosis factor (TNF)-α. Importantly, the systemic cytotoxicity of TC-MTX was not detected. Thus, TC-MTX can be a new therapeutic modality for RA patients without systemic complications.
21459947 A comparison between IgG- and IgA-class antibodies to cyclic citrullinated peptides and to 2011 Jul OBJECTIVE: Because of their slightly higher sensitivity, it has been argued that antibodies to modified citrullinated vimentin (anti-MCV) are superior to antibodies to cyclic citrullinated peptides (anti-CCP), while others claim that anti-CCP is preferable because of higher diagnostic specificity for rheumatoid arthritis (RA). We evaluated IgG- and IgA-class anti-MCV and anti-CCP as diagnostic and prognostic markers in early arthritis. METHODS: Two Swedish arthritis populations were examined: 215 patients with early RA (≤ 12 months' duration) from the Swedish TIRA-1 cohort, and 69 patients with very early arthritis (≤ 3 months' duration) from the Kronoberg Arthritis Incidence cohort, in which 22% were diagnosed with RA. IgG anti-CCP and anti-MCV antibodies were analyzed with commercial kits. These tests were modified for IgA-class antibody detection. Results were related to disease course, smoking habits, and shared epitope status. RESULTS: In the TIRA-1 cohort, occurrence of IgG anti-MCV and IgG anti-CCP showed a 93% overlap, although IgG anti-MCV had higher diagnostic sensitivity. Twenty-four percent tested positive for IgA anti-MCV compared to 29% for IgA anti-CCP. In the Kronoberg Arthritis Incidence cohort, 15% tested positive for IgG anti-MCV and 6% for IgA anti-MCV, compared to 10% positive for IgG anti-CCP and 3% positive for IgA anti-CCP, revealing that anti-CCP had higher diagnostic specificity for RA. As previously reported for IgA anti-CCP, IgA anti-MCV antibodies occurred in a small proportion of high-level IgG antibody-positive sera and were associated with a more aggressive disease course. Smokers were more often positive for antibodies to citrullinated proteins, most strikingly among the patients who were IgA anti-MCV-positive. CONCLUSION: The occurrences of IgG-class anti-MCV and anti-CCP in early RA largely overlap. The sensitivity of anti-MCV is slightly higher, while the diagnostic specificity is higher for anti-CCP. In both instances a positive test predicts an unfavorable disease course, possibly slightly more so for anti-MCV. Although associated with a more active disease over time, IgA-class anti-CCP or anti-MCV do not add any diagnostic advantage.
22703673 Corticotropin releasing hormone (CRH) response in patients with early rheumatoid arthritis 2012 May OBJECTIVES: To further evaluate the impact of corticotropin releasing hormone (CRH) promoter polymorphisms on the stress response in rheumatoid arthritis (RA) patients an insulin hypoglycaemia test (IHT) was performed studying the dynamics of CRH production. METHODS: Polymorphisms of the human CRH promoter were determined in controls and cortisol naive patients with early RA. Serum glucose and plasma CRH were measured at baseline and up to 120 min following induction of hypoglycemia. RESULTS: During IHT RA patients bearing the A2B2 allele exhibited an earlier CRH response compared to A1B1 positive patients. CONCLUSIONS: Stress-induced response of CRH is differentially modulated by CRH promoter polymorphisms in RA patients.
22085519 [Tailored therapy for rheumatic disease within reach]. 2011 Personalised medicine has the potential to increase therapeutic effectiveness, reduce side effects and lower cost. This approach has recently taken off in oncology where different malignancies may be treated with specific drugs based on genetic biomarkers or other tumour characteristics. This type of tailored therapy could also be developed for immune-mediated inflammatory disease, for which rheumatoid arthritis (RA) may serve as a prototype. While novel treatments are able to halt or even prevent disease progression, not all RA patients respond, and stratification of patient groups is needed. The identification of biomarkers predictive of the clinical response to specific treatments in subsets of patients may soon become reality in a variety of diseases.
21696704 The effect of a new syringe design on the ability of rheumatoid arthritis patients to inje 2012 Mar Self-administration of new biological medications can be difficult for Rheumatoid Arthritis patients with functional impairment and hand and dexterity limitation. Twenty-three Rheumatoid Arthritis (RA) patients participated in this study to compare preferences and injection forces using a conventional syringe and a new ergonomically designed syringe. Injection force measurements were collected in two ways: a) isometric forces, with the syringes' plungers in fixed positions (depressed halfway and fully depressed), and b) forces exerted during injection of the medication. Subjects' grip and pinch strengths were measured. A perception questionnaire gauged subjects' impressions and preferences. Subjects were capable of exerting significantly higher isometric forces using the new syringe with the plunger fixed both halfway and fully depressed. During injection of the medication, peak and mean injection forces were significantly higher, and duration was shorter, when using the new syringe. Subjects rated the new syringe higher on all twenty attributes on preference and performance. Therefore, it is expected that the new syringe will benefit self-administration of medication injection for RA patients.
23044063 Revision of failed ankle implants. 2012 Oct Total ankle joint replacement (TAR) has been offered as an alternative to ankle joint arthrodesis since the 1970s. TAR offers the benefit of perseveration of joint motion, with potential decreased occurrence of adjacent joint degeneration, and a more expedient path to weight bearing. Since their introduction, TAR devices have undergone a variety of modifications, specifically in regards to the number and type of components used.
21939785 Extra-articular manifestations of rheumatoid arthritis: An update. 2011 Dec Rheumatoid arthritis (RA) is an immune-mediated disease involving chronic low-grade inflammation that may progressively lead to joint destruction, deformity, disability and even death. Despite its predominant osteoarticular and periarticular manifestations, RA is a systemic disease often associated with cutaneous and organ-specific extra-articular manifestations (EAM). Despite the fact that EAM have been studied in numerous RA cohorts, there is no uniformity in their definition or classification. This paper reviews current knowledge about EAM in terms of frequency, clinical aspects and current therapeutic approaches. In an initial attempt at a classification, we separated EAM from RA co-morbidities and from general, constitutional manifestations of systemic inflammation. Moreover, we distinguished EAM into cutaneous and visceral forms, both severe and not severe. In aggregated data from 12 large RA cohorts, patients with EAM, especially the severe forms, were found to have greater co-morbidity and mortality than patients without EAM. Understanding the complexity of EAM and their management remains a challenge for clinicians, especially since the effectiveness of drug therapy on EAM has not been systematically evaluated in randomized clinical trials.
21254243 Phagocytosis and nitric oxide levels in rheumatic inflammatory states in elderly women. 2011 BACKGROUND: Very few studies have investigated, in the elderly, the effect of rheumatic inflammatory states on phagocyte function and free radical production. The objective of this article is to evaluate phagocytosis by neutrophils and the production of nitric oxide (·NO) by monocytes in elderly women recruited among patients of the Brazilian Public Health System. METHODS: Forty patients aged more than 60 years with rheumatic inflammatory diseases were studied. Phagocytosis was measured by flow cytometry. ·NO production was measured by the total nitrite assay and conventional inflammation markers were determined. Data were analyzed with the Mann-Whitney nonparametric test and P<0.05 was considered significant. RESULTS: C-reactive protein levels and white blood cell counts were significantly higher in inflammation than in the control group (P<0.05). The phagocytosis fluorescence intensity per neutrophil and the percentual of neutrophils expressing phagocytosis were significantly higher (P<0.05) in the test than in the control group. Furthermore, there was significant ·NO overproduction by monocytes, (P<0.05). CONCLUSION: Phagocytosis and ·NO production are affected by rheumatic states. This suggests that the increased ·NO levels may play a part in the increased oxidative stress in rheumatic diseases in elderly women.
23116340 Shoulder function and active motion deficit in patients with rheumatoid arthritis. 2013 Aug PURPOSE: To discover whether there are differences between patients with RA with and without active motion deficit in the shoulder (passive ROM greater than active ROM) concerning disease characteristics and shoulder function, and examine the role of active motion deficit in explaining limitations of shoulder function in daily life. METHODS: This cross-sectional study included 123 patients with RA having shoulder pain. Disease activity and duration of shoulder pain and disease were registered, active and passive shoulder ROM, pain and muscle strength were measured. Shoulder function in daily life was assessed by Disability of the Arm, Shoulder and Hand (DASH). RESULTS: Patients with active motion deficit (36%) had statistical significant worse scores on disease activity, shoulder pain, muscle strength, and DASH function than those without active motion deficit (p ≤ 0.05). No differences between the groups were found for duration of shoulder pain or disease (p > 0.05). Active motion deficit, passive ROM, muscle strength and pain explained 33.7% of the variation in the DASH function score. CONCLUSION: Active motion deficit in the shoulder seems frequent in patients with RA. Together with passive ROM, muscle strength and pain, active motion deficit explained about one-third of the limitations in shoulder function in daily life.