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ID PMID Title PublicationDate abstract
34670422 Decision tree analysis for evaluating disease activity in patients with rheumatoid arthrit 2021 Oct OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by inflammatory synovitis. We developed a new disease activity evaluation system using important cytokines to help doctors better evaluate disease activity in patients with RA. METHODS: Flow cytometry was used to detect the levels of seven cytokines. Then, the results were analyzed using an R language decision tree. RESULTS: The levels of six cytokines, namely interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ, were significantly different between the active disease and remission stages. Decision tree analysis of the six cytokines with statistical significance identified two judgment rules for the remission stage and three judgment rules for the active disease stage. CONCLUSION: We proposed the use of the decision tree method to analyze cytokine levels in patients with RA and obtain a more intuitive and objective RA disease activity scoring system. This method revealed the relationships of IL-6 and TNF-α levels with inflammatory characteristics in patients with RA, which can help predict disease activity.
34491649 [Effect of Bo's abdominal acupuncture as adjunctive therapy on rheumatoid arthritis and ES 2021 Sep 12 OBJECTIVE: To explore the therapeutic effect on rheumatoid arthritis treated with Bo's abdominal acupuncture for "guiding qi to the source" plus "opening four gates on the abdomen" and the relevant effect mechanism. METHODS: A total of 104 patients with rheumatoid arthritis were randomized into and an observation group (52 cases, 1 case dropped off) and a control group (52 cases, 3 cases dropped off). In the control group, methotrexate tablets were prescribed for oral administration, 5 mg each time, once a week. In the observation group, on the base of the treatment as the control group, Bo's abdominal acupuncture was combined. The acupoints included Zhongwan (CV 12), Xiawan (CV 10), Guanyuan (CV 4), Qihai (CV 6), Huaroumen (ST 24), Wailing (ST 26), etc. The treatment was given once every two days, 3 times weekly. Totally 12 weeks were required in the two groups. Before and after treatment, the score of TCM symptoms (including joint pain, the range of motion, joint swelling and morning stiffness), and the levels of erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and C-reactive protein (CRP) were observed and the clinical therapeutic effect was assessed in the two groups. RESULTS: After treatment, the total effective rate was 88.2% (45/51) in the observation group, higher than 73.5% (36/49) in the control group (P<0.05). The score of each TCM symptom and the total scores after treatment were all lower than those before treatment in the two groups (P<0.05), and these scores in the observation group were lower than the control group (P<0.05). After treatment, the levels of ESR, RF and CRP were all lower than those before treatment in the two groups (P<0.05), while the levels of those indexes in the observation group were lower than the control group (P<0.05). CONCLUSION: Bo's abdominal acupuncture for "guiding qi to the source" plus "opening four gates on the abdomen" as the adjunctive therapy effectively relieves the clinical symptoms in the patients with rheumatoid arthritis, which is related to the reduction of ESR, RF and CRP in mechanism.
33337992 Effectiveness and safety of baricitinib in rheumatoid arthritis: a monocentric, longitudin 2021 May OBJECTIVES: Baricitinib is a Janus-kinase (JAK) 1/2 inhibitor, approved for the treatment of moderate-to-severe rheumatoid arthritis (RA) patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). We report the first real-life experience with baricitinib in a monocentric cohort of unselected RA patients. METHODS: We enrolled consecutive RA patients starting baricitinib. At baseline and after 4, 12, 24 and 48 weeks we assessed the disease activity by composite indices (SDAI, CDAI and DAS28CRP) and ultrasonography, and we recorded any adverse events. The primary endpoint was the percentage of patients achieving SDAI remission at week 4. RESULTS: We enrolled 59 patients [(F:M = 50:9, median age 58.1 years (IQR 12.8), median disease duration 144 (IQR 150) months] treated with baricitinib in combination with a csDMARD (52.5%) or monotherapy (47.5%) for a median follow-up of 24 weeks (IQR 36). The 12-month drug retention rate was 74%. At weeks 4, 12, 24 and 48 we observed a significant reduction of DAS28, CDAI and SDAI, global health and pain (p<0.001 for all). After 4 weeks of treatment, 12% of patients achieved SDAI remission. Concomitant csDMARDs, previous biological DMARDs, gender, seropositivity and BMI did not affect the efficacy of baricitinib. Baricitinib allowed a significant reduction in prednisone dose after 12 and 24 weeks and a rapid and sustained ultrasound improvement. No serious adverse events, serious infections or cardiovascular events were recorded. CONCLUSIONS: Our study confirms the efficacy and safety profile and rapid onset of the effect of baricitinib in RA patients in a real-life setting.
34155816 Downregulation of miR-98-5p expression induces interleukin-6 expression in rheumatoid fibr 2021 Aug AIM: The increased level of interleukin-6 (IL-6) plays a significant role in the pathogenesis of rheumatoid arthritis (RA). Specific blockade of IL-6 or its receptor has been used successfully in treating RA. MicroRNAs can regulate gene expression and act as regulators of target genes. Manipulation of specific microRNAs provides a novel therapeutic strategy for treating/preventing diseases. This study explored the role of miR-98-5p in the regulation of IL-6 expression in rheumatoid fibroblast-like synoviocytes (RA-FLSs). METHODS: Real-time PCR was used to detect miR-98-5p expression in RA-FLSs and normal human fibroblast-like synovial cells (HFLSs). Site-directed gene mutagenesis and reporter gene assay were performed to identify the interaction between miR-98-5p and IL-6. Manipulation of miR-98-5p expression in RA-FLS used transfection with miR-98-5p mimic or inhibitor. Stimulation of FLSs with IL-1β induced IL-6 production. Enzyme-linked immunosorbent assay was used to detect the level of IL-6 secreted into the RA-FLS culture supernatant. RESULTS: Compared with HFLSs, the expression of miR-98-5p in RA-FLSs was significantly downregulated, and was negatively correlated with DAS28 scores and rheumatoid factor. In patients with anti-keratin antibody-positive RA, the expression level of miR-98-5p was lower. miR-98-5p negatively regulated the expression of IL-6 in RA-FLSs. After IL-1β stimulation, the expression of miR-98-5p decreased and the level of IL-6 protein was upregulated during IL-6 secretion. CONCLUSION: These data suggest that manipulation of miR-98-5p, which negatively modulates IL-6 expression, may be a potential clinical approach in RA.
34050794 Therapeutic education improves rheumatoid arthritis patients' knowledge about methotrexate 2021 Nov To assess, by means of a questionnaire, the effectiveness of a therapeutic education session on rheumatoid arthritis patients' knowledge about methotrexate. Retrospective study of data collected in routine care. STROBE guidelines were used. Rheumatoid arthritis patients treated with methotrexate had a therapeutic education session conducted by a rheumatology nurse at time 0 and 6 months after. They completed a questionnaire to assess their knowledge about methotrexate before the first therapeutic education session and 6 and 12 months after. A score from 0 to 100 was calculated based on 20 questions. A total of 66 patients were enrolled (50 women), with a mean age of 57 years, median disease duration of 4 years, and methotrexate treatment duration of 2 years. The knowledge score improved 6 months after the first therapeutic education session and was unchanged at 12 months. Significant improvement was observed in knowledge about the need for contraception, the contraindication of trimethoprim, the maximum dose not to be exceeded, reduction in alcohol consumption, and the value of combining folic acid with methotrexate. Knowledge about the risk of hypersensitivity pneumonitis did not improve. Skills related to the need for and timing of laboratory testing and contraception were evaluated using two role-playing situations. None of the skills improved. A therapeutic education session improves patients' knowledge about methotrexate at 6 months.
33770536 Arterial wall inflammation in rheumatoid arthritis is reduced by anti-inflammatory treatme 2021 Apr BACKGROUND: Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD), partly due to an increased prevalence of cardiovascular risk factors, but also due to chronic systemic inflammation inducing atherosclerotic changes of the arterial wall. The aim of this study was to determine whether anti-inflammatory therapy for the treatment of RA has favorable effects on arterial wall inflammation in RA patients. METHODS: Arterial wall inflammation before and after 6 months of anti-inflammatory treatment was assessed in 49 early and established RA patients using 18F-fluorodeoxyglucose-positron emission tomography with computed tomography (18F-FDG-PET/CT). Arterial 18F-FDG uptake was quantified as maximum standardized uptake value (SUVmax) in the thoracic aorta, abdominal aorta, carotid, iliac and femoral arteries. Early RA patients (n = 26) were treated with conventional synthetic disease modifying anti-rheumatic drugs with or without corticosteroids, whereas established RA patients (n = 23) were treated with adalimumab. RESULTS: In RA patients, overall SUVmax was over time reduced by 4% (difference -0.06, 95%CI -0.12 to -0.01, p = 0.02), with largest reductions in carotid (-8%, p = 0.001) and femoral arteries (-7%, p = 0.005). There was no difference in arterial wall inflammation change between early and established RA patients (SUVmax difference 0.003, 95%CI -0.11 to 0.12, p = 0.95). Change in arterial wall inflammation significantly correlated with change in serological inflammatory markers (erythrocyte sedimentation rate and C-reactive protein). CONCLUSION: Arterial wall inflammation in RA patients is reduced by anti-inflammatory treatment and this reduction correlates with reductions of serological inflammatory markers. These results suggest that anti-inflammatory treatment of RA has favorable effects on the risk of cardiovascular events in RA patients.
34477936 Bioinformatics-based study to identify immune infiltration and inflammatory-related hub ge 2021 Dec Rheumatoid arthritis (RA) is a systemic autoimmune disease whose principal pathological change is aggressive chronic synovial inflammation; however, the specific etiology and pathogenesis have not been fully elucidated. We downloaded the synovial tissue gene expression profiles of four human knees from the Gene Expression Omnibus database, analyzed the differentially expressed genes in the normal and RA groups, and assessed their enrichment in functions and pathways using bioinformatics methods and the STRING online database to establish protein-protein interaction networks. Cytoscape software was used to obtain 10 hub genes; receiver operating characteristic (ROC) curves were calculated for each hub gene and differential expression analysis of the two groups of hub genes. The CIBERSORT algorithm was used to impute immune infiltration. We identified the signaling pathways that play important roles in RA and 10 hub genes: Ccr1, Ccr2, Ccr5, Ccr7, Cxcl5, Cxcl6, Cxcl13, Ccl13, Adcy2, and Pnoc. The diagnostic value of these 10 hub genes for RA was confirmed using ROC curves and expression analysis. Adcy2, Cxcl13, and Ccr5 are strongly associated with RA development. The study also revealed that the differential infiltration profile of different inflammatory immune cells in the synovial tissue of RA is an extremely critical factor in RA progression. This study may contribute to the understanding of signaling pathways and biological processes associated with RA and the role of inflammatory immune infiltration in the pathogenesis of RA. In addition, this study shows that Adcy2, Cxcl13, and Ccr5 have the potential to be biomarkers for RA treatment.
33895477 Evaluation of oxidant and intracellular anti-oxidant activity in rheumatoid arthritis pati 2021 Aug Rheumatoid Arthritis (RA) is the most prevalent cause of the systematic inflammatory arthritis that destroys the joints. While the pathogenesis of RA remains to be clarified, the imbalance in the oxidant and anti-oxidant defense system plays a crucial role. This study aims to evaluate oxidant and anti-oxidant levels of RA patients and their impacts on the activity of the disease via in silico studies. 28 patients who had not previously received any treatment for RA and 20 healthy controls were included. Their oxidative stress markers, antioxidant markers, and inflammatory factors were investigated via in silico studies. Compared to the Control Group, serum CRP levels, MDA levels, and XO activities were higher in RA Group. Cu/ZnSOD and GPx activities decreased while CAT activities remained unchanged. Besides, there was a positive correlation between MDA-serum CRP levels but a negative correlation between MDA levels-Cu/ZnSOD activities. Furthermore, we observed a negative correlation between CRP levels and Cu/ZnSOD activities. Based on these results, it was concluded that oxidative stress had increased, the defense system had weakened, and ROS production had increased. Finally, our study results with SOD and CAT activity were confirmed by molecular docking studies.
34638916 Impact of Posttranslational Modification in Pathogenesis of Rheumatoid Arthritis: Focusing 2021 Sep 30 Rheumatoid arthritis (RA) is caused by prolonged periodic interactions between genetic, environmental, and immunologic factors. Posttranslational modifications (PTMs) such as citrullination, carbamylation, and acetylation are correlated with the pathogenesis of RA. PTM and cell death mechanisms such as apoptosis, autophagy, NETosis, leukotoxic hypercitrullination (LTH), and necrosis are related to each other and induce autoantigenicity. Certain microbial infections, such as those caused by Porphyromonasgingivalis, Aggregatibacter actinomycetemcomitans, and Prevotella copri, can induce autoantigens in RA. Anti-modified protein antibodies (AMPA) containing anti-citrullinated protein/peptide antibodies (ACPAs), anti-carbamylated protein (anti-CarP) antibodies, and anti-acetylated protein antibodies (AAPAs) play a role in pathogenesis as well as in prediction, diagnosis, and prognosis. Interestingly, smoking is correlated with both PTMs and AMPAs in the development of RA. However, there is lack of evidence that smoking induces the generation of AMPAs.
33200208 Peripheral blood mononuclear cells are hypomethylated in active rheumatoid arthritis and m 2021 Apr 6 OBJECTIVE: Epigenetic modifications are dynamic and influence cellular disease activity. The aim of this study was to investigate global DNA methylation in peripheral blood mononuclear cells (PBMCs) of RA patients to clarify whether global DNA methylation pattern testing might be useful in monitoring disease activity as well as the response to therapeutics. METHODS: Flow cytometric measurement of 5-methyl-cytosine (5'-mC) was established using the cell line U937. In the subsequent prospective study, 62 blood samples were investigated, including 17 healthy donors and 45 RA patients at baseline and after 3 months of treatment with methotrexate, the IL-6 receptor inhibitor sarilumab, and Janus kinase inhibitors. Methylation status was assessed with an anti-5'-mC antibody and analysed in PBMCs and CD4+, CD8+, CD14+ and CD19+ subsets. Signal intensities of 5'-mC were correlated with 28-joint DASs with ESR and CRP (DAS28-ESR and DAS28-CRP). RESULTS: Compared with healthy individuals, PBMCs of RA patients showed a significant global DNA hypomethylation. Signal intensities of 5'-mC correlated with transcription levels of DNMT1, DNMT3B and MTR genes involved in methylation processes. Using flow cytometry, significant good correlations and linear regression values were achieved in RA patients between global methylation levels and DAS28-ESR values for PBMCs (r = -0.55, P = 0.002), lymphocytes (r = -0.57, P = 0.001), CD4+ (r = -0.57, P = 0.001), CD8+ (r = -0.54, P = 0.001), CD14+ (r = -0.49, P = 0.008) and CD19+ (r = -0.52, P = 0.004) cells. CONCLUSIONS: The degree of global DNA methylation was found to be associated with disease activity. Based on this novel approach, the degree of global methylation is a promising biomarker for therapy monitoring and the prediction of therapy outcome in inflammatory diseases.
33397438 Validation of the adjusted multi-biomarker disease activity score as a prognostic test for 2021 Jan 4 BACKGROUND: The multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors. METHODS: Four cohorts were analyzed: the BRASS and Leiden registries and the OPERA and SWEFOT studies (total N = 953). Treatments included conventional DMARDs and anti-TNFs. Associations of radiographic progression (ΔTSS) per year with the adjusted MBDA score, seropositivity, and clinical measures were evaluated using linear and logistic regression. The adjusted MBDA score was (1) validated in Leiden and SWEFOT, (2) compared with other measures in all four cohorts, and (3) used to generate curves for predicting risk of radiographic progression. RESULTS: Univariable and bivariable analyses validated the adjusted MBDA score and found it to be the strongest, independent predicator of radiographic progression (ΔTSS > 5) compared with seropositivity (rheumatoid factor and/or anti-CCP), baseline TSS, DAS28-CRP, CRP SJC, or CDAI. Neither DAS28-CRP, CDAI, SJC, nor CRP added significant information to the adjusted MBDA score as a predictor, and the frequency of radiographic progression agreed with the adjusted MBDA score when it was discordant with these measures. The rate of progression (ΔTSS > 5) increased from < 2% in the low (1-29) adjusted MBDA category to 16% in the high (45-100) category. A modeled risk curve indicated that risk increased continuously, exceeding 40% for the highest adjusted MBDA scores. CONCLUSION: The adjusted MBDA score was validated as an RA disease activity measure that is prognostic for radiographic progression. The adjusted MBDA score was a stronger predictor of radiographic progression than conventional risk factors, including seropositivity, and its prognostic ability was not significantly improved by the addition of DAS28-CRP, CRP, SJC, or CDAI.
34248117 Immune Reconstitution Inflammatory Syndrome Associated with Pneumocystis jirovecii Pneumon 2022 Jan 15 A 68-year-old woman presenting with rheumatoid arthritis was admitted due to pancytopenia caused by methotrexate. Pneumocystis jirovecii pneumonia was diagnosed based on the abnormal shadows observed on chest computed tomography, the presence of serum β-D-glucan, and positive P. jirovecii-DNA results in a sputum analysis. Subsequently, after treatment with leucovorin and trimethoprim-sulfamethoxazole, lung consolidation was found to be aggravated, along with a rapidly increasing leukocyte count. In addition, cytomegalovirus colitis was diagnosed. Both conditions were associated with immune reconstitution inflammatory syndrome caused by recovery from leukopenia. The patient was successfully treated with intravenous methylprednisolone pulse therapy and ganciclovir.
33427622 Anti-tumour necrosis factor-alpha response associated with combined CD226 and HLA-DRB1[*]0 2021 Mar OBJECTIVES: Predicting response to anti-tumour necrosis factor alpha (anti-TNFα) drugs at baseline remains an elusive goal in rheumatoid arthritis (RA) management. The purpose of this study was to determine if baseline genetic variants of PTPRC, AFF3, myD228, CHUK, MTHFR1, MTHFR2, CD226 and a number of KIR and HLA alleles could predict response to anti-TNF-α in rheumatoid arthritis patients. METHODS: Peripheral blood samples were collected from 238 RA patients treated with anti-TNFα drugs. Genotyping was performed using biochip array technology by Randox Laboratories Ltd. and sequence specific polymerase chain reaction. Linear regression analysis was performed to investigate the role of these genotypes in predicting response to treatment, as defined by European League Against Rheumatism (EULAR) response classification and absolute change in disease activity score (DAS28). RESULTS: Of 238 RA patients analysed, 50.4% received adalimumab, 29.7% received etanercept, 14.8% received infliximab, 3.4% certoluzimab and 1.7% golimumab. The MTHFR1 variant rs1801133 was significantly associated with the EULAR response, p=0.044. Patients with the HLA-DRB1*0404 allele displayed a significantly larger reduction in DAS28 compared to non-carriers (mean -2.22, -1.67 respectively, p=0.033). CD226 rs763361 was the only SNP variant significantly associated with ΔDAS28 (p=0.029). CONCLUSIONS: This study has investigated individual allele associations with reductions in DAS28 across a range of anti-TNFα treatments. A combined predictive model indicates that patients with the HLA-DRB1*0404 allele and without the CD226 rs763361 polymorphism exhibit the largest reduction in DAS28 after anti-TNF-α treatment.
34254354 LncRNA NEAT1_1 suppresses tumor-like biologic behaviors of fibroblast-like synoviocytes by 2022 Mar Fibroblast-like synoviocytes (FLSs) are the predominant effector cells in the pathological progression of rheumatoid arthritis (RA). Therefore, elucidating the underlying molecular mechanism of the biologic behaviors in RA-FLSs will be helpful in developing the potent targets for the treatment of RA. We have previously documented that the tumor-like biologic behaviors of RA-FLSs are exacerbated by urokinase-type plasminogen activator receptor (uPAR), a specifically up-regulated receptor in RA-FLSs. Here, we investigate the further mechanism of uPAR and clarify its function in RA-FLSs. We demonstrate that miR-221-3p positively correlates to uPAR and regulates uPAR level in RA-FLSs. Simultaneously, one long noncoding RNA, nuclear paraspeckle assembly transcript 1_1 (NEAT1_1) is identified, which can predictively target miR-221-3p at three sites, indicating a strong possibility of being a competing endogenous RNA in RA-FLSs. Interestingly, NEAT1_1 and miR-221-3p can colocate in the nucleus and cytoplasm in RA-FLSs. Importantly, NEAT1_1 can act as a rheostat for the miR-221-3p/uPAR axis and the downstream JAK signaling. In line with the biologic function, NEAT1_1 negatively regulates the tumor-like characters, and cytokine secretions of RA-FLSs. Collectively, our data provide new insight into the mechanisms of NEAT1_1 in modulating RA-FLSs tumor-like behaviors. The targeting of NEAT1_1 and miR-221-3p/uPAR axis may have a promising therapeutic role in patients with RA.
33285551 Associations between Polymorphisms in the IL-1 Gene and the Risk of Rheumatoid Arthritis a 2021 BACKGROUND: Previous studies on polymorphisms in interleukin-1 (IL-1) and the risk of rheumatoid arthritis (RA)/systemic lupus erythematosus (SLE) yielded inconsistent results. OBJECTIVES: The authors performed this meta-analysis to more robustly evaluate associations between polymorphisms in the IL-1 gene and the risk of RA/SLE. METHODS: MEDLINE, Embase, Web of Science, Wanfang, VIP, and CNKI were systematically searched for eligible studies, and 34 relevant studies were finally selected to be eligible for inclusion. RESULTS: We found that IL-1A +4845G/T polymorphism was significantly associated with the risk of RA in the overall population (dominant comparison: p = 0.02; overdominant comparison: p = 0.05; allele comparison: p = 0.04), whereas IL-1B +3954C/T polymorphism was significantly associated with the risk of RA in the overall population (overdominant comparison: p = 0.03; allele comparison: p = 0.01) and Asians (recessive comparison: p = 0.007; allele comparison: p = 0.002). In addition, we found that IL-1A -889C/T polymorphism was significantly associated with the risk of SLE in Caucasians (allele comparison: p = 0.04), IL-1B -31T/C polymorphism was significantly associated with the risk of SLE in the overall population (recessive comparison: p = 0.04), and IL-1B -511C/T polymorphism was significantly associated with the risk of SLE in Asians (recessive comparison: p = 0.01; allele comparison: p = 0.03). CONCLUSIONS: This meta-analysis suggests that IL-1A +4845G/T and IL-1B +3954C/T polymorphisms may influence the risk of RA, whereas IL-1A -889C/T, IL-1B -31T/C, and IL-1B -511C/T polymorphisms may influence the risk of SLE.
33691749 Transcriptome-wide study of TNF-inhibitor therapy in rheumatoid arthritis reveals early si 2021 Mar 10 BACKGROUND: Despite the success of TNF-inhibitor therapy in rheumatoid arthritis treatment, up to 40% of patients fail to respond adequately. This study aimed to identify transcriptome-based biomarkers of adalimumab response in rheumatoid arthritis (RA) to aid timely switching in non-responder patients and provide a better mechanistic understanding of the pathways involved in response/non-response. METHODS: The Affymetrix Human Transcriptome Array 2.0 (HTA) was used to measure the transcriptome in whole blood at pre-treatment and at 3 months in EULAR good- and non-responders to adalimumab therapy. Differential expression of transcripts was analysed at the transcript level using multiple linear regression. Differentially expressed genes were validated in independent samples using OpenArray™ RT-qPCR. RESULTS: In total, 813 transcripts were differentially expressed between pre-treatment and 3 months in adalimumab good-responders. No significant differential expression was observed between good- and non-responders at either time-point and no significant changes were observed in non-responders between time-points. OpenArray™ RT-qPCR was performed for 104 differentially expressed transcripts in good-responders, selected based on magnitude of effect or p value or based on prior association with RA or the immune system, validating differential expression for 17 transcripts. CONCLUSIONS: An early transcriptome signature of DAS28 response to adalimumab has been identified and replicated in independent datasets. Whilst treat-to-target approaches encourage early switching in non-responsive patients, registry evidence suggests that this does not always occur. The results herein could guide the development of a blood test to distinguish responders from non-responders at 3 months and support clinical decisions to switch non-responsive patients to an alternative therapy.
32755722 Time to initiation of biologic disease-modifying antirheumatic drugs in the French cohort 2021 Jan OBJECTIVE: To assess the time to initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs) in ESPOIR, the French cohort of patients with rheumatoid arthritis (RA), and factors associated with the timing of bDMARD initiation. METHODS: In total, 658 patients with early RA satisfying the 2010 ACR/EULAR criteria were included between 2003 and 2005 and followed annually for 10 years (end of follow up: 2013-2015). The timing of bDMARD introduction and predictors of use were analysed by the Kaplan-Meier method based on Cox proportional-hazard models. RESULTS: Overall, 178 patients (31.0%, 95% confidence interval [27.0-34.7]) initiated a bDMARD during the 10-year follow-up, with a mean delay of 43.6 months. The penetration rate was higher during the first 2 years of follow-up (6% between the first and second year, approximately 3.3% each year between the second and seventh year, and<2.0% after the eighth year). The first-used bDMARD was etanercept for 72 patients and adalimumab for 71. On multivariate analysis, Disease Activity Score in 28 joints, radiologic progression and positivity for anti-citrullinated protein antibodies were significantly associated with rapid initiation of a bDMARD (P<0.0001), whereas older age at first joint pain was inversely associated (P<0.0001). CONCLUSIONS: Although access to bDMARDs is widespread in France, less than one third of patients with early RA in the ESPOIR cohort initiated a bDMARD over the 10-year follow-up. Poor prognostic factors for RA were associated with more rapid initiation, as expected.
34870735 Usefulness of noninvasive diagnostic procedures for assessment of methotrexate hepatotoxic 2022 Apr Methotrexate (MTX) is recommended as a first-line treatment for rheumatoid arthritis (RA). There are no strict guidelines regarding monitoring for liver damage in RA patients. This study aimed to evaluate noninvasive diagnostic procedures in assessing liver fibrosis in RA patients. Ninety-six RA patients were recruited for this study. The procollagen III N-terminal peptide (PIIINP) serum level was measured in all patients. The Enhanced Liver Fibrosis score (ELF-1) was calculated for 82 patients. Transient elastography (TE) was performed in 91 patients, those examined were divided into two groups: a study and control group, comprising patients with and without risk factors for liver fibrosis, respectively. The TE result correlated only with the body mass index-BMI (p < 0.05); there was no correlation with the cumulative MTX dose (p = 0.33). The TE result was significantly higher in those with risk factors for liver fibrosis than in those without risk factors (TE result >  = 7.1 kPa 28/42 vs 13/41, HR = 2.103, Mann-Whitney U test, approximately 0.02). There was a positive correlation between the PIIINP level and body weight (p = 0.028), cumulative MTX dose (p = 0.007), RA activity (p = 0.028) and diabetes mellitus (DM) (p = 0.001). There was a positive correlation between the ELF-1 score and age (p < 0.001), cumulative MTX dose (p = 0.007) and RA activity (p < 0.001). The PIIINP level and ELF-1 score are not organ specific, and readings may vary depending on RA activity. TE is organ specific and can be performed by a skilled ultrasonographer might be useful to assess actual liver condition.
34153036 Rheumatoid arthritis serotype and synthetic disease-modifying anti-rheumatic drugs in pati 2021 Patients with rheumatoid arthritis (RA) experience a higher prevalence of periodontitis. This study aimed to examine the variation of periodontitis experienced with different serotypes suffered by RA patients and to examine the relationship between the different medications taken for RA that may influence this relationship. Two hundred and sixty RA and control participants underwent standardized periodontal examinations. Medical, serological and radiological (Sharp/van der Heijde) records were assessed. Functional status was assessed using the administered Health Assessment Questionnaire. Moreover, disease parameters, including disease activity (DAS28-ESR) and anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) seropositivity were evaluated. Periodontitis was higher in RA (71.54%) compared with controls (54.62%). The stage of periodontitis experienced by ACPA-positive participants were higher than APCA-negative participants. The probing pocket depth and recession experienced by RF-positive participants were higher than those who were RF-negative. RA participants on methotrexate had lower clinical attachment loss and lower periodontal probing depth compared with participants on a combination methotrexate and other disease-modifying antirheumatic drugs. Participants taking corticosteroids had lower gingival index scores. The association between seropositivity and the type of medications taken with periodontal health parameters in this group of patients suggests that both seropositivity and medications taken are important modifiers in the relationship between periodontitis and RA.
33741378 Protective effect of Bacteroides fragilis LPS on Escherichia coli LPS-induced inflammatory 2021 May It has been reported that patients with rheumatoid arthritis (RA) have significantly less bacteria belonging to the Bacteroides group in their microbiota. We speculate that inhibition of cytokine production is impaired in patients with RA owing to their low levels of intestinal bacteria belonging to the Bacteroidetes group. Here we investigated the effect of Bacteroides fragilis lipopolysaccharide (B-LPS) on cytokine production in vitro and on the development of collagen antibody-induced arthritis (CAIA) in DBA/1 mice, an animal model of RA. in vitro culture experiments showed that Escherichia coli LPS (E-LPS)-induced cytokine production from THP-1 monocytic cells and peripheral blood mononuclear cells was significantly suppressed by B-LPS in a dose-dependent manner. A decrease in TNF-α and IL-1β production was also observed in LPS-tolerized macrophages induced by B-LPS at concentrations equal to and higher than that of E-LPS. Similar results were obtained when autoclaved feces were used to induce cytokine production instead of E-LPS. In in vivo experiments using CAIA models, B-LPS had no adverse effects even when administered at 10 times the concentration of E-LPS, which elicits severe arthritis. In addition, simultaneous administration of high dose B-LPS with E-LPS or administration of B-LPS prior to E-LPS significantly suppressed arthritis development in CAIA model animals when compared with administration of E-LPS alone. These results suggest that increasing certain bacterial groups such as Bacteroides is an effective strategy for preventing arthritis development in patients with RA.