AMSTERDAM, The Netherlands – Adalimumab (Humira®; Abbott) treatment with or without methotrexate (MTX) quickly improves symptoms and reduces flare rates in children with polyarticular juvenile rheumatoid arthritis (JRA), and those improvements are sustained for at least 1 year, Nicolo Ruperto, MD, of the Division of Pediatrics at the Giannana Gaslini Institute in Genoa, Italy, reported at the 2006 EULAR Meeting.1 On behalf of the Paediatric Rheumatology International Trials Organization (PRINTO), Dr. Ruperto presented 48-week data from a phase III trial of adalimumab with or without MTX in children who had previously achieved at least a Pediatric ACR 30 score in response to open-label adalimumab.

The primary study endpoints were incidence of disease flare, time to onset of flare, and rates of ACR 30, ACR 50, and ACR 70 responses.

"Adalimumab patients had a significantly lower rate of flares and maintained substantial ACR responses even when flares occurred." —Nicolo Ruperto, MD
The investigators enrolled 171 children with JRA who had responded to open-label adalimumab. Eligibility criteria for the open-label study included patients age 4–17 years with polyarticular-course JRA and a minimum of five swollen joints and three joints with limitation of motion (LOM). Over 50% of patients achieved a Pediatric ACR 70 response following open-label treatment with adalimumab, Dr. Ruperto said. He also noted that this was the first time children with JRA were treated with a biologic as first-line therapy.

Adalimumab-responsive patients were then randomized to subcutaneous adalimumab (24 mg/m2 every other week, n = 85) or placebo (n = 86) and were followed for an additional 32 weeks to determine if their disease flared. Patients in both groups were also stratified according to whether they were also taking MTX, and those in either group who flared were immediately treated with open-label adalimumab and/or with MTX if they had not been receiving MTX. "As soon as there was even minimal sign of flare, the children were offered open-label treatment, so the time on placebo with flare was very brief," Dr. Ruperto said.

He emphasized that the criteria for flare were such that "a small change in the physician's evaluation of global assessment could decide that a patient is in flare." Criteria included a worsening of >30% in three of six core criteria (from baseline of the double-blind period), with improvement of 30% in no more than one criterion and contingencies, including at least two active joints, or a >30% change in physician global assessment.

At 48 weeks significantly fewer patients treated with adalimumab had flares, regardless of whether they were also taking MTX.

Flare rates were 43% vs 71% for adalimumab alone vs placebo alone, respectively (P = .031), and 36.8% vs 64.9% for adalimumab plus MTX vs placebo plus MTX, respectively (P = .015). Perhaps due to the stringent flare criteria, patients who flared still had very good ACR response rates at the time of flare; 73% still had an ACR 30, 61% an ACR 50, 24% an ACR 70, and 4% an ACR 90 response.

"At the time of flare, these patients were still considered responders according to standard ACR criteria," Dr. Ruperto said.

ACR 30, 50, and 70 responses at week 48 were statistically significantly greater with adalimumab. Time to flare was also significantly longer.

Dr. Rupert acknowledged that no statistical analysis had been done of the baseline characteristics of the patient groups and that patients who were receiving concomitant MTX at baseline had somewhat more severe disease. The most common adverse events were mild upper respiratory infections. No tuberculosis or opportunistic infections were reported.

"Either alone or with MTX, adalimumab provided rapid and substantial improvement in signs and symptoms of disease in children with active JRA, and that improvement was sustained for up to 1 year. Adalimumab patients had a significantly lower rate of flares and maintained substantial ACR responses even when flares occurred," Dr. Ruperto concluded.

Reference

  1. Ruperto N; 2006 EULAR Meeting Proceedings. 48-week data from the study of adalimumab in children with juvenile rheumatoid arthritis (JRA). Ann Rheum Dis. 2000;65(suppl):OP0007.