16 results on '"Piet van Riel"'
Search Results
2. Oral anticoagulant treatment in rheumatoid arthritis patients with atrial fibrillation results of an international audit
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Anne Grete Semb, Silvia Rollefstad, Joseph Sexton, Eirik Ikdahl, Cynthia S. Crowson, Piet van Riel, George Kitas, Ian Graham, Anne M. Kerola, George Athanasios Karpouzas, Miguel A Gonzalez-Gay, Petros P Sfikakis, Maria G Tektonidou, Argyro Lazarini, Dimitrios Vassilopoulos, Bindee Kuriya, Carol Hitchon, Maria Simona Stoenoiu, Patrick Durez, Virginia Pascual-Ramos, Dionicio Angel Galarza-Delgado, Pompilio Faggiano, Durga Prasanna Misra, Andrew A Borg, Rong Mu, Erkin M Mirrakhimov, Diane Gheta, Karen Douglas, Vikas Agarwal, Svetlana Myasoedova, Lev Krougly, Tatiana Valentinovna Popkova, Alena Tuchyňová, Michal Tomcik, Michal Vrablik, Jiri Lastuvka, Pavel Horak, Helena Kaspar Medkova, Faculty of Medicine, Helsinki University Hospital Area, University of Helsinki, and HUS Inflammation Center
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RISK ,COUNTRIES ,Atrial fibrillation ,Pharmacotherapy ,EUROPEAN-SOCIETY ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,2010 ESC GUIDELINES ,Anticoagulation ,All institutes and research themes of the Radboud University Medical Center ,3121 General medicine, internal medicine and other clinical medicine ,MANAGEMENT ,Rheumatoid arthritis ,Cardiology and Cardiovascular Medicine ,STROKE - Abstract
Objective: To describe the prevalence of atrial fibrillation (AF) in patients with rheumatoid arthritis (RA), and to evaluate the proportion of patients with AF receiving guideline-recommended anticoagulation for prevention of stroke, based on data from a large international audit. Methods: The cohort was derived from the international audit SUrvey of cardiovascular disease Risk Factors in patients with Rheumatoid Arthritis (SURF-RA) which collected data from 17 countries during 2014-2019. We evaluated the prevalence of AF across world regions and explored factors associated with the presence of AF with multivariable logistic regression models. The proportion of AF patients at high risk of stroke (CHA(2)DS(2)-VASc & GE; 2 in males and & GE; 3 in females) receiving anticoagulation was examined. Results: Of the total SURF-RA cohort (n = 14,503), we included RA cases with data on whether the diagnosis of AF was present or not (n = 7,665, 75.1% women, mean (SD) age 58.7 (14.1) years). A total of 288 (3.8%) patients had a history of AF (4.4% in North America, 3.4% in Western Europe, 2.8% in Central and Eastern Europe and 1.5% in Asia). Factors associated with the presence of AF were older age, male sex, atherosclerotic cardiovascular disease, heart failure and hypertension. Two-hundred and fifty-five (88.5%) RA patients had a CHA(2)DS(2)-VASc score indicating recommendation for oral anticoagulant treatment, and of them, 164 (64.3%) were anticoagulated. Conclusion: Guideline-recommended anticoagulant therapy for prevention of stroke due to AF may not be optimally implemented among RA patients, and requires special attention.
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- 2022
3. 2017 EULAR recommendations for a core data set to support observational research and clinical care in rheumatoid arthritis
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Helga Radner, Katerina Chatzidionysiou, Elena Nikiphorou, Laure Gossec, Kimme L Hyrich, Condruta Zabalan, Yvonne van Eijk-Hustings, Paula R Williamson, Andra Balanescu, Gerd R Burmester, Loreto Carmona, Maxime Dougados, Axel Finckh, Glenn Haugeberg, Merete Lund Hetland, Susan Oliver, Duncan Porter, Karim Raza, Patrick Ryan, Maria Jose Santos, Annette van der Helm-van Mil, Piet van Riel, Gabrielle von Krause, Jakub Zavada, William G Dixon, Johan Askling, and Rheumatology
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rheumatoid arthritis ,Consensus ,Immunology ,DISEASE-ACTIVITY ,General Biochemistry, Genetics and Molecular Biology ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Arthritis, Rheumatoid ,outcomes research ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,Rheumatology ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,ddc:616 ,030203 arthritis & rheumatology ,Biochemistry, Genetics and Molecular Biology(all) ,Data Collection ,quality indicators ,Observational Studies as Topic ,DEFINITION ,TRIALS - Abstract
Personalised medicine, new discoveries and studies on rare exposures or outcomes require large samples that are increasingly difficult for any single investigator to obtain. Collaborative work is limited by heterogeneities, both what is being collected and how it is defined. To develop a core set for data collection in rheumatoid arthritis (RA) research which (1) allows harmonisation of data collection in future observational studies, (2) acts as a common data model against which existing databases can be mapped and (3) serves as a template for standardised data collection in routine clinical practice to support generation of research-quality data. A multistep, international multistakeholder consensus process was carried out involving voting via online surveys and two face-to-face meetings. A core set of 21 items (‘what to collect’) and their instruments (‘how to collect’) was agreed: age, gender, disease duration, diagnosis of RA, body mass index, smoking, swollen/tender joints, patient/evaluator global, pain, quality of life, function, composite scores, acute phase reactants, serology, structural damage, treatment and comorbidities. The core set should facilitate collaborative research, allow for comparisons across studies and harmonise future data from clinical practice via electronic medical record systems.
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- 2018
4. The spectrum of early rheumatoid arthritis practice across the globe: results from a multinational cross sectional survey
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Elena, Nikiphorou, James, Galloway, Piet, van Riel, Yusuf, Yazici, Glenn, Haugeberg, Andrew, Ostor, Feride, Gogus, Markku, Kauppi, and Tuulikki, Sokka
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Biological Products ,Time Factors ,Delivery of Health Care, Integrated ,United States ,Arthritis, Rheumatoid ,Europe ,Cross-Sectional Studies ,Treatment Outcome ,Adrenal Cortex Hormones ,Antirheumatic Agents ,Health Care Surveys ,Practice Guidelines as Topic ,Critical Pathways ,Humans ,Guideline Adherence ,Healthcare Disparities ,Practice Patterns, Physicians' ,Rheumatologists ,Referral and Consultation - Abstract
To explore patterns of real-world early RA (ERA) care across countries.An online survey was disseminated to practising rheumatologists across Europe and the US, also made accessible on social media between April and May 2015. Survey questions (n=38) assessed the structure and setting of ERA clinics, times to diagnosis and treatment, patient monitoring, guideline use and data recording.A total of 212 rheumatologists from 39 countries (76% European) completed the survey. 62% had an ERA clinic based at a university hospital. Patient referral to rheumatology was mainly (78%) via primary care; 44% had an agreed ERA local referral pathway, 15% a national pathway. Only 16% had dedicated ERA clinics, the majority being practitioners in Northern Europe with access to a local or national referral pathway. Data for research were collected by 42%. Treatment guidelines were followed by the majority, especially rheumatologists practising in Europe. Variations existed in the use of initial DMARDs with treatment decisions reported to be influenced by international/national guidelines in 71%/61%. No significant relationship between country gross national income and the availability of ERA clinics was seen.This study provides comparative benchmark information regarding the global provision of ERA care. Substantial variations exist in referral and early assessment pathways with guidelines having a most apparent impact in Northern Europe. Provision of an ERA service does not appear to be constrained by cost, with conceptual factors, e.g. clinician engagement, perhaps playing a role. These initial insights could potentially help harmonise ERA management across countries.
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- 2016
5. The interferon regulatory factor 5 gene confers susceptibility to rheumatoid arthritis and influences its erosive phenotype
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Karen, Dawidowicz, Yannick, Allanore, Mickaël, Guedj, Céline, Pierlot, Stefano, Bombardieri, Alejandro, Balsa, René, Westhovens, Pilar, Barrera, Helena, Alves, Vitor Hugo, Teixeira, Elisabeth, Petit-Teixeira, Leo, van de Putte, Piet, van Riel, Bernard, Prum, Thomas, Bardin, Olivier, Meyer, François, Cornélis, Philippe, Dieudé, A, Lopez-Vaz, Laboratoire de recherche européen pour la polyarthrite rhumatoïde (GenHotel), Université d'Évry-Val-d'Essonne (UEVE), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Organique et Macromoleculaire (UMR CNRS 8009), Université de Lille, Sciences et Technologies-Ecole Nationale Supérieure de Chimie de Lille (ENSCL), Université de Pise, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Nijmegen Medical Centre [Nijmegen], Hospital de São João [Porto], Universidade de Coimbra [Coimbra], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CHU Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Descartes - Paris 5 (UPD5), Laboratoire de recherche européen pour la polyarthrite rhumatoïde (GenHotel - EA 3886), Hôpital Lariboisière, Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Université de Lille, Sciences et Technologies, and University of Pisa - Università di Pisa
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Adult ,Male ,Genotype ,Genetic Linkage ,Immunology ,Single-nucleotide polymorphism ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,General Biochemistry, Genetics and Molecular Biology ,Autoimmunity ,Arthritis, Rheumatoid ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Rheumatoid Factor ,Humans ,Immunology and Allergy ,Medicine ,SNP ,Rheumatoid factor ,Genetic Predisposition to Disease ,030304 developmental biology ,030203 arthritis & rheumatology ,Genetics ,0303 health sciences ,business.industry ,Haplotype ,Phenotype ,Haplotypes ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Interferon Regulatory Factors ,Evaluation of complex medical interventions Auto-immunity, transplantation and immunotherapy [NCEBP 2] ,Female ,business ,IRF5 ,Interferon regulatory factors - Abstract
Contains fulltext : 96445.pdf (Publisher’s version ) (Closed access) BACKGROUND: Increased expression of type I IFN genes, also referred to as an IFN signature, has been detected in various autoimmune diseases including rheumatoid arthritis (RA). Interferon regulatory factors, such as IRF5, coordinate type I IFN expression. Multiple IRF5 variants were suggested as autoimmunity susceptibility factors. OBJECTIVE: As the linkage proof remains important to establish fully any genetic RA susceptibility factor, the authors took advantage of the largest reported European trio family resource dedicated to RA to test for linkage IRF5 and performed a genotype-phenotype analysis. METHODS: 1140 European Caucasian individuals from 380 RA trio families were genotyped for IRF5 rs3757385, rs2004640 and rs10954213 single nucleotide polymorphisms (SNP). RESULTS: Single marker analysis provided linkage evidence for each IRF5 SNP investigated. IRF5 linked to RA with two haplotypes: the CTA risk haplotype 'R' (transmission (T)=60.6%, p=23.1x10(-5)) and the AGG protective haplotype 'P' (T=39.6%, p=0.0015). Linkage was significantly stronger in non-erosive disease for both IRF5 R and P haplotypes (T=73.9%, p=4.20x10(-5) and T=19.6%, p=3.66x10(-5), respectively). Multivariate logistic regression analysis found IRF5 linked to RA independently of the rheumatoid factor status. IRF5 RR and PP haplotypic genotypes were associated with RA, restricted to the non-erosive phenotype: p=1.68x10(-4), OR 4.80, 95% CI 2.06 to 11.19; p=0.003, OR 0.17, 95% CI 0.05 to 0.57, respectively. CONCLUSION: This study provides the 'association and linkage proof' establishing IRF5 as a RA susceptibility gene and the identification of a genetic factor that seems to contribute to the modulation of the erosive phenotype. Further studies are warranted to clarify the role of IRF5 in RA and its subphenotypes.
- Published
- 2011
6. Assessment of rheumatic disease
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Piet van Riel
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medicine.medical_specialty ,integumentary system ,business.industry ,Internal medicine ,medicine ,Rheumatic disease ,business - Abstract
The clinical examination of the musculoskeletal system is the cornerstone in the diagnostic process of rheumatic diseases. Next to this the clinical examination is important in evaluating the course of the different rheumatic diseases and the response to interventions. For instance in rheumatoid arthritis the joint scores—number of painful and swollen joints—are important in the evaluation of the disease activity of the patient. In systemic sclerosis the severity of skin involvement is measured with a skin score such as the modified Rodnan skin score, and in ankylosing spondylitis the spinal mobility is measured using different clinical scores. In general all these examinations should be carried out as far as possible in a standardized, systematic way.
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- 2013
7. Etanercept-related extensive pulmonary nodulosis in a patient with rheumatoid arthritis
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Annelies, van Ede, Alfons, den Broeder, Michiel, Wagenaar, Piet, van Riel, and Marjonne C W, Creemers
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Male ,Anti-Inflammatory Agents ,Middle Aged ,Receptors, Tumor Necrosis Factor ,Etanercept ,Arthritis, Rheumatoid ,Withholding Treatment ,Antirheumatic Agents ,Immunoglobulin G ,Azathioprine ,Humans ,Prednisone ,Drug Therapy, Combination ,Radiography, Thoracic ,Rheumatoid Nodule ,Tomography, X-Ray Computed ,Immunosuppressive Agents - Abstract
Although nodulosis is a common extraarticular manifestation of rheumatoid arthritis, accelerated pulmonary nodulosis is a rare event. The etiology of rheumatoid nodules is still unknown. Nodulosis is not necessarily associated with active joint inflammation, suggesting different pathogenic mechanisms for nodule formation and synovial tissue inflammation. We describe a patient with extensive pulmonary nodulosis, probably related to etanercept treatment. Our case emphasizes the need for careful monitoring for adverse events during treatment with biologicals, especially since the differential diagnosis often includes a broad spectrum of diseases.
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- 2007
8. Minimal clinically important difference in radiological progression of joint damage. A definition based on patient perspective
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Paco M J, Welsing, George F, Borm, and Piet, van Riel
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Adult ,Male ,Health Status ,Middle Aged ,Severity of Illness Index ,Arthritis, Rheumatoid ,Disability Evaluation ,Disease Progression ,Humans ,Female ,Joints ,Longitudinal Studies ,Arthrography ,Aged - Abstract
To estimate a threshold for minimal clinically important radiological progression of joint damage using its longitudinal relation with functional disability in patients with rheumatoid arthritis (RA). To validate existing estimates of minimal clinically important difference (MCID) using this relation with functional disability.We reanalyzed published data of 185 patients with early RA followed for a maximum of 9 years. Longitudinal regression (mixed models) was used, relating radiological damage (modified Sharp score) to functional disability (HAQ-DI), correcting for age (age at diagnosis and increasing disease duration), disease activity (DAS28), and demographic variables. Several shapes of the relation were investigated. Based on the observed relationship between radiological damage, functional disability, and the minimal clinically relevant increase in functional disability found in earlier studies, MCID for progression of joint damage was discussed. Existing estimates of MCID were evaluated for their influence on functional disability over the disease course.A longitudinal relation between the modified Sharp score and the HAQ-DI was found. Significant covariates were age, gender, and disease activity. The model indicated that the relation between the Sharp score and the HAQ-DI was dependent on the amount of damage (a threshold effect) and on patients' age. With lower age, no effect of joint damage on functional disability could be demonstrated and with higher age the effect of joint damage increased. With a typical patient from our cohort (age at diagnosis 55 yrs, some baseline damage, and an expected disease duration of 30 yrs), a (constant) progression of 6 points per year led to an increase of about 0.2 on the HAQ score, solely related to damage, over the disease course. This estimate of MCID was close to estimates based on expert opinion and equal or smaller than most estimates based on the smallest detectable difference.The MCID, defined using longitudinal effect on functional disability, is dependent on age and (progression of) joint damage. However, with a typical patient population this MCID was similar to thresholds based on expert opinion, adding to the validity of these estimates.
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- 2006
9. Use of combination of leflunomide with biological agents in treatment of rheumatoid arthritis
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Joachim R, Kalden, Christian, Antoni, Jose M, Alvaro-Gracia, Bernard, Combe, Paul, Emery, Joel M, Kremer, C Vibeke, Strand, Piet, Van Riel, and Josef S, Smolen
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Arthritis, Rheumatoid ,Antibodies, Monoclonal ,Humans ,Immunologic Factors ,Drug Therapy, Combination ,Isoxazoles ,Immunosuppressive Agents ,Leflunomide - Abstract
An Expert Panel Meeting was held in May 2004 to assess experience with combination therapy with leflunomide and biological agents in the treatment of rheumatoid arthritis (RA), to identify both optimal use of such combinations and precautions for use. Eleven published prospective or retrospective studies were reviewed, principally evaluating combination of leflunomide with infliximab, as well as patient registry data. Available data suggest that combination therapies are more efficacious than monotherapies, reflecting the complementarity of mechanisms of action. Information on side effects remains contradictory, and tolerability of these combinations may vary between different patient groups. In some studies, tolerability is equivalent to that seen with monotherapy; in others a high rate of adverse events has led to frequent treatment discontinuation. Dermatological reactions may be a specific side effect of these combination therapies. Combination therapy is considered justified for treatment of patients diagnosed early who are at risk for rapid progression and for patients who fail to respond to monotherapy. The majority of participants favored adding biological agents to a previously established leflunomide monotherapy rather than starting both treatments simultaneously. On the other hand, combination therapy should be considered with caution in patients with a history of treatment failure, with hepatic comorbidity, or with other autoimmune disease, and in immunocompromised patients. When considering initiation of combination therapy, it is important to provide full information to the patient on the potential benefits and risks of such treatment and to integrate patients as far as possible into the decision-making process.
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- 2005
10. Leflunomide improves the clinical response in patients with active rheumatoid arthritis treated with methotrexate
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Piet, Van Riel
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Adult ,Male ,Dose-Response Relationship, Drug ,Anti-Inflammatory Agents, Non-Steroidal ,Isoxazoles ,Middle Aged ,Prognosis ,Risk Assessment ,Severity of Illness Index ,Drug Administration Schedule ,Arthritis, Rheumatoid ,Methotrexate ,Treatment Outcome ,Double-Blind Method ,Reference Values ,Humans ,Drug Therapy, Combination ,Female ,Leflunomide ,Aged ,Follow-Up Studies - Published
- 2004
11. Efficacy and safety of leflunomide and predisposing factors for treatment response in patients with active rheumatoid arthritis: RELIEF 6-month data
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Maxime, Dougados, Paul, Emery, Ernst-Martin, Lemmel, Rodriguez, de la Serna, Cristiano A, Zerbini, Sylvie, Brin, and Piet, van Riel
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Adult ,Male ,Health Status ,International Cooperation ,Isoxazoles ,Middle Aged ,Severity of Illness Index ,Arthritis, Rheumatoid ,Cohort Studies ,Disability Evaluation ,Treatment Outcome ,Humans ,Female ,Joints ,Enzyme Inhibitors ,Leflunomide ,Aged - Abstract
The RELIEF investigation was a 48-week, multicenter, international study comprising 2 phases. Results from the first phase, a 24-week open-label cohort study that evaluated the safety and efficacy of leflunomide, as well as predisposing factors to treatment response, are reported here.Patients received leflunomide 100 mg once daily for 3 days, followed by 20 mg once daily thereafter. All adverse events were documented. Efficacy variables were the European League Against Rheumatism (EULAR) response criteria using the Disease Activity Score (DAS 28) responder rate and the response rate according to American College of Rheumatology (ACR) criteria. At Week 24, baseline data were analyzed to determine predictive factors for treatment response.A total of 969 patients were entered in the trial. No adverse events that have not previously been seen with leflunomide were reported. Among 968 evaluable patients, 673 (69.6%) completed 24 weeks of treatment and were responders according to DAS 28 response rate, and 587 (60.6%) completed 24 weeks of treatment and were responders according to ACR 20%. Thus, there was a high correlation between the EULAR and ACR criteria in determining treatment response. In addition, 240 (24.8%) patients had a low DAS 28 (or = 3.2) and 123 (12.7%) patients fulfilled the disease remission criteria (DAS 282.6) at the end of the study.This study demonstrates that leflunomide is well tolerated, with a safety profile similar to that seen previously in Phase III studies, and confirms the efficacy of leflunomide across a range of patient categories.
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- 2004
12. MCID/Low Disease Activity State Workshop: low disease activity state in rheumatoid arthritis
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George, Wells, Maarten, Boers, Beverley, Shea, Jennifer, Anderson, David, Felson, Kent, Johnson, John, Kirwan, Marissa, Lassere, Vivian, Robinson, Lee, Simon, Vibeke, Strand, Piet, van Riel, and Peter, Tugwell
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Arthritis, Rheumatoid ,Outcome Assessment, Health Care ,Remission Induction ,Humans ,Severity of Illness Index - Abstract
The MCID (minimal clinically important difference) module of OMERACT 5 developed a research agenda that led to the conclusion that a state of low disease activity for rheumatoid arthritis (RA) would need to be defined. To develop such a definition the various concepts and terminologies, the process for developing an operational definition, and the availability and design of longitudinal datasets for validation needed to be considered. This article describes the process of the MCID/Low Disease Activity State Workshop at OMERACT 6 to develop such a definition.
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- 2003
13. MCID/Low Disease Activity State Workshop: summary, recommendations, and research agenda
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George, Wells, Jennifer, Anderson, Maarten, Boers, David, Felson, Turid, Heiberg, Sarah, Hewlett, Kent, Johnson, John, Kirwan, Marissa, Lassere, Vivian, Robinson, Beverley, Shea, Lee, Simon, Vibeke, Strand, Piet, van Riel, and Peter, Tugwell
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Arthritis, Rheumatoid ,Outcome and Process Assessment, Health Care ,Humans ,Severity of Illness Index - Abstract
The OMERACT 6 Minimal Clinically Important Difference/Low Disease Activity Workshop was organized with the aim of meeting the many challenges that exist in determining a low disease activity in rheumatoid arthritis (RA). This article presents an overview of that workshop, including results of the voting, a summary of associated discussions, recommendations, and a proposed research agenda.
- Published
- 2003
14. Intravenous human recombinant tumor necrosis factor receptor p55-Fc IgG1 fusion protein Ro 45-2081 (lenercept): a double blind, placebo controlled dose-finding study in rheumatoid arthritis
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Rolf, Rau, Oliver, Sander, Piet, van Riel, Leo, van de Putte, Fritz, Hasler, Michel, Zaug, Johannes, Kneer, Philippe, van der Auwera, and Randall M, Stevens
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Adult ,Male ,Immunoglobulin gamma-Chains ,Recombinant Fusion Proteins ,Middle Aged ,Infections ,Antibodies ,Receptors, Tumor Necrosis Factor ,Arthritis, Rheumatoid ,Placebos ,Treatment Outcome ,Double-Blind Method ,Antirheumatic Agents ,Injections, Intravenous ,Humans ,Female ,Immunoglobulin Heavy Chains ,Aged - Abstract
To determine the optimal dose regimen for intravenous Ro 45-2081 (lenercept) in patients with rheumatoid arthritis (RA) by evaluating efficacy, safety, tolerability, and pharmacokinetic and pharmacodynamic characteristics.Adult patients with longstanding RA who were taking stable doses of nonsteroidal antiinflammatory drug and/or low dose corticosteroids but who had stopped their previous disease-modifying antirheumatic drug were randomly assigned to receive 3 intravenous infusions, one every 4 weeks, of placebo or Ro 45-2081 in a double blind, placebo controlled, parallel group multicenter trial. Patients received one of the following: (1) placebo, (2) low dose Ro 45-2081 (0.05 mg/kg, maximum 5 mg), (3) middle dose (mid-dose) Ro 45-2081 (0.2 mg/kg, maximum 20 mg), or (4) high dose Ro 45-2081 (0.5 mg/kg, maximum 50 mg). Efficacy measures included change from baseline in number of swollen joints and tender joints, scores on physician and patient assessments of disease activity, and patient assessment of pain, as well as acute phase reactants.Patients treated with Ro 45-2081 exhibited improvement after one day of the first intravenous infusion. This treatment benefit maximized by 2 weeks but diminished thereafter. After the second and third infusion, improvement was of shorter duration as non-neutralizing anti-Ro 45-2081 antibodies developed and accelerated clearance of Ro 45-2081. There were no antibodies after the first infusion. This made efficacy transient in the mid-dose group and modest in the low and high dose groups at 12 weeks of treatment, resulting in no statistical differences at most time points or doses of Ro 45-2081. The majority of adverse experiences were mild or moderate, and were not related or only remotely related to study drug. No clinically relevant changes in mean laboratory values were reported. The third dose pharmacokinetic measurements showed that the average Ro 45-2081 clearance rate more than doubled compared with the first dosing interval, thus reducing the average Ro 45-2081 AUC by 36%.Intravenous Ro 45-2081 every 4 weeks proved to be well tolerated and transiently effective in the mid-dose group and modestly effective in the low and high dose groups in patients with longstanding RA. The interactions between Ro 45-2081, its non-neutralizing anti-Ro 45-2081 antibody, and the clinical benefit remain complex, but affected efficacy over the 12 weeks of treatment as Ro 45-2081 concentrations fell.
- Published
- 2003
15. A single dose, placebo controlled study of the fully human anti-tumor necrosis factor-alpha antibody adalimumab (D2E7) in patients with rheumatoid arthritis
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Alfons, den Broeder, Leo, van de Putte, Rolf, Rau, Manfred, Schattenkirchner, Piet, Van Riel, Oliver, Sander, Christina, Binder, Helmut, Fenner, Yvonne, Bankmann, Raja, Velagapudi, Joachim, Kempeni, and Hartmut, Kupper
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Adult ,Male ,Adolescent ,Dose-Response Relationship, Drug ,Adalimumab ,Antibodies, Monoclonal ,Middle Aged ,Antibodies, Monoclonal, Humanized ,Drug Administration Schedule ,Arthritis, Rheumatoid ,Cohort Studies ,Treatment Outcome ,Humans ,Female ,Age of Onset ,Aged - Abstract
To assess the pharmacokinetics, safety profile, and efficacy of the fully human anti-tumor necrosis factor-alpha (anti-TNF-alpha) monoclonal antibody adalimumab (D2E7) in patients with long-standing, active rheumatoid arthritis (RA).This was a randomized, double blind, placebo controlled study of single intravenous injections of ascending doses (0.5 to 10 mg/kg) of adalimumab in 5 cohorts of 24 patients each (18 adalimumab and 6 placebo in all cohorts except the 0.5 mg/kg cohort of 17 adalimumab, 7 placebo). A total of 120 patients participated (adalimumab 89, placebo 31). The clinical response was measured by changes in composite scores defined by the criteria of the European League Against Rheumatism (EULAR) and the American College of Rheumatology.Single doses of adalimumab showed a rapid onset of clinical effect (24 hours to 1 week), with peak efficacy at 1 to 2 weeks that was sustained for at least 4 weeks and for as long as 3 months in some patients. EULAR response was seen at least once during the 4 week period after drug injection in 29% of patients in the placebo group as well as in 41%, 78%, 72%, 89%, and 100% in the 0.5, 1, 3, 5, and 10 mg/kg groups, respectively. No dose related increases in adverse events were observed in the adalimumab patients compared with the placebo group. Adalimumab systemic drug exposure (AUC0-( )) increased linearly with an increase in dose. The mean total serum clearance was 0.012 to 0.017 l/h, and the steady-state volume of distribution ranged from 4.7 to 5.5 l. The estimated mean terminal half-life ranged from 10.0 to 13.6 days for the 5 cohorts, with an overall mean half-life of 12 days.Treatment with the fully human Mab adalimumab was safe and well tolerated when administered as a single intravenous injection at doses up to 10 mg/kg, and was associated with a clinically significant improvement in the signs and symptoms of active RA.
- Published
- 2002
16. Preface
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Barry Bresnihan and Piet van Riel
- Subjects
Rheumatology - Published
- 1999
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