Adalimumab Proves Effective for Children with Juvenile Rheumatoid Arthritis

Newswise — Adalimumab, an injectable anti-TNF therapy that has FDA approval for treating rheumatoid arthritis in adults, has proven effective in children with juvenile rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington, DC.

The immunosuppressant adalimumab, currently used to treat adults with moderate to severe rheumatoid arthritis, targets inflammation by blocking TNF (tumor necrosis factor) proteins in the body. Following studies that demonstrated safety and effectiveness in adults with rheumatoid arthritis, this study in children with juvenile rheumatoid arthritis was performed. Juvenile rheumatoid arthritis affects an estimated 285,000 children in the U.S. The disease, which starts before they reach age 16, can cause joint stiffness, reluctance or refusal to use arms or legs, reduced activity levels, persistent pain and joint swelling. If not effectively treated, it can result in joint damage, growth delay and decreased bone mineralization.

To assess the long-term effectiveness and safety of adalimumab in a younger population, researchers conducted a 48-week randomized study on 171 children, ages 4 to 17, with five or more swollen joints and three or more joints with limited range of motion at the outset of the study. The subjects were categorized as those taking and not taking methotrexate at the beginning of the study. The dose of methotrexate and all other arthritis medications remained stable throughout the trial. Adalimumab doses were based on the child's size, with participants receiving 24 mg/M2 BSA, maximum of 40 mg, given as a subcutaneous injection every 2 weeks over a 16-week period. At the end of the 16 weeks, the 83% (142) of the subjects who met the definition of "responder" for this study were randomized into a double-blind study and assigned to either continue adalimumab or switch to a placebo for the next 32 weeks or until disease flare-up.

Results demonstrated that participants receiving adalimumab had significantly fewer disease flares than those on placebo. Of those not already taking methotrexate, 43% randomized to adalimumab and 71% to placebo flared; of those already on methotrexate, 37% and 65%, respectively flared. The most common problems were mild upper respiratory infections. No tuberculosis or opportunistic infections were reported.

"Based on this data, adalimumab taken with or without methotrexate provided rapid, substantial and sustainable improvement for children with very active juvenile rheumatoid arthritis," explains Daniel J. Lovell, MD, MPH, Chairman, Pediatric Rheumatology Collaborative Study Group, Cincinnati, Ohio and an investigator in the study. "Given that the medication was generally well tolerated, adalimumab has emerged as an excellent treatment option for children with juvenile rheumatoid arthritis."

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 http://www.rheumatology.org/annual.

Presentation Number: 659

Long-Term Efficacy and Safety of Adalimumab in Children with Juvenile Rheumatoid Arthritis (JRA): 48-Week Results

D. J. Lovell1, N. Ruperto2, L. Jung1, A. Reiff3, D. Nemcova2, K. Jarosova2, A. Prieur2, C. Sandborg1, J. Rovensky2, J. Bohnsack1, K. Minden2, L. Wagner Weiner1, R. Vehe1, G. Horneff2, J. Medich4, E. H. Giannini1, A. Martini2. 1PRCSG, Cincinnati, OH; 2PRINTO-IRCCS G Gaslini, Genova, Italy; 3Children's Hospital of Los Angeles, Los Angeles, CA; 4Abbott, Parsipanny, NJ

PURPOSE: This analysis evaluated long-term efficacy and safety of adalimumab (ADA) in pts with JRA.

METHODS: A multi-center, Phase III, randomized, double-blind (DB), placebo (PBO)-controlled withdrawal study was conducted in 171 polyarticular-course JRA pts 4-17 years old with >5 swollen joints and >3 joints with limitation of motion at baseline. At the end of a 16-wk OL phase, pts demonstrating an ACR Ped 30 response were randomized (DB) to either ADA 24 mg /m2 BSA (max 40 mg/dose) or PBO sc eow for an additional 32 wks or until disease flare (primary endpoint). Disease flare criteria were 1) worsening of >30% from baseline in >3 of 6 ACR Ped core criteria, 2) >2 active joints, and 3) improvement of >30% in no more than 1 of the 6 criteria. After 32 wks or at time of flare in DB, pts were allowed to receive OL ADA. Randomization was stratified by use of concomitant MTX. Efficacy and safety assessments were collected at regular intervals.

RESULTS: At the end of the 16-wk OL phase, the % of pts showing ACR Ped 30/50/70 response were 83/74/52. A total of 133 pts entered the DB phase (female, 77%, mean age, 11.2 years, and 65% taking MTX). Only 4% of those entering the DB dropped out (1 protocol violation, 1 withdrew consent, 3 other). In the DB, pts receiving ADA had significantly fewer disease flares than PBO, both without MTX (43.3% vs. 71.4%, p=0.031, primary endpoint) and with MTX (36.8% vs. 64.9%, p=0.015). In ADA pts, ACR30/50/70 responses at Wk 48 (end of DB period) were significantly greater than those in PBO pts (table). Pts who flared in the DB still had good ACR response rates (ACR30/50/70 of 73/61/24) at the time of flare because of stringent flare criteria. Most common AEs were infections (mostly mild upper respiratory). Four ADA and two PBO pts experienced SAEs during the DB phase. No TB or opportunistic infections were reported.

Pediatric ACR Responders at Week 48 ADA PBO (n=68) (n=65)ACR30 60%* 35%ACR50 59%* 35%ACR70 56%* 28%

*p<0.01 for ADA vs PBO.

CONCLUSION: ADA, with or without MTX, provided rapid, substantial, and sustained improvement in signs and symptoms of JRA. ADA pts had a significantly lower rate of flares than PBO pts and despite stringent flare criteria, maintained substantial ACR responses when flares occurred. ADA was generally well-tolerated in pts with JRA.

Disclosure Block: D.J. Lovell, Consulting fees from Amgen, Centocor, Bristol Myers Squibb, Abbott, Regeneron, Xoma, Hoffman-La Roche, and Novartis, 5 Consulting fees; On the speakers bureau for Wyeth and Amgen, 8 Speakers bureau.