Editorial: Autoimmune and Inflammatory Rheumatic Diseases: Identifying Biomarkers of Response to Therapy With Biologics (original) (raw)
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Newer Diagnostic And Therapeutic Modalities For Autoimmune Rheumatic Diseases
2017
There is refinement of classification criteria for various rheumatic diseases like Rheumatoid arthritis (RA) Systemic Lupus Erythematosus (SLE), vasculitis, Sjogren’s syndrome etc. in the last few years which help the clinician in establishing early diagnosis and therapy. In case of uncertainties in the diagnosis, clinicians need to carefully interpret the result of autoantibody tests in the background of the clinical context. A growing number of autoantibodies have specificity for particular clinical phenotypes. They can also offer prognostic information and sometimes diagnostic certainty. Early use of Disease Modifying Anti Rheumatic drugs(DMARDs) and biological agents to attain no or low disease activity measured by primary complex indices markedly changed the outcome in most of the autoimmune rheumatic diseases
Immunologic rheumatic disorders
Journal of Allergy and Clinical Immunology, 2010
We provide the basics for the clinician who might be called on to consider the diagnosis of diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in their practice. We will emphasize clinical recognition and first-line laboratory testing. Only characteristics of the classic rheumatic inflammatory diseases, RA, SLE, Sjögren syndrome, scleroderma, and dermatomyositis/polymyositis, will be covered. In the past decade, RA is the only disease for which treatment has substantially improved. The treatment of RA has been revolutionized by the use of methotrexate and, more recently, tumor necrosis factor inhibitors. The goal of RA treatment today is to induce a complete remission as early as possible in the disease process, with the mantra being "elimination of synovitis equals elimination of joint destruction." The hope is that if the major mediators of Sjögren syndrome or SLE or scleroderma can be identified and then blocked, as in the example of tumor necrosis factor inhibitors in RA, more specific treatments will become available. Thus, RA has become an excellent model of this evolving paradigm. Through the identification of major mediators in its pathogenesis, novel and highly efficacious therapeutic agents have been developed. (J Allergy Clin Immunol 2003;111:S593-601.)
Clinical and immunological effects of anti-TNF therapy in systemic lupus erythematosus (SLE)
Arthritis Research & Therapy - ARTHRITIS RES THER, 2003
Heterogeneity and multifactoriality complicate diagnostics and our understanding of pathogenesis of rheumatoid arthritis (RA). The only accepted serologic parameter (rheumatoid factor [RF]) is not disease specific, nor are any of several novel RA autoantibodies. We aimed at identifying profiles instead of individual autoreactivities allowing for unambiguous prediction of RA. Selected RA autoantigens were tested by ELISA (RF and anti-cyclic citrullinated peptide [anti-CCP]) or Western blot (heavy-chain-binding protein [BiP], heterogeneous ribonucleoprotein particle A2 [RA33/ hnRNP A2], calpastatin and calreticulin). Antibody reactivities were assayed from serum samples of 149 RA patients and 132 patients with other rheumatic diseases and from synovial fluids (SF) (58 RA, 65 non-RA). No single autoreactivity was sufficient for unambiguous prediction of RA. Frequencies of multiparameter profiles consisting of 3, 4, 5 and 6 autoreactivites were determined. Fifteen six-parameter serum profiles were exclusively expressed in RA patients, representing a cumulative sensitivity of 59%. Twelve SF profiles were exclusively expressed in 64% of RA patients. The self-learning classification algorithm CLASSIF1 was capable of accurately predicting RA when these profiles were present. Data profile analysis of RF/CCP/BiP/calpastatin/calreticulin/RA33 provided specific discrimination of 64% of RA. Most importantly, RA specific profiles were observed in 64% of patients with early disease (<12 months). For the first time, the accurate prediction of the class RA has been achieved by the use of multiparametric autoreactivity profiles. Because of early expression in disease, these profiles make it possible to start a disease-modifying therapy long before irreversible bone and joint destruction may develop. Additional RA-specific profiles are required to cover the entire group of RA patients. 2 Investigation of the reactivity patterns of antifilaggrin antibodies in sera and synovial fluids from patients with rheumatoid arthritis using citrullinated synthetic peptides
Guidelines for biomarkers in autoimmune rheumatic diseases - evidence based analysis
Autoimmunity Reviews
Autoimmune rheumatic diseases are characterised by an abnormal immune system response, complement activation, cytokines dysregulation and inflammation. In last years, despite many progresses in managing these patients, it has been shown that clinical remission is reached in less than 50% of patients and a personalised and tailored therapeutic approach is still lacking resulting in a significant gap between guidelines and real-world practice. In this context, the need for biomarkers facilitating early diagnosis and profiling those individuals at the highest risk for a poor outcome has become of crucial interest. A biomarker generally refers to a measured characteristic which may be used as an indicator of some biological state or condition. Three different types of medical biomarkers has been suggested: i. mechanistic markers; ii. clinical disease markers; iii. therapeutic markers. A combination of biomarkers from these different groups could be used for an ideal more accurate diagnosis and treatment. However, although a growing body of evidence is focused on improving biomarkers, a significant amount of this information is not integrated on standard clinical care. The overarching aim of this work was to clarify the meaning of specific biomarkers during autoimmune diseases; their possible role in confirming diagnosis, predicting outcome and suggesting specific treatments.
Autoimmunity reviews, 2017
Autoimmune diseases are a complex set of diseases characterized by immune system activation and, although many progresses have been done in the last 15 years, several unmet needs in the management of these patients may be still identified. Recently, a panel of international Experts, divided in different working groups according to their clinical and scientific expertise, were asked to identify, debate and formulate a list of key unmet needs within the field of rheumatology, serving as a roadmap for research as well as support for clinicians. After a systematic review of the literature, the results and the discussions from each working group were summarised in different statements. Due to the differences among the diseases and their heterogeneity, a large number of statements was produced and voted by the Experts to reach a consensus in a plenary session. At all the steps of this process, including the initial discussions by the steering committee, the identification of the unmet nee...
Biologic therapies in rheumatic diseases: drug and anti-drug antibody levels and clinical efficacy
Journal of Autoimmunity and Cell Responses, 2017
Background: The aim of this study was to evaluate the relevance of drug and anti-drug antibody detection in the clinical management of patients with rheumatoid arthritis (RA) and spondyloarthropaties (SpA) in treatment with anti-tumor necrosis factor alpha (TNFα) biologics. Methods and results: The study included 192 adult consecutive patients treated for at least 6 months with adalimumab (ADA) or etanercept (ETN) or infliximab (IFX); patients underwent clinical observations in the Rheumatologic Unit of 5 Hospitals in Tuscany. Their demographic and clinical characteristics to calculate DAS28 and BASDAI scores were collected. Drug levels and anti-drug antibodies (anti-drug Ab) were evaluated immediately before drug injection or infusion. A total of 192 patients were studied: 62 receiving IFX, 64 ADA, and 66 ETN with a mean age of 57 years (range 18-86 years); the study group was composed of 51% women. Forty percent of the patients were affected by RA, 60% by SpA. Altogether, 81% of patients demonstrated therapeutic drug levels. Anti-drug Ab were found in 19% of patients taking IFX, 10% taking ETN and 5% taking ADA. No significant correlation was found between anti-drug Ab presence and low drug levels, between anti-drug Ab and high DAS28 and BASDAI scores, as well as between low drug levels and high DAS28 and BASDAI scores. Conclusions: Low drug levels were found in 19% of the rheumatic patients and there were not correlations with presence of anti-drug Ab or patient's clinical status.
Arthritis Research & Therapy, 2009
Introduction Anti-TNF therapies have revolutionized the treatment of rheumatoid arthritis (RA), a common systemic autoimmune disease involving destruction of the synovial joints. However, in the practice of rheumatology approximately onethird of patients demonstrate no clinical improvement in response to treatment with anti-TNF therapies, while another third demonstrate a partial response, and one-third an excellent and sustained response. Since no clinical or laboratory tests are available to predict response to anti-TNF therapies, great need exists for predictive biomarkers.
Frontiers in Pharmacology
Background: Patients with systemic lupus erythematosus (SLE) show increased serum levels of tumor necrosis factor (TNF)/TNF receptor (R) superfamily member, e.g. BAFF (B lymphocyte stimulator). Belimumab, a monoclonal antibody against soluble BAFF, is used for treatment of SLE. Although B cells are the main target, a BAFF-dependent T-cell activation pathway also plays a role. High levels of anti-DNA antibodies and low complement at baseline are known predictors of response to Belimumab.Objectives: To explore the association of circulating lymphocytes and serum levels of B- cell related TNF/TNFR superfamily members with response to Belimumab in SLE patients.Methods: Twenty-one SLE patients received Belimumab. Clinical evaluation and laboratory tests were performed at baseline, at 6 and 12 months. TNF super-family members (BAFF, APRIL, sBCMA, sCD40L, sTACI, TWEAK) were tested by high-sensitivity ELISA in all patients, and lymphocyte immunophenotyping was performed by flow cytometry in...
A Review of Clinical Trials of Belimumab in the Management of Systemic Lupus Erythematosus
Current Pharmaceutical Design, 2016
There have been few changes over the last 50 years in the treatment of Systemic lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: non-steroidal anti-inflammatory drugs along with the immune cell modulating agent hydroxy-chloroquine for mild disease, and broad spectrum immunosuppressants plus anti-inflammatories such as corticosteroids, azathioprine, cyclophosphamide, or mycophenolate during flares or severe disease with organ involvement. In some patients, the response is inadequate and side effects appear from mild unpleasant up to severe toxicity. Drug metabolism and clearance may be severely compromised. Therefore, it is a priority to develop better treatments with fewer adverse events that can be used at different stages of disease activity. In recent years, a member of the tumor necrosis factor (TNF) family, soluble human B Lym-phocyte Stimulator protein (BLyS), also referred to as B-cell activating factor (BAFF) and TNFSF13B has been studied extensively. This protein is synthesized by myeloid cell lines, specifically interacts with B lymphocytes and increases their lifespan. BlyS plays a key role in the selection, maturation and survival of B cells and it has a significant role in the pathogenesis of SLE. In this review, we analyzed the role of BLyS as a diagnostic/prognostic marker and/or therapeutic target for lupus patients, and the different clinical studies published using belimumab.