Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis (ACUTE-JIA)

• ClinicalTrials.gov Identifier: NCT01015547
• Recruitment Status: Completed
• First Posted: November 18, 2009
• Last Update Posted: October 15, 2015
• Sponsor: Helsinki University Central Hospital
• Collaborators: Foundation for Paediatric Research, Finland; Päivikki and Sakari Sohlberg Foundation, Finland; Rheumatism Foundation Hospital; Scandinavian Rheumatology Research Foundation; Paijat-Hame Hospital District
• Information provided by (Responsible Party): Pirjo Tynjala, Helsinki University Central Hospital

Tracking Information

• First Submitted Date: November 17, 2009
• First Posted Date: November 18, 2009
• Last Update Posted Date: October 15, 2015
• Study Start Date: May 2003
• Actual Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 17, 2009): ACR Pedi 75 response [ Time Frame: 54 weeks from baseline (0) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 17, 2009)

• clinically inactive disease [ Time Frame: at 54 weeks ]
• time spent in inactive disease [ Time Frame: 0 to 54 weeks ]
• time spent in ACR Pedi 75 [ Time Frame: 0 to 54 weeks ]
• Other ACR Pedi responses (30, 50, 70, 90, 100) [ Time Frame: 0 to 54 weeks ]
• drug survival [ Time Frame: 54 weeks ]
• occurrence of side-effects and adverse events [ Time Frame: 0 to 54 weeks ]
• cost-benefit ratio in each treatment arm [ Time Frame: 0 to 54 weeks ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Aggressive Combination Drug Therapy in Very Early Polyarticular Juvenile Idiopathic Arthritis
• Official Title: Comparison of Anti-TNF Therapy Plus Methotrexate, Combination Therapy of DMARDs, and Methotrexate Alone in Very Early Polyarticular Juvenile Idiopathic Arthritis. A National Randomized Multicenter Clinical Trial.
• Brief Summary: The objective of this study is to compare in very early polyarticular juvenile idiopathic arthritis (JIA) the efficacy, safety, and cost-benefit-ratio of three treatment strategies: biologic combination, combination of conventional disease-modifying drugs (DMARDs), and methotrexate alone.

Detailed Description

DMARD-naive polyarticular JIA patients with an early disease (onset less than 6 months) are randomized into one of three treatment strategies: (1) biological combination, i.e., anti-TNF therapy with infliximab plus methotrexate; (2) Combination of DMARDs with methotrexate, sulfasalazine, plus hydroxychloroquine; and (3) Methotrexate alone.

The efficacy is evaluated by American College of Rheumatology Pediatric (ACR Pedi) criteria based on 6 core set variables (CSVs): 1. no of active joints; 2. no. of joints with pain or tenderness and limitation of motion; 3. ESR (mm/hr); 4. the Childhood Health Assessment Questionnaire (CHAQ); 5. Physician's Visual Analogue Scale (VAS); 6. Patient/Parent VAS. To fulfill ACR Pedi 75 criteria, 3/6 CSVs have to improve 75% and not more than 1/6 CSV worsen more than 30%. All direct and indirect costs are documented.

The first phase of the study is open-label clinical trial lasting for 54 weeks. In the second phase of the study the patients are followed up to 5 years, and the long-term outcome of early aggressive therapy is analyzed. Serum, urine, and saliva samples are collected at 3 and 5 years for translational research.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Juvenile Idiopathic Arthritis

Intervention

• Drug: Infliximab plus methotrexate
  IFX given 3-5mg/kg every 6 weeks, oral MTX given 15mg/m2 weekly. If ACR Pedi 75 is not reached by week 12, MTX dose is doubled up to parenteral 30 mg/m2 weekly dose. If patient does not reach ACR Pedi 30 after dose escalation, failure.
  Other Name: IFX: Remicade, MTX: Trexan or Methotrexate
• Drug: Combination of DMARDs
  IFX given 3-5mg/kg every 6 weeks, oral MTX given 15mg/m2 weekly, SSZ 40mg/kg up to 2000mg daily, HCQ 5mg/kg daily. If ACR Pedi 75 is not reached by week 12, MTX dose is doubled up to parenteral 30 mg/m2 weekly dose. If patient does not reach ACR Pedi 30 after dose escalation, failure.
  Other Name: MTX: Trexan or Methotrexate, SSZ: Salazopyrin, HCQ: Oxiklorin
• Drug: Methotrexate alone
  Oral MTX given 15mg/m2 weekly. If ACR Pedi 75 is not reached by week 12, MTX dose is doubled up to parenteral 30 mg/m2 weekly dose. If patient does not reach ACR Pedi 30 after dose escalation, failure.
  Other Name: MTX: Trexan or Methotrexate

Study Arms

• Experimental: Infliximab plus Methotrexate
  infliximab 3-5 mg/kg every 6 weeks, plus methotrexate 15 mg/m2 weekly given orally (dose escalation if ACR Pedi less than 75). no oral prednisolone. intra-articular steroids allowed.
  Intervention: Drug: Infliximab plus methotrexate
• Experimental: Combination of DMARDs
  methotrexate 15mg/m2 weekly given orally (dose escalation and parenteral injection if ACR Pedi less than 75), plus standard doses of sulfasalazine and hydroxychloroquine. no oral prednisolone. intra-articular steroids allowed.
  Intervention: Drug: Combination of DMARDs
• Active Comparator: Methotrexate alone
  Conventional drug therapy: methotrexate 15mg/m2 weekly given orally (dose escalation and parenteral injection if ACR Pedi less than 75). no oral prednisolone. intra-articular steroids allowed.
  Intervention: Drug: Methotrexate alone

Publications *

• Lahdenne P, Vahasalo P, Honkanen V. Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study. Ann Rheum Dis. 2003 Mar;62(3):245-7. doi: 10.1136/ard.62.3.245.
• Tynjala P, Vahasalo P, Tarkiainen M, Kroger L, Aalto K, Malin M, Putto-Laurila A, Honkanen V, Lahdenne P. Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial. Ann Rheum Dis. 2011 Sep;70(9):1605-12. doi: 10.1136/ard.2010.143347. Epub 2011 May 28.
• Tarkiainen M, Tynjala P, Vahasalo P, Aalto K, Kroger L, Rebane K, Lahdenne P, Martikainen J. Economic evaluation of infliximab, synthetic triple therapy and methotrexate in the treatment of newly diagnosed juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2022 Nov 16;20(1):97. doi: 10.1186/s12969-022-00748-w.
• Tarkiainen M, Tynjala P, Vahasalo P, Kroger L, Aalto K, Lahdenne P. Health-related quality of life during early aggressive treatment in patients with polyarticular juvenile idiopathic arthritis: results from randomized controlled trial. Pediatr Rheumatol Online J. 2019 Dec 16;17(1):80. doi: 10.1186/s12969-019-0370-1.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 17, 2009): 60
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: December 2013
• Actual Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• juvenile idiopathic arthritis
• arthritis lasting for at least 6 weeks but not more than 6 months
• polyarticular disease with at least 5 active joints with at least 3 joints with pain or tenderness and limitation of motion
• no previous treatment with DMARDs

Exclusion Criteria:

• systemic JIA
• any abnormality in the hematopoietic or lymphatic system
• any major concurrent medical condition
• inadequate psychosocial situation
• pregnancy
• a non-abstinent female with reproductive capacity without regular contraceptive use

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 4 Years to 15 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Finland

Administrative Information

• NCT Number: NCT01015547
• Other Study ID Numbers: 211864, 318/E0/2002; 211864 ( Registry Identifier: www.hus.fi )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pirjo Tynjala, Helsinki University Central Hospital
• Original Responsible Party: Pirjo Tynjälä, MD, PhD, Hospital for Children and Adolescents and Hospital District of Helsinki and Uusimaa
• Current Study Sponsor: Helsinki University Central Hospital
• Original Study Sponsor: University of Helsinki

Collaborators

• Foundation for Paediatric Research, Finland
• Päivikki and Sakari Sohlberg Foundation, Finland
• Rheumatism Foundation Hospital
• Scandinavian Rheumatology Research Foundation
• Paijat-Hame Hospital District

Investigators

• Study Director: Pekka Lahdenne, MD, PhD; Hospital for Children and Adolescents in Helsinki University Central Hospital

• PRS Account: Helsinki University Central Hospital
• Verification Date: October 2015