Abstracts tagged "clinical trial"

Abstract Number: 1831 • ACR Convergence 2022
Establishing a Scientific Bridge to Historic VIOXX to Enable a Reintroduction of Rofecoxib: Pharmacokinetic Evaluation of TRM‑201 (Rofecoxib)
Judith Boice¹, Travis Helm¹, Maria Bermudez², Mark Corrigan¹ and Bradford Sippy¹, ¹Tremeau Pharmaceuticals, Inc, Concord, MA, ²Clinical Pharmacology of Miami, LLC, Miami, FL
Background/Purpose: TRM-201 (rofecoxib) is a cyclooxygenase-2 (COX-2) selective inhibitor being developed for the treatment of hemophilic arthropathy (HA) and acute migraine. Previously marketed as VIOXX,…
Abstract Number: 2000 • ACR Convergence 2022
Tapering of Long-term, Low Dose Glucocorticoids in Senior Rheumatoid Arthritis Patients: Follow up of the Pragmatic, Multicentre, Placebo-controlled GLORIA Trial
Abdullah Almayali¹, Maarten Boers², Linda Hartman³, Daniela OPRIS-BELINSKI⁴, Reinhard Bos⁵, Marc Kok⁶, Jose Pereira da Silva⁷, Eduard N Griep⁸, Ruth Klaasen⁹, CF Allaart¹⁰, Paul Baudoin¹¹, Hennie Raterman¹², Zoltan Szekanecz¹³, Frank Buttgereit¹⁴, Pavol MASARYK¹⁵, Willem Lems¹⁶, Maurizio Cutolo¹⁷ and Marieke ter Wee³, ¹Amsterdam University Medical Centers, Vrije Universiteit, Purmerend, Noord-Holland, Netherlands, ²Amsterdam UMC, Vrije Universiteit, Amsterdam, Netherlands, ³Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, Netherlands, ⁴Carol Davila University, Bucharest, Romania, ⁵Medical Centre Leeuwarden, Department of Rheumatology, Leeuwarden, Netherlands, ⁶Department of Rheumatology and Clinical immunology, Maasstad Hospital, Rotterdam, Netherlands, ⁷University of Coimbra, Rheumatology, Columbia, Portugal, ⁸Department of Rheumatology, Antonius Hospital, Leeuwarden, Netherlands, ⁹Department of Rheumatology, Meander Medical Center, Amersfoort, Netherlands, ¹⁰Leiden University Medical Center, Leiden, Netherlands, ¹¹Reumazorg Flevoland, Almere, Netherlands, ¹²Department of Rheumatology, Northwest Clinics, Alkmaar, Netherlands, ¹³Division of Rheumatology, Faculty of Medicine, Debrecen, Hungary, ¹⁴Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin / DRFZ Berlin, Berlin, Germany, ¹⁵National Institute for the Rheumatic Diseases, Piešťany, Slovakia, ¹⁶Amsterdam University Medical Centers, Amsterdam, Netherlands, ¹⁷Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS San Martino Polyclinic Hospital, Genova, Italy
Background/Purpose: Guidelines suggest glucocorticoids (GC) should be used as bridge therapy in rheumatoid arthritis (RA), but many patients are on chronic treatment, and the effects…
Abstract Number: 2139 • ACR Convergence 2022
Sustained Response to Guselkumab Regardless of Baseline Demographic, Disease, and Medication Characteristics in Patients with Active Psoriatic Arthritis and an Inadequate Response to TNF Inhibitors: Results from a Phase 3b Trial
Iain B McInnes¹, Philipp Sewerin², Mohamed Sharaf³, Michela Efficace⁴, May Shawi⁵, Michelle Perate⁶, Miriam Zimmermann⁷ and Laura Coates⁸, ¹Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom, ²Rheumazentrum Ruhrgebiet, Ruhr-Universität-Bochum, Herne, Germany, ³Johnson & Johnson, Middle East FZ LLC, Dubai, United Arab Emirates, ⁴Janssen Cilag SpA, Imperia, Italy, ⁵Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, PA, ⁶Janssen Scientific Affairs, LLC, Horsham, PA, ⁷Janssen Scientific Affairs, LLC, Zug, Switzerland, ⁸Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK, Oxford, England, United Kingdom
Background/Purpose: Guselkumab (GUS) is a human monoclonal antibody targeting the IL-23 p19 subunit. In the Phase 3b COSMOS trial (NCT03796858), GUS significantly improved disease signs/symptoms…
Abstract Number: L07 • ACR Convergence 2021
Depletion of KLRG1+ T Cells in a First-in-human Clinical Trial of ABC008 in Inclusion Body Myositis (IBM)
Niti Goel¹, Dulce Soler-Ferran², Monette Coutreau², Jorge Escobar³, Kate Courtemanche², Merrilee Needham⁴ and Steven Greenberg⁵, ¹Abcuro, Inc.; Duke University, Durham, NC, ²Abcuro, Inc., Newton, MA, ³Abcuro, Inc., Hayward, CA, ⁴Perron Institute, Murdoch University, Perth, Australia, ⁵Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Background/Purpose: Inclusion body myositis (IBM), a relentlessly progressive autoimmune skeletal muscle disease, has no effective available pharmacological therapy. A prominent feature of IBM on microscopy…
Abstract Number: L13 • ACR Convergence 2021
Efficacy and Safety of Subcutaneous Belimumab (BEL) and Rituximab (RTX) Sequential Therapy in Patients with Systemic Lupus Erythematosus: The Phase 3, Randomized, Placebo-Controlled BLISS-BELIEVE Study
Cynthia Aranow¹, Cornelia Allaart², Zahir Amoura³, Ian N Bruce⁴, Patricia Cagnoli⁵, Richard Furie¹, Paul Peter Tak⁶, Murray Urowitz⁷, Ronald van Vollenhoven⁸, Kenneth L Clark⁶, Mark Daniels⁹, Norma Lynn Fox¹⁰, Yun Irene Gregan¹⁰, James Groark¹¹, Robert B Henderson⁹, Mary Oldham⁹, Don Shanahan⁹, Andre van Maurik⁹, David A Roth¹⁰ and YK Onno Teng², ¹Feinstein Institutes for Medical Research, Northwell Health, Great Neck, NY, ²Leiden University Medical Center, Leiden, Netherlands, ³Centre National de reference pour le Lupus, Service de Medecine Interne 2, Institut E3M, Hopital Pitié-Salpétrière, Paris, France, ⁴NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Trust and Centre for Musculoskeletal Research, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom, ⁵University of Michigan Medical Center, Ann Arbor, MI, ⁶GlaxoSmithKline (At the time of the author's contribution to this study), Stevenage, United Kingdom, ⁷Toronto Western Hospital, University of Toronto, Lupus Clinic, Toronto, ON, Canada, ⁸Amsterdam University Medical Center, Amsterdam Rheumatology Center, Amsterdam, Netherlands, ⁹GlaxoSmithKline, Stevenage, United Kingdom, ¹⁰GlaxoSmithKline, Collegeville, PA, ¹¹GlaxoSmithKline (At the time of the author's contribution to this study), Collegeville, PA
Background/Purpose: Disease control remains an unmet need in SLE. The rationale for sequential BEL and RTX therapy in SLE was previously published.1 This study evaluated…
Abstract Number: L20 • ACR Convergence 2021
Efficacy of Emapalumab, an Anti-IFNγ Antibody in Patients with Macrophage Activation Syndrome (MAS) Complicating Systemic Juvenile Idiopathic Arthritis (sJIA) Who Had Failed High-Dose Glucocorticoids (GCs)
Fabrizio De Benedetti¹, Alexei Grom², Paul Brogan³, Claudia Bracaglia¹, Manuela Pardeo¹, Giulia Marucci¹, Despina Eleftheriou³, Charalampia Papadopoulou³, Pierre Quartier⁴, Jordi Antón⁵, Rikke Frederiksen⁶, Veronica Asnaghi⁶ and Cristina De Min⁶, ¹Bambino Gesù Children's Hospital IRCCS, Rome, Italy, ²Cincinnati Children’s Hospital, Division of Rheumatology, Cincinnati, OH, ³UCL Institute of Child Health, and Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom, ⁴Université de Paris, IMAGINE Institute, RAISE reference centre, Pediatric Immuno-Hematology and Rheumatology Unit, Necker Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France, ⁵Hospital Sant Joan de Déu, Division of Pediatric Rheumatology, University of Barcelona, Barcelona, Spain, ⁶Swedish Orphan Biovitrum AG (Sobi), Basel, Switzerland
Background/Purpose: MAS is a life-threatening complication of rheumatic diseases, occurring most frequently in sJIA. The mainstay of MAS treatment is high dose GCs; however, GCs…
Abstract Number: 0453 • ACR Convergence 2021
Efficacy and Safety of Risankizumab for Active Psoriatic Arthritis: 24-Week Integrated Results from 2 Phase 3, Randomized, Double-blind Clinical Trials for CsDMARD-IR and Bio-IR Patients
Andrew Ostor¹, Kim Papp², Mireia Moreno³, Cathy Spargo⁴, Lisa Barcomb⁵, Ahmed M. Soliman⁵, Wenjing Lu⁶, Ann Eldred⁵ and Lars Erik Kristensen⁷, ¹Monash University, Cabrini Hospital, and Emertius Research, Melbourne, Australia, ²K Papp Clinical Research and Probity Medical Research, Waterloo, ON, Canada, ³Rheumatology Department, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí, Universitat Autònoma de Barcelona, Barcelona, Spain, ⁴Vincent Pallotti Hospital, Johannesburg, South Africa, ⁵Abbvie Inc., North Chicago, IL, ⁶AbbVie Inc., North Chicago, ⁷The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Frederiksberg, Denmark
Background/Purpose: Risankizumab (RZB) is a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits interleukin 23 by binding to its p19 subunit. RZB is being investigated…
Abstract Number: 1169 • ACR Convergence 2021
Patient Preferences for Outcome Measures for a Pragmatic Knee Osteoarthritis (OA) Clinical Trial: Results of a Cross-Sectional Patient Survey That Included Racial/Ethnic Minorities
Jasvinder Singh, University of Alabama at Birmingham, Birmingham, AL
Background/Purpose: Many effective treatments are available for knee osteoarthritis (OA), however comparative effectiveness research (CER) of various treatments to each other is limited. One of…
Abstract Number: 1341 • ACR Convergence 2021
Ixekizumab Shows a Pattern of Pain Improvement in Patients with and Without Measurable Inflammation in Psoriatic Arthritis
Kurt de Vlam¹, Gaia Gallo², Philip Mease³, Proton Rahman⁴, Venkatesh Krishnan², David Sandoval², Chen Yen Lin², Danting Zhu², Rebecca Bolce² and Philip Conaghan⁵, ¹University Hospitals Leuven, Leuven, Belgium, ²Eli Lilly and Company, Indianapolis, IN, ³Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, WA, ⁴Department of Medicine, Eastern Health and Memorial University of Newfoundland, St John's, NL, Canada, ⁵Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom
Background/Purpose: The efficacy of ixekizumab (IXE) and adalimumab (ADA) in patients with psoriatic arthritis (PsA) has been previously reported using ACR 50 and Psoriasis Area…
Abstract Number: 1688 • ACR Convergence 2021
Safety Profile of Baricitinib for the Treatment of Rheumatoid Arthritis up to 9.3 Years: An Updated Integrated Safety Analysis
Peter C Taylor¹, Tsutomu Takeuchi², Gerd Burmester³, Patrick DUREZ⁴, Josef Smolen⁵, Walter Deberdt⁶, Jinglin Zhong⁷, Jorge Ross Terres⁶, Natalia Bello⁶ and Kevin Winthrop⁸, ¹University of Oxford, Oxford, United Kingdom, ²Div. Rheumatology, Keio University, Tokyo, Japan, ³Charité University Medicine Berlin, Berlin, Germany, ⁴Pôle de Recherche en Rhumatologie, Institut de Recherche Expérimentale et Clinique, Brussels, Belgium, ⁵Medical University of Vienna, Vienna, Austria, ⁶Eli Lilly and Company, Indianapolis, IN, ⁷IQVIA, Morrisville, NC, ⁸Oregon Health & Science University, Portland, OR
Background/Purpose: Baricitinib (bari) is an oral selective Janus kinase (JAK)1/JAK 2 inhibitor approved for the treatment of adult patients with moderately to severely active rheumatoid…
Abstract Number: 1747 • ACR Convergence 2021
BIIB059 Demonstrates Improvement in Joint Manifestations in Participants with Systemic Lupus Erythematosus in Part a of a Phase 2, Randomized, Double-Blind, Placebo-Controlled Study
Ronald van Vollenhoven¹, Richard Furie², Kenneth Kalunian³, Maria Dall'Era⁴, Victoria Werth⁵, Xiaobi Huang⁶, Hua Carroll⁶, Cristina Musselli⁶, Catherine Barbey⁷ and Nathalie Franchimont⁶, ¹Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam Rheumatology Center, Amsterdam, Netherlands, ²Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, ³UC San Diego, La Jolla, CA, ⁴University of California San Francisco, Corte Madera, CA, ⁵Philadelphia VAMC, Philadelphia, PA, USA and Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, ⁶Biogen, Cambridge, MA, ⁷Biogen, Baar, Switzerland
Background/Purpose: Joint involvement, a frequent manifestation of SLE, can be assessed using global lupus disease activity indices (SLEDAI-2K, BILAG-2004) and/or by assessing joint tenderness and…
Abstract Number: 1806 • ACR Convergence 2021
Designing a Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Investigate the Effect of Guselkumab (TREMFYA®/sup>) Dosing Interval in Psoriatic Arthritis Patients with Inadequate Response to Tumor Necrosis Factor Inhibition
Alexis Ogdie-Beatty¹, Joseph Merola², Philip Mease³, Christopher Ritchlin⁴, Jose Scher⁵, Daphne Chan⁶, Soumya Chakravarty⁷, Wayne Langholff⁸, Olivia Choi⁹, Yevgeniy Krol⁹, Katelyn Rowland⁹ and Alice Gottlieb¹⁰, ¹University of Pennsylvania, Philadelphia, PA, ²Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, ³Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, WA, ⁴Division of Allergy, Immunology, and Rheumatology, School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY, ⁵New York University School of Medicine, New York, NY, ⁶Janssen Scientific Affairs, LLC, Spring House, PA, ⁷Janssen Scientific Affairs, LLC and Drexel University College of Medicine, Horsham, PA, ⁸Janssen Research & Development, LLC, Spring House, PA, ⁹Janssen Scientific Affairs, LLC, Horsham, PA, ¹⁰Icahn School of Medicine at Mount Sinai, New York, NY
Background/Purpose: Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic therapy for patients (pts) with PsA, though a sizeable proportion of pts…
Abstract Number: 0455 • ACR Convergence 2021
Abatacept Reverses Subclinical Arthritis in Patients with High-risk to Develop Rheumatoid Arthritis -results from the Randomized, Placebo-controlled ARIAA Study in RA-at Risk Patients
Juergen Rech¹, Mikkel Ostergaard², Koray Tascilar³, Melanie Hagen⁴, Larissa Valor Mendez⁴, Arnd Kleyer⁴, Gerhard Kroenke⁴, David Simon⁵, Verena Schoenau⁴, Axel Hueber⁶, Stefan Kleinert⁷, Xenofon Baraliakos⁸, Martin Fleck⁹, Andrea Rubbert-Roth¹⁰, Frank Behrens¹¹, David Kofler¹², Martin Feuchtenberger¹³, Michael Zaenker¹⁴, Reinhard Voll¹⁵, Cornelia Glaser¹⁶, Eugen Feist¹⁷, Gerd Burmester¹⁸, Kirsten Karberg¹⁹, Johannes Strunk²⁰, Juan D Cañete²¹, Esperanza Naredo²², Maria Filkova²³, Ladislav Senolt²⁴ and Georg Schett²⁵, ¹Friedrich-Alexander University (FAU) Erlangen-Nuernberg and Universitaetsklinikum Erlangen, Department of Internal Medicine 3 - Rheumatology and Immunology, Germany, Erlangen, Germany, ²Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, and Department of Clinical Medicine, University of Copenhagen, Glostrup, Denmark, ³Friedrich Alexander University of Erlangen Nuremberg, Universitaetsklinikum Erlangen Department of Medicine-3 Rheumatology and Immunology, Erlangen, Germany, ⁴Friedrich-Alexander University (FAU) Erlangen-Nuernberg and Universitaetsklinikum Erlangen, Medical Department 3, Rheumatology & Immunology, Erlangen, Germany, ⁵Department of Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nrnberg, Erlangen, Germany, ⁶sozialstiftung-bamberg.de, Bamberg, Germany, ⁷Praxisgemeinschaft Rheumatologie - Nephrologie (PGRN), Erlangen, Germany, ⁸Rheumazentrum Ruhrgebiet, Herne, Germany, ⁹Asklepios Klinikum Bad Abbach Klinik und Poliklinik für Rheumatologie/ Klin. Immunologie, Bad Abbach, Germany, ¹⁰Kantonspital St Gallen, St.Gallen, Switzerland, ¹¹Rheumatology & Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Fraunhofer Cluster Immune-Mediated Diseases (CIMD), Fraunhofer Cluster Immune-Mediated Diseases (CIMD), Frankfurt/Main, Germany, ¹²Division of Rheumatology and Clinical Immunology, Department I of Internal Medicine; University Hospital Cologne, Cologne, Germany, ¹³MED | BAYERN OST GmbH Fachbereich Rheumatologie, Burghausen, Germany, ¹⁴Immanuel Klinikum Bernau Herzzentrum Brandenburg, Bernau, Germany, ¹⁵Department of Rheumatology and Clinical Immunology, University Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany, ¹⁶Universitätsklinikum Freiburg Klinik für Rheumatologie und Klinische Immunologie, Freiburg, Germany, ¹⁷Helios Department of Rheumatology, Vogelsang-Gommern, Germany, ¹⁸Charité University Medicine Berlin, Berlin, Germany, ¹⁹Praxis für Rheumatologie und Innere Medizin, Berlin, Germany, ²⁰Krankenhaus Porz am Rhein GmbH Rheumaklinik, Köln (Porz), Germany, ²¹Rheumatology Department, Hospital Clinic, Barcelona, Spain, ²²Department of Rheumatology and Joint and Bone Research Unit, Hospital Fundación Jiménez Díaz and Autónoma University, Madrid, Spain, ²³Institute of Rheumatology and Connective Tissue Research Laboratory, Department of Rheumatology of First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic, ²⁴Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, ²⁵Universitätsklinikum Erlangen, Department of Internal Medicine 3 – Rheumatology and Immunology, Erlangen, Germany, Erlangen, Germany
Background/Purpose: Rheumatoid arthritis (RA) has a preclinical phase that is characterized by the presence of antibodies against citrullinated proteins (ACPA), subclinical arthritis and pain. ACPA…
Abstract Number: 1225 • ACR Convergence 2021
Baseline Extracellular Matrix Biomarkers Predict Abatacept Treatment Response in MTX-Naive, ACPA+ Patients with Early RA
Paul Emery¹, Yoshiya Tanaka², Vivian Bykerk³, Clifton Bingham⁴, Tom WJ Huizinga⁵, Gustavo Citera⁶, Chun Wu⁷, Sarah Hu⁷, Peter Schafer⁷, Jinqi Liu⁷, Sean Connolly⁷, Robert Wong⁸ and Roy Fleischmann⁹, ¹Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and Leeds NIHR Biomedical Research Centre, Leeds, United Kingdom, ²University of Occupational and Environmental Health, Kitakyushu, Japan, ³Division of Rheumatology, Hospital for Special Surgery, New York City, NY, ⁴Johns Hopkins University, Baltimore, MD, ⁵Leiden University Medical Center, Leiden, Netherlands, ⁶Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, ⁷Bristol Myers Squibb, Princeton, NJ, ⁸Bristol Myers Squibb, Basking Ridge, NJ, ⁹Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, TX
Background/Purpose: Predictive biomarkers reflecting RA processes and treatment (tmt) efficacy are urgently needed to inform medical options. Markers of bone remodeling and extracellular matrix (ECM)…
Abstract Number: 1345 • ACR Convergence 2021
Long-Term Safety and Effectiveness of Upadacitinib in Patients with Psoriatic Arthritis: Results at 56 Weeks from the SELECT-PsA 1 Study
Iain McInnes¹, Koji Kato², Marina Magrey³, Joseph Merola⁴, Mitsumasa Kishimoto⁵, Cesar Pacheco Tena⁶, Derek Haaland⁷, Liang Chen⁸, Yuanyuan Duan⁹, Patrick Zueger¹⁰, Jianzhong Liu¹¹, Ralph Lippe¹², Aileen Pangan¹¹ and Frank Behrens¹³, ¹University of Glasgow, School of Medicine, Glasgow, Scotland, United Kingdom, ²AbbVie Inc, Shinagawa- Ku, Japan, ³Case Western Reserve University, MetroHealth Medical Center, Cleveland, OH, USA, Richfield, OH, ⁴Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, ⁵Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Yokohama, Japan, ⁶Facultad de Medicina, Universidad Autonoma de Chihuahua, Chihuahua, Mexico, ⁷McMaster University, Hamilton, Ontario and The Waterside Clinic, Oro Medonte, ON, Canada, ⁸AbbVie Inc., North Chicago, ⁹AbbVie Inc, North Chicago, ¹⁰AbbVie Inc., Mettawa, IL, ¹¹AbbVie Inc., North Chicago, IL, ¹²AbbVie Deutschland GmbH & Co. KG, Berlin, Germany, ¹³Rheumatology & Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Fraunhofer Cluster Immune-Mediated Diseases (CIMD), Fraunhofer Cluster Immune-Mediated Diseases (CIMD), Frankfurt/Main, Germany
Background/Purpose: In the SELECT-PsA 1 study, through 24 weeks (wks), once daily upadacitinib 15 mg (UPA15) and 30 mg (UPA30) showed improvements in musculoskeletal symptoms,…

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