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ID PMID Title PublicationDate abstract
33200883 Codevelopment of Patient Self-Examination Methods and Joint Count Reporting for Rheumatoid 2020 Dec OBJECTIVE: To determine whether training increases accuracy of self-reported joint counts in people with rheumatoid arthritis (RA) and describe the knowledge and techniques for self-examination of joints for reporting of RA disease activity. METHODS: This mixed-methods study included 10 patients with RA and four rheumatologists. A rheumatologist presented about joint inflammation and disease monitoring in RA. Patients then self-examined and reported 28-tender joint count (28-TJC) and 28-swollen joint count (28-SJC). Next, two paired rheumatologists examined patients and reported 28-TJC and 28-SJC. After watching a joint examination video for training physicians, patients discussed their training needs for self-examination, with discussion analyzed using thematic analysis. Self-examination techniques were determined by consensus. Finally, patients self-examined and reported 28-TJC and 28-SJC. Reliability between the first and second patient-reported 28-TJCs and 28-SJCs and rheumatologist pair-reported 28-TJC and 28-SJC was determined with the intraclass coefficient. RESULTS: The reliability for patient self-reported joint counts was higher for the 28-TJC than for the 28-SJC. Reliability improved following rheumatologist examination and training. Patients identified a preference for practical information rather than detailed information on joint anatomy and pathophysiology. Clear definitions of "swollen" and "tender" were important; patients found the concept of "tenderness" difficult. Techniques for self-examination and reporting of joint counts were agreed on and demonstrated in an instructional video. CONCLUSION: Training increased reliability of patient-reported joint counts. Patients with RA identified important aspects of training for self-examination and reporting of joint counts. An 8-minute instructional video was codeveloped; the next step is the evaluation of the video's impact on patient-reported joint counts.
33092467 Improving sensitivity of the connective tissue disease screening questionnaire: A comparat 2021 Jan OBJECTIVES: Early detection of autoimmune rheumatic diseases is crucial given their high morbidity and mortality and short window of opportunity to improve patient outcomes. Self-administered screening questionnaires such as the connective tissue disease screening questionnaire (CSQ) have been shown to promote early detection of autoimmune rheumatic diseases. However, optimal scoring of screening questionnaires may differ with prevalence of clinical features and changes in classification criteria. We compared the performance of 3 scoring methods for the CSQ for early detection of autoimmune rheumatic diseases in a multi-ethnic Asian population. METHODS: Patients who were newly referred for evaluation of possible autoimmune rheumatic diseases were invited to answer the cross-culturally adapted CSQ. Detection of autoimmune rheumatic diseases using 1) the original CSQ scoring, 2) a modified CSQ scoring and 3) a scoring based on current classification criteria, were compared to classification of autoimmune rheumatic diseases by classification criteria. RESULTS: Of 819 participants, 85 were classified as having autoimmune rheumatic diseases screened for by the adapted CSQ. The original CSQ scoring yielded relatively lower sensitivities in detecting both any and individual autoimmune rheumatic diseases (67% and 20-57%, respectively) compared to the modified CSQ scoring (81% and 60-73%, respectively) and the scoring based on current classification criteria (89% and 50-88%, respectively). CONCLUSION: The adapted CSQ with the classification criteria-based scoring achieved relatively high sensitivities in detecting autoimmune rheumatic diseases, suggesting this could be employed as the first step in population screening.
32862564 DAS28-CRP Cutoffs for High Disease Activity and Remission Are Lower Than DAS28-ESR in Rheu 2020 Sep OBJECTIVE: Guidelines do not specify how cutoffs for high disease activity differ between the Disease Activity Score 28-joint count indices DAS28-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP). Studies that compare DAS28-CRP and DAS28-ESR depend on data from clinical trials, registries, or practices with multiple providers. Existing studies use data from patients who received immunosuppressive therapy. This study compared the DAS28-ESR and DAS28-CRP values from immunosuppressive treatment-naïve patients in a single physician practice. METHODS: A retrospective electronic medical chart review was conducted for new diagnoses of rheumatoid arthritis (RA; International Classification of Diseases [ICD]-9 714), based on the American College of Rheumatology/European League against Rheumatology 2010 RA classification criteria. The number of patients with high disease activity (>5.1) was compared using ESR and CRP data to calculate the proportion of discordance. A receiver operator curve and Youden index was used to calculate the DAS28-CRP high disease activity cutoff estimation that corresponds with DAS28-ESR of more than 5.1. RESULTS: There were 171 patients included in this study. The baseline mean DAS28-ESR was higher than the baseline mean DAS-28 CRP: 5.1 ± 1.2 versus 4.1 ± 1.0 (P < 0.001); 48.5% of patients met criteria for high disease activity (score >5.1) compared with only 14.6% when measured by DAS28-CRP. Discordance was 33.9%. κ coefficient was only .307. Receiver operator curve and Youden index analysis suggested that the cutoff point for high disease activity of DAS28-CRP greater than 4.1, which corresponds to DAS28-ESR greater than 5.1. Similarly, DAS28-ESR posttreatment scores were significantly higher than DAS28-CRP. When measured by DAS28-ESR, patients in remission had higher scores as measured by DAS28-ESR (1.81) than DAS28-CRP (1.45). CONCLUSION: There is a difference between DAS28-ESR and DAS28-CRP, even when calculated for immunosuppressive treatment-naïve patients. DAS28-CRP is significantly lower than DAS28-ESR.
32553103 Comparison of blood loss between intra-articular and intra-venous administration of tranex 2020 OBJECTIVE: To compare the blood loss between intra-articular and intra-venous administration of tranexamic acid (TXA) in patients undergoing primary total knee arthroplasty. DESIGN OF STUDY: It was a randomized controlled trial. Study duration and settings: This study was carried out at the Orthopedic Departments of Combined Military Hospital Lahore and Rawalpindi from Jan 2016 to March 2018. METHODOLOGY: Patients of both the genders were involved this study who had age in the rage of 40-80 years undergoing primary unilateral total knee arthroplasty for degenerative conditions like osteoarthritis and rheumatoid arthritis. These patients were randomly divided into two treatment groups. Patients in IA group received intra-articular tranexamic acid while those in IV group received intravenous tranexamic acid. From all the patients, a written signed consent was taken. FINDINGS: Females were predominant with male-to-female ratio of 1:3.7. The mean age of the patients was 67.3 ± 8.2 years while the mean BMI was 30.9 ± 2.9 Kg/m(2). Majority (n = 191, 95.5%) of the patients had osteoarthritis while remaining 9 (4.5%) patients had rheumatoid arthritis. There was no statistically significant difference between intra-articular and intra-venous administration of tranexamic acid in terms of mean post-operative hemoglobin (9.93 ± 1.14 vs. 9.87 ± 1.26 g/dL; p-value = 0.724), mean post-operative hematocrit (34.8 ± 1.66 vs. 34.73 ± 1.27%; p-value = 0.594), and mean fall in hemoglobin (2.27 ± 0.34 vs. 2.25 ± 0.30 g/dL; p-value = 0.587) and hematocrit (2.34 ± 0.94 vs. 2.46 ± 0.28%; p-value = 0.216). CONCLUSION: Intra-articular administration of tranexamic acid was found to be as effective and safe as intra-venous administration in reducing blood loss in primary total knee arthroplasty. Due to convenience, the use of intra-articular administration of tranexamic acid after primary TKA may be considered in future practice.
32403306 Generation of Monoclonal Antibodies Specific for Native LL37 and Citrullinated LL37 That D 2020 May 11 Human cathelicidin LL37 is a cationic antimicrobial peptide active against bacteria and viruses and exerting immune modulatory functions. LL37 can be also a target of autoreactive B- and T-lymphocytes in autoimmune settings. Irreversible post-translational modifications, such as citrullination and carbamylation, mainly occurring at the level of cationic amino acids arginine and lysine, can affect the inflammatory properties and reduce antibacterial effects. Moreover, these modifications could be implicated in the rupture of immune tolerance to LL37 in chronic conditions such as psoriatic disease and cutaneous lupus (LE)/systemic lupus erythematosus (SLE). Here, we describe the generation and fine specificity of six recombinant antibodies (MRB137-MRB142), produced as a monovalent mouse antibody with the antigen-binding scFv portion fused to a mouse IgG2a Fc, and their ability to recognize either native or citrullinated LL37 (cit-LL37) and not cross-react to carbamylated LL37. By using these antibodies, we detected native LL37 or cit-LL37 in SLE and rheumatoid arthritis (RA) sera, and in LE skin, by ELISA and immunohistochemistry, respectively. Such antibodies represent previously unavailable and useful tools to address relationships between the presence of post-translational modified LL37 and the immune system status (in terms of innate/adaptive responses activation) and the clinical characteristics of patients affected by chronic immune-mediated diseases or infectious diseases.
32362072 A Proposal to Standardize Low Disease Activity Criteria in Rheumatoid Arthritis Based on t 2020 May OBJECTIVE: We aimed to standardize the definition of low disease activity in rheumatoid arthritis (RA) using the Outcome Measures in Rheumatology (OMERACT) group's proposed definition of minimal disease activity. METHOD: Based on a nationwide RA database, we proposed new Boolean low disease activity criteria using OMERACT's core set definition of minimal disease activity that requires the fulfillment of at least five of the following seven core set measures: a pain score of 2 or less, a swollen joint count (SJC28) of 1 or fewer, a tender joint count of 1 or fewer, a Health Assessment Questionnaire score of 0.5 or less, a Physician's Global Assessment score of 1.5 or less, a Patient's Global Assessment score of 2 or less, and an erythrocyte sedimentation rate (ESR) of 20 mm/h or less. Using receiver operating characteristic analysis, we determined the cutoffs for the Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Routine Assessment of Patient Index Data 3 (RAPID3), and the Disease Activity Score in 28 joints (DAS28)-ESR. RESULTS: Of 8298 patients, 56.2% met the proposed Boolean low disease activity criteria. We determined an SDAI score of 5.5 or less and a CDAI score of 5 or less to be the new cutoffs, and we chose a DAS28 of 2.85 or less (the original cutoff for DAS-based minimal disease activity) and a RAPID3 score of 6 or less (the original cutoff for RAPID3-based low disease activity) with or without a swollen joint count (SJC) (SJC of 2 or fewer) as the cutoffs for DAS28 and RAPID3. The agreement between the new cutoffs for DAS28 of 2.85 or less vs. CDAI score of 5 or less, CDAI score of 5 or less vs. RAPID3 score of 6 or less (with SJC of 2 or fewer), and DAS28 of 2.85 or less vs. RAPID3 score of 6 or less (with SJC of 2 or fewer), was 0.619, 0.612 (0.702), and 0.474 (0.531), respectively. CONCLUSION: OMERACT's minimal disease activity definition may be used to standardize the criteria for low disease activity.
32706070 Unexpected macrophage activation syndrome in a healthy young woman: a case report. 2020 Jul Macrophage activation syndrome (MAS) is a life-threatening condition and a medical emergency with a high-risk of mortality. It belongs to a group of diseases known as "hemophagocytic lymphohistiocytosis", characterized by a cytokine storm, with secretion of tumor necrosis factor, interleukins and interferon-gamma, and an inappropriate activation of macrophages and T-lymphocytes. Some inflammatory and systemic autoimmune diseases, such as systemic juvenile idiopathic arthritis, Still's disease and systemic lupus erythematosus, can develop into macrophage activation syndrome. This is the first episode of macrophage activation syndrome (MAS) in a young healthy woman. She arrived at the Emergency Department complaining of four days of weakness and fever not responsive to paracetamol. She had no significant past medical history, her mother suffered from rheumatoid arthritis. In the Emergency Department, we performed laboratory exams, autoimmune and infectious disease screening, bone marrow biopsy. The final diagnosis was of macrophage activation syndrome. Macrophage activation syndrome, in extremely rare cases, can arise independently years before the manifestation of an autoimmune disease. Persistent fever, high level of inflammatory markers and pancytopenia should raise suspicion in healthy people, especially when associated with a family history of autoimmune disease. Early diagnosis and consequent early treatment are fundamental to avoid progressive tissue damage that can lead to organ failure and death.
33259155 2020 Jul Immune mediated immunological disorders comprise of a group of common conditions that affects the immunomodulatory pathways resulting in lasting and disabling inflammatory conditions. Rheumatological disorders such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic inflammatory conditions that affect predominantly the musculoskeletal system leading to pain, disability, functional impairment and lowered health related quality of life (HrQoL).(,) Treatment of these disorders aim at symptom management and to prevent and control joint and organ damage. They include corticosteroids, non-steroidal anti-inflammatory agents and disease-modifying antirheumatic drugs (DMARDs). Conventional DMARDs (cDMARDs) like methotrexate, sulfasalazine and hydroxychloroquine target the immune pathways, and have been used in early and long-term management of rheumatological disorders. Biologic DMARDs (bDMARDs) and janus kinase inhibitors target the molecules in the inflammatory pathway, thereby suppressing inflammation in RA, PsA and AS among other conditions. The clinical superiority of bDMARDs compared to placebo in rheumatological disorders have been established.(,). Among bDMARDs, tumor necrosis factor-alpha (TNF-α) inhibitors like adalimumab (ADA), infliximab (INF), etanercept (ETN), golimumab (GOL), and certolizumab pegol (CTZ) are approved for used in RA, PsA and AS.(,) In addition, interleukin-6 inhibitors like tocilizumab (TOC) and sarilumab (SAR) and T-cell stimulation blocker, abatacept (ABA) are used for RA, In PsA, secukinumab (SEC) is approved for use, and in AS ixekizumab (IXE) and SEC are also approved.(,) A janus kinase inhibitor, tofacitinib (TOF), is also approved for use in patients with RA. There is a scarcity of head-to-head trials comparing the clinical effectiveness of bDMARDs with each other. bDMARDs and targeted DMARDs being expensive, long term treatments with these agents will result in increased healthcare expenditure.(,) Thus, in the absence of comparative evidence, cost is a major determinant factor in the choice of bDMARDs. The objective of this report is to summarize the evidence regarding the comparative efficacy of ADA compared with other bDMARDs and tofacitinib in patients with rheumatological disorders.
32030657 Management of high-grade hallux rigidus: a narrative review of the literature. 2020 Dec Hallux rigidus is a disease characterized by an osteoarthritic degeneration of the first metatarsophalangeal joint. Aetiology of hallux rigidus is not clear in the literature. History of trauma is considered one of the most common causes of unilateral hallux rigidus. Also, repetitive microtraumas or inflammatory and metabolic causes such as gout, rheumatoid arthritis and seronegative arthropathy can cause degeneration of the joint. The aim of this literature narrative overview is to summarize and expose the great amount of management concepts and information, including the well-codified main operative procedures to treat of hallux rigidus. This may provide current information for med-school students, researchers and physicians. A comprehensive literature search using PubMed database has been performed. The management for hallux rigidus can involve a variety of therapeutic interventions, conservative or operative. High-grade hallux rigidus represents a complex disease characterized by several clinical and pathological findings, and to achieve optimal results, surgical treatment should be chosen between several surgical techniques depending on the degree of arthritis and other different clinical conditions.
32718669 Statins in COVID-19: is there any foundation? 2020 Nov Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19). Acute respiratory distress syndrome is the main cause of death from COVID-19 and occurs due to an exaggerated inflammatory response that causes the release of pro-inflammatory cytokines such as interleukins and tumor necrosis factor-alpha (TNF-α). Statins are lipid lowering drugs with pleiotropic effects. They have shown benefit in the management of inflammatory and autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Furthermore, due to their immunomodulatory properties, they have been used in the treatment of various infectious diseases such as community-acquired pneumonia and influenza. In this review we analyze the pathophysiological foundations that support the use of statins as an adjunctive treatment in patients with COVID-19.
32120325 Janus kinases (JAKs): The efficient therapeutic targets for autoimmune diseases and myelop 2020 Apr 15 The Janus kinases or JAKs are a family of intracellular tyrosine kinases that play an essential role in the signaling of numerous cytokines that have been implicated in the pathogenesis of autoimmune diseases and myeloproliferative disorders. JAKs are activated upon ligand induced receptor homo- or heterodimerization, which results in the immediate phosphorylation of tyrosine residues and the phosphotyrosines then serve as docking sites for cytoplasmic signal transducer and activator of transcription (STAT) proteins which become phosphorylated by the JAKs upon recruitment to the receptor complex. The phosphorylated STAT proteins dimerize and travel to the cellular nucleus, where they act as transcription factors. Interfering in the JAK-STAT pathway has yielded the only approved small molecule kinase inhibitors for immunological indications. Numerous medicinal chemistry studies are currently aimed at the design of novel and potent inhibitors for JAKs. Additionally, whether the second-generation inhibitors which possessed selectivity for JAKs are more efficient are under research. This Perspective summarizes the progress in the discovery and development of JAKs inhibitors, including the potential binding site and approaches for identifying small-molecule inhibitors, as well as future therapeutic perspectives in autoimmune diseases and myeloproliferative disorders are also put forward in order to provide reference and rational for the drug discovery of novel and potent JAKs inhibitors.
32598110 2020 Mar Upadacitinib is a Janus kinase (JAK) inhibitor (also referred to as a targeted synthetic disease-modifying antirheumatic drug [tsDMARD] in practice), indicated for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate. The recommended dose of upadacitinib is 15 mg daily as monotherapy or combination therapy. At the sponsor-submitted price of $48.68 per 15 mg tablet, the annual treatment cost is $17,770. The sponsor submitted a cost-utility analysis that considered upadacitinib as initial treatment for moderate-to-severe RA after an inadequate response or are intolerant to either a conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR population) or a biologic disease-modifying antirheumatic drug (bDMARD-IR population). The sponsor’s analysis was conducted from the perspective of a Canadian publicly funded health care payer over a five-year time horizon. Comparators included csDMARDs, bDMARDs, and other tsDMARDs. The pharmacoeconomic submission was based on a Markov model, where treatment response was evaluated using the American College of Rheumatology (ACR) response criteria. The model was composed of four main health states after the evaluation of initial treatment: 20% improvement in ACR criteria (ACR20); 50% improvement in ACR criteria (ACR50); 70% improvement in ACR criteria (ACR70); and lack of adequate treatment response (i.e., did not achieve minimum of ACR20). Patients who had an inadequate response or discontinued treatment owing to a serious adverse event (SAE) could receive a subsequent treatment and transition to any of the previously mentioned health states. If an adequate response was not achieved on subsequent treatment, patients received best supportive care (BSC), the prior therapy (bDMARD or tsDMARD) which patients achieved the best treatment effect. A sponsor-commissioned network meta-analysis (NMA) was submitted and informed the comparative ACR response at weeks 12 and 24. SAEs were incorporated on the basis of an NMA previously conducted by CADTH4 and updated to include upadacitinib and other missing comparators. Long-term discontinuation was included in the model owing to a loss of treatment effect over time. Health state utility values for ACR response and nonresponse were based on Health Assessment Questionnaire (HAQ) scores mapped to the Health Utility Index 3 (HUI-3) tool. In the sponsor’s base case, upadacitinib + csDMARD was associated with both higher total costs and quality-adjusted life-years (QALYs) when compared to csDMARD monotherapy in both target populations. In the csDMARD-IR population, the preferred option is csDMARD monotherapy if the decision-maker’s willingness to pay (WTP) is below $74,979 per QALY, infliximab 3 mg/kg + csDMARD if the decision-maker’s WTP is between $74,979 and $80,897 per QALY, etanercept 50 mg + csDMARD if the decision-maker’s WTP is between $80,897 and $107,659 per QALY, and upadacitinib + csDMARD if the decision-maker’s WTP is more than $107,659 per QALY. In the bDMARD-IR population, the preferred option is a csDMARD if the decision-maker’s WTP is below $104,193 per QALY, upadacitinib + csDMARD if the decision-maker’s WTP is between $104,193 and $303,516 per QALY, and tocilizumab 8 mg/kg + csDMARD if the decision-maker’s WTP is more than $303,516 per QALY. Other treatments were dominated or extendedly dominated.
32043832 Predicting Remission Among Patients With Rheumatoid Arthritis Starting Tocilizumab Monothe 2020 Feb OBJECTIVE: Most patients with rheumatoid arthritis (RA) strive to consolidate their treatment from methotrexate combinations. The objective of this analysis was to identify patients with RA most likely to achieve remission with tocilizumab (TCZ) monotherapy by developing and validating a prediction model and associated remission score. METHODS: We identified four TCZ monotherapy randomized controlled trials in RA and chose two for derivation and two for internal validation. Remission was defined as a Clinical Disease Activity Index score less than 2.8 at 24 weeks post randomization. We used logistic regression to assess the association between each predictor and remission. After selecting variables and assessing model performance in the derivation data set, we assessed model performance in the validation data set. The cohorts were combined to calculate a remission prediction score. RESULTS: The variables selected included younger age, male sex, lower baseline Clinical Disease Activity Index score, shorter RA disease duration, region of the world (Europe and South America [increased odds of remission] versus Asia and North America), no previous exposure to disease-modifying antirheumatic drugs and/or methotrexate, lower baseline Health Assessment Questionnaire Disability Index score, and baseline hematocrit. The area under the receiver operating characteristic curve was 0.739 in the derivation data set and 0.756 in the validation data set. Patients were categorized into three remission prediction categories based on the remission prediction score: 40% in the low (less than 10% probability of remission), 45% in the intermediate (10%-25% probability), and 15% in the moderate remission prediction category (greater than 25% probability). CONCLUSION: We used easily accessible factors to develop a remission prediction score to predict RA remission at 24 weeks after initializing TCZ monotherapy. These results may provide guidance to clinicians tailoring treatment options based on clinical characteristics.
33380844 Physical and Emotional Burden of Rheumatoid Arthritis in Saudi Arabia: An Exploratory Cros 2020 PURPOSE: The aim of this study was to better understand the physical and emotional impacts of rheumatoid arthritis (RA) on the lives of patients in Saudi Arabia, and to determine whether there are any discrepancies between how healthcare providers (HCPs) perceive the feelings of patients with RA and how patients actually feel. PATIENTS AND METHODS: An online survey of adults with RA and HCPs was conducted in Saudi Arabia between January and June 2018. The survey used closed-ended questions with nominal and interval scales to cover relationships with others, ability to work and career progression, ability to perform normal activities, and aspirations for the future. RESULTS: In total, 85 patients and 24 HCPs were surveyed. Patients were more likely than HCPs to feel that the people around them understood the emotional and physical impacts of RA (emotional impact understood: 67% of patients vs 42% of HCPs; physical impact understood: 61% vs 38%, respectively). Additionally, a larger proportion of younger (aged <40 years) than older patients (aged 40-59 and ≥60 years) felt that these impacts were not understood by others. For patients, the greatest barrier to working was difficulty using hands (52% vs 41% of HCPs), whereas HCPs considered pain the greatest barrier (50% vs 38% of patients). Both patients (59%) and HCPs (81%) considered pain to be a common barrier to undertaking everyday activities. Regarding future aspirations, 40% of patients wished to accept their RA despite the barriers it caused. CONCLUSION: Discrepancies between how HCPs perceived the feelings of patients with RA and how patients actually felt suggest that HCP-patient communication could be improved. This is the first study of its kind in Saudi Arabia and should help increase awareness of the difficulties and concerns of patients with RA in the Arabic world.
32598578 The ISCCA flow protocol for the monitoring of anti-CD20 therapies in autoimmune disorders. 2021 Mar BACKGROUND: Anti-CD20 monoclonals (MoAbs) are used in a variety of autoimmune disorders. The aim is to eliminate memory B cells sustaining the tissue damage and the production of pathogenic autoantibodies, while preserving naïve cells. The disappearance of memory B cells and the repopulation by naïve cells correlate with good clinical response, while the reappearance of memory B cells and plasmablasts correlates with relapse or resistance to therapy. Anti-CD20 induce extremely low B cell levels, requiring high-resolution techniques. The immune monitoring protocol developed by ISCCA is described and validated, to provide a standardized method for the clinical decision-making process during anti-CD20 therapies in autoimmune diseases. METHODS: A 10-marker, 8-color staining panel (CD20-V450, CD45-V500c, CD4-FITC + sIgM-FITC, CD38-PE, CD3-PerCP Cy5.5, CD19-PE-Cy7, CD27-APC, CD8-APC H7 + sIgG-APC-H7) is used to identify B cells, plasma cells/blasts, naïve and memory B cells, sIgM+ and sIgG-switched memory B cells, T and NK cells, with high-sensitivity analysis (>10(6) CD45+ cells). RESULTS: After an anti-CD20 dose, the B cell level is about zero in most patients. If B cells remain virtually absent (<0.1/μl), subsetting is not reliable nor meaningful. If B cells raise >0.3-0.5/μl, subsetting is possible and informative, acquiring >1.0-1.5 × 10(6) CD45+ events. Further testings can follow the quality of B cell repopulation. If B cells become detectable (>1/μl), the prevalence of memory B cells indicates non-responsiveness or a possible relapse. CONCLUSIONS: The ISCCA Protocol is proposed for a standardized prospective monitoring of patients with autoimmune disorders, to assist the safe and rational usage of anti-CD20 therapies.
32267094 Comparative Risk of Diabetes Mellitus in Patients With Rheumatoid Arthritis Treated With B 2020 Apr OBJECTIVE: The objective of this study is to compare the risk of incident diabetes mellitus (DM) in patients with rheumatoid arthritis (RA) treated with biologic or targeted synthetic disease-modifying antirheumatic drugs. METHODS: A new-user observational cohort study was conducted using data from a US commercial (Truven MarketScan, 2005-2016) claims database and a public insurance (Medicare, 2010-2014) claims database. Patients with RA who did not have DM were selected into one of eight exposure groups (abatacept, infliximab, adalimumab, golimumab, certolizumab, etanercept, tocilizumab, or tofacitinib) and observed for the outcome of incident DM, defined as a combination of a diagnosis code and initiation of a hypoglycemic treatment. A stabilized inverse probability-weighted Cox proportional hazards model was used to account for 56 confounding variables and estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All analyses were conducted separately in two databases, and estimates were combined using inverse variance meta-analysis. RESULTS: Among a total of 50 505 patients with RA from Truven and 17 251 patients with RA from Medicare, incidence rates (95% CI) for DM were 6.8 (6.1-7.6) and 6.6 (5.4-7.9) per 1000 person-years, respectively. After confounding adjustment, the pooled HRs (95% CI) indicated a significantly higher risk of DM among adalimumab (2.00 [1.11-3.03]) and infliximab initiators (2.34 [1.38-3.98]) compared with abatacept initiators. The pooled HR (95% CI) for the etanercept versus abatacept comparison was elevated but not statistically significant (1.65 [0.91-2.98]). The effect estimates for certolizumab, golimumab, tocilizumab, and tofacitinib, compared with abatacept, were highly imprecise because of a limited sample size. CONCLUSION: Initiation of abatacept was associated with a lower risk of incident DM in patients with RA compared with infliximab or adalimumab.
31913579 The Endogenous Plasma Small RNAome of Rheumatoid Arthritis. 2020 Feb OBJECTIVE: Small RNA (sRNA) sequencing has revealed new sRNA classes beyond microRNAs (miRNAs). These sRNAs can regulate genes and act as biomarkers. The aim of this study was to determine if the endogenous plasma sRNA landscape is altered in patients with rheumatoid arthritis (RA) compared with control subjects and to determine its association with disease-related parameters in RA. METHODS: sRNA sequencing was performed on plasma from 165 RA and 90 control subjects who were frequency-matched for age, race, and sex. Endogenous sRNAs, such as miRNAs, isomiRs, sRNAs derived from small nuclear RNAs (snDRs), small nucleolar RNAs (snoDRs), Y RNAs (yDRs), transfer-derived RNAs (tDRs), long noncoding RNAs (lncDRs) as well as miscellaneous sRNAs (miscRNAs), were quantified using Tools for Integrative Genome analysis of Extracellular sRNAs (TIGER). Individual and categories of sRNAs were compared between RA and controls, and significantly altered sRNAs and sRNA categories were correlated with disease activity and general laboratory measures in RA. RESULTS: Patients with RA had more miRNAs (1.42-fold, P = 0.01), more tDRs (1.14-fold, P = 0.04), and fewer yDRs (-1.41-fold, P = 0.009) compared with control subjects. Disease duration was inversely associated with yDRs. Disease-related parameters, such as Disease Activity Score-28 (DAS28), swollen joint count, and inflammatory markers were significantly positively associated with tDRs and miscRNAs, and miR-22-3p and related sequences and isomiRs were most significantly associated with DAS28. CONCLUSION: Endogenous plasma sRNAs are altered in RA compared with control subjects. Although individual miRNAs have been well studied and many are excellent biomarkers in RA, several non-miRNA sRNAs were significantly associated with disease-related parameters as classes and may represent novel biomarkers for RA.
32195671 Chemokine-like factor-like MARVEL transmembrane domain-containing family in autoimmune dis 2020 Apr 20 The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM) is widely expressed in the immune system. Abnormal expression of CMTM is associated with the development of various diseases. This article summarizes the relevant research on the role of the CMTM family in immune disorders. This information will increase our understanding of pathogenesis and identify promising targets for the diagnosis and treatment of autoimmune diseases. The CMTM family is highly expressed in peripheral blood mononuclear cells. CKLF1 may be involved in the development of arthritis through its interaction with C-C chemokine receptor 4. CKLF1 is associated with the pathogenesis of lupus nephritis and psoriasis. Both CMTM4 and CMTM5 are associated with the pathogenesis of systemic lupus erythematosus. CMTM1, CMTM2, CMTM3, and CMTM6 play a role in rheumatoid arthritis, systemic sclerosis, Sjögren syndrome, and anti-phospholipid syndrome, respectively. The CMTM family has been implicated in various autoimmune diseases. Further research on the mechanism of the action of CMTM family members may lead to the development of new treatment strategies for autoimmune diseases.
33237566 Filgotinib: First Approval. 2020 Dec Filgotinib (Jyseleca(®)) is an oral, ATP-competitive, reversible JAK1 preferential inhibitor that is being developed by Galapagos NV and Gilead Sciences for the treatment of inflammatory autoimmune diseases, including inflammatory arthritis and inflammatory bowel disease. The JAK-STAT signalling pathway has been implicated in the pathogenesis of inflammatory and autoimmune diseases, and filgotinib modulates this pathway by preventing the phosphorylation and activation of STATs. In September 2020, filgotinib received its first approvals in the EU and Japan. In the EU, filgotinib is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adults who have responded inadequately to, or who are intolerant to, one or more disease-modifying anti-rheumatic drugs (DMARDs). In Japan, filgotinib is indicated for the treatment of RA in patients who had an inadequate response to conventional therapies (including prevention of structural damage to joints). Clinical studies of filgotinib for the treatment of inflammatory autoimmune diseases are ongoing worldwide. This article summarizes the milestones in the development of filgotinib leading to this first approval.
32890026 Biologic therapies for systemic lupus erythematosus: where are we now? 2020 Nov PURPOSE OF REVIEW: Conventional approaches using hydroxychloroquine, corticosteroids and immunosuppressives have improved the prognosis for systemic lupus erythematosus (SLE) patients. Unfortunately, they have reached the limits of what they can achieve and patients still die prematurely and/or find their quality of life greatly impaired. Here, we discuss the problems of assessing activity in SLE, optimizing clinical trial design and more recent biologic approaches. RECENT FINDINGS: The success of B-cell depletion using Rituximab in open clinical studies, the approval of Belimumab (blocks the B-cell activating factor BAFF) and improvements in clinical trial design, gives cause for hope. Approaches including the use of fully humanized anti-CD20 and CD19 monoclonals, blocking interferons, inhibiting Bruton's tyrosine kinase (BTK), blocking the CD40 ligand (CD40L), utilizing an analogue of the Fc[Latin Small Letter Gamma]RIIB and an IL12-23 blocker and targeting the JAK-STAT pathway have met end points in phase II and III trials. SUMMARY: For 20 years, we hoped that the successes of the biologic therapies in rheumatoid arthritis and psoriatic arthritis would be replicated in SLE but we have been generally disappointed. However, the encouraging recent results with monoclonals that block interferon and fully humanized anti-CD20 in particular, offer the prospect of a real revolution in the treatment of SLE.