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Patients with rheumatoid arthritis (RA) with positive antibodies against carbamylated proteins (anti-CarP) have a more severe clinical course. The primary objective of this study in adult subject with RA is as follows: To explore the clinical differences in activity indexes (Disease Activity Score of 28 joints with Erythro Sedimentaion Rate (DAS28-ESR)) at 6, 12 and 18 months of follow up according the anti-CarP antibodies status.
Full description
Clinical follow-up of Anti-Carbamylated Antibody Status in Rheumatoid Arthritis patients at 6, 12 and 18 months.
Concept
Patients with rheumatoid arthritis (RA) with positive antibodies against carbamylated proteins (anti-CarP) have a more severe clinical course.
Background
The immune based pathophysiology of RA is one of the most studied. We already know that the citrullinated peptide antigen inducing antibody formation and subsequent anti-cyclic citrullinated peptide (anti-CCP) antibodies. In some patients can explain the clinical manifestations. However it is also apparent that some groups of patients with rheumatoid arthritis who do not have anti-CCP antibodies. It is possible then the presence of a variety of antigens exposed during the disease, and perhaps different clinical presentations associated with each.
The use of anti-CCP antibodies has been included in the classification criteria of RA developed by the American College of Rheumatology (ACR) in 2010 and generated the presence of two sub-groups of patients with RA, the positive and negative for anti-CCP. It is very important to study the presence of anti-CCP antibodies in RA population because it influences the clinical behavior and response to treatment. In very early or undifferentiated arthritis, the presence of anti-CCP antibodies can predict the presence of erosions in the course of the disease. On the other hand, patients with negative anti-CCP antibodies tend to have better responses to treatment with methotrexate.
Initially it was thought that the obvious pathophysiological link between RA and citrullinated peptides leading to formation of antibodies was the apparent cause of the clinical manifestations, but soon it was demonstrated that there were groups of patients with clinical manifestations of RA that did not had anti-CCP antibodies so its genesis was not explained by citrullination. Then it is possible a diversity of antigens exposed during the illness and perhaps different clinical presentations associated with each one or its combinations. So actually, some studies are attempting to show other possible antigens involved in RA and one of them uses homocitrulline as an antigenic basis to RA pathophysiology. The carbamylation or homocitrullination is a posttranslational modification of proteins that occurs when the amino acid lysine reacts with cyanate in a non-enzyme-mediated process generating homocitrulline. Mydel, Bokarewa and cols. demonstrated that immunization of mice with homocitrulline- and citrulline-containing peptides leads to development of erosive arthritis following intra-articular injection of homocitrulline-containing peptides and proposed that homocitrulline induced activation of T cells is a key mechanism in the pathogenesis of autoimmune arthritis as it serves as an initial triggering event for neo-epitope recognition of citrulline containing peptides. Recently It has been shown that rheumatoid arthritis patients has homocitrullinated proteins in his joints which can trigger an inflammatory response with formation of antibodies against homocitrulline.
Shi et al. showed in a study of 571 RA patients and 350 healthy subjects the following statements:
Thus, autoantibodies recognizing anti-CarP are a promising new serological marker for anti CCP antibodies negative RA and are associated with a more severe clinical course.
Hypothesis
Patients with RA with positive antibodies against anti-CarP have a more severe clinical course and elevated cardiovascular risk.
Design
It is a parallel study for clinical follow-up , observational.
Description of Subject Population(s)
Primary Objective
The primary objective of this study in adult subject with RA is as follows:
Study Secondary Objective(s)
One secondary objective is as follows:
Study Design
Study Primary Efficacy Endpoints
The primary efficacy endpoitns is as follows:
Study Secondary Efficacy Endpoints
The secondary efficacy endpoints are as follows:
Study Sample Size Calculation
A total of 262 subjects will be followed in this study. According the pilot study it was found a 12 month remission rate in the Anti CarP positive antibody of 33% arm compared Anti CarP negative antibody arm of 50%, with a difference of 17% in remission rate at 12 month follow-up. One hundred and thirty-three patients are needed per group. A 2 group continuity corrected chi square test with a 2-sided significance level (alpha) of 0.05 was used to compare sample size and a 0.2 (beta) to power.
Study Statistical Methods
Descriptive statistic for categorical and numerical variables will be used. Categorical variables will be expressed in frequency and percentage; comparisons will be done by chi square test. Numerical variables, after normality test we will describe them as mean and median with standard deviation (SD) and interquartile range (IQR) as corresponds, respectively.
For the primary end point, chi square test the percentage of DAS28-ESR remission by group will be compared.
For the secondary end points we will compared by t test or Mann Whitnney U the mean o median of the accumulative dose of prednisone and number of DMARD used.
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278 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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