COPENHAGEN — Long-term treatment with abatacept was safe and effective in patients with juvenile idiopathic arthritis in a study with 153 patients.
The best response rate was in patients who were maintained on continuous abatacept treatment for up to 31 months. In this subgroup of 58 patients, 75% had an American College of Rheumatology (ACR) 70 response after 2 years of treatment, 57% had an ACR 90 response, and 43% had inactive disease, Dr. Nicolino Ruperto said at the annual European Congress of Rheumatology. Response rates were higher in these patients than in patients who briefly stopped abatacept or those who didn't respond to abatacept early, said Dr. Ruperto, a pediatric rheumatologist at the Pediatric Rheumatology International Trials Organization of the IRCCS (Istituto di Rivovero e Cura a Carattere Scientifico) in Genoa, Italy.
The findings support continuing abatacept treatment of patients with juvenile idiopathic arthritis (JIA) once the regimen starts, in order to optimize the response rate and give every opportunity for late responses among patients without an early response.
The study was funded by Bristol-Myers Squibb Co. (BMS), the company that markets abatacept (Orencia). Dr. Ruperto said that he has received research support from BMS but has no other relationships with the company. Several of his coauthors also reported relationships with BMS and with other drug companies, and some coauthors were employees of BMS.
The long-term assessment in the new report involved most of the 190 patients who participated in a double-blind, placebo-controlled comparison of abatacept and placebo. The enrolled JIA patients failed prior treatment with at least one disease-modifying antirheumatic drug. Patients were an average age of 12 years old (range, 6-17 years), and they had been diagnosed with JIA for an average of 4 years. In the study, patients received either 10 mg/kg IV abatacept or placebo. Patients received treatment every 2 weeks for the first month, followed by monthly treatment. The study was conducted at 45 pediatric rheumatology centers in Europe, the United States, and Latin America.
Results from the first 4 months showed that abatacept significantly prolonged the time to an arthritis flare, the study's primary end point. Flares occurred in 20% of 60 patients on abatacept and in 53% of 62 control patients. The risk for a flare was cut by 69% in abatacept-treated patients, compared with those on placebo (Lancet 2008;372:383-91).
The long-term follow-up study involved 153 of the 190 patients. Of the 153 patients, 58 began abatacept treatment in the study and continued without stopping; 59 started on abatacept and responded during an open-label, 4-month course, were withdrawn for 4 months as the placebo group for the initial study, and then went back on abatacept when the trial was over; and the 36 patients who did not respond to abatacept during the initial, open-label 4 months were put back on the drug later.
Of the 153 patients, 42 dropped out during extended abatacept treatment. Although the best response rates were in patients on continuous abatacept treatment, even those who at first didn't respond to the drug showed notable responses, with 46% having an ACR 70 response, 18% having an ACR 90 response, and 5% attaining disease inactivity.
Patients who responded to abatacept initially but who were taken off while they served as the placebo arm in the randomized phase had the same ACR 70 response rate as did patients whose treatment wasn't interrupted (75%). But fewer patients who missed 4 months of abatacept treatment achieved complete disease inactivity during follow-up (23%, compared with 43% among those on uninterrupted abatacept).
Serious adverse events occurred in 23 patients (15%). Five of these patients had a serious infection, but no patient had an opportunistic infection, tuberculosis, pneumonia, or malignancy. Overall, long-term abatacept was safe and well tolerated, Dr. Ruperto said.