Predicting Which Children with Juvenile Idiopathic Arthritis Will Not Attain Early Remission with Conventional Treatment: Results from the ReACCh-Out Cohort

Jaime Guzman; Andrew Henrey; Thomas Loughin; Roberta A Berard; Natalie J Shiff; Roman Jurencak; Adam M Huber; Kiem Oen; Kerstin Gerhold; Brian M Feldman; Rosie Scuccimarri; Kristin Houghton; Gaëlle Chédeville; Kimberly Morishita; Bianca Lang; Paul Dancey; Alan M Rosenberg; Julie Barsalou; Alessandra Bruns; Karen Watanabe Duffy; Susanne Benseler; Ciaran M Duffy; Lori B Tucker; ReACCh-Out Investigators

doi:10.3899/jrheum.180456

Predicting Which Children with Juvenile Idiopathic Arthritis Will Not Attain Early Remission with Conventional Treatment: Results from the ReACCh-Out Cohort

J Rheumatol. 2019 Jun;46(6):628-635. doi: 10.3899/jrheum.180456. Epub 2019 Jan 15.

Authors

Jaime Guzman^{1

2

3}, Andrew Henrey^{4

5

6}, Thomas Loughin^{4

5

6}, Roberta A Berard^{4

5

6}, Natalie J Shiff^{4

5

6}, Roman Jurencak^{4

5

6}, Adam M Huber^{4

5

6}, Kiem Oen^{4

5

6}, Kerstin Gerhold^{4

5

6}, Brian M Feldman^{4

5

6}, Rosie Scuccimarri^{4

5

6}, Kristin Houghton^{4

5

6}, Gaëlle Chédeville^{4

5

6}, Kimberly Morishita^{4

5

6}, Bianca Lang^{4

5

6}, Paul Dancey^{4

5

6}, Alan M Rosenberg^{4

5

6}, Julie Barsalou^{4

5

6}, Alessandra Bruns^{4

5

6}, Karen Watanabe Duffy^{4

5

6}, Susanne Benseler^{4

5

6}, Ciaran M Duffy^{4

5

6}, Lori B Tucker^{4

5

6}; ReACCh-Out Investigators

Affiliations

¹ From the British Columbia Children's Hospital and the University of British Columbia, Vancouver; Simon Fraser University, Burnaby, British Columbia; London Health Sciences Centre and Western University, London; Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario; IWK Health Centre and Dalhousie University, Halifax, Nova Scotia; Winnipeg Children's Hospital and University of Manitoba, Winnipeg, Manitoba; Hospital for Sick Children and University of Toronto, Toronto, Ontario; McGill University Health Centre and McGill University, Montreal, Quebec; Janeway Children's Health and Rehabilitation Centre and Memorial University, Saint John's, Newfoundland and Labrador; Royal University Hospital and University of Saskatchewan, Saskatoon, Saskatchewan; Centre Hospitalier Universitaire Sainte-Justine and Université de Montréal, Montreal; Centre Hospitalier Universitaire de Sherbrooke and Université de Sherbrooke, Sherbrooke, Quebec; Alberta Children's Hospital and University of Calgary, Alberta, Canada; Shands Children's Hospital and University of Florida, Gainesville, Florida, USA. jguzman@cw.bc.ca.
² The Research in Arthritis in Canadian Children Emphasizing Outcomes cohort was funded by a New Emerging Team research grant from the Canadian Institutes of Health Research (funding reference QNT 69301). Dr. Guzman was funded by a Clinical Investigator Award from the BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada. jguzman@cw.bc.ca.
³ J. Guzman, MD, MSc, Department of Pediatrics, University of British Columbia; A. Henrey, PhD, Department of Statistics and Actuarial Sciences, Simon Fraser University; T. Loughin, PhD, Department of Statistics and Actuarial Sciences, Simon Fraser University; R.A. Berard, MD, MSc, Department of Pediatrics, Western University; N.J. Shiff, MD, MHSc, Department of Pediatrics, University of Florida; R. Jurencak, MD, Department of Pediatrics, University of Ottawa; A.M. Huber, MD, MSc, Department of Pediatrics, Dalhousie University; K. Oen, MD, Department of Pediatrics and Child Health, University of Manitoba; K. Gerhold, MD, Department of Pediatrics and Child Health, University of Manitoba; B.M. Feldman, MD, MSc, Department of Pediatrics and Dalla Lana School of Public Health, University of Toronto; R. Scuccimarri, MD, Research Institute of the McGill University Health Centre; K. Houghton, MD, MSc, Department of Pediatrics, University of British Columbia; G. Chédeville, MD, Research Institute of the McGill University Health Centre; K. Morishita, MD, MHSc, Department of Pediatrics, University of British Columbia; B. Lang, MD, Department of Pediatrics, Dalhousie University; P. Dancey, MD, Department of Pediatrics, Memorial University; A.M. Rosenberg, MD, Department of Pediatrics, University of Saskatchewan; J. Barsalou, MD, MSc, Centre Hospitalier Universitaire Sainte-Justine and Université de Montréal; A. Bruns, MD, MSc, Centre Hospitalier Universitaire de Sherbrooke and Université de Sherbrooke; K. Watanabe Duffy, MD, Department of Pediatrics, University of Ottawa; S. Benseler, MD, PhD, Department of Pediatrics, University of Calgary; C.M. Duffy, MB, MSc, Department of Pediatrics, University of Ottawa; L.B. Tucker, MD, Department of Pediatrics, University of British Columbia. jguzman@cw.bc.ca.
⁴ From the British Columbia Children's Hospital and the University of British Columbia, Vancouver; Simon Fraser University, Burnaby, British Columbia; London Health Sciences Centre and Western University, London; Children's Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario; IWK Health Centre and Dalhousie University, Halifax, Nova Scotia; Winnipeg Children's Hospital and University of Manitoba, Winnipeg, Manitoba; Hospital for Sick Children and University of Toronto, Toronto, Ontario; McGill University Health Centre and McGill University, Montreal, Quebec; Janeway Children's Health and Rehabilitation Centre and Memorial University, Saint John's, Newfoundland and Labrador; Royal University Hospital and University of Saskatchewan, Saskatoon, Saskatchewan; Centre Hospitalier Universitaire Sainte-Justine and Université de Montréal, Montreal; Centre Hospitalier Universitaire de Sherbrooke and Université de Sherbrooke, Sherbrooke, Quebec; Alberta Children's Hospital and University of Calgary, Alberta, Canada; Shands Children's Hospital and University of Florida, Gainesville, Florida, USA.
⁵ The Research in Arthritis in Canadian Children Emphasizing Outcomes cohort was funded by a New Emerging Team research grant from the Canadian Institutes of Health Research (funding reference QNT 69301). Dr. Guzman was funded by a Clinical Investigator Award from the BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
⁶ J. Guzman, MD, MSc, Department of Pediatrics, University of British Columbia; A. Henrey, PhD, Department of Statistics and Actuarial Sciences, Simon Fraser University; T. Loughin, PhD, Department of Statistics and Actuarial Sciences, Simon Fraser University; R.A. Berard, MD, MSc, Department of Pediatrics, Western University; N.J. Shiff, MD, MHSc, Department of Pediatrics, University of Florida; R. Jurencak, MD, Department of Pediatrics, University of Ottawa; A.M. Huber, MD, MSc, Department of Pediatrics, Dalhousie University; K. Oen, MD, Department of Pediatrics and Child Health, University of Manitoba; K. Gerhold, MD, Department of Pediatrics and Child Health, University of Manitoba; B.M. Feldman, MD, MSc, Department of Pediatrics and Dalla Lana School of Public Health, University of Toronto; R. Scuccimarri, MD, Research Institute of the McGill University Health Centre; K. Houghton, MD, MSc, Department of Pediatrics, University of British Columbia; G. Chédeville, MD, Research Institute of the McGill University Health Centre; K. Morishita, MD, MHSc, Department of Pediatrics, University of British Columbia; B. Lang, MD, Department of Pediatrics, Dalhousie University; P. Dancey, MD, Department of Pediatrics, Memorial University; A.M. Rosenberg, MD, Department of Pediatrics, University of Saskatchewan; J. Barsalou, MD, MSc, Centre Hospitalier Universitaire Sainte-Justine and Université de Montréal; A. Bruns, MD, MSc, Centre Hospitalier Universitaire de Sherbrooke and Université de Sherbrooke; K. Watanabe Duffy, MD, Department of Pediatrics, University of Ottawa; S. Benseler, MD, PhD, Department of Pediatrics, University of Calgary; C.M. Duffy, MB, MSc, Department of Pediatrics, University of Ottawa; L.B. Tucker, MD, Department of Pediatrics, University of British Columbia.

PMID: 30647178
DOI: 10.3899/jrheum.180456

Abstract

Objective: To estimate the probability of early remission with conventional treatment for each child with juvenile idiopathic arthritis (JIA). Children with a low chance of remission may be candidates for initial treatment with biologics or triple disease-modifying antirheumatic drugs (DMARD).

Methods: We used data from 1074 subjects in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort. The predicted outcome was clinically inactive disease for ≥ 6 months starting within 1 year of JIA diagnosis in patients who did not receive early biologic agents or triple DMARD. Models were developed in 200 random splits of 75% of the cohort and tested on the remaining 25% of subjects, calculating expected and observed frequencies of remission and c-index values.

Results: Our best Cox logistic model combining 18 clinical variables a median of 2 days after diagnosis had a c-index of 0.69 (95% CI 0.67-0.71), better than using JIA category alone (0.59, 95% CI 0.56-0.63). Children in the lowest probability decile had a 20% chance of remission and 21% attained remission; children in the highest decile had a 69% chance of remission and 73% attained remission. Compared to 5% of subjects identified by JIA category alone, the model identified 14% of subjects as low chance of remission (probability < 0.25), of whom 77% failed to attain remission.

Conclusion: Although the model did not meet our a priori performance threshold (c-index > 0.70), it identified 3 times more subjects with low chance of remission than did JIA category alone, and it may serve as a benchmark for assessing value added by future laboratory/imaging biomarkers.

Keywords: COHORT STUDIES; JUVENILE IDIOPATHIC ARTHRITIS; PREDICTION; PROGNOSIS; RISK STRATIFICATION.

MeSH terms

Adolescent
Antirheumatic Agents / therapeutic use*
Arthritis, Juvenile / diagnosis
Arthritis, Juvenile / drug therapy*
Biological Products / therapeutic use*
Child
Child, Preschool
Female
Humans
Logistic Models
Male
Prognosis
Remission Induction
Severity of Illness Index
Treatment Failure
Treatment Outcome

Substances

Antirheumatic Agents
Biological Products