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ID PMID Title PublicationDate abstract
31492169 Dynamic profiles, biodistribution and integration evaluation after intramuscular/intraveno 2019 Sep 6 BACKGROUND: The persistence, biodistribution, and risk of integration into the host genome of any new therapeutic DNA vaccine must be established in preclinical studies. We previously developed the DNA vaccine pcDNA-CCOL2A1 encoding chicken type II collagen (CCII) for the treatment of rheumatoid arthritis (RA). In the present study, we characterized its dynamic profile, biodistribution, and potential for genomic DNA integration in normal vaccinated rodent. RESULTS: A real-time quantitative PCR analysis (RT-qPCR) of animals administered a single dose of pcDNA-CCOL2A1 (300 μg/kg by intramuscular injection) showed that CCOL2A1 mRNA level in the blood peaked between 2 and 6 h post-immunization and then rapidly declined, and was undetectable between day 1-42. CCOL2A1 transcript was detected at the muscle injection site on days 3-14 post-immunization. Starting from day 14, the transcript was detected in the heart, liver, lung, and kidney but not in the spleen or thymus, and was expressed only in the lung on day 28. There was no CCOL2A1 mRNA present in the testes or ovaries at any time point. Non-invasive in vivo fluorescence imaging revealed CCII protein expression from 2 h up to day 10 and from 2 h up to day 35 after administration of pcDNA-CCOL2A1 via the intravenous and intramuscular routes, respectively; the protein had disappeared by day 42. Importantly, CCOL2A1 was not integrated into the host genome. CONCLUSIONS: These results indicate that pcDNA-CCOL2A1 vaccine is rapidly cleared within a short period of time and is therefore safe, and merits further development as a therapeutic vaccine for RA treatment.
30415451 Patient-reported outcomes with golimumab in patients with rheumatoid arthritis, psoriatic 2019 Jan The TNF inhibitor golimumab (GLM) is a treatment option in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). The GO-NICE study assessed patient-reported outcomes (PRO) in patients newly treated with monthly GLM 50 mg subcutaneously (SC) under real-life conditions in Germany. A prospective non-interventional study with 24-month observation per patient was conducted at 158 sites. Available for analysis were 1,458 patients, 474 with rheumatoid arthritis (RA: 54.9 ± 13.4 years, 72.8% females, 60.4% biologic-naïve), 501 with psoriatic arthritis (PsA: 50.5 ± 12.1 years, 54.1% females; 47.5% biologic-naïve), and 483 with ankylosing spondylitis (AS: 43.6 ± 12.3 years, 66.5% males; 58.4% biologic-naïve). A total of 664 patients completed follow-up to month 24. An improvement of QoL by EuroQoL EQ-5D-3L was seen after 6 months and was maintained over 24 months. The patients' health state today (EQ visual analog scale) improved statistically significantly (p < 0.0001 vs. BL) from 51.0 at baseline (BL) to 63.4 (RA), from 48.4 to 64.3 (PsA) and from 46.8 to 66.5 (AS). Functional ability (FFbH) improved significantly (p < 0.003 vs. BL) from BL 68.2 to 76.1 points (RA), from 69.0 to 76.8 points (PsA), and from 69.0 to 78.5 points (AS). The mean FACIT-Fatigue score increased significantly (p < 0.0001 vs. BL) from BL 32.4 to 38.3 points (RA), from 30.0 to 35.9 points (PsA), and from 29.9 to 37.9 points after 24 months (AS); p < 0.0001 vs. BL each. On treatment with GLM SC once monthly, significant improvements in patient-reported QoL parameters were noted in a very similar manner in all three diseases.Trial registration ClinTrials.gov Identifier: NCT01313858. Registered March 14, 2011; https://clinicaltrials.gov/ct2/show/record/NCT01313858 .
31674342 Nuclear Factor kappa B (NF-κB) Targeted Self-Assembled Nanoparticles Loaded with Methotre 2019 Nov 1 BACKGROUND Nanotechnology is one of the most productive approaches for specifically delivering drug payloads to the region of interest to decrease nonspecific distribution and unwanted toxicities. MATERIAL AND METHODS We prepared glycol chitosan stearate self-assembled nanoparticles loaded with methotrexate (MTX) for NF-kappaB targeting in treatment of rheumatoid arthritis (RA). The nanoparticles were prepared using hydrophobic modification of glycol chitosan (GC) with steric acid (SA) and was characterized using IR. The efficiency of nanoparticles after their physiochemical characterization was measured in vitro and by in vivo studies in mice. RESULTS The nanoparticles thus prepared were spherical in shape, 235 nm in diameter, and had negative zeta potential. The entrapment efficiency of MTX-GC-SA was more than 70%. The in vitro higher uptake of MTX-GC-SA in murine macrophage cells (RAW 264.7) was confirmed using confocal microscopy and FACS analysis. Systemic administration of MTX-GC-SA into collagen-induced arthritis (CIA) mice resulted in high accumulation in inflamed joints. The MTX-GS-SA revealed significantly better therapeutic efficacy against CIA mice compared to free MTX. CONCLUSIONS These findings highlight the potential of using this MTX-GC-SA nanoparticle formulation in suppressing inflammatory arthritis for effective treatment of RA.
31240687 Androgen Deprivation Therapy for Prostate Cancer and the Risk of Rheumatoid Arthritis: A P 2019 Aug INTRODUCTION: Two recent observational studies have investigated the association between androgen deprivation therapy (ADT) and rheumatoid arthritis (RA), but generated discrepant findings and had important methodological limitations. Thus, the objective of this study was to determine whether the use of ADT is associated with an increased risk of RA in men with prostate cancer. PATIENTS AND METHODS: We conducted a population-based cohort study using the United Kingdom Clinical Practice Research Datalink. The cohort included all men, at least 40 years of age, newly diagnosed with prostate cancer between 1 January 1988 and 31 March 2014, with follow-up until 30 September 2014. Exposure to ADT was treated as a time-varying variable and lagged by 1 year to account for diagnostic delays and latency. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of RA, comparing use of ADT with non-use. Secondary analyses were conducted to assess whether the association varied according to ADT type and cumulative duration of use. Finally, we conducted several sensitivity analyses to assess the robustness of our findings. RESULTS: The cohort included 32,302 men followed for a median of 3.3 years. During follow-up, 63 patients were newly diagnosed with RA, generating an incidence rate of 46.5/100,000 person-years. Compared with non-use, the use of ADT was not associated with an increased risk of RA (HR 0.84, 95% CI 0.49-1.45). In secondary analyses, the association did not vary according to ADT type or with cumulative duration of use (p trend = 0.53). The results remained consistent in sensitivity analyses. CONCLUSION: In this population-based study, the use of ADT was not associated with an increased risk of RA in men with prostate cancer.
30443790 Sclerostin rather than Dickkopf-1 is associated with mSASSS but not with disease activity 2019 Apr OBJECTIVE: To determine the serum levels of Dickkopf-1 (DKK-1) and sclerostin, as well as their correlations with the structural damage assessed by modified stoke ankylosing spondylitis spine score (mSASSS) and the disease activity evaluated by ankylosing spondylitis disease activity score (ASDAS) in patients with ankylosing spondylitis (AS). METHODS: Eighty-eight AS patients, 26 rheumatoid arthritis (RA) patients, and 26 age- and gender-matched healthy controls (HC) were collected from rheumatic clinic of the Second Affiliated Hospital of Zhejiang University, School of Medicine, between March 2015 and July 2015. Demographic data, parameters of ASDAS, and image evaluations of spine (i.e., mSASSS) were collected. The serum levels of DKK-1 and sclerostin were measured using commercially available ELISA kits. RESULTS: Both DKK-1 and sclerostin were significantly higher in the AS patients than in the controls (1855 ± 84.58 vs. 1406 ± 99.76 pg/ml and 106 ± 6.75 vs. 62.78 ± 6.39 pmol/l, respectively, P < 0.05). The correlation analysis suggested a negative correlation between serum sclerostin and mSASSS (P = 0.019, r(2) = 0.062). DKK-1 had a trend of positive correlation with mSASSS, but was not statistically significant (P > 0.05). There was no association between the serum levels of DKK-1 or sclerostin and disease activity assessed by ASDAS (P > 0.05). DKK-1 and sclerostin had a negative correlation (P = 0.013, r(2) = 0.07). CONCLUSION: In the present study, the expressions of serum DKK-1 and sclerostin were independent of disease activity. Sclerostin was negatively correlated with the mSASSS, which suggests that sclerostin may be a potential marker indicating the spine ossification process in AS. The specific mechanism remains to be investigated.
30876919 Useful message in choosing optimal biological agents for patients with autoimmune arthriti 2019 Jul The introduction of biological disease-modifying antirheumatic drug (bDMARD) treatments for various types of autoimmune arthritis, such as rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis, represents a new era of treatment for patients with a refractory response to conventional synthetic DMARDs (csDMARDs). Many new bDMARDs with different modalities or that target different pro-inflammatory molecules, likely cytokines, are rapidly emerging. Hence, physicians in the field may be confused about choosing appropriate bDMARDs for their patients. Considering the high cost of bDMARDs and the rapid destructive process of autoimmune arthritis in patients, the choice of optimal bDMARDs for patients who fail to respond or show an inadequate therapeutic response to csDMARDs designed to control the disease is very critical. Here, we summarize the strengths and weaknesses of bDMARDs and specifically focus on their uses in patients with comorbid conditions or with specific medical conditions, such as pregnancy. This commentary provides a solid up-to-date review on commercially available bDMARDs and very useful information for physicians to facilitate the choice of more appropriate bDMARDs to treat patients with autoimmune arthritis and for basic researchers to understand the current strategies of bDMARD usage and hopefully to develop more powerful bDMARDs with fewer safety concerns.
31622068 Real-world outcomes among patients with early rapidly progressive rheumatoid arthritis. 2019 Oct 1 OBJECTIVES: To characterize treatment patterns, healthcare resource utilization (HRU), and disease activity among patients with early rapidly progressive rheumatoid arthritis (eRPRA) in the United States when treated with a first-line biologic disease-modifying antirheumatic drug (bDMARD) tumor necrosis factor-α (TNF) inhibitor or first-line abatacept. STUDY DESIGN: Observational, multicenter, retrospective, longitudinal, medical records-based, cohort study. METHODS: Patients with eRPRA were identified by anti-citrullinated protein antibody positivity, 28-joint Disease Activity Score-C-reactive protein of 3.2 or greater, symptomatic synovitis in 2 or more joints for at least 8 weeks prior to the index date, and onset of symptoms within 2 years or less of the index date. Patients received abatacept or a TNF inhibitor as first-line treatment. Patient characteristics, treatment patterns, HRU, and disease activity following bDMARD initiation were compared across the 2 groups. Odds ratios (ORs) of HRU in the first 6 months of bDMARD treatment were estimated using multivariable logistic regression to adjust for patient mix. RESULTS: There were 60 patients treated with abatacept and 192 treated with a TNF inhibitor in the first line. Those treated with first-line abatacept had lower adjusted odds of hospitalization (OR, 0.42; 95% CI, 0.18-0.95), emergency department (ED) visits (OR, 0.39; 95% CI, 0.16-0.93), and magnetic resonance imaging (MRI) (OR, 0.45; 95% CI, 0.21-0.97) than those treated with a first-line TNF inhibitor (all P <.05). Adjusted odds of achieving low disease activity as measured by clinical disease activity index within 100 days of bDMARD initiation favored first-line abatacept versus a first-line TNF inhibitor (OR, 4.37; 95% CI, 1.34-13.94; P = .01). CONCLUSIONS: Adjusting for disease severity, patients with eRPRA who were treated with first-line abatacept were less likely to have hospitalizations, ED visits, and MRI use during the first 6 months of bDMARD treatment and more likely to achieve low disease activity within 100 days of bDMARD start compared with those who received a first-line TNF inhibitor.
31067000 N-Linked Glycans in the Variable Domain of IgG Anti-Citrullinated Protein Antibodies Predi 2019 Oct OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) are disease-specific biomarkers in rheumatoid arthritis (RA). More than 90% of IgG ACPAs harbor N-linked glycans in the antibody variable (V) domain. The corresponding N-glycosylation sites in ACPA V-region sequences result from somatic hypermutation, a T cell-dependent process. As ample evidence indicates that T cells drive the maturation of the ACPA response prior to arthritis onset, we undertook this study to investigate whether the presence of glycans in IgG ACPA V domains predicts the transition from predisease autoimmunity to overt RA. METHODS: We analyzed 2 independent sets of serum samples obtained from 126 ACPA-positive first-degree relatives (FDRs) of RA patients. Both sets originated from an Indigenous North American population and comprised cross-sectional and longitudinal samples of individuals who did or did not develop inflammatory arthritis. Serum IgG ACPAs were affinity-purified and subjected to ultra high-performance liquid chromatography-based glycan analysis. RESULTS: In both data sets, FDR-derived IgG ACPA displayed markedly lower levels of V domain glycans (<50%) compared to IgG ACPA from RA patients. Notably, FDRs who later developed RA showed extensive V-domain glycosylation before the onset of arthritis. Moreover, IgG ACPA V-domain glycosylation was strongly associated with future development of RA (hazard ratio 6.07 [95% confidence interval 1.46-25.2]; P = 0.013). CONCLUSION: Extensive glycosylation of the IgG ACPA V domain is present in a subset of predisposed FDRs of Indigenous North American RA patients. The presence of this feature substantially increases the risk of RA development. Based on these findings, we propose that glycosylation of the IgG ACPA V domain represents a predictive marker for RA development in ACPA-positive individuals and may serve to better target prevention measures.
28551175 Long-term survival of subcutaneous anti-tumor necrosis factor biological drugs administere 2019 Jan OBJECTIVE: To compare the survival of subcutaneous anti-tumor necrosis factor (TNF) drugs used between 2008 and 2012 prescribed in accordance with clinical practice. MATERIAL AND METHODS: Retrospective, observational study of the patients in our center diagnosed with rheumatoid arthritis (RA). We included patients who had received a subcutaneous anti-TNF agent for at least 6 months. The data were analyzed using the SPSS V17.0 statistical package. RESULTS: Forty-nine RA patients started subcutaneous biological treatment with an anti-TNF agent (32 with etanercept and 17 with adalimumab). The mean age was 45.94 years (75.5% female). The mean disease duration prior to starting anti-TNF administration was 2.67 years. The mean age at the start of treatment was 51.84 years, and the average Disease Activity Score 28 was 4.93. The median survival of the anti-TNF treatment was 8.40 years; the survival of etanercept was the longer of the two. The main reason for discontinuation was secondary failure (90.9%). CONCLUSIONS: In routine clinical practice, the survival of subcutaneous anti-TNF treatment was extensive and was independent of whether or not the patients received concomitant immunosuppressive therapy.
28552437 Tofacitinib, an oral Janus kinase inhibitor, in patients from Mexico with rheumatoid arthr 2019 Jan OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized efficacy and safety of tofacitinib in Mexican patients from RA Phase 3 and long-term extension (LTE) studies. METHODS: Data from Mexican patients with RA and an inadequate response to disease-modifying antirheumatic drugs (DMARDs) were taken from four Phase 3 studies (pooled across studies) and one open-label LTE study of tofacitinib. Patients received tofacitinib 5 or 10mg twice daily, adalimumab (one Phase 3 study) or placebo (four Phase 3 studies) as monotherapy or in combination with conventional synthetic DMARDs. Efficacy up to Month 12 (Phase 3) and Month 36 (LTE) was assessed by American College of Rheumatology 20/50/70 response rates, Disease Activity Score (erythrocyte sedimentation rate), and Health Assessment Questionnaire-Disability Index. Safety, including incidence rates (IRs; patients with events/100 patient-years) for adverse events (AEs) of special interest, was assessed throughout the studies. RESULTS: 119 and 212 Mexican patients were included in the Phase 3 and LTE analyses, respectively. Tofacitinib-treated patients in Phase 3 had numerically greater improvements in efficacy responses versus placebo at Month 3. Efficacy was sustained in Phase 3 and LTE studies. IRs for AEs of special interest were similar to those with tofacitinib in the global and Latin American RA populations. CONCLUSIONS: In Mexican patients from the tofacitinib global RA program, tofacitinib efficacy was demonstrated up to Month 12 in Phase 3 studies and Month 36 in the LTE study, with a safety profile consistent with tofacitinib global population.
31092771 A Study of the Vascular Endothelial Function in Patients with Type 2 Diabetes Mellitus and 2019 Objective Type 2 diabetes mellitus (T2DM) and rheumatoid arthritis (RA) are both complicated by arteriosclerosis, resulting in increased rates of cardiovascular events. No previous studies have compared the index between RA and T2DM. We assessed the vascular endothelial function in early-stage arteriosclerosis for each disease to determine the influential factors and compared the extent to which these two diseases cause vascular endothelial dysfunction. Methods This study is a retrospective study based on medical records. Differences in the reactive hyperemia index (RHI) among the groups and factors affecting the RHI in each group was analyzed. The vascular endothelial function was assessed by measuring the RHI using peripheral arterial tonometry. Patients The study subjects were 114 patients with non-functional thyroid tumors (healthy n=14), T2DM (T2DM n=64), and RA (RA n=36). Results The RHI was 2.29 in the control, 1.85 in the T2DM, and 1.83 in the RA group, with values lower in the T2DM and RA groups than in the control group (p=0.033) but not markedly different between the two disease groups. The RHI distribution (<1.68/1.68 to <2.10/≥2.1) was as follows: control group: 14.3%/28.6%/57.1%; T2DM group: 42.2%/39.1%/18.8%; and RA group: 36.1%/44.4%/19.4% (p=0.031), respectively. A multivariate analysis identified the triglyceride level and dyslipidemia in the control group and the Disease Activity Score in 28 joints with the erythrocyte sedimentation rate and fasting plasma glucose level in the RA group to influence the RHI. Conclusion The vascular endothelial function was impaired in approximately 80% of patients with T2DM and RA, with comparable degrees of impairment between the two diseases. No factors affecting the function were identified in the T2DM group, while the function was more impaired in patients with a higher disease activity in the RA group.
31699133 CRUP: a comprehensive framework to predict condition-specific regulatory units. 2019 Nov 8 We present the software Condition-specific Regulatory Units Prediction (CRUP) to infer from epigenetic marks a list of regulatory units consisting of dynamically changing enhancers with their target genes. The workflow consists of a novel pre-trained enhancer predictor that can be reliably applied across cell types and species, solely based on histone modification ChIP-seq data. Enhancers are subsequently assigned to different conditions and correlated with gene expression to derive regulatory units. We thoroughly test and then apply CRUP to a rheumatoid arthritis model, identifying enhancer-gene pairs comprising known disease genes as well as new candidate genes.
30242110 High-throughput Serum N-Glycomics: Method Comparison and Application to Study Rheumatoid A 2019 Jan N-Glycosylation is a fundamentally important protein modification with a major impact on glycoprotein characteristics such as serum half-life and receptor interaction. More than half of the proteins in human serum are glycosylated, and the relative abundances of protein glycoforms often reflect alterations in health and disease. Several analytical methods are currently capable of analyzing the total serum N-glycosylation in a high-throughput manner.Here we evaluate and compare the performance of three high-throughput released N-glycome analysis methods. Included were hydrophilic-interaction ultra-high-performance liquid chromatography with fluorescence detection (HILIC-UHPLC-FLD) with 2-aminobenzamide labeling of the glycans, multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (xCGE-LIF) with 8-aminopyrene-1,3,6-trisulfonic acid labeling, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) with linkage-specific sialic acid esterification. All methods assessed the same panel of serum samples, which were obtained at multiple time points during the pregnancies and postpartum periods of healthy women and patients with rheumatoid arthritis (RA). We compared the analytical methods on their technical performance as well as on their ability to describe serum protein N-glycosylation changes throughout pregnancy, with RA, and with RA disease activity.Overall, the methods proved to be similar in their detection and relative quantification of serum protein N-glycosylation. However, the non-MS methods showed superior repeatability over MALDI-TOF-MS and allowed the best structural separation of low-complexity N-glycans. MALDI-TOF-MS achieved the highest throughput and provided compositional information on higher-complexity N-glycans. Consequentially, MALDI-TOF-MS could establish the linkage-specific sialylation differences within pregnancy and RA, whereas HILIC-UHPLC-FLD and xCGE-LIF demonstrated differences in α1,3- and α1,6-branch galactosylation. While the combination of methods proved to be the most beneficial for the analysis of total serum protein N-glycosylation, informed method choices can be made for the glycosylation analysis of single proteins or samples of varying complexity.
31176730 Circulating microRNA-23b as a new biomarker for rheumatoid arthritis. 2019 Sep 5 MicroRNA-23b (miR-23b) is associated with inflammation and autoimmune diseases. This study evaluated miR-23b expression and assessed its potential as a biomarker of disease activity for rheumatoid arthritis (RA). Differential expression of microRNAs was determined by miRNA microarray analysis in fibroblast-like synoviocytes (FLSs) from four trauma patients as healthy controls (HCs) and eight RA patients. The microarray results showed elevated expression of miR-23b in FLSs from RA patients and this finding was corroborated by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization using synovial tissues (STs). Furthermore, we found miR-23b levels in plasma of RA patients were significantly higher than in HCs, and plasma miR-23b levels positively correlated with the erythrocyte sedimentation rate (ESR), hypersensitive C-reactive protein (hs-CRP), C-reactive protein (CRP), DAS28, and platelet (PLT) count (P < 0.05). MiR-23b levels in plasma inversely correlated with the levels of hemoglobin (Hb), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (P < 0.05), but not with rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibodies (ACPA) (P > 0.05). Moreover, patients with anorexia showed higher levels of miR-23b in plasma than those without anorexia. Similar results were observed with fatigue. Appropriate treatment for RA not only ameliorated the disease condition but also reversed the elevated plasma miR-23b level remarkably. These results suggest that circulating miR-23b may be a promising biomarker for RA disease activity.
31165341 Meta-analysis of IL-17 inhibitors in two populations of rheumatoid arthritis patients: bio 2019 Oct OBJECTIVES: To evaluate the efficacy and safety of interleukin 17 (IL-17) inhibitors in two rheumatoid arthritis (RA) populations: biologic-naïve or tumor necrosis factor inhibitor inadequate responders (TNF-IR). METHOD: A systematic search was performed in major electronic databases to identify relevant randomized controlled trials (RCTs) reporting the American College of Rheumatology 20% (ACR20), ACR50, ACR70 responses and adverse events (AEs) of IL-17 inhibitors versus placebo in patients with RA. We divided these patients into two subgroups: biologic-naïve or TNF-IR. The meta-analysis was performed using Review Manager 5.3 software. Results were expressed as risk ratio (RR) with pertinent 95% confidence interval (95% CI). RESULTS: Ten studies with a total of 2499 patients were included. For biologic-naïve patients, ACR50 and ACR70 responses were significantly better with IL-17 inhibitors than placebo (RR = 1.71, 95% CI 1.23-2.38, P = 0.001 and RR = 2.63, 95% CI 1.10-6.25, P = 0.03, respectively), but ACR20 responses for IL-17 inhibitors were not statistically superior to placebo (RR = 1.34, 95% CI 0.94-1.91, P = 0.11). For TNF-IR, IL-17 inhibitors were effective in achieving ACR20 (RR = 1.67, 95% CI 1.40-2.00, P < 0.00001), ACR50 (RR = 1.94, 95% CI 1.43-2.63, P < 0.0001), and ACR70 (RR = 2.11, 95% CI 1.26-3.55, P = 0.005) compared to placebo. In the safety analysis, IL-17 inhibitors did not show increased risk of any AEs by comparing to placebo in both biologic-naïve patients and TNF-IR. CONCLUSION: IL-17 inhibitors were effective in the treatment of RA without increased risk of AEs, whether for biologic-naïve patients or TNF-IR. Key Points • In this meta-analysis comparing IL-17 inhibitors with placebo in 2499 rheumatoid arthritis patients, IL-17 inhibitors improved ACR50 and ACR70, but not ACR20, responses in biologic-naïve patients. • IL-17 inhibitors improved ACR20, ACR50, and ACR70 responses in tumor necrosis factor inhibitor inadequate responders.
30474720 Persistence with biological drugs in patients treated in rheumatology practices in Germany 2019 Mar The goal of this study was to investigate the persistence with biological drugs in patients treated in rheumatology practices in Germany. This study included patients diagnosed with rheumatoid arthritis (RA), psoriatic arthritis (PA), or ankylosing spondylitis (AS) who received a first prescription of biological drugs between 2008 and 2016 (index date) in 21 rheumatology practices in Germany (n = 4925; Disease Analyzer database). The main outcome measure was the rate of persistence within 5 years of the index date. Kaplan-Meier analyses were performed to study treatment persistence as a function of diagnosis, gender and age. A Cox proportional hazards regression model was used to estimate the relationship between non-persistence and diagnosis, gender, age, and comorbidities. After 5 years of follow-up, the rate of persistence was 31.8% in patients with RA, 35.2% in those with AS, and 33.2% in those with PA (log-rank p value = 0.028). Furthermore, 33.8% of men and 31.9% of women were persistent (log-rank p value = 0.035). The rate of persistence was 20.8%, 27.9%, 33.0%, 36.6%, 35.2%, and 32.0% in people aged ≤ 30, 31-40, 41-50, 51-60, 61-70, and > 70 years, respectively (log-rank p value = 0.002). The risk of discontinuation was lower in participants diagnosed with AS than in those diagnosed with RA [hazard ratio (HR) = 0.87; 95% confidence interval (CI) 0.79-0.96]. In addition, patients aged ≤ 30 years were more likely to discontinue their biological therapy than those aged > 70 years (HR = 1.29; 95% CI 1.10-1.52). Persistence with biological drugs was low after 5 years of follow-up in rheumatology practices.
31820729 Antibodies to citrullinated peptides in serum and saliva in patients with rheumatoid arthr 2020 Jul OBJECTIVES: A connection between prevalence of rheumatoid arthritis (RA) and periodontitis has been reported. The hypothesis for this association involves increased citrullination in the oral mucosa in patients with periodontitis. Whether ongoing periodontitis has an effect on IgA antibodies to citrullinated peptides (ACPA) in saliva is unknown. We studied IgA ACPA in saliva and serum and their relation to periodontitis and smoking in a population-based elderly RA cohort. METHODS: A population-based cohort of patients with RA ≥61 years of age (n=132) was examined by rheumatologists and a dental hygienist. Analyses of IgG ACPA in serum and IgA ACPA in serum and saliva were performed. The presence of ACPA was compared in patients with RA with and without periodontitis. RESULTS: IgA ACPA in serum occurred in 35% of RA patients with periodontitis and in 43% of RA patients without periodontitis (p=0.740). IgG ACPA in serum was found in 66% of RA patients with periodontitis, and in 69% without periodontitis (p=0.740). IgA ACPA in saliva occurred in 20% with periodontitis and 55% without periodontitis (p=0.062). A logistic regression analysis adjusting for age, gender and smoking gave an odds ratio (OR) of 0.456 (95% CI=0.183-1.137, p=0.092) for saliva IgA ACPA positive individuals to have periodontitis. CONCLUSIONS: IgA ACPA in serum or saliva was not more common in RA patients with periodontitis. This implies that local production of ACPA by the oral mucosa is not enhanced by periodontal inflammation, in patients with established RA.
31119962 In Asian women undergoing total knee arthroplasty, lower leg morphology in those with rheu 2020 May Objectives: This retrospective, single-center study aimed to compare leg morphology between patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA) undergoing total knee arthroplasty (TKA).Methods: We enrolled 70 RA and 327 OA female patients undergoing TKA. Hip-knee-ankle angle (HKA), femorotibial angle (FTA), valgus correction angle (VCA), and femoral/tibial bowing were measured using full-length radiographs. Femoral bowing of more than 3° or tibial bowing more than 2°, either laterally or medially, was considered substantial. Distribution of these results and the incidence of substantial bowing in RA and OA were compared.Results: HKA, FTA, and VCA were significantly smaller in RA than those in OA. Femoral bowing was significantly smaller in RA (mean angle: 0.04° ± 3.1°) than that in OA (mean angle: 2.1° ± 3.6°) (p < .05). In almost half of the patients with RA (48.6%), femoral bowing occurred medially, whereas femoral bowing occurred laterally in approximately three quarters of OA patients (73.1%). Tibial bowing did not differ. The incidence of substantial femoral bowing was significantly lower in RA (27.1%) than that in OA (43.0%) (p < .05).Conclusion: RA patients undergoing TKA had different leg morphology than OA patients. These findings have implications for surgical planning.
30092161 Three-year safety and two-year effectiveness of etanercept in patients with rheumatoid art 2019 Sep Objectives: To evaluate the real-world safety and effectiveness of etanercept (ETN) in Japanese patients with rheumatoid arthritis. Methods: This postmarketing surveillance study (NCT00503139) assessed the safety and effectiveness of ETN treatment over 3 and 2 years (from June 2007 to September 2011), respectively. Safety was evaluated by occurrence and seriousness of adverse drug reactions (ADRs), and of adverse events (AEs) for malignancies. Effectiveness was assessed using the Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate (ESR) with four variables (swollen and tender joint counts, ESR, and patient global assessment; DAS28-4/ESR). Treatment was considered effective if patients had a good/moderate response by the European League Against Rheumatism response criteria. Results: ADRs occurred in 256/675 (37.9%) patients, the most common being injection site reactions (4.4%) and nasopharyngitis (3.3%). Serious ADRs occurred in 60/675 (8.9%) patients, the most frequent being pneumonia (1.2%). The incident rate of malignancies (AEs) was 1.06 per 100 patient-years. Mean baseline DAS28-4/ESR for the 581 patients included in effectiveness analysis was 5.42, which decreased to 3.32 at 2 years. Eighty-two percent of patients achieved a moderate/good response at 2 years. Conclusion: Long-term ETN treatment safety and effectiveness were sustained over 3 and 2 years, respectively.
31358361 Four-year follow-up of inflammatory arthropathy patients treated with golimumab: Data from 2020 Feb OBJECTIVE: To compare (1) golimumab drug survival and efficacy in bDMARD naïve compared with non-naïve rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (ax-SpA) patients, (2) golimumab drug survival in RA and PsA patients treated with/without concomitant csDMARDs, (3) predictors of golimumab drug discontinuation. METHODS: Patients starting golimumab were included from the prospective observational multicenter Norwegian DMARD study. Drug survival was explored by Kaplan-Meier analyses with log rank test. Treatment responses were compared using ANCOVA. Univariate and multivariate Cox regression analyses were performed to identify predictors of golimumab discontinuation. RESULTS: We included 808 patients (163 RA, 266 PsA, 379 ax-SpA). Golimumab drug survival after 1/2/4 years were not significantly different between bDMARD naïve and non-naïve patients (all, p ≥ 0.12; RA, p ≥ 0.07; PsA, p ≥ 0.28; ax-SpA, p ≥ 0.61), nor between RA (p ≥ 0.10) and PsA (p ≥ 0.07) patients treated with vs. without csDMARD comedication. bDMARD naïve compared with non-naïve ax-SpA patients had better 3-month ASDAS/BASDAI/MHAQ responses (p ≤ 0.02). bDMARD naïve compared with non-naïve RA and PsA patients had a trend towards better treatment responses. Identified predictors of 4-year golimumab discontinuation were patient's global and female gender in patients overall and in subgroups of PsA and ax-SpA patients, and patient's global and CRP in RA. CONCLUSION: Golimumab drug survival was not significantly different between bDMARD naïve and non-naïve RA, PsA and ax-SpA patients, nor between RA and PsA patients treated with vs. without concomitant csDMARDs. Treatment responses were significantly better for bDMARD naïve than non-naïve ax-SpA patients. Identified predictors of golimumab discontinuation were patient's global and female gender in patients overall and in subgroups of PsA and ax-SpA patients, and patient's global and CRP in RA.