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ID PMID Title PublicationDate abstract
34894239 Drug efficacy and safety of biologics and Janus kinase inhibitors in elderly patients with 2022 Feb 28 Elderly patients with rheumatoid arthritis (RA) are frequently associated with higher disease activity and impaired physical function, although they show intolerance for conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate, because of their comorbidities. However, the present treatment recommendation based on randomized controlled trials is not distinguished by age or comorbidities. Therefore, this review aimed to investigate the efficacy and safety of biological DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) in elderly patients. Present bDMARDs, including tumor necrosis factor inhibitors (TNFi), cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (abatacept), interleukin (IL)-6 receptor antibody (tocilizumab and salirumab), and anti-CD20 antibody (rituximab), may be similarly or slightly less effective or safe in elderly patients compared with younger patients. Oral glucocorticoid use, prolonged disease duration, and very old patients appear to be associated with an increased risk of adverse events, such as serious infection. Some recent cohort studies demonstrated that non-TNFi showed better retention than TNFi in elderly patients. Both TNFi and non-TNFi agents may not strongly influence the risk of adverse events such as cardiovascular events and malignancy in elderly patients. Regarding JAKi, the efficacy appears to be similar, although the safety (particularly for serious infections, including herpes zoster) may be attenuated by aging.
35168456 Affecting the effectors: JAK inhibitors modulation of immune cell numbers and functions in 2022 Mar INTRODUCTION: The Janus kinase family includes four members - JAK1, JAK2, JAK3, TYK2 - that are selectively associated with type I and II cytokine receptors. Jak-inhibitors (Jakinibs) are a new class of drugs for treating inflammatory diseases. Five Jakinibs are currently available for Rheumatoid Arthritis (RA): tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib. Considering the role of cytokines and growth factors in immune cell survival and activation, the anti-proliferative and suppressive effects of Jakinibs on these cells are predictable. AREAS COVERED: This review summarizes Jakinibs' effects on immune populations in vitro and in vivo. In vitro, Jakinibs affected T and B lymphocytes, monocytes, neutrophils and dendritic cell proliferation. T helper, B cell differentiation, and cytokine secretion . Accordingly, changes in the number of lymphocytes, natural killer (NK) cells, and neutrophils have been reported during the randomized clinical trials with all the Jakinibs, reverting after drug withdrawal. EXPERT OPINION: In vitro and in vivo studies showed that the numbers and the function of immune cells are influenced by Jakinibs. Nonetheless, their effects do not seem to represent a major safety issue as these changes do not correlate with the onset of serious infection despite the increased rates of herpes zoster reactivation.
33740386 Filgotinib, a novel JAK1-preferential inhibitor for the treatment of rheumatoid arthritis: 2022 Jan 5 In the treatment of rheumatoid arthritis (RA), Janus kinase inhibitors (jakinibs) represent an emerging class of targeted therapies in addition to biologics. The number of jakinibs has been growing and as of 2020, filgotinib was the latest jakinib to enter the international market for treating RA. Filgotinib has demonstrated preferential inhibition of JAK1-dependent cytokine signaling in in vitro assays. It has been evaluated in the DARWIN (phase 2) and FINCH (phase 3) series of clinical studies for treating patients with moderately-to-severely active RA. Filgotinib received regulatory approval in Japan and Europe in September 2020, while in August 2020 the United States Food and Drug Administration requested additional data from two ongoing clinical studies assessing the potential impact of filgotinib on sperm parameters. This article will review the pharmacological properties, efficacy, and safety of filgotinib as demonstrated in clinical studies. Expert opinion will be provided on jakinibs for RA treatment from the viewpoints of basic research and clinical practice.
34404254 Exercise therapy for sarcopenia in rheumatoid arthritis: A meta-analysis and meta-regressi 2022 Feb OBJECTIVE: Rheumatoid arthritis and age are associated with high sarcopenia risk. Exercise is an effective treatment for preventing muscle mass loss in older adult populations. It remains unclear whether exercise affects muscle mass in people with rheumatoid arthritis. Thus, this meta-analysis investigated the effect of exercise on muscle mass gain in patients with rheumatoid arthritis. DATA SOURCES: PubMed, EMBASE, the Cochrane Library, the Physiotherapy Evidence Database (PEDro), the China Knowledge Resource Integrated Database, and Google Scholar were systematically searched until June 2021. METHODS: The present study was conducted according to the guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Randomized controlled trials (RCTs) that reported the effects of exercise on muscle mass for rheumatoid arthritis were identified. The included RCTs were subject to meta-analysis and risk of bias assessment. Subgroup and random-effects meta-regression analyses were performed to identify any heterogeneity (I(2)) of treatment effects across studies. RESULTS: We included nine RCTs with a median PEDro score of 6/10 (range: 4/10-8/10). The weighted mean effect size for muscle mass was 0.77 (95% CI: 0.30-1.24; P = 0.001; I(2) = 77%). Meta-regression analyses indicated that the disease duration significantly explained variance of treatment effects across studies (β = -0.006, R(2) = 69.7%, P = 0.005). CONCLUSIONS: Exercise therapy effectively increased muscle mass in patients with rheumatoid arthritis. Treatment effects may be attenuated in those who have had rheumatoid arthritis for a relatively long time.
35112192 Rheumatoid arthritis-related interstitial lung disease (RA-ILD): a possible association be 2022 Jun OBJECTIVES: We hypothesized that RA disease activity might be associated with the survival of RA-ILD patients. To evaluate this possibility, we analyzed data on disease activity during follow-up in an RA-ILD cohort and compared disease activity between surviving patients and those who died during follow-up. METHODS: RA-ILD patients referred for medical evaluation and treatment at a single center, with CDAI scores during all follow up were included. We estimated the HR of the mean of the CDAI score during follow-up with survival. Also, we compared the survival function of patients with high disease activity (CDAI scores ≥ 22) during all follow-up with those with moderate and low disease activity. RESULTS: Thirty-seven patients were included. The mean of the CDAI score during follow-up was higher in death patients (median 30.8 ± 18.5 Vs. 16.8 ± 11.3), and a single unit increase in the mean of the CDAI score was associated with non-survival, HR:1.07 (95% CI: 1.02 -1.12). Patients with high disease activity during all follow-up (CDAI scores > 22) had lower survival function in comparison with moderate and low disease activity (P = 0.042). CONCLUSION: The results of the study suggest that higher RA disease activity is associated with a worse prognosis of RA-ILD patients. The hypothesis that high disease activity is associated with worse survival in RA-ILD patients must be evaluated in more extensive cohort studies and clinical trials. KEY POINTS: • RA-ILD patients with high disease activity during follow-up had a worse prognosis than those with moderate or low disease activity. • The study results suggest the hypothesis that patients with RA-ILD must be treated with a treat to target strategy, with the aim of remission or low RA disease activity.
35029907 Consensus recommendations on managing the selected comorbidities including cardiovascular 2022 Jan 7 BACKGROUND: Rheumatoid arthritis (RA)-related comorbidities, including cardiovascular disease (CVD), osteoporosis (OP), and interstitial lung disease (ILD), are sub-optimally managed. RA-related comorbidities affect disease control and lead to impairment in quality of life. We aimed to develop consensus recommendations for managing RA-related comorbidities. METHODS: The consensus statements were formulated based on emerging evidence during a face-to-face meeting of Taiwan rheumatology experts and modified through three-round Delphi exercises. The quality of evidence and strength of recommendation of each statement were graded after a literature review, followed by voting for agreement. Through a review of English-language literature, we focused on the existing evidence of management of RA-related comorbidities. RESULTS: Based on experts' consensus, eleven recommendations were developed. CVD risk should be assessed in patients at RA diagnosis, once every 5 years, and at changes in DMARDs therapy. Considering the detrimental effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids on CVD risks, we recommend using the lowest possible dose of corticosteroids and prescribing NSAIDs cautiously. The OP/fragility fracture risk assessment includes dual-energy X-ray absorptiometry and fracture risk assessment (FRAX) in RA. The FRAX-based approach with intervention threshold is a useful strategy for managing OP. RA-ILD assessment includes risk factors, pulmonary function tests, HRCT imaging and a multidisciplinary decision approach to determine RA-ILD severity. A treat-to-target strategy would limit RA-related comorbidities. CONCLUSIONS: These consensus statements emphasize that adequate control of disease activity and the risk factors are needed for managing RA-related comorbidities, and may provide useful recommendations for rheumatologists on managing RA-related comorbidities.
34601110 How to taper glucocorticoids in inflammatory rheumatic diseases? A narrative review of nov 2022 Jan Glucocorticoids (GCs) remain regularly used drugs in patients with chronic inflammatory rheumatic diseases. As long-term intake at high dosages is associated with harm, it is generally advised that GCs be tapered and stopped. However, most recommendations concerning tapering have been eminence- or consensus-based. In this narrative review, we present novel data from recent studies (SEMIRA, CORTICOLUP, and GiACTA) shedding light from different angles on the effects of tapering GCs in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and giant cell arteritis (GCA). In RA and SLE, our main findings comprise that (a) the majority of RA and SLE patients can successfully taper their GC, but that (b) tapering increases the risk of flare. In GCA, tocilizumab was shown to be a potent GC-sparing agent. Finally, we also present exemplary tapering schemes for RA, SLE, and GCA, although different tapering regimens have not yet been sufficiently compared in randomized trials.
35366946 High prevalence of rheumatoid arthritis and its risk factors among Tibetan highlanders liv 2022 Apr 2 BACKGROUND: In Tsarang (at 3560 m), which is located in Mustang, 62.7% of the residents answered that they had a subjective medical history of arthritis, and 41.1% of the residents answered that their families had a subjective medical history of arthritis on a survey conducted in 2017. The expression of hypoxia-inducible factor (HIF) and its effects are deeply involved in hypoxic adaptation in Tibetan highlanders. At the same time, HIF is also related to the onset of rheumatoid arthritis. Therefore, the adaptive mechanism acquired by Tibetan highlanders may promote the development of rheumatoid arthritis. The prevalence of rheumatoid arthritis is estimated to be approximately 0.5-1.0% worldwide. The objective of this study was to estimate the prevalence of rheumatoid arthritis in Tsarang residents using existing diagnostic criteria and to explore its risk factors. METHODS: An epidemiological survey was conducted in Tsarang in 2019. Data obtained from anthropometry and questionnaires were statistically analyzed. Biochemical measurements using blood samples were also performed, and the results were used to assess arthritis status. Residents' joint status was scored, and arthritis was assessed based on the clinical disease activity index and ACR/EULAR 2010 criteria. RESULTS: Twenty-seven males and 50 females participated in this survey. In Tsarang, ACR/EULAR 2010 classified 4.3% of males and 7.1% of females as having rheumatoid arthritis, indicating a very high estimated prevalence. We also performed a multivariate analysis to explore its risk factors, and two factors, older age (standardized parameter estimate = 4.84E-01, 95% CI = [9.19E-02, 8.76E-01], p = 0.0170) and a history of living in urban areas (standardized parameter estimate = - 5.49E-01, 95% CI = [- 9.21E-01, 1.77E-01], p = 0.0050), significantly contributed to the higher ACR/EULAR 2010 score in females. In addition, three factors, having no spouse (standardized parameter estimate = 3.17E-01, 95% CI = [5.74E-02, 5.77E-01], p = 0.0179), having a smoking habit (standardized parameter estimate = 2.88E-01, 95% CI = [1.71E-02, 5.59E-01], p = 0.0377), and a history of living in urban areas (standardized parameter estimate = - 3.69E-01, 95% CI = [- 6.83E-01, - 5.60E-02], p = 0.0219), resulted in significantly higher clinical disease activity index scores in females. Furthermore, smoking habits were found to significantly increase blood hyaluronic acid in both males (standardized parameter estimate = 6.03E-01, 95% CI = [3.06E-01, 9.01E-01], p = 0.0020) and females (standardized parameter estimate = 4.87E-01, 95% CI = [5.63E-02, 9.18E-01], p = 0.0291). CONCLUSIONS: In this study, we evaluated the symptoms of arthritis and estimated the prevalence of rheumatoid arthritis using classification criteria for Tibetan highlanders who have adapted to the hypoxic environment and fostered their own culture. The high prevalence of rheumatoid arthritis among Tsarang residents suggests that the hypoxic adaptation mechanism involving HIF in Tibetan highlanders may promote the onset or exacerbation of rheumatoid arthritis. The high prevalence of rheumatoid arthritis among Tibetan highlanders may be related not only to the environmental factors analyzed in this study but also to hypoxic adaptation genes. Further investigation is needed to clarify the genetic factors involved.
34454117 Systematic review and meta-analysis of cardiovascular risk in rheumatological disease: Sym 2022 Jan Although each autoimmune disease is associated with specific tissue or organ damage, rheumatic diseases share a pro-inflammatory pattern that might increase cardiovascular risk. Retrospective and prospective studies on patients affected by systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) highlighted the concept of "accelerated atherosclerosis". Therefore, the purpose of this systematic review and meta-analysis is the assessment of symptomatic or asymptomatic cardiovascular events among patients with rheumatic diseases as RA and SLE. The literature research obtained all manuscripts published in the English language between 2015 and 2019 for a total of 2355 manuscripts. After selection through inclusion and exclusion criteria, four articles examined cardiovascular risk in RA patients, 8 in SLE patients, and 2 in RA and SLE patients. Patients with SLE had a RR of 1.98 (95% CI: 1.18-3.31) of symptomatic cardiovascular events compared to the unexposed cohort. The meta-regression analysis showed that younger patient (age per year increase β = -0.12 95%CI: -0.20, -0.4), belonging to studies conducted in continent different from America (β = -0.89; -95% CI: 1.67, -0.10), after 2000 (β = 0.87; 95% CI: 0.09, 1.65) and with a higher quality score 0.80 (95% CI: 0.31, 1.29) had a higher risk of cardiovascular events. In patients with RA, the RR of cardiovascular events was 1.55 (95% CI: 1.18-2.02). These data are helpful to implement cardiovascular preventive strategies among people suffering from rheumatologic diseases to decrease the incidence of cardiovascular events. However, these implementation needs to build a higher network between rheumatologists and primary care healthcare workers to furnish the same information to patients and monitor their preventive practice compliance.
35535405 Janus kinase versus TNF inhibitors: where we stand today in rheumatoid arthritis. 2022 May INTRODUCTION: In recent decades, Rheumatoid arthritis (RA) treatment landscape has evolved with the induction of new biological and targeted therapies that provide significant therapeutic benefits in patients with sustained disease. AREAS COVERED: Tumor necrosis factor inhibitors (TNFi) were the first biologics used in the treatment of RA. Although they present a significant efficacy, an insufficient response of some patients led to further research and discovery of targeted therapies, such as Janus kinase inhibitors (JAKi), which act at a molecular level, regulating many cytokines. Clinical benefits have been seen with both TNFi and JAKi as monotherapy and combined with conventional synthetic disease-modifying antirheumatic drugs. Still, some significant side effects have been reported with JAKi, and several questions remain about their safety and selectivity in action. This review summarizes the current knowledge on the mechanism of action, the clinical efficacy, and safety of TNFi vs. JAKi. EXPERT OPINION: TNFi and JAKi are particularly useful in treating inflammatory arthropathies. Both drug categories are recommended by ACR and EULAR institutions in RA patients suffering from moderate to severe disease. Safety data in long-term studies are required to determine the optimal benefit to the risk profile of JAKi use.
34937466 Tailored first-line biologic and targeted synthetic disease modifying anti-rheumatic drugs 2022 May INTRODUCTION: In 2015, the Italian board for the TAilored BIOlogic therapy (ITABIO) proposed evidence-based decisional statements for first-line tailored biologic therapy in patients with rheumatoid arthritis (RA). Taking into account the new licensed drugs, the aim of the present review was to update the previous statements. AREAS COVERED: A narrative review of the most recent evidence on the efficacy and safety of old and newly licensed drugs for the treatment of articular and extra-articular RA was performed. In addition, host-related variables potentially driving the therapy choice, such as the infection risk, the cardiovascular risk, the risk of deep vein thrombosis, thromboembolism, pregnancy, and obesity were analyzed. Consequently, several statements for personalized therapy were formulated, thus providing a decisional algorithm useful for proper personalized therapy of RA patients in clinical practice. EXPERT OPINION: Several clinical variables related to specific drug and host characteristics may drive the choice toward anti-TNF and non-anti-TNF biologics, or anti-JAKs, thus allowing to personalize the therapy. Consequently, the right therapy for the right patient would ensure a successful therapeutic intervention.
33635230 Improving rheumatoid arthritis management within the Spanish National Health System: a soc 2022 Jan OBJECTIVES: To define a set of proposals that would improve the current management of patients with rheumatoid arthritis (RA) within the Spanish National Health System (SNHS), and to estimate the impact of their implementation from a social perspective. METHODS: A one-year forecast-type Social Return on Investment (SROI) analysis was performed on the basis of information collected from a scientific literature review, official data, and multiple stakeholders regarding RA. A sub-analysis was performed within the areas of diagnosis, early RA (<2 years from diagnosis), and established RA (≥2 years from diagnosis). RESULTS: Stakeholders agreed on a set of 22 proposals, which included incorporating specialised nursing, addressing adherence issues, providing psychological support, or promoting the role of patient associations, among others. Their implementation would require an investment of 289 million euros and yield a social return of 913 million euros, i.e. a social return of 3.16 euros per euro invested (2.92 euros in the worst-case scenario and 3.40 euros in the best-case scenario). The greatest social return relative to investment and the greatest attributed to intangible aspects were observed within the area of early RA. CONCLUSIONS: Evidence-based recommendations for the management of RA are aspirational. Nevertheless, the present study estimated that the implementation of the set of proposals would result in a positive impact relative to the investment needed to implement them. The results may guide management decisions to reduce the burden associated with RA, and help bridge the gap between evidence-based recommendations and routine clinical practice.
34874262 The Diagnosis and Treatment of Rheumatoid and Juvenile Idiopathic Arthritis of the Temporo 2022 Jan 28 BACKGROUND: Involvement of the temporomandibular joint can be shown in 40-90% of patients with rheumatoid arthritis and juvenile idiopathic arthritis (JIA), although it is often asymptomatic. Restricted jaw mobility and jaw pain can be found in approximately 20% of patients with JIA (prevalence: 70 per 100 000 persons). Early diagnosis and treatment of the underlying disease are essential for a good outcome, but uniform, consensus-based management is still lacking. METHODS: The clinical practice guideline is based on the findings of a systematic literature review in multiple databases and a Delphi procedure to obtain consensus on the recommendations. RESULTS: Most of the identified studies were retrospective. Patients with JIA should undergo clinical screening with a structured examination protocol once per year in childhood and adolescence, and thereafter as well if the temporomandibular joint is involved. The diagnosis of chronic rheumatoid arthritis of the temporomandibular joint is established with contrast-enhanced magnetic resonance imaging. Conservative treatment (antirheumatic basal therapy, local measures) is unsuccessful in less than 10% of patients. In such cases, arthroscopy and arthrocentesis can be used for temporary symptom relief and functional improvement. Intra-articular corticosteroid injections should be given only once, and only in otherwise intractable cases. In severe cases where all other options have been exhausted (<1%), open surgical treatment can be considered, including alloplastic joint replacement. CONCLUSION: Oligosymptomatic and asymptomatic cases are common even with radiologic evidence of marked joint damage. The possibility of rheumatic involvement of the temporomandibular joint must be kept in mind so that serious complications can be avoided. Regular clinical evaluation of the temporomandibular joint is recommended, particularly for patients with juvenile idiopathic arthritis.
34842032 CT-P13 SC for the treatment of rheumatoid arthritis. 2022 Jan INTRODUCTION: Management of Rheumatoid Arthritis (RA) has improved following the implementation of early intensive treat to target recommendations and the availability of different biologicals. Most experience is with TNF blockers, but challenges remain in the efficacy/safety balance, immunogenicity, and long-term drug survival as well as availability and affordability despite the introduction of biosimilars. AREA COVERED: We provide an overview of the development of CT-P13 SC based on infliximab biosimilar CT-P13 IV. The one-year pivotal phase I/III trial in RA showed CT-P13 120 mg SC fixed dose to have favorable pharmacokinetics compared to CT-P13 IV classical weight adapted dosing, similar to lower anti-drug antibodies, similar safety and non-inferiority for efficacy at 6 months. EXPERT OPINION: CT-P13 SC is an additional option in RA treatment and by extension for other inflammatory diseases as Inflammatory Bowel Disease. This new way of administration has the potential to improve long-term drug survival of infliximab, improve patient outcomes, and patient comfort.
32925445 Rheumatoid Arthritis Patients Have Better Outcomes Than Non-Rheumatoid Arthritis Patients 2022 Jan 1 OBJECTIVES: The aims of this study were to compare the outcomes of patients primarily admitted for ischemic stroke with and without a secondary diagnosis of RA. METHODS: Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 database. The NIS was searched for hospitalizations for adult patients with ischemic stroke as principal diagnosis with and without RA as secondary diagnosis using International Classification of Diseases, 10th Revision codes. The primary outcome was inpatient mortality. Hospital length of stay (LOS), total hospital charges, odds of receiving tissue plasminogen activator, and mechanical thrombectomy were secondary outcomes of interest. Multivariate logistic and linear regression analyses were used accordingly to adjust for confounders. RESULTS: There were more than 71 million discharges included in the combined 2016 and 2017 NIS database. Of 525,570 patients with ischemic stroke, 8670 (1.7%) had RA. Hospitalizations for ischemic stroke with RA had less inpatient mortality (4.7% vs. 5.5%; adjusted odds ratio, 0.66; 95% confidence interval, 0.52-0.85; p = 0.001), shorter LOS (5.1 vs 5.7 days, p < 0.0001), lower mean total hospital charges ($61,626 vs. $70,345, p < 0.0001), and less odds of undergoing mechanical thrombectomy (3.9% vs. 5.1%; adjusted odds ratio, 0.55; 95% confidence interval, 0.42-0.72; p < 0.0001) compared with those without RA. CONCLUSIONS: Hospitalizations for ischemic stroke with RA had less inpatient mortality, shorter LOS, lower total hospital charges, and less likelihood of undergoing mechanical thrombectomy compared with those without RA. However, the odds of receiving tissue plasminogen activator were similar between both groups. Further studies to understand its mechanism would be helpful.
35318462 Oral surveillance and JAK inhibitor safety: the theory of relativity. 2022 May The published results of the post-marketing ORAL Surveillance study, which compared the Janus kinase (JAK) inhibitor tofacitinib with anti-TNF therapy in older patients with rheumatoid arthritis who have cardiovascular risk factors, have led to changes in the recommendations for the use of JAK inhibitors. Although new safety signals have emerged for tofacitinib, namely malignancy and cardiovascular disease, it should be noted that these signals are relative to those seen with TNF blockers. The new data further raise our intrigue that venous thromboembolism might be a true risk related to JAK inhibition. Reassuringly, the totality of the findings from this newly published study and the other data collected to date suggest that JAK inhibitors can be used safely at approved doses by many patients with rheumatoid arthritis.
34979770 [The standardized diagnosis and treatment of rheumatoid arthritis]. 2022 Jan 1 Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of the joints with high risk of disability. In recent years, remarkable progress has been made towards the diagnosis and treatment of RA, and the international RA guidelines have been also kept updated. Nevertheless, there are many challenges in China, especially inadequate number of rheumatologists and insufficient experience in the diagnosis and treatment of RA. Therefore, Chinese Rheumatology Association drafted the standardized diagnosis and treatment of RA based on the available evidence, so as to improve the management of RA patients in China.
34766472 lncRNA BZRAP1-AS1 alleviates rheumatoid arthritis by regulating miR-1286/COL5A2 axis. 2022 Feb BACKGROUND: Dysregulation of BZRAP1-AS1 was associated with immune statuses of cancer or Alzheimer's disease patients, yet little is known about its role in rheumatoid arthritis. METHODS: RT-qPCR and western blot were applied to assess the expression of indicated expression. CCK-8 and BrdU proliferation assays were used to measure the proliferation of RA-HFLS. Apoptosis in RA-HFLS was evidenced by the alteration of caspase-3 activity and apoptosis-related factors. ELISA was performed to detect IL-6, IL-1β, and TNF-α level. Luciferase reporter, RIP, and pull-down assays were used to confirm the BZRAP1-AS1/miR-1286/COL5A2 cascade predicted by bioinformatics analysis. RESULTS: BZRAP1-AS1 and COL5A2 were downregulated in RA tissues and RA-HFLS while miR-1286 was amplified. Overexpression of BZRAP1-AS1 reduced the RA-HFLS proliferation, IL-6, IL-1β, and TNF-α level and induced cell apoptosis while BZRAP1-AS1 silence produced an opposite effect. Overexpression of BZRAP1-AS1 reduced the miR-1286 expression which in turn increased the COL5A2 expression, thereby relieving the excessive proliferation and limited apoptosis in RA-HFLS. CONCLUSION: Our findings suggested that BZRAP1-AS1 sequestered miR-1286 and reshaped the COL5A2 expression, thereby suppressed RA-HFLS proliferation and inflammation, and triggered cell apoptosis, resulting in the attenuation of RA progression.
35564772 Tailoring Tofacitinib Oral Therapy in Rheumatoid Arthritis: The TuTOR App. 2022 Apr 28 To support the management of rheumatoid arthritis (RA) patients treated with tofacitinib, we designed the TuTOR (tailoring tofacitinib oral therapy in rheumatoid arthritis) mobile app. The impact of the app on medical adherence was evaluated using a crossover design alternating a paper-diary and the TuTOR App. Twenty patients with RA (mean age at inclusion, 59 ± 13 years) were included in the study. A statistically significant decrease in DAS28 was observed since the first month of therapy (mean DAS28 at baseline, 3.9 ± 1 vs. 1° month 3.1 ± 1, p = 0.0016). Similarly, the numerical rating scale (NRS) of perceived activity of disease and subjective fatigue progressively decreased. No differences were reported in DAS28 or NRS between the TuTOR app and the paper-diary groups. A significant decrease was observed in HAQ during the follow-up (baseline 1.38 ± 1.11 vs. six months 0.83 ± 0.9; p = 0.01). When filling out the self-reporting questionnaires, most of the patients (82%) preferred the TuTOR App helping them to remember to take the pills. Furthermore, 82% of patients used the app regularly (vs. 53% for the paper diary). Three patients suspended tofacitinib due to gastrointestinal intolerance. Both digital and paper devices can help maximize adherence to therapy; however, the TuTOR app was preferred by the patients for its simplicity and immediacy.
35392076 Polycyclic Aromatic Hydrocarbons Affect Rheumatoid Arthritis Pathogenesis via Aryl Hydroca 2022 Rheumatoid arthritis (RA), the most common autoimmune disease, is characterized by symmetrical synovial inflammation of multiple joints with the infiltration of pro-inflammatory immune cells and increased cytokines (CKs) levels. In the past few years, numerous studies have indicated that several factors could affect RA, such as mutations in susceptibility genes, epigenetic modifications, age, and race. Recently, environmental factors, particularly polycyclic aromatic hydrocarbons (PAHs), have attracted increasing attention in RA pathogenesis. Therefore, exploring the specific mechanisms of PAHs in RA is vitally critical. In this review, we summarize the recent progress in understanding the mechanisms of PAHs and aryl hydrocarbon receptors (AHRs) in RA. Additionally, the development of therapeutic drugs that target AHR is also reviewed. Finally, we discuss the challenges and perspectives on AHR application in the future.