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ID PMID Title PublicationDate abstract
30385707 Ultrasound of Subtalar Joint Synovitis in Patients with Rheumatoid Arthritis: Results of a 2019 Apr OBJECTIVE: To evaluate the intraobserver and interobserver reliability of the ultrasonographic (US) assessment of subtalar joint (STJ) synovitis in patients with rheumatoid arthritis (RA). METHODS: Following a Delphi process, 12 sonographers conducted an US reliability exercise on 10 RA patients with hindfoot pain. The anteromedial, posteromedial, and posterolateral STJ was assessed using B-mode and power Doppler (PD) techniques according to an agreed US protocol and using a 4-grade semiquantitative grading score for synovitis [synovial hypertrophy (SH) and signal] and a dichotomous score for the presence of joint effusion (JE). Intraobserver and interobserver reliability were computed by Cohen's and Light's κ. Weighted κ coefficients with absolute weighting were computed for B-mode and PD signal. RESULTS: Mean weighted Cohen's κ for SH, PD, and JE were 0.80 (95% CI 0.62-0.98), 0.61 (95% CI 0.48-0.73), and 0.52 (95% CI 0.36-0.67), respectively. Weighted Cohen's κ for SH, PD, and JE in the anteromedial, posteromedial, and posterolateral STJ were -0.04 to 0.79, 0.42-0.95, and 0.28-0.77; 0.31-1, -0.05 to 0.65, and -0.2 to 0.69; 0.66-1, 0.52-1, and 0.42-0.88, respectively. Weighted Light's κ for SH was 0.67 (95% CI 0.58-0.74), 0.46 (95% CI 0.35-0.59) for PD, and 0.16 (95% CI 0.08-0.27) for JE. Weighted Light's κ for SH, PD, and JE were 0.63 (95% CI 0.45-0.82), 0.33 (95% CI 0.19-0.42), and 0.09 (95% CI -0.01 to 0.19), for the anteromedial; 0.49 (95% CI 0.27-0.64), 0.35 (95% CI 0.27-0.4), and 0.04 (95% CI -0.06 to 0.1) for posteromedial; and 0.82 (95% CI 0.75-0.89), 0.66 (95% CI 0.56-0.8), and 0.18 (95% CI 0.04-0.34) for posterolateral STJ, respectively. CONCLUSION: Using a multisite assessment, US appears to be a reliable tool for assessing synovitis of STJ in RA.
30201476 Safety of biological agents in paediatric rheumatic diseases: A real-life multicenter retr 2019 May OBJECTIVE: To analyse and report the incidence of side effects of biological agents in paediatric patients with inflammatory diseases using of real-life follow-up cohort. METHODS: In this international, observational, retrospective, multicentre study of children treated by biological agents and followed in the Juvenile Inflammatory Rheumatism (JIR) cohort (JIRcohorte) network, a Kaplan-Meier method was used to estimate the occurrence of adverse events. A Cox model was constructed to identify independent predictors of adverse events. RESULTS: Overall 813 patients totalling 3439 patients-year (PY) of biological agents were included. The main diagnosis was juvenile idiopathic arthritis (84%). A total of 222 patients (27.3%) had 419 adverse events, representing an incidence rate of 12.2 per 100 PY 95% CI [11.0; 13.4]. The overall incidence rate of serious adverse events was 3.9 per 100 PY 95% CI [3.2; 4.6]. Tocilizumab and infliximab were significantly associated with adverse events and canakinumab with serious adverse events. Univariate and multivariable analysis of adverse events and serious adverse events indicated that patients under biological agents with concomitant immunosuppressive drugs (excluding methotrexate) suffered from more of these events. CONCLUSION: This study suggests an overall an acceptable safety of biologic agents in children with inflammatory rheumatic diseases treated with biological agents. However, the concomitant prescription of immunosuppressive drugs with biological agents represents a substantial risk of adverse events.
28699378 Reasons for cesarean and medically indicated deliveries in pregnancies in women with syste 2018 Mar Objective To determine reasons for cesarean and medically indicated deliveries in a registry of pregnant women with SLE compared to RA. Methods Pregnant women with SLE or RA were prospectively followed, and pregnancy outcomes were collected, including whether labor was spontaneous or medically indicated and delivery was vaginal or cesarean. Preterm birth was defined as a birth <37 weeks gestation. Differences in reasons for cesarean delivery and indication of delivery between term and preterm births were determined by Fisher's exact test. Results Compared to RA pregnancies, SLE pregnancies had modestly higher rates of preterm birth (24% SLE vs 14% RA), pre-eclampsia (15% SLE vs 7% RA), and cesarean delivery (48% SLE vs 30% RA). The majority of preterm births among women with SLE were indicated (70%), most commonly for pre-eclampsia or the health of the infant or mother. The majority of preterm births among women with RA, however, were spontaneous, primarily due to premature rupture of membranes. Conclusion Pre-eclampsia and maternal SLE activity appear to be the key drivers for the high rate of preterm birth and medically indicated delivery in SLE. This contrasts with RA, where preterm labor is most often due to spontaneous onset of labor.
29335343 Association Between Glucocorticoid Exposure and Healthcare Expenditures for Potential Gluc 2018 Mar OBJECTIVE: Oral glucocorticoid (OGC) use for rheumatoid arthritis (RA) is debated because of the adverse event (AE) profile of OGC. We evaluated the associations between cumulative doses of OGC and potential OGC-related AE, and quantified the associated healthcare expenditures. METHODS: Using the MarketScan databases, patients ≥ 18 years old who have RA with continuous enrollment from January 1 to December 31, 2012 (baseline), and from January 1 to December 31, 2013 (evaluation period), were identified. Cumulative OGC dose was measured using prescription claims during the baseline period. Potential OGC-related AE (osteoporosis, fracture, aseptic necrosis of the bone, type 2 diabetes, ulcer/gastrointestinal bleeding, cataract, hospitalization for opportunistic infection, myocardial infarction, or stroke) and AE-related expenditures (2013 US$) were gathered during the evaluation period. Multivariable regression models were fitted to estimate OR of AE and incremental costs for patients with AE. RESULTS: There were 84,357 patients analyzed, of whom 48% used OGC during the baseline period and 26% had an AE during the evaluation period. A cumulative OGC dose > 1800 mg was associated with an increased risk of any AE compared with no OGC exposure (OR 1.19, 99.65% CI 1.09-1.30). Incremental costs per patient with any AE were significantly greater for cumulative OGC dose > 1800 mg compared with no OGC exposure (incremental cost = $3528, 99.65% CI $2402-$4793). CONCLUSION: Chronic exposure to low to medium doses of OGC was associated with significantly increased risk of potential OGC-related AE in patients with RA, and greater cumulative OGC dose was associated with substantially higher AE-related healthcare expenditures among patients with AE.
28736929 Impact of Cost-Sharing Increases on Continuity of Specialty Drug Use: A Quasi-Experimental 2018 Aug OBJECTIVE: To examine the impact of cost-sharing increases on continuity of specialty drug use in Medicare beneficiaries with multiple sclerosis (MS) or rheumatoid arthritis (RA). DATA SOURCES/STUDY SETTING: Five percent Medicare claims data (2007-2010). STUDY DESIGN: Quasi-experimental study examining changes in specialty drug use among a group of Medicare Part D beneficiaries without low-income subsidies (non-LIS) as they transitioned from a 5 percent cost-sharing preperiod to a ≥25 percent cost-sharing postperiod, as compared to changes among a disease-matched contemporaneous control group of patients eligible for full low-income subsidies (LIS), who faced minor cost sharing (≤$6.30 copayment) in both the pre- and postperiods. DATA COLLECTION/EXTRACTION METHODS: Key variables were extracted from Medicare data. PRINCIPAL FINDINGS: Relative to the LIS group, the non-LIS group had a greater increase in incidence of 30-day continuous gaps in any Part D treatment from the lower cost-sharing period to the higher cost-sharing period (MS, absolute increase = 10.1 percent, OR = 1.61, 95% CI 1.19-2.17; RA, absolute increase = 21.9 percent, OR = 2.75, 95% CI 2.15-3.51). The increase in Part D treatment gaps was not offset by increased Part B specialty drug use. CONCLUSIONS: Cost-sharing increases due to specialty tier-level cost sharing were associated with interruptions in MS and RA specialty drug treatments.
29341286 Test-1 analyzer and conventional Westergren method for erythrocyte sedimentation rate: A c 2018 Jun BACKGROUND: Measurement of the length of sedimentation reaction in blood (LSRB), also called erythrocyte sedimentation rate (ESR), is a widely used hematology test. This study intends to compare ESR levels measured by Test-1 method and International Council for Standardization in Hematology's (ICSH) reference method, and analyzes the effect of hematocrit (Hct) on ESR results. MATERIAL AND METHODS: A total of 755 patients from 2 hospitals were included in the study, and samples with EDTA were studied by Test-1 method for ESR measurement and total blood count, whereas citrated samples were studied with reference Westergren method. Then, 2 methods were compared. Distribution of ESR results according to the ESR(≤20, >20 mm/h) and Hct(≥35%, <35%) levels and hospital type was analyzed. ESR levels with Hct levels<35% were corrected with Fabry's formula. RESULTS: The mean and SD values for the Test-1 method, reference Westergren method, and corrected ESR measurement were 21.30 ± 18.39, 28.59 ± 25.82, and 24.92 ± 20.58 mm/h, respectively. Within the whole group, the correlation coefficient (r) was .77 (.7-.80) with a significance level P < .001. Passing-Bablok regression analysis of the methods resulted in a regression equation y = 1.00 (95% Cl: 0.43-1.88) + 0.75 (95% Cl: 0.70-0.78)x while the significance of linearity was acceptable (P < .01). All subgroup linear regression analyses revealed that the correlation was acceptable, except ESR > 20 mm/h group, Hct < 35% group, and corrected ESR group (significance level were P > .10). CONCLUSION: The study showed that the role of the hospital and the capacity of testing are important in choosing the instrument for measuring ESR. Furthermore, the patient profile, especially malignancy possibility and Hct level, may be important for instrument selection.
29288042 STAT3 mutation and its clinical and histopathologic correlation in T-cell large granular l 2018 Mar Although T-cell large granular lymphocytic leukemia (T-LGLL) is a clinically indolent disorder, patients with moderate to severe cytopenia require therapeutic intervention. The recent discovery of STAT3 mutations has shed light on the genetic basis of T-LGLL pathogenesis. However, the association of STAT3 mutational status with patients' clinical, histopathologic, and other laboratory features has not been thoroughly evaluated in T-LGLL. In this study, STAT3 mutations were identified in 18 of 36 patients with T-LGLL (50%), including Y640F (12/18, 66.7%), N647I (3/18, 16.7%), E638Q (1/18, 5.6%), I659L (1/18, 5.6%), and K657R (1/18, 5.6%). Interestingly, pure red cell aplasia was seen exclusively in T-LGLL patients without STAT3 mutations (6/15 in the wild-type STAT3 group versus 0/13 in the mutant STAT3 group; P = .02); these patients also were the only responders to T-LGLL therapy (mainly cyclophosphamide) in wild-type STAT3 group. Patients harboring STAT3 mutations were more prone to rheumatoid arthritis (4/13 versus 0/15 in the wild-type STAT3 group; P = .04), frequently requiring therapy for neutropenia/neutropenia-associated infections, and demonstrated good therapeutic responses to methotrexate. No significant differences were seen in complete blood count, flow cytometric immunophenotypic features, T-cell receptor γ V-J rearrangement repertoire, and bone marrow biopsy morphology among the STAT3-mutation and wild-type groups other than significantly larger tumor burden in patients with STAT3 mutations. The distinct disease association and therapeutic responses observed in patients with mutant and wild-type STAT3 warrant further investigation to elucidate the underlying mechanisms. They also highlight the importance of identifying STAT3 mutational status in patients with T-LGLL, which may aid in clinical therapeutic choice.
30043229 Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Oppo 2018 Oct Subcutaneous delivery of biotherapeutics has become a valuable alternative to intravenous administration across many disease areas. Although the pharmacokinetic profiles of subcutaneous and intravenous formulations differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and to result in reduced drug delivery-related healthcare costs and resource use. The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from both health-economic and scientific perspectives. The article covers different indications, treatment settings, administration volumes, and injection devices. We focus on biotherapeutics in rheumatoid arthritis (RA), immunoglobulin-replacement therapy in primary immunodeficiency (PI), beta interferons in multiple sclerosis (MS), and monoclonal antibodies (mAbs) in oncology. While most subcutaneous biotherapeutics in RA, PI, and MS are self-administered at home, mAbs for oncology are still only approved for administration in a healthcare setting. Beside concerns around the safety of biotherapeutics in oncology, a key challenge for self-administration in this area is that doses and dosing volumes can be comparatively large; however, this difficulty has recently been overcome to some extent by the development of high-concentration solutions, the use of infusion pumps, and the coadministration of the dispersion enhancer hyaluronidase. Furthermore, given the increasing number of biotherapeutics being considered for combination therapy and the high dosing complexity associated with these, especially when administered intravenously, subcutaneous delivery of fixed-dose combinations might be an alternative that will diminish these burdens on healthcare systems.
30403262 Evaluation of toxic retinopathy caused by antimalarial medications with spectral domain op 2019 Jan PURPOSE: To investigate the frequency of toxic retinopathy in patients with lupus erythematosus and rheumatoid arthritis with long-term use of chloroquine diphosphate or hydroxychloroquine through spectral domain optical coherence tomography and the outcomes of ophthalmological exams (visual acuity - Snellen's table, color vision test - Ishihara's table, fundoscopy, and retinography - red-free). METHODS: A cross-sectional study was carried out involving the ophthalmologic evaluation of patients using regular chloroquine diphosphate or hydroxychloroquine for a period of 1 year or longer. The patients completed a questionnaire on their opinions and treatment regularity. The same patients underwent ophthalmologic examination and spectral domain optical coherence tomography. RESULTS: The prevalence of toxic retinopathy caused by antimalarials was 4.15% (9 of 217 patients), 7.4% (4 of 54 patients) following chloroquine diphosphate usage, and 0.82% (1 of 121 patients) following hydroxychloroquine usage. Only patients with advanced stage maculopathy presented abnormalities during the ophthalmologic exam: the color vision test was altered in 11.1%, and visual acuity and fundoscopy were altered in 33.3%. Identification of early toxic retinopathy, detected in six patients, was possible using spectral domain optical coherence tomography. The mean duration of antimalarial drug usage among patients with toxic retinopathy was 10.4 years. Only 31% of the patients reported some symptoms during treatment, and although 24% were afraid to use the medication, they did so as prescribed. CONCLUSION: Use of spectral domain optical coherence tomography was essential for the diagnosis of early-stage antimalarial toxic retinopathy in patients with the following characteristics: asymptomatic, antimalarial use 7 days a week for a period of more than 5 years, and normal clinical ophthalmologic examination.
29054755 Association of polymorphic variants in IL1B gene with secretion of IL-1β protein and infl 2018 Jan 30 The proinflammatory cytokine interleukin-1beta (IL-1β) is a key mediator of inflammation which affects cell proliferation and differentiation. IL-1β is considered to contribute to the pathophysiology of rheumatoid arthritis (RA). Polymorphisms in cytokine genes are highly influenced by ethnicity. Hence, in this study polymorphism of the IL1B-511(C/T) within promoter region was analyzed by using polymerase chain reaction-restriction fragment length Polymorphism (PCR-RFLP) in 187 RA patients and 214 controls. The prevalence of different genotypes and allelic frequency distribution was compared in RA patients and controls. Levels of inflammatory markers and serum levels of IL-1β were estimated by ELISA The serum inflammatory markers levels were significantly higher in RA patients as compared to controls (RF=127.3±21.3U/mL, Anti-CCP=17.8±8.3U/mL, CRP=17.86±7.1mg/L and IL-1β=21.25±4.19pg/mL in RA patients p<0.01). The frequency of heterozygous mutant (C/T) and homozygous mutant (T/T) variants were significantly higher in RA patients as compared to controls and the odds ratios by logistic regression were (OR=2.2, p<0.001) and (OR=3.21, p<0.01) respectively. The association persisted on combining the heterozygous mutant and homozygous mutant (CT+TT) together as compared to controls (OR=2.39; p<0.001). Positive and significant (p<0.05) correlation of circulating IL-1β levels with RF (r=0.232), anti-CCP (r=0.207) and CRP (r=0.166) among RA patients were found. The levels of anti-CCP were significantly higher in homozygous mutant variants (TT) as well as the heterozygous mutant variants (C/T) in comparison to the wild variants (CC) (p<0.01). The results of this study reveal that mutant allele (T) of IL1B-511 promoter SNP tends to be associated with elevated anti-CCP and IL-1β levels as observed in RA patients and hence disease susceptibility.
29477400 A Comparison of Different Approaches for Costing Medication Use in an Economic Evaluation. 2018 Feb BACKGROUND: Estimating individual-level medication costs in an economic evaluation can involve extensive data collection and handling. Implications of detailed versus general approaches are unclear. OBJECTIVES: To compare costing approaches in a trial-based economic evaluation. METHODS: We applied four costing approaches to prescribed medication data from the Tumour necrosis factor inhibitors Against Combination Intensive Therapy randomized controlled trial. A detailed micro-costing approach was used as a base case, against which other approaches were compared: costing medications used by at least 1.5% of patients; costing medications on the basis of only chemical name; applying a generic prescription charge rather than a medication-specific cost. We quantitatively examined resulting estimates of prescribed medication and total care costs, and qualitatively examined trial conclusions. RESULTS: Medication costs made up 6% of the total health and social care costs. There was good agreement in prescribed medication costs (concordance correlation coefficient [CCC] 0.815, 0.819, and 0.989) and excellent agreement in total costs (CCC 0.990, 0.995, and 0.995) between approaches 1 and 2. Approaches 3 and 4 had poor agreement with approach 1 on prescribed medication costs (CCC 0.246-0.700 and 0.033-0.333, respectively), but agreement on total care costs remained good (CCC 0.778-0.993 and 0.729-0.986, respectively). CONCLUSIONS: Because medication costs comprised only a small proportion of total costs, the less resource-intensive approaches had substantial impacts on medication cost estimates, but had little impact on total care costs and did not significantly impact the trial's cost-effectiveness conclusions. There is room for research efficiencies without detriment to an evaluation in which medication costs are likely to form a small proportion of total costs.
29481970 Combining Biologics in Inflammatory Bowel Disease and Other Immune Mediated Inflammatory D 2018 Sep Current therapies used in the treatment of inflammatory bowel disease (IBD) are not effective in all patients. Biologic agents result in approximately 40% remission rates at 1 year in selected populations, prompting a growing interest in combining biologic therapy to improve outcomes. There are limited published data regarding the efficacy and safety of combination targeted therapy in IBD specifically, which include only 1 exploratory randomized control trial and 3 case reports or series. This review evaluates the published literature regarding this therapeutic paradigm in IBD and its extensive utilization in the treatment of other immune-mediated inflammatory disorders. The combination of biologic therapies demonstrates variable degrees of efficacy and highlights some safety concerns, depending upon the agents used and the disease state treated. A trial (Clinical Trials.gov Identifier: NCT02764762) combining vedolizumab and adalimumab is currently underway evaluating the effectiveness and safety of this approach in patients with Crohn's disease, which should provide further insight into this treatment concept. While combination biologic therapy is an attractive strategy, the lack of consistent superior efficacy as well as safety concerns militates the need for further trials prior to its general application in IBD.
29448880 Migration and clinical outcome of mobile-bearing versus fixed-bearing single-radius total 2018 Apr Background and purpose - Mobile-bearing total knee prostheses (TKPs) were developed in the 1970s in an attempt to increase function and improve implant longevity. However, modern fixed-bearing designs like the single-radius TKP may provide similar advantages. We compared tibial component migration measured with radiostereometric analysis (RSA) and clinical outcome of otherwise similarly designed cemented fixed-bearing and mobile-bearing single-radius TKPs. Patients and methods - RSA measurements and clinical scores were assessed in 46 randomized patients at baseline, 6 months, 1 year, and annually thereafter up to 6 years postoperatively. A linear mixed-effects model was used to analyze the repeated measurements. Results - Both groups showed comparable migration (p = 0.3), with a mean migration at 6-year follow-up of 0.90 mm (95% CI 0.49-1.41) for the fixed-bearing group compared with 1.22 mm (95% CI 0.75-1.80) for the mobile-bearing group. Clinical outcomes were similar between groups. 1 fixed-bearing knee was revised for aseptic loosening after 6 years and 2 knees (1 in each group) were revised for late infection. 2 knees (1 in each group) were suspected for loosening due to excessive migration. Another mobile-bearing knee was revised after an insert dislocation due to failure of the locking mechanism 6 weeks postoperatively, after which study inclusion was preliminary terminated. Interpretation - Fixed-bearing and mobile-bearing single-radius TKPs showed similar migration. The latter may, however, expose patients to more complex surgical techniques and risks such as insert dislocations inherent to this rotating-platform design.
30284646 Imbalance of circulating Tfr/Tfh ratio in patients with rheumatoid arthritis. 2019 Feb Follicular helper T(Tfh) cells and follicular regulatory T(Tfr) cells are critical for the development and maintenance of germinal center and humoral immune responses. Accumulating evidence has demonstrated that the dysregulation of either Tfh or Tfr cells contributes to the pathogenesis of autoimmune diseases. The aim of this study was to examine the numbers of Tfh and Tfr cells in patients with rheumatoid arthritis (RA). Twenty-four patients with RA patients and 20 health controls (HCs) were enrolled in this study. We analyzed the numbers of Tfh (CD4(+) CXCR5(+) PD-1(hi)) cells and Tfr (CD4(+) CXCR5(+)CD127(lo)) cells in 24 RA patients via flow cytometry. The level of the soluble PD-1 and its ligands (sPD-L1 and sPDL-2) were examined by ELISA. Flow cytometry revealed that both circulating Tfh and Tfr cells were increased in RA patients compared with HCs. More importantly, the ratio of Tfr/Tfh was decreased, indicating a disruption of the balance between Tfh and Tfr. The Tfr/Tfh ratio was inversely correlated with level of serum CRP, ESR, RF, anti-CCP, IgG and DAS28 index. We also found that the serum level of sPD-1 was significantly elevated in the RA patients, which was positively correlated with CRP, ESR and the number of Tfh cells. These results indicate that an imbalance of circulating Tfr and Tfh cells may be involved in the immunopathogenesis of RA and may provide novel insight for the development of RA therapies.
30430682 Use of tumor necrosis factor-alpha inhibitors during pregnancy among women who delivered l 2019 Mar PURPOSE: To describe the use of tumor necrosis factor-alpha inhibitors (TNFis) among pregnancies ending in a live birth and with a diagnosis of ankylosing spondylitis (AS), Crohn's disease (CD), juvenile idiopathic arthritis (JIA), psoriasis (PsO), psoriatic arthritis (PsA), rheumatoid arthritis (RA), or ulcerative colitis (UC). METHODS: We identified pregnancies among women aged 15 to 54 years between 01/01/2004 and 09/30/2015 from 16 health plans participating in Sentinel. We inferred indication using ICD-9-CM codes in the 183-day period before conception. We assessed proportion of infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab by calendar year, indication, and maternal age, and compared them to proportions in an age-matched, indication-matched, and date-matched non-pregnant cohort. RESULTS: Among 19 681 pregnancies with at least one chronic inflammatory condition, 2990 (15.2%) received a TNFi. In both pregnancies and matched non-pregnant cohort, TNFi use was highest (34.4%; 55.8%) for PsA patients and lowest (6.2%; 13.4%) for PsO patients. Etanercept was most frequently used among AS/JIA/PsA/PsO/RA patients, while infliximab was the preferred TNFi for CD/UC patients. Except for infliximab and certolizumab, TNFi use during pregnancy decreased after the first trimester. Pregnancies among older pregnant women (45-54 years) were more likely to be treated compared with the matched non-pregnant cohort. CONCLUSION: There was a preference for etanercept among pregnancies with AS/JIA/PsA/PsO/RA, despite the availability of other TNFis. Decline in TNFi use after the first trimester may be related to the desire to reduce TNFis transplacental transfer and to minimize infection risk to the fetus or baby associated with live vaccine immunizations after birth.
29196381 Sharing Ongoing Care with Primary Care Physicians Opens Up Opportunity for Timelier and Ea 2018 Feb OBJECTIVE: In our region in Quebec, Canada, access to rheumatologists is very limited. Sharing followup of stable patients with their primary care physicians (PCP) could increase access to rheumatologists. In our study, we assessed the feasibility and potential benefits of sharing followup of inflammatory arthritis (IA) patients with their PCP. METHODS: We reviewed the clinical records of 300 patients with peripheral arthritis who presented at our rheumatology outpatient clinic between July and October 2015. We distributed questionnaires to their treating rheumatologist, asking whether a PCP could participate in the followup of the patient and whether there were any factors that would prevent shared followup. We also distributed questionnaires to PCP to assess their level of comfort in participating in the followup care of patients with arthritis. RESULTS: Chart review was completed on 300 patients. There was no treatment modification in 49% of the cases, and 38% of the visits were deemed unnecessary by the attending rheumatologist. We found that 74% of PCP were very interested in sharing the arthritis followup care of their patients. According to PCP, the main barriers to shared followup were treatment with biological agents, active disease, and need for infiltrations. Main organizational barriers were the lack of rheumatologist availability to see patients urgently (46%) and the lack of clear guidelines for the management of IA (58%). CONCLUSION: Up to 38% of peripheral IA visits to a rheumatologist could have been prevented and done by a PCP. In our department, this represented up to 19 followup visits per week that could have been avoided by involving a PCP.
29587202 Stattic inhibits RANKL-mediated osteoclastogenesis by suppressing activation of STAT3 and 2018 May Tofacitinib, a small molecule JAK inhibitor, has been widely used to reduce inflammation and inhibit progression of bone destruction in rheumatoid arthritis. STAT3, a downstream signaling molecule of JAK, plays a key role in the activation of signaling in response to inflammatory cytokines. Thus, targeting STAT3 may be an inspiring strategy for treating osteoclast-related diseases such as rheumatoid arthritis. In this study, we first investigated the effects of Stattic, a STAT3 inhibitor, on receptor activator of NF-κB ligand (RANKL)-mediated osteoclastogenesis. Stattic inhibited osteoclast differentiation and bone resorption in RANKL-induced RAW264.7 cells in a dose-dependent manner. Stattic also suppressed RANKL-induced upregulation of osteoclast-related genes tartrate-resistant acid phosphatase, matrix metalloproteinase 9, cathepsin K, RANK, tumor necrosis factor receptor-associated factor 6, and osteoclast-associated receptor in RAW264.7 cells. Moreover, Stattic exhibited an inhibitory effect on cell proliferation and cell cycle progression at higher dosages. At the molecular level, Stattic inhibited RANKL-induced activation of STAT3 and NF-κB pathways, without significantly affecting MAPK signaling. In addition, Stattic inhibited RANKL-induced expression of osteoclast-related transcription factors c-Fos and NFATc1. Importantly, Stattic also prevented bone loss caused by ovariectomy. Together, our data confirm that Stattic restricts osteoclastogenesis and bone loss by disturbing RANKL-induced STAT3 and NF-κB signaling. Thus, Stattic represents a novel type of osteoclast inhibitor that could be useful for conditions such as osteoporosis and rheumatoid arthritis.
29973268 Chemerin 156F, generated by chymase cleavage of prochemerin, is elevated in joint fluids o 2018 Jul 4 BACKGROUND: Chemerin is a chemoattractant involved in immunity that also functions as an adipokine. Chemerin is secreted as an inactive precursor (chem163S), and its activation requires proteolytic cleavages at its C-terminus, involving proteases in coagulation, fibrinolysis, and inflammation. Previously, we found chem158K was the dominant chemerin form in synovial fluids from patients with arthritis. In this study, we aimed to characterize a distinct cleaved chemerin form, chem156F, in osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: Purified chem156F was produced in transfected CHO cells. To quantify chem156F in OA and RA samples, we developed a specific ELISA for chem156F using antibody raised against a peptide representing the C-terminus of chem156F. RESULTS: Ca(2+) mobilization assays showed that the EC(50) values for chem163S, chem156F, and chem157S were 252 ± 141 nM, 133 ± 41.5 nM, and 5.83 ± 2.48 nM, respectively. chem156F was more active than its precursor, chem163S, but very much less potent than chem157S, the most active chemerin form. Chymase was shown to be capable of cleaving chem163S at a relevant rate. Using the chem156F ELISA we found a substantial amount of chem156F present in synovial fluids from patients with OA and RA, 24.06 ± 5.51 ng/ml and 20.35 ± 5.19 ng/ml (mean ± SEM, n = 25) respectively, representing 20% of total chemerin in OA and 76.7% of chemerin in RA synovial fluids. CONCLUSIONS: Our data show that chymase cleavage of chem163S to partially active chem156F can be found in synovial fluids where it can play a role in modulation of the inflammation in joints.
30684216 A novel third-generation TSH receptor antibody (TRAb) enzyme-linked immunosorbent assay ba 2018 Dec TSH receptor (TSHR) autoantibody (TRAb) is the serological hallmark of Graves' disease (GD). Third-generation enzyme-linked immunosorbent assays (ELISAs) using monoclonal TRAbs instead of TSH have been found useful for TRAb analysis recently. For the first time, a mouse monoclonal antibody (mAb) against TSHR was analyzed for TRAb detection and compared with human mAb M22 and TSH by the same competitive binding assay technique. A mouse monoclonal antibody (T7) binding to the TSH receptor and inhibiting TSH binding was generated and used for TRAb analysis in a third-generation ELISA. Obtained TRAb levels were compared with a second-generation TRAb assay employing bovine TSH and a third-generation assay with human mAb M22 as TSHR-binding reagents by investigating 89 patients with GD, 56 with Hashimoto's thyroiditis (HT), 73 with non-autoimmune thyroid diseases, 17 with rheumatoid arthritis, and 100 healthy subjects. The T7-based TRAb ELISA did not reveal a significantly different assay performance (area under the curve [AUC]) in contrast to the TSH and M22-based TRAb ELISAs by receiver operating characteristic (ROC) curve analysis (AUC-T7 0.967, AUC-TSH 0.972, AUC-M22 0.958, p > 0.05, respectively). After adjustment of cutoffs by ROC, all three TRAb ELISAs demonstrated sensitivities and specificities above 89.9% and 96.0%, respectively. Both third-generation TRAb ELISAs showed a tendency for a higher prevalence of TRAb positives in HT in contrast to the second-generation ELISA. Mouse mAbs against the TSHR may be used for the reliable detection of TRAb by third-generation TRAb ELISA. The earlier reported higher sensitivity of third-generation TRAb ELISA in GD needs to be considered in the context of a slightly lower specificity regarding HT.
30397034 Blocking Matrix Metalloproteinase-9 Abrogates Collagen-Induced Arthritis via Inhibiting De 2018 Dec 15 Trafficking of dendritic cells (DCs) to lymph nodes (LNs) to present Ags is a crucial step in the pathogenesis of rheumatoid arthritis (RA). Matrix metalloproteinase-9 (MMP-9) is the key molecule for DC migration. Thus, blocking MMP-9 to inhibit DC migration may be a novel strategy to treat RA. In this study, we used anti-MMP-9 Ab to treat collagen-induced arthritis (CIA) in DBA/1J mice and demonstrated that anti-MMP-9 Ab treatment significantly suppressed the development of CIA via the modulation of DC trafficking. In anti-MMP-9 Ab-treated CIA mice, the number of DCs in draining LNs was obviously decreased. In vitro, anti-MMP-9 Ab and MMP-9 inhibitor restrained the migration of mature bone marrow-derived DCs in Matrigel in response to CCR7 ligand CCL21. In addition, blocking MMP-9 decreased T and B cell numbers in LNs of CIA mice but had no direct influence on the T cell response to collagen II by CD4(+) T cells purified from LNs or spleen. Besides, anti-MMP-9 Ab did not impact on the expression of MHC class II, CD40, CD80, CD86, and chemokine receptors (CCR5 and CCR7) of DCs both in vivo and in vitro. Furthermore, we discovered the number of MMP-9(-/-) DCs trafficking from footpads to popliteal LNs was dramatically reduced as compared with wild type DCs in both MMP-9(-/-) mice and wild type mice. Taken together, these results indicated that DC-derived MMP-9 is the crucial factor for DC migration, and blocking MMP-9 to inhibit DC migration may constitute a novel strategy of future therapy for RA and other similar autoimmune diseases.