Etanercept and methotrexate are shown to be safe and effective for long-term, continuous treatment of juvenile arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Francisco, Calif.

There are many terms used to describe a child with chronic arthritis. These include juvenile rheumatoid arthritis, juvenile chronic arthritis, and juvenile idiopathic arthritis.

There are several types of JIA, all involving chronic (long-term) joint inflammation. This inflammation begins before patients reach the age of 16, may involve one or many joints, and can cause other symptoms such as fevers, rash and/or eye inflammation. Systemic onset JIA is a subset of JIA that affects about 10 percent of children with arthritis. It begins with recurrent fevers that can be 103° F or higher, often accompanied by a pink rash that comes and goes. Systemic onset JIA may cause inflammation of the internal organs as well as the joints, though joint swelling may not appear until months or even years after the symptoms begin.

Polyarticular JIA affects five or more joints and can begin at any age. Children diagnosed with polyarticular JIA in their teens may actually have the adult form of rheumatoid arthritis at an earlier-than-usual age.

In a recent three-year study, researchers followed children aged two to 18 years with a diagnosis of polyarticular or systemic JIA to determine if methotrexate and etanercept are safe and effective for the long-term treatment of juvenile arthritis. Only patients on methotrexate, etanercept or a combination of both were included in the study, although all were allowed to take other conventional, non-biologic anti-rheumatic drugs. In addition, patients who were taking methotrexate were allowed to add or switch to etanercept within 30 months of the start of the study.

In all, 602 patients participated in this study. Of these, 204 patients completed the three-year registry – with 66 taking methotrexate alone, 333 taking etanercept alone, and 105 taking a combination of the two drugs. Etanercept was administered as either a 0.4 mg/kg injection twice weekly or 0.8 mg/kg weekly, and methotrexate was given at a dose greater than or equal to 10 mg/m2 once a week.

To determine safety, researchers monitored the occurrence of serious side effects, including medically important infections and death, and, they used joint counts and the physician’s assessment of a patient’s overall health to determine effectiveness of the medications.

A total of 66, 33, and 105 patients taking methotrexate, etanercept and a combination of the two, respectively, completed the three-year study, and 15 etanercept patients, along with 36 patients on the combination of medications, are currently continuing the study. Some patients in each group withdrew from the study due to insufficient therapeutic effect, side effects or remission.

During the course of the study, one case of lupus occurred in a patient taking methotrexate and two cases of sepsis occurred in patients taking etanercept and the combination of medications. No cases of lymphoma, malignancy, tuberculosis, or death were reported.

“The results of a three-year, open label, non randomized registry of children with either polyarticular or systemic onset juvenile rheumatoid arthritis who were treated with methotrexate, etanercept or the combination of methotrexate and etanercept are reported,” explains Norman T. Ilowite, MD; chief, division of rheumatology, Children’s Hospital at Montefiore; professor of pediatrics, Albert Einstein College of Medicine, Bronx, N.Y., and an investigator in the study. “Determining the safety of these agents was the primary goal; serious adverse events and medically important infections were prospectively and systematically collected in 594 patients representing over 1,200 years of exposure. These data suggest that etanercept, alone or in combination with methotrexate, is safe as long-term continuous therapy for the treatment of juvenile rheumatoid arthritis.”

Patients should talk to their rheumatologists to determine their best course of treatment.

The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see http://www.rheumatology.org/annual.

Editor’s Notes: Edward H. Giannini, MSc, DrPH will present this research during the ACR Annual Scientific Meeting at the Moscone Center from 9:00 – 11:00 AM on Tuesday, October 28, in Hall A. Dr. Ilowite will be available for media questions and briefing at 8:30 AM on Monday, October 27 in the on-site press conference room, 114.

Presentation Number: 1496

Safety Data from Over 1,200 Patients-years of Methotrexate and/or Etanercept Treatment in Children with Polyarticular or Systemic Juvenile Rheumatoid Arthritis

Edward H. Giannini1, N. T. Ilowite2, D. J. Lovell1, C. A. Wallace3, E. B. Rabinovich4, A. Reiff5, G. Higgins6, B. Gottlieb7, Y. Chon8, S. W. Baumgartner8, S-L Lin8. 1Cincinnati Children’s Hosp Med Center, Cincinnati, OH; 2Einstein College of Med, Bronx, NY; 3Children’s Hosp and Regional Med Center, Seattle, WA; 4Duke University Medical Center, Durham, NC; 5Childrens Hosp of Los Angeles, Los Angeles, CA; 6Ohio State Univ and Children’s Hosp, Columbus, OH; 7Schneider Children’s Hosp, New Hyde Park, NY; 8Amgen, Thousand Oaks, CA

Purpose: To evaluate the safety of etanercept in children with polyarticular or systemic juvenile rheumatoid arthritis (JRA) for up to 3 years.

Methods: This 3-year, open-label, non-randomized registry included patients, age 2-18, with a diagnosis of polyarticular or systemic JRA. Patients treated with methotrexate (MTX), etanercept (ETN), or methotrexate/etanercept in combination (MTX/ETN) were eligible. Co-administration of non-biologic DMARDs was allowed. Patients enrolled in the MTX arm could switch to and reenroll into the ETN or MTX/ETN arms within 30 months. Etanercept was administered subcutaneously twice weekly at a dose of 0.4 mg/kg (maximum dose of 25 mg) or once weekly at a dose of 0.8 mg/kg (maximum dose 50 mg). MTX was administered at a dose ≥10 mg/m2/wk (not to exceed 1 mg/kg/wk). Safety data included incidence of serious adverse events (SAEs), medically important infections (MIIs), and death. Joint counts and Physician’s Global Assessment (PhGA) were used to assess effectiveness.

Results: 602 patients enrolled, 198 received MTX, 105 received ETN, and 299 received MTX/ETN. Most patients in the 3 groups were female (73-81%) and Caucasian (73-76%). The mean duration of MTX use prior to enrollment was 93, 781, and 716 days for the MTX, ETN, and MTX/ETN groups, respectively. The mean duration of etanercept use prior to enrollment was 79 days and 78 days for the ETN and MTX/ETN groups. A total of 66 (33%), 33 (31%), and 105 (35%) patients from the MTX, ETN, and MTX/ETN groups have completed the 3-year registry for a total of 388, 210, and 610 subject-years of exposure. A total of 0 (0%), 15 (14%), and 36 (12%) patients from the MTX, ETN, and MTX/ETN groups are ongoing in this registry. Withdrawals from the study included 36 (18%), 8 (8%), and 55 (19%) patients who discontinued due to insufficient therapeutic effect, 3 (2%), 2 (2%), and 1 (0.3%) who discontinued due to AEs, and 24 (12%), 8 (8%), and 11 (4%) who discontinued due to remission. The rates of SAEs and MIIs per 100 pt-yrs were 4.4, 7.6, and 5.7, and 1.3, 1.9, and 2.1 respectively, for patients receiving MTX, ETN, or MTX/ETN. One case of lupus (MTX) and 2 cases of sepsis (ETN and MTX/ETN) were reported. No cases of lymphoma, malignancy, tuberculosis, or death were reported. Improvements in outcome measures for all groups were similar and maintained for 36 months.

Conclusion: These data suggest etanercept is safe as a long-term, continuous therapy for treatment of JRA.
Funded by Immunex Corp, a wholly owned subsidiary of Amgen Inc, and by Wyeth Pharmaceuticals.

Disclosure Block: E.H. Giannini, Amgen, 2; Pfizer, 2; Genzyme, 2; BMS, 2; N.T. Ilowite, Novartis, 5; Abbott, 5; Bristol Meyers Squib, 5; D.J. Lovell, Roche, 2; Amgen Inc, 5; Wyeth, 8; Centocor, 9; Bristol-Meyers Squibb, 9; Abbott, 9; Regeneron, 9; Novartis, 9; Xoma, 9; C.A. Wallace, Amgen, 2; Pfizer, 2; Amgen Inc, 5; BMS, 5; Novartis, 5; Centocor, 2; E.B. Rabinovich, Amgen, 2; CARRA, 2; Abbott, 5; Pfizer, 5; A. Reiff, Amgen Inc, 5; Wyeth, 5; Merck, 5; Abbott, 5; Pfizer, 5; Novartis, 5; Amgen Inc, 8; Wyeth, 8; Merck, 8; Abbott, 8; G. Higgins, Abbott, 2; Amgen, 2; B. Gottlieb, None; Y. Chon, Amgen Inc, 1; Amgen, Inc, 3; S.W. Baumgartner, Amgen Inc, 1; Amgen, Inc, 3; S. Lin, Amgen Inc, 1; Amgen Inc, 3.

Source: American College of Rheumatology (ACR)