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ID PMID Title PublicationDate abstract
33592912 ETS1 polymorphism rs73013527 in relation to serum RANKL levels among patients with RA. 2021 Feb 5 We previously identified E26 transformation specific sequence 1 (ETS1) rs73013527 single nucleotide polymorphism associated with RA susceptibility and disease activity. In the present study, we aims to further investigate the association between ETS1 rs73013527 and receptor activator of nuclear factor kappa B ligand (RANKL), an index related to bone destruction and was reported to elevate in RA.We determined genotypes of ETS1 rs73013527, serum RANKL concentration, clinical characteristics (disease duration, disease activity score for 28 painful/swollen joints), and laboratory markers (rheumatoid factor, anti-citrullinated protein antibody, anti-keratin antibody, c-reactive protein, erythrocyte sedimentation rate) of 254 RA cases. Univariate and multivariate analysis were employed to explore the association between ETS1 rs73013527 and serum RANKL levels in RA patients.Univariate and multivariate analysis indicated no association of serum RANKL levels with patient age, gender, clinical characteristics, and laboratory markers. Univariate analysis, not multivariate analysis indicated genotype CT/TT of ETS1 rs73013527 was significantly associated with elevated RANKL levels in RA patients.ETS1 rs73013527 is in relation to serum RANKL levels among patients with RA. ETS1 probably might be an indirect factors involved in RANKL regulation in RA.
33337994 Occurrence and predictive factors of high blood pressure, type 2 diabetes, and metabolic s 2021 Sep OBJECTIVES: In rheumatoid arthritis (RA), "traditional" cardiovascular (CV) risk factors continue to be underdiagnosed and undertreated, thus increasing the risk of developing atherosclerosis. In this work, we evaluated the occurrence and predictive factors of "traditional" cardiovascular risk factors, with a focus on high blood pressure (HBP), type 2 diabetes (T2D), and metabolic syndrome (MetS), in participants with RA, in a 3-year, multicentre, prospective, observational study. METHODS: To assess the occurrence and predictive factors of HBP, T2D, and MetS, consecutive participants with RA, admitted to Italian Rheumatology Units, were evaluated in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort, a 3-year, multicentre, prospective, observational study. RESULTS: In the present evaluation, 841 participants, who were fully followed up with 3-year of prospective follow-up were assessed. At the end of follow-up, a significant increased incidence of HBP, T2D, and MetS was recorded. Assessing predictive factors, the mean values of C-reactive protein during the follow-up were independent predictors of occurrence of those comorbidities, whereas participants maintaining remission showed a significant lower risk. Furthermore, therapy with hydroxychloroquine (HCQ) reduced the risk of occurrence of T2D and MetS. CONCLUSIONS: An increased incidence of HBP, T2D, and MetS was observed in assessed participants, prospectively followed-up. Furthermore, the analysis of predictive factors suggested that the rheumatoid pro-inflammatory process could increase the occurrence of these comorbidities. Conversely, metabolic and cardiovascular benefits of maintaining remission as well as of therapy with HCQ were reported.
32573416 Severely destructive unilateral wrist arthritis as a rare variant of rheumatoid arthritis: 2021 Mar OBJECTIVES: Rheumatoid arthritis (RA) is a common autoimmune disease typically affecting joints symmetrically. A small number of patients develop unilateral and severely destructive wrist arthritis (DWA). The objective of our study was to characterise patients with this type of affection. METHODS: This was a retrospective cohort study of RA patients with positive RF/anti-CCP antibodies. Clinical characteristics, including, age, gender, disease duration, dexterity, occupational history, smoking status, and the number of prescribed DMARDs were recorded. Conventional radiographs were evaluated using the modified Sharp/van der Heijde scoring (mSS) method. RESULTS: We analysed our laboratory database of 1247 patients and identified 559 patients with a clinical diagnosis of RA. For 395 of the patients, radiographs of the hands were available for evaluation. 25 patients had extensive unilateral DWA, corresponding to a prevalence of 6.3% (25 of 395 patients). 11 patients were excluded due to incomplete data. Of the remaining 14 patients, 13 were female with a median age of 61 (33-83) years, and median disease duration of 18 (1-33) years. 8 of 11 (72.7%) patients were smokers; in three, smoking status was not known. 80% with known dexterity developed unilateral DWA in the dominant hand. Total mSS was significantly higher on the affected side (39, interquartile range 35.25-46.25) versus non-affected (13, IQR 3-23). MSS were not different if the carpal bones were excluded from scoring. Side of involvement (left vs. right), or dominant versus non-dominant hand, did not result in a different mSS. CONCLUSIONS: Unilateral DWA is a rare variant of RA which predominantly affects women who smoke.
32744971 Current Biomedical and Diagnostic Applications of Gold Micro and Nanoparticles. 2021 Production of particles and their adaptation in the pharmacology became an object of interest, and they are the currently introduced therapies based on the use of micro and nanoparticles. The use of gold particles is not an exception. This review has focused on the application of gold micro and nanoparticles in pharmacology and biomedicine. The particles can be used for diagnosis respective theranostic of cancer, rheumatoid arthritis and as antimicrobial means. Besides these applications, specifications of gold, gold particles, and colloidal gold manufacturing and their comparison with the solid gold, are described as well. This review is based on a survey of actual scientific literature.
34778939 Pregnancy outcomes in patients with rheumatoid arthritis who discontinue methotrexate trea 2022 Mar INTRODUCTION/OBJECTIVES: Rheumatoid arthritis (RA) develops at reproductive age. Methotrexate (MTX), the anchor drug for RA treatment, is contraindicated during pregnancy. We investigated pregnancy outcomes in RA patients in whom MTX was withdrawn. METHOD: Pregnancy outcomes, RA treatment, and infertility factors were examined in patients with RA who discontinued MTX prior to attempting conception. The Mann-Whitney U test and Fisher's exact test were used to evaluate differences between the groups. RESULTS: Of the 52 patients enrolled in this study, 33 gave birth after discontinuing MTX and 19 did not. The age at MTX discontinuation was significantly different between the childbirth and non-childbirth groups (p = 0.0258). The use of non-steroidal anti-inflammatory drugs (NSAIDs) and salazosulfapyridine was significantly different between the groups (p = 0.0079 and p = 0.0438, respectively). Patients whose time from MTX discontinuation to pregnancy was longer than 12 months had a longer previous MTX administration period (p = 0.0182) and were older at the time of pregnancy (p = 0.0128) than those whose was shorter. CONCLUSIONS: The results suggest that to ensure successful childbirth in women with RA, the decision to conceive should be made at the youngest possible age, NSAIDs should not be used, and a shorter duration of MTX treatment should be considered before pregnancy. Nevertheless, additional studies with larger sample sizes are warranted to analyse the effects of other factors on pregnancies in patients with RA. KEY POINTS: • Patients with RA who plan to conceive must discontinue MTX therapy. • To achieve successful pregnancy outcomes, female patients with RA should become pregnant when they are young, discontinue NSAIDs prior to conception, and shorten their durations of MTX therapy before attempting pregnancy.
34193517 Risk factors for venous thromboembolism and atherosclerotic cardiovascular disease: do the 2021 Jun OBJECTIVE: Venous thromboembolism (VTE) is an increasing concern in rheumatoid arthritis (RA) with little known about risk factors. We aimed to compare risk factors for unprovoked VTE and atherosclerotic cardiovascular disease (ASCVD) in patients with RA and to assess subsequent ASCVD risk after an unprovoked VTE. METHODS: People with RA participating in a US-wide longitudinal observational registry from 1998 to 2018 were assessed for incident unprovoked VTE (deep venous thrombosis and pulmonary emboli not associated with cancer, recent surgery, hospitalisation, fracture and pregnancy) and ASCVD (myocardial infarction and stroke) validated from hospital/death records. Risk factors for VTE and ASCVD and the risk of ASCVD after an unprovoked VTE were determined using Cox proportional hazards models. RESULTS: During median (IQR) 4 (1.5-7) years of follow-up in 31 366 patients with RA, 539 unprovoked VTE and 1648 ASCVD events were identified. The adjusted models showed increased VTE and ASCVD risk with older age, male sex, comorbidities, prior fracture, worse disability, higher disease activity and glucocorticoids. Traditional cardiovascular disease risk factors were common in both ASCVD and VTE but only increased ASCVD risk with obesity as the exception (VTE HR (95% CI), 1.46 (1.13-1.87)) and ASCVD, 0.58 (0.50-0.68)). ASCVD risk doubled after an unprovoked VTE (HR (95% CI), 2.05 (1.43-2.95)). CONCLUSION: Our findings suggest that unprovoked VTE is mediated by inflammation of RA and may be considered a spectrum of pan-cardiovascular syndrome.
33514671 Diagnostic issues in difficult-to-treat rheumatoid arthritis: a systematic literature revi 2021 Jan OBJECTIVES: To summarise the evidence on diagnostic issues in difficult-to-treat rheumatoid arthritis (D2T RA) informing the EULAR recommendations for the management of D2T RA. METHODS: A systematic literature review (SLR) was performed regarding the optimal confirmation of a diagnosis of rheumatoid arthritis (RA) and of mimicking diseases and the assessment of inflammatory disease activity. PubMed and Embase databases were searched up to December 2019. Relevant papers were selected and appraised. RESULTS: Eighty-two papers were selected for detailed assessment. The identified evidence had several limitations: (1) no studies were found including D2T RA patients specifically, and only the minority of studies included RA patients in whom there was explicit doubt about the diagnosis of RA or presence of inflammatory activity; (2) mostly only correlations were reported, not directly useful to evaluate the accuracy of detecting inflammatory activity in clinical practice; (3) heterogeneous, and often suboptimal, reference standards were used and (4) (thus) only very few studies had a low risk of bias.To ascertain a diagnosis of RA or relevant mimicking disease, no diagnostic test with sufficient validity and accuracy was identified. To ascertain inflammatory activity in patients with RA in general and in those with obesity and fibromyalgia, ultrasonography (US) was studied most extensively and was found to be the most promising diagnostic test. CONCLUSIONS: This SLR highlights the scarcity of high-quality studies regarding diagnostic issues in D2T RA. No diagnostic tests with sufficient validity and accuracy were found to confirm nor exclude the diagnosis of RA nor its mimicking diseases in D2T RA patients. Despite the lack of high-quality direct evidence, US may have an additional value to assess the presence of inflammatory activity in D2T RA patients, including those with concomitant obesity or fibromyalgia.
34099538 Treatment journey in rheumatoid arthritis with biosimilars: from better access to good dis 2021 Jun Early diagnosis and treatment of rheumatoid arthritis (RA) are of critical importance to halt the progression of the disease. Optimal use of advanced imaging techniques or biomarkers may facilitate early diagnosis of RA. Even though many disease-modifying anti-rheumatic drugs (DMARDs) are available for RA treatment, biological DMARDs (bDMARDs) offer expanding therapeutic options and good outcomes in patients with RA who do not have a sufficient response to conventional synthetic DMARDs. However, high costs of bDMARDs have limited patient access to optimised disease management and increased the cost burden for healthcare systems. The advent of biosimilars led to significant cost savings driven by price competition among the reference products, which could be beneficial for healthcare systems. Healthcare provider (HCP)-patient communication and informed shared decision-making are crucial to prevent the occurrence of a nocebo effect, which results from negative perceptions that patients may have and could lead to less effective outcomes. Research has demonstrated that effective communication between HCPs and patients utilising positive framing can improve acceptance by patients to be initiated on or switched to a biosimilar and can help to integrate biosimilars into routine clinical practice to maximise benefits for patients with RA.
34379040 Relation between anti-Porphyromonas gingivalis antibody titers and HLA-DRB1 neutral allele 2022 Mar OBJECTIVE: This study aimed to determine the relation between titres of anti-Porphyromonas gingivalis (P. gingivalis) antibody and rheumatoid arthritis (RA) HLA-DRB1 susceptibility region associated with shared epitope (SE) using the Gregersen's and de Vries's classification methods. MATERIAL AND METHODS: In this cross-sectional study, results of immunoglobulin G1 (IgG1) and immunoglobulin G2 (IgG2) anti-P. gingivalis antibodies, anti-citrullinated protein antibodies (ACPA), diagnosis for RA, and periodontal disease (PD), and a genetic study of the HLA DRB1 region were obtained from 50 patients with RA and 50 control individuals. RESULTS: Anti-P. gingivalis antibody levels and PD parameters were similar in control and RA groups. Anti-P. gingivalis antibodies were not associated with SE or ACPA. There was no association between ACPA and SE. However, de Vries' classification in RA patients revealed an association between the HLA DRB1 neutral alleles and higher titres of anti-P. gingivalis antibodies as follows: IgG1 anti-P. gingivalis ≥ 1:400 (p = .039); IgG2 anti-P. gingivalis ≥ 1:400 with neutral/neutral genotype (N/N), being exclusive for RA (p = .008); and IgG2 anti-P. gingivalis ≥ 1:200 and N/N (p = .016). CONCLUSIONS: Although no association was found between SE and anti-P. gingivalis antibodies; according to the de Vries' classification, there was an existing association between HLA DRB1 neutral alleles, with high titres of IgG anti-P.gingivalis antibodies for RA, focussing on novel associations between P.gingivalis and RA.
33030132 Atherogenic Index of Plasma in Women with Rheumatoid Arthritis and Systemic Lupus Erythema 2021 BACKGROUND: Women with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are at high risk of cardiovascular diseases (CVD). The atherogenic index of plasma (AIP) is a new marker for the assessment of CVD. OBJECTIVE: This study aimed to determine the predictive value of AIP with long-term CVD risk among women with RA and SLE. METHODS: This is a cross-sectional study of 99 RA and 59 SLE women. Demographic, clinical, and biochemical data were obtained, and disease activities were calculated. For each patient, the longterm risk of CVD was calculated using the Framingham risk score (FRS); AIP was derived according to the logarithmic (triglycerides/high-density lipoproteins cholesterol). RESULTS: The mean age of the RA and SLE patients was 47.97 ± 8.78 and 36.75 ± 9.09 years, respectively. The median (interquartile range) of AIP values in RA and SLE patients were 0.34 (-0.15, 1.02) and 0.33 (-0.53, 0.96), respectively, while FRS values of RA patients and SLE patients were 6.38 ± 5.58 and 4.86 ± 4.5, respectively (p >0.05). There was a moderate correlation between AIP and FRS in RA and SLE patients (r=0.42, p=0.002 and r=0.33, p=0.007, respectively). According to the multivariate regression analyses, we found that AIP value is an independent factor for FRS in RA (β: 4.13, 95% confidence interval; 1.71, 6.18; p=0.008) and in SLE patients (β: 6.19, 95% confidence interval; 2.58, 9.81; p<0.001). CONCLUSIONS: We reported that AIP can be used as an independent indicator for long-term CVD risk in RA and SLE patients.
33651725 Osteoporosis and fractures in rheumatoid arthritis. 2021 May 1 PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is associated with increased risk for osteoporotic fracture. We highlight RA-specific risk factors for bone mineral density (BMD) loss and fractures and considerations regarding the diagnosis and treatment of osteoporosis in patients with RA. RECENT FINDINGS: Anticitrullinated protein antibody (ACPA) positivity, although associated with low BMD in early RA, is not associated with accelerated BMD loss over time when compared to ACPA negative individuals. Studies have found reduced BMD in individuals on low doses of glucocorticoids (GCs). Poor functional status and frailty are additional important risk factors for low BMD and fractures. Heightened fracture risk in RA may be mitigated by tight disease control, and biologic therapies are associated with more stable BMD compared to nonbiologic therapies. Evidence-based guidelines specific for treating osteoporosis in patients with RA do not exist. Thus, treatment decisions are based on general osteoporosis guidelines, taking into account additional RA-specific risk factors. SUMMARY: Recent studies have advanced knowledge of RA-specific risk factors for BMD loss and fractures. Future studies applying these findings to modify established fracture risk algorithms as well as evaluating osteoporosis treatments in RA cohorts are needed to reduce the risk of disabling fractures in these patients.
32324126 Effectiveness and safety of biologic and targeted synthetic disease-modifying anti-rheumat 2021 Mar OBJECTIVES: We aimed to evaluate the clinical outcomes and safety of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and to identify predictors of treatment responses to b/tsDMARDs in elderly patients with rheumatoid arthritis (RA). METHODS: Data from the nationwide cohort of elderly (≥ 65 years) patients enrolled in the KOBIO Registry were analysed. Clinical outcomes were assessed, including changes in the Simplified Disease Activity Index, after treatment. Adverse events and reasons for drug discontinuation were assessed. Multivariable logistic regression analyses were performed to determine which baseline variables affected treatment responses and adverse events (AE). RESULTS: Elderly patients treated with b/tsDMARDs (n=355) or conventional synthetic DMARDs (csDMARDs) (n=104) were included. The median age was 70 years and 77% were female. After 1 year, 63% of patients in the b/tsDMARD group and 68% in the csDMARD group achieved remission or low disease activity (LDA). Overall, 27% of patients in the b/tsDMARDs group and 24% in the csDMARDs group experienced AE. A total of 43.4% of patients on b/tsDMARDs discontinued therapy due to lack of effectiveness (27%), AE (34%), or other reasons (35%). The estimated median retention of b/tsDMARDs was 2.5 years. Male sex and non-exposure to tobacco at baseline were independent factors associated with achieving remission or LDA after 1 year. Interstitial lung disease (ILD) was the most prominent comorbidity associated with AE. CONCLUSIONS: Treatment with b/tsDMARDs is effective and well tolerated in elderly patients with RA; nonetheless, ILD is a key comorbidity that should be monitored carefully.
33775211 Heterogenous bone response to biologic DMARD therapies in rheumatoid arthritis patients an 2021 Nov Objectives: Previous studies of high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging of hand joints in patients with rheumatoid arthritis (RA) have suggested that erosion healing may occur. Our objective was to examine changes in erosion volume, joint space width (JSW), bone mineral density (BMD), and bone remodelling, and their association with clinical outcomes and measures of patient hand function.Method: We examined 48 patients who achieved a good response to a newly initiated biologic therapy. HR-pQCT images of the dominant hands' second and third metacarpophalangeal joints were obtained 3 and 12 months after therapy initiation. Bone erosion volume, JSW, BMD, and bone remodelling were quantified from HR-pQCT images, with improvement, no change (unchanged), or progression in these measures determined by least significant change. Disease activity and hand function measures were collected.Results: There were no significant group changes in HR-pQCT outcomes over the 9 month period. Twenty-two patients had total erosion volumes that remained unchanged, nine showed improvement, and two progressed. The majority of JSW and BMD measures remained unchanged. There was a significant association between the baseline Health Assessment Questionnaire score and the change in minimum JSW, but no other significant associations between HR-pQCT outcomes and function were observed.Conclusions: The vast majority of patients maintained unchanged JSW and BMD over the course of follow-up. Significant improvements in total erosion volume occurred in 27% of patients, suggesting that biologic therapies may lead to erosion healing in some patients, although this did not have an impact on self-reported and demonstrated hand function.
33840694 Immune Reconstitution Inflammatory Syndrome-like Condition Associated with Pneumocystis ji 2021 Oct 1 A 94-year-old woman with rheumatoid arthritis who had been treated with low-dose methotrexate was referred to our hospital because of a 3-day history of a fever and pancytopenia. With a diagnosis of febrile neutropenia of unknown origin, empirical antibiotic treatment and folinic acid therapy were initiated. Despite a recovery from pancytopenia, the high fever remained, and dyspnea developed. She was clinically diagnosed with Pneumocystis jirovecii pneumonia (PCP) and successfully treated with trimethoprim/sulfamethoxazole and adjunctive corticosteroid therapy. Folinic acid treatment effectively brought about rapid immune recovery but might have led to a clinical manifestation of PCP resembling immune reconstruction inflammatory syndrome.
33882889 Interactions between rheumatoid arthritis antibodies are associated with the response to a 2021 Apr 21 BACKGROUND: Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50-60% of rheumatoid arthritis (RA) patients. However, there are yet no biomarkers to stratify patients for anti-TNF therapy. Rheumatoid factor (RF) and anti-cyclic-citrullinated antibodies (anti-CCP) have been evaluated as biomarkers of response but the results have shown limited consistency. Anti-carbamylated protein (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4) antibodies have been much less studied. Despite being linked to common immune processes, the interaction between these markers has not been evaluated yet. Our aim was to analyze the interaction between these four antibodies in relation to the response to anti-TNF therapy. METHODS: For this objective, a prospective cohort of n = 80 RA patients starting anti-TNF therapy was recruited. Serum determinations at baseline were performed for RF, anti-CCP, anti-CarP and anti-PAD4 antibodies using enzyme-linked immunosorbent assays (ELISA). The clinical response to anti-TNF therapy was determined at week 12 using the change in DAS28 score. Association was performed using multivariate linear regression adjusting for baseline DAS28, sex and age. RESULTS: The interaction between pairs of antibodies was tested by the addition of an interaction term. We found two highly significant antibody interactions associated with treatment response: anti-CarP with anti-PAD4 (p = 0.0062), and anti-CCP with RF (p = 0.00068). The latter antibody interaction was replicated in an independent retrospective cohort of RA patients (n = 199, p = 0.04). CONCLUSIONS: The results of this study suggest that antibody interaction effects are important factors in the response to anti-TNF therapy in RA.
33889152 Efficacy and Safety of Adalimumab Biosimilars: Current Critical Clinical Data in Rheumatoi 2021 Adalimumab, as a TNF inhibitor biologic for the treatment of rheumatoid arthritis, is one of the top-selling drugs worldwide. As its various patents have gradually expired, experiments on its biosimilars are constantly being implemented. In this review, we summarized clinical trials of seven biosimilars currently approved by the FDA and/or EMA for the treatment of rheumatoid arthritis, namely: ABP 501 (Amjevita/Amgevita/Solymbic), BI 695501 (Cyltezo), SB5 (Imraldi/Hadlima), GP2017 (Hyrimoz/Hefiya/Halimatoz), MSB11022 (Idacio), FKB327 (Hulio), and PF-06410293 (Abrilada). Overall, these biosimilars showed similar efficacy, safety, and immunogenicity to adalimumab. All biosimilar switching trials indicated that switching from adalimumab to a biosimilar does not have a significant impact on efficacy, safety, and immunogenicity.
33427626 Real-world effectiveness of tofacitinib in patients with rheumatoid arthritis: a prospecti 2021 Nov OBJECTIVES: Tofacitinib is an approved treatment for rheumatoid arthritis (RA), but data on its use in the "real-world" are limited. We sought to analyse tofacitinib drug survival in the Israeli registry and compare it to other biologic agents. METHODS: We included RA patients treated with tofacitinib, etanercept, golimumab, tocilizumab, or abatacept between 2010-2019. The primary endpoint was event-free survival (EFS), defined as the time from treatment initiation to a treatment failure event from any cause (i.e., inefficacy or intolerability). EFS was compared between agents using Cox regression and Kaplan-Meier analysis, stratifying patients by treatment line. RESULTS: A total of 964 eligible treatment courses were included (tocilizumab [325], etanercept [284], abatacept [127], tofacitinib [139], and golimumab [109]). In a univariate analysis, EFS with tofacitinib in the complete cohort was similar to etanercept, golimumab, and abatacept but was lower than tocilizumab) 3-year EFS 43% vs. 53%, HR 0.65). In a multivariable analysis, tofacitinib was similar to all other drugs, except for etanercept, which was inferior (HR 1.70); advanced treatment line was also associated with greater risk for failure (HR 1.64). In a univariable analysis stratified by the treatment line, tofacitinib had similar or better drug survival than other agents in the first and second lines. In the third line and beyond, tocilizumab had a higher EFS compared to tofacitinib (HR 0.57). CONLUSIONS: Drug survival with tofacitinib is related to treatment line. Early introduction is associated with similar or better survival than other agents, whereas tocilizumab was superior in the third line or later.
33338002 Good pain, bad pain: illness perception and physician attitudes towards rheumatoid arthrit 2021 May OBJECTIVES: Rheumatoid arthritis (RA) and fibromyalgia syndrome (FM) are common diagnoses encountered in rheumatology practice, but do not enjoy the same status. We aimed to examine physician's illness perceptions regarding these two rheumatologic disorders and to evaluate how they correlate with their relationship with these patients. METHODS: Forty-five rheumatologists were enrolled in the study. Demographic data were registered. Measures collected included the Brief Illness Perception Questionnaire (BIPQ) and the Difficult Doctor- Patient Relation Questionnaire (DDPRQ-10). Both were recorded twice, related to FM and RA. Empathy and burnout were also assessed. RESULTS: Of 45 physicians included in the study, only 53% were willing to accept FM patients. FM was considered a more severe disease than RA (FM-BIPQ mean score 54, SD 5.5 versus RA-BIPQ mean 45.6 SD 6.5, p<0.00) in terms of treatment control, understanding and emotional response generated by the disease. Doctor-patient relationship was perceived more difficult with FM patients compared to RA patients (FM-DDPRQ mean score 35.1, SD 9.2 versus RA-DDPRQ mean 19.6, SD 7.1, p<0.00), and was significantly correlated to the patient's concern about the illness (p<0.034) and patient's emotional response (p<0.036). Resistance to accept FM patients was largely influenced by difficult doctor-patient relationship. Higher levels of empathy were found in physicians experiencing less difficulty with FM patients. CONCLUSIONS: FM patients were perceived as more difficult than RA patients, with a high level of concern and emotional response. A high proportion of physicians were reluctant to accept them because they feel emotional/psychological difficulties meeting and coping with these patients.
34887865 Addition of Fibroblast-Stromal Cell Markers to Immune Synovium Pathotypes Better Predicts 2021 OBJECTIVES: This study aims to investigate if addition of fibroblast-stromal cell markers to a classification of synovial pathotypes improves their predictive value on clinical outcomes in rheumatoid arthritis (RA). METHODS: Active RA patients with a knee needle synovial biopsy at baseline and finished 1-year follow-up were recruited from a real-world prospective cohort. Positive staining for CD20, CD38, CD3, CD68, CD31, and CD90 were scored semiquantitatively (0-4). The primary outcome was radiographic progression defined as a minimum increase of 0.5 units of the modified total Sharp score from baseline to 1 year. RESULTS: Among 150 recruited RA patients, 123 (82%) had qualified synovial tissue. Higher scores of CD20+ B cells, sublining CD68+ macrophages, CD31+ endothelial cells, and CD90+ fibroblasts were associated with less decrease in disease activity and greater increase in radiographic progression. A new fibroblast-based classification of synovial pathotypes giving more priority to myeloid and stromal cells classified samples as myeloid-stromal (57.7%, 71/123), lymphoid (31.7%, 39/123), and paucicellular pathotypes (10.6%, 13/123). RA patients with myeloid-stromal pathotype showed the highest rate of radiographic progression (43.7% vs. 23.1% vs. 7.7%, p = 0.011), together with the lowest rate of Boolean remission at 3, 6, and 12 months. Baseline synovial myeloid-stromal pathotype independently predicted radiographic progression at 1 year (adjusted OR: 3.199, 95% confidence interval (95% CI): 1.278, 8.010). Similar results were obtained in a subgroup analysis of treatment-naive RA. CONCLUSIONS: This novel fibroblast-based myeloid-stromal pathotype could predict radiographic progression at 1 year in active RA patients which may contribute to the shift of therapeutic decision in RA.
34402699 Evaluating filgotinib for the treatment of rheumatoid arthritis. 2021 Dec INTRODUCTION: Despite the availability of an extensive armamentarium, rheumatoid arthritis (RA) remains a therapeutic challenge for rheumatologists. Janus kinase inhibitors (JAKi) are an emerging class of targeted therapies. The number of JAKi has been growing and to date, filgotinib is the latest JAKi to be approved for use in RA. AREAS COVERED: This review focuses on the pharmacodynamics, pharmacokinetics, efficacy and safety of filgotinib in patients with RA. EXPERT OPINION: Filgotinib is an oral targeted synthetic disease-modifying antirheumatic drug (DMARD) that specifically inhibits JAKi. Filgotinib monotherapy, or a combination regimen with conventional synthetic (cs) DMARDs, has demonstrated efficacy in decreasing disease activity, with a well-managed safety profile in patients with early RA naive to DMARDs, and in RA that does not adequately respond to csDMARDs and/or biologic DMARDs. The selective inhibition of JAK1 may confer an improved safety profile, but further study is required as a potential testicular toxicity has been suggested. Filgotinib offers several advantages: oral administration, rapidity of action, efficacy as monotherapy, and demonstrated activity in difficult to treat RA. However, the placement of filgotinib in the therapeutic arsenal for RA may be influenced by the ongoing collection of long-term safety data from JAKi as a class.