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ID PMID Title PublicationDate abstract
35389481 Influence of Concomitant Methotrexate use on the Clinical Effectiveness, Retention, and Sa 2022 Apr 7 OBJECTIVES: We performed post-hoc analyses of ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naïve patients with rheumatoid arthritis. METHODS: Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. RESULTS: At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6) and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. CONCLUSION: The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.
35377443 The Impact of Disease Severity Measures on Survival in U.S. Veterans with Rheumatoid Arthr 2022 Apr 4 OBJECTIVES: To determine whether rheumatoid arthritis (RA) and interstitial lung disease (ILD) severity measures are associated with survival in patients with RA-ILD. METHODS: We studied U.S. veterans with RA-ILD participating in a multicentre, prospective RA cohort study. RA disease activity (28-joint disease activity score [DAS28-ESR]) and functional status (multidimensional health assessment questionnaire [MDHAQ]) were collected longitudinally while pulmonary function tests (forced vital capacity [FVC], diffusion capacity [DLCO]) were obtained from medical records. Vital status and cause of death were determined from the National Death Index and administrative data. Predictors of death were assessed using multivariable Cox regression models adjusting for age, sex, smoking status, ILD duration, comorbidity burden, and medications. RESULTS: We followed 227 RA-ILD participants (93% male and mean age of 69 years) over 1,073 person-years. Median survival after RA-ILD diagnosis was 8.5 years. Respiratory diseases (28%) were the leading cause of death, with ILD accounting for 58% of respiratory deaths. Time-varying DAS28-ESR (adjusted hazard ratio [aHR] 1.21 [1.03-1.41]) and MDHAQ (aHR 1.85 [1.29-2.65]) were separately associated with mortality independent of FVC and other confounders. Modeled together, the presence of either uncontrolled disease activity (moderate/high DAS28-ESR) or FVC impairment (<80% predicted) was significantly associated with mortality risk. Those with a combination of moderate/high disease activity and FVC <80% predicted had the highest risk of death (aHR 4.43 [95% CI 1.70-11.55]). CONCLUSION: Both RA and ILD disease severity measures are independent predictors of survival in RA-ILD. These findings demonstrate the prognostic value of monitoring the systemic features of RA-ILD.
35347662 Towards a Better Implementation of Treat-to-Target Strategy in Rheumatoid Arthritis: A Com 2022 Jun INTRODUCTION: Treat-to-target (T2T) strategy has been the core of rheumatoid arthritis (RA) management for over a decade, although it implementation has varied distinctly in real practices. We report here our investigation of the differences in disease activity and target achievement of two patient cohorts with different T2T implementations. METHODS: Data of the CENTRA (Collaboratively intENsive Treat-to-target in RA) and TARRA (Treat-to-TARget in RA) cohorts were used. The CENTRA cohort is a RA cohort prospectively followed up by a fixed team with tight control, while the TARRA is a longitudinal observational cohort followed up by a rheumatologist with casual control. Patients from the two cohorts were matched 1:3 by propensity score matching. The primary outcome was the Simplified Disease Activity Index (SDAI) at the 1-year follow-up. RESULTS: Included in this analysis were 102 patients from the CENTRA cohort and 271 patients from the TARRA cohort. Both groups were comparable in terms of age, gender, disease course, and seropositivity. At the end of the 1-year follow-up, the SDAI of patients in the CENTRA cohort was significantly lower than that of patients in the TARRA cohort (2.1 vs. 3.4; p < 0.001). A similar result was obtained based on the generalized estimating equation (GEE) model (p = 0.009). In addition, more patients in the CENTRA cohort achieved SDAI-defined remission compared to the TARRA cohort [72 (70.6%) vs. 134 (49.4%); p < 0.001]. CONCLUSION: Patients with RA may benefit more from a tight control T2T strategy with closer follow-up and appropriate education compared with those with a casual T2T strategy.
35464808 Comparison of the efficacy and risk of discontinuation between non-TNF-targeted treatment 2022 OBJECTIVES: Despite improved care for rheumatoid arthritis (RA) patients, many still experience treatment failure with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs [tsDMARDs; typically Janus kinase inhibitors (JAKi)], and eventually switch to other agents. We compared the efficacy of a second tumor necrosis factor inhibitor (TNFi) and non-TNF-targeted treatment as the second-line treatment in patients showing an insufficient response to the first TNFi. METHODS: Patients were included if they had received at least one prescription for a TNFi, and at least one follow-up prescription for a second TNFi or non-TNF-targeted treatment after discontinuation of the first drug. In total, 209 patients were analyzed, including 69 with a second TNFi and 140 with a non-TNF-targeted treatment (106 non-TNFi biologics and 34 JAKi). Cox regression was used to estimate the hazard ratio (HR) for discontinuation. RESULTS: The mean follow-up period after switching was 28.0 (range: 0-80) months and 24.4% of the 209 patients switched or discontinued the second drug. In multivariate Cox proportional hazard analysis, the non-TNF-targeted treatment group had a lower likelihood of discontinuing their treatment than the second TNFi group [HR = 0.326, 95% confidence interval (CI): 0.170-0.626, p = 0.001]. When analyzed separately, the risk of discontinuation was significantly lower in both the non-TNFi biologic (HR = 0.318, 95% CI: 0.160-0.633, p = 0.001) and JAKi (HR = 0.356, 95% CI: 0.129-0.980, p = 0.046) groups than in the second TNFi group. CONCLUSION: Our study supported switching to a non-TNF-targeted treatment instead of TNF cycling in patients with RA showing an inadequate response to initial TNFi.
35445720 Cost-Effectiveness Analyses of Biologic and Targeted Synthetic Disease-Modifying Anti-Rheu 2022 Apr 21 OBJECTIVE: To assess cost-effectiveness of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in rheumatoid arthritis. METHODS: We conducted 3 analyses: a lifetime analysis with a cohort model (study A) and 2 short-term analyses (studies B and C). Study A evaluated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained from costs of standard treatments. Study B evaluated yearly costs per person achieving American College of Rheumatology (ACR) response (ACR20, ACR50, and ACR70), and study C, costs per person achieving previously defined claims-based effectiveness (equivalent to 28-joint Disease Activity Score [DAS28] ≤ 3.2). The proportion of ACR responders to the drugs of interest were determined by mixed treatment comparisons. Studies B and C estimated costs using a claims database. RESULTS: In study A, ICERs of all b/tsDMARDs were lower than 5.0 million JPY per QALY. In study B, yearly costs per person with ACR50 response were lower for subcutaneous tocilizumab (1.9 million JPY) and subcutaneous abatacept (2.3 million JPY). In study C, costs per person were lower for subcutaneous tocilizumab (1.3 million JPY) and intravenous tocilizumab (1.6 million JPY) and effectiveness rates were higher for intravenous tocilizumab (45.3%) and infliximab (43.0%). CONCLUSION: The b/tsDMARDs with lower prices showed higher cost-effectiveness.
35640490 Critical appraisal and future outlook on anti-inflammatory biosimilar use in chronic immun 2022 May 7 Biosimilars represent a novel category in the world of follow-up medicinal products with the requirement that they are highly similar but not identical to an approved originator biologic medicine, with no clinically meaningful differences in safety, purity, and potency. In this review, we discuss recent pivotal biosimilar developments for anti-inflammatory therapy in rheumatology, gastroenterology, and dermatology, and the influence of biosimilar availability on patients and payers. Finally, we provide our perspective on the evolution of biosimilar use in these indications in the United States (US) and in Europe and on where this evolution in biopharmaceuticals may lead in the future. Although biosimilars are commonly used in the European Union (EU), there will be an inevitable sea change of acceptance by clinicians, patients, payers, and regulators in the US. It is paramount to educate about biosimilarity, highlighting currently available data gathered from other geographies, in addition to gradually providing clinicians and patients with the necessary experience with these agents ultimately restoring competition in the biologics landscape.
35190930 YWHAH Genetic Variants are Associated with Increased Hypoxia Inducible Factor-1α/Vascular 2022 Feb 21 The 14-3-3 Eta (14-3-3 η) biomarker platform is a relatively recent discovery with the potential to significantly address the diagnosis and prognosis of rheumatoid arthritis (RA) disease. Hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) have been implicated in inflammatory mechanisms in RA. We hypothesized a molecular association of the coding YWHAH gene and its expressed protein 14-3-3 η with hypoxia and angiogenesis in RA. One hundred healthy subjects and 100 RA patients were enrolled in the study. YWHAH gene expression was determined using quantitative PCR, and its gene polymorphism rs2858750 was assessed by Taqman genotyping assay. Serum levels of 14-3-3 η, HIF-1α, and VEGF were measured using the ELISA technique, and clinical parameters were routinely examined. In RA patients, significant positive correlations were found between 14-3-3 η, HIF-1α (r = 0.84), and VEGF (r = 0.85). YWHAH gene expression was upregulated 10.8 fold (CI 95% 10.1-11.5) in RA patients and significantly correlated with all disease activity parameters, ACPA, and levels of 14-3-3 η, HIF-1α, and VEGF. RA patients showed a higher frequency of YWHAH rs2858750 A allele than healthy subjects (p = 0.02). The risk A allele carriers showed higher disease activity parameters, ACPA, YWHAH gene expression, and increased serum levels of 14-3-3 η (p < 0.001), HIF-1α (p = 0.002), and VEGF (p = 0.001) than the G allele. Serum 14-3-3 η and its rs2858750 genetic variant are associated with increased hypoxia and angiogenesis in RA and activity, and severity of the disease.
35057057 Efficient Treatment of Rheumatoid Arthritis by Degradable LPCE Nano-Conjugate-Delivered p6 2022 Jan 11 Rheumatoid arthritis (RA) is one of the most common autoimmune diseases worldwide, causing severe cartilage damage and disability. Despite the recent progress made in RA treatment, limitations remain in achieving early and efficient therapeutic intervention. Advanced therapeutic strategies are in high demand, and siRNA-based therapeutic technology with a gene-silencing ability represents a new approach for RA treatment. In this study, we created a cationic delivery micelle consisting of low-molecular-weight (LMW) polyethylenimine (PEI)-cholesterol-polyethylene glycol (PEG) (LPCE) for small interfering RNA (siRNA)-based RA gene therapy. The carrier is based on LMW PEI and modified with cholesterol and PEG. With these two modifications, the LPCE micelle becomes multifunctional, and it efficiently delivered siRNA to macrophages with a high efficiency greater than 70%. The synthesized LPCE exhibits strong siRNA protection ability and high safety. By delivering nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 siRNA, the p65 siRNA/LPCE complex efficiently inhibited macrophage-based cytokine release in vitro. Local administration of the p65 siRNA/LPCE complex exhibited a fast and potent anti-inflammatory effect against RA in a mouse model. According to the results of this study, the functionalized LPCE micelle that we prepared has potential gene therapeutic implications for RA.
35456202 Risk of New-Onset Diabetes Mellitus Associated with Antirheumatic Drugs in Patients with R 2022 Apr 10 BACKGROUND: This study aimed to investigate the effect of disease-modifying antirheumatic drugs (DMARDs) on diabetes mellitus (DM) development in rheumatoid arthritis (RA). METHODS: This nested case-control study with a cohort of 69,779 DM-naïve adult patients with RA was conducted from 2011 to 2019 in South Korea. Cases with incident DM were identified and individually matched to randomly selected controls (1:4). DMARDs use was measured for 1 year before the index date and stratified by exposure duration. The association of each DMARD use with DM risk was estimated using conditional logistic regression adjusted for comorbidities and concomitant drug use. RESULTS: Of the patients, 5.4% were newly diagnosed with DM. The use of statins and a higher cumulative dose of corticosteroids were associated with an increased DM risk. In a multivariable-adjusted analysis, cumulative duration of exposure (CDE) >270 days/year, hydroxychloroquine (HCQ; adjusted odds ratio [aOR], 0.76) and methotrexate (MTX; aOR, 0.81) were associated with a significant decrease in DM risk, and tacrolimus (TAC; aOR, 1.27) was associated with an increased risk. CONCLUSIONS: Long-term use of HCQ and MTX (>270 days/year) was associated with a reduction in DM incidence as opposed to TAC.
35455757 Genetic and Clinical Factors Associated with Olokizumab Treatment in Russian Patients with 2022 Apr 15 Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease and its treatment is an urgent problem of rheumatology. Olokizumab (OKZ) is a new humanized monoclonal antibody targeting IL-6 and is one of the few promising drugs for RA therapy. One-hundred-and-twenty-five DNA samples from Russian patients with RA, treated with olokizumab, were genotyped with an NGS panel containing 60 single nucleotide polymorphisms (SNPs) and the whole coding sequences of IL6, IL6R, TNFRSF1A, CTLA4, IL10, IL23R, and PADI4; and by RT-PCR for HLA-DRB1 and HLA-B. Associations of polymorphic variants with olokizumab efficacy according to the scores ACR20, ACR50, and DAS28-CRP were determined. We analyzed the obtained data by using logistic regression, ROC curves, and multivariate ANOVA. A high predictive value of the response to olokizumab therapy at 24 weeks was found for the combination of HLA-DRB1*04 and HLA-B*27 alleles with SNPs located in non-HLA genes (IL1B, IL17A, PADI4, DHODH, GLCCI1, IL23R, and TNFAIP3), and clinical characteristics (age, RA duration, and intensity) according to ACR20. Thus, the comprehensive assessment of polymorphic variants of HLA and non-HLA genes considering population characteristics in combination with clinical parameters allows for the elaboration of an RA prognostic panel.
35445929 Peripheral distributions of IL-4-producing CD4 + T cells and CD4 + CD25 + FoxP 2022 Apr 21 Specific profiling of CD4 + T cell subsets in the circulation and inflamed joints of rheumatoid arthritis (RA) patients may have therapeutic implications. This study aimed to evaluate the peripheral distributions of Th2 and Treg cells in relation to HLA-shared epitope (SE) alleles and anti-cyclic citrullinated peptide antibody (ACPAs) status in patients with good response (GR) and poor response (PR) to treatment. The frequencies of IL-4-producing CD4 + T cells (Th2) and CD4 + CD25 + Foxp3 + T cells (Tregs) were determined by flow cytometry in 167 RA patients including 114 GR and 53 PR cases. CD4 + T cell subsets were also analyzed based on HLA-SE and ACPAs statuses. One hundred nine of 167 patients were positives for HLA-SE, 63.4% for ACPAs, 43.7% for SE/ACPAs and 14.9% were negatives for SE/ACPAs. Higher frequencies of Th2 (P = 0.001) and Treg cells (P = 0.03) were found in the patients versus controls. Increased and decreased frequencies of Th2 and Tregs cells were observed in the PR versus GR patients respectively (P = 0.003 and P = 0.004). Higher proportions of Th2 cells were observed in the SE(+)RA versus SE(-)RA (P = 0.001), in ACPA(+)RA versus ACPA(-)RA (P = 0.005) and in the SE(+)ACPA(+)RA versus SE(-)ACPA(-)RA patients (P = 0.002). Treg cells frequencies decreased in the SE(+)RA versus SE(-)RA (P = 0.03) and in SE(+)ACPA(+)RA versus SE(-)ACPA(-)RA (P = 0.02). ACPA(+)GR and SE(+)PR patients showed higher proportions of Th2 cells than ACPA(-)GR and SE(-)PR patients respectively (P = 0.02 and P = 0.01). Analysis of the CD4 + T cell subsets profiles in conjunction with genetic background and autoantibodies patterns can be useful for precise therapeutic response monitoring in the RA patients.
35382894 Health-related quality of life and treatment satisfaction in Palestinians with rheumatoid 2022 Apr 6 BACKGROUND: Studying health-related quality of life (HRQoL) and treatment satisfaction have helped in understanding how to optimize rheumatoid arthritis (RA) treatment outcomes and find ways to alleviate signs and symptoms among patients. OBJECTIVE: In this study, our objective was to evaluate the association between satisfaction with care and HRQoL among RA patients from northern Palestine. In addition, this study also aimed to determine the associations between the clinical characteristics of patients with RA with treatment satisfaction and HRQoL. METHODS: This was a multicenter cross-sectional study conducted between July and October 2018. Patients with RA diagnosis who presented at rheumatology clinics were interviewed. The SF-36 short questionnaire was used to assess HRQoL and Treatment Satisfaction Questionnaire for Medication (TSQM) version 1.4 to assess treatment satisfaction among study groups. We use descriptive and comparative statistics to present the results. RESULTS: A total of 283 patients were included. Several sociodemographic and clinical characteristics were found to be associated with poor HRQoL scores and low treatment satisfaction. The physical component summary (PCS) was negatively associated with age, patients' self-reported disease activity, duration of the disease, and the total number of medications taken by the patient, and was positively associated with educational background, employment, and household income. The mental component summary (MCS) was negatively associated with patients' self-reported disease activity and the patient's total number of comorbid diseases. The number of comorbid diseases was negatively associated with effectiveness. All HRQoL subscales were significantly correlated with treatment satisfaction. The range of correlation with PCS was between 0.272 for convenience and 0.425 for side effects (p < 0.001). Similarly, the highest correlation with MCS was 0.458 for side effects, and the lowest was 0.337 for convenience (p < 0.001). CONCLUSIONS: The current study found that HRQoL was significantly correlated with treatment satisfaction. Furthermore, the results of this study showed that HRQoL and treatment satisfaction are likely to be affected by sociodemographic and clinical characteristics. These results may be beneficial in clinical practice, mainly in the early treatment of patients with RA, at a stage where it is still possible to increase treatment satisfaction.
35281960 Prevalence of depressive symptoms in patients with rheumatoid arthritis at a regional hosp 2022 BACKGROUND: Depression affects 14.8% - 38.8% of patients with rheumatoid arthritis (RA) in developed countries. The prevalence and risk factors for depression in patients with RA in sub-Saharan Africa is not well established. AIM: To determine the prevalence of depressive symptoms in patients with RA. SETTING: Public sector regional hospital in South Africa. METHODS: A cross-sectional descriptive study was undertaken with 110 adult RA patients. A structured socio-demographic and clinical questionnaire, the modified health assessment questionnaire (mHAQ), the simplified disease activity index (SDAI) for RA, the patient health questionnaire (PHQ-9), and the Household Food Insecurity Access scale (HFIAS) for nutritional status, were used. Correlates of depressive symptomatology in participants with RA were identified using t-tests and regression analyses. RESULTS: Most of the participants were women (90.9%), 67% had moderate to severe RA disease on the SDAI score, 92.7% reported functional disability (HAQ score of ≥ 1), and 87.2% reported mild to severe depressive symptoms. Unemployment (p < 0.01), severe food insecurity (p < 0.01) and functional disability (p = 0.02), were significantly associated with the depressive symptoms, but not with disease activity (p = 0.8) or inflammatory markers (p = 0.63). Unemployment (adjusted β = -5.07, p < 0.01) and severe food insecurity (adjusted β = -4.47, p < 0.01) were significantly associated with depressive symptoms, based on the adjusted regression model. CONCLUSION: As RA effects functional status, with the impact of the resulting unemployment and food insecurity being associated with depression, affected people should be screened for depression and managed using a multidisciplinary approach, especially considering the role of social determinants in RA patients with depression.
35184268 Post Hoc Analysis of Predictors of Clinical Response to Repository Corticotropin Injection 2022 Apr INTRODUCTION: A phase IV clinical trial confirmed the safety and efficacy of repository corticotropin injection (RCI, Acthar(®) Gel) in patients with refractory rheumatoid arthritis (RA) that was nonresponsive to standard-of-care therapies. The objective of this post hoc analysis was to identify baseline demographics and clinical characteristics that may be predictors of response to RCI. METHODS: The phase IV trial was a two-part, randomized, placebo-controlled withdrawal study. Post hoc analysis was conducted with the open-label portion of the trial data, in which all 258 subjects received RCI (80 U) twice weekly for 12 weeks. Responders were subjects who achieved low disease activity (LDA) by a Disease Activity Score with 28-joint count and erythrocyte sedimentation rate (DAS28-ESR) of < 3.2 at week 12. Responders were compared with nonresponders by assessing the proportion of subjects in each group for demographics and clinical characteristics, including weight, disease duration, medical history including osteoarthritis and unrelated joint conditions, hemoglobin A1c, C-reactive protein, ESR, DAS28-ESR, Clinical Disease Activity Index (CDAI), depression, anxiety, tender joint count (TJC), and swollen joint count (SJC). Bivariate analysis followed by multiple logistic regression analysis were conducted to identify significant baseline predictors for the outcome of achieving LDA by week 12. RESULTS: Bivariate analysis showed that RCI responders had significantly lower baseline TJC (p = 0.0310), SJC (p = 0.0018), ESR (p = 0.0487), and CDAI (p = 0.0112) and shorter RA disease duration (p = 0.0446). Subjects were less likely to achieve LDA if they had osteoarthritis (p < 0.0001), other joint-related conditions unrelated to RA (p < 0.0001), anemia (p = 0.0132), depression (p = 0.0006), or prior or concomitant use of targeted-synthetic or biologic disease-modifying antirheumatic drugs (p < 0.0001). Multiple logistic regression analysis revealed that, of the above, only ongoing osteoarthritis (p = 0.0272) or other joint-related conditions (p = 0.0193) were significant negative predictors of RCI response. CONCLUSIONS: These results identify specific patient characteristics that may be considered predictors of positive or negative clinical response to RCI.
35179510 A Serious Puzzle Game to Enhance Adherence to Antirheumatic Drugs in Patients With Rheumat 2022 Feb 18 BACKGROUND: Patients' implicit attitudes toward medication need and concerns may influence their adherence. Targeting these implicit attitudes by combining game-entertainment with medication-related triggers might improve medication adherence in patients with rheumatoid arthritis (RA). OBJECTIVE: The aim of this study was to describe the systematic development of a serious game to enhance adherence to antirheumatic drugs by using intervention mapping. METHODS: A serious game was developed using the intervention mapping framework guided by a multidisciplinary expert group, which proceeded along 6 steps: (1) exploring the problem by assessing the relationship between medication adherence and implicit attitudes, (2) defining change objectives, (3) selecting evidence-based behavior change techniques that focused on adjusting implicit attitudes, (4) designing the intervention, (5) guaranteeing implementation by focusing on intrinsic motivation, and (6) planning a scientific evaluation. RESULTS: Based on the problem assessment and guided by the Dual-Attitude Model, implicit negative and illness-related attitudes of patients with RA were defined as the main target for the intervention. Consequently, the change objective was "after the intervention, participants have a more positive attitude toward antirheumatic drugs." Attention bias modification, evaluative conditioning, and goal priming were the techniques chosen to implicitly target medication needs. These techniques were redesigned into medication-related triggers and built in the serious puzzle game. Thirty-seven patients with RA tested the game at several stages. Intrinsic motivation was led by the self-determination theory and addressed the 3 needs, that is, competence, autonomy, and relatedness. The intervention will be evaluated in a randomized clinical trial that assesses the effect of playing the serious game on antirheumatic drug adherence. CONCLUSIONS: We systematically developed a serious game app to enhance adherence to antirheumatic drugs among patients with RA by using the intervention mapping framework. This paper could serve as a guideline for other health care providers when developing similar interventions.
35645414 Could IL-1β, IL-6, IFN-γ, and sP-selectin serum levels be considered as objective and qu 2022 OBJECTIVES: Rheumatoid arthritis (RA) is a multisystem, chronic, T-cell-mediated disease in which immunological abnormalities result in symmetrical small joint inflammation, articular destruction due to synovitis, and extra-articular organ involvement. An important role in the pathogenesis of RA is attributed to a combination of genetic factors and environmental triggers. Literature data on the utility of circulating IL-1β, IL-6, IFN-γ, and sP-selectin concentration evaluation depending on the activity and advancement of RA seems to be inconclusive. The aim was a case-control study evaluating IL-1β, IL-6, IFN-γ, and sP-selectin concentrations in 77 RA patients dependent on the Steinbrocker classification as well as the disease activity score with examination of 28 joints (DAS28), and compared to 30 control subjects. MATERIAL AND METHODS: Serum IL-1β, IL-6, IFN-γ, and sP-selectin concentrations were measured using ELISA kits. RESULTS: The concentrations of all molecules tested, except for IL-1β, were significantly different from the control group. Univariate logistic regression analysis indicated that their levels significantly influenced the likelihood of RA diagnosis. Differences between IL-1β, IL-6, IFN-γ, and sP-selectin concentrations dependent on the disease activity assessed on the basis of the DAS28 score, as well as the severity of the disease assessed based on the Steinbrocker classification, were not observed. IL-6 positively correlated with the DAS28 score. CONCLUSIONS: Among the tested molecules, only IL-6 positively correlated with the DAS28 score. Thus, we postulate that next to C-reactive protein and the erythrocyte sedimentation rate, also IL-6 could be clinically relevant and possibly reflects RA activity. Because recently the IL-6 concentration can be determined in applied in vitro diagnostic tests, it presents us with the possibility to test this protein as a marker of RA activity in routine laboratory practice.
35493315 Anti-rheumatoid activity of a hexane-insoluble fraction from Plantago major in female Wist 2022 May BACKGROUND AND AIM: Plantago major has long been used for medical purposes in Indonesia. However, reports on the anti-arthritic activities of P. major are limited. EXPERIMENTAL PROCEDURE: The anti-arthritic properties of an n-hexane-insoluble fraction of dichloromethane extracts of P. major (IPM) were evaluated using Complete Freund's Adjuvant (CFA)-induced arthritis induced in female Wistar rat by CFA. Diclofenac was used as a positive control. The volume of paw oedema, white blood cell count, lymphocytes, neutrophils, expression of TNF-α and Interleukin-6 and the histopathological features of the joint tissues were assessed to characterise IPM activity. RESULTS: The IPM extract at doses of 280 and 420 mg/kg BW and diclofenac inhibited paw oedema by 15.70 %, 15.94 % and 19.71 % respectively. IPM also reduced the incidence of arthritis and arthritic index. Unlike untreated rats, animals treated with IPM showed a significant decrease in the number of neutrophils and decreased expression of TNF-α and Interleukin-6. Histopathological examination showed a reduction in the number of inflammatory cells and hyperplasia of the synovium after IPM treatment. CONCLUSION: This study showed that P. major displays anti-rheumatoid arthritis activity.
29494032 Tumor Necrosis Factor Inhibitors. 2022 Jan Tumor necrosis factor (TNF)-alpha inhibitors, including etanercept (E), infliximab (I), adalimumab (A), certolizumab pegol (C), and golimumab (G), are biologic agents which are FDA-approved to treat ankylosing spondylitis (E, I, A, C, and G), Crohn disease (I, A and C), hidradenitis suppurativa (A), juvenile idiopathic arthritis (A), plaque psoriasis (E, I and A), polyarticular juvenile idiopathic arthritis (E), psoriatic arthritis (E, I, A, C, and G), rheumatoid arthritis (E, I, A, C, and G), ulcerative colitis (I, A and G), and uveitis (A). There are also several off-label indications. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, toxicity, and monitoring, of tumor necrosis factors, so providers can direct patient therapy where they are indicated as part of the interprofessional team.
34881869 In Situ Synthesis of Natural Antioxidase Mimics for Catalytic Anti-Inflammatory Treatments 2022 Jan 12 Mimicking the coordination geometry of the active metal sites of natural enzymes is an efficient strategy in designing therapeutic chemicals with enzymelike in vivo reaction thermodynamics and kinetics. In this study, this chemical concept has been applied for the in situ synthesis of natural antioxidase mimics for catalytic anti-inflammatory treatment by using rheumatoid arthritis, a common and hardly curable immune-mediated diseases, as an example. Briefly, a composite nanomedicine has been first constructed by loading cationic porphyrin ligands into a manganese-engineered mesoporous silica nanocarrier, which can respond to a mildly acidic environment to concurrently release manganous ions and porphyrin ligands, enabling their subsequent coordination and synthesis of manganese porphyrin with a coordination environment of an active Mn site similar to those of the metal sites in natural superoxide dismutase (SOD) and catalase. Due to the strong metal-ligand exchange coupling enabled by the N-ethylpyridinium-2-yl groups tetrasubstituted in the meso positions of N(4)-macroheterocycles, such a manganese porphyrin presents the SOD-like activity of disproportionating superoxide anions via outer-sphere proton-coupled one-electron transfer (diaquamanganese(III)/monoaquamanganese(II) cycling), as well as the catalase-like activity of disproportionating hydrogen peroxide via inner-sphere proton-coupled two-electron transfer (diaquamanganese(III)/dioxomanganese(V) cycling). Cellular experiments demonstrated the high antioxidative efficacy of the composite nanomedicine in M1 macrophages by promoting their polarization shift to the anti-inflammatory M2 phenotype. Equally importantly, the silicon-containing oligomers released from the manganese silicate nanocarrier can act as heterogeneous nucleation centers of hydroxyapatite for facilitating biomineralization by bone mesenchymal stem cells. Finally, an in vivo adjuvant-induced arthritis animal model further reveals the high efficacy of the nanomedicine in treating rheumatoid arthritis.
35116046 Case Report: A Rare Case of Elderly-Onset Adult-Onset Still's Disease in a Patient With Sy 2022 The rare systemic inflammatory disorder 'adult-onset Still's disease (AOSD)' is characterized by recurrent fever, evanescent rash, arthralgia, and leukocytosis with neutrophilia. The Yamaguchi criteria are widely used to diagnose AOSD; these criteria can be used for diagnosis after a wide range of infectious, rheumatic, and neoplastic diseases have been excluded. AOSD generally does not overlap with other rheumatic diseases. We present the rare case of an 80-year-old Japanese woman who presented with arthralgia, fever, and skin rash during treatment for systemic lupus erythematosus (SLE), which was finally diagnosed as an overlap of AOSD. Blood tests revealed leukocytosis with neutrophilia, high C-reactive protein (CRP), and liver dysfunction. Her anti-ds-DNA antibody titer and serum complement titer were at the same level as before and remained stable. We suspected AOSD based on the high serum ferritin level but hesitated to diagnose AOSD because of the patient's SLE history. We measured serum interleukin (IL)-18; it was extremely high at 161,221 pg/mL, which was strongly suggestive of AOSD. We thus diagnosed AOSD complicated during the course of treatment for SLE. The patient's arthralgia and high CRP level persisted after we increased her oral prednisolone dose and added oral methotrexate, but her symptoms eventually improved with the addition of intravenous tocilizumab. We note that the presence of autoantibodies or other rheumatic diseases cannot be absolutely ruled out in the diagnosis of AOSD. Although high serum IL-18 levels are not specific for AOSD, the measurement of serum IL-18 may aid in the diagnosis of AOSD in similar rare cases.