Development of Preliminary Remission Criteria for Gout Using Delphi and 1000Minds Consensus Exercises
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Arthritis Care & Research Vol. 68, No. 5, May 2016, pp 667–672 DOI 10.1002/acr.22741 VC 2016, American College of Rheumatology ORIGINAL ARTICLE Development of Preliminary Remission Criteria for Gout Using Delphi and 1000Minds Consensus Exercises 1 2 3 4 HUGH DE LAUTOUR, WILLIAM J. TAYLOR, ADE ADEBAJO, RIEKE ALTEN, RUBEN BURGOS-VARGAS,5 PETER CHAPMAN,6 MARCO A. CIMMINO,7 8 9 10 GERALDO DA ROCHA CASTELAR PINHEIRO, RIC DAY, LESLIE R. HARROLD, PHILIP HELLIWELL,11 MATTHIJS JANSSEN,12 GAIL KERR,13 ARTHUR KAVANAUGH,14 DINESH KHANNA,15 PUJA P. KHANNA,16 CHINGTSAI LIN,17 WORAWIT LOUTHRENOO,18 GERALDINE MCCARTHY,19 JANITZIA VAZQUEZ-MELLADO,5 TED R. MIKULS,20 TUHINA NEOGI,21 ALEXIS OGDIE,22 FERNANDO PEREZ-RUIZ,23 NAOMI SCHLESINGER,24 H. RALPH SCHUMACHER,22 CARLO A. SCIRE, 25 JASVINDER A. SINGH,26 FRANCISCA SIVERA,27 OLE SLOT,28 LISA K. STAMP,29 30 31 32 33 ANNE-KATHRIN TAUSCHE, ROBERT TERKELTAUB, TILL UHLIG, MART VAN DE LAAR, 34 35 36 37 DOUGLAS WHITE, HISASHI YAMANAKA, XUEJUN ZENG, AND NICOLA DALBETH Objective. To establish consensus for potential remission criteria to use in clinical trials of gout. Methods. Experts (n 5 88) in gout from multiple countries were invited to participate in a web-based questionnaire study. Three rounds of Delphi consensus exercises were conducted using SurveyMonkey, followed by a discrete- choice experiment using 1000Minds software. The exercises focused on identifying domains, definitions for each domain, and the timeframe over which remission should be defined. Results. There were 49 respondents (56% response) to the initial survey, with subsequent response rates ranging from 57% to 90%. Consensus was reached for the inclusion of serum urate (98% agreement), flares (96%), tophi (92%), pain (83%), and patient global assessment of disease activity (93%) as measurement domains in remission criteria. Consen- sus was also reached for domain definitions, including serum urate (<0.36 mm), pain (<2 on a 10-point scale), and patient global assessment (<2 on a 10-point scale), all of which should be measured at least twice over a set time inter- val. Consensus was not achieved in the Delphi exercise for the timeframe for remission, with equal responses for 6 months (51%) and 1 year (49%). In the discrete-choice experiment, there was a preference towards 12 months as a timeframe for remission. Conclusion. These consensus exercises have identified domains and provisional definitions for gout remission criteria. Based on the results of these exercises, preliminary remission criteria are proposed with domains of serum urate, acute flares, tophus, pain, and patient global assessment. These preliminary criteria now require testing in clinical data sets. INTRODUCTION uncontrolled hyperuricemia, flares become more frequent and severe, with eventual development of tophi, joint Gout is a chronic disease of monosodium urate crystal damage, and chronic gouty arthropathy. The cornerstone (MSU) deposition (1). Early disease is characterized by of effective gout management is long-term urate lowering intermittent flares of an acute inflammatory arthritis. With therapy (ULT). Over time, this therapy can lead to dissolu- 1Hugh de Lautour, MBChB: Auckland District Health 2 Pinheiro, MD: Pedro Ernesto University Hospital, Rio de Board, Auckland, New Zealand; William J. Taylor, PhD: 9 3 Janeiro, Brazil; Ric Day, MD: University of New South Wales University of Otago, Wellington, New Zealand; Ade Adebajo, 10 MD: University of Sheffield, Sheffield, UK; 4Rieke Alten, MD: and St Vincent’s Hospital, Sydney, Australia; Leslie R. Harrold, MD: University of Massachusetts Medical School, Schlosspark-Klinik, Charite, University Medicine Berlin, 11 Berlin, Germany; 5Ruben Burgos-Vargas, MD, Janitzia Worcester, and Corrona, LLC, Southborough; Philip Helliwell, MD: Leeds Institute of Rheumatic and Vazquez-Mellado, MD: Hospital General de Mexico, Mexico 12 6 Musculoskeletal Medicine, Leeds, UK; Matthijs Janssen, City, Mexico; Peter Chapman, FRACP: Christchurch Hospital, 13 Christchurch, New Zealand; 7Marco A. Cimmino, MD: Uni- MD: Rijnstate Hospital, Arnhem, The Netherlands; Gail versita di Genova, Genova, Italy; 8Geraldo da Rocha Castelar Kerr, MD: Veterans Affairs Medical Center, Georgetown and 667 AQ3 4 668 de Lautour et al outcome measures for clinical trials in gout became appar- Significance & Innovations ent (5). For more than a decade, the Outcome Measures in There are currently no agreed upon remission Rheumatology (OMERACT) group has worked on the criteria for gout. These consensus exercises have development of valid outcome measures for use in gout identified domains and provisional definitions clinical trials. This work has led to endorsement of for gout remission criteria. domains for both acute and chronic gout studies (and Based on the results of these exercises, prelimi- endorsement of instruments for most of the individual nary remission criteria are proposed, with domains) (6–10). Whether these individual domains can domains of serum urate, acute flares, tophus, be usefully captured within a single outcome measure pain, and patient global assessment. Remission remains uncertain, however, either as a composite score requires all of the criteria to be fulfilled. or response criteria (11,12). Remission can be defined as the absence of signs and There remains an important lack of consensus symptoms attributable to a disease, when the symptoms for the timeframe over which these domains and signs can return in the future, with the understand- should indicate absence of disease activity in ing that the momentary absence of signs and symptoms, order to define remission status. These prelimi- particularly in conditions characterized by intermittent nary criteria now require testing in clinical data symptoms, does not equate to remission (13). With the sets and will be used as part of further consen- availability of highly effective ULT, remission in gout sus exercises to reach formal remission criteria should be possible and, indeed, a goal of therapy. Impor- for gout. tantly, remission in gout should represent more than simply resolution of gout flare, since the natural history of gout includes periods without symptoms and would not ordinarily be considered to represent periods of tion of MSU crystals, suppression of gout flares, and remission. To date, there are no remission criteria estab- regression of tophi (2–4). lished for gout (5). The importance of remission or inac- With the development of new ULT and antiinflamma- tory agents for management of gout, the lack of validated Union Medical College, Beijing, China; 37Nicola Dalbeth, MD: University of Auckland and Auckland District Health Board, Howard University Hospitals, Washington, DC; 14Arthur Auckland, New Zealand. Kavanaugh, MD: University of California School of Medicine, Dr. da Rocha Castelar Pinheiro has received consulting San Diego; 15Dinesh Khanna, MD: University of Michigan, fees from AstraZeneca (less than $10,000). Dr. Harrold has Ann Arbor; 16Puja P. Khanna, MD: University of Michigan received grants from AstraZeneca, Takeda, and Pfizer and Ann Arbor VA Medical Center, Ann Arbor; 17Chingtsai (less than $10,000 each). Dr. Kerr has received a grant Lin, MD: Taichung Veteran’s General Hospital, Taichung, from AstraZeneca (more than $10,000). Dr. D. Khanna has Taiwan; 18Worawit Louthrenoo, MD: Faculty of Medicine, received consulting fees and/or grants from AstraZeneca Chiang Mai University, Chiang Mai, Thailand; 19Geraldine and Takeda (less than $10,000 each). Dr. P. Khanna is the McCarthy, MD: Mater Misericordiae University Hospital and Principal Investigator on a study funded by AstraZeneca University College, Dublin, Ireland; 20Ted R. Mikuls, MD: and on studies funded by Ardea and Crealta. Dr. Nebraska–Western Iowa Health Care System and University Schlesinger has received grants and/or is on the advisory of Nebraska Medical Center, Omaha; 21Tuhina Neogi, PhD: board for Takeda, AstraZeneca, Novartis, and Sobi (less Boston University School of Medicine, Boston, Massachu- than $10,000 each), and has received speaking fees from setts; 22Alexis Ogdie, MD, H. Ralph Schumacher, MD: Univer- Novartis and Takeda (less than $10,000 each). Dr. Singh sity of Pennsylvania, Philadelphia; 23Fernando Perez-Ruiz, has received grants from Takeda (more than $10,000) and MD: Hospital Universitario Cruces, OSI-EEC, and Biocruces Savient (less than $10,000) and consulting fees from Health Research Institute, Biscay, Spain; 24Naomi Schlesinger, Savient, Takeda, Regeneron, Merz, Bioiberica, Crealta, MD: Rutgers University Robert Wood Johnson Medical and Allergan (less than $10,000 each), and is the Principal School, New Brunswick, New Jersey; 25Carlo A. Scire`,MD: Investigator on a study funded by Horizon through a grant IRCCS Policlinico San Matteo Foundation, University of to DINORA (less than $10,000). Dr. Stamp has received Pavia, Pavia, Italy; 26Jasvinder A. Singh, MBBS, MPH: Uni- speaking and/or consulting fees from AstraZeneca (less versity of Alabama at Birmingham and the Birmingham VA than $10,000). Dr. Tausche has received speaking fees Medical Center, Birmingham; 27Francisca Sivera, MD: Hospi- and/or honoraria from Berlin Chemie Menarini, Novartis, tal General Universitario Elda, Elda, Spain; 28Ole Slot, MD: Ardea Bioscience, AstraZeneca, and Savient (less than Copenhagen University Hospital Glostrup, Glostrup, Den- $10,000 each). Dr. Terkeltaub has received consulting fees mark; 29Lisa K. Stamp, PhD: University of Otago, Christ- from Ardea, AstraZeneca, Sobi, Takeda, Relburn, and church, New