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ID PMID Title PublicationDate abstract
33800462 Role of ADAM10 and ADAM17 in Regulating CD137 Function. 2021 Mar 8 Human CD137 (4-1BB), a member of the TNF receptor family, and its ligand CD137L (4-1BBL), are expressed on immune cells and tumor cells. CD137/CD137L interaction mediates bidirectional cellular responses of potential relevance in inflammatory diseases, autoimmunity and oncology. A soluble form of CD137 exists, elevated levels of which have been reported in patients with rheumatoid arthritis and various malignancies. Soluble CD137 (sCD137) is considered to represent a splice variant of CD137. In this report, however, evidence is presented that A Disintegrin and Metalloproteinase (ADAM)10 and potentially also ADAM17 are centrally involved in its generation. Release of sCD137 by transfected cell lines and primary T cells was uniformly inhibitable by ADAM10 inhibition. The shedding function of ADAM10 can be blocked through inhibition of its interaction with surface exposed phosphatidylserine (PS), and this effectively inhibited sCD137 generation. The phospholipid scramblase Anoctamin-6 (ANO6) traffics PS to the outer membrane and thus modifies ADAM10 function. Overexpression of ANO6 increased stimulated shedding, and hyperactive ANO6 led to maximal constitutive shedding of CD137. sCD137 was functionally active and augmented T cell proliferation. Our findings shed new light on the regulation of CD137/CD137L immune responses with potential impact on immunotherapeutic approaches targeting CD137.
33600008 Comparative effectiveness and safety of non-tumour necrosis factor biologics and Janus kin 2021 Aug WHAT IS KNOWN AND OBJECTIVE: Both biologic and Janus kinase (JAK) inhibitor therapies have demonstrated substantial effectiveness in placebo-controlled studies in patients with active rheumatoid arthritis (RA) showing inadequate responses to tumour necrosis factor (TNF) inhibitors. The purpose of this study was to determine the relative effectiveness and safety of non-TNF biologics and JAK inhibitors in patients with RA showing insufficient response to TNF inhibitors. METHODS: A Bayesian network meta-analysis incorporating direct and indirect data from randomized controlled trials (RCTs) was used to investigate the effectiveness and safety of non-TNF biologics (abatacept, rituximab, tocilizumab, salirumab and sirukumab) and JAK inhibitors (tofacitinib, baricitinib, upadacitinib and filgotinib) in patients with RA showing insufficient response to TNF inhibitors. RESULTS: Nine RCTs, evaluating 3577 patients for 12 weeks fulfilled the inclusion requirements. JAK inhibitors and non-TNF biologics achieved a significant American College of Rheumatology 20% (ACR20) response relative to the placebo. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) showed that JAK inhibitor treatment was most likely to achieve the highest ACR20 response rate, followed by non-TNF biologics and placebo. The ACR50 rate displayed similar patterns as the ACR20 response rate, but non-TNF biologics have a higher value than JAK inhibitors based on the ACR70 response rate. Adverse events did not reach statistical significance nor did serious adverse events when looking at safety over 12 weeks. The confidence intervals overlap, and there is no clinical significance to these safety data, even compared with placebo. WHAT IS NEW AND CONCLUSION: Both non-TNF biologics and JAK inhibitors have similar effects in patients with active RA that are refractory to anti-TNF treatment, and there were no differences with regard to safety among the treatments.
34233727 Switching from TNFα inhibitor to tacrolimus as maintenance therapy in rheumatoid arthriti 2021 Jul 8 BACKGROUND: Tapering or stopping biological disease-modifying anti-rheumatic drugs has been proposed for patients with rheumatoid arthritis (RA) in remission, but it frequently results in high rates of recurrence. This study evaluates the efficacy and safety of tacrolimus (TAC) as maintenance therapy in patients with established RA in remission after receiving combination therapy with tumor necrosis factor inhibitor (TNFi) and methotrexate (MTX). METHODS: This 24-week, prospective, open-label trial included patients who received TNFi and MTX at stable doses for ≥24 weeks and had low disease activity (LDA), measured by Disease Activity Score-28 for ≥12 weeks. Patients selected one of two arms: maintenance (TNFi plus MTX) or switched (TAC plus MTX). The primary outcome was the difference in the proportion of patients maintaining LDA at week 24, which was assessed using a logistic regression model. Adverse events were monitored throughout the study period. RESULTS: In efficacy analysis, 80 and 34 patients were included in the maintenance and switched arms, respectively. At week 24, LDA was maintained in 99% and 91% of patients in the maintenance and switched arms, respectively (odds ratio, 0.14; 95% confidence interval, 0.01-1.59). Drug-related adverse effects tended to be more common in the switched arm than in the maintenance arm (20.9% versus 7.1%, respectively) but were well-tolerated. CONCLUSION: This controlled study tested a novel treatment strategy of switching from TNFi to TAC in RA patients with sustained LDA, and the findings suggested that TNFi can be replaced with TAC in most patients without the patients experiencing flare-ups for at least 24 weeks. TRIAL REGISTRATION: Korea CDC CRIS, KCT0005868 . Registered 4 February 2021-retrospectively registered.
33583754 Contrast-enhanced T1-weighted Dixon water- and fat-only images to assess osteitis and eros 2021 Jul PURPOSE: To assess the agreement between readers using contrast-enhanced T1-weighted Dixon water- and fat-only images and OMERACT-recommended sequences for the scoring of osteitis and erosions according to the rheumatoid arthritis (RA) MRI scoring system (RAMRIS) in hands of patients with early RA. MATERIALS AND METHODS: Both hands of 24 patients (16 women, 8 men; mean age, 45.7±14.5 [SD] years; age range: 25-70 years) with early RA were prospectively imaged with fat-saturated T2-weighted sequences, non-Dixon T1-weighted imaging prior to contrast material injection and T1-weighted Dixon imaging after contrast material injection at 1.5T. There were Two radiologists separately quantified osteitis and erosions according to RAMRIS using contrast-enhanced T1-weighted Dixon water-only and fat-saturated T2-weighted images for osteitis and contrast-enhanced T1-weighted Dixon fat-only and T1-weighted images prior to contrast material injection for erosions. Intraclass correlation coefficients (ICC) were calculated to assess inter-technique, intra-observer and inter-observer agreement. RESULTS: Mean ICC for the agreement between Dixon and non-Dixon images ranged from 0.68 (95%CI: 0.20-0.90) to 0.99 (95%CI: 0.95-1.00) for the scoring of osteitis and from 0.77 (95%CI: 0.38-0.93) to 0.99 (95%CI: 0.95-1.00) for the scoring of erosions. Mean ICC for the agreement between first and second readings ranged from 0.94 (95%CI: 0.81-0.98) to 0.97 (95%CI: 0.91-0.99) for the scoring of osteitis using Dixon and 0.91 (95%CI: 0.72-0.97) to 0.98 (95%CI: 0.92-0.99) using non-Dixon images and from 0.80 (95%CI: 0.45-0.94) to 0.97 (95%CI: 0.91-0.99) for the scoring of erosions using Dixon and 0.72 (95%CI: 0.29-0.91) to 0.98 (95%CI: 0.92-0.99) using non-Dixon images. CONCLUSION: Contrast-enhanced T1-weighted Dixon water- and fat-only images can serve as an alternative to fat-saturated T2-weighted and T1-weighted MRI sequences for the assessment of osteitis and erosions according to the RAMRIS scoring system in hands of patients with early RA.
33873113 Cyclic mechanical stimulation inhibits rheumatoid arthritis fibroblast-like synoviocytes p 2021 May 24 The imbalance between proliferation and apoptosis of fibroblast-like synoviocytes (FLSs) has been the main cause of rheumatoid arthritis (RA) synovial hyperplasia. Our previous study confirmed that the cyclic mechanical stimulation (CMS) inhibited the proliferation of RA FLSs, but the underlying mechanisms are still unclear. This study aimed to investigate these underlying mechanisms. The in vitro cultured human RA FLSs were subjected to CMS (6%, 1.0 Hz). Cell cycle was detected by flow cytometry. The expression of cyclin D1, cyclin E1, CDK-2 and p27 was detected by reverse transcription-polymerase chain reaction (RT-PCR). MTS assay was used to detect cell viability. Cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) levels in RA FLSs were detected by western blotting and enzyme-linked immunosorbent assay (ELISA), respectively. The results showed that CMS significantly inhibited the cell cycle transformation of RA FLSs from G1 phase to S phase, which significantly decreased the cell proliferation index. Meanwhile, both cyclin E1 and CDK-2 gene expressions were significantly decreased, p27 gene expression was increased, and no significant change was observed in the expression of cyclin D1. The inhibition of COX-2/PGE(2) pathway in RA FLSs by celecoxib treatment showed no effect on the inhibition of RA FLSs proliferation by CMS. In conclusion, CMS inhibited the proliferation of RA FLSs by modulating the expression of cell cycle-related molecules such as cyclin E1, CDK2 and p27 to arrest cell cycle transformation, which is independent of COX-2/PGE(2) signaling pathway.
33671049 Thromboembolic Adverse Drug Reactions in Janus Kinase (JAK) Inhibitors: Does the Inhibitor 2021 Feb 28 Recent advances in immunology enabled the characterization of several signal transmitting pathways responsible for proper cytokine and chemokine signaling. Among them, Janus kinases (JAKs) are essential components of receptor activation systems. The discovery of JAK kinases enabled the synthesis of JAK kinase inhibitors (JAKi or Jakinibs), which have proven to be efficacious in the treatment of hematologic malignancies and several rheumatological disorders and continue to be investigated in many clinical indications. Blocking multiple cytokines belonging to several cytokine families with a single small molecule may, however, create a potential risk for the patients. Recently, a higher risk of thromboembolic complications, namely, deep vein thrombosis and pulmonary embolism, has been recognized as the main concern during treatment with Jakinibs. At present, it is not entirely clear whether this increased risk is related to direct cytokine blockade, the presence of concomitant diseases in treated patients or other unknown circumstances that work together to increase the risk of this side effect. In this review, we discuss data on the risk of thromboembolic side effects, with special emphasis on the mechanism that may be responsible for this increased risk. Many indirect data indicate that higher thromboembolic risk may be related to the specificity of JAK inhibitor action, such that preferentially blocking one signaling pathway upsets the balance between pro and anti-thrombotic activities.
32735145 Radiographic and clinical effects of 10 mg and 25 mg twice-weekly etanercept over 52 w 2021 Mar OBJECTIVES: To compare the radiographic and clinical effects of 25 versus 10 mg twice-weekly (BIW) etanercept over 52 weeks in Japanese patients with active rheumatoid arthritis (RA). METHODS: This was a post-hoc analysis of a Phase 3 study where Japanese patients with active RA were randomized to receive BIW etanercept 25 mg (n = 182), etanercept 10 mg (n = 192), or methotrexate (n = 176) for 52 weeks (NCT00445770). This analysis included assessments of week-24 and week-52 disease activity, week-52 radiographic progression, and the relationship between baseline characteristics and week 52 clinical outcomes with clinically relevant radiographic progression (CRRP) at week 52. RESULTS: At week 52, there were no significant differences between 25 and 10 mg etanercept in terms of achieving low disease activity or remission. CRRP was observed in 36% and 32% of patients in the 10 and 25 mg groups, respectively. Predictor analysis suggested that worse background disease status, treatment with methotrexate rather than etanercept, and poorer clinical outcomes at week 52 were associated with CRRP. CONCLUSIONS: The 25 mg BIW etanercept dosage does not appear to be significantly more efficacious than 10 mg in Japanese patients with RA. Further studies evaluating the optimal etanercept dosing regimen in this patient population may be merited. NCT: NCT00445770.
34228594 Rhupus: dual rheumatic disease. 2022 Mar 4 Autoimmune disorders are typically categorized into systematic and local diseases that affect a single organ or tissue. Organs and tissues affected by autoimmune disorders include components of the endocrine system, such as thyroid, pancreas, and adrenal glands; blood, such as red blood cells; and the connective tissues, skin, muscles, and joints. Rhupus is a complex musculoskeletal autoimmune disease (AD) in which features of both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are simultaneously present. The cause and trigger of rhupus is still unknown, suggesting the role of genetic, immunological, hormonal, and environmental factors in the initiation and progression of the disease. The role of immune system has been established by the presence of specific autoantibodies as markers for diagnosis of rhupus and the formation of immune complex in serum. The complications of rhupus include the presence of rheumatoid factor (RF) and nodules and the involvement of nervous and renal systems that complicates its diagnosis and prognosis. The rhupus arthritis resembles RA-like pathophysiology and leads to inflammation, deformation, and disability. Due to the heterogeneity and rarity of the disease, the prevalence, pathophysiology, and natural history as well as radiological and immunological profiles of rhupus are still not properly understood.
34163464 A 8-mer Peptide of PGLYRP1/Tag7 Innate Immunity Protein Binds to TNFR1 Receptor and Inhibi 2021 Search for novel regulatory protein fragments with potential functional roles is required both for understanding the immune response mechanisms and the development of targeted immunotherapy. Earlier we demonstrated that the PGLYRP1/Tag7 innate immunity protein can be regarded as an inhibitor of TNFα cytotoxic activity via the interaction with its TNF receptor 1 (TNFR1). A C-terminal peptide fragment 17.1 of the molecule is responsible for this function. In this study we have identified a minimal 8-mer region of this peptide (hereinafter - 17.1A) capable to bind to TNFR1. As a result of such interaction, the cytotoxic signals induced by this receptor are blocked. Also, this peptide demonstrates an anti-inflammatory activity in vivo in the complete Freund's adjuvant (CFA)-induced arthritis model in laboratory mice. Peptide 17.1A is capable to reduce periarticular inflammation, inhibit the development of synovitis and exhibit a protective effect on cartilage and bone tissues. This peptide can turn out to be a promising medicinal agent for autoimmune arthritis and other diseases.
32892510 Health Assessment Questionnaire at One Year Predicts All-Cause Mortality in Patients With 2021 Feb OBJECTIVE: Higher self-reported disability (high Health Assessment Questionnaire [HAQ] score) has been associated with hospitalizations and mortality in established rheumatoid arthritis (RA), but associations in early RA are unknown. METHODS: Patients with early RA (symptom duration <1 year) enrolled in the Canadian Early Arthritis Cohort who initiated disease-modifying antirheumatic drugs and had completed HAQ data at baseline and 1 year were included in the study. Discrete-time proportional hazards models were used to estimate crude and multi-adjusted associations of baseline HAQ and HAQ at 1 year with all-cause mortality in each year of follow-up. RESULTS: A total of 1,724 patients with early RA were included. The mean age was 55 years, and 72% were women. Over 10 years, 62 deaths (3.6%) were recorded. Deceased patients had higher HAQ scores at baseline (mean ± SD 1.2 ± 0.7) and at 1 year (0.9 ± 0.7) than living patients (1.0 ± 0.7 and 0.5 ± 0.6, respectively; P < 0.001). Disease Activity Score in 28 joints (DAS28) was higher in deceased versus living patients at baseline (mean ± SD 5.4 ± 1.3 versus 4.9 ± 1.4) and at 1 year (mean ± SD 3.6 ± 1.4 versus 2.8 ± 1.4) (P < 0.001). Older age, male sex, lower education level, smoking, more comorbidities, higher baseline DAS28, and glucocorticoid use were associated with mortality. Contrary to HAQ score at baseline, the association between all-cause mortality and HAQ score at 1 year remained significant even after adjustment for confounders. For baseline HAQ score, the unadjusted hazard ratio (HR) was 1.46 (95% confidence interval [95% CI] 1.02-2.09), and the adjusted HR was 1.25 (95% CI 0.81-1.94). For HAQ score at 1 year, the unadjusted HR was 2.58 (95% CI 1.78-3.72), and the adjusted HR was 1.75 (95% CI 1.10-2.77). CONCLUSION: Our findings indicate that higher HAQ score and DAS28 at 1 year are significantly associated with all-cause mortality in a large early RA cohort.
34343136 IL-1β-driven osteoclastogenic Tregs accelerate bone erosion in arthritis. 2021 Sep 15 IL-1β is a proinflammatory mediator with roles in innate and adaptive immunity. Here we show that IL-1β contributes to autoimmune arthritis by inducing osteoclastogenic capacity in Tregs. Using mice with joint inflammation arising through deficiency of the IL-1 receptor antagonist (Il1rn-/-), we observed that IL-1β blockade attenuated disease more effectively in early arthritis than in established arthritis, especially with respect to bone erosion. Protection was accompanied by a reduction in synovial CD4+Foxp3+ Tregs that displayed preserved suppressive capacity and aerobic metabolism but aberrant expression of RANKL and a striking capacity to drive RANKL-dependent osteoclast differentiation. Both Il1rn-/- Tregs and wild-type Tregs differentiated with IL-1β accelerated bone erosion upon adoptive transfer. Human Tregs exhibited analogous differentiation, and corresponding RANKLhiFoxp3+ T cells could be identified in rheumatoid arthritis synovial tissue. Together, these findings identify IL-1β-induced osteoclastogenic Tregs as a contributor to bone erosion in arthritis.
33757859 Auto-antibodies to post-translationally modified proteins in osteoarthritis. 2021 Jun OBJECTIVE: Autoantibodies (AutoAbs) have been observed in osteoarthritis (OA) with broad antigenicity, although their prevalence and role remain unclear. Post-translational modification (PTMs) of proteins (oxidation, carbamylation, citrullination) is associated with synovitis and can lead to AutoAb development. Given the prevalence of synovitis, we explored whether AutoAbs to PTM-antigens are common in OA compared with rheumatoid arthritis (RA). METHODS: Serum (n = 895) was obtained from healthy controls, OA and RA patients; and arthritic synovial fluid (SF, n = 290). ELISAs were used to quantify anti-citrullinated peptide (ACPA), anti-carbamylated protein (anti-CarP), anti-oxidized collagen (anti-ROS-CI/CII) antibodies. RESULTS: In sera, positivity for PTM-antigens AutoAbs was observed at a lower frequency in OA with 64.1% (95%CI: 57.2-70.1%) more ACPA+ and 29.8% (21.0-37.3%) more anti-CarP + patients in RA (both P < 0.0001). Levels of ACPA, anti-CarP were also lower in OA (P < 0.0001). Anti-ROS-CII positivity was lower in OA compared to RA (16.6%, 4.8-28.6%) less frequent, P = 0.033) but not anti-native-CII. There was no impact of age/gender on AutoAbs associations with diseases either looking at positivity or levels. In SF, OA patients were often ACPA+ (45.9%) although less frequently than in RA (P = 0.004). Anti-CarP were rarely observed (<5% all samples). All collagen AutoAbs were more frequent in RA compared to OA (all P < 0.010) but only levels of anti-CII and anti-ROS-CII were significantly higher in they RA (P < 0.050). CONCLUSION: Although the frequency of AutoAbs for PTM proteins were lower in OA sera compared to RA, a higher proportion of OA SF were positive. The relative retention of AutoAbs in the OA joint requires further investigation.
34161884 Mesenchymal stem/stromal cell-based therapy for the treatment of rheumatoid arthritis: An 2021 Jul Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and progressive joint destruction and is a primary cause of disability worldwide. Despite the existence of numerous anti-rheumatic drugs, a significant number of patients with RA do not respond or are intolerant to current treatments. Mesenchymal stem/stromal cell (MSCs) therapy represents a promising therapeutic tool to treat RA, mainly attributable to the immunomodulatory effects of these cells. This review comprises a comprehensive analysis of the scientific literature related to preclinical studies of MSC-based therapy in RA to analyse key aspects of current protocols as well as novel approaches which aim to improve the efficacy of MSC-based therapy.
32185699 Structural Basis of a Conventional Recognition Mode of IGHV1-69 Rheumatoid Factors. 2021 Rheumatoid factors (RFs) are autoantibodies that recognize the fragment crystallizable (Fc) region of immunoglobulin G (IgG). Genetically diverse RFs are produced in rheumatoid arthritis patients; however, in hematologic diseases, such as cryoglobulinemia and B cell lymphoma, RFs from a limited combination of heavy chain V-region genes and J-region genes are produced in large quantities and forms immune complexes with IgG. These genetically limited RFs have historically been used for the immunochemical characterization of RFs. Among them, RFs derived from the heavy-chain germline gene IGHV1-69 are the most common. Recently, the crystal structure of an IGHV1-69-derived RF named YES8c was elucidated in complex with human IgG1-Fc. Based on the structure and mutant analyses, a recognition mechanism for the autoantigen (IgG-Fc) common to IGHV1-69-derived RFs was proposed. This review summarizes the immunochemical character of the IGHV1-69-derived RFs, and then focuses on the recognition mechanism of the IGHV1-69-derived RFs, referring the structural features of the IGHV1-69-derived neutralizing antibodies.
33780033 Effects of vitamin K(2) combined with methotrexate against mitogen-activated peripheral bl 2021 Oct BACKGROUND: Methotrexate (MTX) is used as anchor drug for patients with early and established rheumatoid arthritis (RA). Vitamin K(2) administration was also reported to be associated with decreased disease activity in RA. OBJECTIVES: Immunosuppressive pharmacodynamics of vitamin K(2) combined with MTX was investigated. METHODS: Mitogen-activated peripheral blood mononuclear cells (PBMCs) were used to evaluate immunosuppressive pharmacodynamics of drugs in vitro. RESULTS: Vitamin K(2) alone dose-dependently suppressed T cell mitogen-activated proliferation of PBMCs of both healthy subjects and RA patients. 446.5 and 2232.5 ng/mL vitamin K(2) significantly decreased the IC(50) values of MTX on the proliferation of PBMCs of RA patients, with little influences on the pharmacodynamics of MTX in the healthy PBMCs. 4465 ng/mL vitamin K(2) potentiated the pharmacodynamics of MTX in both RA patients and healthy PBMCs. The additional effects of vitamin K(2) to potentiate the suppressive effects of MTX seemed not to be related to the regulation of CD4(+) CD25(+) T cells or CD4(+) CD25(+) Foxp3(+) Treg cells. MTX alone at 100 ng/mL significantly decreased the percentage of CD4(+) T cells in PBMCs of healthy subjects (p < 0.001) with a slight influence in that of RA patients (not significant) and the combination did not show synergistic inhibitory effect. Vitamin K(2) alone tended to suppress the secretion of IL-17, IFN-γ, and TNF-α from the activated PBMCs of RA patients with smaller influences on the cytokine productions from healthy PBMCs. These additional effects of vitamin K(2) were also observed in combination with MTX. CONCLUSION: The above information may partially elucidate the potentiation effects of vitamin K(2) on the immunosuppressive efficacy of MTX.
34672095 Modified Hidden Blood Loss Based on Drainage in Posterior Surgery on Lumbar Stenosis Syndr 2021 Dec OBJECTIVE: Publications on hidden blood loss (HBL) after posterior lumbar interbody fusion (PLIF) for lumbar spine stenosis syndrome (LSS) have been reported, but the modified HBL (mHBL) was different from HBL obtained by classical formula and there are few studies on lumbar spine hemorrhage with rheumatoid arthritis (RA). Therefore, the aim of our study is to respectively evaluate the importance of hidden blood loss (HBL) and modified HBL (mHBL) after posterior lumbar interbody fusion (PLIF) in patients diagnosed with LSS and RA, to explore the correlation between RA activity and HBL as well as mHBL. METHODS: A total of 61 patients (nine males and 52 females) diagnosed with LSS and RA who underwent PLIF were included. Data contained demographics, RA-related parameters such as duration of RA, Steinbrocker classification (used to evaluated RA activity), the disease-modifying anti-rheumatic drugs (DMARDs), osteoporosis and total knee arthroplasty; operation and hemorrhage parameters. Then HBL and mHBL were calculated by Gross formula and modified formula, respectively. Subgroup analysis on HBL and mHBL was performed based on gender, age (≤60 years and ˃60 years), different number of surgical segments (single segment, double segment, and ≥3 segments), and taking DMARDs or not. ANOVA analysis was performed on HBL and mHBL in different surgery segment number and Steinbrocker classification of RA. Independent sample t-test was used in comparison of gender and age, as well as in comparison between HBL and mHBL based on whether the patient took DMARDs or not. Furthermore, paired t-test was used to compare the volume between HBL and mHBL. RESULTS: The mean age and duration of RA was 65.2 ± 9.3 years and 14.3 ± 10.7 years, respectively. There were 13 grade I cases, 34 grade II cases, and 14 grade III cases as assessed by Steinbrocker classification and the most common anti-RA drugs were DMARDs (57.4%). The mean intraoperative bleeding, drainage, and blood loss in drainage (DBL) was 453.3 ± 377.8 mL, 489.1 ± 253.8 mL, and 304.6 ± 156.3 mL, respectively. There was no difference on HBL and mHBL in gender. HBL and mHBL was larger in patients over 60 years (P = 0.040 and P = 0.023). There were differences in intraoperative blood loss, drainage, and DBL based on different number of segments but not in HBL and mHBL, or on Steinbrocker classification. DBL was lower in DMARDs group than non-drugged group (P = 0.03), while HBL and mHBL were both of no significance. The comparison of HBL and mHBL showed statistical difference (P < 0.001), suggesting that mHBL volume is larger than HBL. CONCLUSIONS: Patients diagnosed as LSS with RA have amounts of HBL or mHBL after PLIF. HBL or mHBL is not associated with RA activity, which may not increase in RA patients compared with common ones. Taking DMARDs may reduce postoperative DBL. The fact that mHBL is larger than HBL provides an all-round basis for measuring factual HBL.
33004333 Dysbiosis in the oral microbiomes of anti-CCP positive individuals at risk of developing r 2021 Feb OBJECTIVES: An increased prevalence of periodontitis and perturbation of the oral microbiome has been identified in patients with rheumatoid arthritis (RA). The periodontal pathogen Porphyromonas gingivalis may cause local citrullination of proteins, potentially triggering anti-citrullinated protein antibody production. However, it is not known if oral dysbiosis precedes the onset of clinical arthritis. This study comprehensively characterised the oral microbiome in anti-cyclic citrullinated peptide (anti-CCP) positive at-risk individuals without clinical synovitis (CCP+at risk). METHODS: Subgingival plaque was collected from periodontally healthy and diseased sites in 48 CCP+at risk, 26 early RA and 32 asymptomatic healthy control (HC) individuals. DNA libraries were sequenced on the Illumina HiSeq 3000 platform. Taxonomic profile and functional capability of the subgingival microbiome were compared between groups. RESULTS: At periodontally healthy sites, CCP+at risk individuals had significantly lower microbial richness compared with HC and early RA groups (p=0.004 and 0.021). Microbial community alterations were found at phylum, genus and species levels. A large proportion of the community differed significantly in membership (523 species; 35.6%) and structure (575 species; 39.1%) comparing CCP+at risk and HC groups. Certain core species, including P. gingivalis, had higher relative abundance in the CCP+at risk group. Seventeen clusters of orthologous gene functional units were significantly over-represented in the CCP+at risk group compared with HC (adjusted p value <0.05). CONCLUSION: Anti-CCP positive at-risk individuals have dysbiotic subgingival microbiomes and increased abundance of P. gingivalis compared with controls. This supports the hypothesis that the oral microbiome and specifically P. gingivalis are important in RA initiation.
33323529 Safety and Efficacy of Poseltinib, Bruton's Tyrosine Kinase Inhibitor, in Patients With Rh 2021 Jul OBJECTIVE: To evaluate the efficacy and safety of poseltinib (formerly LY3337641/HM71224), an irreversible covalent inhibitor of Bruton's tyrosine kinase in a 2-part, phase II trial (RAjuvenate; ClinicalTrials.gov: NCT02628028) in adults with active rheumatoid arthritis (RA). METHODS: In Part A, 36 patients with mildly active RA were randomized 1:1:1:1 to oral poseltinib 5, 10, or 30 mg or placebo once daily for 4 weeks to assess safety and tolerability. No safety signals precluded moving to Part B, where 250 patients with moderate-to-severe RA were randomized 1:1:1:1 to oral poseltinib 5 mg (n = 63), 10 mg (n = 62), or 30 mg (n = 63), or placebo (n = 62) once daily for 12 weeks. Parts A and B permitted stable doses of background disease-modifying antirheumatic drugs. The primary endpoint in Part B was proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 12. Logistic regression compared each poseltinib dose to placebo for primary and secondary endpoints. Nonresponder imputation was used for missing data. RESULTS: After interim analysis showed low likelihood of demonstrating significant efficacy, the sponsor discontinued Part B of the study. One hundred and eighty-nine (76%) patients completed 12 weeks in Part B; 61 discontinued study treatment (27 [44%] due to study termination by sponsor). There was no statistically significant difference in ACR20 response between any dose of poseltinib and placebo at Week 12 (P > 0.05 for all comparisons). Five serious adverse events occurred (n = 2, placebo; n = 3, 30 mg); there was 1 death due to a fall. CONCLUSION: While no safety findings precluded continuation, the study was terminated after interim data demonstrated low likelihood of benefit in RA.
34173843 Prevalence of latent tuberculosis before biotherapy initiation in rheumatoid arthritis and 2021 Sep Before the initiation of biotherapy in the treatment of rheumatic diseases, it is highly recommended for the patients to be screened for latent tuberculosis infection (LTBI). The objective of this study is to identify the prevalence of LTBI among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) before the initiation of biologic therapy in the Moroccan biotherapy registry (RBSMR). A cross sectional study was conducted using the baseline data of the Moroccan biotherapy registry. Tuberculin skin test or IGRA test or both tests were done before starting anti-TNF treatment for screening LTBI. The comparisons between positive and negative LTBI patients according to rheumatic disease were examined using categorical comparisons. 259 patients were included in this study.94 patients had RA and 165 had SpA. The mean age of the RA patients was 50.49 ± 11.82 years with a majority of females (84%). The mean age for the SpA patients was 36 ± 13.7 years with a majority of males (67.3%). The prevalence of LTBI in the RBSMR was 21.6%. This prevalence was at 24.8% in SpA patients, while it was at 15.9% for RA patients. After the comparison between positive and negative LTBI patients according to rheumatic disease, no demographic, clinical, or therapeutic characteristics were statistically associated with LTBI. This study found that in an endemic TB country like Morocco, a high prevalence of patients with SpA and RA had LTBI, and that RA patients had a lower prevalence than SpA patients.
33144158 Outcomes of Percutaneous Coronary Intervention in Patients With Rheumatoid Arthritis. 2021 Feb 1 Rheumatoid arthritis (RA) is the most common inflammatory arthritis and is associated with increased risk of cardiovascular events and mortality. Evidence regarding outcomes following PCI is limited. This study aimed to assess differences in outcomes following percutaneous coronary intervention (PCI) between patients with and without RA. The Melbourne Interventional Group PCI registry (2005 to 2018) was used to identify 756 patients with RA. Outcomes were compared with the remaining cohort (n = 38,579). Patients with RA were older, more often female, with higher rates of hypertension, previous stroke, peripheral vascular disease, obstructive sleep apnea, chronic lung disease, myocardial infarction, and renal impairment, whereas rates of dyslipidemia and current smoking were lower, all p <0.05. Lesions in patients with RA were more frequently complex (ACC/AHA type B2/C), requiring longer stents, with higher rates of no reflow, all p <0.05. Risk of long-term mortality, adjusted for potential confounders, was higher for patients with RA (hazard ratio 1.53, 95% confidence interval 1.30 to 1.80; median follow-up 5.0 years), whereas 30-day outcomes including mortality, major adverse cardiovascular events, bleeding, stroke, myocardial infarction, coronary artery bypass surgery, and target vessel revascularization were similar. In subgroup analysis, patients with RA and lower BMI (P(for interaction) < 0.001) and/or acute coronary syndromes (P(for interaction) = 0.05) had disproportionately higher risk of long-term mortality compared with patients without RA. In conclusion, patients with RA who underwent PCI had more co-morbidities and longer, complex coronary lesions. Risk of short-term adverse outcomes was similar, whereas risk of long-term mortality was higher, especially among patients with acute coronary syndromes and lower body mass index.