Clinical and associated inflammatory biomarker features predictive of short-term outcomes in non-systemic juvenile idiopathic arthritis

Author:

Rezaei Elham1,Hogan Daniel2,Trost Brett2,Kusalik Anthony J2,Boire Gilles3,Cabral David A4,Campillo Sarah5,Chédeville Gaëlle5,Chetaille Anne-Laure6,Dancey Paul7,Duffy Ciaran8,Watanabe Duffy Karen8,Gordon John9,Guzman Jaime4,Houghton Kristin4,Huber Adam M10,Jurencak Roman8,Lang Bianca10,Morishita Kimberly4,Oen Kiem G11,Petty Ross E4,Ramsey Suzanne E10,Scuccimarri Rosie5,Spiegel Lynn12,Stringer Elizabeth10,Taylor-Gjevre Regina M9ORCID,Tse Shirley M L12,Tucker Lori B4,Turvey Stuart E4,Tupper Susan1,Yeung Rae S M12,Benseler Susanne13ORCID,Ellsworth Janet14,Guillet Chantal15,Karananayake Chandima9,Muhajarine Nazeem16,Roth Johannes8,Schneider Rayfel12,Rosenberg Alan M1

Affiliation:

1. Department of PediatricsUniversity of Saskatchewan, Saskatoon, SK, Canada

2. Department of Computer Sciences, University of Saskatchewan, Saskatoon, SKCanada

3. Département de Médecine, Université de Sherbrooke, Sherbrooke, QCCanada

4. Department of Pediatrics, British Columbia Children’s Hospital, Vancouver, BCCanada

5. Department of Pediatrics, McGill University Health Center, Montreal, QCCanada

6. Département de Médecine le, Centre Hospitalier Universitaire de Quebec, Quebec, QCCanada

7. Department of Pediatrics, Janeway Children’s Health and Rehabilitation Centre, St John’s, NLCanada

8. Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, ONCanada

9. Department of Medicine, University of Saskatchewan, Saskatoon, SKCanada

10. Department of Pediatrics, IWK Health Centre and Dalhousie University, Halifax, NSCanada

11. Department of Pediatrics, University of Manitoba, Winnipeg, MBCanada

12. Department of Paediatrics, University of Toronto and the Hospital for Sick Children, Toronto, ONCanada

13. Department of Pediatrics, University of Calgary, Calgary, ABCanada

14. Department of Pediatrics, University of Alberta, Edmonton, ABCanada

15. Department of Pediatrics, Hôpital Fleurimont (CHUS), Quebec, QCCanada

16. Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, SK, Canada

Abstract

Abstract Objective To identify early predictors of disease activity at 18 months in JIA using clinical and biomarker profiling. Methods Clinical and biomarker data were collected at JIA diagnosis in a prospective longitudinal inception cohort of 82 children with non-systemic JIA, and their ability to predict an active joint count of 0, a physician global assessment of disease activity of ≤1 cm, and inactive disease by Wallace 2004 criteria 18 months later was assessed. Correlation-based feature selection and ReliefF were used to shortlist predictors and random forest models were trained to predict outcomes. Results From the original 112 features, 13 effectively predicted 18-month outcomes. They included age, number of active/effused joints, wrist, ankle and/or knee involvement, ESR, ANA positivity and plasma levels of five inflammatory biomarkers (IL-10, IL-17, IL-12p70, soluble low-density lipoprotein receptor-related protein 1 and vitamin D), at enrolment. The clinical plus biomarker panel predicted active joint count = 0, physician global assessment ≤ 1, and inactive disease after 18 months with 0.79, 0.80 and 0.83 accuracy and 0.84, 0.83, 0.88 area under the curve, respectively. Using clinical features alone resulted in 0.75, 0.72 and 0.80 accuracy, and area under the curve values of 0.81, 0.78 and 0.83, respectively. Conclusion A panel of five plasma biomarkers combined with clinical features at the time of diagnosis more accurately predicted short-term disease activity in JIA than clinical characteristics alone. If validated in external cohorts, such a panel may guide more rationally conceived, biologically based, personalized treatment strategies in early JIA.

Funder

Canadian Institutes of Health Research

Institute of Musculoskeletal Health and Arthritis and Institute of Infection and Immunity

Arthritis Society

Canadian Arthritis Network

University of Saskatchewan

Manitoba Institute of Child Health

McGill University

Division of Pediatric Rheumatology

Memorial University

University of British Columbia

Clinical Research Centre of the Centre Hospitalier Universitaire de Sherbrooke

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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