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ID PMID Title PublicationDate abstract
32378971 Galantamine transdermal patch shows higher tolerability over oral galantamine in rheumatoi 2020 Jun Rheumatoid arthritis (RA) is a chronic autoimmune disease of idiopathic etiology that triggers inflammatory cytokines compromising the joint mobility. Epidemiological evidences recommend the utilization of galantamine (GH) to reverse the anti-inflammatory reactions induced RA. Oral administration of GH is non-selectivity due to its association with serious gastrointestinal symptoms which, could hinder its therapeutic success. Therefore, the present study aimed to validate the therapeutic potential of GH transdermal patches as a novel application to constitute an effective and tolerable delivery system for managing RA in adjuvant arthritis model. RA was induced in Sprague-Dawley rats intradermally by Heat-killed M (0.12 ml/day). Oral GH (1.25 mg/kg/day) and GH transdermal patch (2.5 mg/kg/2 days) were administrated for 14 days, during which the hind paw and body weight (BW) were assessed. Effects of C-reactive protein (CRP), inflammatory cytokines (TNF-α, IL-10 and IL-1β) and Janus kinase (JAK-2) were evaluated. Oral- and transdermal GH significantly improved the hind paw edema in arthritis animal model and offered a protective impact against RA. Oral GH group showed marked decrease in BW than that of transdermal patches group. Transdermal patch group showed a significant decrease in the level of IL-1β more than the oral group. However, no significant difference was detected in the levels of TNF-α and IL-10 between the two groups. It is concluded that GH transdermal patch can be a promising drug delivery system that copes with side effects better than oral GH consequently represents novel strategy in management of RA.
32025734 Equal rights in autoimmunity: is Sjögren's syndrome ever 'secondary'? 2020 Jun 1 Sjögren's syndrome (SjS) accompanied by other systemic autoimmune rheumatic connective tissue diseases has historically been termed 'secondary' in contrast to 'primary' SjS as a standalone entity. However, it is a matter of a long-standing debate whether the prefixes 'primary' and 'secondary', including a temporal component, are obsolete in the terminology of SjS. We review the history and the pathophysiological, chronological, genetic, histological and clinical data underlying the concept of 'secondary' SjS. There are important unintended consequences of the nomenclature; notably 'secondary' SjS has been much less researched and is often excluded from clinical trials. We argue for further research, a change in terminology and more stringent classification. Further we highlight possible opportunities for trials in SjS and other systemic autoimmune diseases that might contribute to an advance in care for all patients with SjS.
32795341 Radiographic progression based on baseline characteristics from TNF inhibitor biosimilar s 2020 Aug 14 OBJECTIVE: Phase III clinical trials of the tumour necrosis factor inhibitors SB4, SB2, and SB5 (biosimilars to etanercept, infliximab, and adalimumab, respectively) have demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA). Data from these trials were used to identify baseline characteristics associated with radiographic progression and to build a matrix risk model for its prediction. METHODS: Patients with radiographic progression and baseline demographic and disease characteristic data were pooled across the 3 phase III studies of each biosimilar and its reference product. Baseline demographics and disease characteristics were evaluated for their relationship with radiographic progression (1-year mean change in mTSS > 0); 3 factors were selected based on strongest Pearson's correlation coefficient with the change in modified Total Sharp Score. Univariate logistic regression was performed to assess the association between each baseline factor and the rate of radiographic progression, with subsequent matrix model development performed using multivariate logistic regression. RESULTS: A total of 1371 patients were included in the analysis, with a radiographic progression rate of 27.4%. The 3 baseline predictors of radiographic progression, based on Pearson's correlation coefficient, were 28 swollen joint count (SJC28), C-reactive protein (CRP), and physician global assessment (PhGA). A matrix model showed that the predicted risk of radiographic progression was higher with the increased level of SJC28, CRP, and PhGA (P < 0.001). CONCLUSIONS: In this pooled analysis of phase III clinical trial data of biosimilars for RA, identifiable baseline factors (SJC28, CRP, and PhGA) associated with radiographic progression were similar to those described in prior studies. Even though radiographic progression was minimal, a small number of patients who have increased SJC28, CRP, and PhGA at baseline should be closely monitored and follow treat-to-target approach. CLINICAL TRIAL REGISTRATION NUMBERS: EudraCT 2012-005026-30. Registered 30 April 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005026-30/results EudraCT 2012-005733-37. Registered 10 July 2013, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005733-37/results EudraCT 2013-005013-13. Registered 01 April 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-005013-13/results.
32851511 Cinnamaldehyde Attenuates the Progression of Rheumatoid Arthritis through Down-Regulation 2020 Oct Cinnamaldehyde (CA), as an active compound isolated from the bark of Cinnamomum cassia, has been reported to possess the anti-fungal, anti-bacterial, anti-inflammatory, anti-mutagenic, and anti-oxidant properties. However, the possible effects and underlying mechanisms of CA on rheumatoid arthritis (RA) have not been revealed yet. In the present study, we found that CA obviously improved the type II collagen-induced RA in rats, accompanied with decreasing pro-inflammatory factors, proliferation and metastasis. In addition, CA decreased the expression levels of TNF-α, IL-1β, and IL-6 in RA-FLSs. Besides, CA remarkably inhibited the proliferation, downregulated the EdU-positive cells, and promoted apoptosis of RA-FLSs by CCK-8, EdU and flow cytometry analysis. Moreover, the results of wound healing, transwell migration and invasion assays showed that CA inhibited the migration and invasion of RA-FLSs. Further, western blot experiment showed CA inhibited the activation of PI3K/AKT signaling pathway in RA-FLSs. Finally, 740Y-P, the PI3K/AKT signaling pathway activator, could reverse the effects of CA on the proliferation and metastasis in RA-FLSs. In conclusion, we confirmed that CA exhibited potential therapeutic properties against RA via suppressing proliferation and metastasis of RA-FLSs by blockage of PI3K/AKT signaling pathway. Therefore, our study provides evidence that CA may emerge as a therapeutic option for RA treatment.
33170478 Distinctive Clinical Characteristics and Outcome of ILD-Onset Rheumatoid Arthritis and ACP 2021 Feb The aim of this study is to investigate the clinical features and outcome of interstitial lung disease (ILD)-onset rheumatoid arthritis (RA) and anti-citrullinated protein antibody (ACPA)-positive ILD-only patients. Arthritis-onset and ILD-onset RA-ILD and ACPA-positive ILD-only patients consecutively admitted to Peking Union Medical College Hospital from January 2008 to December 2017 were enrolled and followed-up. Their demographic, clinical, and laboratory features as well as outcome were collected and analyzed. Compared with arthritis-onset RA-ILD (n = 166, median arthritis-to-ILD interval: 60 months), the ILD-onset RA-ILD (n = 75, median ILD-to-arthritis interval: 2 months) had less rheumatoid nodules and higher titer of ACPA, and manifested more stable ILD (median estimated progression-free survival: 120 vs. 100 months, p = 0.019). Elder age (≥ 65 years) at ILD diagnosis and UIP pattern were associated with ILD progression by both univariate and Cox hazards modeling analysis (p < 0.05). In ACPA-positive ILD-only patients (n = 41), arthritis developed in 7 (17.1%) female patients after a median interval of 24 months. ACPA-positive ILD who subsequently developed arthritis exhibited higher frequency of rheumatoid factor (RF), higher titer of ACPA, and higher levels of ESR and CRP (p < 0.05). Multivariate regression analysis showed that positive RF (OR 12.55, 95% CI 1.31 to 120.48) was the independent risk factor for arthritis development in ACPA-positive ILD-only patients. ILD-onset RA-ILD had more stable ILD compared with arthritis-onset RA-ILD. ACPA-positive ILD patients with positive RF are at increased risk of developing RA.
32828139 Role of prostaglandins in rheumatoid arthritis. 2021 Jan Rheumatoid arthritis (RA) is an autoimmune disease characterised by systemic and chronic synovitis that lead to joint destruction, pain, and many complications. Treatments only relieve certain symptoms, but do not cure RA completely. Prostaglandins (PGs) are lipid signalling molecules and released in the early phase of RA. Increasing evidences have shown five main contribution of PGs to the different stages and symptoms of RA. First, PGs maintain the autoimmune response and immune-system inflammation by modulating the differentiation, maturation, and cytokine production of immune cells. Second, PGs are beneficial for leukocyte infiltration, synovial hyperplasia, and angiogenesis to promote synovitis. Third, PGs are involved in cartilage degradation and bone resorption. Fourth, PGs are important mediators of joint-pain regulation. Finally, in the late stage of RA inflammation, PGs play a part in joint protection. Those findings suggest that PGs are potential therapy targets for RA. This review highlights recent advances in the RA development caused by PGs, and provides recommendations for future research directions.
31913553 Aerobic capacity is associated with disease activity and cardiovascular risk factors in ea 2020 Jul OBJECTIVES: The aim of this study was to investigate aerobic capacity and its associations with disease activity and risk factors for cardiovascular disease (CVD) in early rheumatoid arthritis (RA). METHODS: This cross-sectional study included 67 patients with early RA. Aerobic capacity was estimated with the Åstrand submaximal test adjusted according to the Nord-Tröndelag Health Study formula. The following were also assessed: subclinical atherosclerosis by carotid intima-media thickness and pulse wave analysis; body composition by dual X-ray absorptiometry; estimated CVD mortality risk by the Systematic Coronary Risk Evaluation; disease activity by the Disease Activity Score 28, C-reactive protein and erythrocyte sedimentation rate; blood lipids by total cholesterol, low-density lipoproteins, high-density lipoproteins, and triglycerides; and functional ability by the Stanford health assessment questionnaire. Univariate and multiple linear regression analyses were performed to explore the associations between variables. RESULTS: The mean (SD) aerobic capacity was 31.6 (8.7) ml O(2) (-1) kg min(-1) . Disease activity and risk factors for CVD were more favourable for patients with aerobic capacity above the median value. Aerobic capacity was associated with ESR and several CVD risk factors, independent of age and sex. In a multiple regression model that was adjusted for age and sex, aerobic capacity was significantly associated with per cent body fat (β = -0.502, 95% CI [-0.671, -0.333]) and triglycerides (β = -2.365, 95% CI [-4.252, -0.479]). CONCLUSIONS: Disease activity and risk factors for CVD were in favour for patients with a higher aerobic capacity. Aerobic capacity was associated with disease activity and several risk factors for CVD, independent of age and sex. In RA, these findings may provide insights into the benefits of using aerobic capacity as a marker to prevent CVD.
32390364 Contribution of Personality Traits, Psychological Factors, and Health-Related Quality of L 2020 May PURPOSE: This study sought to investigate the associations between personality traits and medication adherence and to identify predictors of good medication adherence in rheumatoid arthritis (RA) patients. MATERIALS AND METHODS: A total of 207 RA patients using disease-modifying anti-rheumatic drugs were invited for an interview and questionnaire study. Medication adherence was measured using the Compliance Questionnaire for Rheumatology (CQR). Personality traits were analyzed with the five-factor model of the Korean version of the Big Five Inventory 10. Psychological factors were assessed with the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and British Columbia Cognitive Inventory. Health-related Quality of Life (HRQoL) and functional disability were evaluated with the EuroQoL-5 dimension questionnaire and Health Assessment Questionnaire. Multivariate logistic regression analyses were performed to investigate predictors of good medication adherence. RESULTS: Nonadherence to medication was reported by 66.7%. The number of daily prescribed pills was higher in the medication adherence group than in the nonadherence group. Concomitant oral glucocorticoid doses were associated with medication adherence. A high level of conscientiousness and diabetes mellitus comorbidity were associated with better medication adherence [odds ratio (OR), 2.11; 95% confidence interval (CI), 1.01-4.38 and OR, 3.00; 95% CI, 1.12-8.07, respectively]. There were no significant differences in psychological factors or HRQoL between medication adherence and nonadherence groups. CONCLUSION: The personality trait of conscientiousness was associated with medication adherence among the five personality traits evaluated. Patients with diabetes mellitus also showed higher medication adherence than those without this comorbidity.
32790722 Association of significant risk perception with the use of complementary and alternative m 2020 BACKGROUND: Risk perception (RP) describes patient´s judgment of the likelihood of experiencing something unpleasant, and has been associated to the adoption of health behaviors. Current rheumatoid arthritis (RA) guidelines recommend early and intensive treatment, although patients also commonly use Complementary and Alternative Medicine (CAM). We aimed to investigate if significant RP was associated to CAM use in Hispanic RA outpatients and to describe additional associated factors. METHODS: Between March and August 2019, 266 consecutive outpatients were invited to a face-to-face interview to collect socio-demographic and RA-related information, to assess comorbidity and the following patient-reported-outcomes: pain, overall-disease and treatment adherence with visual analogue scales, disease activity with RAPID-3, RP with a validated questionnaire, and CAM use with a translated and cross-culturally adapted for Argentina version of the International CAM questionnaire. Medical records were reviewed to corroborate the data provided by the patients. CAM use definition was restricted to "in the last 3 months". Significant RP was defined based on published cut-off. Multiple logistic regression analysis was used to investigate factors associated to CAM use. The study received IRB approval. RESULTS: There were 246 patients included, primarily middle-aged women, with substantial disease duration, moderate disease activity and 70 patients (28.5%) had significant RP. Two hundreds patients (81.3%) were CAM users. Significant RP (OR: 2.388, 95%CI: 1.044-5.464, p = 0.039) and access to Federal health care system (OR: 2.916, 95%CI: 1.081-7.866, p = 0.035) were associated to CAM use. CONCLUSIONS: Patient´s perception of RA-related negative consequences was associated to recent CAM use in Hispanic RA outpatients.
32700875 Effects of mannuronic acid (M2000) on gene expression profile of signal transducer and act 2020 Jul 23 Rheumatoid arthritis (RA), a form of inflammatory arthritis, is a chronic joint disease characterized by pain and inflammation that affects 0.5% to 1% of the population worldwide. The safety, efficacy, tolerability, and potency of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property has been reported by several in vitro studies, experimental models and clinical trials phase I/II and III in ankylosing spondylitis and rheumatoid arthritis (RA) patients This research is designed to study the therapeutic efficacy of oral administration of mannuronic acid in RA patients who had inadequate response to conventional drugs and to assess the effect of this drug on gene expression of the signal transducer and activator of transcription (STATs) protein (STAT1, STAT3, STAT4, and STAT6). The study has included 15 RA patients who had an insufficient response to the conventional therapy. The oral dose of mannuronic acid was 1000mg divided into two 500 mg doses per day for 3 months as an addition to conventional therapy. There were 15 healthy volunteer in the control group. Blood samples were collected from both groups, once from healthy controls and twice from RA patients before and after treatment by M2000. The peripheral blood mononuclear cells (PBMCs) were isolated to assess the gene expression level of STAT1, STAT3, STAT4, and STAT6 using the real-time PCR method. Results obtained in this study demonstrated a significant difference in the gene expression level of STAT1 between healthy controls and patients before treatment as well as a significant reduction in RA patients after treatment compared with the level before treatment. In addition, the gene expression level of STAT3 and STAT4 showed a significant reduction in RA patients after treatment compared to patients before treatment, while there was no significant difference between RA patients before treatment and the healthy control group for both molecules. On the other hand, there was no change in the gene expression level of STAT6 among all groups. The outcomes of this study confirmed that β-D-mannuronic acid (M2000) has the ability to control the levels of STAT1, STAT3 and STAT4 in RA patients, and might be beneficial in the management and therapy of RA.
32450605 Acute Total Knee Replacement in Rheumatoid Arthritis Patients with Proximal Tibial Fractur 2021 Dec Management of proximal tibial fractures is a challenging issue in patients with rheumatoid arthritis (RA). In the present study, we aimed to describe our experience of acute total knee replacement in RA patients. This case series included 11 RA patients with simultaneous insufficiency fractures of the proximal tibia, who were treated by acute total knee replacement. Midterm functional results, severity of pain, Hospital for Special Surgery (HSS), and Knee Society Score (KSS) parameters were evaluated in this study. The patients were followed up for 24 months. Eleven women with proximal tibial fractures and history of RA (mean age: 54.3 ± 4.7 years) were enrolled in this study. The mean score of Tegner activity scale was 2.2 ± 1.4 preoperatively, which significantly improved to 4.3 ± 1.4 postoperatively (p < 0.001). The two sections of KSS (knee and function section) averaged 88.7 ± 5.4 and 59.4 ± 8.2, respectively. There wasn't poor outcome and excellent result was in knee section 54.5% and function section 36.3% based on KSS. The mean score of pain severity during normal activity before fracture was 65.2 ± 12.3, which significantly reduced to 35.5 ± 11.3 in the final follow-up (p = 0.02). The score of HSS scale improved from 42 (range: 16-58) in the preoperative stage to 78 (range: 72-91) after surgery (p < 0.001). In the 6-month follow-up, deep vein thrombosis was reported in two patients. The time required to return to normal activity was 5.5 ± 2.3 months. Based on the findings, total knee replacement therapy in patients with RA and proximal tibial fractures produced excellent clinical outcomes, which led to rapid return to normal activity. This is a Level IV, therapeutic study.
32670287 Sonic Hedgehog Regulates Proliferation, Migration and Invasion of Synoviocytes in Rheumato 2020 Activated fibroblast-like synoviocytes (FLSs) play a central role in the formation of synovial pannus and joint destruction in rheumatoid arthritis (RA). Targeting FLSs could be a potential therapeutic strategy. The objective of this study is to explore the role of c-Jun N-terminal kinase (JNK) in proliferation, migration and invasion of FLSs promoted by the sonic hedeghog (SHH) signaling pathway in patients with RA. Activation of SHH signaling was evaluated by real-time PCR and Western Blot. Levels of phosphorylation of JNK and c-Jun were detected by Western Blot. FLSs proliferation was quantified by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Cell migration and invasion were assessed by wound healing assay and Transwell chamber assay. Invasiveness of FLSs in vivo was evaluated using a humanized synovitis animal model. We observed that treatment of SHH agonist (SAG) significantly increased the levels of phosphorylation of JNK and c-Jun, while SHH antagonist (cyclopamine) significantly decreased the expression of phospho-JNK and phospho-c-Jun in FLSs. The elevated level of phospho-c-Jun stimulated by SAG was decreased in the presence of JNK inhibitor (SP600125) (P < 0.001). FLSs proliferation, migration and invasion were promoted by SHH agonist (P < 0.05). However, the enhanced aggressiveness of FLSs was abolished in the presence of JNK inhibitor (P < 0.05). In vivo study showed that the invasion of FLSs into cartilage was increased by SHH overexpression and the excessive invasiveness was inhibited by blockade of JNK signaling (P < 0.01). These results suggest that JNK is one of the downstream molecules mediating the effect of SHH signaling in FLSs. These findings indicate that SHH-JNK signaling could be a potential therapeutic target to suppress the aggressiveness of FLSs and prevent articular damage of RA.
32845377 Differentiating rheumatoid and psoriatic arthritis: a systematic analysis of high-resoluti 2021 Mar BACKGROUND: Because of overlapping phenotypical presentations, the diagnostic differentiation of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) remains challenging. Thus, this study aimed to examine the diagnostic value of distinct imaging features obtained by high-resolution 3-T MRI for the diagnostic differentiation. MATERIALS AND METHODS: Seventeen patients with PsA and 28 patients with RA were imaged at high resolution using 3-T MRI scanners and a dedicated 16-channel hand coil. All images were analyzed according to the outcome measures in rheumatology clinical trials' (OMERACT) RAMRIS (Rheumatoid Arthritis Magnetic Resonance Imaging Score) and PsAMRIS (Psoriatic Arthritis Magnetic Resonance Imaging Score) for the presence and intensity of synovitis, flexor tenosynovitis, bone edema, bone erosion, periarticular inflammation, bone proliferation, and joint space narrowing. Next, odds ratios (OR) were calculated to determine the strength of the associations between these imaging features, demographic characteristics, and the outcome RA vs. PsA. RESULTS: PsA could be differentiated from RA by extracapsular inflammatory changes (PsAMRIS sub-score "periarticular inflammation"), with low odds for the presence of RA (OR of 0.06, p < 0.01) at all metacarpophalangeal (MCP) joints. A prediction model informed by the items that were strongest associated with the presence of RA or PsA demonstrated excellent differentiating capability with an area under the curve of 98.1%. CONCLUSION: High-resolution imaging is beneficial for the identification of relevant imaging features that may assist the clinical differentiation of inflammatory conditions of the hand. At the MCP level, extracapsular inflammatory changes were strongly associated with PsA and may consequently allow the imaging differentiation of PsA and RA.
32300128 Imaging evaluation of the cartilage in rheumatoid arthritis patients with an x-ray phase i 2020 Apr 16 X-ray Talbot-Lau interferometry is one of the x-ray phase imaging methods that has high sensitivity in depicting soft tissues. Unlike earlier x-ray phase imaging methods that required particular types of x-ray sources, such as a synchrotron or a micro-focus x-ray tube, x-ray Talbot-Lau interferometry enables to perform clinical x-ray phase imaging using a conventional x-ray source with a relatively compact configuration. We developed an apparatus to depict cartilage in the metacarpophalangeal joints of the hands. In addition, we examined the apparatus performance by applying it to healthy volunteers and patients with rheumatoid arthritis (RA). Cartilage deformation, which is thought to be a precursor of destruction of the joints, was successfully depicted by the apparatus, suggesting a potential early diagnosis of RA.
31856612 Effects of guluronic acid, as a new NSAID with immunomodulatory properties on IL-17, RORγ 2020 Feb Aim: Rheumatoid arthritis (RA) is a prevalent inflammatory, autoimmune diseases characterized by inflammation and destruction of joints. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can have modulatory interference in disease process. In this study, the effect of Guluronic Acid (G2013) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunomodulatory effects was evaluated on IL-17, RORγt, IL-4 and GATA-3 gene expression in RA patients.Methods: Fourteen patients with RA who had an inadequate response to conventional treatments were included in this clinical trial. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. G2013 was administered orally at dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the gene expression levels of IL-4, GATA-3, IL-17 and RORγt.Results: Primary and secondary efficacy endpoints and Disease Activity Score (DAS) 28 showed an improvement after 12 weeks of treatment. G2013 has a potent efficacy on gene expression of these molecules, so that it could decrease IL-17 and RORγt levels and increase IL-4 and GATA-3 levels after 12 weeks of treatment. Reduction of IL-17 was statistically non-significant whereas for its transcription factor (RORγt) was statistically significant. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments.Conclusion: G2013 as a natural novel drug showed a significant increase on IL-4 and GATA-3 and a significant decrease on RORγt gene expression after 12 weeks oral administration of this drug in RA patients. (Clinical trial identifier: IRCT2016092813739N5).
32813188 Does healthcare regime affiliation influence the clinical outcomes of patients with rheuma 2021 Mar BACKGROUND/PURPOSE: Adequate control of disease activity in rheumatoid arthritis (RA) depends, to a great extent, on the access to a rheumatologist. This study aimed to compare the disease outcomes of patients with RA, based on their healthcare regime affiliation. METHODS: A retrospective observational study of Colombian patients with RA in three outpatient services of different regimes: Contributory (CR, workers and their families with a monthly income above a yearly defined threshold, approximately US$ 220, who allocate a percentage of their income to financing the national health fund and to get access to healthcare services), subsidized (SR, a vulnerable population with a monthly income below the threshold, who have access to healthcare through the national health fund; comparable to the USA Medicaid population), and an excellence clinical care center (C3, access to specialized care, regardless of their healthcare affiliation regime). Data were collected from clinical records for 2 years of follow-up and included demographics, lag times between appointments, and time in high disease activity. We used the Mantel-Cox test for the analysis of time to remission/low disease activity. RESULTS: A total of 240 patients were included (80 patients per regime). At the start of follow-up, mean age was 53.7 years; 21.6% of patients were men; 79.6% of patients had established RA; 72.9% of patients had high disease activity. Patients in the CR had longer lag times between scheduled appointments (p < 0.0001). During follow-up, SR had the highest proportion of patients with high disease activity. Survival curve analysis showed no significant difference between SR and CR groups (p = 0.2903), but was significantly different compared with the C3 group (p < 0.0001). Median survival in high disease activity was greater in the SR group (293 days), followed by CR (254 days), and finally by C3 (64 days). CONCLUSION: Patients that were treated in the excellence clinical care center had better outcomes when compared with other regimes. These data support that healthcare regime may influence disease outcome in patients with RA. Key Points • Prompt access to healthcare in patients with rheumatoid arthritis is pivotal for an adequate control of the disease, for timely adjustment of treatment, and to reduce both the societal burden of the disease and its impact on individual well-being. • As an example of "structural iatrogenesis," healthcare regime affiliation appears to influence disease outcomes in patients with rheumatoid arthritis, in whom differences between regimes are observed. The most vulnerable patients appear to experience the worst outcomes. • Excellence clinical care centers for patients with rheumatoid arthritis should be implemented as an alternative to counteract structural healthcare barriers and as an approach to improve clinical outcomes through a tighter disease control.
30801951 Systematic Review of Economic Evaluations of Cycling Versus Swapping Medications in Patien 2020 Mar OBJECTIVE: To systematically review the modeling approaches and quality of economic analyses comparing cycling tumor necrosis factor inhibitors (TNFi) to swapping to a therapy with a different mode of action in patients with rheumatoid arthritis whose initial TNFi failed. METHODS: We searched electronic databases, gray literature, and references of included publications until July 2017. Two reviewers independently screened citations. Reporting quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Data regarding modeling methodology were extracted. RESULTS: We included 7 articles comprising 19 comparisons. Three studies scored ≥16 of 24 on the CHEERS checklist. Most models used a lifetime horizon, took a payer perspective, employed a 6-month cycle length, and measured treatment efficacy in terms of the American College of Rheumatology improvement criteria. We noted possible sources of bias in terms of transparency and study sponsorship. In the cost-utility comparisons, the median incremental cost-effectiveness ratio was US $70,332 per quality-adjusted life-year for swapping versus cycling strategies. Rituximab was more effective and less expensive than TNFi in 7 of 11 comparisons. Abatacept (intravenous) compared to TNFi was less cost-effective than rituximab. Common influential parameters in sensitivity analyses were the rituximab dosing schedule, assumptions regarding disease progression, and the estimation of utilities. CONCLUSION: Differences in the design, key assumptions, and model structure chosen had a major impact on the individual study conclusions. Despite the existence of multiple reporting standards, there continues to be a need for more uniformity in the methodology reported in economic evaluations of cycling versus swapping strategies after TNFi in patients with rheumatoid arthritis.
31350056 Different risk profiles of biologic agents for new-onset psoriasis in patients with rheuma 2020 Feb OBJECTIVE: To investigate rates and risk factors for incident and recurrent psoriasis in rheumatoid arthritis (RA) patients treated with different biologic (b) and conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs). METHODS: RA patients enrolled in the German biologics register RABBIT without (n = 14,525) or with a history of psoriasis (n = 375) were analyzed separately. All first events of psoriasis reported until October 2017 were assigned to the treatments prescribed in the previous 3 months. Crude incidence rates (IR) of psoriasis were calculated per 1000 patient-years. To investigate risk factors for psoriasis, cox regressions with and without inverse probability weights were applied to adjust for confounding by indication. RESULTS: 117 incident and 37 recurrent psoriatic events were reported. Patients exposed to TNFi had a significantly higher incidence rate (IR = 3.04/1,000 PY) than those exposed to csDMARDs only (IR = 0.65), whereas IRs for abatacept, rituximab and tocilizumab did not differ significantly from csDMARDs. Adjusted Cox regression confirmed a higher risk for TNFi. Female sex (HR: 1.7) and smoking (HR: 2.1) were significantly associated with incident psoriasis while methotrexate decreased the risk (HR: 0.5). For recurrent psoriasis, IRs for TNFi, abatacept and rituximab were significantly higher than for csDMARDs. CONCLUSIONS: Our data confirm a previously observed increased risk of incident psoriasis in patients exposed to TNFi compared to csDMARDs. However, the overall risk is low and the event is usually non-serious. Comedication of TNFi with methotrexate seems to lower the risk of incident psoriasis. In patients with a history of psoriasis, recurrence as adverse event is rare.
32708286 Identification of Subclinical Lung Involvement in ACPA-Positive Subjects through Functiona 2020 Jul 21 Lung involvement is related to the natural history of anti-citrullinated proteins antibodies (ACPA)-positive rheumatoid arthritis (RA), both during the pathogenesis of the disease and as a site of disease-related injury. Increasing evidence suggests that there is a subclinical, early lung involvement during the course of the disease, even before the onset of articular manifestations, which can potentially progress to a symptomatic interstitial lung disease. To date, reliable, non-invasive markers of subclinical lung involvement are still lacking in clinical practice. The aim of this study is to evaluate the diagnostic potential of functional assessment and serum biomarkers in the identification of subclinical lung involvement in ACPA-positive subjects. Fifty ACPA-positive subjects with or without confirmed diagnosis of RA (2010 ARC-EULAR criteria) were consecutively enrolled. Each subject underwent clinical evaluation, pulmonary function testing (PFT) with assessment of diffusion lung capacity for carbon monoxide (DL(CO)), cardiopulmonary exercise testing (CPET), surfactant protein D (SPD) serum levels dosage and high-resolution computed tomography (HRCT) of the chest. The cohort was composed of 21 ACPA-positive subjects without arthritis (ND), 10 early (disease duration < 6 months, treatment-naïve) RA (ERA) and 17 long-standing (disease duration < 36 months, on treatment) RA (LSRA). LSRA patients had a significantly higher frequency of overall HRCT abnormalities compared to the other groups (p = 0.001). SPD serum levels were significantly higher in ACPA-positive subjects compared with healthy controls (158.5 ± 132.3 ng/mL vs 61.27 ± 34.11 ng/mL; p < 0.0001) and showed an increasing trend from ND subjects to LSRD patients (p = 0.004). Patients with HRCT abnormalities showed significantly lower values of DL(CO) (74.19 ± 13.2% pred. vs 131.7 ± 93% pred.; p = 0.009), evidence of ventilatory inefficiency at CPET and significantly higher SPD serum levels compared with subjects with no HRCT abnormalities (213.5 ± 157.2 ng/mL vs 117.7 ± 157.3 ng/mL; p = 0.018). Abnormal CPET responses and higher SPD levels were also associated with specific radiological findings. Impaired DL(CO) and increased SPD serum levels were independently associated with the presence of HRCT abnormalities. Subclinical lung abnormalities occur early in RA-associated autoimmunity. The presence of subclinical HRCT abnormalities is associated with several functional abnormalities and increased SPD serum levels of SPD. Functional evaluation through PFT and CPET, together with SPD assessment, may have a diagnostic potential in ACPA-positive subjects, contributing to the identification of those patients to be referred to HRCT scan.
32388428 Novel formyl peptide receptor (FPR) agonists with pyridinone and pyrimidindione scaffolds 2020 Jul The resolution of inflammation is an active response involving the interaction of pro-resolving mediators with specific receptors, such as N-formyl peptide receptor 2 (FPR2). FPRs represent potentially important therapeutic targets for the treatment of some pathologies, including asthma and rheumatoid arthritis. Previously, we identified selective or mixed FPR agonists with a pyridazin-3(2H)-one scaffold, all containing a 4-bromophenylacetamide fragment at N-2. The most effective compounds in this series were EC3, a potent mixed FPR1/FPR2/FPR3 agonist, and EC10, which had a preference for FPR1. We report here a new series of pyridinone and pyrimidindione derivatives containing the 4-(bromophenyl)acetamide substituent that was essential for activity in the pyridazinone series. All new compounds were evaluated for FPR agonist activity in HL60 cells transfected with FPR1 or FPR2 and in human neutrophils. While most of the pyridinone derivatives had reasonable FPR agonist activity in the submicromolar/micromolar range, the pyrimidindione derivatives were less active. Compound 2a (N-(4-bromophenyl)-2-[3-cyano-5-(3-methoxyphenyl)-6-methyl-2-oxopyridin-1(2H)-yl]acetamide) was the most active pyridinone derivative and had a 10-fold preference for FPR2 (EC(50) = 120 nM) versus FPR1 (EC(50) = 1.6 μM). To assess their therapeutic activity, compounds 2a, EC3, and EC10 were evaluated in vivo using a rat model of rheumatoid arthritis. All three compounds increased the pain threshold and reduced pain hypersensitivity in the treated rats versus control rats, although 2a and EC10 were much more effective than EC3. Thus, these FPR agonists represent potential leads to develop for the treatment of inflammatory diseases such as rheumatoid arthritis.