Bristol-Myers Squibb Company (NYSE: BMY) announced results of radiographic analyses from the AIM (Abatacept in Inadequate responders to Methotrexate) study, which demonstrated that ORENCIA® (abatacept) provides significant inhibition in the progression of structural damage over three years of treatment in adult patients with moderate-to-severe rheumatoid arthritis (RA), who have had an inadequate response to methotrexate (MTX). The increasing disease-modifying benefit of ORENCIA on structural damage caused by RA was observed in the first year, with increasing inhibition in Year 2 and Year 3, and was consistent for both erosions and joint space narrowing. These data were presented at the Annual Congress of the European League Against Rheumatism (EULAR).
"Rheumatoid arthritis is a serious, chronic condition that worsens over time," said Joel Kremer M.D., Pfaff Family Professor of Medicine, Albany Medical College. "Identifying long-term therapies that not only inhibit radiographic progression of the disease, but do so over an extended period of time, is critical to effectively treat this patient population."
Progressive structural damage is associated with increasing disability over time.[i] In the AIM study, a phase III randomized, double-blind, placebo-controlled trial, the effects of long-term treatment with ORENCIA on radiographic outcomes were assessed over time in the open-label extension phase of the study.
Study Design and Findings
During the double-blind period of this study, 433 patients who had an inadequate response to MTX received a fixed dose of ORENCIA (approximately 10 mg/kg, according to weight range) or placebo in addition to background MTX, on days 1, 15 and 29 and every four weeks thereafter for one year. Patients completing the double-blind phase were eligible to enter the open label, long-term extension phase and received a dose of approximately 10 mg/kg ORENCIA plus MTX every 28 days. During the study, radiographs of hands and feet were performed at baseline and Years 1, 2 and 3, or upon early termination.
Radiographic assessment for total score (TS), erosion score (ES) and joint space narrowing score (JSNS) was performed using the Genant-modified Sharp scoring method. Radiographs from baseline and Years 1, 2 and 3 were all re-read at Year 3 by two independent expert readers blinded to the original treatment allocation and the sequence of films. For patients who did not complete the study, radiographs were taken at the time of discontinuation and data were imputed for up to one year using linear extrapolation of the scores.
Of the 433 patients initially randomized to ORENCIA plus MTX, radiographs were available at baseline and at the end of Years 1, 2 and 3 from approximately 70 percent of the patients. The mean change in the TS, JSNS and ES were lower from Year 2 to Year 3 (0.25, 0.12, 0.14 units respectively) than those from Year 1 to Year 2 (0.43, 0.18 and 0.25 units, respectively), which were also lower than the mean change in these scores from baseline to Year 1 (0.89, 0.35 and 0.53 units, respectively). The decreases seen in Year 3 relative to Year 2 were statistically significant for total score (p=0.022).
In addition, RA disease progression analysis showed that patients with no progression or disease improvement increased throughout each year of ORENCIA treatment, as measured radiographically by total score. Of the 304 patients with evaluable radiographs at Year 1, 139 (45.7 percent) had no progression from baseline. At year 2, 135 had evaluable radiographs, of which 92 (68.1 percent) remained non-progressors. At year 3, 69 out of 91 patients (75.8 percent) with evaluable radiographs remained non-progressors.
The clinical benefits demonstrated by ORENCIA were accompanied by a consistent safety and tolerability profile through three years in patients with RA.[ii],[iii],[iv]
About ORENCIA
ORENCIA® is the first selective co-stimulation modulator of T-cell activation. ORENCIA® is the first biologic discovered and developed in Bristol-Myers Squibb research centres and was approved in May 2007 by the European Commission.
Medicinal products, including ORENCIA®, which affect the immune system, may affect host defences against infections and malignancies. Serious infections at least possibly related to treatment were reported in 1.8% of patients with ORENCIA® and in 1.0% of patients not treated by ORENCIA® (receiving placebo). There is a need to evaluate and monitor the patients regarding the risk of infection prior to and during treatment. In the placebo-controlled clinical trials, the frequency of malignancies with ORENCIA® was 1.4% and with placebo 1.1%. These rates are similar to that observed in the general rheumatoid arthritis population.[v]
ORENCIA®, like other biologics, is contraindicated in patients with severe and uncontrolled infections such as sepsis and opportunistic infections and in patients with hypersensitivity to the active substance or to any of the excipients. Allergic reactions have been reported uncommonly with ORENCIA® in clinical trials, where patients were not required to be pretreated to prevent allergic reactions. In the case of any serious allergic/anaphylactic reaction, ORENCIA® should be discontinued.
About Rheumatoid Arthritis
Rheumatoid arthritis is a systemic, chronic, autoimmune disease characterized by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness and swelling. RA causes limited range of motion and decreased function as a result of affected joints losing their shape and alignment. RA may affect up to 4.5 million people in the European Union.[vi],[vii]
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to extend and enhance human life. bms
ORENCIA® (abatacept) is a trademark of Bristol-Myers Squibb Company.
References
[i] DL Scott, et al. Rheumatology (Oxford) 2000;39:122-32.
[ii] J Kremer, R Westhovens, M Luggen, A Russell, R Aranda, J-C Becker, C Joshi, M Gandhi, MC Genovese. Long-term Efficacy and Safety of Abatacept Through 3 Years of Treatment in Rheumatoid Arthritis Patients in the AIM and ATTAIN Trials. Oral presentation at: annual meeting of the American College of Rheumatology, Boston, Massachusetts, Thursday, November 8, 2:30 p.m. - 4:00 p.m.
[iii] J Kremer, H Genant, L Moreland, A Russell, P Emery, C Abud-Mendoza, J Szechinski, T Li, Z Ge, JC Becker, R Westhovens. Effects of Abatacept in Patients with Methotrexate-Resistant Active Rheumatoid Arthritis: A Randomized Trial. Ann Intern Med. 2006; 144:865-876.
[iv] J Kremer, H Genant, W Moreland, A Russell, P Emery, C Abud-Mendoza, J Szechi?„ski, T Li, Teng, J Becker, R Westhovens. Results of a two-year follow up study of patients with rheumatoid arthritis who received a combination of abatacept and methotrexate. Arthritis Rheum. 2008 Apr;58(4):953-963.
[v] Simon T et al. Ann Rheum Dis 2006;65(Suppl II):489
[vi] epp.eurostat.ec.europa.eu/cache/ITY_OFFPUB/KS-SF-07-041/EN/KS-SF-07-041-EN.PDF accessed 23-05-08.
[vii] ec.europa.eu/health/ph_information/dissemination/diseases/musculo_en.htm accessed 23-05-08.
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