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ID PMID Title PublicationDate abstract
34419080 A comparative study of total knee arthroplasty outcome for stiff knee with or without sequ 2021 Aug 21 BACKGROUND: The aim of this study was to evaluate the influence of antirheumatic drug treatment on knee function of stiff knee patients after total knee arthroplasty (TKA). METHODS: Twenty-seven patients (44 knees) of active RA (rheumatoid arthritis) or AS (ankylosing spondylitis) with stiff knees were included in this study. And they were divided into two groups according to continue antirheumatic drug treatment or not after TKA: the therapeutic group (16 patients, 27 knees) and the controlled group (11 patients, 17 knees). The outcomes were assessed by Knee Society Score (KSS), Visual Analogue Scale (VAS), range of motion (ROM) (at week 6, month 6, year 1, and year 2), "Forgotten Joint" Scale (FJS), with or without crutch, satisfaction, and revision (at year 2). The knee prosthetic loosening was evaluated by the followed X-ray at each following time. RESULTS: The mean follow-up time was 51 months (34-69 months). The KSS was higher at week 6 after TKA in the therapeutic group (p < 0.05); however, the functional scores of KSS at month 6, year 1, and year 2 in the controlled group were more points improved. The therapeutic patients preferred the knee more at month 6, year 1, and year 2. The differences of KSS clinical scores (at month 6, year 1, and year 2), VAS, ROM, Crutch and FJS between the two groups were not statistically significant (p > 0.05). CONCLUSION: For patients with stiff knees, the sequential antirheumatic drug treatment after TKA had no obvious effect on postoperative KSS, but can improve the satisfaction. LEVEL OF EVIDENCE: Therapeutic level II. See Instructions for Authors for a complete description of levels of evidence.
33310262 Subjects at-risk for future development of rheumatoid arthritis demonstrate a PAD4-and TLR 2021 Feb The presence of anti-citrullinated protein/peptide antibodies (ACPA) and epitope spreading across the target autoantigens is a unique feature of rheumatoid arthritis (RA). ACPA are present in the peripheral blood for several years prior to the onset of arthritis and clinical classification of RA. ACPA recognize multiple citrullinated proteins, including histone H3 (H3). Intracellular citrullination of H3 in neutrophils and T cells is known to regulate immune cell function by promoting neutrophil extracellular trap formation and citrullinated autoantigen release as well as regulating the Th2/Th17 T cell phenotypic balance. However, the roles of H3 citrullination in other immune cells are not fully elucidated. We aimed to explore H3 citrullination and cytokine/metabolomic signatures in peripheral blood immune cells from subjects prior to and after the onset of RA, at baseline and in response to ex vivo toll-like receptor (TLR) stimulation. Here, we analyzed 13 ACPA (+) subjects without arthritis but at-risk for future development of RA, 14 early RA patients, and 13 healthy controls. We found significantly elevated H3 citrullination in CD14(hi) monocytes, as well as CD1c(+) dendritic cells and CD66(+) granulocytes. Unsupervised analysis identified two distinct subsets in CD14(hi) monocytes characterized by H3 modification and unique cytokine/metabolomic signatures. CD14(hi) monocytes with elevated TLR-stimulated H3 citrullination were significantly increased in ACPA (+) at-risk subjects. These cells were skewed to produce TNFα, MIP1β, IFNα, and partially IL-12. Additionally, they demonstrate peptidyl arginine deiminase 4 (PAD4) mediated upregulation of the glycolytic enzyme PFKFB3. These CD14(hi) monocytes with elevated H3 citrullination morphologically formed monocyte extracellular traps (METs). Taken together, dysregulated PAD4-driven cytokine production as well as MET formation in CD14(hi) monocytes in ACPA (+) at-risk subjects likely plays an important role in the development of RA via promoting and perpetuating inflammation and generation of citrullinated autoantigens.
33949151 Differences in the Oral Microbiome in Patients With Early Rheumatoid Arthritis and Individ 2021 Nov OBJECTIVE: It has been suggested that rheumatoid arthritis (RA) may originate at the oral mucosa. The aim of the present study was to assess the oral microbiome and periodontal condition in patients with early RA and individuals at risk of developing RA compared to healthy controls. METHODS: Three groups were recruited (n = 50 participants per group): 1) patients with early RA (meeting the American College of Rheumatology/European Alliance of Associations for Rheumatology 2010 classification criteria), 2) individuals at risk of developing RA (those with arthralgia who were positive for RA-associated autoantibodies), and 3) healthy controls. A periodontal examination was conducted to assess the presence of bleeding on probing (BOP), pocket probing depth (PPD), and periodontal inflamed surface area (PISA). The microbial composition of subgingival dental plaque, saliva, and tongue coating was assessed using 16S ribosomal DNA amplicon sequencing, and findings were compared between groups with permutational multivariate analysis of variance (PERMANOVA). RESULTS: There were no significant differences in any of the 3 periodontal variables between patients with early RA, at-risk individuals, and healthy controls (P = 0.70 for BOP, P = 0.30 for PPD, and P = 0.57 for PISA, by Kruskal-Wallis test). PERMANOVA analyses comparing microbial composition between the groups showed significant differences in the microbial composition of saliva (F = 2.08, P = 0.0002) and tongue coating (F = 2.04, P = 0.008), but not subgingival dental plaque (F = 0.948, P = 0.51). However, in post hoc tests, no significant differences in microbial composition of the saliva or tongue coating were observed between the early RA group and the at-risk group (F = 1.12, P = 0.28 for saliva; F = 0.834, P = 0.59 for tongue coating). In assessing microbial diversity based on the number of zero-radius operational taxonomic units per sample, Prevotella in the saliva and Veillonella in the saliva and tongue coating were each found at a higher relative abundance in samples from patients with early RA and at-risk individuals compared to healthy controls. CONCLUSION: The results show similarities in the oral microbiome between patients with early RA and at-risk individuals, since in both groups, the oral microbiome was characterized by an increased relative abundance of potentially proinflammatory species when compared to that in healthy controls. These findings suggest a possible association between the oral microbiome and the onset of RA.
33727634 S100A11 (calgizzarin) is released via NETosis in rheumatoid arthritis (RA) and stimulates 2021 Mar 16 S100A11 (calgizzarin), a member of S100 family, is associated with several autoimmune diseases, including rheumatoid arthritis (RA). Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of RA and in the externalization of some S100 family members. Therefore, we aimed to determine the association between S100A11 and NETs in RA. For this purpose, the levels of S100A11 and NETosis markers were detected in the RA synovial fluid by immunoassays. The expression of S100A11 by neutrophils in the RA synovial tissue was assessed. Neutrophils isolated from peripheral blood were exposed to S100A11 or stimulated to release NETs. The levels of NETosis- and inflammation-associated proteins were analysed by immunoassays. NETs were visualized by immunofluorescence. We showed that S100A11 was expressed by the neutrophils in the RA synovial tissue. Moreover, S100A11 in the RA synovial fluid correlated with several NETosis markers. In vitro, S100A11 was abundantly released by neutrophils undergoing NETosis compared to untreated cells (p < 0.001). Extracellular S100A11 increased the secretion of IL-6 (p < 0.05) and TNF (p < 0.05) by neutrophils but did not induce NETosis. This study demonstrates, for the first time, that the release of S100A11 is dependent on NETosis and that extracellular S100A11 augments the inflammatory response by inducing pro-inflammatory cytokines in neutrophils.
33349609 Polyherbal formula SC-E3 inhibits rheumatoid arthritis activity in a mouse model of type-I 2021 May OBJECTIVE: SC-E3 is a polyherbal formula that contains five medicinal herbs used frequently in traditional herbal medicine. In our previous study, we demonstrated the antioxidant and anti-inflammatory effects of SC-E3. The present study examined the effects of SC-E3 in a mouse model of type-II collagen-induced arthritis (CIA). METHODS: In vivo, male DBA/1J mice were immunized by intradermal injection of bovine type-II collagen and complete or incomplete Freund's adjuvant, to induce arthritis. SC-E3 was orally administered daily for 23 days. In vitro, bone marrow-derived macrophages (BMMs) were treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) in the absence or presence of SC-E3. RESULTS: Administrations of SC-E3 were found to have anti-arthritic effects in the joints of CIA mice, as evidenced by reduced paw swelling, bone erosion and deformation, inflammatory cell infiltration, and inflammation in synovial membrane. SC-E3 also reduced serum levels of tumor necrosis factor-α, interleukin-1β, aspartate aminotransferase and alanine aminotransferase. Furthermore, tartrate-resistant acid phosphatase-positive osteoclast numbers in the joints were significantly lower in SC-E3-treated CIA mice than in CIA mice. In addition, the differentiations of BMMs to multinucleated osteoclasts induced by M-CSF and RANKL stimulation were dose-dependently reduced by SC-E3. CONCLUSION: These results suggest that SC-E3 possesses substantial anti-arthritic activity because it inhibits pro-inflammatory cytokines and osteoclastogenesis, and that SC-E3 has potential therapeutic use for the treatment of rheumatoid arthritis.
34014426 Positive rate and prognostic significance of the superb microvascular imaging signal in jo 2021 Jul PURPOSE: This study aimed to evaluate the positive rate and prognostic significance of superb microvascular imaging (SMI) in rheumatoid arthritis (RA) patients in remission with normal C-reactive protein (CRP) levels and erythrocyte sedimentation rates (ESR). METHODS: The study enrolled 112 RA patients, and ultrasound (US) assessment was performed on 28 joints of each patient. RESULTS: The SMI signal-positive rates for each joint were: metacarpophalangeal (MCP) joints: 20.5%, wrist joints: 43.8%, metatarsophalangeal (MTP) joints: 17.0%, and other foot joints: 25.0%. Investigation of the prognostic significance of the SMI signal in each joint revealed that only in the MTP joints was the total score of the SMI signal in the patients with relapse significantly higher than that in the patients with remission (P = 0.01). Comparison of the receiver operating characteristics curves for predicting relapse showed that the area under the curve (AUC) of the MTP joints was the highest (AUC = 0.66) of the investigated joints. The optimal threshold for the total MTP SMI score was 1 (accuracy = 83.3%). Positive/negative data of the SMI signal in the MTP joints were not significantly associated with the values of conventional disease activity markers. CONCLUSION: In RA patients in remission with normal CRP and ESR levels, the percentage of positive SMI signal was highest in the wrist joints. However, the accuracy of the SMI signal for predicting relapse was greatest for the MTP joints, suggesting that US assessment of the MTP joints by SMI is useful for predicting relapse in these patients.
33499006 Adipokines and Autoimmunity in Inflammatory Arthritis. 2021 Jan 22 Adipokines are adipose tissue-derived factors not only playing an important role in metabolism but also influencing other central processes of the body, such as inflammation. In autoimmune diseases, adipokines are involved in inflammatory pathways affecting different cell types. Many rheumatic diseases belong to the group of autoimmune diseases, for example rheumatoid arthritis (RA) and psoriatic arthritis. Due to the autoimmune responses, a chronic inflammatory milieu develops, which affects the whole body, including adipose tissue. Metabolic alterations such as obesity influence inflammatory responses in autoimmune diseases. Adipokines are bioactive mediators mainly produced by adipose tissue. Due to alterations of systemic adipokine levels, their role as biomarkers with diagnostic potential has been suggested in the context of rheumatic diseases. In the affected joints of RA patients, different synoviocytes but also osteoclasts, osteoblasts, and chondrocytes produce several adipokines, contributing to the unique inflammatory microenvironment. Adipokines have been shown to be potent modulatory effectors on different cell types of the immune system but also local cells in synovial tissue, cartilage, and bone. This review highlights the most recent findings on the role of adipokines in the pathophysiology of inflammatory arthritis with a distinct focus on RA in the quickly developing research field.
34923285 Cost-Effectiveness Analysis of Etanercept 25 mg Maintenance Therapy After Treatment With E 2022 Mar OBJECTIVES: To use Markov modeling to estimate the cost-effectiveness of treatment with etanercept 25 mg once weekly plus methotrexate (MTX) in Japanese patients with rheumatoid arthritis who had achieved remission or low disease activity with etanercept 50 mg once weekly plus MTX. METHODS: Effectiveness data were estimated based on results from a clinical trial (PRESERVE) in patients with rheumatoid arthritis who had achieved remission or low disease activity and who were then randomized to receive etanercept 25 mg plus MTX or placebo plus MTX. A Markov model was established and included flare rates of 21% and 62% in the etanercept 25 mg and placebo groups, respectively. EQ-5D was calculated using an ordinary least-squares model that included the health assessment questionnaire disability index and pain visual analog scale. Worsening of the health assessment questionnaire score over 1 year was estimated to be 0.047 for patients with flare, and when associated with radiographic progression it was estimated to increase by 0.006 and 0.025 in the etanercept 25 mg and placebo groups, respectively. A cycle length of 1 year was applied to calculate the cumulative cost and effectiveness for a 10-year time span. RESULTS: Compared with the placebo group, the quality-adjusted life-years for the etanercept 25 mg group was increased by 0.841. The incremental cost-effectiveness ratio was ¥6 173 772. CONCLUSION: These results suggest that maintenance treatment with etanercept 25 mg is cost-effective.
33756027 Evaluation of dysfunctional high-density lipoprotein levels with myeloperoxidase/paraoxona 2021 Jul BACKGROUND: The aim of this study is to evaluate dysfunctional high-density lipoprotein cholesterol (HDL) by measuring myeloperoxidase (MPO)/paraoxonase 1 (PON1) ratio in patients with rheumatoid arthritis (RA) and to investigate the relationship between dysfunctional HDL and cardiovascular disease (CVD) in RA patients. METHODS: Sixty-seven healthy individuals and 130 RA patients were included in the study. Routine lipid panels (triglyceride (TG), low-density lipoprotein cholesterol (LDL), HDL, total cholesterol (TC), PON1 and MPO levels were measured. Disease activity scores-28 (DAS28) of RA patients were calculated. Cardiological examination records of the patients were assessed to detect patients who also have CVD. RESULTS: There were no significant differences between RA and control groups in routine lipid profiles (P > .05 for all). MPO/PON1 ratios were significantly elevated in the RA group compared with the control group (P < .001). MPO/PON1 ratios were higher in RA patients with CVD history compared with those without CVD (P < .05). MPO/PON1 ratios were correlated with DAS28 scores (rho: 0.357, P < .001). CONCLUSION: HDL dysfunction determined by the MPO/PON1 ratio may be associated with the pathophysiology of increased CVD in RA. Thus, evaluating dysfunctional HDL levels by measuring the MPO/PON1 ratio in RA patients may allow more detailed patient follow-up, as well as the reduction of CVD events in RA patients with therapeutic agents aiming to increase the functional properties of HDL by decreasing this ratio.
34600768 Ultrasonography of Shoulder in Rheumatoid Arthritis: A Reliability Exercise Using Consensu 2021 Dec The shoulder may be affected in a large portion of patients with rheumatoid arthritis (RA) worldwide. However, this joint does not receive the attention required during follow-up. Indeed, although numerous clinical tests for diagnosis of a painful shoulder are available, differentiating articular from peri-articular lesions may be difficult in daily practice. Fortunately, the precise diagnosis of shoulder pain in RA has benefited from a reliable imaging modality used to detect its exact origin-ultrasonography (US). This study was aimed at assessing the intra- and inter-observer reliability of ultrasonographic findings for patients with established RA with shoulder pain in a patient-based exercise as a clinical challenge among Maghrebian rheumatologist experts in US. A total of 7 operators examined 10 patients in two rounds independently and blindly of each other. Before beginning the session, all of the rheumatologists reached a consensus on sites and US settings by performing a brief exercise on a normal shoulder. Outcome Measures in Rheumatology Clinical Trials (OMERACT) definitions of US-detected pathologies were used. Each patient underwent US scanning of the painful shoulder in predefined sites based on US technical guidelines of the European Society of Musculoskeletal Radiology: long head of biceps (LHB), subscapularis recess, posterior recess and axillary recess. The presence of subdeltoid or subcoracoid bursitis or full rupture of the suprasupinatus was identified if present. Intra- and inter-observer reliability measures were calculated using the κ coefficient. Intra-observer reliability was good for gray-scale (GS) synovitis in subscapularis and posterior recesses (κ = 0.77 and 0.73, respectively). It was moderate in the presence of GS synovitis and effusion in LHB (κ =0.53 and 0.40, respectively), posterior and subscapularis recess effusion (κ = 0.56 and 0.60, respectively) and GS and power Doppler (PD) synovitis in axillary recesses (κ = 0.58 and 0.49, respectively). Inter-observer reliability was good for PD for LHB signals (κ = 0.78). It was moderate for GS for LHB synovitis (κ = 0.54). Inter-observer agreement was poor for effusion and GS synovitis for subscapularis, posterior and axillary recesses, and very poor for PD signals in these recesses. US was a reliable imaging tool for detecting tenosynovitis in the LHB. However, reliability was moderate to poor in detecting synovitis in subscapularis, posterior and axillary recesses. These findings could be optimized by standardization of sites to assess.
34135030 Association of biological antirheumatic therapy with risk for type 2 diabetes: a retrospec 2021 Jun 16 OBJECTIVE: To explore possible associations of treatment with biological disease-modifying antirheumatic drugs (bDMARDs), including T-cell-based and interleukin-6 inhibition (IL-6i)-based therapies, and the risk for type 2 diabetes mellitus (T2DM) in patients with rheumatoid arthritis (RA). STUDY DESIGN, SETTING AND PARTICIPANTS: Five treatment groups were selected from a United States Electronic Medical Records database of 283 756 patients with RA (mean follow-up, 5 years): never received bDMARD (No bDMARD, n=125 337), tumour necrosis factor inhibitors (TNFi, n=34 873), IL-6i (n=1884), T-cell inhibitors (n=5935) and IL-6i+T cell inhibitor abatacept (n=1213). Probability and risk for T2DM were estimated with adjustment for relevant confounders. RESULTS: In the cohort of 169 242 patients with a mean 4.5 years of follow-up and a mean 641 200 person years of follow-up, the adjusted probability of developing T2DM was significantly lower in the IL-6i (probability, 1%; 95% CI 0.6 to 2.0), T-cell inhibitor (probability, 3%; 95% CI 2.3 to 3.3) and IL-6i+T cell inhibitor (probability, 2%; 95% CI 0.1 to 2.9) groups than in the No bDMARD (probability, 5%; 95% CI 4.6 to 4.9) and TNFi (probability, 4%; 95% CI 3.7 to 4.7) groups. Compared with No bDMARD, the IL-6i and IL-6i+T cell inhibitor groups had 37% (95% CI of HR 0.42 to 0.96) and 34% (95% CI of HR 0.46 to 0.93) significantly lower risk for T2DM, respectively; there was no significant difference in risk in the TNFi (HR 0.99; 95% CI 0.93 to 1.06) and T-cell inhibitor (HR 0.96; 95% CI 0.82 to 1.12) groups. CONCLUSIONS: Treatment with IL-6i, with or without T-cell inhibitors, was associated with reduced risk for T2DM compared with TNFi or No bDMARDs; a less pronounced association was observed for the T-cell inhibitor abatacept.
32623650 Intra-articular injection of etanercept versus glucocorticoids in rheumatoid arthritis pat 2021 Feb OBJECTIVES: This study was conducted to assess the safety and efficacy of intra-articular injection of etanercept and compare it with corticosteroid injection in rheumatoid arthritis (RA) patients. METHODS: Fifty patients with RA who suffered from activity in one joint were randomized into two groups, received an intra-articular injection of either etanercept or corticosteroid guided by musculoskeletal ultrasound. All patients were assessed for disease activity by disease activity score (DAS28), functional assessment using the Modified Health Assessment Questionnaire (MHAQ), and laboratory investigations (erythrocyte sedimentation rate and C-reactive protein). Joints affected were evaluated for pain by visual analog scale (VAS), tenderness, and swelling scores and by ultrasound for estimation of synovial hypertrophy, synovial effusion, and power Doppler. Follow-up of the patients was done at weeks 1, 4, and 12 after injection by clinical assessment and ultrasound. RESULTS: There was a significant improvement of joint pain assessed by VAS, tenderness, and swelling scores in the etanercept group at week 1 and week 4 follow-up periods but there were insignificant changes at week 12. There was a significant decrease in synovial effusion at week 1 and week 4 and in power Doppler at week 1 but no significant change was noticed in synovial hypertrophy during the follow-up periods. In comparison of the two groups, etanercept has shown better results on joint scores at week 1; however, glucocorticoid had more sustained effects. No major or life-threatening side effects were noticed following intra-articular injection of etanercept. CONCLUSION: Intra-articular injection of etanercept is a safe and promising option; with comparable results to intra-articular injection of corticosteroid; however, its rapid absorption from the synovium may necessitate frequent injections. Key Points • Persistent inflammatory mono-arthritis is a common clinical problem that is often difficult to treat; it is a debilitating and destructive condition. • Intra-articular injection of TNF inhibitors is an encouraging treatment modality in managing refractory mono-arthritis in rheumatoid arthritis.
34160668 Lack of association between CYB5A gene rs1790834 polymorphism and the response to leflunom 2021 Nov AIM: Leflunomide is a disease-modifying antirheumatic drug used in therapy for rheumatoid arthritis (RA). Previous studies indicated that oestrogens and androgens may affect the response to leflunomide in RA patients. The synthesis of androgens is regulated by cytochrome CYB5A. The aim of this study was to examine the association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA. METHODS: The study included 111 women diagnosed with RA. Leflunomide was administered in monotherapy at a dose of 20 mg/day. All patients underwent a monthly evaluation for 12 months after the initiation of treatment with leflunomide. RESULTS: After 12 months of therapy, the changes in individual disease activity parameters, such as: DAS28, ESR, CRP and VAS, were not statistically significantly different between rs1790834 genotypes in the Kruskal-Wallis test. CONCLUSIONS: The results of our study suggest lack of statistically significant association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA.
34364500 Simultaneous determination of CXCL7 chemokine and MMP3 metalloproteinase as biomarkers for 2021 Nov 1 This paper reports the preparation of the first dual electrochemical immunosensor for the simultaneous determination of the CXCL7 chemokine and the MMP3 metalloproteinase as relevant biomarkers for the better diagnosis and monitoring of rheumatoid arthritis derived from the multiple biomarkers measurement. The developed immunosensor involves the use of carboxylated magnetic beads (MBs) and dual screen-printed carbon electrodes (SPdCEs). Sandwich-type configurations implied the covalent immobilization of specific anti-CXCL7 (cAb1) or anti-MMP3 (cAb2) capture antibodies onto MBs and the use of biotinylated detection antibodies with further labelling with HRP-Strept conjugates. The resulting MBS bioconjugates were magnetically captured on the respective working electrode of the SPdCE and the determination of the antigens was accomplished by measuring the amperometric responses of H(2)O(2) mediated by hydroquinone (HQ) at a potential value of -0.20 V. The dual immunosensor provided calibration plots with linear ranges between 1 and 75 ng mL(-1) (CXCL7) (R(2) = 0.997) and from 2.0 to 2000 pg mL(-1) (MMP3) (R(2) = 0.998) with detection limits of 0.8 ng mL(-1) and 1.2 pg mL(-1), respectively. The assay took 2 h 20 min for the simultaneous determination of both biomarkers. The dual immunosensor was successfully applied to the analysis of human serum from positive and negative RA patients.
34214354 The maximum dose and duration in the therapy single use methotrexate to achieve remission 2021 Jun 25 OBJECTIVES: One of the treatments for rheumatoid arthritis (RA) was methotrexate which a disease modifying antirheumatic drug therapy. The use of methotrexate required the right dose and length of therapy to achieve remission. The effectivity of methotrexate could be accounted by disease activity score 28 (DAS28) as a tool has been used clinically with a combination number of tender joints, swollen joints, erythrocyte sedimentation rate, and global clinical assessment by the patient. The aim of this study was to determine the effective dose and length of therapy methotrexate was measured by DAS28 score. METHODS: This research was a cross-sectional study and data was collected from patient medical records in Saiful Anwar Hospital, Malang, from February to July 2018. The research has been given ethical clearance. The inclusion criteria for the 88 subjects were men and women, over 20 years of age, usage of only methotrexate for at least three months, an erythrocyte sedimentation rate score, uncomplicated inflammatory bowel disease, cancer, and systemic lupus erythematosus. All data obtained was entered in formula DAS28. The Statistic analysis used both Pearson and Spearman's rank correlation. RESULTS: Only 16 patients achieved remission. There were not significant correlation in statistical analysis between DAS score and cumulative dose (r=-0.091; p=0.400), average dose (r=0.043; p = 0.692), maximum dose (r=0.074; p=0.492), and length of therapy (r=-0.075; p = 0.489). The initial dose of therapy methotrexate was different and the length of therapy was adjusted to the patient's health condition. CONCLUSIONS: The maximum dose and length of therapy methotrexate was required to achieve remission in RA.
32420757 Rheumatoid arthritis is associated with negatively variable impacts on domains of sleep di 2021 Mar The aim of this study was to identify the impact of rheumatoid arthritis (RA) on specific sleep quality domains and to determine its prevalence. A systematic literature search was performed on PubMed, Web of Science, Cochrane Library, and Embase until January 2018 to obtain eligible studies. Score of the Pittsburgh Sleep Quality Index (PSQI) was used as the outcome measurement, and weight mean differences (WMD) with 95% confidence intervals (CI) were calculated. In total, eight studies were eligible for inclusion criteria, comprising 658 RA patients and 485 healthy controls. In this meta-analysis, each domain of the PSQI score: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disorders, use of sleep medication, daytime dysfunction and the total score were higher in RA patients than healthy controls. In addition, the relative risk of sleep disturbances among people with RA was 2.37 (95% CI: 1.80, 3.11) compared with people without RA.In conclusion, RA patients scored higher in each dimension of PSQI, and sleep disturbances was more prevalent in RA patients than in controls. Further research is needed to identify effective strategies for preventing and treating sleep disturbances among RA patients.
33200731 JAK/STAT pathway and nociceptive cytokine signalling in rheumatoid arthritis and psoriatic 2021 May The key role of pro-inflammatory cytokines in the pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) is strongly supported by the observation that their blockage is effective in the treatment of these diseases. Indeed, blockade of cytokine signal transduction mechanisms, including the JAK-STAT pathway, may be critical in the treatment of RA and PsA. The Janus kinase (JAK) inhibitors tofacitinib and baricitinib target JAKs with high potency and have a well-established rationale for clinical therapeutic use in RA and PsA by affecting multiple cytokines involved in both development and propagation of the disease. Nociceptive responses are also important to consider in the treatment RA and PsA. In this regard, cytokines have also been implicated in modulation of pain and nociception and the JAK/STAT pathway is receiving increasing attention in modulation of nociceptive responses given to its clear role in cytokine signalling. Therefore, inhibition of JAK/STAT pathway with specific JAK inhibitors has the potential to modulate pain in patients with RA and PsA. Data from randomised controlled trials and real-world settings on large numbers of patients with RA (tofacitinib and baricitinib) and randomised controlled trials in patients with PsA (tofacitinib) have shown that a rapid effect on the pain component in these diseases is observed. Thus, it can be hypothesised that JAK inhibitors may have a dual therapeutic role by modulating inflammation and nociception, which leads to clinical benefits including reduction of pain beyond that related to inflammation. The present review will overview the impact of pain in patients with rheumatic disease and the physiological basis of modulating nociceptive pain. Current knowledge about the role of cytokines in mediation of pain and the involvement of the JAK/STAT pathway in modulating nociceptive responses will then be summarised, followed by an analysis of clinical data on pain modulation by JAK inhibitors in the treatment of RA and PsA.
34781416 Tissue engineered skeletal muscle model of rheumatoid arthritis using human primary skelet 2022 Feb Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily targeting the joints. Autoreactive immune cells involved in RA affect other tissues, including skeletal muscle. Patients with RA experience diminished physical function, limited mobility, reduced muscle function, chronic pain, and increased mortality. To explore the impact of RA on skeletal muscle, we engineered electrically responsive, contractile human skeletal muscle constructs (myobundles) using primary skeletal muscle cells isolated from the vastus lateralis muscle of 11 RA patients (aged 57-74) and 10 aged healthy donors (aged 55-76), as well as from the hamstring muscle of six young healthy donors (less than 18 years of age) as a benchmark. Since all patients were receiving treatment for the disease, RA disease activity was mild. In 2D culture, RA myoblast purity, growth rate, and senescence were not statistically different than aged controls; however, RA myoblast purity showed greater variance compared to controls. Surprisingly, in 3D culture, contractile force production by RA myobundles was greater compared to aged controls. In support of this finding, assessment of RA myofiber maturation showed increased area of sarcomeric α-actinin (SAA) expression over time compared to aged controls. Furthermore, a linear regression test indicated a positive correlation between SAA protein levels and tetanus force production in RA and controls. Our findings suggest that medications prescribed to RA patients may maintain-or even enhance-muscle function, and this effect is retained and observed in in vitro culture. Future studies regarding the effects of RA therapeutics on RA skeletal muscle, in vivo and in vitro, are warranted.
33446222 Predictors of radiographic erosion and joint space narrowing progression in patients with 2021 Jan 14 BACKGROUND: Radiographic damage in rheumatoid arthritis (RA) includes erosions and joint space narrowing (JSN). Different mechanisms may underlie their development. The objective of this study was to evaluate predictors of these entities separately. METHODS: Consecutive early RA patients (symptom duration ≤12 months) from a defined area (Malmö, Sweden) recruited during 1995-2005 were investigated. Radiographs of hands and feet were scored by a trained reader according to the modified Sharp-van der Heijde score. Fat mass and lean mass distribution were measured at baseline using dual energy x-ray absorptiometry. Potential predictors of erosion and JSN progression from inclusion to the 5-year follow-up were evaluated. RESULTS: Two hundred and thirty-three patients were included. Radiographs at baseline and 5 years were available for 162 patients. The median (interquartile) progression of erosion and JSN scores were 4 (0-8) and 8 (1-16), respectively. Rheumatoid factor (RF) was a robust significant predictor of both erosion and JSN score progression. In adjusted analyses, anti-CCP antibodies predicted erosions while the erythrocyte sedimentation rate was predictive of both outcomes. Smoking and high baseline disease activity (DAS28 > 5.1) predicted progression of erosions. Baseline erosion score was associated with progression of both erosion and JSN progression, while baseline JSN score was predictive only of the progression of JSN. Overweight/obesity (BMI ≥ 25 kg/m(2)) was a significant negative predictor of JSN score progression (β = - 0.14, p = 0.018, adjusted for RF, age, baseline JSN score) also when additionally adjusting for ever smoking (p = 0.041). Among female patients, this effect was observed in those of estimated post-menopausal age (> 51 years), but not in younger women. The truncal to peripheral fat ratio was associated with less JSN score progression in women, but not in men. CONCLUSIONS: Overweight RA patients had less JSN progression, independent of smoking status. This effect was seen in particular among older women (mainly post-menopausal), but not younger. Truncal fat was associated with less JSN progression in female patients. Smoking predicted erosion progression, and erosions may precede JSN. BMI and fat distribution may influence cartilage damage in early RA and might be related to hormonal factors.
33792744 [Atypical arthritis of the hands : Collagenosis-part 2]. 2021 May BACKGROUND: Progressive systemic scleroderma (PSS) and mixed connective tissue disease (MCTD) represent vasculitic autoimmune diseases from the group of collagenoses with manifestations in various organ systems such as the skin, the internal organs and the joints. OBJECTIVE: To present the atypical arthritis patterns of the hands in PSS and MCTD that differ from those in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in the context of clinical and serologic findings and in consideration of the classification of PSS and MCTD. MATERIALS AND METHODS: Narrative review based on the current literature on the subject from the radiological and rheumatological point of view. RESULTS: In PSS, combinations of acral soft tissue atrophy, nonreactive acro-osteolysis, and interstitial calcifications can be visualized by projection radiography, which in the final stage can lead to a scleroderma claw hand. Digital pharmacoangiography of the hands can be used to reliably diagnose manifest vascular occlusions of the digital arteries. MCTD is characterized by various overlapping symptoms of at least two systemic autoimmune diseases and most frequently presents in the hand with symmetrical involvement of the PIP (proximal interphalangeal), MCP (metacarpophalangeal) and wrist joints with the manifestation of so-called "puffy fingers". CONCLUSIONS: The presented morphological atypical arthritis patterns of the hands in PSS and MCTD differ considerably from the typical patterns in the hands in RA and PsA. MRI is useful to diagnose early stages and pharmacoangiography can be used to differentiate between temporary and manifest digital vascular occlusions.