Bristol-Myers Squibb Company announced that cumulative five-year data from an open-label long-term extension of a phase IIb trial demonstrated long-term efficacy and safety of Orencia (abatacept) in adult rheumatoid arthritis (RA) patients who had an inadequate response to methotrexate (MTX).
The data show that, in these patients, Orencia provided sustained improvements in ACR responses, physical function and health-related quality of life. These data, combined with the retention rates observed in this study, demonstrate that Orencia provides durable long-term clinical benefits in patients with active RA who had an inadequate response to MTX. Results of this study were presented at the 2007 American College of Rheumatology (ACR) Annual Scientific Meeting.
"Studying the long-term efficacy of a treatment is important because RA is a chronic disease," said Joel Kremer, M.D., chief of rheumatology, Albany Medical College. "These data are important because they show that Orencia is efficacious and has an acceptable safety profile over an extended period of time in patients with an inadequate response to methotrexate."
Patients in the initial one-year, double blind, placebo-controlled randomised trial received MTX and either Orencia (10 mg/kg or 2 mg/kg) or placebo administered as a 30-minute intravenous infusion on Days 1, 15 and 30, and every four weeks thereafter, in addition to MTX. The primary endpoint of the double-blind portion of the study was ACR 20 at 6 months (60 per cent for Orencia (abatacept) vs. 35.5 per cent for placebo). All patients completing the double-blind period were eligible to continue in the open-label long-term extension, in which all participants received a fixed dose of ORENCIA approximating 10 mg/kg every four weeks, in addition to MTX. Efficacy, health- related quality of life and safety were assessed.
Of the 235 patients completing the double-blind period, 219 entered the long-term extension, and 130 continued in the trial for five years. Baseline RA characteristics for long-term extension patients were similar between groups at initial randomisation (mean disease duration: 8.2 - 9.9 years).
Physical function and health-related quality of life were assessed using the modified Health Assessment Questionnaire Disability Index (mHAQ-DI) and Short-Form 36 (SF-36), respectively. Clinically meaningful improvement in physical function was observed in 54.8 per cent of patients at Year 1 and 52.8 per cent of patients at Year 5 (n=53). Improvements in health-related quality of life were also maintained at Year 5. The mean improvement from baseline in the physical component summary was 9.7 at Year 1 (mean score 40.6) and was stable at 9.7 at Year 5 (mean score 41.7). The mean improvement in the mental component was 6.1 at Year 1 (mean score 52.3) and 5.4 at Year 5 (mean score 50.8). Improvements in all individual component scores of the SF-36 were also observed at Year 1 and maintained at Year 5.
The safety analysis represents five years of cumulative data. This includes all patients who received at least one dose of Orencia during the one-year double-blind period and all patients who entered the open-label period who received at least one dose of Orencia plus all patients randomised to receive placebo. The incidence rates observed during the five-year cumulative period for serious adverse events (SAEs), infections, serious infections, malignancies and autoimmune events were consistent with both the double-blind period and the integrated safety summary, which is comprised of seven core RA studies representing approximately 8,400 patient years of exposure. The incidence rates for SAEs in the double-blind period, five-year cumulative period and the integrated safety summary were 20/100 pt-years, 18.9/100 pt-yrs and 15.4/100 pt-yrs, respectively.
The incidence rates for infections in the double-blind period, five-year cumulative period and the integrated safety summary were 94.2/100 pt-years, 77.3/100 pt-yrs and 79.2/100 pt-yrs, respectively. The incidence rates for serious infections in the double-blind period, five-year cumulative period and the integrated safety summary were 2.1/100 pt-years, 3.0/100 pt-yrs and 3.0/100 pt-yrs, respectively. The incidence rates for malignancies in the double-blind period, five-year cumulative period and the integrated safety summary were 2.1/100 pt- years, 1.5/100 pt-yrs and 1.3/100 pt-yrs, respectively. A total of 12 autoimmune disorders, the most frequent of which were psoriasis and cutaneous vasculitis, were reported in 12 patients in the cumulative study period.
During the five-year cumulative period, 32 patients (11.1 per cent) discontinued due to SAEs. A total of five deaths occurred through five years of the study; all were considered to be unlikely related or unrelated to study medication.
Orencia is indicated in the United States for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more DMARDs, such as methotrexate or TNF antagonists. Orencia may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists. Orencia should not be administered concomitantly with TNF antagonists and is not recommended for use concomitantly with anakinra.
There have been rare cases of certain kinds of cancer in people receiving Orencia. The role of Orencia in the development of cancer is not known, the company said in a recent press release.