Clinically inactive disease in a cohort of children with new-onset polyarticular juvenile idiopathic arthritis treated with early aggressive therapy: time to achievement, total duration, and predictors

Carol A Wallace; Edward H Giannini; Steven J Spalding; Philip J Hashkes; Kathleen M O'Neil; Andrew S Zeft; Ilona S Szer; Sarah Ringold; Hermine I Brunner; Laura E Schanberg; Robert P Sundel; Diana S Milojevic; Marilynn G Punaro; Peter Chira; Beth S Gottlieb; Gloria C Higgins; Norman T Ilowite; Yukiko Kimura; Anne Johnson; Bin Huang; Daniel J Lovell; Childhood Arthritis and Rheumatology Research Alliance (CARRA)

doi:10.3899/jrheum.131503

Clinically inactive disease in a cohort of children with new-onset polyarticular juvenile idiopathic arthritis treated with early aggressive therapy: time to achievement, total duration, and predictors

J Rheumatol. 2014 Jun;41(6):1163-70. doi: 10.3899/jrheum.131503. Epub 2014 May 1.

Authors

Carol A Wallace¹, Edward H Giannini¹, Steven J Spalding¹, Philip J Hashkes¹, Kathleen M O'Neil¹, Andrew S Zeft¹, Ilona S Szer¹, Sarah Ringold¹, Hermine I Brunner¹, Laura E Schanberg¹, Robert P Sundel¹, Diana S Milojevic¹, Marilynn G Punaro¹, Peter Chira¹, Beth S Gottlieb¹, Gloria C Higgins¹, Norman T Ilowite¹, Yukiko Kimura¹, Anne Johnson¹, Bin Huang¹, Daniel J Lovell¹; Childhood Arthritis and Rheumatology Research Alliance (CARRA)

Affiliation

¹ From the Seattle Children's Hospital and Research Institute, Seattle, Washington; Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati; Cleveland Clinic, Cleveland, Ohio, USA; Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem, Israel; Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indianapolis; Rady Children's Hospital, San Diego, California; Duke University Medical Center, Durham, North Carolina; Children's Hospital of Boston; Department of Pediatrics, Floating Hospital for Children, Tufts Medical Center, Boston, Massachusetts; Department of Pediatrics, Texas Scottish Rite Hospital, Dallas, Texas; Hofstra North Shore-LIJ School of Medicine, New York, New York; Ohio State University and Nationwide Children's Hospital, Columbus, Ohio; Children's Hospital at Montefiore, New York, New York; Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center, Hackensack, New Jersey, USA.C.A. Wallace, MD; S. Ringold, MD, MS, Seattle Children's Hospital and Research Institute; E.H. Giannini, MSc, DrPH; H.I. Brunner, MD, MSc, MBA, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine; S.J. Spalding, MD, Cleveland Clinic; P.J. Hashkes, MD, MSc, Shaare Zedek Medical Center; K.M. O'Neil, MD, Riley Hospital for Children, Indiana University School of Medicine; A.S. Zeft, MD, Cleveland Clinic; I.S. Szer, MD, Rady Children's Hospital; L.E. Schanberg, MD, Duke University Medical Center; R.P. Sundel, MD, Children's Hospital of Boston; D. Milojevic, MD, Floating Hospital for Children, Tufts Medical Center; M.G. Punaro, MD, Texas Scottish Rite Hospital; P. Chira, MD, Riley Hospital for Children, Indiana University School of Medicine; B.S. Gottlieb, MD, MS, Hofstra North Shore-LIJ School of Medicine; G.C. Higgins, PhD, MD, The Ohio State University and Nationwide Children's Hospital; N.T. Ilowite, MD, Children's Hospital at Montefiore; Y.

PMID: 24786928
DOI: 10.3899/jrheum.131503

Abstract

Objective: To determine the elapsed time while receiving aggressive therapy to the first observation of clinically inactive disease (CID), total duration of CID and potential predictors of this response in a cohort of children with recent onset of polyarticular juvenile idiopathic arthritis (poly-JIA).

Methods: Eighty-five children were randomized blindly to methotrexate (MTX), etanercept, and rapidly tapered prednisolone (MEP) or MTX monotherapy and assessed for CID over 1 year of treatment. Patients who failed to achieve intermediary endpoints were switched to open-label MEP treatment.

Results: Fifty-eight (68.2%) of the 85 patients achieved CID at 1 or more visits including 18 who received blinded MEP, 11 while receiving MTX monotherapy, and 29 while receiving open-label MEP. Patients starting on MEP achieved CID earlier and had more study days in CID compared to those starting MTX, but the differences were not significantly different. Patients given MEP (more aggressive therapy) earlier in the disease course were statistically more likely to have a higher proportion of followup visits in CID than those with longer disease course at baseline. Those who achieved American College of Rheumatology Pediatric 70 response at 4 months had a significantly greater proportion of followup visits in CID, compared to those who failed to achieve this improvement (p < 0.0001). Of the 32 patients who met criteria for CID and then lost CID status, only 3 fulfilled the definition of disease flare.

Conclusion: Shorter disease duration prior to treatment, a robust response at 4 months, and more aggressive therapy result in a higher likelihood and longer duration of CID in patients with poly-JIA. The original trial from which data for this analysis were obtained is registered on www.clinicaltrials.gov NCT 00443430.

Trial registration: ClinicalTrials.gov NCT00443430.

Keywords: CHILDREN 2–16 YEARS; CLINICAL TRIAL; CLINICALLY INACTIVE DISEASE; EARLY AGGRESSIVE THERAPY; JUVENILE IDIOPATHIC ARTHRITIS.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Antirheumatic Agents / therapeutic use*
Arthritis, Juvenile / drug therapy*
Child
Child, Preschool
Disease Progression
Double-Blind Method
Drug Therapy, Combination
Etanercept
Female
Humans
Immunoglobulin G / therapeutic use*
Male
Methotrexate / therapeutic use*
Prednisolone / therapeutic use*
Receptors, Tumor Necrosis Factor / therapeutic use*
Remission Induction
Treatment Outcome

Substances

Antirheumatic Agents
Immunoglobulin G
Receptors, Tumor Necrosis Factor
Prednisolone
Etanercept
Methotrexate

Associated data

ClinicalTrials.gov/NCT00443430

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding