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ID PMID Title PublicationDate abstract
34535196 Isopsoralen ameliorates rheumatoid arthritis by targeting MIF. 2021 Sep 17 BACKGROUND: Isopsoralen (IPRN), one of the active ingredients of Psoralea corylifolia Linn, has anti-inflammatory properties. We attempted to investigate the inhibitory effects of IPRN on rheumatoid arthritis (RA) and characterize its potential mechanism. METHODS: RA fibroblast-like synoviocytes (FLSs) and mice with collagen-induced arthritis (CIA) were used as in vitro and in vivo models to analyze the antiarthritic effect of IPRN. Histological analysis of the inflamed joints from mice with CIA was performed using microcomputed tomography (micro-CT) and hematoxylin-eosin (HE) staining. RNA sequencing (RNA-Seq), network pharmacology analysis, molecular docking, drug affinity responsive target stability (DARTS) assay, and cellular thermal shift assay (CETSA) were performed to evaluate the targets of IPRN. RESULTS: IPRN ameliorated the inflammatory phenotype of RA FLSs by inhibiting their cytokine production, migration, invasion, and proangiogenic ability. IPRN also significantly reduced the severity of CIA in mice by decreasing paw thickness, arthritis score, bone damage, and serum inflammatory cytokine levels. A mechanistic study demonstrated that macrophage migration inhibitory factor (MIF), a key protein in the inflammatory process, was the specific target by which IPRN exerted its anti-inflammatory effects in RA FLSs. CONCLUSION: Our study demonstrates the antiarthritic effect of IPRN, which suggests the therapeutic potential of IPRN in RA.
34347587 When a virus lies in wait. 2021 Aug 4 A mouse model supports the hypothesis that latent Epstein-Barr virus exacerbates the symptoms of rheumatoid arthritis.
32812344 Musculoskeletal stiffness is common in healthy adults and increases with age. 2021 Mar INTRODUCTION/OBJECTIVE: Musculoskeletal stiffness is a common feature in rheumatologic inflammatory diseases but little is known about background joint stiffness in the healthy population. The aim of this survey was to determine the variation in musculoskeletal stiffness with age in a cohort of healthy adults using a patient reported outcome instrument designed to assess stiffness in rheumatoid arthritis. METHODS: Healthy subjects ≥18 years old were enrolled at two sites. Those with a diagnosis of rheumatological disease were excluded. Each subject completed a 21-item questionnaire designed to evaluate the severity of musculoskeletal stiffness, its physical impact and psychosocial impact, and to provide an overall stiffness score, expressed as a percentage. Scores were analyzed by age group. RESULTS: Two hundred eighty-two subjects were included with a mean age of 42 years (±17, range 18-85). More than 50% of subjects reported stiffness in each age group but with a low median overall stiffness score of 5.4% (IQR 0, 12.6). Scores were markedly higher in those aged ≥60 years, median 10.0% (IQR 2.6, 21.9), and only in this age group did the majority of subjects report a physical or psychosocial impact of stiffness. Scores in males and females were similar. CONCLUSION: The prevalence of musculoskeletal stiffness in healthy subjects of all ages is not negligible, and the high frequency of stiffness and greater severity in the upper age cohort suggest that the background joint stiffness amongst older subjects should be considered when interpreting stiffness in rheumatologic patients.
33402443 Self-protection strategies and health behaviour in patients with inflammatory rheumatic di 2021 Jan AIMS: In Danish patients with inflammatory rheumatic diseases to explore self-protection strategies and health behaviour including adherence to disease-modifying antirheumatic treatment (DMARD) during the initial phase of the COVID-19 pandemic and again after the reopening of the society started. Furthermore, to identify characteristics of patients with high levels of anxiety and self-isolation. METHODS: Patients in routine care followed prospectively in the nationwide DANBIO registry were invited to answer an online questionnaire regarding disease activity and COVID-19 infection, behaviour in March and June 2020. Responses were linked to patient data in DANBIO. Characteristics potentially associated with anxiety, self-isolation and medication adherence (gender/age/diagnosis/education/work status/comorbidity/DMARD/smoking/EQ-5D/disease activity) were explored with multivariable logistic regression analyses. RESULTS: We included 12 789 patients (8168 rheumatoid arthritis/2068 psoriatic arthritis/1758 axial spondyloarthritis/795 other) of whom 65% were women and 36% treated with biological DMARD. Self-reported COVID-19 prevalence was 0.3%. Patients reported that they were worried to get COVID-19 infection (March/June: 70%/45%) and self-isolated more than others of the same age (48%/38%). The fraction of patients who changed medication due to fear of COVID-19 were 4.1%/0.6%. Female gender, comorbidities, not working, lower education, biological treatment and poor European Quality of life, 5 dimensions were associated with both anxiety and self-isolation. CONCLUSION: In >12 000 patients with inflammatory arthritis, we found widespread anxiety and self-isolation, but high medication adherence, in the initial phase of the COVID-19 pandemic. This persisted during the gradual opening of society during the following months. Attention to patients' anxiety and self-isolation is important during this and potential future epidemics.
34248943 Gene Expression Profiles Analyzed Using Integrating RNA Sequencing, and Microarray Reveals 2021 BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare condition that involves benign proliferation of the synovial tissue and is characterized by severe joint destruction and high recurrence even after surgical resection. However, poor understanding of the pathogenesis limits its effective therapy. METHOD: In this study, gene expression profiles of six patients with PVNS, 11 patients with osteoarthritis (OA), nine patients with rheumatoid arthritis (RA) (E-MTAB-6141), and three healthy subjects (GSE143514) were analyzed using integrating RNA sequencing (RNA-seq) and microarray to investigate the PVNS transcriptome. Gene ontology, string, and cytoscape were used to determine the gene functional enrichment. Cell functional molecules were detected using flow cytometry or immunohistochemical test to identify the cell subset and function. CD14(+) cells were isolated and induced to osteoclast to evaluate the monocyte/macrophage function. RESULTS: The most obvious local manifestations of PVNS were inflammation, including increased immune cells infiltration and cytokine secretion, and tumor phenotypes. High proportion of inflammatory cells, including T cells, natural killer (NK) cells, NKT cells, and B cells were recruited from the blood. Th17 and monocytes, especially classical monocytes but not nonclassical monocytes, increased in PVNS synovium. An obvious increase in osteoclastogenesis and macrophage activation was observed locally. Elevated expression of MMP9, SIGLEC 15, and RANK were observed in myeloid cell of PVNS than OA. When compared with RA, osteoclast differentiation and myeloid cell activation are PVNS-specific characters, whereas T cell activation is shared by PVNS and RA. CONCLUSION: The transcriptional expression characteristics of PVNS showed increased immune response, cell migration, and osteoclastogenesis. Osteoclast differentiation is only observed in PVNS but not RA, whereas T-cell activation is common in inflammatory arthritis.
34758437 Anti-inflammatory and osteoprotective effects of Chikusetsusaponin Ⅳa on rheumatoid arth 2021 Dec BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease, for which no economical and safe target drug treatment is available. Chikusetsusaponin Ⅳa (CS-IVa), an active compound in Panax japonicus C.A. Mey, has a good anti-inflammatory effect, but whether this compound can serve as a targeted drug for RA and the corresponding therapeutic mechanism remain unclear. PURPOSE: To investigate the anti-inflammatory and bone-protecting effects of CS-IVa on RA and the possible corresponding mechanisms of action. METHODS: Biomarkers and underlying pathological mechanisms were examined by performing a bioinformatics analysis of RA synovial gene expression data profiles, and the feasibility of CS-IVa treatment for RA was predicted using molecular docking and molecular dynamics simulation techniques. Histomorphological and molecular biology techniques were used to verify the feasibility and molecular mechanism of CS-IVa treatment for RA in vivo using a collagen-induced arthritis (CIA) model. RESULTS: CS-IVa alleviated symptoms and reduced the immune organ index, arthritis index, hind paw thickness, and number of swollen joints in the foot for CIA mice. Bioinformatics analysis suggested that interferon-gamma (IFN-γ), interleukin-1 β (IL-1β), and the Janus kinase/signal transduction and activator of transcription (JAK/STAT) pathway played important roles in the pathogenesis of RA. The results of molecular docking and molecular dynamics simulations showed that CS-IVa bound effectively to IFN-γ and IL-1β and that the combined pose has good stability and flexibility. The histomorphological results showed that CS-IVa reduced joint histopathology scores, OARSI scores, and TRAP-positive cell counts. Molecular biology analysis indicated that CS-IVa reduced the concentration of inflammatory factors in the peripheral serum of CIA mice and suppressed the mRNA expression of these factors in the spleen in a dose-dependent manner. The protein expression level of the JAK/STAT pathway was also inhibited by CS-IVa. CONCLUSION: The results of the current study demonstrate a novel inhibitory effect of CS-IVa on inflammation and bone destruction in CIA mice, and the mechanism may be related to the JAK/STAT signaling pathway, which provides new insights into the development of CS-IVa as a therapeutic agent for RA.
34673223 Small molecule drugs for atopic dermatitis, rheumatoid arthritis, and hereditary angioedem 2022 Mar OBJECTIVE: To review recent trends in the development of targeted small molecule drugs (SMDs) for the treatment of immunologically driven disorders, including atopic dermatitis, rheumatoid arthritis, and hereditary angioedema. DATA SOURCES: Data sources included peer-reviewed published literature from the PubMed database, published abstracts from scientific and medical meetings, and medication information from the Drugs@FDA database. STUDY SELECTIONS: Articles with primary or retrospective trial results, articles with patient or physician survey results, articles providing expert perspectives, and commentary on chronic immunologic disorders, Food and Drug Administration package inserts, and abstracts from scientific meetings were selected. RESULTS: Targeted biological therapies have greatly improved response rates and symptom relief for patients with long-term immunologically driven disorders over the past 2 decades. However, recent advances in the understanding of molecular pathways involved in the pathogenesis of these disorders have led to the development of novel targeted SMDs, such as tofacitinib and berotralstat, that can be delivered orally or topically. Few head-to-head studies that compare the safety and efficacy of biologics to SMDs in immunologically driven disorders exist, although some studies suggest that oral and topical modes of administration are preferred by patients and may improve patient quality of life over time. CONCLUSION: Scientific advances have led to an increase in the development of targeted SMDs for the treatment of chronic immunologic disorders, which may revolutionize the management of these diseases. Head-to-head studies and real-world evidence are needed to fully compare treatment attributes between biologics and SMDs, including safety, efficacy, adherence, impact on quality of life, and cost-effectiveness.
32729616 Clinical Value of Detecting Anti-Mutated Citrullinated Vimentin, Anti-Cyclic Citrullinated 2021 Jan 4 OBJECTIVES: To investigate the clinical value of detecting anti-mutated citrullinated vimentin (anti-MCV), anti-citrullinated peptide (anti-CCP), red-blood-cell distribution width (RDW), and 25-hydroxyvitamin D (25-[OH]D) in the diagnosis of rheumatoid arthritis (RA). METHODS: We enrolled 119 patients with RA, 114 control individuals without RA (disease controls), and 40 healthy controls in our study (Han Chinese). Anti-CCP and anti-MCV were detected by enzyme-linked immunosorbent assay (ELISA), 25-(OH)D was detected by electrochemical luminescence, and RDW was calculated by erythrocyte parameters detected via the electric resistance method. RESULTS: The serum levels of anti-CCP and anti-MCV in RA were higher than those in disease controls and healthy controls (P <.01). The areas under the curve (AUCs) of anti-MCV, anti-CCP, RDW, and 25-(OH)D were 0.857, 0.890, 0.611, and 0.569 respectively (P <.05). In various combinations of indicators, when RDW, 25-(OH)D, and anti-CCP; or RDW, 25-(OH)D, anti-CCP, and anti-MCV were connected in parallel, the sensitivity was the highest (all 94.1%). Also, when RDW, 25-(OH)D, anti-CCP, and anti-MCV were connected in series, the sensitivity was the lowest (13.4%). CONCLUSIONS: Anti-CCP and anti-MCV are ideal indices for RA diagnosis. Also, in combination with RDW and 25-(OH)D, the diagnostic level will be improved, as well as the sensitivity and specificity, which is significant for the differential diagnosis of RA.
34579044 Metabolic Profile and Bone Status in Post-Menopausal Women with Rheumatoid Arthritis: A Mo 2021 Sep 11 Background: Rheumatoid arthritis (RA) and metabolic syndrome (MetS) are chronic conditions that share common inflammatory mechanisms. Both diseases can lead to an impairment of the bone microarchitecture. The aims of our study were to evaluate clinical, metabolic, and bone parameters in RA patients with or without MetS (MetS+, MetS-) and potential correlations between the glico-lipidic profile, RA disease activity, and bone status. Methods: A total of thirty-nine RA female post-menopausal patients were recruited (median age 66.6 ± 10.4, disease duration 3 ± 2.7). Anthropometric data, medical history, and current treatment were recorded along with basal blood tests, bone, and lipid metabolism biomarkers. RA disease activity and insulin resistance were evaluated through standard scores. Quantitative assessment of the bone (bone mineral density-BMD) was performed by dual-energy-X ray absorption (DXA), whereas bone quality was quantified with the trabecular bone score (TBS). Results: No statistically significant differences concerning both BMD and TBS were detected between the MetS+ and MetS- RA patients. However, the MetS+ RA patients exhibited significantly higher disease activity and lower serum 25-hydroxyvitamin D [25(OH)D] concentrations (respectively, p = 0.04 and p = 0.01). In all RA patients, a significant negative correlation emerged between the BMD of the femoral trochanter with plasmatic triglycerides (TG) concentrations (r = -0.38, p = 0.01), whereas the lumbar BMD was positively correlated with the abdominal waist (AW) and fasting glucose (FG) concentrations. On the other hand, the TBS was negatively correlated with insulin concentrations, FG, and RA disease activity (respectively, r = -0.45, p = 0.01, r = -0.40, p = 0.03, r = -0.37, p = 0.04), the last one was further negatively correlated with 25-OHD serum concentrations (r = -0.6, p = 0.0006) and insulin-resistance (r = 0.3, p = 0.04). Conclusions: Bone quantity (BMD) and quality (TBS) do not seem significantly changed among MetS+ and MetS- RA patients; however, among MetS+ patients, both significantly higher disease activity and lower vitamin D serum concentrations were observed. In addition, the significant negative correlations between the alterations of metabolic parameters limited to the TBS in all RA patients might suggest that qualitative bone microarchitecture impairments (TBS) might manifest despite unchanged BMD values.
34654466 bFGF could be a biomarker of malignancy in RS(3)PE syndrome: an ambispective single-center 2021 Oct 15 OBJECTIVES: Remitting seronegative symmetrical synovitis with pitting edema (RS(3)PE) is a rare inflammatory arthritis, with a higher incidence of malignancy. The aim of this study is to identify biomarkers for predicting malignancy in RS(3)PE. METHODS: A total of 51 patients with RS(3)PE from September 2007 to May 2019 were retrospectively reviewed and followed for up to 5 years, with 15 patients with osteoarthritis (OA) and 14 patients with elderly-onset rheumatoid arthritis (EORA) as disease controls. Serum levels of angiogenesis cytokines were measured by electrochemiluminescent immunoassay and Luminex Human Magnetic Assay. Clinical data and laboratory parameters were analyzed to identify risk factors for malignancy. RESULTS: A total of forty-eight RS(3)PE patients (94.1%) were available with follow-up data; 8 patients (16.7%) were diagnosed with malignancy, of which 6 patients were hematological tumor; and 2 patients were solid tumors. Serum levels of basic fibroblast growth factor (bFGF) were exclusively higher in RS(3)PE patients with malignancy [14.21 (7.52, 23.18) ng/mL] than RS(3)PE patients without malignancy [4.32 (2.88, 7.42) ng/mL], OA [3.20 (2.20, 5.30) ng/mL], and EORA [3.20 (2.20, 5.30) ng/mL]. The optimal cut-off value of bFGF for malignancy was 10ng/mL in RS(3)PE. Logistic regression analysis indicated that elevation of bFGF was a risk factor for malignancy in RS(3)PE. CONCLUSIONS: This study indicated that bFGF was elevated in RS(3)PE patients with malignancy and could serve as a biomarker for predicting paraneoplastic RS(3)PE.
33684874 Preparation and characterization of cyclic citrullinated peptide-immobilized latex beads f 2021 Apr 12 The anti-citrillinated protein antibody (ACPA) plays an important role in early diagnosis of rheumatoid arthritis (RA), and is usually detected by using cyclic citrullinated peptide (CCP) as antigen. The ACPA against CCP test is usually performed utilizing enzyme-linked immunosorbent assay (ELISA), but the ELISA is expensive and time-consuming. Here, latex particle-enhanced turbidimetric immunoassay (LTIA) based on CCP-immobilized latex bead was proposed for fast measurements of ACPA of RA patients. CCP-immobilized latex bead was fabricated through three methods, including direct coupling, overall coupling and layer by layer coupling. According to the optimized experiments, layer-by-layer coupling was the best method with advantages of time-saving, simple operation and good repeatability. In addition, a spacer arm of appropriate length between latex beads and CCP could avoid stereoscopic obstacles and make ACPA closer to CCP. The CCP-immobilized latex bead based on layer by layer coupling (CCP-LB-LLC) was used for assembling the homemade kit, which was applied in fast measurements of ACPA through LTIA. The homemade kit possessed a low limit of detection (0.2 U/mL) and an acceptable the batch-to-batch reproducibility. In addition, the homemade kit can be stored at 4 °C for at least one month. When used to detect 20 clinical samples, the results of homemade kit were consistent with commercial ELISA. Furthermore, LTIA based on the homemade kit was simpler and cheaper than ELISA. These results demonstrated that the homemade kit could be useful for diagnosis of RA patients.
33767091 Role of Janus Kinase inhibitors in rheumatoid arthritis treatment. 2021 May 1 PURPOSE OF REVIEW: To review recently published articles on use of Janus Kinase inhibitors (Jaki) in the clinic for rheumatoid arthritis (RA). RECENT FINDINGS: Several Jaki have been approved for RA patients failing csDMARDS. Over the last 2 years, EULAR and ACR have published updated recommendations for the pharmacologic management of RA providing guidance on the utilization of Jaki after csDMARD failure. Clinical trials have been published addressing the efficacy of Jaki monotherapy as patients often choose monotherapy because of a desire to avoid multiple therapies and aggravating adverse events with csDMARDs. Previous clinical trials have compared the efficacy and safety of Jaki to adalimumab, and a trial comparing abatacept to upadacitinib has recently been published. An increased risk of venous thromboembolism (VTE) has been suggested with Jaki and additional information has recently become available with conflicting results. SUMMARY: Jaki are now standard therapy for RA patients failing csDMARDs and are being utilized frequently as an alternative to biologics in patients without risk factors for VTE. Jaki monotherapy has been demonstrated to be effective, although combination therapy has been demonstrated to be superior in clinical and radiographic outcomes. Preliminary data suggests that cycling through Jaki in patients with incomplete response to initial Jaki treatment may be an appropriate strategy.
32075475 A phase 2a, randomized, double-blind, placebo-controlled trial of the efficacy and safety 2021 Jan OBJECTIVES: Many patients with rheumatoid arthritis (RA) are not able to achieve long-term disease remission. This phase 2a study (NCT02884635) evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of the novel, oral, gonadotropin-releasing hormone antagonist, ASP1707, in combination with methotrexate (MTX) for treatment of RA. METHODS: Postmenopausal women with RA who had been receiving MTX for ≥90 days were randomized to ASP1707 30 mg twice daily or placebo for 12 weeks. The primary endpoint was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Secondary endpoints included: ACR20, ACR50, and ACR70 response rates; disease activity score (DAS)28-CRP; DAS28-ESR; Tender or Swollen Joint Counts; and remission rates. RESULTS: Of 105 patients screened, 72 were randomized to ASP1707 30 mg twice daily (n = 37) or placebo (n = 35). ASP1707 did not improve ACR20, ACR50, or ACR70 response rates at any time point and did not improve any secondary efficacy endpoint. Plasma luteinizing hormone (LH) concentration decreased >90% in >90% of patients receiving ASP1707, with a rapid decrease to <1 IU/L at week 1 that remained stable throughout the treatment. CONCLUSION: In the current study, ASP1707 did not demonstrate a clinical benefit.
33958440 Tofacitinib versus tocilizumab in the treatment of biological-naïve or previous biologica 2021 May OBJECTIVES: To compare effectiveness between tofacitinib and tocilizumab treatments for biological disease-modifying antirheumatic drug (bDMARD)-naïve patients or previous bDMARD-failure patients with active rheumatoid arthritis (RA) refractory to methotrexate (MTX). METHODS: We used two ongoing real-world registries of patients with RA who had first started tofacitinib or tocilizumab between August 2013 and February 2019 at our institutions. Clinical disease activity index (CDAI)-based improvements at 12 months were used for comparisons between tofacitinib and tocilizumab treatments, separately for bDMARD-naïve and previous bDMARD-failure patients. RESULTS: A total of 464 patients with RA with high or moderate CDAI were enrolled (247 with tofacitinib and 217 with tocilizumab). After adjustments for treatment-selection bias by propensity score matching, we showed that tofacitinib was more likely to induce and maintain ≥85% improvement in CDAI (CDAI85), CDAI70 and remission at 12 months compared with tocilizumab in bDMARD-naïve patients. After adjusting for concurrent use of MTX and prednisolone, the ORs of tofacitinib versus tocilizumab were 3.88 (95% CI 1.87 to 8.03) for CDAI85, 2.89 (95% CI 1.43 to 5.84) for CDAI70 and 3.31 (95% CI 1.69 to 6.48) for remission. These effects were not observed in bDMARD-failure patients. In tofacitinib treatment for bDMARD-failure patients, the number of previously failed bDMARD classes was not associated with CDAI-based improvements. The rate of overall adverse events was similar between both treatments. Similar ORs were obtained from patients adjusted by inverse probability of treatment weighting. CONCLUSIONS: Compared with tocilizumab, tofacitinib can induce greater improvements during the first 12-month treatment in bDMARD-naïve patients, but this difference was not observed in previous bDMARD-failure patients.
34747629 Frequency and impact of DHODH, ABCG2 and CYP2C19 SNPs on the therapeutic efficacy, tolerab 2021 Dec Introduction: Leflunomide is one of the commonly used drugs in treatment of rheumatoid arthritis (RA), which on administration is converted into its active metabolite teriflunomide. Aim: Our aim is to evaluate the frequencies of dihydrooroate dehydrogenase (DHODH) (rs3213422), ABCG2 (rs2231142) and CYP2C19 (rs4244285) allele distribution among patients receiving leflunomide for RA and their possible impact on leflunomide performance in disease control. Patients & methods: Patients (>18 years) who fulfilled the 2010 ACR classification criteria for RA receiving leflunomide (20 mg/day) were included in the study. Disease activity score 28 was used to assess patients disease activity. Blood samples were collected for full blood count and blood chemistry. Genomic DNA was extracted from peripheral blood. The selection of SNPs was based on the criteria of minor allele frequency among Caucasians. Results: A significant association between the therapeutic outcome of leflunomide and DHODH genotyping was observed but not with CYP2C19 and ABCG2. Importantly, there is a significant association between DHODH (rs3213422) CC genotype and the number of patients with controlled disease. Conclusion: We strongly suggest that polymorphisms in the DHODH are the major factor affecting leflunomide pharmacogenetics and therapeutic efficacy.
33517870 Recovery of borderline oxacillin-resistant Staphylococcus pseudintermedius (BORSP) from bo 2021 Sep We report a case of borderline oxacillin-resistant S. pseudintermedius (BORSP) in a rheumatoid arthritis patient with severe osteoporosis. The organism is also resistant to erythromycin and clindamycin. We also present clear evidence on transmission from the family dog.
33325280 Tapering and discontinuation of oral glucocorticoids without deterioration of disease stat 2021 Jul OBJECTIVE: To retrospectively evaluate whether oral glucocorticoid (GC) administration can be tapered or discontinued over a 2-year observation period in patients with rheumatoid arthritis (RA) undergoing a stable oral GC treatment, without deterioration in the disease status. METHODS: Methotrexate (MTX) and prednisolone (PSL) dosages were increased and decreased, respectively, to the maximum extent possible. Concomitant biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) were used as required. Changes in PSL and MTX use and disease status were evaluated at baseline (BL), year-1, and year-2. RESULTS: Thirty-six patients were enrolled (median age, 65.4 years; disease duration, 7.1 years). The proportion of patients using PSL decreased over 2 years (100-13.9%, p < .0001). While no change was observed in the proportion of patients using MTX, the average administered dose increased at year-1 (p = .06). Moreover, b/tsDMARDs were administered in nine patients (two in year-1, seven in year-2). The Clinical Disease Activity Index remission rate increased from 25.0% to 38.9%. Serious adverse events were identified in two patients. CONCLUSIONS: Oral GC administration was discontinued without deterioration in the rheumatoid arthritis disease control.
33806304 Effect of Anti-Rheumatic Treatment on the Periodontal Condition of Rheumatoid Arthritis Pa 2021 Mar 4 Periodontitis, a bacterial-induced infection of the supporting soft and hard tissues of the teeth (the periodontium), is common in patients with rheumatoid arthritis (RA). As RA and periodontitis underlie common inflammatory pathways, targeting the progression of RA might mediate both periodontitis and RA. On the other hand, patients with RA on immunosuppressive medication have an increased risk of infection. Therefore, the objective of this longitudinal observation study was to assess the effect of methotrexate (MTX) and anti-tumor necrosis factor-α (anti-TNF, etanercept) treatment on the periodontal condition of RA patients. Overall, 14 dentate treatment-naive RA patients starting with MTX and 12 dentate RA patients starting with anti-TNF therapy in addition to MTX were included. Follow-up was scheduled matching the routine protocol for the respective treatments. Prior to the anti-rheumatic treatment with MTX or the anti-TNF therapy in addition to MTX, and during follow-up, i.e., 2 months for MTX, and 3 and 6 months for the anti-TNF therapy in addition to MTX, the periodontal inflamed surface area (PISA) was measured. The efficacy of the anti-rheumatic treatment was assessed by determining the change in RA disease activity (DAS28-ESR). Furthermore, the erythrocyte sedimentation rates were determined and the levels of C-reactive protein, IgM-rheumatoid factor, anti-cyclic citrullinated protein antibodies, and antibodies to the periodontal pathogen Porphyromonas gingivalis, were measured. Subgingival sampling and microbiological characterization of the subgingival microflora was done at baseline. MTX or anti-TNF treatment did not result in an improvement of the periodontal condition, while both treatments significantly improved DAS28 scores (both p < 0.01), and reduced C-reactive protein levels and erythrocyte sedimentation rates (both p < 0.05). It is concluded that anti-rheumatic treatment (MTX and anti-TNF) has negligible influence on the periodontal condition of RA patients.
34810197 Influenza outcomes in patients with inflammatory joint diseases and DMARDs: how do they co 2022 Mar OBJECTIVES: To estimate absolute and relative risks for seasonal influenza outcomes in patients with inflammatory joint diseases (IJDs) and disease-modifying antirheumatic drugs (DMARDs). To contextualise recent findings on corresponding COVID-19 risks. METHODS: Using Swedish nationwide registers for this cohort study, we followed 116 989 patients with IJD and matched population comparators across four influenza seasons (2015-2019). We quantified absolute risks of hospitalisation and death due to influenza, and compared IJD to comparators via Cox regression. We identified 71 556 patients with IJD on active treatment with conventional synthetic DMARDs and biological disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drug (tsDMARDs) at the start of each influenza season, estimated risks for the same outcomes and compared these risks across DMARDs via Cox regression. RESULTS: Per season, average risks for hospitalisation listing influenza were 0.25% in IJD and 0.1% in the general population, corresponding to a crude HR of 2.38 (95% CI 2.21 to 2.56) that decreased to 1.44 (95% CI 1.33 to 1.56) following adjustments for comorbidities. For death listing influenza, the corresponding numbers were 0.015% and 0.006% (HR=2.63, 95% CI 1.93 to 3.58, and HR=1.46, 95% CI 1.07 to 2.01). Absolute risks for influenza outcomes were half (hospitalisation) and one-tenth (death) of those for COVID-19, but relative estimates comparing IJD to the general population were similar. CONCLUSIONS: In absolute terms, COVID-19 in IJD outnumbers that of average seasonal influenza, but IJD entails a 50%-100% increase in risk for hospitalisation and death for both types of infections, which is largely dependent on associated comorbidities. Overall, bDMARDs/tsDMARDs do not seem to confer additional risk for hospitalisation or death related to seasonal influenza.
33761603 Artesunate attenuates bone erosion in rheumatoid arthritis by suppressing reactive oxygen 2021 May Accumulating studies have indicated that reactive oxygen species (ROS) may be implicated into the destructive pathological events of rheumatoid arthritis (RA). As an effective antioxidant, artesunate (ARS) was reported to exert antiarthritic effects. However, whether ARS attenuates the bone erosion during RA progression by regulating ROS production remains to be defined. To address this problem, the inhibitive effects of ARS on osteoclastogenesis were observed in vitro. Mechanically, ARS significantly inhibited the NFATc1 signaling accompanied by markedly suppressing ROS production, which was abnormally enhanced during the pathological process of bone erosion. In addition, ARS may function as a potent ROS scavenger and significantly elevate the expression of HO-1 and NQO1 by activating Nrf2. Moreover, p62 accumulation induced by ARS was responsible for the activation of Nrf2, while the knockdown of p62 in osteoclast precursor cells diminished the suppressive effect of ARS on ROS production during osteoclastogenesis. Consistently, we also demonstrated that ARS effectively suppressed ROS production, leading to the inhibition of arthritic bone destruction by activating antioxidant enzyme and Nrf2/p62 signaling in the knee and ankle tissues of CIA rats. Collectively, our data offer the convincing evidence that ARS may inhibit osteoclastogenesis and ameliorate arthritic bone erosion through suppressing the generation of ROS via activating the p62/Nrf2 signaling.