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Rheumatoid Arthritis: HELP
Articles by Rene Westhovens
Based on 82 articles published since 2008

Between 2008 and 2019, R. Westhovens wrote the following 82 articles about Arthritis, Rheumatoid.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Editorial Separately tackling the development of erosions with denosumab: ultimately closing a gap in the treatment of patients with rheumatoid arthritis or trying too hard too late? 2016

Verschueren, P / Westhovens, R. ·Department of Development and Regeneration KU Leuven, Skeletal Biology and Engineering Research Center, Leuven, Belgium Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium. ·Ann Rheum Dis · Pubmed #26861701.

ABSTRACT: -- No abstract --

2 Editorial Provisional classification [corrected] criteria for polymyalgia rheumatica: moving beyond clinical intuition? 2012

Spiera, Robert / Westhovens, René. · ·Arthritis Rheum · Pubmed #22389041.

ABSTRACT: -- No abstract --

3 Editorial Methotrexate: the gold standard without standardisation. 2009

Kay, Jonathan / Westhovens, Rene. · ·Ann Rheum Dis · Pubmed #19525405.

ABSTRACT: -- No abstract --

4 Review Solid phase assays versus automated indirect immunofluorescence for detection of antinuclear antibodies. 2018

Claessens, Jolien / Belmondo, Thibaut / De Langhe, Ellen / Westhovens, Rene / Poesen, Koen / Hüe, Sophie / Blockmans, Daniel / Mahler, Michael / Fritzler, Marvin J / Bossuyt, Xavier. ·Laboratory Medicine, University Hospitals Leuven, Belgium. · Department of Laboratory Medicine, Henri Mondor Hospital, Créteil, France. · Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium. · Laboratory Medicine, University Hospitals Leuven, Belgium; Department of Neurosciences, KU Leuven, Leuven, Belgium. · Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium; Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium. · Research and Development, Inova Diagnostics, San Diego, USA. · Cumming School of Medicine, University of Calgary, Alberta, Canada. · Laboratory Medicine, University Hospitals Leuven, Belgium; Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium. Electronic address: Xavier.Bossuyt@uzleuven.be. ·Autoimmun Rev · Pubmed #29526634.

ABSTRACT: Solid phase assays (SPAs) and automated microscope systems are increasingly used to screen for antinuclear antibodies (ANAs). The goal of this study was to evaluate the performance of three automated ANA screening assays; NOVA Lite HEp-2 using NOVA View® (NV, Inova Diagnostics), an automated indirect immunofluorescence method, EliA™ CTD Screen (Fluorescence Enzyme Immunoassay, FEIA; Thermo Fisher) and QUANTA Flash® CTD Screen Plus (Chemiluminescence immunoassay, CIA; Inova Diagnostics). The assays were performed on 480 diagnostic samples from patients with an ANA-associated rheumatic disease (AARD; systemic lupus erythematosus, primary Sjögren's syndrome, systemic sclerosis, inflammatory myopathy, mixed connective tissue disease) and on 767 samples from diseased and healthy controls. Using cut-offs proposed by the manufacturers, the sensitivity was 95%, 80.5% and 86% for NV, FEIA and CIA, respectively. The corresponding specificity was 61% (NV), 97.5% (FEIA) and 88% (CIA). The sensitivity associated with a specificity of ~95% was 79%, 82% and 78% for NV, FEIA, and CIA, respectively. Receiver operating characteristics (ROC) curve analysis revealed no differences in area under the curve (AUC) between the 3 assays when all diseases were grouped. For Sjögren's syndrome, the AUC was higher for SPAs than for NV, whereas for systemic sclerosis, the AUC was higher for NV than for CIA. For all assays, the likelihood ratio for AARD increased with increasing antibody levels and for double positivity of NV with SPA. In conclusion, the performance of automated SPA and IIF was assay- and disease-dependent. Taking into account antibody levels and combining IIF with SPA adds value.

5 Review The use of glucocorticoids in early rheumatoid arthritis. 2018

Verschueren, Patrick / Westhovens, Rene. ·Department of Development and Regeneration KU Leuven, Skeletal Biology and Engineering Research Center, University Hospitals Leuven, Leuven, Belgium. · Rheumatology, University Hospitals Leuven, Leuven, Belgium. ·Rheumatology (Oxford) · Pubmed #28968687.

ABSTRACT: -- No abstract --

6 Review EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. 2017

Smolen, Josef S / Landewé, Robert / Bijlsma, Johannes / Burmester, Gerd / Chatzidionysiou, Katerina / Dougados, Maxime / Nam, Jackie / Ramiro, Sofia / Voshaar, Marieke / van Vollenhoven, Ronald / Aletaha, Daniel / Aringer, Martin / Boers, Maarten / Buckley, Chris D / Buttgereit, Frank / Bykerk, Vivian / Cardiel, Mario / Combe, Bernard / Cutolo, Maurizio / van Eijk-Hustings, Yvonne / Emery, Paul / Finckh, Axel / Gabay, Cem / Gomez-Reino, Juan / Gossec, Laure / Gottenberg, Jacques-Eric / Hazes, Johanna M W / Huizinga, Tom / Jani, Meghna / Karateev, Dmitry / Kouloumas, Marios / Kvien, Tore / Li, Zhanguo / Mariette, Xavier / McInnes, Iain / Mysler, Eduardo / Nash, Peter / Pavelka, Karel / Poór, Gyula / Richez, Christophe / van Riel, Piet / Rubbert-Roth, Andrea / Saag, Kenneth / da Silva, Jose / Stamm, Tanja / Takeuchi, Tsutomu / Westhovens, René / de Wit, Maarten / van der Heijde, Désirée. ·Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria. · Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands. · Zuyderland Medical Center, Heerlen, The Netherlands. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany. · Rheumatology Department, Karolinska Institute, Stockholm, Sweden. · Rhumatologie B, Hopital Cochin, Paris, France. · NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK. · Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. · Department of Psychology, Health and Technology, University of Twente, Enschede, The Netherlands. · Division of Rheumatology, Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. · Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. · Birmingham NIHR Wellcome Trust Clinical Research Facility, Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK. · Department of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, New York, USA. · Rebecca McDonald Center for Arthritis & Autoimmune Disease, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. · Centro de Investigación Clínica de Morelia SC, Michoacán, México. · Rheumatology Department, Lapeyronie Hospital, Montpellier University, UMR 5535, Montpellier, France. · Research Laboratory and Division of Clinical Rheumatology, University of Genoa, Genoa, Italy. · Department of Patient & Care and Department of Rheumatology, University of Maastricht, Maastricht, The Netherlands. · Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland. · Fundación Ramón Dominguez, Hospital Clinico Universitario, Santiago, Spain. · Department of Rheumatology, Sorbonne Universités, Pitié Salpêtrière Hospital, Paris, France. · Institut de Biologie Moléculaire et Cellulaire, Immunopathologie, et Chimie Thérapeutique, Strasbourg University Hospital and University of Strasbourg, CNRS, Strasbourg, France. · Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. · Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK. · V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation. · European League Against Rheumatism, Zurich, Switzerland. · Cyprus League against Rheumatism, Nicosia, Cyprus. · Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. · Department of Rheumatology and Immunology, Beijing University People's Hospital, Beijing, China. · Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, INSERM U1184, Center for Immunology of viral Infections and Autoimmune Diseases (IMVA), Le Kremlin Bicêtre, France. · Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. · Organización Médica de Investigación, Buenos Aires, Argentina. · Department of Medicine, University of Queensland, Queensland, Australia. · Institute of Rheumatology and Clinic of Rheumatology, Charles University, Prague, Czech Republic. · National Institute of Rheumatology and Physiotherapy, Semmelweis University, Budapest, Hungary. · Rheumatology Department, FHU ACRONIM, Pellegrin Hospital and UMR CNRS 5164, Bordeaux University, Bordeaux, France. · Department of Rheumatology, Bernhoven, Uden, The Netherlands. · University of Cologne, Cologne, Germany. · Division of Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Serviço de Reumatologia, Centro Hospitalar e Universitário de Coimbra Praceta Mota Pinto, Coimbra, Portugal. · Section for Outcomes Research, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria. · Keio University School of Medicine, Keio University Hospital, Tokyo, Japan. · Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium. · Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium. · Department Medical Humanities, VU Medical Centre, Amsterdam, The Netherlands. ·Ann Rheum Dis · Pubmed #28264816.

ABSTRACT: Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.

7 Review The optimal combination therapy for the treatment of early rheumatoid arthritis. 2015

De Cock, Diederik / Van der Elst, Kristien / Meyfroidt, Sabrina / Verschueren, Patrick / Westhovens, René. ·Skeletal Biology and Engineering Research Center, KU Leuven Department of Development and Regeneration , Leuven , Belgium +016 346 350 ; +016 342 543 ; diederik.decock@med.kuleuven.be. ·Expert Opin Pharmacother · Pubmed #26058860.

ABSTRACT: INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition traditionally viewed as a severe destructive disease affecting physical health and global wellbeing. The treatment strategies for RA have changed in the last decades from mainly symptomatic towards a more vigorous and targeted approach. AREA COVERED: Reviewing recent literature enhanced by own expertise and research, a case is made for starting early with an intensive combination treatment with glucocorticoids, followed by a treat to target approach in a tight control setting. Implementation issues that need to be addressed to make optimal use of the 'window of opportunity' are highlighted. EXPERT OPINION: There is strong evidence in favor of traditional synthetic disease-modifying anti-rheumatic drugs (DMARDs) combined with a remission induction scheme of glucocorticoids to achieve adequate efficacy in controlling early rheumatoid arthritis with good safety and feasibility in daily clinical practice. Furthermore, the most optimal RA treatment should address not only the physician-oriented clinical disease outcomes but also the patient perspective. There is still a need for working on improving implementation of this approach in daily practice in order to provide optimal treatment benefit to more patients.

8 Review Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques. 2014

Put, Stéphanie / Westhovens, René / Lahoutte, Tony / Matthys, Patrick. · ·Arthritis Res Ther · Pubmed #25099015.

ABSTRACT: Early diagnosis and effective monitoring of rheumatoid arthritis (RA) are important for a positive outcome. Instant treatment often results in faster reduction of inflammation and, as a consequence, less structural damage. Anatomical imaging techniques have been in use for a long time, facilitating diagnosis and monitoring of RA. However, mere imaging of anatomical structures provides little information on the processes preceding changes in synovial tissue, cartilage, and bone. Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis. A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes. Here, we review which cells and molecules can be targeted in the RA joint and discuss the advances that have been made in imaging of arthritis with a focus on such molecular targets as folate receptor, F4/80, macrophage mannose receptor, E-selectin, intercellular adhesion molecule-1, phosphatidylserine, and matrix metalloproteinases. In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers. Finally, we describe additional molecules displaying specific features in joint inflammation and propose these as potential new molecular imaging targets, more specifically receptor activator of nuclear factor κB and its ligand, chemokine receptors, vascular cell adhesion molecule-1, αVβ₃ integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein.

9 Review Optimal care for early RA patients: the challenge of translating scientific data into clinical practice. 2011

Verschueren, Patrick / Westhovens, René. ·Department of Rheumatology, University Hospital Leuven, Herestraat 49, B-3000 Leuven, Belgium. patrick.verschueren@uz.kuleuven.ac.be ·Rheumatology (Oxford) · Pubmed #21454307.

ABSTRACT: Although the evidence is clear and most rheumatologists agree that RA should be treated early and intensively, it obviously remains a challenge to put this paradigm into practice. Patient- as well as physician-related factors determine the delay before the disease is recognized and treated appropriately. There is still a need for education in this context. Optimal treatment allocation depends on the determination of prognostic factors, but should also take into account the patient's perspective to be effective. Patients' perceptions about the disease and its medical management need to be adjusted as soon as possible. Initiation of intensive or complex treatment regimens is most feasible in a clinical setting, where rheumatologists work together with other health-care professionals, such as nurse specialists. Until now there does not seem to have been a difference in terms of efficacy between intensive RA treatment strategies based on a combination of classical DMARDs with glucocorticoids or with TNF-blocking agents, but given the costs biologicals cannot be considered first-line therapy. More scientific work is needed to identify individuals that could benefit from biologicals early in the disease. Given the long-term benefits of rapid disease control, health authorities should consider investing in a better implementation of intensive treatment regimens based on combinations of classical DMARDs and glucocorticoids.

10 Review Translating co-stimulation blockade into clinical practice. 2008

Westhovens, Rene / Verschueren, Patrick. ·Department of Rheumatology, University Hospitals KU Leuven, Herestraat, B-3000 Leuven, Belgium. rene.westhovens@uz.kuleuven.be ·Arthritis Res Ther · Pubmed #19007424.

ABSTRACT: Currently available information from clinical trials and open-label extensions suggest that abatacept is a good alternative to other biologicals in rheumatoid arthritis. Although at first glance the efficacy of all biologicals appears to be the same, in routine practice one might expect there to be differences in effectiveness, safety profiles and specific patient-centered outcomes. These patient-centered outcomes, as well as safety, deserve further attention in follow-up registries, but also in prospective studies, if we are to optimize patient care. After failing a first tumor necrosis factor blocker, patients have several treatment options - starting a second tumor necrosis factor blocker, or rituximab or abatacept - but no formal randomized studies are available to indicate what is the optimal strategy. Potential differences between treatments with biologicals with different modes of action in very early disease also require more study. It is difficult to determine how co-stimulation blockade will influence Crohn's disease or psoriatic arthritis as well as other diseases characterized by a specific role of the adaptive immune system, such as systemic lupus erythematosus and multiple sclerosis. It is clear, however, that every additional targeted therapy creates new opportunities for treatment in many different patient populations.

11 Clinical Trial Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate in patients with rheumatoid arthritis: patient-reported outcomes. 2018

Genovese, Mark / Westhovens, Rene / Meuleners, Luc / Van der Aa, Annegret / Harrison, Pille / Tasset, Chantal / Kavanaugh, Arthur. ·Division of Immunology and Rheumatology, Stanford School of Medicine, Stanford, CA, USA. genovese@stanford.edu. · Division of Immunology and Rheumatology, Stanford School of Medicine, 1000 Welch RD #203, Palo Alto, CA, 94304, USA. genovese@stanford.edu. · Department of Development and Regeneration KU Leuven, Skeletal Biology and Engineering Research Center; Rheumatology, University Hospitals Leuven, Leuven, Belgium. · Galapagos NV, Mechelen, Belgium. · University of California San Diego, La Jolla, CA, USA. ·Arthritis Res Ther · Pubmed #29566740.

ABSTRACT: BACKGROUND: The aim was to assess patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) treated with filgotinib during two phase 2b, 24-week, randomized, placebo-controlled studies. METHODS: Patients with moderate-to-severe active RA and an inadequate response to methotrexate (MTX) were randomized to daily placebo or filgotinib 50 mg, 100 mg, or 200 mg as add-on therapy to MTX (NCT01888874) or as monotherapy (NCT01894516). At week 12, nonresponders receiving filgotinib 50 mg in both studies or placebo in the add-on study, and all patients receiving placebo as monotherapy, were re-assigned to filgotinib 100 mg. PROs were measured using the Health Assessment Questionnaire - Disability Index (HAQ-DI) including Patient Pain assessed by visual analog scale, and the Patient Global Assessment of Disease Activity (Patient Global), the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale (Version 4), and the 36-Item Short Form Health Survey (SF-36). RESULTS: At week 12, improvements in all PROs, apart from the SF-36 mental component in the add-on study, were statistically better with filgotinib than placebo; some improvements were noted as early as the first assessment time point (week 1 or week 4). Filgotinib improved HAQ-DI by 0.58-0.84 points, FACIT-Fatigue by 6.9-11.4 points, Patient Global by 25.2-35.6 mm, and Pain by 24.2-37.9 mm; scores were maintained or improved to week 24. Across all PROs, more patients achieved minimal clinically important differences and normative values with filgotinib 200 mg than placebo. Patients re-assigned to filgotinib 100 mg at week 12 experienced improvements in PROs between weeks 12 to 24. CONCLUSIONS: Filgotinib as MTX add-on therapy or as monotherapy demonstrated rapid and sustained (to 24 weeks) improvements in health-related quality of life and functional status in patients with active RA. TRIAL REGISTRATION: MTX add-on study: ClinicalTrials.gov , NCT01888874 . Registered on 28 June 2013. Monotherapy study: ClinicalTrials.gov , NCT01894516 . Registered on 10 July 2013.

12 Clinical Trial Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1). 2017

Westhovens, R / Taylor, P C / Alten, R / Pavlova, D / Enríquez-Sosa, F / Mazur, M / Greenwald, M / Van der Aa, A / Vanhoutte, F / Tasset, C / Harrison, P. ·Department of Development and Regeneration KU Leuven, Skeletal Biology and Engineering Research Center, Leuven, Belgium. · Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium. · Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK. · Schlosspark-Klinik Innere Medizin II, Berlin, Germany. · LTD "M&M CENTRS", Adazi, Latvia. · CLINSTILE, S.A. DE C.V., Mexico City, Mexico. · IMSP Institul de Cardiologie, Chisinau, Moldova. · Desert Medical Advances, Palm Desert, California, USA. · Galapagos NV, Mechelen, Belgium. ·Ann Rheum Dis · Pubmed #27993829.

ABSTRACT: OBJECTIVES: To evaluate the efficacy and safety of different doses and regimens of filgotinib, an oral Janus kinase 1 inhibitor, as add-on treatment to methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and inadequate response to MTX. METHODS: In this 24-week phase IIb study, patients with moderate-to-severe active RA receiving a stable dose of MTX were randomised (1:1:1:1:1:1:1) to receive placebo or 50, 100 or 200 mg filgotinib, administered once daily or twice daily. Primary end point was the percentage of patients achieving a week 12 American College of Rheumatology (ACR)20 response. RESULTS: Overall, 594 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib 100 mg once daily or 200 mg daily (both regimens) achieved an ACR20 response versus placebo. For other key end points at week 12 (ACR50, ACR-N, Disease Activity Score based on 28 joints and C reactive protein value, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index), differences in favour of 100  or 200 mg filgotinib daily were seen versus placebo; responses were maintained or improved through to week 24. Rapid onset of action and dose-dependent responses were observed for most efficacy end points and were associated with an increased haemoglobin concentration. No significant differences between once-daily and twice-daily regimens were seen. Treatment-emergent adverse event rates were similar in placebo and filgotinib groups. Serious infections occurred in one and five patients in the placebo and filgotinib groups, respectively. No tuberculosis or opportunistic infections were reported. CONCLUSIONS: Filgotinib as add-on to MTX improved the signs and symptoms of active RA over 24 weeks and was associated with a rapid onset of action. Filgotinib was generally well tolerated. TRIAL REGISTRATION NUMBER: NCT01888874.

13 Clinical Trial Maintenance of Clinical and Radiographic Benefit With Intravenous Golimumab Therapy in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy: Week-112 Efficacy and Safety Results of the Open-Label Long-Term Extension of a Phase III, Double-Blind, Randomized, Placebo-Controlled Trial. 2015

Bingham, Clifton O / Mendelsohn, Alan M / Kim, Lilianne / Xu, Zhenhua / Leu, Jocelyn / Han, Chenglong / Lo, Kim Hung / Westhovens, Rene / Weinblatt, Michael E / Anonymous310819. ·Johns Hopkins University, Baltimore, Maryland. · Janssen Research and Development, Spring House, Pennsylvania. · Janssen Global Service, Malvern, Pennsylvania. · UZ KU, Leuven, Belgium. · Brigham and Women's Hospital, Boston, Massachusetts. ·Arthritis Care Res (Hoboken) · Pubmed #25623393.

ABSTRACT: OBJECTIVE: To evaluate the safety, efficacy, pharmacokinetics, immunogenicity, and radiographic progression through 2 years of treatment with intravenous (IV) golimumab plus methotrexate (MTX) in an open-label extension of a phase III trial of patients with active rheumatoid arthritis (RA) despite MTX therapy. METHODS: In the phase III, double-blind, randomized, placebo-controlled GO-FURTHER trial, 592 patients with active RA were randomized (2:1) to intravenous golimumab 2 mg/kg plus MTX (Group 1) or placebo plus MTX (Group 2) at weeks 0 and 4, then every 8 weeks thereafter; placebo patients crossed over to golimumab at week 16 (early escape) or week 24 (crossover). The final golimumab infusion was at week 100. Assessments included American College of Rheumatology 20%, 50%, 70% (ACR20, ACR50, ACR70) response criteria, 28-joint count disease activity score using the C-reactive protein level (DAS28-CRP), physical function and quality of life measures, and changes in the modified Sharp/van der Heijde scores (SHS). Safety was monitored through week 112. RESULTS: In total, 486 patients (82.1%) continued treatment through week 100, and 68.1%, 43.8%, and 23.5% had an ACR20/50/70 response, respectively, at week 100. Clinical response and improvements in physical function and quality of life were generally maintained from week 24 through 2 years. Mean change from baseline to week 100 in SHS score was 0.74 in Group 1 and 2.10 in Group 2 (P = 0.005); progression from week 52 to week 100 was clinically insignificant in both groups. A total of 481 patients completed the safety followup through week 112; 79.1% had an adverse event, and 18.2% had a serious adverse event. CONCLUSION: Clinical response to IV golimumab plus MTX was maintained through week 100. Radiographic progression following golimumab treatment was clinically insignificant between week 52 and week 100. No unexpected adverse events occurred through week 112, and the safety profile was consistent with anti-tumor necrosis factor therapy.

14 Clinical Trial Long-term safety and efficacy of abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: a 7-year extended study. 2014

Westhovens, Rene / Kremer, Joel M / Emery, Paul / Russell, Anthony S / Alten, Rieke / Barré, Emilie / Dougados, Maxime. ·Department of Development and Regeneration, Neuro-musculo-skeletal Research Unit, KU Leuven, Belgium. rene.westhovens@uz.kuleuven.ac.be. ·Clin Exp Rheumatol · Pubmed #25005467.

ABSTRACT: OBJECTIVES: To assess the safety and efficacy of intravenous (IV) abatacept plus methotrexate (MTX) over 7 years, the longest observational period to date, in patients with established rheumatoid arthritis (RA) and an inadequate response to MTX. METHODS: Patients randomised to IV abatacept (10 or 2 mg/kg) or placebo, plus MTX, during the 1-year double-blind (DB) period of a Phase 2b study could enter the long-term extension (LTE) and receive IV abatacept 10 mg/kg monthly. Safety was assessed in patients who received ≥1 dose of abatacept; efficacy was assessed in patients originally randomised to 10 mg/kg abatacept (as-observed data). RESULTS: A total of 219 patients entered the LTE; 114 (52.1%) completed 7 years of treatment with abatacept plus MTX. Cumulative (DB + LTE) incidence rates of serious adverse events, serious infections, malignancies, and autoimmune events were 17.6, 3.2, 1.8, and 1.2/100 patient-years, respectively. Safety was consistent between the DB (n=220) and cumulative (n=287) periods. Improvements in American College of Rheumatology responses, disease activity, and normalisation of physical function and health-related quality of life were maintained over time. Approximately 80% of patients who achieved low disease activity or normalised modified Health Assessment Questionnaire scores at Year 1, and who remained in the study, sustained these responses in each subsequent year. CONCLUSIONS: IV abatacept in combination with MTX demonstrated consistent safety and sustained efficacy over 7 years in MTX inadequate responders with established RA. Furthermore, some patients demonstrated a normalisation of physical function and health-related quality of life that was sustained over time.

15 Clinical Trial The effect of intravenous golimumab on health-related quality of life in rheumatoid arthritis: 24-week results of the phase III GO-FURTHER trial. 2014

Bingham, Clifton O / Weinblatt, Michael / Han, Chenglong / Gathany, Timothy A / Kim, Lilianne / Lo, Kim Hung / Baker, Dan / Mendelsohn, Alan / Westhovens, Rene. ·From the Division of Rheumatology and Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, Maryland; Department of Clinical Rheumatology, Brigham and Women's Hospital, Boston, Massachusetts; Patient Reported Outcomes, Janssen Global Services LLC, Malvern, Pennsylvania; Biostatistics and Immunology, Janssen Research & Development LLC, Spring House, Pennsylvania, USA; Department of Rheumatology, UZ Gasthuisberg, KU Leuven, Belgium.C.O. Bingham III, MD, Division of Rheumatology and Allergy and Clinical Immunology, Johns Hopkins University; M. Weinblatt, MD, Department of Clinical Rheumatology, Brigham and Women's Hospital; C. Han, PhD; T.A. Gathany, PhD, Patient Reported Outcomes, Janssen Global Services; L. Kim, PhD; K.H. Lo, PhD, Biostatistics, Janssen Research & Development LLC; D. Baker, MD; A. Mendelsohn, MD, Immunology, Janssen Research & Development LLC; R. Westhovens, MD, Department of Rheumatology, University Hospitals Leuven; Department of Development and Regeneration, KU Leuven. ·J Rheumatol · Pubmed #24786931.

ABSTRACT: OBJECTIVE: To evaluate the effects of intravenous (IV) golimumab 2 mg/kg + methotrexate (MTX) on patient-reported measures of health-related quality of life (HRQOL) in patients with active rheumatoid arthritis (RA) despite prior MTX therapy. METHODS: In this randomized, multicenter, double-blind, placebo-controlled, phase III trial, adults with RA were randomly assigned to receive IV placebo (n = 197) or golimumab 2 mg/kg (n = 395) infusions at Week 0, Week 4, and every 8 weeks thereafter. All patients continued stable oral MTX (15-25 mg/wk). HRQOL assessments included Health Assessment Questionnaire-Disability Index (HAQ-DI; physical function), Medical Outcomes Study Short Form-36 questionnaire physical/mental component summary (SF-36 PCS/MCS) scores, EQ-5D assessment of current health state, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire, and disease effect on productivity [10-cm visual analog scale (VAS)]. RESULTS: Mean HAQ-DI improvements from baseline were significantly greater with golimumab + MTX than placebo + MTX at Week 14 and Week 24 (p < 0.001). Significantly greater improvements in all 8 individual SF-36 subscores and both the SF-36 PCS and MCS scores (p < 0.001) also accompanied golimumab + MTX therapy. Improved EQ-5D and EQ-5D VAS (p < 0.001) and FACIT-Fatigue (p < 0.001) scores were also observed for golimumab + MTX-treated patients at Week 12, Week 16, and Week 24, and greater proportions of golimumab + MTX-treated patients had clinically meaningful improvements in these measures. Greater reductions in disease effect on productivity were observed with golimumab + MTX versus placebo + MTX at Week 24 (p < 0.001). Improvements in physical function, HRQOL, fatigue, and productivity significantly correlated with disease activity improvement. CONCLUSION: In active RA, IV golimumab + MTX significantly improved physical function, HRQOL, fatigue, and productivity using multiple measurement tools; all correlated with improvements in disease activity (NCT00973479, EudraCT 2008-006064-11).

16 Clinical Trial The early clinical course of infliximab treatment in rheumatoid arthritis: results from the REMARK observational study. 2014

Westhovens, R / van Vollenhoven, R F / Boumpas, D T / Brzosko, M / Svensson, K / Bjorneboe, O / Meeuwisse, C M / Srinivasan, S / Gaudin, P / Smolen, J S / Rahman, M U / Nelissen, R L / Vastesaeger, N. ·Skeletal Biology and Engineering Research Center, Department of Development and Regeneration KU Leuven; Rheumatology, University Hospitals Leuven, Belgium. rene.westhovens@uz.kuleuven.ac.be. ·Clin Exp Rheumatol · Pubmed #24529163.

ABSTRACT: OBJECTIVES: We aimed to describe patterns of disease activity during infliximab plus methotrexate (MTX) treatment and explore C-reactive protein (CRP) as a potential marker of early response. METHODS: REMARK was a phase IV, open-label, observational study of infliximab-naïve adults with rheumatoid arthritis (RA) who received infliximab 3 mg/kg plus MTX for 14 weeks. Treatment response was evaluated in 3 subgroups: patients with <1 year disease duration who were TNF-inhibitor (TNFi)-naïve, patients with ≥ 1 year disease duration who were TNFi-naïve, and patients who had previous TNFi failure or intolerance. In post hoc analyses, CRP kinetic profiles were analysed by EULAR response (good, moderate, non-response) in REMARK and in an independent replication with data from the ASPIRE study. RESULTS: In the efficacy-evaluable population (n=662), median 28-joint disease activity score (DAS28) improved from baseline to Week 14 (5.2 vs. 3.6, p<0.0001). Regardless of disease history subgroup, most patients had good or moderate EULAR responses at Weeks 2 (64.9%), 6 (74.1%), and 14 (73.6%). DAS28 and its components did not differ across patient subgroups. Disease flare occurred in 16.2% of patients. CRP levels declined markedly at Week 2, but patients who were EULAR non-responders at Week 14 showed a CRP rebound at Weeks 6 and 14. This CRP pattern was independently replicated in data from ASPIRE. Adverse events were consistent with the known risk profile of infliximab. CONCLUSIONS: Infliximab plus MTX treatment in patients with RA rapidly diminished disease activity. A unique pattern of CRP rebound was found in non-responders early in treatment.

17 Clinical Trial Radiographic benefit and maintenance of clinical benefit with intravenous golimumab therapy in patients with active rheumatoid arthritis despite methotrexate therapy: results up to 1 year of the phase 3, randomised, multicentre, double blind, placebo controlled GO-FURTHER trial. 2014

Weinblatt, Michael E / Westhovens, Rene / Mendelsohn, Alan M / Kim, Lilianne / Lo, Kim Hung / Sheng, Shihong / Noonan, Lenore / Lu, Jiandong / Xu, Zhenhua / Leu, Jocelyn / Baker, Daniel / Bingham, Clifton O / Anonymous4380768. ·Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Development and Regeneration KU Leuven, Skeletal Biology and Engineering Research Centre, Leuven, Belgium Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium. · Janssen Research & Development, LLC, Spring House, Pennsylvania, USA. · Johns Hopkins University Baltimore, Baltimore, Maryland, USA. ·Ann Rheum Dis · Pubmed #24001888.

ABSTRACT: OBJECTIVE: Report on radiographic effects and maintenance of clinical benefit with intravenous golimumab 2 mg/kg+methotrexate (MTX) for up to week (wk) 52 in active rheumatoid arthritis (RA). METHODS: Patients (n=592) with active RA (≥6/66 swollen, ≥6/68 tender joints, C reactive protein (CRP) ≥1.0 mg/dL and positive for rheumatoid factor and/or anticyclic citrullinated protein antibody at screening) despite MTX ≥3 months (stable dose of 15-25 mg/week for ≥4 weeks) participated in this multicentre, international, randomised, double blind, placebo controlled, phase 3 study. Patients were randomised (2:1) to receive intravenous golimumab 2 mg/kg or placebo infusions at weeks 0 and 4 and then every 8 weeks; patients continued their stable MTX regimen. Placebo patients started golimumab 2 mg/kg at wk16 (early escape; <10% improvement in tender and swollen joints) or wk24 (crossover by design). Week 24 and wk52 radiographic (van der Heijde-Sharp (vdH-S) scores), clinical efficacy and safety data up to 1 year are reported here. RESULTS: Significant and rapid clinical improvement was observed up to wk24 of intravenous golimumab therapy. Golimumab+MTX treated patients demonstrated less radiographic progression than placebo treated patients at wk24 (vdH-S score mean change 0.03 vs 1.09; p<0.001) and wk52 (0.13 vs 1.22; p=0.001). Among patients with ≥20% improvement in the American College of Rheumatology response criteria or who achieved a 'good' or 'moderate' response according to the 28 joint Disease Activity Score employing CRP at wk24, approximately 80% maintained this response up until wk52. Through an average of 43.5 weeks of follow-up, 64.6% of patients receiving golimumab+MTX reported adverse events, most commonly non-serious infections. CONCLUSIONS: In patients with active RA despite MTX, intravenous golimumab+MTX yielded significant inhibition of structural damage at wk24 and wk52, and sustained clinical improvement in signs and symptoms with no new safety signals up to 1 year. CLINICALTRIALSGOV: NCT00973479, EudraCT 2008-006 064-11.

18 Clinical Trial Safety of abatacept administered intravenously in treatment of rheumatoid arthritis: integrated analyses of up to 8 years of treatment from the abatacept clinical trial program. 2013

Weinblatt, Michael E / Moreland, Larry W / Westhovens, Rene / Cohen, Roger B / Kelly, Sheila M / Khan, Nader / Pappu, Ramesh / Delaet, Ingrid / Luo, Allison / Gujrathi, Sheila / Hochberg, Marc C. ·Brigham and Women's Hospital, Boston, MA, USA. mweinblatt@partners.org ·J Rheumatol · Pubmed #23588946.

ABSTRACT: OBJECTIVE: To assess the overall safety, including rare events, of intravenous (IV) abatacept treatment in rheumatoid arthritis (RA). METHODS: Data from 8 clinical trials of IV abatacept in RA were pooled. Safety events were assessed during the short-term (duration ≤ 12 months) and cumulative (short-term plus longterm extensions) abatacept treatment periods. Incidence rates per 100 patient-years were calculated. Standardized incidence ratios (SIR) for hospitalized infections and malignancies were compared with external RA cohorts and, for malignancies, with the US general population. RESULTS: There were 3173 IV abatacept-treated patients with 2331 patient-years of exposure in the short-term periods, and 4149 IV abatacept-treated patients with 12,132 patient-years of exposure in the cumulative period. Incidence rates for serious infections were low and consistent over time (3.68 for abatacept vs 2.60 for placebo during the short-term, and 2.87 for abatacept during the cumulative period). Hospitalized infections were generally similar to external RA patient cohorts and were consistent over time. Incidence rates of malignancies were similar for abatacept- and placebo-treated patients during the short-term period (0.73 vs 0.59) and remained low during the abatacept cumulative period (0.73). SIR of some tissue-specific malignancies (e.g., colorectal and breast) in the cumulative period tended to be lower, while others (lymphoma and lung) tended to be higher, compared with the general population; however, incidence rates were comparable with RA cohorts. Autoimmune events were rare and infusion reactions uncommon. CONCLUSION: Longterm safety of IV abatacept was consistent with the short-term, with no unexpected events and low incidence rates of serious infections, malignancies, and autoimmune events.

19 Clinical Trial Oral administration of GLPG0259, an inhibitor of MAPKAPK5, a new target for the treatment of rheumatoid arthritis: a phase II, randomised, double-blind, placebo-controlled, multicentre trial. 2013

Westhovens, René / Keyser, Filip De / Rekalov, Dmytro / Nasonov, Evgeny L / Beetens, Johan / Van der Aa, Annegret / Wigerinck, Piet / Namour, Florence / Vanhoutte, Frédéric / Durez, Patrick. ·Department of Rheumatology, University Hospital KU Leuven, Leuven, Belgium. ·Ann Rheum Dis · Pubmed #23161899.

ABSTRACT: BACKGROUND: Mitogen-activated protein (MAP) kinases are key regulators of cytokine production, and are therefore potential targets for treatment of rheumatoid arthritis (RA). OBJECTIVE: This two-part phase II study investigated the efficacy and safety of a once-daily 50 mg GLPG0259 (an inhibitor of MAP kinase-activated protein kinase 5) dose vs placebo (part A). An interim analysis after part A would determine whether the dose-finding part (part B) would be performed. METHODS: In part A, eligible methotrexate (MTX)-refractory patients with RA were randomised to receive either a once-daily 50 mg dose of GLPG0259 or placebo, in addition to a stable dose of MTX, for 12 weeks. The primary efficacy end point was the percentage of patients achieving an American College of Rheumatology 20% improvement (ACR20) response after 12 weeks. RESULTS: The interim analysis showed no difference between the percentage of subjects achieving the primary efficacy variable of ACR20 or the secondary efficacy variables (ACR50, ACR70 and Disease Activity Score 28) at week 12 in the GLPG0259-treated (n=19) and placebo-treated (n=11) groups. Owing to lack of efficacy, the study was terminated, and part B was not initiated. CONCLUSIONS: This innovative study design quickly provided conclusive results on the lack of efficacy of GLPG0259 in patients with RA.

20 Clinical Trial Intravenous golimumab is effective in patients with active rheumatoid arthritis despite methotrexate therapy with responses as early as week 2: results of the phase 3, randomised, multicentre, double-blind, placebo-controlled GO-FURTHER trial. 2013

Weinblatt, Michael E / Bingham, Clifton O / Mendelsohn, Alan M / Kim, Lilianne / Mack, Michael / Lu, Jiandong / Baker, Daniel / Westhovens, Rene. ·Department of Rheumatology, Brigham and Women's Hospital, 75 Francis St, Boston, Massachusetts, 02115, USA. mweinblatt@partners.org ·Ann Rheum Dis · Pubmed #22661646.

ABSTRACT: OBJECTIVES: Evaluate the efficacy of intravenous golimumab 2 mg/kg+methotrexate (MTX) in patients with active rheumatoid arthritis (RA) receiving MTX. METHODS: Patients (n=592) with active disease (≥6/66 swollen, ≥6/68 tender joints, C-reactive protein ≥1.0 mg/dl, rheumatoid factor positive and/or anticyclic citrullinated protein antibody positive at screening) despite MTX (15-25 mg/week) participated in this double-blind, placebo-controlled, phase 3 study. Patients were randomised (2:1) to receive intravenous golimumab 2 mg/kg, or placebo infusions at weeks 0 and 4 and every (q) 8 weeks; patients continued MTX. Placebo patients with <10% improvement in combined swollen/tender joint counts at week 16 could early escape to intravenous golimumab 2 mg/kg. The primary endpoint was week 14 American College of Rheumatology 20% (ACR20) response. Analyses employed non-responder imputation and last-observation-carried-forward. RESULTS: At week 14, significantly (p<0.001) larger proportions of golimumab+MTX than placebo+MTX patients achieved ACR20 response (59% vs 25%, respectively), a disease activity score of good/moderate (EULAR) response (81% vs 40%), and greater median improvement in health assessment questionnaire scores (0.500 vs 0.125). Improvements versus placebo+MTX were observed by week 2. Similar proportions of patients receiving golimumab+MTX and placebo+MTX, respectively, reported adverse events through week 16 (47% and 44%) and week 24 (53% and 49%). Serious adverse events were reported by more golimumab+MTX (4.1%) than placebo+MTX (2%) patients at week 24. CONCLUSION: The addition of intravenous golimumab rapidly and significantly improved signs and symptoms in patients with active RA despite ongoing MTX, in some patients by week 2.

21 Clinical Trial Safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the monoclonal antibody ASK8007 blocking osteopontin in patients with rheumatoid arthritis: a randomised, placebo controlled, proof-of-concept study. 2012

Boumans, M J H / Houbiers, J G A / Verschueren, P / Ishikura, H / Westhovens, R / Brouwer, E / Rojkovich, B / Kelly, S / den Adel, M / Isaacs, J / Jacobs, H / Gomez-Reino, J / Holtkamp, G M / Hastings, A / Gerlag, D M / Tak, P P. ·Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, The Netherlands. ·Ann Rheum Dis · Pubmed #21917822.

ABSTRACT: OBJECTIVES: Osteopontin is an extracellular matrix protein with diverse immunomodulatory functions. The authors assessed the safety, tolerability, pharmacokinetics, pharmacodynamics and initial efficacy of the humanised monoclonal antibody ASK8007, which blocks osteopontin. METHODS: In this double-blind, multicentre, combined first-in-man, single-dose escalation (phase I, part A) and proof-of-concept, multiple-dose (phase IIA, part B) study, rheumatoid arthritis (RA) patients with active disease were randomly assigned to receive ASK8007 or placebo intravenously. Safety monitoring, pharmacokinetic and pharmacodynamic analyses and clinical assessments were performed throughout the study. The expression of phenotypic cell markers was evaluated in synovial tissue biopsy samples obtained at baseline and 43 days after initiation of treatment (part B) by immunohistochemistry and digital image analysis. Two co-primary efficacy endpoints were the change from baseline in the disease activity score evaluated in 28 joints (DAS28) and the change from baseline in the number of CD68 synovial sublining macrophages, both assessed on day 43 (part B). RESULTS: ASK8007 was overall safe and well tolerated up to the highest studied dose (20 mg/kg). Quantifiable concentrations of ASK8007 were detected in synovial fluid. No differences were observed for changes from baseline in DAS28 and CD68 sublining macrophages between ASK8007 and placebo-treated patients. Within the ASK8007 treatment group, there were also no apparent clinical responses or changes in sublining macrophages. In addition, ASK8007 treatment did not change other assessed biomarkers. CONCLUSIONS: Osteopontin blockade is well tolerated and not related to safety concerns. These results consistently show that osteopontin blockade is unlikely to induce robust clinical improvement in RA patients.

22 Clinical Trial Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes. 2011

Bathon, J / Robles, M / Ximenes, A C / Nayiager, S / Wollenhaupt, J / Durez, P / Gomez-Reino, J / Grassi, W / Haraoui, B / Shergy, W / Park, S-H / Genant, H / Peterfy, C / Becker, J-C / Covucci, A / Moniz Reed, D / Helfrick, R / Westhovens, R. ·College of Physician and Surgeons, Columbia University, 630 West 168th Street, P&S 10-445, New York, NY 10023, USA. jmb2311@columbia.edu ·Ann Rheum Dis · Pubmed #21821865.

ABSTRACT: OBJECTIVE: To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA). METHODS: The AGREE was a 2-year phase IIIb multinational study in early (≤ 2 years) RA. During the double-blind period (year 1), patients were randomly assigned 1:1 to receive abatacept+methotrexate or methotrexate alone; all patients received open-label abatacept+methotrexate during year 2. Clinical outcomes assessed included 28-joint disease activity score (DAS28) defined remission, low disease activity score (LDAS), American College of Rheumatology (ACR) responses and physical function. Radiographic outcomes were assessed using the Genant-modified Sharp total score (TS). Safety was monitored throughout. RESULTS: Of the 459 patients completing year 1, 433 patients (94.3%) completed year 2. DAS28-defined remission, LDAS, ACR and physical function were sustained through year 2 in the original abatacept+methotrexate group, with 55.2% in remission at 2 years. Upon introduction of abatacept in the methotrexate-alone group, additional patients achieved DAS28-defined remission (44.5% vs 26.9%), LDAS (60.4% vs 43.2%) and improved ACR 70 (49.8% vs 31.7%) for year 2 versus year 1. Less radiographic progression was observed at 2 years in the original abatacept+methotrexate group than the methotrexate-alone group (change in TS 0.84 vs 1.75, p<0.001). No new safety issues were seen. Similar rates of serious adverse events, serious infections and autoimmune events were observed in years 1 and 2. CONCLUSIONS: The AGREE trial was the first to examine the impact of T-cell co-stimulation modulation with abatacept in patients with early erosive RA. Early treatment with abatacept+methotrexate resulted in greater sustainable clinical, functional and radiographic benefits than methotrexate alone, with acceptable safety and tolerability. TRIAL REGISTRATION: NCT00122382.

23 Clinical Trial Improvements in participation in usual daily activities in patients with rheumatoid arthritis treated with abatacept. 2011

Li, Tracy / Wells, George / Westhovens, Rene / Emery, Paul / Becker, Jean-Claude / Tugwell, Peter. ·Global Health Outcomes, Bristol-Myers Squibb, Princeton, NJ 08543, USA. TL3242@yahoo.com ·Value Health · Pubmed #21296603.

ABSTRACT: OBJECTIVE: To examine changes in activity participation following abatacept treatment for rheumatoid arthritis (RA), and which factors contributed to such changes. METHODS: Data were analyzed from the Abatacept in Inadequate responders to Methotrexate (AIM) and Abatacept Trial in Treatment of Anti-TNF INadequate responders (ATTAIN) clinical trials of abatacept in patients with RA. Activity participation was evaluated by the validated Activity Participation Questionnaire (APaQ), along with measures of clinical response and health-related quality of life. Changes in the APaQ during the two study periods were compared between treatment groups. Multiple regression analyses were performed to investigate the determinants of change in activity participation. The relationship between clinical efficacy measures (including low disease activity state [LDAS], Disease Activity Score 28-defined remission, and European League Against Rheumatism [EULAR] responses) and changes in activity participation were investigated. RESULTS: Statistically significant, substantive improvements in activity participation were observed over the entire study period in patients treated with abatacept. Abatacept-treated patients showed improvements from baseline of 8.4 and 7.3 days in activity participation, compared with 4.5 and 1.4 days in the placebo group (P < 0.005 vs. placebo in both trials), at the end of AIM and ATTAIN, respectively. The Short Form-36 physical and mental component scores, patient global assessment, and the Health Assessment Questionnaire-Disability Index score were found to be the strongest determinants of changes in activity participation. Patients who achieved LDAS, disease remission and good EULAR responses experienced greater improvements in activity participation measures. CONCLUSIONS: Abatacept treatment substantively and significantly improved patients' ability to participate in their usual activities. The gain in activity was closely related to improvements in clinical status, physical function and quality of life.

24 Clinical Trial Safety and efficacy of the selective costimulation modulator abatacept in patients with rheumatoid arthritis receiving background methotrexate: a 5-year extended phase IIB study. 2009

Westhovens, Rene / Kremer, Joel M / Moreland, Larry W / Emery, Paul / Russell, Anthony S / Li, Tracy / Aranda, Richard / Becker, Jean-Claude / Qi, Keqin / Dougados, Maxime. ·Department of Rheumatology, KU Leuven, Herestraat 49, B 3000 Leuven, Belgium. rene.westhovens@uz.kuleuven.ac.be ·J Rheumatol · Pubmed #19273451.

ABSTRACT: OBJECTIVE: To evaluate the safety and efficacy of abatacept plus methotrexate (MTX) over 5 years in patients with rheumatoid arthritis. METHODS: Patients were randomized to abatacept 10 or 2 mg/kg or placebo, plus MTX. Patients completing the 1-year, double-blind period entered the longterm extension, where all patients received a fixed dose of abatacept ~10 mg/kg. We describe safety analyses for all patients who received at least 1 dose of abatacept and efficacy analyses for the original ~10 mg/kg abatacept-treated group, over 5 years. RESULTS: Of the 235 abatacept- or placebo-treated patients completing the double-blind period, 219 entered the longterm extension; 130 (59.4%) were continuing at Year 5. No unexpected safety events were observed during the longterm extension compared with the double-blind period. Incidence rates of adverse events (AE) and serious AE were 489.7 and 20.0/100 patient-years in Year 1 versus 374.9 and 18.9/100 patient-years in the cumulative period, respectively. Using exploratory analyses, improvements observed at Year 1 in the 10 mg/kg group were maintained at Year 5, as assessed by ACR responses (ACR20=77.1% vs 82.7%; ACR50=53.0% vs 65.4%; ACR70=28.9% vs 40.4% at Years 1 and 5, respectively) and disease activity (Low Disease Activity State=48.2% vs 58.5%; Disease Activity Score-28-defined remission=25.3% vs 45.3% at Years 1 and 5, respectively). CONCLUSION: Abatacept maintained the efficacy observed at Year 1 over 5 years of treatment, and demonstrated consistent safety and tolerability. These data, along with relatively high retention rates, support the longterm clinical benefit provided by selective T cell costimulation modulation. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov; clinical trial registration number: NCT00254293.

25 Clinical Trial Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors. 2009

Westhovens, R / Robles, M / Ximenes, A C / Nayiager, S / Wollenhaupt, J / Durez, P / Gomez-Reino, J / Grassi, W / Haraoui, B / Shergy, W / Park, S-H / Genant, H / Peterfy, C / Becker, J-C / Covucci, A / Helfrick, R / Bathon, J. ·UZ Gasthuisberg, Department of Rheumatology, B-3000 Leuven, Belgium. rene.westhovens@uz.kuleuven.ac.be ·Ann Rheum Dis · Pubmed #19124524.

ABSTRACT: OBJECTIVES: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. METHODS: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (approximately 10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. RESULTS: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. CONCLUSIONS: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.