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Embargoed for Release at 6:15 pm
ET , Sunday Oct. 17, 2004
Arthritis News
DMARDS SHOW ON-GOING BENEFIT IN JUVENILE
ARTHRITIS PATIENTS
SAN ANTONIO, TEXAS - Children with juvenile arthritis have long-term
improvement in joint pain and swelling when treated with leflunomide
or methotrexate, drugs commonly used to treat rheumatoid arthritis
in adults, according to research presented this week at the American
College of Rheumatology Annual Scientific Meeting in San Antonio,
Texas.
One in every 1,000 children will develop juvenile rheumatoid
arthritis (also referred to as JRA or juvenile chronic arthritis).
The resulting joint inflammation can last from several months
to many years, sometimes extending into adulthood. These patients
are often treated with disease-modifying antirheumatic drugs
(DMARDS) such as methotrexate and leflunomide to reduce or prevent
joint damage, and preserve joint integrity and function. In a
trial being conducted to assess the on-going efficacy, safety
and tolerance to leflunomide and methotrexate in children with
juvenile rheumatoid arthritis, researchers studied 94 patients
between the ages of three and 17 in a 16-week randomized controlled
trial. Patients were given either leflunomide or methotrexate,
at a dose based on body weight, and assessed every four weeks
for improvement in arthritis signs and symptoms including physical
function. Seventy of the 94 patient were then enrolled in a 32-week
blinded extension study, and re-assessed every eight weeks for
efficacy and safety.
Results showed that both drugs were well tolerated and that
the improvements patients had in their arthritis during the first
16 weeks, including physical function, were maintained throughout
the 48-week test period. Physical function was measured by the
Childhood Health Assessment Questionnaire which assesses ability
to perform daily activities such as walking, dressing, and eating.
"Not every child with juvenile arthritis responds to treatment
with methotrexate, and it is important to have other treatment
alternatives," said Earl Silverman, MD, Hospital for Sick Children,
Toronto, Canada, and an investigator in the study. "Leflunomide,
a tablet taken orally, is an effective and well-tolerated alternative
to methotrexate for these patients."
The American College of Rheumatology is the professional organization
for rheumatologists and health professionals who share a dedication
to healing, preventing disability and curing arthritis and related
rheumatic and musculoskeletal diseases. For more information
on the ACR's annual meeting, see www.rheumatology.org/annual.
###
Editor's Notes: Dr. Silverman will present this research
during a scientific session at the ACR Annual Scientific Meeting
from 12:15 - 2:00 pm CT (1:15 - 3:00 pm ET) Monday, October18,
in Exhibit Hall C-D of the Henry B. Gonzalez Convention Center.
He will be available for media questions during a briefing
at 1:30pm CT (2:30pm ET) on Tuesday, October 19, in the on-site
Press Conference Room, Room 218.
Presentation Number: 72
Durability of Efficacy, Safety, and Tolerability
of Leflunomide (LEF) or Methotrexate (MTX) Over 48 Weeks of Treatment
in Pediatric Patients With Juvenile Rheumatoid Arthritis (JRA)
Earl Silverman 1, Richard Mouy 2, Lynn Spiegel 1, Lawrence Jung
3, Rotraud Saurenmann 4, Pekka Lahdenne 5, Ilona Szer 6, Karen
Simpson 7, John A. Stewart 8, Vibeke Strand 9. 1 Hospital for
Sick Children, Toronto, ON, Canada; 2 Hopital des Enfants Malades,
Paris, France; 3 Creighton University Medical Center, Omaha,
NE; 4 University Children's Hospital, Zurich, Switzerland; 5
Hospital for Children and Adolescents, University of Helsinki,
Helsinki, Finland; 6 Children's Hospital San Diego, San Diego,
CA; 7 Aventis Pharmaceuticals, Bridgewater, NJ; 8 Aventis Pharma
Canada, Laval, PQ, Canada; 9 Stanford University, Palo Alto,
CA
Purpose: To evaluate durability of efficacy,
continued safety, and tolerability of LEF or MTX treatment in
subjects with polyarticular course JRA who enrolled in a 32-week
extension after completing 16 weeks of treatment.
Methods: 94 patients 3-17 years old enrolled
in a 16-week randomized controlled trial (RCT). Patients received
LEF according to body weight (10 mg every other day, 10 mg/d,
or 20 mg/d; loading dose 100 mg/d for 1-3 d, respectively) or
MTX 0.5 mg/kg/week up to 25 mg/week. Of the 86 completing the
16-week RCT, 70 subsequently enrolled into a 32-week blinded
extension. Percent Improvement Index (PII) and JRA Definition
of Improvement ≥30% responses (JRA30) were assessed at baseline,
every 4 weeks for the RCT, and every 8 weeks for the 32-week
extension.
Results: Results from the 16-week RCT were
presented previously (Silverman et al, ACR 2003; Abstract LB2).
Median disease duration was 0.33 y in both randomized groups
at baseline. In the extension trial, the PII at week 16 was maintained
at week 48 for both LEF (-54.66% and -55.36%, P =0.088) and MTX
(-57.96% and -65.51%, P =0.058). The JRA30 responder rate was
the same at weeks 16 and 48 within each treatment group (LEF
78.8%; MTX 91.4%). JRA50 and JRA70 responder rates at week 16
were also maintained at week 48 for both LEF and MTX. Improvement
in physical function (Childhood Health Assessment Questionnaire
Disability Index) was also maintained between week 16 and 48
in both treatment groups (LEF: -0.49 and -0.51; MTX: -0.45 and
-0.55). Both drugs were generally well tolerated; in the extension,
1 LEF subject and 5 MTX subjects withdrew because of an adverse
event. As in the initial 16-week RCT, transaminase elevations
were more frequent with MTX over the 32-week extension (n=11
vs n=5 for LEF).
Conclusions: Both LEF and MTX resulted in clinically
meaningful improvements by JRA30 and PII. At 48 weeks, clinical
benefit was maintained in both treatment groups. LEF is an effective
and well-tolerated alternative to MTX for polyarticular JRA.
Within-Group Comparisons Between Week 16
and 48 of Treatment |
|
Week 16 |
Week 48 |
P value |
PII, adjusted mean (SE) |
|
|
|
LEF (N=33) |
-54.66 (3.17) |
-55.36 (3.17) |
0.8774 |
MTX (N=35) |
-57.96 (2.72) |
-65.51 (2.72) |
0.0580 |
JRA30, n (%) |
|
|
|
LEF (N=33) |
26 (78.8) |
26 (78.8) |
1.0000 |
MTX (N=35) |
32 (91.4) |
32 (91.4) |
1.0000 |
JRA50, n (%) |
|
|
|
LEF (N=33) |
24 (72.7) |
25 (75.8) |
0.7389 |
MTX (N=35) |
30 (85.7) |
30 (85.7) |
1.0000 |
JRA70, n (%) |
|
|
|
LEF (N=33) |
18 (54.5) |
23 (69.7) |
0.0956 |
MTX (N=35) |
23 (65.7) |
29 (82.9) |
0.0578 |
Disclosure: E. Silverman, Aventis
Pharmaceuticals 5; R. Mouy, None; L. Spiegel, None; L.
Jung, None; R. Saurenmann, None; P. Lahdenne, None; I.
Szer, None; K. Simpson, Aventis Pharmaceuticals 3; J.A. Stewart,
Aventis Pharmaceuticals 3; V. Strand, Aventis 5; Abbott Immunology
5; Centocor 5, 8; Amgen 5, 8; Pfizer 5, 8
