Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 30730912 | TIM family gene polymorphism and susceptibility to rheumatoid arthritis: Systematic review | 2019 | BACKGROUND: TIM-family proteins are expressed on different immune cells such as dendritic cells, macrophages, type 1 and 2 T helper (Th) cells. Therefore, they have the ability to contribute to the various intracellular signals and immune responses, importantly the regulation of Th1 and Th17 cell differentiation, which plays a remarked role in fight against inflammatory and autoimmune diseases. Association of TIM family gene polymorphisms with rheumatoid arthritis (RA) has been frequently investigated. The findings however are not entirely consistent. Therefore, we carried out the present meta-analysis to examine the association between RA and the following TIM family gene polymorphisms: rs41297579, rs1036199, rs10515746, and rs7700944. METHODS: A systematic search of Scopus, PubMed, and Web of Science databases was conducted through December 2018. Combined odds ratios (OR) with their corresponding 95% confidence intervals (CI) were calculated under different possible genetic models. RESULTS: A total of eight case-control studies were included in the present meta-analysis. The results demonstrated significant association of RA with TIM-3 rs1036199 polymorphism under dominant (OR, 1.93, 95% CI, 1.43-2.61) and allelic models (OR, 1.74, 95% CI, 1.31-2.30). None of the other examined polymorphisms indicated significant association with RA. CONCLUSIONS: The present meta-analysis revealed that the TIM-3 rs1036199 polymorphism might confer susceptibility to RA. Further studies are required to reassert our findings. | |
| 31771618 | A search to the target tissue in which RA-specific inflammation starts: a detailed MRI stu | 2019 Nov 27 | OBJECTIVE: Based on a unique cohort of clinically suspect arthralgia (CSA) patients, we analysed which combinations of MRI features at onset were predictive for rheumatoid arthritis (RA) development. This was done to increase our comprehension of locations of RA onset and improve the predictive accuracy of MRI in CSA. METHODS: In the discovery cohort, 225 CSA patients were followed on clinical arthritis development. Contrast-enhanced 1.5 T MRIs were made of unilateral metacarpophalangeal (MCP) (2-5), wrist, and metatarsophalangeal (1-5) joints at baseline and scored for synovitis, tenosynovitis, and bone marrow edema. Severity, number, and combinations of locations (joint/tendon/bone) with subclinical inflammation were determined, with symptom-free controls of similar age category as reference. Cox regression was used for predictor selection. Predictive values were determined at 1 year follow-up. Results were validated in 209 CSA patients. RESULTS: In both cohorts, 15% developed arthritis < 1 year. The multivariable Cox model selected presence of MCP-extensor peritendinitis (HR 4.38 (2.07-9.25)) and the number of locations with subclinical inflammation (1-2 locations HR 2.54 (1.11-5.82); ≥ 3 locations HR 3.75 (1.49-9.48)) as predictors. Severity and combinations of inflammatory lesions were not selected. Based on these variables, five risk categories were defined: no subclinical inflammation, 1-2 locations, or ≥ 3 locations, with or without MCP-extensor peritendinitis. Positive predictive values (PPVs) ranged 5% (lowest category; NPV 95%) to 67% (highest category). Similar findings were obtained in the validation cohort; PPVs ranged 4% (lowest category; NPV 96%) to 63% (highest category). CONCLUSION: Tenosynovitis, particularly MCP-extensor peritendinitis, is among the first tissues affected by RA. Incorporating this feature and number of locations with subclinical inflammation improved prediction making with PPVs up to 63-67%. | |
| 30747496 | Investigating Asthma, Allergic Disease, Passive Smoke Exposure, and Risk of Rheumatoid Art | 2019 Aug | OBJECTIVE: Rheumatoid arthritis (RA) is postulated to originate at mucosal surfaces, particularly the airway mucosa. To investigate this hypothesis, we determined the association between RA and asthma, passive smoke exposure, and age at start of smoking. METHODS: For this case-control study, we identified 1,023 cases of RA (175 incident) within a single-center biobank population, using a rules-based algorithm that combined self-report with 2 diagnostic codes. Exposures were self-reported on biobank questionnaires. Logistic regression models were used to calculate the association of exposures with RA, adjusting for potential confounders. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. RESULTS: After adjustment for allergies, urban environment, and passive smoke exposure, asthma was found to be associated with RA in the full cohort (OR 1.28 [95% CI 1.04-1.58; P = 0.02]) but not the incident RA cohort (OR 1.17 [95% CI 0.66-2.06; P = 0.60]). History of allergic disease was associated with RA in both the full cohort (OR 1.30 [95% CI 1.12-1.51; P < 0.001]) and the incident RA cohort (OR 1.61 [95% CI 1.11-2.33; P = 0.01]), especially food allergy, which was significantly associated with RA in the full cohort (OR 1.38 [95% CI 1.08-1.75; P = 0.01]) and showed a trend toward significance in the incident RA cohort (OR 1.83 [95% CI 0.97-3.45; P = 0.06]). Passive smoke exposure at home or work was not associated with RA. Finally, age at start of smoking was not associated with increased odds of developing RA in either the full cohort (OR 1.03 [95% CI 1.00-1.06; P = 0.03]) or the incident RA cohort (OR 1.00 [95% CI 0.92-1.08; P = 0.98]). CONCLUSION: Asthma and allergies may be associated with increased risk of RA. Passive smoke exposure and early age at start of smoking do not appear to influence risk of RA. | |
| 30915483 | [Metacarpophalangeal joint replacement]. | 2019 May | BACKGROUND: Arthroplasty of metacarpophalangeal (MCP) joints is crucial for patients with rheumatoid arthritis. Motion preserving therapies are mandatory for this joint, since loss of function of the MCP joint is detrimental. Many protheses or spacers have been introduced over the last 80Â years, but most of them have been dismissed due to major complications. CURRENT PROCEDURES: Since the 1960s the Swanson spacer has been established as the reference standard for motion preserving procedures of the finger MCP joints. High fracture rates of the spacer do not seem to limit function and patient satisfaction after all. Current long-term studies show at least promising results for pyrolytic carbon protheses with respect to range of motion, survival, and revision rates in comparison to the Swanson spacer. | |
| 31813561 | Risk of exacerbation of pulmonary comorbidities in patients with rheumatoid arthritis afte | 2020 Jun | BACKGROUND: Biologic agents may pose a potential risk for exacerbations of pulmonary comorbidities in rheumatoid arthritis (RA) patients. METHODS: Using U.S. Medicare and Truven MarketScan databases, we identified three cohorts of RA patients with interstitial lung disease (ILD), chronic obstructive pulmonary disease (COPD), or asthma who initiated abatacept or a TNF inhibitor (TNFi). The primary outcome was a composite exacerbation of individual pulmonary comorbidities based on inpatient or emergency department (ED) visits due to exacerbation of the given pulmonary comorbidity. To adjust for >60 baseline confounders, we used propensity-score fine stratification (PSS) and weighting. Negative binomial regression model estimated a cohort-specific incidence rate ratio (IRR) and 95% confidence interval (CI) of the primary outcome per database, comparing abatacept versus TNFi. Database-specific IRRs were combined using a random-effects meta-analysis. RESULTS: We identified 3,295 ILD, 7,161 COPD, and 5,613 asthma patients with RA who initiated either abatacept or a TNFi. IR of composite exacerbation was high in all three pulmonary cohorts but highest in COPD cohort (3.59-11.80 per 100 person-years in ILD, 20.68-34.97 in COPD, and 4.66-13.78 in asthma). After PSS weighting, the combined IRR (95%CI) in abatacept initiators versus TNFi initiators was 0.44 (0.18-1.09) for ILD exacerbation, 0.91 (0.80-1.03) for COPD exacerbation, and 0.81 (0.54-1.22) for asthma exacerbation. CONCLUSION: Among patients with RA and pulmonary comorbidities, exacerbations requiring inpatient or ED visits occurred frequently after initiating abatacept or TNFi. Overall, we found no significant difference in the risk of ILD, COPD or asthma exacerbation between abatacept and TNFi initiators, but precision of our estimates is limited. | |
| 31732558 | Cervical Spine Involvement among Patients with Rheumatoid Arthritis Treated Actively with | 2020 Aug 1 | OBJECTIVE: To evaluate the development of radiological changes of the cervical spine in patients with rheumatoid arthritis (RA) in the NEO-RACo trial treated with an intensive, remission-targeted combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and additional infliximab (IFX) or placebo (PLA) for the first 6 months. METHODS: Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARD and prednisolone, and randomized to double-blindly receive either IFX (FIN-RACo+IFX) or PLA (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict NEO-RACo remission. At the 10-year visit, radiographs of the cervical spine were taken of 85 patients (38 in the FIN-RACo+IFX group and 47 in the FIN-RACo+PLA group). The study was registered at ClinicalTrials.gov (NCT00908089). RESULTS: There were 4/85 patients (4.7%) with cervical spine involvement (CSI) by 10 years. Atlantoaxial subluxation was found in 2/85 patients (2.4%), both in the FIN-RACo+IFX group, and none in the FIN-RACo+PLA group. Atlantoaxial impaction was found in 1/85 patients (1.2%) in the FIN-RACo+IFX group. Subaxial subluxation was found in 1/85 patients (1.2%). CONCLUSION: Early and intensive remission-targeted treatment has reduced the incidence of CSI and our results show that intensive treatment also prevents its development in the long run. | |
| 31263067 | Toward Defining Primary and Secondary Nonresponse in Rheumatoid Arthritis Patients Treated | 2020 Apr | OBJECTIVE: Although most patients with rheumatoid arthritis (RA) respond to anti-tumor necrosis factor (anti-TNF) treatment, some present with initial nonresponse (1ry nonresponse) or lose initial responsiveness (2ry nonresponse). We compared the rate of real-world "nonresponse" to first anti-TNF as reported by treating physicians to the nonresponse rate per accepted definitions and recommended treat-to-target strategies. METHODS: Patients were included from the Biologic Treatment Registry Across Canada (BioTRAC) and Ontario Best Practices Research Initiative (OBRI) registries who were taking their first anti-TNF, with ≥ 1 followup visit. Posthoc reclassification of physician-reported nonresponse was based on prior achievement of 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), Clinical Disease Activity Index (CDAI) LDA, or good/moderate European League Against Rheumatism (EULAR) response, and actual time of physician-reported nonresponse. RESULTS: Among 736 BioTRAC and 640 OBRI patients, 13.7% and 18%, respectively, discontinued their anti-TNF because of physician-reported nonresponse. Based on reclassification using disease activity, 65.6% (BioTRAC) and 87.2% (OBRI) of 1ry nonresponders did not achieve DAS28-ESR LDA, 65.6%/90.7% CDAI LDA, and 46.9%/61.5% good/moderate EULAR response. Among 2ry nonresponders, 50.7%/47.8% did not achieve DAS28-ESR LDA, 37.7%/52.9% CDAI LDA, and 15.9%/19.6% good/moderate EULAR response before treatment discontinuation. Regarding actual time of nonresponse, 18.8% of BioTRAC and 60.8% of OBRI 1ry nonresponders discontinued at ≤ 6 months. In both registries, a high proportion of 2ry nonresponders discontinued their anti-TNF after 12 months (87.0% BioTRAC, 60.9% OBRI). CONCLUSION: Physician-reported 1ry nonresponse was more correlated with non-achievement of DAS28-ESR LDA or CDAI LDA, whereas 2ry nonresponse with actual time of discontinuation. Further work is needed to confirm the importance of response and type of response to the initial anti-TNF in identifying patients most likely to benefit from a second biologic agent treatment. | |
| 31088558 | Incidence of Cytomegalovirus Antigenemia in patients with autoimmune rheumatic diseases: a | 2019 May 14 | OBJECTIVE: To determine the incidence of positive CMV antigenemia (CMV-Ag) in patients with autoimmune rheumatic diseases (AIRD) and to describe the outcomes of these patients. METHODS: From January 2011 to December 2014, a total of 443 patients with AIRD were enrolled in this retrospective analysis. Demographic, clinical and laboratory data, current clinical manifestations, organs affected by CMV infection, therapeutic management and outcomes were evaluated. The CMV-Ag was considered positive when one cell was detected at least. RESULTS: CMV-Ag was requested in 70 (15.8%) patients with suspicious CMV infection and was positive in 24 (34.3%). The incidence rate of positive CMV-Ag was 4.97% (95% CI 3.1-7.4%). Systemic lupus erythematosus (SLE) (59%), followed by ANCA-related vasculitis (18.2%) and rheumatoid arthritis (9%) were the diseases more associated with positive CMV-Ag. At the time of CMV infection, SLE patients had moderate to severe disease activity, with high frequency of positive anti-dsDNA antibody (69.2%) and complement consumption (61.5%), as well as high doses of corticosteroids and use of immunosuppressants. The main CMV sites involved were lung (45.5%), bone marrow (40.9%) and gut (27.3%). Mortality rate was 45.5%, especially in those with higher doses of daily oral corticosteroids (107 ± 55.4 mg vs. 71.7 ± 46.3 mg; p = 0.07) and lower number of lymphocytes (309 ± 368.2/mm(3) vs. 821 ± 692.9/mm(3); p = 0.06). CONCLUSIONS: Our data showed high incidence of CMV-Ag in AIRD patients, particularly those with SLE and greater disease severity. In addition, it was observed high mortality in these patients, highlighting the CMV infection should be included in differential diagnosis. | |
| 31364282 | Can ultrasound differentiate acute erosive arthritis associated with osteomyelitis, rheuma | 2019 Nov | AIM: The study intended to determine the specific ultrasonographic features of acute arthritis with periarticular bone erosions caused by acute osteomyelitis (OM), rheumatoid arthritis (RA) and gouty arthritis (GA). METHOD: We included 33 patients (seven with acute OM, 18 with RA flares, and eight with GA attacks) having acute monoarthritis or oligoarthritis, and receiving ultrasound (US) examinations in the acute stage. The US images were rated by three rheumatologists blinded to the diagnosis. The median scores of their evaluation of the subcutaneous tissue, periosteum, and synovium were compared. Interrater reliability was calculated using Cronbach's alpha. RESULTS: The highest mean grade of subcutaneous edema appeared in patients with acute OM, and grade 2 edema was more frequent than patients with RA and GA (P = .003 and P = .026, respectively; α = .869). The prevalence of subcutaneous power Doppler signal was also higher in patients with acute OM than in those with RA and GA (P < .001 and P = .041, respectively; α = .756). Periosteal vascularity presented more frequently in acute OM (P = .003 compared with RA; P = .041 compared with GA), but the interrater reliability was poor (α = .518). The tophaceous material in GA was distinctive from OM and RA (P = .010 and P < .001, respectively; α = .774). CONCLUSION: The most discriminative US features in this study were the subcutaneous tissue changes in addition to the periosteal findings. US could contribute to the differential diagnosis of acute erosive arthritis. | |
| 31197369 | Dose-Response Relationship Between Neuromuscular Electrical Stimulation and Muscle Functio | 2019 Sep 1 | BACKGROUND: Neuromuscular electrical stimulation (NMES) is a viable intervention for improving impaired muscle function in individuals with rheumatoid arthritis (RA). However, there is limited evidence about the dose-response relationship between NMES and muscle function in these individuals. OBJECTIVE: The objectives of this study were to investigate the dose-response relationship between NMES and muscle function in individuals with RA and to establish the minimal NMES training intensity for promoting improvements. DESIGN: This study was a secondary analysis of data obtained before and after an NMES intervention in a randomized study. METHODS: The study took place at a research clinic. Only adults diagnosed with RA were included. The intervention consisted of 36 NMES treatment sessions for the quadriceps muscles over 16 weeks. Muscle function was measured before and after the intervention; quadriceps cross-sectional area and muscle quality were assessed using computed tomography, and strength was measured with an isokinetic dynamometer. NMES training intensity was calculated as a percentage by dividing NMES-elicited quadriceps muscle torque by the maximum voluntary isometric contraction. Improvements in muscle function were calculated using paired-sample t tests. The dose-response relationship was determined using curve estimation regression statistics. The minimum NMES training intensity was defined as that sufficient to significantly improve all muscle function measures. RESULTS: Twenty-four people (48 legs) participated (75% women; mean [SD] age = 58 [8] years; mean body mass index = 32 [7] kg/m2). Quadriceps cross-sectional area, muscle quality, and strength improved after the intervention. Associations between NMES training intensity and muscle quality (r2 = 0.20) and strength (r2 = 0.23) were statistically significant, but that between NMES training intensity and muscle cross-sectional area was not (r2 = 0.02). The minimum NMES training intensity necessary to improve all measures of muscle function ranged from 11% to 20% of the maximum voluntary isometric contraction. LIMITATIONS: The relatively small sample size was a limitation. CONCLUSIONS: The minimum NMES training intensity for significant gains in muscle function was ∼15%. Higher NMES intensities may promote better muscle quality and strength in individuals with RA. | |
| 30762811 | IL-1 inhibition improves insulin resistance and adipokines in rheumatoid arthritis patient | 2019 Feb | Recently, it has been shown that some well-known pathogenic mediators in rheumatoid arthritis (RA), such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF), could play a pathogenic role in insulin resistance and (IR) and type 2 diabetes (T2D).In this 6-month longitudinal study, we aimed at investigating if the inhibition of IL-1 or TNF is associated with an improvement of IR in RA patients with comorbid T2D and the possible effects on selected serum adipokines. RA patients with comorbid T2D were recruited among those undergoing treatment with anakinra (ANA) or with TNF inhibitor (TNFi). The 1998-updated version of the Homeostasis Model Assessment (HOMA2) was used to calculate surrogate indexes of IR (HOMA2-IR) and steady-state beta cell function (%B) from fasting values of glucose and C-peptide. Glucagon, adiponectin, adipsin, leptin, and resistin were also measured. All these parameters were collected at baseline, after 3 and 6 months of treatment.ANA-treated patients showed a significant improvement in HOMA2-%β, HOMA2-IR, and glucagon. In TNFi-treated patients, no significant difference was observed analyzing these metabolic parameters. Adipsin and resistin decreased after 6 months in ANA-treated patients whereas, no difference was recognized analyzing adiponectin and leptin. In TNFi-treated patients, leptin and resistin significantly increased, whereas no difference was found analyzing adiponectin and adipsin, during the follow-up.Our data may suggest a beneficial effect of IL-1 inhibition on measures of metabolic derangement in RA-associated T2D. If further confirmed by larger studies, IL-1 targeting therapies may represent a tailored approach in these patients. | |
| 31801395 | LBEC0101, an etanercept biosimilar for the treatment of rheumatoid arthritis. | 2021 Jan | Introduction: Treatment of rheumatoid arthritis (RA) has been revolutionized by the introduction of biologic disease-modifying antirheumatic drugs, such as tumor necrosis factor (TNF) inhibitors. With patent expiry approaching for many expensive biologic molecules, such as etanercept, more affordable biosimilar drugs are being developed. LBEC0101 is an etanercept biosimilar approved in Japan and South Korea for all etanercept indications including RA. Areas covered: We discuss the pharmacological characteristics, pharmacokinetics, efficacy, and safety of LBEC0101 compared with the etanercept reference product (ETN-RP). Preclinical studies showed that the binding affinity to TNFα and biological activity of LBEC0101 were similar to those of the ETN-RP. The pharmacokinetic profile of LBEC0101 was also similar to that of the ETN-RP. A Phase III, randomized, double-blind, 54-week study showed that the efficacy of LBEC0101 was equivalent to that of the ETN-RP in RA patients. An extension study showed that efficacy was sustained long-term in patients receiving LBEC0101 and in those switching from the ETN-RP to LBEC0101. The safety profile of LBEC0101 was also confirmed to be comparable with the ETN-RP. Expert opinion: LBEC0101 has shown equivalent pharmacokinetics and efficacy and comparable safety to the ETN-RP, and the lower cost of LBEC0101 provides a good cost-benefit ratio. | |
| 31832865 | Application of Non-invasive Imaging in Inflammatory Disease Conditions to Evaluate Subclin | 2019 Dec 12 | PURPOSE OF REVIEW: Traditional risk models, such as the Framingham risk score, fail to capture the increased cardiovascular disease risk seen in patients with chronic inflammatory diseases. This review will cover imaging modalities and their emerging applications in assessing subclinical cardiovascular disease for both research and clinical care in patients with chronic inflammatory diseases. RECENT FINDINGS: Multiple imaging modalities have been studied to assess for subclinical cardiovascular disease via functional/physiologic, inflammatory, and anatomic assessment in patients with chronic inflammatory diseases. The use of imaging to evaluate subclinical cardiovascular disease in patients with chronic inflammatory diseases has the potential to capture early sub-clinical atherosclerosis, to improve risk stratification of future cardiovascular events, and to guide effective disease management. | |
| 31283217 | Linear and Rationally Designed Stapled Peptides Abrogate TLR4 Pathway and Relieve Inflamma | 2019 Jul 25 | A mounting evidence exists for the despicable role of the aberrant immune response in the pathogenesis of rheumatoid arthritis (RA), where toll-like receptor 4 (TLR4) can activate synovial fibroblasts that lead to the chronic inflammation and joint destruction, thus making TLR4 a potent drug target in RA. We report that novel TLR4-antagonizing peptide, PIP2, inhibits the induction of inflammatory biomarkers in vitro as well as in vivo. Systemically, PIP2 inhibits the lipopolysaccharide (LPS)-elicited TNF-α, IL-6, and IL-12p40 in a mouse model. The rationally designed cyclic derivative, cPIP2, is capable of inhibiting LPS-induced proinflammatory cytokines at significantly lower concentration as compared to PIP2 (PIP2 IC(50) = 20 μM, cPIP2 IC(50) = 5 μM). Finally, cPIP2 was able to relieve the inflammatory symptoms and synovial tissue destruction in the RA rat model. Cumulatively, these data suggest that PIP2 and cPIP2 hold strong promise for the development of peptide-based immunotherapeutics that could be of great value in curbing TLR-related immune complications including RA. | |
| 31191116 | Periodontitis and Rheumatoid Arthritis: The Same Inflammatory Mediators? | 2019 | The strict link between periodontitis (PD) and rheumatoid arthritis (RA) has been widely demonstrated by several studies. PD is significantly more frequent in RA patients in comparison with healthy subjects: this prevalence is higher in individuals at the earliest stages of disease and in seropositive patients. This is probably related to the role of P. gingivalis in inducing citrullination and leading to the development of the new antigens. Despite the many studies conducted on this topic, there is very little data available concerning the possibility to use the same biomarkers to evaluate both RA and PD patients. The aim of the review is to summarize this issue. Starting from genetic factors, data from literature demonstrated the association between HLA-DRB1 alleles and PD susceptibility, similar to RA patients; moreover, SE-positive patients showed simultaneously structural damage to the wrist and periodontal sites. Contrasting results are available concerning other genetic polymorphisms. Moreover, the possible role of proinflammatory cytokines, such as TNF and IL6 and autoantibodies, specifically anticyclic citrullinated peptide antibodies, has been examined, suggesting the need to perform further studies to better define this issue. | |
| 30133181 | Factors Associated With Preterm Delivery Among Women With Rheumatoid Arthritis and Women W | 2019 Aug | OBJECTIVE: Pregnant women with inflammatory arthritis may be at increased risk for preterm delivery (PTD), yet it is unclear what drives this risk. This aim of this prospective cohort study of pregnant women with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), or healthier comparison women was to analyze the independent effects of maternal disease activity, medication use, and comorbid pregnancy conditions on PTD risk. METHODS: Women were enrolled before 19 weeks completed gestation as part of the Organization of Teratology Information Specialists (OTIS) Autoimmune Disease in Pregnancy Project. Data on pregnancy events, medications, disease activity, and outcomes were obtained by maternal report and validated by medical records. Poisson regression with robust standard errors estimated risk ratios (RR), multivariable adjusted risk ratios (ARRs), and 95% confidence intervals (95% CIs). RESULTS: A total of 657 women with RA, 170 with JIA, and 564 comparison women without autoimmune disease who delivered live born infants, from 2004 to 2017 were included for analysis. Both the RA and JIA groups had an increased risk of PTD versus the comparison group (RR 2.09 [95% CI 1.50-2.91] and RR 1.81 [95% CI 1.14-2.89], respectively). Active RA at enrollment (ARR 1.58 [95% CI 1.10-2.27]) and any time during pregnancy (ARR 1.52 [95% CI 1.06-2.18]) was associated with PTD. Corticosteroid use in every trimester was associated with an approximate 2- to 5-fold increased risk for PTD for both arthritis groups, independent of disease activity. CONCLUSION: Women with RA and women with JIA are at increased risk for PTD. Maternal disease activity and corticosteroid use may contribute to some of this excess risk. | |
| 31696419 | Reliability of stemless shoulder arthroplasty in rheumatoid arthritis: observation of earl | 2021 Aug | PURPOSE: To evaluate whether stemless shoulder implants in rheumatoid arthritis (RA) patients provide comparable functional outcomes to patients with osteoarthritis or post-traumatic arthritis. In addition, the study assessed for differences in incidence of radiolucent lines or proximal humeral bone loss during radiographic follow-up. METHODS: Consecutive stemless shoulder arthroplasties performed in RA patients and a matched control group were retrospectively identified between February 2012 and 2018. Thirty-five patients were included in each group: 24 total shoulder arthroplasty (TSA) and 11 hemiarthroplasty (HA). Patients were evaluated annually using the Oxford Shoulder Score (OSS) and radiographically. RESULTS: The mean OSS significantly improved in all groups until 24 months. The mean improvement for RA TSA and HA patients at 24 months was 19.86 (95% CI 10.66-29.05, p = 0.0004) and 19.71 (95% CI 7.33-32.31, p = 0.0084), respectively. The mean improvement in the control TSA and HA patients at 24 months was 20.86 (95% CI 17-24.71, p = 0.0001) and 17.86 (95% CI 1.36-34.35, p = 0.0381), respectively. During the study period, two patients in the RA TSA group (8%), one patient in the control TSA group (4%) and one patient in the control HA group (9%) required revision. The proportion of progressive proximal humeral bone loss after TSA was 33% in the RA group and 13% in the control group. CONCLUSION: Stemless shoulder implants can provide significant improvement in functional scores in RA patients in the short term. However, early bone loss around the humeral implant is a concern and the authors recommend long-term clinical and radiological follow-up. | |
| 31196645 | Preferences of Patients and At-risk Individuals for Preventive Approaches to Rheumatoid Ar | 2019 Jul | Effective treatments for rheumatoid arthritis (RA) are available and can lead to remission for some patients, but most patients remain on potentially toxic and expensive medications in the long term. Interest is increasingly turning to the disease phases preceding the development of RA that represent opportunities for preventive interventions. At-risk target populations include individuals with genetic and environmental risk factors, those who have developed systemic autoimmunity, and those who have developed clinically suspect symptoms (eg, arthralgias without synovitis, or an early arthritis). Ongoing prospective studies will inform the development of increasingly accurate predictive tools to identify individuals at risk of developing RA. Furthermore, a range of preventive approaches has been suggested, including lifestyle modification (eg, smoking cessation) and pharmacologic interventions (eg, hydroxychloroquine, methotrexate, abatacept, rituximab) that are currently the subject of randomized controlled trials. As prediction and prevention of RA evolve, it is increasingly likely that individuals at risk (including asymptomatic individuals) may be faced with complex decisions about whether to accept assessment of their risk status or to take a preventive intervention associated with risk of serious adverse events and uncertain benefit. Acceptance of preventive medication in other contexts can be low. For example, <25% of women at high risk of breast cancer are willing to take preventive hormonal treatments. Actual uptake is lower still. Patients' beliefs and preferences predict treatment uptake and adherence. Before the dream of preventing RA can become reality, health care providers need to understand the perspectives of individuals in the target population and to identify barriers and facilitators for this approach. This commentary reviews what is currently known about the perspectives of patients and individuals at risk about predictive and preventive approaches for RA and identifies gaps to be addressed to inform the development of efficient preventive strategies. | |
| 31404890 | Interleukin-35 stimulates tumor necrosis factor-α activated osteoblasts differentiation t | 2019 Oct | Interleukin (IL)-35 plays an important role in the pathogenesis of rheumatoid arthritis (RA), which is characterized by tumor necrosis factor (TNF)-α activated bone loss beginning early and persisting over time. The aim of this study was to explore the effects and signaling pathway of IL-35 on osteoblasts differentiation in MC3T3E1 cells and TNF-α activated MC3T3E1 cells. A microenvironment was established with low concentration and short-term treatment of TNF-α to mimic inflammatory activated osteoblasts of RA in vitro. The role of IL-35 on osteoblasts proliferation and apoptosis were assessed using cell counting kit (CCK)-8 assay and flow cytometry, respectively. Alkaline phosphatase (ALP) activity was measured by p-nitrophenyl phosphate assay. Extracellular matrix mineralization was measured by Alizarin red S staining. Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in response to IL-35 were investigated using real-time polymerase chain reaction and western blot analysis. Wnt/β-catenin signaling pathway in osteoblasts was investigated. In basal and TNF-α activated osteoblasts, IL-35 promoted proliferation and inhibited apoptosis. Basal and TNF-α activated ALP activity and mineralization in vitro was increased stimulated by IL-35. Furthermore, IL-35 increased the basal and TNF-α activated OPG expression and decreased basal and TNF-α activated RANKL expression. Blocking Wnt/β-catenin signaling pathway with Dickkopf (Dkk)-1 inhibited the osteogenic effects of IL-35. IL-35 stimulates basal and TNF-α activated osteoblasts differentiation through the Wnt/β-catenin signaling pathway, thus highlighting the IL-35 for pharmaceutical and medicinal applications for treating RA bone loss. | |
| 31371657 | Longterm, Real-world Safety of Adalimumab in Rheumatoid Arthritis: Analysis of a Prospecti | 2020 Jul 1 | OBJECTIVE: To assess longterm safety in a US cohort of patients with rheumatoid arthritis (RA) treated with adalimumab (ADA) in real-world clinical care settings. METHODS: This observational study analyzed the longterm incidence of safety outcomes among patients with RA initiating ADA, using data from the Corrona RA registry. Patients were adults (≥ 18 yrs) who initiated ADA treatment between January 2008 and June 2017, and who had at least 1 followup visit. RESULTS: In total, 2798 ADA initiators were available for analysis, with a mean age of 54.5 years, 77% female, and mean disease duration of 8.3 years. Nearly half (48%) were biologic-naive, and 9% were using prednisone ≥ 10 mg at ADA initiation. The incidence rates per 100 person-years for serious infections, congestive heart failure requiring hospitalization, malignancy (excluding nonmelanoma skin cancer), and all-cause mortality were 1.86, 0.15, 0.64, and 0.33, respectively. The incidence of serious infections was higher in the first year of therapy (3.44, 95% CI 2.45-4.84) than in subsequent years, while other measured adverse effects did not vary substantially by duration of exposure. The median time to ADA discontinuation was 11 months, while the median time to first serious infection among those experiencing a serious infection event was 12 months. CONCLUSION: Analysis of longterm data from this prospective real-world registry demonstrated a safety profile consistent with previous studies in patients with RA. This analysis did not identify any new safety signals associated with ADA treatment and provides guidance for physicians prescribing ADA for extended periods. |