Etanercept Plus Methotrexate Versus Methotrexate Alone in Children With Polyarticular Course Juvenile Rheumatoid Arthritis
Condition: Juvenile Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid; Arthritis, Juvenile
Intervention: Etanercept; Placebo to Etanerceot; Methotrexate
Intervention description: Administered by subcutaneous injection twice a week; Administered by subcutaneous injection twice a week; Administered orally or subcutaneously once a week at the same dose as prior to study entry
Intervention MeSH terms: Etanercept; Methotrexate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 25.0
Sex: All
Healthy volunteers: No

Summary:

      The primary objective of this study was to determine the efficacy of etanercept plus
      methotrexate vs methotrexate alone in pediatric patients with active polyarticular course
      juvenile rheumatoid arthritis (JRA).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have had a diagnosis of JRA by the American College of Rheumatology
             (ACR) criteria. Disease onset may have been systemic, polyarticular, or pauciarticular

          -  Disease course must have been polyarticular with at least 5 active joints

          -  Duration of disease was not limited, but must have been long enough for the patient to
             have been given a 3-month trial of non-steroidal anti-inflammatory drugs (NSAIDs) and
             methotrexate at a dose between 0.3 and 1.0 mg/kg/week, orally (PO) or subcutaneously
             (SC)

          -  Receiving methotrexate at a dose between 0.3 mg/kg/wk and 1 mg/kg/wk at time of
             randomization. The dose of methotrexate must have been stable for one month prior to
             entry

          -  Patients may have failed prednisone, or been on a dosage of prednisone not to have
             exceeded 10 mg/day or 0.20 mg/kg/day (whichever was less)

          -  At the time of qualification (screening) for study and prior to wash-out of all
             disease modifying anti-rheumatic drugs (DMARDs), the patient must have had active
             disease, defined as ≥ 5 swollen joints accompanied by pain, and/or tenderness and/or
             warmth, and ≥ 3 joints with limitation of motion (LOM). (The joints with LOM may have
             been the same as those with swelling)

          -  Had good venous access and stable hematocrit ≥ 24 mL/dL

          -  Patients must have been pre-pubescent, or if post-pubertal at anytime during the
             study, and of child-bearing potential, must have been practicing adequate
             contraception

          -  Parent or legal guardian was able and willing to give informed consent

          -  Parent or legal guardian must have been willing to actively supervise storage and
             administration of study drug and ensure that the date and time of each dose was
             accurately recorded in the subject's diary

        Exclusion Criteria:

          -  Was unable to meet the concurrent medication restrictions as described in the protocol

          -  Pregnant or nursing female

          -  Patients were excluded if they demonstrated clinically significant deviations from
             normal (as defined below) in any of the following laboratory parameters:

               -  thrombocytopenia; platelet count < 100,000/cmm

               -  leukopenia; total white cell count < 4000 cells/cmm

               -  neutropenia; neutrophils < 1000 cells/cmm

               -  hepatic transaminase levels > two times the upper limit of normal (ULN)

               -  serum bilirubin > two times the ULN

               -  estimated creatinine clearance of < 90 mL/min/1.73 M² body surface area (BSA)

               -  known human immunodeficiency virus (HIV), hepatitis B surface antigen positivity
                  not related to vaccination, or hepatitis C antibody positivity

          -  Had received etanercept, antibody to tumor necrosis factor (TNF) (i.e. infliximab or
             D2E7), antibody to cluster of differentiation (CD)4 (anti-CD4), diphtheria interleukin
             (IL)-2 fusion protein (DAB-IL-2) or leflunomide

          -  Had received DMARDs including D-penicillamine, hydroxychloroquine, sulfasalazine, oral
             or injectable gold, cyclosporin, azathioprine; intravenous immunoglobulin (IV Ig); or
             broadly immunosuppressant chemotherapeutic agents (e.g. cyclophosphamide, FK506,
             mycophenolate mofetil [CellCept]), for at least 28 days prior to enrollment and dosing
             of study drug. All DMARDs, other than methotrexate, must have been washed-out for a
             minimum of 28 days

          -  Had received intraarticular glucocorticoid injection within 28 days prior to
             enrollment on study

          -  Had previously received live virus vaccine within 3 months prior to study entry

          -  Had participated in a study of an investigational drug or biologic requiring
             informed-consent within three months prior to study entry

          -  Any concurrent medical condition which would have, in the investigator's opinion,
             compromised the patient's ability to tolerate the study drug or would have made the
             patient unable to cooperate with the protocol

          -  History of/or current psychiatric illness that would have interfered with ability to
             comply with protocol requirements or give informed consent

          -  Chronic or recurrent infections, or currently active infection at screening

          -  History of alcohol or drug abuse that would have interfered with ability to comply
             with protocol requirements

          -  Inability to have complied with the study requirements