The Chinese University of Hong Kong Early Arthritis Study (ERA)

The purpose of this study is:

1. To ascertain whether the quantitative assessment of enhancing synovial volume and perfusion indices on serial Magnetic Resonance Imaging (MRI) examination are useful indicators of responsiveness to treatment in early Rheumatoid Arthritis (RA) using biologic therapy and Methotrexate (MTX) compared with Methotrexate(MTX) alone.
2. To assess the cost-effectiveness of Tumor Necrosis Factor (TNF) blockers compared with Methotrexate(MTX) monotherapy for Rheumatoid Arthritis(RA).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Methotrexate; Drug: Infliximab

Detailed Description

This was a 24-week open-label randomized study. Forty patients are randomly assigned to receive either combination infliximab plus Methotrexate(MTX) (n=20) or Methotrexate(MTX) alone (n=20)

All participants received oral Methotrexate(MTX), starting at 7.5 mg/week. In patients with persistent tender or swollen joints, the dose was escalated in a graduated manner (2.5 mg/week every 1-2 weeks) to 15 mg/week by week 4 or 20 mg/week by week 8 Patients in combination group receive infliximab 3mg/kg at weeks 0, 2, and 6 and every 8 week thereafter. Comprehensive assessment will be made on week 0, 12, 24.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • Prince of Wales Hospital
  • Hong Kong, China
    • Department of Medicine and Therapeutics
  • Hong Kong, China
    • The Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women, 18 years of age or older
• Clinical diagnosis of RA with a duration not more than 24 months (Fulfilled the 1987 American College of Rheumatology (ACR) criteria for RA)
• Patients at risk of developing persistent or erosive arthritis
• DAS 28 ≥ 3.2
• Prednisolone < 10mg/day and started at least 4 weeks before baseline
• Either has ESR ≥ 28, CRP ≥ 10, presence of rheumatoid factor or anti-CCP, present of HLADRB*0401 or DRB1*0404, and radiographic erosions
• Informed consent

Exclusion Criteria:

• Little or no ability for self-care
• Previous treatment with DMARDs other than antimalarials
• Concomitant treatment with an experimental drug
• Malignancy within the last 5 years
• Bone marrow hypoplasia
• Clinically significant renal disease ( serum creatinine level ≥ 150µmol/L) or estimated creatinine clearance > 75ml/min, alanine aminotransferase (ALT) exceeds the upper limit of normal
• History of any clinically significant adverse reaction to murine or chimeric proteins
• History of TB in the last 5 years
• Known to have hepatitis B, or hepatitis C
• Had an opportunistic infection (e.g. herpes zoster, cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months before screening
• History or ongoing chronic or recurrent disease; renal infection, chest infection, urinary tract infection, ulcer or skin wound
• History of infected joint prosthesis and use of antibiotics for the joint
• Received intravenous antibiotics within 30 days or oral antibiotics within 14 days for screening
• History of known demyelinating diseases (multiple sclerosis or optic neuritis)
• Current signs or symptoms of severe diseases (renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, etc)
• History or concurrent CHF
• History of lymphoproliferative disease, splenomegaly
• Female of childbearing potential, unwilling to use adequate contraception during the study
• Current or recent ( within the past 3 months) pregnancy and cancer
• Active smoker, alcohol or drug abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methotrexate; A drug for RA patient	Drug: Methotrexate; All participants received oral Methotrexate(MTX), starting at 7.5 mg/week. In patients with persistent tender or swollen joints, the dose was escalated in a graduated manner (2.5 mg/week every 1-2 weeks) to 15 mg/week by week 4 or 20 mg/week by week 8; Other Names: MTX
Active Comparator: Infliximab; for RA treatment	Drug: Infliximab; Patients in combination group receive infliximab 3mg/kg at weeks 0, 2, and 6 and every 8 week thereafter.; Other Names: Remicade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in the volume of enhancing synovitis measured by Magnetic Resonance Imaging(MRI) as it corresponds to active, inflamed tissue and is therefore expected to be a better marker of disease activity.	week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
changes in the synovitis grading and the perfusion indices	24 week
proportion of patients achieving ACR and EULAR responses	week 24
Correlation between the Magnetic Resonance Imaging(MRI) findings and changes on x-ray	week 24

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Edmund K Li, MD, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: May 13, 2009
• First Submitted That Met QC Criteria: May 13, 2009
• First Posted (Estimate): May 14, 2009

Study Record Updates

• Last Update Posted (Estimate): August 2, 2012
• Last Update Submitted That Met QC Criteria: July 31, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: anti-TNF; MTX; Early RA
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Arthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate; Infliximab
• Other Study ID Numbers: ERA_2008