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ID PMID Title PublicationDate abstract
34825303 Myeloperoxidase as an important predictor of cardiovascular risk in individuals with rheum 2021 Dec BACKGROUND: Rheumatoid arthritis is an inflammatory disease with joint manifestations. In the presence of extra-articular manifestations, the morbidity and severity of the disease increase. Glucocorticoid is used as a treatment and may result in side effects related to cardiovascular risk. METHODS: This was a cross-sectional study including 59 volunteers with rheumatoid arthritis receiving treatment at a hospital of Campos Gerais that aimed to establish the relation between cardiovascular risk, glucocorticoid treatment and myeloperoxidase in these patients. Subjects were divided into two groups: using (n = 39) and without glucocorticoids (n = 20). They underwent clinical evaluation, physical examination and blood samples were taken. Statistical analysis was performed using Student's t test and Mann-Whitney test. Logistic regression was performed to assess the cardiovascular risk. The significance level was 5% (α = 0.05). Calculations were performed using the Statistical Package for the Social Science version 21.0. RESULTS: There has been a significant difference between groups in blood glucose values (p = 0.012), which can be explained by the different percentage of diabetic patients in the groups. When assessing cardiovascular risk using the predictors of glucocorticoid dose, time of glucocorticoid use, myeloperoxidase, and C-reactive protein together, these were responsible for significantly predicting this risk (p = 0.015). CONCLUSION: A significant relation between the predictor myeloperoxidase alone was also demonstrated (p = 0.037), it may be an important predictor of cardiovascular risk among individuals with rheumatoid arthritis.
33866790 Leflunomide as a cause of collagenous colitis: an entity to consider. 2021 Oct Leflunomide belongs in the group of disease-modifying anti-rheumatic drugs (DMARDs) used in the treatment of psoriatic, rheumatoid, and reactive arthritis. Approximately 20 % of patients will experience some adverse event, mainly weight loss, abdominal pain, and diarrhea. We describe the clinical, endoscopic, and histological findings in a patient with psoriatic arthritis (PA) who developed severe chronic diarrhea after drug use.
32866240 Increased levels of plasma nucleotides in patients with rheumatoid arthritis. 2021 Jan 28 Novel biomarkers of rheumatoid arthritis (RA), in addition to antibodies against cyclic citrullinated peptides, are required. Metabolome analysis is a promising approach to identify metabolite biomarkers for clinical diagnosis. We adopted a comprehensive non-targeted metabolomics approach combining capillary electrophoresis time-of-flight mass spectrometry (TOFMS) and liquid chromatography TOFMS. We constructed metabolomics profiling of 286 plasma samples of a Japanese population [92 RA patients, 13 systemic lupus erythematosus (SLE) patients and 181 healthy controls). RA case-control association tests showed that seven metabolites exhibited significantly increased levels in RA samples compared with controls (P < 1.0 × 10-4; UTP, ethanolamine phosphate, ATP, GDP, ADP, 6-aminohexanoic acid and taurine), whereas one exhibited a decreased level (xanthine). The plasma levels of these eight metabolites were not significantly different between seropositive and seronegative RA patients (P > 0.05; n = 68 and 24, respectively). The four nucleotide levels (UTP, ATP, GDP and ADP) were significantly higher in the non-treatment patients in comparison between patients with and without treatment (P < 0.014; n = 57 and 35, respectively). Furthermore, we found that none of the four nucleotide levels showed significant differences in SLE case-control association tests (P > 0.2; 13 patients with SLE and the 181 shared controls) and psoriatic arthritis (PsA) case-control association tests (P > 0.11; 42 patients with PsA and 38 healthy controls), indicating disease specificity in RA. In conclusion, our large-scale metabolome analysis demonstrated the increased plasma nucleotide levels in RA patients, which could be used as potential clinical biomarkers of RA, especially for seronegative RA.
34806241 AGER gene variant as a risk factor for juvenile idiopathic arthritis. 2022 Feb BACKGROUND: The AGER gene encodes a cell surface multiligand receptor of advanced glycation end-products that is also capable of binding other molecules and is involved in numerous pathways related to inflammation, apoptosis, immunity and so on. In the present study, we aimed to investigate whether the AGER rs1035798 (G>A) intronic polymorphism, showing an association with multiple sclerosis and rheumatoid arthritis in adults, is related to juvenile idiopathic arthritis (JIA). METHODS: Caucasian children from the Belarusian population were enrolled in the study. In total, there were 201 cases with JIA, 37 with juvenile systemic lupus erythematosus, 222 children with the articular syndrome of non-autoimmune etiology (positive control for JIA) and 365 negative controls (children without any autoimmune or inflammatory diseases). Genomic DNA samples from the patients and controls were genotyped by a real-time polymerase chain reaction. RESULTS: A marked association of the homozygous AA rs1035798 genotype with JIA (p = 5 × 10(-4) ) was found. Allele A was also associated with JIA (p = 0.0058), as well as with the articular syndrome of non-autoimmune etiology (p = 0.0264). The highest frequencies of the AA genotype were found in the subgroups of JIA patients with polyarthritis or severe oligoarthritis. The AA genotype patients also had the smallest mean age of the JIA onset. CONCLUSIONS: Our results demonstrate that the AGER rs1035798 AA genotype is a risk factor for JIA in Belarusian children. They also suggest a link between the AGER AA genotype and the risk of JIA early onset and severity. However, the functional relevance of the rs1035798 polymorphism is still unclear.
34279701 Oral health-related quality of life in patients with early rheumatoid arthritis is associa 2022 Jan OBJECTIVES: To evaluate oral health-related quality of life (OHRQoL) in early rheumatoid arthritis (ERA) patients and individuals at risk of rheumatoid arthritis (RA) compared to healthy controls, and to explore possible associated factors. MATERIALS AND METHODS: Fifty ERA patients, 50 at-risk individuals, and 50 age and gender matched healthy controls were recruited. OHRQoL (Oral Health Impact Profile-14 (OHIP-14)); number of decayed, missing, and filled teeth (DMFT); denture use; periodontal inflamed surface area (PISA); xerostomia (xerostomia inventory (XI)); and possible TMD (-pain) diagnoses were recorded. The groups were compared on these variables. Subsequently, backward multiple regression analyses were performed for the ERA and at-risk groups, with OHRQoL as the dependent variable and gender, age, DMFT, denture use, PISA, XI, non-painful TMD, and TMD pain as independent variables. RESULTS: At-risk individuals had higher XI scores (U = 789.5, z = -3.181, p = 0.001, r = -0.32) and higher prevalence of TMD pain (p = 0.046, OR = 4.57; 95% CI 0.92-22.73) than healthy controls and higher OHIP-14 scores than the ERA group (U = 894.5, z = -2.418, p = 0.016, r = -0.24), while no difference in OHIP-14 was found between the control group and both other groups. For ERA patients, OHRQoL was associated with PISA and TMD pain (R(2) = 0.498, p < 0.001). For at-risk individuals, OHRQoL was associated with XI score (R(2) = 0.410, p < 0.001). CONCLUSIONS: Alertness of health professionals to TMD pain and periodontal inflammation in ERA patients and to xerostomia and TMD pain in at-risk individuals is recommended. CLINICAL RELEVANCE: The results of this study address orofacial aspects that require attention of health professionals in the timeframe around RA onset. TRIAL REGISTRATION: Dutch National Trial Register (NTR, NTR6362).
34948462 Shaping of Monocyte-Derived Dendritic Cell Development and Function by Environmental Facto 2021 Dec 20 Dendritic cells (DC) are heterogeneous cell populations essential for both inducing immunity and maintaining immune tolerance. Chronic inflammatory contexts, such as found in rheumatoid arthritis (RA), severely affect the distribution and the function of DC, contributing to defective tolerance and fueling inflammation. In RA, the synovial fluid of patients is enriched by a subset of DC that derive from monocytes (Mo-DC), which promote deleterious Th17 responses. The characterization of environmental factors in the joint that impact on the development and the fate of human Mo-DC is therefore of great importance in RA. When monocytes leave the blood and infiltrate inflamed synovial tissues, the process of differentiation into Mo-DC can be influenced by interactions with soluble factors such as cytokines, local acidosis and dysregulated synoviocytes. Other molecular factors, such as the citrullination process, can also enhance osteoclast differentiation from Mo-DC, favoring bone damages in RA. Conversely, biotherapies used to control inflammation in RA, modulate also the process of monocyte differentiation into DC. The identification of the environmental mediators that control the differentiation of Mo-DC, as well as the underlying molecular signaling pathways, could constitute a major breakthrough for the development of new therapies in RA.
32734288 A patient-initiated DMARD self-monitoring service for people with rheumatoid or psoriatic 2021 Jan 5 OBJECTIVE: To determine whether a patient-initiated DMARD self-monitoring service for people on MTX is a cost-effective model of care for patients with RA or PsA. METHODS: An economic evaluation was undertaken alongside a randomized controlled trial involving 100 patients. Outcome measures were quality of life and ESR assessed at baseline and post-intervention. Costs were calculated for healthcare usage using a United Kingdom National Health Service economic perspective. Sensitivity analysis was performed to explore the impact of nurse-led telephone helplines. Uncertainty around the cost-effectiveness ratios was estimated by bootstrapping and analysing the cost-effectiveness planes. RESULTS: Fifty-two patients received the intervention and 48 usual care. The difference in mean cost per case indicated that the intervention was £263 more expensive (P < 0.001; 95% CI: £149.14, £375.86) when the helpline costs were accounted for and £94 cheaper (P = 0.08; 95% CI: -£199.26, £10.41) when these costs were absorbed by the usual service. There were, however, statistically significant savings for the patient (P = 0.02; 95% CI: -£28.98, £3.00). When costs and effectiveness measures of ESR and quality of life measured, using the Short Form-12v1, were combined this did not show the patient-initiated service to be cost-effective at a statistically significant level. CONCLUSION: This patient-initiated service led to reductions in primary and secondary healthcare services that translated into reduced costs, in comparison with usual care, but were not cost-effective. Further work is needed to establish how nurse-led telephone triage services are integrated into rheumatology services and the associated costs of setting up and delivering them. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, ISRCTN21613721.
32934121 Reliability and Change in Erosion Measurements by High-resolution Peripheral Quantitative 2021 Mar OBJECTIVE: The aim of this multireader exercise was to assess the reliability and change over time of erosion measurements in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: HR-pQCT scans of 23 patients with RA were assessed at baseline and 12 months. Four experienced readers examined the dorsal, palmar, radial, and ulnar surfaces of the metacarpal head (MH) and phalangeal base (PB) of the second and third digits, blinded to time order. In total, 368 surfaces (23 patients´ 16 surfaces) were evaluated per timepoint to characterize cortical breaks as pathological (erosion) or physiological, and to quantify erosion width and depth. Reliability was evaluated by intraclass correlation coefficients (ICC), percentage agreement, and Light k; change over time was defined by means ± SD of erosion numbers and dimensions. RESULTS: ICC for the mean measurements of width and depth of the pathological breaks ranged between 0.819-0.883, and 0.771-0.907, respectively. Most physiological cortical breaks were found at the palmar PB, whereas most pathological cortical breaks were located at the radial MH. There was a significant increase in both the numbers and the dimensions of erosions between baseline and follow-up (P = 0.0001 for erosion numbers, width, and depth in axial plane; P = 0.001 for depth in perpendicular plane). CONCLUSION: This exercise confirmed good reliability of HR-pQCT erosion measurements and their ability to detect change over time.
33775544 Effectiveness of the First Metatarsophalangeal Joint Arthrodesis Versus Arthroplasty for R 2021 Jul To compare the clinical outcomes of resection arthroplasty of metatarsals 2-5 with either first metatarsophalangeal joint arthrodesis or arthroplasty for rheumatoid forefoot deformity treatment. Comparative studies on the clinical effects of resection arthroplasty of metatarsals 2-5 with either first metatarsophalangeal joint arthrodesis or arthroplasty for the treatment of rheumatoid forefoot deformity were systematically reviewed and a meta-analysis conducted. A total of 337 patients (459 feet) with rheumatoid forefoot deformity from 6 comparative studies were included, with the mean follow-up times ranging from 25 to 80 months in the arthrodesis group and 35 to 102 months in the arthroplasty group. Postoperative pain, satisfaction, hallux valgus angle, the 1(st) -2(nd) intermetatarsal angle, adverse events mainly including non-union and the reoperation rate, and pedobarographic data were reported. In the pooled analysis, there were no significant pain score differences between 1(st) metatarsophalangeal joint arthrodesis and arthroplasty groups (SMD = 0.04, p = .734; I(2) = 43.7%, p = .149), but the hallux valgus angle and the 1(st) -2(nd) intermetatarsal angle showed significant differences between these 2 groups (For hallux valgus angle, SMD = -0.439, p = .002; I(2) = 96.6%, p = .000; for 1(st) -2(nd) intermetatarsal angle, SMD = -0.569, p = .000; I(2) = 98.2%, p = .000). The rate of non-union varied from 0% to 26% in the arthrodesis group. The reoperation rate varied from 3% to 9.6% in the arthrodesis group and from 4% to 11.6% in the arthroplasty group. A comparison of the procedures showed that first metatarsophalangeal joint arthrodesis with resection arthroplasty of the lesser rays produced similar postoperative pain relief and better maintenance of the hallux valgus angle and the 1(st) -2(nd) intermetatarsal angle for rheumatoid forefoot deformity. However, the results should be interpreted with caution due to the high heterogeneity and relatively low quality of the reviewed articles.
34198264 miR-let-7c-5p and miR-149-5p inhibit proinflammatory cytokine production in osteoarthritis 2021 Jul 1 Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common types of arthritis. Both are characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. miRNAs play critical roles in the disease processes of arthritic disorders. However, little is known about the effects of miRNAs on critical inflammatory cytokine production with OA and RA progression. Here, we found higher levels of proinflammatory cytokines including interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in human OA and RA synovial fibroblasts (SFs) compared with normal SFs. Searches of open-source microRNA (miRNA) software determined that miR-let-7c-5p and miR-149-5p interfere with IL-1β, IL-6 and TNF-α transcription; levels of all three proinflammatory cytokines were lower in human OA and RA patients compared with normal controls. Anti-inflammatory agents dexamethasone, celecoxib and indomethacin reduced proinflammatory cytokine production by promoting the expression of miR-let-7c-5p and miR-149-5p. Similarly, ibuprofen and methotrexate also enhanced miR-let-7c-5p and miR-149-5p expression in human SFs. The evidence suggests that increasing miR-let-7c-5p and miR-149-5p expression is a novel strategy for OA and RA.
33291148 Detection of circulating highly expanded T-cell clones in at-risk individuals for rheumato 2021 Jul 1 OBJECTIVES: To quantitatively profile the T-cell repertoire in the peripheral blood of individuals genetically at risk for RA, namely first-degree relatives of RA patients (RA-FDR) at different phases of disease development. METHODS: Next-generation sequencing of the TCR CDR3β repertoire was performed on genomic DNA isolated from whole blood samples of RA-FDR selected at three different pre-clinical stages and of matched RA patients (n = 20/group). T-cell clones were identified by their unique sequence and their degree of expansion (frequency) within each sample was characterized. Clones with a frequency over 0.5% were considered highly expanded clones (HEC). RESULTS: The absolute number of HEC was significantly higher in established RA patients (mean 4.65) and tended to be higher in symptomatic RA-FDR (mean 3.4) compared with asymptomatic RA-FDR (mean 1.55, P =0.003 and P =0.07, respectively). Asymptomatic individuals with high levels of ACPA did not differ from asymptomatic RA-FDR in terms of absolute number and frequency of clones. The number of HEC tended to be slightly higher at the time of RA onset (P =0.055). Neither clones shared by several patients, nor clones previously associated with RA, were preferentially present within or between the different groups. Finally, a longitudinal analysis did not allow to uncover a kinetic expansion of RA-specific clones closely correlated with disease development. CONCLUSIONS: HEC were detected in the peripheral blood before the clinical onset of RA, in particular in the later pre-clinical phase of RA development, and their presence increased over time.
33237533 Rapid Onset of Efficacy of Baricitinib in Chinese Patients with Moderate to Severe Rheumat 2021 Jan INTRODUCTION: Baricitinib is an oral, selective inhibitor of Janus kinase which demonstrates clinical efficacy in patients with rheumatoid arthritis (RA). This report aims to analyze the onset time of baricitinib in Chinese patients with moderately to severely active RA who had an inadequate response to methotrexate. METHODS: This post hoc analysis evaluated clinical improvements of Chinese patients treated with baricitinib 4 mg once daily compared with placebo, based on data from a phase 3 study RA-BALANCE. Efficacy measures including American College of Rheumatology 20% (ACR20) response, ACR core set values, Disease Activity Score modified to include the 28 diarthrodial joint count (DAS28) using high-sensitivity C-reactive protein (hsCRP), DAS28-erythrocyte sedimentation rate, Simplified Disease Activity Index, Clinical Disease Activity Index, DAS28-hsCRP ≤ 3.2 response (low disease activity), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated at weeks 1, 2, 4, 8, 12, 14, 16, 20, and 24 (except for FACIT-F evaluated every 4 weeks). A logistic regression model and an analysis of covariance model were used to analyze treatment comparisons of categorical and continuous measures, respectively. RESULTS: Statistically significant (p ≤ 0.05) improvements were observed as early as week 1 or 2 for the baricitinib group compared to placebo in almost all main efficacy measures. For other outcomes including 66 swollen joint count, 68 tender joint count, FACIT-F, and DAS28-hsCRP ≤ 3.2 response rate, differences were evident (p ≤ 0.05) by week 4 in the baricitinib group compared with placebo. Significant improvements in all efficacy measures were sustained through 24 weeks. CONCLUSIONS: Baricitinib demonstrated a rapid onset of efficacy on ACR20 response, ACR core set values, disease activity, and patient-reported outcome improvements in Chinese patients from RA-BALANCE. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02265705.
33303554 Two sides of the same coin? A review of the similarities and differences between idiopathi 2021 May Rheumatoid arthritis associated interstitial lung disease (RA-ILD) and idiopathic pulmonary fibrosis (IPF) are distinct diseases; however, they share several clinical, radiographic and genetic features. For instance, usual interstitial pneumonia (UIP), which is an ILD pattern required for a diagnosis of IPF, is also the most common ILD pattern in RA-ILD. The presence of UIP in RA-ILD is a poor prognostic sign with outcomes similar to those seen in IPF. The recent finding of a shared genetic susceptibility between IPF and RA-ILD has sparked additional interest in this relationship. This review outlines these similarities and differences in clinical presentation, appearance and outcomes in RA-ILD and IPF.In addition, this review highlights previous research in molecular biomarkers in both conditions, exploring areas of overlap and distinction. This focus on biomarkers in IPF and RA-ILD aims to highlight potential areas of discovery and clues to a potential shared pathobiology through investigation of novel molecular markers or the repurposing of biomarkers from one condition to the other.The drive to better understand RA-ILD by leveraging our knowledge of IPF is underscored by our divergent treatment paradigms for these conditions and the concern for potential harm. As a result of advancing our understanding of the links between IPF and RA-ILD, current strategies for diagnosis, screening and treatment of ILD may fundamentally change in the coming years. Until then, clinicians face difficult clinical questions regarding the co-management of the articular disease and the ILD in RA.
33128074 Methotrexate osteopathy: five cases and systematic literature review. 2021 Feb INTRODUCTION: Methotrexate (MTX)-related osteopathy is rare, defined by the triad of pain, osteoporosis, and "atypical fractures" when it was first described in the 1970s in children treated with high doses MTX for acute leukemia. Since then, several cases have been reported in patients treated with low-dose MTX for inflammatory diseases. METHODS: A systematic research of cases of MTX-related osteopathy was performed in records of Rheumatology Department of Rennes University Hospital. Data collection focused on demographic data, corticosteroid doses, MTX doses and intake method, cumulative doses, year of diagnosis, fracture location, bone densitometry value, and osteoporosis treatment if necessary. A literature review was also conducted to identify other cases in literature and try to understand the pathophysiological mechanisms of this rare entity. RESULTS: We report 5 cases identified between 2011 and 2019, which represents the largest cohort described excluding oncology cases. Fracture locations were atypical for osteoporotic fractures. All patients improved in the following months with MTX withdrawal. All patients except one were treated with antiresorptives (bisphosphonates, denosumab). Two patients, treated with bisphosphonates, had a recurrence of fracture, once again of atypical location. Twenty-five cases were collected in literature with similar clinical presentation. The cellular studies that investigated the bone toxicity of MTX mainly showed a decrease in the number of osteoblasts, osteocytes, and chondrocytes in the growth plate and an increase in the number and activity of osteoclasts. In vitro, consequences of mechanical stimulation on human trabecular bone cells in the presence of MTX showed an alteration in mechano-transduction, with membrane hyperpolarization, acting on the integrin pathway. In contrast with our report, the cases described in the literature were not consistently associated with a decrease in bone mineral density (BMD). CONCLUSION: MTX osteopathy while rare must be known by the rheumatologist, especially when using this treatment for inflammatory conditions. The mechanisms are still poorly understood, raising the question of a possible remnant effect of MTX on osteo-forming bone cells, potentially dose-dependent. Methotrexate (MTX) osteopathy, described as a clinical triad, pain, osteoporosis, and atypical stress fractures, while rare, must be known by the rheumatologist. Our cohort of 5 cases represent the largest series of the literature. Pathophysiological studies raised the question of a dose-dependent remnant effect of MTX on osteo-forming bone cells.
34628537 Handgrip Strength Features in Rheumatoid Arthritis Patients Assessed Using an Innovative C 2021 Oct 9 To investigate the relationship between handgrip strength (HGs) features, evaluated with an innovative cylindrical-shaped grip device, and demographic, anthropometric and clinical variables, in patients with rheumatoid arthritis (RA). Consecutive RA patients were prospectively enrolled for this cross-sectional study. For each patient were collected demographic, anthropometric, clinical data related to disease activity. HGs was assessed in terms of area under the force-time curve (AUC-FeT), peak grip force and time to reach the curve plateau. The correlations between the variables were studied with the Spearman's rho correlation coefficient. The receiver operating characteristic (ROC) curve analysis was used to test the discriminant accuracy of HGs features in identifying patients in moderate/high disease activity. A multivariate analysis was performed to estimate the contribution of covariates on the AUC-FeT. A significant correlation was found among AUC-FeT, age, Simplified Disease Activity Index (SDAI), Ultrasound-Clinical Arthritis Activity (US-CLARA) (all at p < 0.0001), and body mass index (BMI) (p = 0.0001). Any correlation was found between HGs and radiographic damage. The discriminatory power of AUC-FeT was good [area under-ROC curve = 0.810 (95% CI 0.746-0.864)]. Variables significantly associated with AUC-FeT in multivariate analysis were age (p = 0.0006), BMI (p = 0.012), gender (p = 0.004), SDAI (p = 0.047) and US-CLARA (p = 0.023). HGs is negatively influenced by demographic (gender and age), anthropometric (BMI), and disease activity variables (SDAI and US-CLARA). These findings highlight the role of HGs in RA patients' functional impairment and disability.
33485336 Diet intervention improves cardiovascular profile in patients with rheumatoid arthritis: r 2021 Jan 23 BACKGROUND: The chronic inflammation in patients with rheumatoid arthritis (RA) increases the risk for cardiovascular diseases (CVD). The contribution of diet as a risk factor for CVD among these patients is however not fully understood. The aim of this study is to investigate if a proposed anti-inflammatory diet improves cardiovascular profile in weight stable patients with RA. METHODS: Patients (n = 50) with RA were included in a cross-over trial. They were randomized to either a diet rich in whole grain, fatty fish, nuts, vegetables and fruit and supplemented with probiotics, or a control diet resembling average nutritional intake in Sweden, for ten weeks. After a 4-month washout they switched diet. Participants received food bags and dietary guidelines. Primary outcome was triglyceride (TG) concentration. Secondary outcomes were total-, high density lipoprotein- (HDL) and low density lipoprotein- (LDL) cholesterol, Apolipoprotein-B100 and -A1, lipoprotein composition, plasma phospholipid fatty acids and blood pressure. RESULTS: Forty-seven patients completed at least one period and they remained weight stable. There was a significant between-dietary treatment effect in TG and HDL-cholesterol concentration in favor of intervention (p = 0.007 and p = 0.049, respectively). Likewise, Apolipoprotein-B100/A1 ratio shifted toward a less atherogenic profile in favor of the intervention (p = 0.007). Plasma fatty acids increased in polyunsaturated- and decreased in monounsaturated- and saturated fatty acids between diet periods in favor of the intervention period. CONCLUSION: Blood lipid profile improved indicating cardioprotective effects from an anti-inflammatory dietary intervention in patients with RA. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov as NCT02941055 .
32433827 Pain Over Two Years After Start of Biologic Versus Conventional Combination Treatment in E 2021 Sep OBJECTIVE: To compare the pain course between methotrexate (MTX)-refractory early rheumatoid arthritis (RA) patients randomized to infliximab (IFX) versus sulfasalazine (SSZ) plus hydroxychloroquine (HCQ). METHODS: The randomized, controlled, open-label Swedish Pharmacotherapy (SWEFOT) trial enrolled new-onset RA patients from October 2002 to December 2005. After 3 months of receiving MTX, patients not reaching low disease activity (Disease Activity Score in 28 joints score ≤3.2) were randomized to adding IFX (n = 128) or SSZ plus HCQ (n = 130) and followed for 21 months. Here, outcomes included area under the curve (AUC) for visual analog scale (VAS) scores for pain, unacceptable pain (VAS pain score >40 mm [range 0-100]), and unacceptable pain despite inflammation control (refractory pain; VAS pain score >40 plus C-reactive protein level <10 mg/liter). Between-group differences were analyzed with multivariate regression models. RESULTS: Overall, 50% of randomized patients (n = 258) in the crude setting reported unacceptable pain at randomization, declining to 29% at 21 months (P < 0.001), when refractory pain constituted 82% of all unacceptable pain. Comparing randomized arms (intent-to-treat analysis), the AUC for VAS pain was lower in the MTX plus IFX group (P = 0.01), and at 21 months, 32% of patients receiving MTX plus IFX and 45% receiving MTX plus SSZ plus HCQ had unacceptable pain (adjusted relative risk 0.68 [95% confidence interval 0.51, 0.90]; P = 0.008). Regarding refractory pain, no between-group differences were observed. CONCLUSION: Despite active combination treatment, almost one-third of new-onset RA patients reported unacceptable pain after 21 months, and refractory pain constituted more than 4/5 of this pain load. Adding IFX versus SSZ plus HCQ to MTX reduced both cumulative pain and unacceptable pain at 21 months, suggesting less long-term pain for the biologic therapy. These results display insufficient effects of current treatment strategies on inflammation-independent pain components, warranting alternative approaches in affected patients.
34248985 In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated Wit 2021 OBJECTIVES: Rheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5-amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein/peptide antibodies (ACPAs). Citrulline is a neutral amino acid resulting from post-translational modification of arginine involved in peptidic bounds (arginyl residue) by PeptidylArginine Deiminases (PADs). ACPAs recognize epitopes from citrullinated human fibrin(ogen) (hFib) and can be specifically detected by the AhFibA assay. Five citrullinated peptides derived from hFib together represent almost all of the epitopes recognized by patients with ACPA-positive RA, namely: α36-50cit, α171-185cit, α501-515cit, α621-635cit, and β60-74cit. The use of antibody fine specificities as markers of clinical phenotypes has become a major challenge. Our objective was to study whether RA clinical characteristics and HLA-DRB1 genetic background were associated with a specific reactivity against the epitopes borne by the five peptides. METHODS: 184 ACPA-positive RA patients fulfilling the 2010 ACR/EULAR criteria were studied. Patient characteristics including HLA-DRB1 genotype, were collected from their medical files. Anti-CCP2 antibodies, AhFibA, and antibodies against the five citrullinated hFib (hFib-cit) peptides were analyzed by ELISA. RESULTS: Anti-α505-515cit antibodies were associated with HLA-DRB1*04:01 (OR = 5.52 [2.00 - 13.64]; p = 0.0003). High level anti-α505-515cit antibodies were associated with rheumatoid nodules (OR = 2.71 [1.00 - 7.16], p= 0.044). CONCLUSION: Immune complexes containing anti-α501-515cit antibodies and rheumatoid factors might be involved in the development of rheumatoid nodules on the HLA-DRB1*04:01 background. Apheresis of these epitope-specific antibodies might be a new therapeutic opportunity for patients with rheumatoid nodules.
33682887 Medication adherence in older people with rheumatoid arthritis is lower according to elect 2021 Nov 3 OBJECTIVES: Suboptimal medication adherence is a serious problem in the treatment of chronic inflammatory diseases. To measure medication adherence, electronic monitoring is regarded as superior to pill count. GLORIA is an ongoing two-year trial on the addition of low-dose (5 mg/d) prednisolone or placebo to standard care in older people (65+ years) with RA. During the entire trial, adherence is measured with electronic caps, and with pill counts. The objective is to describe medication adherence patterns, and to compare the adherence results of the two methods. METHODS: The recorded adherence patterns of patients (blinded for treatment group) were classified according to descriptive categories. The cutoff for good adherence was set at 80% of prescribed pills taken. RESULTS: Trial inclusion closed in 2018 at 451 patients, but trial follow-up is ongoing; the current dataset contains adherence data of 371 patients. Mean number of recorded 90-day periods per patient was 4 (range 1-8). Based on pill count over all periods, 90% of the patients had good adherence; based on cap data, only 20%. Cap data classified 30% of patients as non-user (<20% of days an opening) and 40% as irregular user (different adherence patterns, in or between periods). CONCLUSION: In our trial of older people with RA, the majority appeared to be adherent to medication according to pill count. Results from caps conflicted with those of pill counts, with patterns suggesting patients did not use the bottle for daily dispensing, despite specific advice to do so. TRIAL REGISTRATION: NCT02585258. ClinicalTrials.gov (https://www.clinicaltrials.gov/).
34301311 Real-world comparative effectiveness and safety of tofacitinib and baricitinib in patients 2021 Jul 23 OBJECTIVE: To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting. METHODS: A total of 242 patients with RA who were treated with tofacitinib (n = 161) or baricitinib (n = 81) were enrolled. We evaluated efficacy and safety between tofacitinib and baricitinib using multivariable analyses to avoid confounding. Their clinical disease activity and AEs were evaluated for 24 weeks. RESULTS: The mean (SD) DAS28-ESR change from baseline to 24 weeks was 1.57 (1.55) (tofacitinib) and 1.46 (1.36) (baricitinib). There was no significant difference in the clinical response between the two groups (adjusted mean difference, 0.04; 95% CI, -0.35 to 0.28). The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in the tofacitinib group, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was associated. CONCLUSIONS: Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, there is a possibility that the influence of clinical characteristics on the treatment response differs. The comparison provides useful information to the optimal use of JAK inhibitors in real-world settings.