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ID PMID Title PublicationDate abstract
30797146 Quercetin loaded nanoemulsion-based gel for rheumatoid arthritis: In vivo and in vitro stu 2019 Apr Current research reports the development, optimization and evaluation of Quercetin (QCT) loaded nanoemulsion (NE)-based gel for the effective rheumatoid arthritis (RA) management. The formulation of QCT- NE was developed using spontaneous emulsification techniques using the Box- Behnken experimental design. The cytotoxicity study and effect on TNF-α production were evaluated respectively on HIG-82 and RAW 264.7 cells. The study showed that QCT- NE has no toxic effect on synoviocytes and a strong inhibitory effect on LPS-induced TNF-α production. QCT- NE gel has confirmed adequate rheological behavior with a good texture profile and improved drug permeation compared to free QCT gel. In addition, the gel was found to be non-irritating and showed the inhibition of paw edema in rats induced by CFA over 24 h contrary to free QCT gel. In conclusion, the formulation of QCT- NE gel is an efficient topical treatment strategy for rheumatoid arthritis.
30830311 Elevated circulating asymmetric dimethylarginine levels in rheumatoid arthritis: a systema 2019 May Rheumatoid arthritis (RA) patients have increased risk of cardiovascular disease (CVD) death. Elevated asymmetric dimethylarginine (ADMA) levels have been reported to be an independent predictor of CVD morbidity and mortality, however, the role of ADMA in RA remains undetermined. To derive a more accurate estimation on circulating ADMA levels in RA patients, a meta-analysis was performed. Embase, PubMed, and The Cochrane Library database (up to October 7 2018) were used to acquire published literatures. Heterogeneity test was performed by the Q statistic and quantified using I(2). Publication bias was evaluated using a funnel plot and Egger's linear regression test. A total of 174 articles were identified, 16 studies with 1365 subjects (666 RA patients and 699 healthy individuals) were ultimately included. Plasma/serum ADMA levels appeared to be higher in RA patients than healthy controls (SMD = 0.84, 95% CI 0.32, 1.35). By assessing the BMI, age, disease duration and disease activity as subgroups, BMI ≥ 24 and BMI < 24 groups both showed elevated ADMA levels than controls, disease duration ≥ 8, age < 50 and disease activity ≥ 3.2 and < 5.1 group had a higher ADMA level than control groups. However, disease duration < 8, disease activity ≥ 5.1 and age ≥ 50 groups showed no difference between two groups. Circulating ADMA levels are higher in RA patients compared with healthy controls. In addition, ADMA levels are influenced by age, disease duration and disease activity.
30630515 Significant association between joint ultrasonographic parameters and synovial inflammator 2019 Jan 10 BACKGROUND: Ultrasonography (US) can directly demonstrate joint inflammation, including grayscale (GS) signs of synovial hypertrophy and power Doppler (PD) techniques to demonstrate increased blood flow and vascularization. Recently, echogenicity, especially hypoechoic synovium, has also been associated with local inflammatory activity. However, only a few studies have demonstrated correlation between histopathologic and immunopathologic evaluation and US findings. The aim of this study was to clarify whether joint US findings including synovial hypertrophy, vascularity, and echogenicity can accurately characterize synovial pathophysiology in patients with active rheumatoid arthritis (RA). METHODS: A total of 44 patients with RA were included, both treated (n = 25) and untreated (n = 19) and scheduled for US examination of the knee joint with synovial fluid (SF) aspiration and two treated patients also underwent synovial biopsy. US images were quantitatively analyzed using grayscale assessment of synovial hypertrophy and PD for vascularity and echogenicity. Levels of nine SF cytokines and growth factors were also measured. RESULTS: Both US synovial hypertrophy and PD vascularity significantly correlated with SF inflammatory cytokine levels such as IL-6, IL-8, IL-1β and IL-10 in untreated patients. Angiogenic factors, including vascular endothelial growth factor (VEGF), only correlated with PD vascularity. In the treated patients, the associations between synovial hypertrophy and any cytokines were diminished, although synovial vascularity and echogenicity correlated with IL-6 and VEGF (p < 0.05). Histopathologic analysis revealed that hypoechogenicity of the synovium correlated with marked infiltration of lymphocytes and hypervascularity. CONCLUSIONS: We demonstrated the pathophysiological origins of US findings in the joint. The degree of US vascularity of the synovium correlated with local inflammatory cytokine levels and angiogenetic factors in patients with active RA. Synovial echogenicity, and not hypertrophy, correlated with inflammation, especially in treated patients with RA.
31308625 Effect of tumor necrosis factor inhibitors on interstitial lung disease in rheumatoid arth 2019 Objectives: This study evaluated the correlation between tumor necrosis factor alpha inhibitor (TNF-I) and interstitial lung disease (ILD) in rheumatoid arthritis (RA). We aimed to raise awareness and consummate therapy by summarizing the characteristics of the adverse events of ILD. Methods: A comprehensive search of the PubMed, Embase, Ovid, Cochrane, China National Knowledge Infrastructure, and Wanfang databases was performed from inception to November 2018. Statistical analysis of demographic characteristics, clinical features, and relative risks was performed using Microsoft Excel 2007 and SPSS version 20.0. Results: A total of 7 eligible articles and another 28 case reports were enrolled. The 7 cohort studies demonstrated the tendency that ILD cases might not benefit from TNF-I therapy. TNF-I might be associated with ILD adverse events. The case reports further confirmed these findings, as most (87.5%) of the cases showed that TNF-1 was harmful to patients with ILD and even resulted in a 35% mortality rate. Further investigation revealed that ILD adverse events tended to appear in female patients with a long RA history (p<0.05). The subgroup analysis suggested that early detection and precise treatment are key factors in determining survival or death when an ILD adverse event occurs. A large proportion of ILD adverse events (48.6%) appeared at 2.38±1.03 weeks after the infusion of infliximab. Conclusion: A fresh look at the evidence highlights that TNF-I might be associated with ILD adverse events in RA, which can induce more severe pulmonary symptoms and even result in death. Therefore, more attention should be paid to effective prevention, early diagnosis, and precise management. Notably, further prospective cohort studies are warranted to better interpret the association or causality between TNF-I and ILD.
31085028 Detection of Increased Vascular Signal in Arthritis-Prone Rats Without Joint Swelling Usin 2019 Aug This study aimed to determine whether ultrasonography (US) can detect increased vascular signal in the synovial tissue before overt synovitis in rheumatoid arthritis (RA). Env-pX rats that spontaneously develop RA-like synovitis were used. Ankle joints of 15 pre-morbid env-pX rats were observed with power Doppler and superb microvascular imaging (SMI) using an ultrahigh-frequency (8-24 MHz) probe. Signal values were counted as the number of pixels. The total number of vessels and vessel area in the synovial tissue were histologically evaluated. Dilated vessels were determined from the mean value of synovial vessels in three wild-type rats. In all env-pX rats, apparent synovial proliferation was not observed. However, vasodilation was evident. Only SMI values were significantly correlated with the number of dilated vessels (r = 0.585, p = 0.022) but not with the total number of vessels. US with SMI using ultrahigh-frequency probe can detect increased vascular signal in the synovial tissue of arthritis-prone rats.
30830763 Synergistic Oxygen Generation and Reactive Oxygen Species Scavenging by Manganese Ferrite/ 2019 Mar 26 Poor O(2) supply to the infiltrated immune cells in the joint synovium of rheumatoid arthritis (RA) up-regulates hypoxia-inducible factor (HIF-1α) expression and induces reactive oxygen species (ROS) generation, both of which exacerbate synovial inflammation. Synovial inflammation in RA can be resolved by eliminating pro-inflammatory M1 macrophages and inducing anti-inflammatory M2 macrophages. Because hypoxia and ROS in the RA synovium play a crucial role in the induction of M1 macrophages and reduction of M2 macrophages, herein, we develop manganese ferrite and ceria nanoparticle-anchored mesoporous silica nanoparticles (MFC-MSNs) that can synergistically scavenge ROS and produce O(2) for reducing M1 macrophage levels and inducing M2 macrophages for RA treatment. MFC-MSNs exhibit a synergistic effect on O(2) generation and ROS scavenging that is attributed to the complementary reaction of ceria nanoparticles (NPs) that can scavenge intermediate hydroxyl radicals generated by manganese ferrite NPs in the process of O(2) generation during the Fenton reaction, leading to the efficient polarization of M1 to M2 macrophages both in vitro and in vivo. Intra-articular administration of MFC-MSNs to rat RA models alleviated hypoxia, inflammation, and pathological features in the joint. Furthermore, MSNs were used as a drug-delivery vehicle, releasing the anti-rheumatic drug methotrexate in a sustained manner to augment the therapeutic effect of MFC-MSNs. This study highlights the therapeutic potential of MFC-MSNs that simultaneously generate O(2) and scavenge ROS, subsequently driving inflammatory macrophages to the anti-inflammatory subtype for RA treatment.
31485846 Management of rheumatoid arthritis: 2019 updated consensus recommendations from the Hong K 2019 Dec The expanding range of treatment options for rheumatoid arthritis (RA), from conventional synthetic disease-modifying antirheumatic drugs (DMARDs) to biological DMARDs (bDMARDs), biosimilar bDMARDs, and targeted synthetic DMARDs, has improved patient outcomes but increased the complexity of treatment decisions. These updated consensus recommendations from the Hong Kong Society of Rheumatology provide guidance on the management of RA, with a focus on how to integrate newly available DMARDs into clinical practice. The recommendations were developed based on evidence from the literature along with local expert opinion. Early diagnosis of RA and prompt initiation of effective therapy remain crucial and we suggest a treat-to-target approach to guide optimal sequencing of DMARDs in RA patients to achieve tight disease control. Newly available DMARDs are incorporated in the treatment algorithm, resulting in a greater range of second-line treatment options. In the event of treatment failure or intolerance, switching to another DMARD with a similar or different mode of action may be considered. Given the variety of available treatments and the heterogeneity of patients with RA, treatment decisions should be tailored to the individual patient taking into consideration prognostic factors, medical comorbidities, drug safety, cost of treatment, and patient preference.
31413868 Occupational exposure to asbestos and silica and risk of developing rheumatoid arthritis: 2019 OBJECTIVE: Airborne agents including cigarette smoke associate with an increased risk of rheumatoid arthritis (RA). We analysed to which extent occupational exposure to asbestos and silica confers an increased risk of developing serologically defined subsets of RA. METHODS: This Swedish population-based case-control study enrolled incident RA cases between 1996 and 2013 (n=11 285), identified through national public authority and quality registers, as well as from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) Study. Controls (n=1 15 249) were randomly selected from Sweden's population register and matched on sex, age, index year and county. Occupational histories were obtained from national censuses. Exposure to asbestos and silica was assessed by job-exposure matrices. Logistic regression was used to calculate ORs adjusted for age, sex, county, index year, alcohol use and smoking. RESULTS: Results showed that male workers exposed to asbestos had higher risk of seropositive RA (OR=1.2, 95% CI 1.0 to 1.4) and seronegative RA (OR=1.2, 95% CI 1.0 to 1.5) compared with unexposed workers. The risk was highest among workers exposed to asbestos from 1970, before a national ban was introduced. Male workers exposed to silica also had higher risk of RA (seropositive RA: OR=1.4, 95% CI 1.2 to 1.6; seronegative RA: OR=1.3, 95% CI 1.0 to 1.5). For the largest subset, seropositive RA, the OR increased with the number of years exposed to silica, up to OR=2.3 (95% CI 1.4 to 3.8, p for trend <0.0001). Women overall had lower ORs than men, but the duration and intensity of their exposure were lower. CONCLUSIONS: In conclusion, we observed an association between asbestos exposure and risk of developing RA and extended previous findings of an association between silica exposure and RA risk, where a dose-response relationship was observed.
31339920 Identification of pathological RA endotypes using blood-based biomarkers reflecting tissue 2019 There is an increasing demand for accurate endotyping of patients according to their pathogenesis to allow more targeted treatment. We explore a combination of blood-based joint tissue metabolites (neoepitopes) to enable patient clustering through distinct disease profiles. We analysed data from two RA studies (LITHE (N = 574, follow-up 24 and 52 weeks), OSKIRA-1 (N = 131, follow-up 24 weeks)). Two osteoarthritis (OA) studies (SMC01 (N = 447), SMC02 (N = 81)) were included as non-RA comparators. Specific tissue-derived neoepitopes measured at baseline, included: C2M (cartilage degradation); CTX-I and PINP (bone turnover); C1M and C3M (interstitial matrix degradation); CRPM (CRP metabolite) and VICM (macrophage activity). Clustering was performed to identify putative endotypes. We identified five clusters (A-E). Clusters A and B were characterized by generally higher levels of biomarkers than other clusters, except VICM which was significantly higher in cluster B than in cluster A (p<0.001). Biomarker levels in Cluster C were all close to the median, whilst Cluster D was characterised by low levels of all biomarkers. Cluster E also had low levels of most biomarkers, but with significantly higher levels of CTX-I compared to cluster D. There was a significant difference in ΔSHP score observed at 52 weeks (p<0.05). We describe putative RA endotypes based on biomarkers reflecting joint tissue metabolism. These endotypes differ in their underlining pathogenesis, and may in the future have utility for patient treatment selection.
31314615 Muscle stiffness in rheumatoid arthritis is not altered or associated with muscle weakness 2020 Jul Objectives: To investigate muscle stiffness and strength in rheumatoid arthritis patients compared to healthy controls.Methods: A sample of 80 RA patients from three discrete groups: 1 - newly diagnosed treatment-naïve RA (n = 29), 2 - active RA for at least 1 year (n = 18) and 3 - in remission RA for at least 1 year (n = 33), was compared to 40 healthy controls. Shear wave velocity (SWV) was measured using shear wave elastography as a surrogate for tissue stiffness in multiple muscles. All participants performed isometric grip strength, timed get-up-and-go test, 30-s chair stand test and isokinetic knee extension/flexion (60°/s). The difference in SWV amongst the groups was tested using one-way ANOVA, and the correlation between SWV and muscle strength results were calculated using Pearson's coefficients.Results: The mean age ± SD was 61.2 ± 12.8 for RA patients and 61.5 ± 10.5 years for controls. SWV was not significantly different amongst the groups on all muscles (p > .05). In comparison to controls, the new and active RA groups showed a significantly lower isokinetic strength by -29% (p = .013) and -28% (p = .040), fewer chair stands by -28% (p = .001) and -44% (p < .001), longer walking times by -25% (p = .025) and -30% (p = .001), respectively, and weaker grip strength by -45% for both (p < .001). The muscle strength in the remission RA groups was not significantly lower, except in the isokinetic knee strength (-21%; p = .027). The correlations between SWE and the muscle assessment results were weak and insignificant (r < 0.30; p > .05).Conclusion: Significant muscle weakness was demonstrated in patients with RA disease. However, muscle stiffness was normal and not associated with muscle strength.
31366403 Rheumatoid arthritis-relevant DNA methylation changes identified in ACPA-positive asymptom 2019 Jul 31 OBJECTIVE: To compare DNA methylation in subjects positive vs negative for anti-citrullinated protein antibodies (ACPA), a key serological marker of rheumatoid arthritis (RA) risk. METHODS: With banked serum from a random subset (N = 3600) of a large general population cohort, we identified ACPA-positive samples and compared them to age- and sex-matched ACPA-negative controls. We used a custom-designed methylome panel to conduct targeted bisulfite sequencing of 5 million CpGs located in regulatory or hypomethylated regions of DNA from whole blood (red blood cell lysed). Using binomial regression models, we investigated the differentially methylated regions (DMRs) between ACPA-positive vs ACPA-negative subjects. An independent set of T cells from RA patients was used to "validate" the differentially methylated sites. RESULTS: We measured DNA methylation in 137 subjects, of whom 63 were ACPA-positive, 66 were ACPA-negative, and 8 had self-reported RA. We identified 1303 DMRs of relevance, of which one third (402) had underlying genetic effects. These DMRs were enriched in intergenic CpG islands (CGI) and CGI shore regions. Furthermore, the genes associated with these DMRs were enriched in pathways related to Epstein-Barr virus infection and immune response. In addition, 80 (38%) of 208 RA-specific DMRs were replicated in T cells from RA samples. CONCLUSIONS: Sequencing-based high-resolution methylome mapping revealed biologically relevant DNA methylation changes in asymptomatic individuals positive for ACPA that overlap with those seen in RA. Pathway analyses suggested roles for viral infections, which may represent the effect of environmental triggers upstream of disease onset.
31865066 Effects of daphnetin on the autophagy signaling pathway of fibroblast-like synoviocytes in 2020 Mar Daphnetin (DAP), an active ingredient extracted from Daphne odora, has pharmacological effects such as anti-inflammatory, antioxidation and anti-tumor properties. The current study aims to investigate the relationship between the anti-rheumatoid effect of DAP and the inhibition of both the PI3K/AKT/mTOR and autophagy signaling pathways. DAP inhibited the proliferation of CIA-FLS in a dose-dependent manner and induce apoptosis, accelerated the G1/G0 phase and inhibited the S phase. DAP reduced the phosphorylation of AKT and mTOR and the expression of Atg5, Beclin-1 and LC3-II/LC3-I in CIA-FLS induced by TNF-α. DAP also reduced the inflammatory response in CIA-FLS induced by TNF-α by inhibiting the cytokine expression of TNF-α, IL-6, TGF-β, IL-17, and INF-γ and promoting IL-10 expression. Overall, DAP inhibited the proliferation of CIA-FLS by down-regulating the PI3K/AKT/mTOR signaling pathway and inhibited autophagy in order to induces apoptosis, which may be potential therapeutic approach in treatment of RA.
31155669 Predictors, demographics and frequency of sustained remission and low disease activity in 2019 Dec 1 OBJECTIVES: To investigate the frequency and predictors of sustained 28-joint DAS (DAS28) remission and low disease activity (LDA) in patients receiving anti-TNF therapy and changes in responses over a 12 year period. METHODS: Data from the British Society for Rheumatology Biologics Registry for Rheumatoid Arthritis were used. Sustained remission and LDA were defined according to DAS28-ESR thresholds sustained for 6 months. The dataset was dichotomized into sequential chronological subgroups (2001-2010 and 2010-2013). Predictive variables were identified from a previous systematic review and modelled using multivariable logistic regression. RESULTS: Overall, 2144 (14.9%) and 3802 (26.3%) patients achieved sustained remission or LDA, respectively. Positive predictors of sustained remission/LDA included adalimumab (vs etanercept), greater patient global assessment, never- and ex-smoker status (vs current smoking), greater swollen joint count, more recent commencement of anti-TNF and MTX co-prescription (except in the 2010-2013 subgroup). Negative predictors of sustained remission and LDA included poor baseline functional status (HAQ), female gender, older age at starting anti-TNF, infliximab use (vs etanercept), increasing BMI and greater baseline ESR. Increasing tender joint count was negatively associated with sustained LDA only. The overall proportion of patients achieving sustained remission and LDA has increased significantly over time. CONCLUSION: Sustained remission/LDA on anti-TNF treatment remains uncommon. Adalimumab use, greater patient global assessment, never- and ex-smoker status, greater swollen joint count, more recent commencement of anti-TNF and MTX co-prescription are associated with achievement of sustained remission/LDA. However, co-prescription of MTX was not associated with an increased likelihood of achieving sustained remission or LDA in the analysis of more recent anti-TNF responses.
29885551 Prealbumin, platelet factor 4 and S100A12 combination at baseline predicts good response t 2019 Mar OBJECTIVES: Tumour necrosis factor-alpha inhibitors (TNFi) are effective treatments for Rheumatoid Arthritis (RA). Responses to treatment are barely predictable. As these treatments are costly and may induce a number of side effects, we aimed at identifying a panel of protein biomarkers that could be used to predict clinical response to TNFi for RA patients. METHODS: Baseline blood levels of C-reactive protein, platelet factor 4, apolipoprotein A1, prealbumin, α1-antitrypsin, haptoglobin, S100A8/A9 and S100A12 proteins in bDMARD naive patients at the time of TNFi treatment initiation were assessed in a multicentric prospective French cohort. Patients fulfilling good EULAR response at 6 months were considered as responders. Logistic regression was used to determine best biomarker set that could predict good clinical response to TNFi. RESULTS: A combination of biomarkers (prealbumin, platelet factor 4 and S100A12) was identified and could predict response to TNFi in RA with sensitivity of 78%, specificity of 77%, positive predictive values (PPV) of 72%, negative predictive values (NPV) of 82%, positive likelihood ratio (LR+) of 3.35 and negative likelihood ratio (LR-) of 0.28. Lower levels of prealbumin and S100A12 and higher level of platelet factor 4 than the determined cutoff at baseline in RA patients are good predictors for response to TNFi treatment globally as well as to Infliximab, Etanercept and Adalimumab individually. CONCLUSION: A multivariate model combining 3 biomarkers (prealbumin, platelet factor 4 and S100A12) accurately predicted response of RA patients to TNFi and has potential in a daily practice personalized treatment.
30941802 miR-124a inhibits the proliferation and inflammation in rheumatoid arthritis fibroblast-li 2019 Jun Abnormal hyperplasia of fibroblast-like synoviocytes (FLS) leads to the progression of rheumatoid arthritis (RA). This study aimed to investigate the role of miR-124a in the pathogenesis of RA. The viability and cell cycle of FLS in rheumatoid arthritis (RAFLS) were evaluated by Cell Counting Kit 8 and flow cytometry assay. The expression of PIK3CA, Akt, and NF-κB in RAFLS was examined by real-time PCR and Western blot analysis. The production of tumour necrosis factor (TNF)-α and interleukin (IL)-6 was detected by ELISA. The joint swelling and inflammation in collagen-induced arthritis (CIA) mice were examined by histological and immunohistochemical analysis. We found that miR-124a suppressed the viability and proliferation of RAFLS and increased the percentage of cells in the G1 phase. miR-124a suppressed PIK3CA 3'UTR luciferase reporter activity and decreased the expression of PIK3CA at mRNA and protein levels. Furthermore, miR-124a inhibited the expression of the key components of the PIK3/Akt/NF-κB signal pathway and inhibited the expression of pro-inflammatory factors TNF-α and IL-6. Local overexpression of miR-124a in the joints of CIA mice inhibited inflammation and promoted apoptosis in FLS by decreasing PIK3CA expression. In conclusion, miR-124a inhibits the proliferation and inflammation in RAFLS via targeting PIK3/NF-κB pathway. miR-124a is a promising therapeutic target for RA.
31349410 Preparation and in vitro evaluation of radiolabeled HA-PLGA nanoparticles as novel MTX del 2019 Oct Radiosynovectomy is a technique used to decrease inflammation of the synovial tissue by intraarticular injection of a β-emitting radionuclide, such as (177)Lu, which is suitable for radiotherapy due to its decay characteristics. Drug-encapsulating nanoparticles based on poly lactic‑co‑glycolic acid (PLGA) polymer are a suitable option to treat several arthritic diseases, used as anti-inflammatory drugs transporters of such as methotrexate (MTX), which has been widely used in the arthritis treatment (RA), and hyaluronic acid (HA), which specifically binds the CD44 and hyaluronan receptors overexpressed on the inflamed synovial tissue cells. The 1,4,7,10‑Tetraazacyclododecane‑1,4,7,10‑tetraacetic acid (DOTA) was used as complexing agent of Lutetium-177 for radiotherapy porpoises. The aim of this research was to synthesize (177)Lu-DOTA-HA-PLGA(MTX) as a novel, smart drug delivery system with target-specific recognition, potentially useful in radiosynovectomy for local treatment of rheumatoid arthritis. The polymeric nanoparticle system was prepared and chemically characterized. The MTX encapsulation and radiolabelling were performed with suitable characteristics for its in vitro evaluation. The HA-PLGA(MTX) nanoparticle mean diameter was 167.6 nm ± 57.4 with a monomodal and narrow distribution. Spectroscopic techniques demonstrated the effective conjugation of HA and chelating agent DOTA to the polymeric nanosystem. The MTX encapsulation was 95.2% and the loading efficiency was 6%. The radiochemical purity was 96 ± 2%, determined by ITLC. Conclusion: (177)Lu-DOTA-HA-PLGA(MTX) was prepared as a biocompatible polymeric PLGA nanoparticle conjugated to HA for specific targeting. The therapeutic nanosystem is based on bi-modal mechanisms using MTX as a disease-modifying antirheumatic drug (DMARD) and (177)Lu as a radiotherapeutic component. The (177)Lu-DOTA-HA-PLGA(MTX) nanoparticles showed properties suitable for radiosynovectomy and further specific targeted anti-rheumatic therapy.
30474933 Chronic Opioid Use in Rheumatoid Arthritis: Prevalence and Predictors. 2019 May OBJECTIVE: The opioid epidemic is a major public health concern. However, little is known about opioid use among rheumatoid arthritis (RA) patients. We undertook this study to examine trends in chronic opioid use in RA patients in 2002-2015 and to identify clinical predictors. METHODS: RA patients were identified from the Corrona registry. Opioid use was ascertained from surveys obtained at clinical visits as often as every 3 months. Chronic opioid use was defined as any opioid use reported during ≥2 consecutive study visits. Annual prevalence of chronic opioid use was calculated using data from 33,739 RA patients with information on opioid use from ≥2 visits. Among the 26,288 individuals who were not taking opioids at baseline, Cox proportional hazards models identified associations between patient characteristics and incident chronic opioid use. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: Chronic opioid use increased from 7.4% in 2002 to 16.9% in 2015. Severe pain (HR 2.53 [95% CI 2.19-2.92]) and antidepressant use (HR 1.79 [95% CI 1.64-1.92]) were associated with an increased risk of chronic opioid use. High disease activity (HR 1.55 [95% CI 1.30-1.84]) and a high level of disability (HR 1.45 [95% CI 1.27-1.65]) were also associated with chronic opioid use, whereas Asian ethnicity (HR 0.49 [95% CI 0.36-0.68]) was associated with a decreased risk of chronic opioid use. CONCLUSION: Among RA patients, chronic opioid use doubled from 2002 to 2015. Pain and antidepressant use were the strongest predictors of chronic opioid use. To curb the rise in chronic opioid use, strategies for stringent control of RA disease activity and management of pain and depression should be research priorities.
31770283 Association of HLA-DRB1 genotype with younger age onset and elder age onset rheumatoid art 2019 Nov Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint destructions and human leukocyte antigen (HLA)-DRB1 is an important genetic risk factor for RA and influences the phenotype of RA. The clinical features of elder age onset RA (EORA) were known to be different from those of younger age onset RA (YORA). Previous studies reported the different association pattern of DRB1 alleles with YORA or EORA. The associations of DRB1 genotype with these RA subsets remained almost unknown. We investigated the genotype association of DRB1 with YORA or EORA in Japanese populations.HLA genotyping was performed in Japanese RA patients and the association of allele or genotype carrier frequencies were analyzed.The genotype frequency of DRB104:05/DRB104:06 (P = .0204, OR 7.69, 95%CI 1.39-42.72), DRB104:05/DRB112:01 (P = .0050, OR 5.53, 95%CI 1.71-17.88), and DRB104:05/DRB115:01 (P = .0124, OR 3.34, 95%CI 1.39-8.02) in YORA was higher than EORA. However, the frequencies of DRB101:01/DRB104:05 in YORA was tended to be lower than EORA (P = .0784, OR 0.14, 95%CI 0.01-2.42). The gene dosage effect of the shared epitope alleles was detected in EORA, but not in YORA. Trans-complementing DQ heterodimer molecules, formed by DQA1 and DQB1 of the haplotypes with and without shared epitope alleles, might explain the higher genotype frequencies of "shared epitope /not shared epitope". Linear regression analyses showed the primary role of DQB104:01 allele for the age at onset of RA.This is the first report for the associations of DRB1 genotype with YORA or EORA in the Japanese population and the differential distribution of the genotypes was noted between these RA subsets. The involvement of DQ molecules for the age at onset of RA was suggested.
31524046 Responsiveness of different dynamic contrast-enhanced magnetic resonance imaging approache 2020 Mar Objective: The aim was to explore dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as an early marker of therapeutic response in patients with rheumatoid arthritis (RA) starting treatment with certolizumab pegol (CZP).Method: In 40 RA patients initiating CZP (27 patients) or 2 weeks of placebo (PCB) followed by CZP (13 patients), DCE-MRI of the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints was performed at weeks 0, 1, 2, 4, 8, and 16. Using semi-automated software, three methods for drawing volume regions of interest (ROIs) in MCP2-5 and PIP2-5 were applied: 'Standard' (slices: all; joints: MCP2-5 together and PIP2-5 together), 'Detailed' (slices: slices with high-quality visualization; joints: as Standard), and 'Single-joint' (slices: as Detailed; joints: each joint separately). The number of enhancing voxels (Nvoxel), initial rate of enhancement (IRE), and maximum enhancement (ME) were extracted and analysed for each method.Results: Nvoxel in MCP2-5, and IRE and ME in PIP2-5 decreased statistically significantly (Wilcoxon rank-sum test, p < 0.02-0.03) after 16 weeks of treatment for the Standard method. Nvoxel and ME decreased significantly more in the CZP group than in the PCB group after 1 week of treatment, but not at later time-points. There were no significant changes for DCE-MRI parameters for the Detailed and Single-joint methods.Conclusions: Certain DCE-MRI parameters detected decreased inflammation during CZP treatment in RA patients. Using specific criteria for ROIs, as in the Detailed and Single-joint methods, decreased the statistical power and could not show any changes over time.
29953733 Preference Phenotypes in Support of Shared Decision-Making at Point-of-Care for Patients W 2019 May OBJECTIVE: In this proof-of-concept study, we sought to evaluate whether a value clarification tool enabling patients to view a set of rheumatoid arthritis (RA) treatment preference phenotypes could be used to support shared decision-making at the point-of-care. METHODS: We conducted a pretest/post test study. English-speaking patients with RA presenting to their scheduled outpatient visits were asked to participate. Visits for patients with active RA were transcribed. Shared decision-making components were measured using a quantitative coding scheme based on an established model of shared decision-making. RESULTS: Forty-six visits were included in the pretest and 40 in the post test phases. Providers offered more disease-modifying antirheumatic drugs (DMARDs) (2 or more) in the post test visits (60%) compared to the pretest visits (47.8%). Overall, more patients vocalized their values and/or preferences in the post test visits compared to the pretest visits for treatment escalation decisions including a choice of 1 new DMARD (90.9% versus 56.3%), 2 or more new DMARDs (95.8% versus 86.4%), as well as prednisone (87.5% versus 66.7%). Providers were also more likely to base their recommendations on patients' values and/or preferences in the post test (100% of 6 visits) than the pretest (64.3% of 14 visits) phases during visits in which a recommendation was made. The mean ± SD length of the visit was 29.9 ± 11.6 minutes and 25.1 ± 10.7 minutes in the pretest and post test phases, respectively. CONCLUSION: This study provides an early indication that a value clarification tool allowing patients to consider a set of preference phenotypes can support shared decision-making at the point-of-care without extending visit time.