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ID PMID Title PublicationDate abstract
26345140 Molecular targets in arthritis and recent trends in nanotherapy. 2015 Due to its severity and increasing epidemiology, arthritis needs no description. There are various forms of arthritis most of which are disabling, very painful, and common. In spite of breakthroughs in the field of drug discovery, there is no cure for arthritis that can eliminate the disease permanently and ease the pain. The present review focuses on some of the most successful drugs in arthritis therapy and their side effects. Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities. Mechanisms for different forms of arthritis have been discussed along with the molecules that act as potential biomarkers for arthritis. Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers. The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis. The review also focuses on the recent trends in nanoformulation development used for arthritis therapy. This review is, therefore, important because it describes the relevance and need for more arthritis research, it brings forth a critical discussion of successful drugs in arthritis and analyses the key molecular targets. The review also identifies several knowledge gaps in the published research so far along with the proposal of new ideas and future directions in arthritis therapy.
27964791 Orofacial manifestations in patients with inflammatory rheumatic diseases. 2016 Oct The main orofacial manifestation of the inflammatory rheumatic diseases is that of Sjögren's syndrome. In addition, there is a constellation of orofacial manifestations of the inflammatory rheumatic diseases, many of which are extra-articular with some constituting presenting signs of the underlying rheumatic disease. This review will discuss the orofacial manifestations in a variety of connective tissue diseases and will also allude to the oral adverse drug reactions that may occur as a consequence of therapy.
27730250 Developing connections amongst B lymphocytes and deregulated pathways in autoimmunity. 2016 Dec Immunologists have long investigated B lymphocytes as solely antibody producing cells. With further studies, it became clear that B cells are able to exert a variety of functions within the immune system, and beyond. As a result, B cells are considered promising targets for immunotherapy in a variety of disorders. Recently, experts in B cell biology and autoimmunity convened to discuss important stepping stones to decipher the complexity of B lymphocyte-mediated pathways in autoimmune diseases.
27826168 Comparative analysis of educational needs of patients with rheumatic diseases selected bas 2016 OBJECTIVES: Chronic rheumatic diseases, which have a progressive course, lead to large deficits in physical, mental and social functioning. In the process of the planned and systematic education of patients/families, it is extremely important to identify patients' health problems as well as their needs and expectations. Study objectives: To assess the learning needs of patients with rheumatoid arthritis (RA) and systemic sclerosis (SSc). MATERIAL AND METHODS: This was a multicenter, cross-sectional study conducted in seven rheumatology centers in Poland. Health problems were defined as disability (HAQ-DI), pain (Pain VAS), fatigue (Fatigue VAS) and severity of disease (0-100). The educational needs were measured using the Pol-ENAT (0-156). Statistical analysis was performed using PQStat v.1.4.2 and Excel. RESULTS: The study involved 277 patients with rheumatoid arthritis and 140 with systemic sclerosis. The average age of respondents was comparable in RA (53.3 ±13.0 years) and SSc (54.1 ±14.2 years). Patients suffered from RA on average for 13.7 ±10.6 years and from SSc for 10.9 ±10.3 years. With age and duration of disease, the health problems worsened (p < 0.05). The reported needs of education (Pol-ENAT) were generally at the secondary level - RA 66.4 ±29.3 - younger people (p = 0.008) and those with early RA (r = -0.151, p = 0.011); SSc 71.5 ±27.7 - regardless of age and duration of SSc. Educational needs of patients with SSc correlated with the severity of certain health problems and health evaluation (pain r = 0.334, p < 0.001; fatigue r = 0.243, p = 0.004; severity of disease r = 0.242, p = 0.004 and disability r = 0.291, p < 0.001). CONCLUSIONS: All patients reported the need for education, although it was slightly higher in patients with SSc. There was a decline in interest in education with progressive disability in RA, while in SSc interest in education increased with the progress and severity of the disease.
27099776 Effectiveness of four dynamic treatment strategies in patients with anticitrullinated prot 2016 OBJECTIVE: To determine the most effective treatment strategy among anticitrullinated protein antibodies (ACPA)-negative patients with early rheumatoid arthritis. METHODS: In the BeSt study, 184 ACPA-negative patients were randomised to: (1) sequential monotherapy, (2) step-up therapy, (3) initial combination including prednisone, (4) initial combination including infliximab. Treatment was targeted at the disease activity score (DAS) ≤2.4. Early response and 10-year outcomes were compared between the four strategy-arms in ACPA-negative patients. RESULTS: ACPA-negative patients achieved more short-term functional improvement from initial combination therapy than when on monotherapy (at month 3, mean Health Assessment Questionnaire (HAQ) 0.71 vs 0.98, p=0.006; at month 6, 0.59 vs 0.87, p=0.004). Functional ability over time was comparable between the strategy-arms (p=0.551) with a mean HAQ of 0.6 at year 10 (p=0.580 for comparison across the strategy-arms). 10-year radiographic progression was negligible (median 0.5) and comparable between the 4 strategy-arms (p=0.082). At year 10, remission was achieved by 11/40 (28%), 9/45 (20%), 17/56 (30%) and 17/43 patients (40%) in strategy-arms 1-4, respectively (p=0.434). Over time, similar remission percentages were achieved in all strategy-arms (p=0.815). 18%, 16%, 20% and 21% in strategy-arms 1 to 4 (p=0.742) were in drug-free remission at year 10, with a median duration of 60 months across the arms. CONCLUSIONS: Initial combination therapy with methotrexate, sulfasalazine and prednisone, or methotrexate and infliximab, is the most effective treatment strategy for ACPA-negative patients, resulting in earlier functional improvement than when on initial methotrexate monotherapy. After 10 years of targeted treatment, in all strategy-arms favourable clinical outcomes were achieved and radiographic progression was limited. TRIAL REGISTRATION NUMBER: NTR262, NTR265.
27064652 Respiratory mechanics measured by forced oscillation technique in rheumatoid arthritis-rel 2016 Rheumatoid arthritis (RA)-related pulmonary disorders specifically airway abnormalities and interstitial pneumonia (IP) are important extra-articular manifestations. The forced oscillation technique (FOT) is a useful method to assess respiratory impedance, respiratory resistance (Rrs) and reactance (Xrs), at different oscillatory frequencies during tidal breathing. The aim of this study was to characterize the respiratory mechanics of patients with RA and to relate them to parameters of the pulmonary function test and findings of chest CT images. Respiratory impedance of RA patients (n = 69) was measured as a function of frequency from 4 to 36 Hz using the FOT device and compared with that of healthy subjects (n = 10). Data were retrospectively reviewed. Patients were female-dominant (60.9 %) and 95.7 % had abnormal CT findings including airway and parenchymal abnormalities. Thirty-seven of 69 patients (53.6 %) were smokers. Rrs was significantly frequency-dependent in RA patients but not in the healthy subjects. Xrs were significantly frequency-dependent in both RA and healthy groups. Rrs was significantly higher during an expiratory phase in both RA and healthy groups. Xrs was significantly lower (more negative) during an expiratory phase than that during an inspiratory phase in RA patients but not in healthy subjects. Xrs of the RA group was significantly more negative than that of the normal control. There was no difference in impedance parameters between the airway lesion dominant (n = 27) and IP dominant groups (n = 23) in the RA group. The impedance parameters of the RA group significantly correlated with most parameters of the pulmonary function test. In pulmonary function test results, % of the predicted value for forced expiratory flow from 25 to 75 % of forced vital capacity was significantly lower and % of the predicted value for diffusing capacity of the lung for carbon monoxide was higher in the airway lesion dominant group than those in the IP dominant group. Krebs von den Lungen-6, a serum indicator of IP, was significantly higher in the IP group than that in the airway lesion dominant group. Taken together, the impedance results reflect abnormalities in pulmonary functions and structures in patients with RA.
27042302 Prostaglandin D2 metabolites as a biomarker of in vivo mast cell activation in systemic ma 2016 Mar Mast cells (MCs) participate in diseases such as systemic mastocytosis (SM) and allergic conditions. Less well understood is the role of MCs in non-allergic inflammatory disorders like rheumatoid arthritis (RA). Studying definitive roles for MCs in human diseases has been hampered by the lack of a well-accepted biomarker for monitoring in vivo MC activation. This study aimed to investigate the utility of urinary tetranor PGDM (T-PGDM) as a biomarker of in vivo MC activation in patients with SM, and apply this biomarker to assess MC involvement in relation to RA disease activity. A prospective, cross-sectional cohort study was conducted to measure a major urinary metabolite of prostaglandin D2, T-PGDM. Urine samples were collected from patients with RA (n = 60), SM (n = 17) and healthy normal controls (n = 16) and T-PGDM excretion was determined by enzyme immunoassay as nanograms per milligram of urinary creatinine (ng/mg Cr). Mean urinary T-PGDM excretion was significantly higher (p < 0.01) in patients with SM compared to controls (37.2 vs. 11.5 ng/mg Cr) with 65% of SM patients showing elevated levels. One third of patients with RA had elevated T-PGDM excretion, and the mean level in the RA group (20.0 ng/mg Cr) was significantly higher than controls (p < 0.01). Medications inhibiting cyclooxygenase reduced T-PGDM excretion. Urinary T-PGDM excretion appears promising as a biomarker of in vivo MC activity and elevated levels in 33% of patients with RA provides evidence of MC activation in this disease.
26925252 Adalimumab discontinuation in patients with early rheumatoid arthritis who were initially 2016 OBJECTIVES: To evaluate the impact of discontinuation of adalimumab (ADA) for 1 year in Japanese patients with early rheumatoid arthritis (RA). METHODS: This 52-week postmarketing study, HOPEFUL-2, enrolled patients who had completed HOPEFUL-1 for early RA, in which patients received either ADA + methotrexate (MTX) or MTX alone in a 26-week randomised phase, followed by ADA+MTX in a 26-week open-label phase. RESULTS: A total of 220 patients (ADA discontinuation: 114 patients vs ADA continuation: 106 patients) were enrolled in this study. The proportion of patients with sustained low disease activity (LDA) in the ADA discontinuation group was significantly lower than that in the continuation group (80% (64/80 patients) vs 97% (71/73 patients); p=0.001); however, most patients sustained LDA in both groups. In patients with 28-joint disease activity score (DAS28)-C reactive protein ≤2.0 at week 52, the proportion of patients who achieved sustained LDA at week 104 was 93%, suggesting that DAS28 remission may be a predictor to indicate biological-free disease control in patients with early RA. The incidence of adverse events (AE) was significantly lower in the ADA discontinuation group than in the continuation group (34.2% (39/114 patients) vs 48.1% (51/106 patients); p=0.04), most notably for infection (14.9% vs 27.4%, p=0.031). CONCLUSIONS: Although ADA discontinuation was associated with an increase in disease activity, a large proportion of patients maintained LDA with MTX monotherapy after ADA discontinuation. Since ADA discontinuation was associated with a lower AE incidence, physicians should weigh the risks and benefits of ADA discontinuation. TRIAL REGISTRATION NUMBER: NCT01163292.
26604680 Drug usage analysis and health care resources consumption in naïve patients with rheumato 2015 OBJECTIVES: The use of biologic agents has revolutionized the management of rheumatoid arthritis (RA) in the past 2 decades. These biologic agents directly target molecules and cells involved in the pathogenesis of RA. The purpose of this study was to assess the usage of biologic agents in terms of persistence to treatment, dose escalation, and consumption of health care resources (hospitalizations, drugs, and outpatients service) in the real clinical practice in naïve patients with RA. METHODS: We conducted a real-world, retrospective, observational cohort study based on data obtained from administrative databases of three Local Health Units in Italy. The population included adults diagnosed with RA who had at least one prescription between January 1, 2009 and December 31, 2011, for a biologic that was approved for treatment of RA. The patients were followed for 12 months after enrollment. The clinical characteristics of the patients enrolled in this study were also investigated in the 1-year period before the index date. The main and secondary endpoints were evaluated only in biologic-naïve patients without switches. The overall health care costs for patients were evaluated. RESULTS: A total of 594 patients met the study criteria (mean age 53.5±13.5, female:male ratio =3:1). Thirty-nine percent received etanercept, 25% adalimumab, 14% infliximab, 10% abatacept, 9% tocilizumab, and 3% golimumab. After 1 year of observation, patients showed similar use of other RA-related medication. For the naïve patients without switches, the persistence levels were: 78% for etanercept, 72% for tocilizumab, 71% for adalimumab, 69% for infliximab, and 64% for abatacept. For all agents, dose escalation was 21.4% for infliximab, 11.5% for adalimumab, 5.6% for abatacept, 4% for tocilizumab, and 3.8% for etanercept. The annual costs per treated patients were €12,803 for adalimumab, €11,924 for etanercept, €11,830 for tocilizumab, €11,201 for infliximab, and €10,943 for abatacept. CONCLUSION: The role of biologic therapies in the treatment of RA continues to evolve; our study reflects real-world drug utilization data in adult patients with RA. These observations could be used by decision makers to support formulary decisions, although further research is needed using a larger sample to validate these results.
25999757 Management of rheumatoid arthritis in People's Republic of China - focus on tocilizumab an 2015 The prevalence of rheumatoid arthritis (RA) is 0.19%-0.41% in Chinese population. RA exerts profound influence on health-related quality of life (HRQoL), which imposed huge burdens on patients physically, mentally, and economically. As a developing country, People's Republic of China faces enormous challenges in management of RA. Conventional-synthesized disease-modifying antirheumatic drugs (csDMARDs) remain the most selective therapeutic options for RA in People's Republic of China owing to their affordable price and fair efficacy as well as tolerability. Unfortunately, there are substantial RA patients who are poor responders to csDMARDs, even to subsequently combined therapy with tumor necrosis factor antagonist (anti-TNF). Tocilizumab (TCZ) has been approved as a subsequent-line biological agent in patients with moderate-to-severe RA worldwide including People's Republic of China. TCZ is the first biological agent approved for the treatment of RA inhibiting interlukin-6 (IL-6) by blocking both membrane-bound and soluble IL-6 receptors. Open-label studies in real-life practice and strictly controlled clinical trials demonstrated its high efficacy and safety profile in treatment of patients with RA who have inadequate responses to csDMARDs and anti-TNF. HRQoL of RA patients was improved in various measurements. TCZ was associated with 1.2 times the risk of adverse events, such as infections, dyslipidemia, and hepatic transaminases elevation, compared with pooled placebo. A relatively long half-life allowing for monthly intravenous administration and a newly developed subcutaneous injection make TCZ more acceptable. However, data are not enough so far comparing TCZ to anti-TNF. Lack of evidence in Chinese patients and high cost of TCZ limit its prescription in People's Republic of China being a developing country. Further clinical trials and post-marketing surveillance may offer a comprehensive assessment of patient satisfaction and acceptability, which may help us define the optimal role for TCZ in therapeutic strategy.
27068752 Enhanced activity of hormone sensitive lipase (HSL) in mesenteric but not epididymal fat c 2016 Jun Cachectic rheumatoid arthritis, the less frequent form of the disease, is associated with loss of fat mass and often more severe course of the disease. Its experimental model represents rat adjuvant arthritis (AA) characterized by edema, lack of appetite, sharp body weight and fat loss. As individual fat depots display functional differences, here we studied lipolytic activity and sensitivity to lipolytic stimuli of nodeless epididymal fat (eWAT) and perinodal mesenteric fat (mWAT) depots at the peak of AA. We also examined changes in catecholamine and cytokine levels involved in lipolysis in plasma and/or isolated adipocytes from both WATs to identify the contribution of local, adipocyte-based processes and/or systemic events to adiposity loss in cachectic rheumatoid arthritis. AA was induced to male Lewis rats by complete Freund's adjuvant. Groups of ad libitum-fed and pair-fed controls were used to distinguish the effects of food restriction from inflammation-induced cachexia. Adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and its phosphorylated form (pHSL) were analyzed by western blot. CRP and catecholamine levels in plasma or adipocyte lysates were determined using ELISA kits. Cytokine-induced neutrophil chemoattractant-1 (CINC-1/CXCL1), monocyte chemoattractant protein-1 (MCP-1/CCL2), IL-1β, IL-6, IL-10 and leptin in adipocyte lysate were analyzed by quantitative protein microarray. Plasma glycerol and FFA were measured spectrophotometrically. AA rats developed severe cachexia, with lower adiposity in mWAT compared to normal and pair-fed controls, whereas in eWAT the adiposity was similarly reduced in AA and pair-fed groups. ATGL levels in both WATs were not affected by AA or pair feeding. AA upregulated levels of HSL, pHSL and pHSL/HSL ratio in mWAT, whereas none of these parameters has changed in eWAT of AA rats or in either WATs of pair-fed rats. In AA rats plasma glycerol was elevated, whereas FFA concentration was reduced. Plasma norepinephrine and epinephrine were increased in AA compared with both groups of controls. In eWAT adipocytes, AA but not pair feeding, upregulated norepinephrine levels. In mWAT adipocytes, AA rats showed higher epinephrine levels than pair-fed controls. Leptin levels in both WATs were depleted in AA animals in accordance with body weight loss. None of the measured cytokines in eWAT and mWAT was enhanced. Our results demonstrate augmented lipolytic activity in mWAT and not eWAT during cachectic arthritis. The adipocyte-derived cytokines do not seem to contribute to activated lipolysis. We first demonstrated enhanced presence of norepinephrine in perinodal adipocytes that may contribute to the regulation of local lipolytic activity by auto/paracrine fashion and thus provide independent fuel supply to activated lymph nodes.
27508016 T helper 17 and T helper 1 cells are increased but regulatory T cells are decreased in sub 2016 OBJECTIVES: The present study is to investigate the profiles of Th17, Th1 and Treg cells in bone marrow of patients with rheumatoid arthritis (RA). METHODS: Flow cytometry was used to analyze the frequencies of Th17, Th1 and Treg cells in paired peripheral blood and bone marrow of 26 RA patients and 11 osteoarthritis (OA) patients, as well as 10 healthy controls. In addition, the disease activity was analyzed by the 28-joint disease activity score (DAS28). RESULTS: The frequencies of Th17 and Th1 cells were significantly elevated in bone marrow of RA patients. Importantly, Th17 and Th1 cells were significantly elevated in bone marrow compared with the matched peripheral blood from RA patients. However, Treg cells were significantly decreased in bone marrow of RA patients compared with the matched peripheral blood of RA patients and bone marrow of osteoarthritis patients and healthy controls. Moreover, the frequencies of tumor necrosis factor-α-producing T cells were significantly elevated in bone marrow from RA patients. Additionally, Th17 and Th1 cells in bone marrow were positively correlated with DAS28, while Treg cells were negatively correlated with DAS28. CONCLUSIONS: The present study demonstrates that Th17 and Th1 cells are markedly increased in bone marrow from RA patients. By contrast, Treg cells are significantly decreased in bone marrow from RA patients. These results suggest that local abnormality of Th17, Th1 and Treg cells in bone marrow of RA patients may contribute to bone destruction in skeletal system.
27347021 Understanding the diverse functions of Huatan Tongluo Fang on rheumatoid arthritis from a 2016 Jul Huatan Tongluo Fang (HTTLF) is a traditional herbal formula that can resolve phlegm and dredge collaterals. HTTLF has also been used to treat rheumatoid arthritis (RA); however, the mechanism underlying the therapeutic effects of HTTLF on RA has not been clearly elucidated at the molecular level. In the present study, an integrated model of system pharmacology containing chemical space analysis, potential active compound prediction and compound-target-disease network was constructed to investigate the molecular mechanisms of HTTLF. The compounds from HTTLF dispersed well in the chemical space. Most of the compounds from HTTLF had similar chemical spaces to drug/drug-like compounds associated with RA, according to the MDL Drug Data Report. A total of 127 potentially active compounds and 17 targets of RA were identified. Among them, 50 compounds interacted with ≥2 targets, while 77 compounds interacted with only one target. In addition, 17 targets were associated with 82 diseases that belonged to 26 categories. These results indicate that HTTLF has diverse chemical spaces and polypharmacology with regards to the treatment of RA. In addition, HTTLF demonstrated therapeutic potential against diverse diseases other than RA, including osteoarthritis, atherosclerosis and brain cancer. This study provides a novel platform for understanding how HTTLF treats RA; this is beneficial for explaining the diverse functions of HTTLF with regards to RA, and may help develop novel compounds with desirable therapeutic targets to treat RA.
26819752 A multicentre, randomised, controlled, open-label pilot study on the feasibility of discon 2016 OBJECTIVES: Treatment with tumour necrosis factor (TNF) blockers, once started as therapy for rheumatoid arthritis (RA), is usually continued indefinitely. The aim of this trial was to assess the possibility of discontinuing treatment with adalimumab (ADA) while maintaining remission in patients with RA with established disease in stable remission on combination therapy with ADA and methotrexate (MTX). METHODS: In a randomised, controlled, open-label pilot study of patients with RA in stable remission treated with ADA+MTX, patients were randomised in a 1:1 ratio to continue with ADA plus MTX (arm AM) or MTX monotherapy (arm M) for 52 weeks. Flare was defined as Disease Activity Score (DAS28) ≥2.6 or a change in DAS28 (ΔDAS28) of >1.2 from baseline at any time. Patients in arm M with a flare restarted ADA. The primary end point was the proportion of patients in remission at week 28. RESULTS: 31 patients were enrolled in the study and randomised to arm AM (n=16) or arm M (n=15). At 28 weeks, 15/16 patients (94%) and 5/15 patients (33%) in arms AM and M, respectively, were in remission (p=0.001). During the first 28 weeks, 50% (8/16) in the AM arm and 80% (12/15) in the M arm had a flare (p=0.08). The number of patients in the AM and M arms with ≥1 ΔDAS28 >1.2 during the first 28 weeks was 1/16 (6%) and 8/15 (53%), respectively (p=0.005). CONCLUSIONS: In this study, remission was rarely maintained in patients with long-standing disease who discontinued ADA. Discontinuation may be feasible in only a minority of patients with established RA in stable clinical remission. TRIAL REGISTRATION NUMBER: NCT00808509.
26535138 Longer durations of antitumour necrosis factor treatment are associated with reduced risk 2015 OBJECTIVE: To assess the effects of treatment with antitumour necrosis factor (TNF) agents, methotrexate, or other non-biological disease-modifying antirheumatic drugs (DMARDs) on cardiovascular event risks among patients with rheumatoid arthritis (RA). METHODS: We conducted a retrospective study using data from the MarketScan claims database. Patients with RA with ≥1 prescription for an index drug were included. Each patient's use of an index drug was calculated cumulatively as a time-varying exposure. The incidence of cardiovascular events among patients with RA was determined. Associations between drug exposures and occurrence of cardiovascular events were assessed with Cox proportional hazards models. RESULTS: Of 113 677 patients identified, 35.8%, 41.1% and 23.1% received anti-TNF agents, methotrexate and other DMARDs, respectively. Patients were treated for an average of 7.6 months; 2138 patients (1.9%) had a cardiovascular event following their index prescription. Each additional 6 months of anti-TNF therapy use versus non-use reduced the risk (HR; 95% CI) for any cardiovascular event by 12% (0.88; 0.81 to 0.95, p=0.002). Anti-TNF therapy was associated with a 13% and 12% reduction in cardiovascular events in patients aged ≥50 years (0.87; 0.80 to 0.95, p=0.002) and in those without prior methotrexate use (0.88; 0.78 to 0.99, p=0.04), respectively. Cumulative use of 1, 2 or 3 years of anti-TNF therapy versus non-use is expected to reduce cardiovascular event risks by 21%, 38% and 51%, respectively. CONCLUSIONS: Anti-TNF therapy was associated with a significantly lower risk of cardiovascular events among patients with RA, older patients with RA and patients without prior exposure to methotrexate.
26535135 Estimating the monetary value of the annual productivity gained in patients with early rhe 2015 OBJECTIVE: To measure and value the impact of combined etanercept (ETN) and methotrexate (MTX) therapy on work productivity in patients with early rheumatoid arthritis (RA) over 52 weeks. METHODS: MTX- and biological-naïve patients with RA (symptom onset ≤12 months; Disease Activity Score based on a 28-joint count (DAS28) >3.2) received open-label ETN50/MTX for 52 weeks. The Valuation of Lost Productivity (VOLP) questionnaire, measuring paid and unpaid work productivity impacts, was completed approximately every 13 weeks. Bootstrapping methods were used to test changes in VOLP outcomes over time. One-year productivity impacts were compared between responders (DAS28 ≤3.2) at week 13 and non-responders using zero-inflated models for time loss and two-part models for total costs of lost productivity. RESULTS: 196 patients were employed at baseline and had ≥1 follow-up with VOLP. Compared with baseline, at week 52, patients gained 33.4 h per 3 months in paid work and 4.2 h per week in unpaid work. Total monetary productivity gains were €1322 per 3 months. Over the 1-year period, responders gained paid (231 h) and unpaid work loss (122 h) compared with non-responders, which amounted to a gain of €3670 for responders. CONCLUSIONS: This is the first clinical trial to measure and value the impact of biological treatment on all the labour input components that affect overall productivity. Combination therapy with ETN50/MTX was associated with a significant productivity gain for patients with early RA who were still observed at week 52. Over the 1-year treatment period, responders at week 13 suffered significantly less productivity loss than non-responders suggesting this gain was related to treatment response. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number NCT00913458.
26298525 Association of PDCD1 polymorphism to Systemic Lupus Erythematosus and Rheumatoid Arthritis 2015 Jul 17 OBJECTIVE: This study aims to analyze the relationship of programmed cell death 1 (PDCD1) gene polymorphism (PD1.3G/A - rs11568821) with features of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a Southern Brazilian population. METHODS: Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was performed in 95 SLE and 87 RA patients and 128 control group individuals from Santa Catarina, Southern Brazil. The Hardy-Weinberg Equilibrium (HWE) test, and odds ratio (OR) were analyzed, considering CI 95% and p≤0.05. RESULTS: The PD1.3A allele frequencies were 0.095 (SLE), 0.115 (RA) and 0.078 (controls). The genotypes of the control group were in HWE, while those of SLE and RA patients were not. However, we found no association between PD1.3 polymorphism and the SLE or RA susceptibility, nor clinical or epidemiological data. CONCLUSION: There was no significant association between PD1.3 polymorphism and SLE or RA susceptibility in this Southern Brazilian population.
26150752 Chemokine receptors expression on peripheral CD4-lymphocytes in rheumatoid arthritis: Coex 2015 Jul Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation triggered by infiltrating CD4 lymphocytes. The positioning and activation of lymphocyte in inflamed synovial tissues are dependent on a number of factors including their chemokine receptor expression profile. We aimed to investigate which chemokine receptors pattern correlate with serum cytokine levels and with disease activity. Forty patients with RA (34 female and 6 male) with age range from 21 to 68 years were included. Twenty healthy volunteers (16 female and 4 male) with matched age (range 21-48 years) were served as healthy controls (HCs). Expression of chemokine receptors (CCR5, CX3CR1 and CCR7) together with the apoptosis-related marker (CD95) was analyzed using three-color flow cytometry analysis after gating on CD4(+) peripheral blood lymphocytes. Plasma levels of IL-6, IL-10, IL-12 and TNF-α cytokines were measured in all participants using ELISA. Disease activity score (DAS28-CRP) system was assessed and active disease was defined as DAS28 ⩾3.2. Twenty-five (62.4%) patients were classified as active RA (ARA) and 15 (37.5%) patients with inactive RA (IRA). Percentages of CD4(+) lymphocytes expressing CD95 with either of CCR7 or CCR5 were significantly higher in ARA compared to IRA and HCs groups, while the expression of CX3CR1 on T-cells was found significantly lower in both CD95(-) and CD95(+) T-cells in RA groups than HC. Percentages of CD4(+)CD95(+)CCR7(+) cells correlated positively with IL-6 (r = 0.390). Whereas CD4(+)CD95(+)CX3CR1(+) were negatively correlated with TNF-α (r = -0.261). Correlation of CD4(+)CD95(+)CCR7(+) T cell subset with disease activity and inflammatory cytokines suggests a role for this cell subset in the pathogenesis of RA. Further investigation will be required to fully characterize this cell subset and its role in disease progression.
27427194 The effects of orally administered Bacillus coagulans and inulin on prevention and progres 2016 BACKGROUND: Probiotics have been considered as an approach to addressing the consequences of different inflammatory disorders. The spore-forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic inulin also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. OBJECTIVE: In the present study, an in vivo model was conducted to investigate the possible influences of probiotic B. coagulans and prebiotic inulin, both in combination and/or separately, on the downregulation of immune responses and the progression of rheumatoid arthritis (RA), using arthritis-induced rat model. DESIGN: Forty-eight healthy male Wistar rats were randomly categorized into six experimental groups as follows: 1) control: normal healthy rats fed with standard diet, 2) disease control (RA): arthritis-induced rats fed with standard diet, 3) prebiotic (PRE): RA+ 5% w/w long-chain inulin, 4) probiotic (PRO): RA+ 10(9) spores/day B. coagulans by orogastric gavage, 5) synbiotic (SYN): RA+ 5% w/w long-chain inulin and 10(9) spores/day B. coagulans, and 6) treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with the listed diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund's adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by the biochemical parameters and paw thickness. Biochemical assay for fibrinogen (Fn), serum amyloid A (SAA), and TNF-α and alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28, and 35 (7, 14 and 21 days post RA induction), respectively. RESULTS: Pretreatment with PRE, PRO, and SYN diets significantly inhibits SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in the production of pro-inflammatory cytokines, such as TNF-α, was seen in the PRE, PRO, and SYN groups (P < 0.001), which was similar to the anti-inflammatory effect of indomethacin. Furthermore, no significant anti-inflammatory effects were observed following different treatments using α1 AGp as an RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). CONCLUSION: The results of this study indicate that the oral intake of probiotic B. coagulans and prebiotic inulin can improve the biochemical and clinical parameters of induced RA in rat.
26938367 Complementary and Alternative Medicine Use by Normal Weight, Overweight, and Obese Patient 2016 Mar OBJECTIVES: The Centers for Disease Control and Prevention estimates that 50 million Americans have been diagnosed with arthritis and other musculoskeletal diseases. The purpose of the current study was to (1) estimate the prevalence of overall complementary and alternative medicine (CAM) use and (2) examine the role of body mass index (BMI) on CAM use among normal weight, overweight, and obese persons with chronic lower back pain, chronic neck pain, chronic/rheumatoid arthritis, or musculoskeletal diseases, while controlling for other covariates. DESIGN: Cross-sectional design using secondary data for 9724 adults from the 2007 National Health Interview Survey. Data were weighted and analyzed by using Stata 12 for Windows (Stata Corp., College Station, TX). Descriptive, bivariate, and multivariate logistic regression statistics were computed. PARTICIPANTS: The participants were randomly surveyed from U.S. households. OUTCOME MEASURES: CAM use was measured as reported use of any modality within the five National Center for Complementary and Integrative Health domains. RESULTS: CAM use was statistically significantly associated with female sex; race/ethnicity; having chronic neck pain, lower back pain, or chronic/rheumatoid arthritis; having limitations due to chronic disease; and geographic region (p < 0.05). Factors significantly associated with decreased odds of CAM use included age 50-64 years, income categorized as "other/missing," and having musculoskeletal diseases. Stratification by body mass index suggested increased odds of CAM use among normal/underweight persons with chronic neck pain but decreased odds for those with chronic musculoskeletal diseases. For overweight patients, increased odds of CAM use were significant for chronic lower back pain, musculoskeletal diseases, and chronic/rheumatoid arthritis. CONCLUSIONS: Musculoskeletal diseases and arthritis represent important public health problems with economic implications for the well-being of individuals and society. Identifying CAM use trends by patient weight can be used to improve strategies to increase awareness and access to CAM as part of comprehensive and cost-effective approaches for the management and treatment of these conditions.