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30653389 The economic burden of switching targeted disease-modifying anti-rheumatic drugs among rhe 2019 Apr AIMS: To estimate real world healthcare costs and resource utilization of rheumatoid arthritis (RA) patients associated with targeted disease modifying anti-rheumatic drugs (tDMARD) switching in general and switching to abatacept specifically. MATERIALS AND METHODS: RA patients initiating a tDMARD were identified in IMS PharMetrics Plus health insurance claims data (2010-2016), and outcomes measured included monthly healthcare costs per patient (all-cause, RA-related) and resource utilization (inpatient stays, outpatient visits, emergency department [ED] visits). Generalized linear models were used to assess (i) average monthly costs per patient associated with tDMARD switching, and (ii) among switchers only, costs of switching to abatacept vs tumor necrosis factor inhibitors (TNFi) or other non-TNFi. Negative binomial regressions were used to determine incident rate ratios of resource utilization associated with switching to abatacept. RESULTS: Among 11,856 RA patients who initiated a tDMARD, 2,708 switched tDMARDs once and 814 switched twice (to a third tDMARD). Adjusted average monthly costs were higher among patients who switched to a second tDMARD vs non-switchers (all-cause: $4,785 vs $3,491, p < .001; RA-related: $3,364 vs $2,297, p < .001). Monthly RA-related costs were higher for patients switching to a third tDMARD compared to non-switchers remaining on their second tDMARD ($3,835 vs $3,383, p < .001). Switchers to abatacept had significantly lower RA-related monthly costs vs switchers to TNFi ($3,129 vs $3,436, p = .021), and numerically lower all-cause costs ($4,444 vs $4,741, p = 0.188). Switchers to TNFi relative to abatacept had more frequent inpatient stays after switch (incidence rate ratio (IRR) = 1.85, p = .031), and numerically higher ED visits (IRR = 1.32, p = .093). Outpatient visits were less frequent for TNFi switchers (IRR = 0.83, p < .001) compared to switchers to abatacept. LIMITATIONS AND CONCLUSIONS: Switching to another tDMARD was associated with higher healthcare costs. Switching to abatacept, however, was associated with lower RA-related costs, fewer inpatient stays, but more frequent outpatient visits compared to switching to a TNFi.
31780862 Changes in Serum Cytokines May Predict Therapeutic Efficacy of Tofacitinib in Rheumatoid A 2019 OBJECTIVE: Tofacitinib is a novel therapy for rheumatoid arthritis (RA). The aim of this study was to measure various serum cytokines levels and to explore potential markers predictive of therapeutic efficacy of tofacitinib for RA patients. METHODS: Thirty-two patients with RA were given tofacitinib (5 mg bid). Serum cytokines levels of Th1 (IFN-γ), Th2 (IL-6), Th17 (IL-17), Tregs (IL-35), and TNF-α were detected by enzyme-linked immunosorbent assays. RESULTS: Disease activity was significantly decreased as early as week 4 after tofacitinib treatment. Serum IL-35 levels were significantly increased and serum levels of TNF-α, IL-17, IL-6, and IFN-γ were significantly reduced in response to tofacitinib since week 4. CONCLUSIONS: After treatment with tofacitinib, RA patients may benefit from monitoring of disease activity as early as week 4. IL-35 also might be a predictive indicator of the disease activity and drug efficacy. Meanwhile, tofacitinib might be CS-sparing in RA.
31479688 ATP and adenosine: Role in the immunopathogenesis of rheumatoid arthritis. 2019 Oct Rheumatoid arthritis (RA) is a classic inflammatory autoimmune disease. Local joint destruction and extra-articular manifestations of RA deeply compromise the life quality of the affected patients. RA immunopathogenesis depends on continuous immunogenic activation in which the purinergic system participates. The purinergic system comprises the signaling and metabolism of purines such as adenosine triphosphate (ATP) and adenosine. ATP signaling is involved in the activation and maintenance of the inflammatory state of RA through the activation of P2X7 and the production of cytokines, which orchestrate the pathogenesis of RA. The breakdown of ATP through the CD39/CD73 axis produces adenosine, which mostly inhibits the inflammatory process through activation of specific P1 receptors. Adenosine is hydrolyzed by adenosine deaminase (ADA) that interacts with other molecules playing additional roles in this disease. This review explores the release, metabolism, and the effects of binding of ATP and adenosine to their respective receptors in the context of RA, as well as their potential use as biomarkers and therapeutic targets.
31316517 Plasma MicroRNAs in Established Rheumatoid Arthritis Relate to Adiposity and Altered Plasm 2019 Background: MicroRNAs have been implicated in the pathogenesis of rheumatoid arthritis (RA), obesity, and altered metabolism. Although RA is associated with both obesity and altered metabolism, expression of RA-related microRNA in the setting of these cardiometabolic comorbidities is unclear. Our objective was to determine relationships between six RA-related microRNAs and RA disease activity, inflammation, body composition, and metabolic function. Methods: Expression of plasma miR-21, miR-23b, miR-27a, miR-143, miR-146a, and miR-223 was measured in 48 persons with seropositive and/or erosive RA (mean DAS-28-ESR 3.0, SD 1.4) and 23 age-, sex-, and BMI-matched healthy controls. Disease activity in RA was assessed by DAS-28-ESR. Plasma cytokine concentrations were determined by ELISA. Body composition was assessed using CT scan to determine central and muscle adipose and thigh muscle tissue size and tissue density. Plasma and skeletal muscle acylcarnitine, amino acid, and organic acid metabolites were measured via mass-spectroscopy. Plasma lipoproteins were measured via nuclear magnetic resonance (NMR) spectroscopy. Spearman correlations were used to assess relationships for microRNA with inflammation and cardiometabolic measures. RA and control associations were compared using Fisher transformations. Results: Among RA subjects, plasma miR-143 was associated with plasma IL-6 and IL-8. No other RA microRNA was positively associated with disease activity or inflammatory markers. In RA, microRNA expression was associated with adiposity, both visceral adiposity (miR-146a, miR-21, miR-23b, and miR-27a) and thigh intra-muscular adiposity (miR-146a and miR-223). RA miR-146a was associated with greater concentrations of cardiometabolic risk markers (plasma short-chain dicarboxyl/hydroxyl acylcarnitines, triglycerides, large VLDL particles, and small HDL particles) and lower concentrations of muscle energy substrates (long-chain acylcarnitines and pyruvate). Despite RA and controls having similar microRNA levels, RA, and controls differed in magnitude and direction for several associations with cytokines and plasma and skeletal muscle metabolic intermediates. Conclusion: Most microRNAs thought to be associated with RA disease activity and inflammation were more reflective of RA adiposity and impaired metabolism. These associations show that microRNAs in RA may serve as an epigenetic link between RA inflammation and cardiometabolic comorbidities.
30989332 Discordance between doctor and patient assessments and non-adherence to subcutaneous biolo 2019 Jun To estimate the agreement level between patient and physician assessment of disease activity and to explore whether agreement is associated with adherence to subcutaneous (SC) biological drugs in rheumatoid arthritis (RA). Cross-sectional study of RA patients who had been prescribed a SC biological drug in the past 12-18 months was performed. Patients and physicians global disease activity on visual analogue scale (VAS) were collected. Disagreement was defined as an absolute difference ≥ 3 points between VAS scores. Adherence was assessed by the Medication Possession Ratio (MPR), considering adherence an MPR > 80%. We analysed 360 patients of whom 15.5% presented disagreement with their physicians. The mean patient global VAS was 5.75 ± 1.8 (median 5.5 [5-7]) in the disagreement group versus 2.7 ± 2.2 (median 2 [1-4]) in the agreement group (p < 0.001). There were also differences in physicians global VAS between groups (p = 0.01). The non-adherence to SC biological drugs rate was 10.7% and 14.5% in the disagreement and agreement groups (p = 0.45). No association between adherence and discordance was found. Disagreement in the global disease activity between patients and physicians was detected in 15.5% of patients. In general, patients perceived higher disease activity. No associations between patient-physician disagreement in VAS and adherence were observed.
30953230 Extractable synovial fluid in inflammatory and non-inflammatory arthritis of the knee. 2019 Aug INTRODUCTION/OBJECTIVES: We hypothesized that mechanical compression of the knee in rheumatoid arthritis (RA) would mobilize occult extractable fluid and improve arthrocentesis success. METHODS: Sixty-seven consecutive knees with RA and 186 knees with OA and were included. Conventional arthrocentesis was performed and success and volume (milliliters) determined; the needle was left intraarticularly, and mechanical compression was applied with an elastomeric knee brace. Arthrocentesis was then resumed until fluid return ceased. Fluid was characterized as to volume and cell counts. RESULTS: In the RA, knee mechanical compression decreased failed diagnostic arthrocentesis from 56.7% (38/67) to 26.9% (18/67) (- 47.4%, p = 0.003) and increased absolute arthrocentesis yield from 4.7 ± 10.3 ml to 9.8 ± 9.8 ml (108% increase, 95% CI - 8.5 < - 5.1 < - 1.7 p = 0.0038). Total extractable fluid yield was 96% greater in RA (9.8 ± 9.8 ml) than OA (5.0 ± 9.4 ml, p = 0.0008), and occult extractable fluid was 77% greater in RA than OA (RA 5.3 ± 8.7 ml, OA 3.0 ± 5.5 ml, p = 0.046). Large effusions versus small effusions in RA demonstrated increased neutrophils in synovial fluid (p = 0.04) but no difference in radiologic arthritis grade (p = 0.87). In contrast, large effusions versus small effusions in OA demonstrated no difference in neutrophils in synovial fluid (p = 0.87) but significant different radiologic arthritis grade (p = 0.04). CONCLUSION: Mechanical compression improves the success of diagnostic and therapeutic knee arthrocentesis in both RA and OA. Large effusions in RA are associated with increased neutrophil counts but not arthritis grade; in contrast, large effusions in OA are associated with more severe arthritis grades but not increased neutrophil counts. Key points• Mechanical compression of the painful knee improves arthrocentesis success and fluid yield in both rheumatoid arthritis and osteoarthritis.• The painful rheumatoid knee contains approximately 100% more fluid than the osteoarthritic knee.• Large effusions in the osteoarthritic knee are characterized by higher grades of mechanical destruction but not increased neutrophil counts.• In contrast, large effusions in the rheumatoid knee are characterized by higher synovial fluid neutrophil counts but not the grade of mechanical destruction, indicating different mechanisms of effusion formation in rheumatoid arthritis versus osteoarthritis.
29534234 Cost-effectiveness of hydrotherapy versus land-based therapy in patients with musculoskele 2019 Jun 1 BACKGROUND: The study evaluated the cost-effectiveness of hydrotherapy versus land-based therapy in patients with musculoskeletal disorders (MSDs) in Singapore. METHODS: A decision-analytic model was constructed to compare the cost-effectiveness of hydrotherapy to land-based therapy over 3 months from societal perspective. Target population comprised patients with low back pain (LBP), osteoarthritis (OA), rheumatoid arthritis (RA), total hip replacement (THR) and total knee replacement (TKR). Subgroup analyses were carried out to determine the cost-effectiveness of hydrotherapy in individual MSDs. Relative treatment effects were obtained through a systematic review of published data. RESULTS: Compared to land-based therapy, hydrotherapy was associated with an incremental cost-effectiveness ratio (ICER) of SGD 27 471 per quality-adjusted life-year (QALY) gained, which was below the willingness-to-pay threshold of SGD 70 000 per QALY (one gross domestic product per capita in Singapore in 2015). For the respective MSDs, hydrotherapy were dominant (more effective and less costly) in THR and TKR, cost-effective for LBP and RA, and not cost-effective for OA. Treatment adherence and cost of hydrotherapy were key drivers to the ICER values. CONCLUSIONS: Hydrotherapy was a cost-effective rehabilitation compared to land-based therapy for a population with MSDs in Singapore. However, the benefit of hydrotherapy was not observed in patients with OA.
31154414 Magnetic Resonance Imaging (MRI) Results Following Discontinuation of Methotrexate in Rheu 2020 Mar OBJECTIVE: To assess differences in joint damage and inflammation using magnetic resonance imaging (MRI) between patients with rheumatoid arthritis (RA) who achieved low disease activity with tocilizumab (TCZ) + methotrexate (MTX) and subsequently continued or discontinued MTX. METHODS: In the COMP-ACT trial, US patients with RA received subcutaneous TCZ 162 mg + MTX. Those who achieved 28-joint count Disease Activity Score calculated with erythrocyte sedimentation rate (DAS28-ESR) ≤ 3.2 at Week 24 were randomized 1:1 (double-blind) to discontinue MTX (TCZ monotherapy; mono) or continue TCZ + MTX until Week 52. In a subset of patients, 1.5-Tesla MRI was used to obtain images of bilateral hands and wrists at weeks 24 and 40. Outcomes included changes in MRI-assessed synovitis, osteitis, erosion, and cartilage loss from Week 24 to Week 40, and in the proportion of patients with progression of each score. RESULTS: Of 296 patients who achieved DAS28-ESR ≤ 3.2 at Week 24, 79 were enrolled in the pilot MRI substudy and randomized to TCZ mono (n = 38) or TCZ + MTX (n = 41). Treatment with either TCZ mono or TCZ + MTX suppressed erosion progression, synovitis, osteitis, and cartilage loss. The proportion of patients with no progression in each outcome measure was similar between groups (range, TCZ mono: 84.8-97.0%; TCZ + MTX: 92.3-100%). CONCLUSION: In a subset of patients who achieved low disease activity with TCZ + MTX, MRI changes were minimal in intraarticular inflammation and damage measures in patients who discontinued MTX versus those who continued TCZ + MTX.
30259817 TMJ Arthritis Imaging: Conventional Radiograph vs. CT Scan - Is CT Actually Needed? 2019 OBJECTIVE: The present study was conducted to evaluate the efficacy of conventional TMJ imaging in depicting osseous changes in mandibular condyle and glenoid fossa in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) by comparing the finding against CT and with an objective that if conventional TMJ imaging modality can appreciate the osseous changes in RA and OA then what is the need for CT scan. Thus further reducing the patient's radiation dose. MATERIALS AND METHODS: A total of 70 patients (40 Rheumatoid Arthritis; 30 Osteoarthritis) were taken in the study aged between 40 - 60 years and divided in to age groups. Then according to clinical history they were divided according to being symptomatic and asymptomatic. Further radiographic examination was carried out. First the trans-cranial view was obtained (conventional view left and right TMJ) and subsequently a CT scan was obtained and the interpretation was carried out to note the osseous changes like erosion, flattening, sclerosis and osteophyte formation. RESULTS: After comparison of the two radiographic methods it was observed that both were equally efficacious in evaluating the osseous changes in arthritic patients. CONCLUSION: Thus, it was concluded that when both the radiographic methods (conventional and CT scan) are equally efficacious in evaluating the osseous degenerative changes of TMJ in arthritis. Thus we should prefer the conventional technique so that the patient in not exposed to unnecessary radiation dosage.
30883031 Exploring the Lipid Paradox Theory in Rheumatoid Arthritis: Associations of Low Circulatin 2019 Sep OBJECTIVE: Rheumatoid arthritis (RA) patients with the lowest circulating low-density lipoprotein (LDL) concentrations are at heightened risk of cardiovascular events. However, the atherosclerosis burden within this subgroup is unknown. METHODS: RA patients pooled from 4 cohort studies of cardiovascular disease (CVD; n = 546) were compared with non-RA controls from the Multi-Ethnic Study of Atherosclerosis (n = 5,279). Those taking lipid-lowering medications were excluded. Differences in cardiac computed tomography-derived Agatston coronary artery calcium (CAC) scores between the RA and control groups were compared across strata of LDL concentration. RESULTS: Among those with low LDL concentrations (<70 mg/dl), mean adjusted CAC scores were >4-fold higher for RA patients than for controls (18.6 versus 4.6 Agatston units, respectively; P < 0.001), a difference significantly greater than that in any other LDL concentration stratum except LDL concentration ≥160 mg/dl. Similarly, 32% of the RA patients with low LDL concentration had a CAC score of ≥100 Agatston units compared with only 7% of controls in the same LDL concentration stratum (odds ratio 5.97; P < 0.001), a difference significantly greater than that in all of the other LDL concentration strata. Low LDL concentration was most strongly associated with higher CAC score among RA patients who were white, had ever smoked, or were not obese. Other than a higher frequency of current smokers, RA patients with low LDL concentrations did not have more CVD risk factors or higher measures of RA disease activity or severity than RA patients with higher LDL concentrations. CONCLUSION: RA patients with low LDL concentration may represent a group for whom heightened screening and prevention of atherosclerotic CVD is appropriate.
31631321 Bayesian design of biosimilars clinical programs involving multiple therapeutic indication 2020 Jun In this paper, we propose a Bayesian design framework for a biosimilars clinical program that entails conducting concurrent trials in multiple therapeutic indications to establish equivalent efficacy for a proposed biologic compared to a reference biologic in each indication to support approval of the proposed biologic as a biosimilar. Our method facilitates information borrowing across indications through the use of a multivariate normal correlated parameter prior (CPP), which is constructed from easily interpretable hyperparameters that represent direct statements about the equivalence hypotheses to be tested. The CPP accommodates different endpoints and data types across indications (eg, binary and continuous) and can, therefore, be used in a wide context of models without having to modify the data (eg, rescaling) to provide reasonable information-borrowing properties. We illustrate how one can evaluate the design using Bayesian versions of the type I error rate and power with the objective of determining the sample size required for each indication such that the design has high power to demonstrate equivalent efficacy in each indication, reasonably high power to demonstrate equivalent efficacy simultaneously in all indications (ie, globally), and reasonable type I error control from a Bayesian perspective. We illustrate the method with several examples, including designing biosimilars trials for follicular lymphoma and rheumatoid arthritis using binary and continuous endpoints, respectively.
31122104 Physical activity, sedentary behavior, and long-term cardiovascular risk in individuals wi 2019 Nov Objective: Individuals with rheumatoid arthritis (RA) have increased risk of cardiovascular disease (CVD). Lifestyle factors such as prolonged sedentary behavior (SB) and reduced physical activity (PA) may heighten the risk of CVD. The objective of the study was to investigate the role of SB and PA as predictors for long-term CVD risk in RA patients.Methods: A subsample of 273 people diagnosed with RA was extracted from the 2003-2006 National Health and Nutrition Examination Survey and included in this cross-sectional study. Valid accelerometry data were categorized into sedentary behavior, very light, light, and moderate-to-vigorous physical activity. Functional limitations were assessed using a physical function questionnaire. The Framingham risk score (FRS) was used to calculate 10-year CVD risk. Regression models were used to examine the relationships between SB, PA, and 10-year CVD risk while controlling for potential confounders.Results: Participants spent an average of 9 h/day sedentary, 4 h in very light PA, 1 h in light PA, and 0.4 h in moderate-to-vigorous PA. Greater sedentary time was associated with higher 10-year CVD risk (p= 0.019). Increased daily PA, at all intensities, was inversely associated with 10-year CVD risk (p< 0.01). In the fully adjusted regression model, associations between 10-year CVD risk and SB (β = 0.31, R(2) = 0.27, p< 0.01), very light PA (β = -0.19, R(2) = 0.26, p< 0.01), light PA (β = -0.16, R(2) = 0.25, p< 0.01), and moderate-to-vigorous PA (β = -0.15, R(2) = 0.25, p< 0.01) remained significant.Conclusions: Strategies for decreasing SB and increasing PA should be explored with individuals with RA in order to decrease long-term CVD risk.
31670976 Real-world treatment persistence of non-tumor necrosis factor inhibitors versus tumor necr 2020 Feb Aims: We aimed to assess treatment persistence of tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors in two groups of rheumatoid arthritis (RA) patients: biologic disease-modifying antirheumatic drug (bDMARD) initiators and switchers.Patients and methods: This retrospective cohort study utilized a national health insurance claims database. Patients aged ≥18 years initiating/switching bDMARD between 1 December 2013 and 31 December 2014, the index period, were followed for 12 months. Initiators who began treatment with a bDMARD during the index period were defined as having no bDMARD prescriptions for the previous year. Switchers who changed treatment from the previous bDMARD to the index bDMARD were defined as having different bDMARDs during the index period. Treatment persistence rates during the follow-up period were measured, and factors associated with non-persistence were assessed with the Cox proportional hazard model.Results: Of 2684 patients, treatment persistence rates were the highest for abatacept in initiators (69.3%) and tocilizumab in switchers (77.0%), while adalimumab showed the lowest persistence rates for both initiators and switchers (48.2%, 28.8%), followed by etanercept (51.3%, 41.0%). Adalimumab and etanercept were significantly more likely to show non-persistence (HR 1.58, 95% CI 1.27-1.96; HR 1.42, 95% CI 1.14-1.76) compared to infliximab for initiators, while tocilizumab was significantly more likely to show persistence (HR 0.411, 95% CI 0.206-0.819) in switchers.Conclusions: Non-TNF inhibitors showed higher persistence rates than TNF inhibitors in South Korean RA patients, and tocilizumab especially was associated with higher persistence in patients with inadequate response to TNF inhibitors. Good persistence with non-TNF inhibitors indicates the potential for long-term efficacy as first-line treatment.
30822348 Causes of synthetic disease-modifying drug discontinuation in rheumatoid arthritis: Data f 2019 The treatment of rheumatoid arthritis (RA) has evolved rapidly in recent years. Nonetheless, conventional synthetic disease-modifying drugs (csDMARDs) remain the gold standard for RA treatment. The treatment for RA is expensive and this has a negative impact on public health. Given the low cost of csDMARDs compared to those of other treatment strategies, it is important to manage this type of treatment properly. Information on the duration of use of each drug and the reasons for their discontinuation is relevant to medical practitioners as it could improve the information available regarding side effects and their proper management. Moreover, data from clinical practice in the population can provide health care managers with information for resource allocation and optimization of csDMARD use with a consequent cost reduction in the treatment of RA. In this cross-sectional study, we aimed to describe the use of csDMARDs in public health services in Brazil, emphasizing on the duration of use and reasons for discontinuation of each drug. This study is a part of the REAL, a multicenter project that evaluated Brazilian patients with RA from eleven rheumatology services from August to October 2015. Patients were examined clinically, and an analysis of complementary exams and medical records was performed. A total of 1125 patients were included. 98.5% were women with a median age of 55.6 years. 36% and 90.84% patients were using biological disease-modifying drugs (bDMARDs) and csDMARDs, respectively. The duration of use and doses of each medication and the causes of suspension were analyzed. Most of the patients analyzed in this study were using csDMARDs for prolonged periods and methotrexate showed the longest duration of use. Interruption indexes due to ineffectiveness and side effects were analyzed. The knowledge of common adverse effects may alert attending physicians to the proper management of effective and low-cost therapeutic groups.
30629334 Translating Treatment Effects Between Rheumatoid Arthritis Activity Measures and American 2019 Nov OBJECTIVE: Direct comparison trials in rheumatoid arthritis (RA) increasingly use changes in continuous disease activity measures as endpoints. However, the between-arm differences in these scores that are clinically meaningful are uncertain. To aid interpretation of clinical trials that use the Disease Activity Score in 28 joints (DAS28) or Simplified Disease Activity Index (SDAI) as endpoints, we developed statistical equivalences between changes in these measures and American College of Rheumatology (ACR) responses. METHODS: For superiority trials, we computed the minimal detectable difference in DAS28 changes and SDAI changes that correspond to the ACR criteria for 20% improvement (ACR20) and 50% improvement (ACR50) responses at the same type I and type II errors and same sample size. For noninferiority trials, we computed noninferiority margins that were statistically equivalent across measures. Standard deviations of the changes in the DAS28 and SDAI from a recent observational study were used as the basis of calculations in our examples. RESULTS: In the base scenario with type 1 error 0.05 and power 0.80, a trial with 300 subjects per arm would detect a 0.31-point difference in mean DAS28 change scores and 3.71-point difference in mean SDAI change scores as statistically equivalent to an absolute difference of 11% in ACR20 between treatment arms. We developed a web-based utility that provides equivalent differences among these measures for customized sample sizes, error rates, and standard deviations of the DAS28 and SDAI between-arm differences. CONCLUSION: The DAS28 and SDAI responses can be related to statistically equivalent changes in ACR responses, which can aid the interpretation of trials that use these measures.
31584880 Time Effect of Intra-articular Injection With Triamcinolone Hexacetonide and Its Correlati 2019 Oct OBJECTIVE: The aim of the study was to assess the time effect of intra-articular injection with triamcinolone hexacetonide in rheumatic patients. DESIGN: A prospective case-control study with patients submitted to one intra-articular injection with triamcinolone hexacetonide. Patients were followed monthly (12 mos) for pain and swelling. RESULTS: Two hundred sixty-two joints were assessed in 158 patients with mean ± SD age of 60 ± 13.7 yrs. Remission was observed at 3, 6, and 12 mos in 142 (54.19%), 111 (42.36%), and 105 (40.07%) joints, respectively. The mean ± SD time effect were 8 ± 4.0 mos; 8.4 ± 3.9 for rheumatoid arthritis patients and 6.9 ± 4.0 for osteoarthritis patients (P = 0.012) and 10.4 ± 2.7 mos for small, 7.7 ± 4.1 for medium, and 6.8 ± 4.0 for large joints. The joints were divided into two groups: long-term group (time effect of intra-articular injection longer than 6 mos) and short-term group. The following are the variables associated (P < 0.05) with long-term group: rheumatoid arthritis, small and medium-sized joints, female sex, lower pain and swelling visual analog scale scores, and use of leflunomide. The following are the variables associated with short-term group: receiving only one intra-articular injection, hypertension, diabetes mellitus, and biological therapy. CONCLUSIONS: The mean ± SD time effect of intra-articular injection with triamcinolone hexacetonide was 8.0 ± 4.0 mos. The associated predictors were rheumatoid arthritis, small and medium joints, lower pain/swelling visual analog scale scores, and use of leflunomide.
31485714 [Biologics in rheumatology]. 2019 Oct BACKGROUND: Monoclonal antibodies and fusion proteins were introduced into clinical rheumatology 20 years ago. Nowadays they are an established component of modern internal medical practice. OBJECTIVE: This article gives an overview of the breadth of biologics currently in clinical use. MATERIAL AND METHODS: Evaluation of published approval studies and guideline recommendations, discussion of the immunological principles and targets in the treatment with biologics. RESULTS: Monoclonal antibodies and fusion proteins for influencing cytokine signals, T‑cell costimulation and B‑cell function are the most important innovations in the treatment of rheumatological diseases. Nowadays they are indispensible for the treatment of moderate and severe disease courses of rheumatoid arthritis, spondylarthropathies and vasculitides. CONCLUSION: Although a cure or permanent freedom from symptoms in rheumatological autoimmune diseases is still not possible, much more favorable disease courses with less long-term limitations can be achieved by the early administration of biologics.
31715278 Nanomedicine - advantages for their use in rheumatoid arthritis theranostics. 2019 Dec 28 Rheumatoid arthritis (RA) is an autoimmune disease accompanies with synovial inflammation and progressive bone destruction. Currently, anti-rheumatic drugs need high dose and frequent use for a long-term, which lead to serious side effect and low patient compliance. To overcome above problems and improve clinical efficacy, nano-technology with targeting ability, sustained release and so forth, has been proposed on RA treatment and already achieved success in RA animal models. In this review, authors summarize and illustrate representative nanomedicine targeting to RA states, which is achieved either through passive or active targeting with high affinity to the receptors that are over-expressed in macrophages or angiogenesis. In particular, authors highlight the new strategies to promote the efficacy of nanoscale treatments through phototherapy and the addition of contrast elements for theranostic application. The described advances may pave the way to better understanding and designing the novel nanomedicine and multifunctional nano-system on efficient RA treatment.
30990587 Helios but not CD226, TIGIT and Foxp3 is a Potential Marker for CD4(+) Treg Cells in Patie 2019 BACKGROUND/AIMS: Rheumatoid arthritis (RA) is a progressive, chronic, even disabling systemic autoimmune disease. Imbalance between pathogenic immune cells and immunosuppressive cells is associated with the pathogenesis and development of RA and other autoimmune diseases. As Foxp3 is also expressed on activated CD4(+) cells in the presence of inflammation, the identification of Treg cells in patients with RA remains a challenge. METHODS: Comprehensive analyses were carried out by Flow cytometry. Expression of Helios, CD226, T cell immunoreceptor with Ig and ITIM domains clinical samples and healthy controls. RESULTS: We have systemically examined three potential markers, Helios, CD226 and TIGIT, that are possibly related to Treg identification, and found that Helios expression on CD4(+)Foxp3(+)cells was decreased and negatively correlated with the disease activity of RA patients, while CD226 and TIGIT both showed elevated expression levels in CD4(+)Foxp3(+)cells in RA patients and they were not associated with disease activity of RA patients. CONCLUSION: Taken together, our findings indicate that CD4(+)CD25(hi)CD127(low/-)Foxp3(+)Helios(+) may represent the real Treg cell population in patients with RA.
30659920 Patients' information and perspectives on biosimilars in rheumatology: A French nation-wid 2019 Jul OBJECTIVE: To assess the patients' information about biosimilars and to identify the patients' incentives and deterrents to concur with the use of biosimilars. METHODS: Nation-wide cross-sectional study assessing information and concerns about biosimilars of French patients treated for rheumatic inflammatory diseases, whether they were treated or not by a biological DMARD. The assessment was available online from March to July 2017. RESULTS: Among the 629 respondents, 43% knew what biosimilars were. The main sources of information were rheumatologists and patient associations. Among patients treated with a biosimilar, 44% were not informed before they received the treatment. The patients' concerns focused on the non-similar molecular structure (46%), efficacy (60%) and safety (57%) comparatively to the originator biologic. 15% of respondents would refuse to switch their biologic to its biosimilar. More than 50% of respondents would warily accept to switch medications and interrupt the treatment if in doubt. Being informed about biosimilars and a good understanding of the definition of biosimilars were characteristics associated with better adherence to biosimilars. The rheumatologist was considered the most influent source of information about biosimilars and was considered reliable when deciding to switch a biologic to its biosimilar. Patient were reluctant to substitution of the medications by pharmacists (2%). Medico-economical issues acted as an incentive and a deterrent to accept the switch of medication. CONCLUSION: Biosimilars are largely unknown to patients. Information seems to be instrumental in improving the patients' adherence to biosimilars and could help preserving the therapeutic relationship and avoiding a nocebo effect.