Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease

Kaleb D Michaud, Niklas Berglind, Stefan Franzén, Thomas Frisell, Christopher Garwood, Jeffrey D. Greenberg, Meilien Ho, Marie Holmqvist, Laura Horne, Eisuke Inoue, Fredrik Nyberg, Dimitrios A. Pappas, George Reed, Deborah Symmons, Eiichi Tanaka, Trung N. Tran, Suzanne M M Verstappen, Eveline Wesby-van Swaay, Hisashi Yamanaka, Johan Askling

Research output: Contribution to journalArticle

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Abstract

Background We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. Methods Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. Results The combined registry cohorts included 57 251 patients with RA (234 089 person-years)-24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. Conclusions This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes.

Original languageEnglish (US)
JournalAnnals of the Rheumatic Diseases
DOIs
StateAccepted/In press - Feb 8 2016

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Registries
Rheumatoid Arthritis
Rheumatology
Cardiovascular Diseases
Clinical Trials
ametantrone
Safety
Randomized Controlled Trials
Mortality
North America
Research Personnel
Arthritis
Standardization
Sensitivity analysis
Latin America
Quality of Health Care
Sweden
India
Japan
Myocardial Infarction

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease. / Michaud, Kaleb D; Berglind, Niklas; Franzén, Stefan; Frisell, Thomas; Garwood, Christopher; Greenberg, Jeffrey D.; Ho, Meilien; Holmqvist, Marie; Horne, Laura; Inoue, Eisuke; Nyberg, Fredrik; Pappas, Dimitrios A.; Reed, George; Symmons, Deborah; Tanaka, Eiichi; Tran, Trung N.; Verstappen, Suzanne M M; Wesby-van Swaay, Eveline; Yamanaka, Hisashi; Askling, Johan.

In: Annals of the Rheumatic Diseases, 08.02.2016.

Research output: Contribution to journalArticle

Michaud, KD, Berglind, N, Franzén, S, Frisell, T, Garwood, C, Greenberg, JD, Ho, M, Holmqvist, M, Horne, L, Inoue, E, Nyberg, F, Pappas, DA, Reed, G, Symmons, D, Tanaka, E, Tran, TN, Verstappen, SMM, Wesby-van Swaay, E, Yamanaka, H & Askling, J 2016, 'Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease', Annals of the Rheumatic Diseases. https://doi.org/10.1136/annrheumdis-2015-208698
Michaud, Kaleb D ; Berglind, Niklas ; Franzén, Stefan ; Frisell, Thomas ; Garwood, Christopher ; Greenberg, Jeffrey D. ; Ho, Meilien ; Holmqvist, Marie ; Horne, Laura ; Inoue, Eisuke ; Nyberg, Fredrik ; Pappas, Dimitrios A. ; Reed, George ; Symmons, Deborah ; Tanaka, Eiichi ; Tran, Trung N. ; Verstappen, Suzanne M M ; Wesby-van Swaay, Eveline ; Yamanaka, Hisashi ; Askling, Johan. / Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease. In: Annals of the Rheumatic Diseases. 2016.
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AU - Michaud, Kaleb D

AU - Berglind, Niklas

AU - Franzén, Stefan

AU - Frisell, Thomas

AU - Garwood, Christopher

AU - Greenberg, Jeffrey D.

AU - Ho, Meilien

AU - Holmqvist, Marie

AU - Horne, Laura

AU - Inoue, Eisuke

AU - Nyberg, Fredrik

AU - Pappas, Dimitrios A.

AU - Reed, George

AU - Symmons, Deborah

AU - Tanaka, Eiichi

AU - Tran, Trung N.

AU - Verstappen, Suzanne M M

AU - Wesby-van Swaay, Eveline

AU - Yamanaka, Hisashi

AU - Askling, Johan

PY - 2016/2/8

Y1 - 2016/2/8

N2 - Background We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. Methods Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. Results The combined registry cohorts included 57 251 patients with RA (234 089 person-years)-24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. Conclusions This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes.

AB - Background We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. Methods Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. Results The combined registry cohorts included 57 251 patients with RA (234 089 person-years)-24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. Conclusions This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes.

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