Novel methodology to discern predictors of remission and patterns of disease activity over time using rheumatoid arthritis clinical trials data

被引：4

作者：

Tom, Brian D. M. ^{[1
]}

Symmons, Deborah ^{[2
,3
,31
]}

Brockbank, Sarah ^{[4
]}

Carini, Claudio ^{[5
,59
]}

Cope, Andrew P. ^{[6
]}

Ehrenstein, Michael R. ^{[7
]}

Fisher, Benjamin A. ^{[8
,9
,10
]}

Goodyear, Carl S. ^{[11
]}

Gozzard, Neil ^{[12
]}

Harris, Ray ^{[13
]}

Hicks, Kirsty ^{[14
,54
]}

Hollis, Sally ^{[15
,46
,47
]}

Hughes-Morley, Adwoa ^{[2
,3
,31
,32
]}

Isaacs, John ^{[4
,16
,17
]}

Kola, Blerina ^{[18
,58
]}

McInnes, Iain B. ^{[11
]}

Mela, Christopher M. ^{[19
]}

Parker, Gerry ^{[12
]}

Pedersen, Ayako Wakatsuki ^{[4
]}

Ponchel, Frederique ^{[20
]}

Sabin, Tony ^{[21
,40
,42
]}

Scott, David L. ^{[6
]}

Scott, Ian C. ^{[6
]}

Sleeman, Matthew A. ^{[22
]}

Taylor, Peter C. ^{[23
,24
]}

Tsuji, Wayne ^{[25
,40
,41
]}

Zhong, Yujie ^{[1
]}

Hilkens, Catharien ^{[4
]}

Anderson, Amy ^{[4
]}

Stocks, Philip ^{[4
]}

Lendrem, Dennis ^{[4
]}

Tarn, Jessica ^{[4
]}

Smith, Graham ^{[4
]}

Allen, Ben ^{[4
]}

Casement, John ^{[4
]}

Diboll, Julie ^{[4
]}

Harry, Rachel ^{[4
]}

Simpson, Gemma ^{[6
]}

Toward, Ruth ^{[6
]}

Noble, Hayley ^{[6
]}

Parke, Angela ^{[6
]}

Wu, Wing ^{[6
]}

Clarke, Fiona ^{[6
]}

Galloway, James ^{[6
]}

Lempp, Heidi ^{[6
]}

Ibrahim, Fowzia ^{[6
]}

Schwank, Samana ^{[6
]}

Molyneux, Gemma ^{[6
]}

Lazarov, Tomi ^{[26
,27
]}

Geissmann, Frederic ^{[26
,27
]}

机构：

[1] Univ Cambridge, MRC Biostat Unit, Cambridge, England

[2] Univ Manchester, Ctr Musculoskeletal Res, Sch Biol Sci, Fac Biol Med & Hlth, Manchester, Lancs, England

[3] Manchester Acad Hlth Sci Ctr, Cent Manchester NHS Fdn Trust, NIHR Manchester Musculoskeletal Biomed Res Unit, Manchester, Lancs, England

[4] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England

[5] Pfizer Inc, Inflammat & Immunol RU, Worldwide Res & Dev, New York, NY USA

[6] Kings Coll London, Acad Dept Rheumatol, Fac Life Sci, Div Immunol Infect & Inflammatory Dis, London, England

[7] UCL, Div Med, London, England

[8] Univ Birmingham, Birmingham, W Midlands, England

[9] Univ Hosp Birmingham NHS Trust, Birmingham, W Midlands, England

[10] Sandwell & West Birmingham Hosp NHS Trust, Birmingham, W Midlands, England

[11] Univ Glasgow, Coll Med Vet & Life Sci, Inst Infect Immun & Inflammat, Glasgow, Lanark, Scotland

[12] UCB Pharma, Brussels, Belgium

[13] Eisai Ltd, European Knowledge Ctr, Mosquito Way, Hatfield, Herts, England

[14] GlaxoSmithKline, Pharma R&D, Stat & Programming, Brentwood, Essex, England

[15] AstraZeneca, Global Med Dev, Biometr & Informat Sci, Cambridge, MA USA

[16] Newcastle Univ, Inst Cellular Med, NIHR Newcastle Biomed Res Ctr Ageing & Long Term, Newcastle Upon Tyne, Tyne & Wear, England

[17] Newcastle Upon Tyne Hosp NHS Fdn Trust, Musculoskeletal Unit, Newcastle Upon Tyne, Tyne & Wear, England

[18] Pfizer Ltd, Med Director Inflammat, Walton Hill, Surrey KT20 7NS, England

[19] Roche Prod Ltd, 6 Falcon Way,Shire Pk, Welwyn Garden City AL7 1TW, Herts, England

[20] Univ Leeds, Leeds Inst Rheumat & Musculoskeletal Med, Leeds, W Yorkshire, England

[21] Amgen Inc, Med Sci Biostat Grp, Thousand Oaks, CA USA

[22] MedImmune Ltd, Resp Inflammat & Autoimmun, Cambridge, England

[23] Univ Oxford, Musculoskeletal Sci, Botnar Res Ctr, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Windmill Rd, Oxford OX3 7LD, England

[24] Univ Oxford, Clin Sci, Botnar Res Ctr, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Windmill Rd, Oxford OX3 7LD, England

[25] Amgen Inc, Early Dev, Med Sci, Thousand Oaks, CA USA

[26] Kings Coll London, Dept Immunobiol, Div Immunol Infect & Inflammatory Dis, Fac Life Sci, London, England

[27] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[28] Univ Glasgow, Gartnavel Gen Hosp, Glasgow, Lanark, Scotland

[29] Queen Mary Univ London, Ctr Expt Med & Rheumatol, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England

[30] Queen Mary Univ London, Ctr Translat Bioinformat, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England

[31] Manchester Univ Fdn Trust, NIHR Manchester Biomed Res Ctr, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England

[32] Univ York, York Trials Unit, Dept Hlth Sci, Fac Sci, Heslington YO10 5DD, England

[33] Abbvie Ltd, Med Affairs, Maidenhead SL6 4UB, Berks, England

[34] AbbVie Biores Ctr Inc, Translat Immunol, Worcester, MA USA

[35] AbbVie Biores Ctr Inc, Immunol Clin Dev, Worcester, MA USA

[36] AbbVie Biores Ctr Inc, Immunol Pharmacol, Worcester, MA USA

[37] AbbVie Biores Ctr Inc, Informat Res, Worcester, MA USA

[38] AbbVie Biores Ctr Inc, Global Biol, Worcester, MA USA

[39] AbbVie Biores Ctr Inc, Exploratory Stat, Worcester, MA USA

[40] Amgen Inc, Thousand Oaks, CA 91320 USA

[41] Amgen Inc, Cascadia Drug Dev Grp, Thousand Oaks, CA 91320 USA

[42] AstraZeneca, Biostat & Informat Practice Dept, Cambridge, England

[43] Regeneron Pharmaceut, Dept Immunol & Inflammat, Tarrytown, NY USA

[44] MedImmune Ltd, Biostat, Cambridge, England

[45] Novartis Pharmaceut UK Ltd, Camberley GU16 7SR, Surrey, England

[46] Astrazeneca, Global Med Dev, Cambridge, England

[47] Phastar, Statist Consulting, London, England

[48] BioSci Consulting, Maasmechelen, Belgium

[49] Janssen Pharmaceut NV, B-2340 Beerse, Belgium

[50] Janssen Res & Dev LLC, Spring House, PA USA

来源：

RMD OPEN | 2018年 / 4卷 / 02期

基金：

英国医学研究理事会;

关键词：

DRUG-FREE REMISSION; TRAJECTORIES; ASSOCIATION; VALIDATION; DEPRESSION; SYMPTOMS; CRITERIA; OUTCOMES; ANXIETY;

D O I：

10.1136/rmdopen-2018-000721

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives To identify predictors of remission and disease activity patterns in patients with rheumatoid arthritis (RA) using individual participant data (IPD) from clinical trials. Methods Phase II and III clinical trials completed between 2002 and 2012 were identified by systematic literature review and contact with UK market authorisation holders. Anonymised baseline and follow-up IPD from non-biological arms were amalgamated. Multiple imputation was used to handle missing outcome and covariate information. Random effects logistic regression was used to identify predictors of remission, measured by the Disease Activity Score 28 (DAS28) at 6 months. Novel latent class mixed models characterised DAS28 over time. Results IPD of 3290 participants from 18 trials were included. Of these participants, 92% received methotrexate (MTX). Remission rates were estimated at 8.4%(95% CI 7.4%to9.5%) overall, 17%(95% CI 14.8%to19.4%) for MTX-naive patients with early RA and 3.2% (95% CI 2.4% to 4.3%) for those with prior MTX exposure at entry. In prior MTX-exposed patients, lower baseline DAS28 and MTX reinitiation were associated with remission. In MTX-naive patients, being young, white, male, with better functional and mental health, lower baseline DAS28 and receiving concomitant glucocorticoids were associated with remission. Three DAS28 trajectory subpopulations were identified in MTX-naive and MTX-exposed patients. A number of variables were associated with subpopulation membership and DAS28 levels within subpopulations. Conclusions Predictors of remission differed between MTX-naive and prior MTX-exposed patients at entry. Latent class mixed models supported differential non-biological therapy response, with three distinct trajectories observed in both MTX-naive and MTX-exposed patients. Findings should be useful when designing future RA trials and interpreting results of biomarker studies.

引用

页数：12

共 38 条

[1] THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS [J].

ARNETT, FC ;

EDWORTHY, SM ;

BLOCH, DA ;

MCSHANE, DJ ;

FRIES, JF ;

COOPER, NS ;

HEALEY, LA ;

KAPLAN, SR ;

LIANG, MH ;

LUTHRA, HS ;

MEDSGER, TA ;

MITCHELL, DM ;

NEUSTADT, DH ;

PINALS, RS ;

SCHALLER, JG ;

SHARP, JT ;

WILDER, RL ;

HUNDER, GG .

ARTHRITIS AND RHEUMATISM, 1988, 31 (03) :315-324

[2]

Bates D., 2020, lme4: linear mixed-effects models using Eigen and S4. R package version 1.1-7, V1, P1, DOI DOI 10.18637/JSS.V067.I01

[3] Prediction of Remission in a French Early Arthritis Cohort by RAPID3 and other Core Data Set Measures, but Not by the Absence of Rheumatoid Factor, Anticitrullinated Protein Antibodies, or Radiographic Erosions [J].

Castrejon, Isabel ;

Dougados, Maxime ;

Combe, Bernard ;

Fautrel, Bruno ;

Guillemin, Francis ;

Pincus, Theodore .

JOURNAL OF RHEUMATOLOGY, 2016, 43 (07) :1285-1291

[4] An entropy criterion for assessing the number of clusters in a mixture model [J].

Celeux, G ;

Soromenho, G .

JOURNAL OF CLASSIFICATION, 1996, 13 (02) :195-212

[5] The RA-MAP Consortium: a working model for academia-industry collaboration (vol 14, pg 53, 2018) [J].

Cope, Andrew P. ;

Barnes, Michael R. ;

Belson, Alexandra ;

Binks, Michael ;

Brockbank, Sarah ;

Bonachela-Capdevila, Francisco ;

Carini, Claudio ;

Fisher, Benjamin A. ;

Goodyear, Carl S. ;

Emery, Paul ;

Ehrenstein, Michael R. ;

Gozzard, Neil ;

Harris, Ray ;

Hollis, Sally ;

Keidel, Sarah ;

Levesque, Marc ;

Lindholm, Catharina ;

McDermott, Michael F. ;

McInnes, Iain B. ;

Mela, Christopher M. ;

Parker, Gerry ;

Read, Simon ;

Pedersen, Ayako Wakatsuki ;

Ponchel, Frederique ;

Porter, Duncan ;

Rao, Ravi ;

Rowe, Anthony ;

Schulz-Knappe, Peter ;

Sleeman, Matthew A. ;

Symmons, Deborah ;

Taylor, Peter C. ;

Tom, Brian ;

Tsuji, Wayne ;

Verbeeck, Denny ;

Isaacs, John D. .

NATURE REVIEWS RHEUMATOLOGY, 2018, 14 (02) :119-119

[6] Sex:: a major predictor of remission in early rheumatoid arthritis? [J].

Forslind, K. ;

Hafstrom, I. ;

Ahlmen, M. ;

Svensson, B. .

ANNALS OF THE RHEUMATIC DISEASES, 2007, 66 (01) :46-52

[7] Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the ARA preliminary remission criteria [J].

Fransen, J ;

Creemers, MCW ;

Van Riel, PLCM .

RHEUMATOLOGY, 2004, 43 (10) :1252-1255

[8] Greater Likelihood of Remission in Rheumatoid Arthritis Patients Treated Earlier in the Disease Course: Results From the Consortium of Rheumatology Researchers of North America Registry [J].

Furst, Daniel E. ;

Pangan, Aileen L. ;

Harrold, Leslie R. ;

Chang, Hong ;

Reed, George ;

Kremer, Joel M. ;

Greenberg, Jeffrey D. .

ARTHRITIS CARE & RESEARCH, 2011, 63 (06) :856-864

[9] Psychological state is related to the remission of the Boolean-based definition of patient global assessment in patients with rheumatoid arthritis [J].

Fusama, Mie ;

Miura, Yasushi ;

Yukioka, Kumiko ;

Kuroiwa, Takanori ;

Yukioka, Chikako ;

Inoue, Miyako ;

Nakanishi, Tae ;

Murata, Norikazu ;

Takai, Noriko ;

Higashi, Kayoko ;

Kuritani, Taro ;

Maeda, Keiji ;

Sano, Hajime ;

Yukioka, Masao ;

Nakahara, Hideko .

MODERN RHEUMATOLOGY, 2015, 25 (05) :679-682

[10] Racial and Ethnic Disparities in Disease Activity in Patients with Rheumatoid Arthritis [J].

Greenberg, Jeffrey D. ;

Spruill, Tanya M. ;

Shan, Ying ;

Reed, George ;

Kremer, Joel M. ;

Potter, Jeffrey ;

Yazici, Yusuf ;

Ogedegbe, Gbenga ;

Harrold, Leslie R. .

AMERICAN JOURNAL OF MEDICINE, 2013, 126 (12) :1089-1098

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