WASHINGTON, Nov. 14 /PRNewswire-FirstCall/ -- Bristol-Myers Squibb Company today announced results from a study providing further evidence of the efficacy, safety and durability of response of ORENCIA(R) (abatacept) through 12 months in adults with moderate to severe rheumatoid arthritis (RA) who have had an inadequate response to methotrexate (MTX). At six months, the data demonstrated that the efficacy, as measured by Disease Activity Score-28 (DAS28), of ORENCIA or REMICADE(R)(infliximab) was superior to placebo. At 12 months, ORENCIA showed both a durable response as measured by DAS28 (mean change at six months: -2.53; mean change at twelve months: -2.88) and a more favorable safety profile as demonstrated by fewer serious infections, acute infusional events and discontinuations due to adverse events (AEs) than REMICADE through 12 months. These data were presented at a late-breaking session of the 2006 American College of Rheumatology (ACR) Annual Scientific Meeting.
Details of the Trial
This double-blind, double-dummy, placebo-controlled trial randomized participants with moderate to severe RA who have had an inadequate response to MTX and no prior anti-TNF therapy. Participants were randomized to one of three treatment groups: ORENCIA (approximately 10 mg/kg) every four weeks (n=156) for 12 months, REMICADE (3 mg/kg) every eight weeks (n=165) for 12 months, or placebo every four weeks (n=110) for six months. Participants randomized to placebo were switched to ORENCIA after six months, but were not included in the 12-month analysis. The REMICADE dosage reflects the global dose for the treatment of RA. It is the recommended initial dose in the United States. The ORENCIA dosage is the approved or recommended dosage globally. All groups continued to receive MTX through 12 months. After the first 6 months, additional oral DMARD therapy could be added as determined by the investigator.
The primary endpoint of the trial was mean reduction in DAS28 in the group receiving ORENCIA vs. placebo at six months. DAS28 is a standard score used to measure the disease activity of RA. The secondary objectives presented included mean reduction in DAS28 with REMICADE vs. placebo at six months, mean reduction in DAS28 with ORENCIA and REMICADE at one year and ACR 20, 50 and 70 scores through one year for ORENCIA and REMICADE.
At baseline, clinical characteristics and demographics were similar between the three groups, with mean scores of approximately 1.7 for Health Assessment Questionnaire Disability Index (HAQ-DI) and 6.8 for DAS28. Changes in DAS28 scores at six months compared to baseline were -2.53 and -1.48 for ORENCIA and placebo, respectively (p-value less than 0.001). Changes in DAS28 scores at six months compared to baseline were -2.25 and -1.48 for REMICADE and placebo, respectively (p-value less than 0.001).
At 12 months, the changes from baseline in DAS28 were -2.88 for ORENCIA and -2.25 for REMICADE. Percent of participants with DAS28 improvement of greater than or equal to 1.2 were 86 for ORENCIA and 75 for REMICADE. Percent of participants with DAS28 scores less than or equal to 3.2 were 35.3 for ORENCIA and 22.4 for REMICADE.
At 12 months, the ACR 20, 50 and 70 scores were 72.4 percent, 45.5 percent and 26.3 percent, respectively, for ORENCIA and 55.8 percent, 36.4 percent and 20.6 percent, respectively, for REMICADE.
Safety and tolerability of ORENCIA and REMICADE were assessed at each visit. At six months, the frequency of serious adverse events (SAEs) for the ORENCIA, REMICADE and placebo groups were 5.1 percent, 11.5 percent and 11.8 percent, respectively. The frequency of AEs for the ORENCIA, REMICADE and placebo groups was 82.7 percent, 84.8 percent and 83.6 percent, respectively. Discontinuation due to AEs was 1.9 percent for ORENCIA, 4.8 percent for REMICADE and 0.9 percent for placebo.
Through 12 months, ORENCIA had fewer serious infections, acute infusional events and discontinuations due to AEs than REMICADE. The frequency of SAEs was 9.6 percent for ORENCIA and 18.2 percent for REMICADE. The frequency of discontinuations due to SAEs was 2.6 percent for ORENCIA and 3.6 percent for REMICADE. The frequency of AEs for the ORENCIA and REMICADE groups was 89.1 percent and 93.3 percent, respectively. Discontinuation due to AEs was 3.2 percent for ORENCIA and 7.3 percent for REMICADE. Infections reported as SAEs in the ORENCIA group were 1.9 percent and 8.5 percent in the REMICADE group. The frequency of acute infusional AEs was 7.1 percent in patients receiving ORENCIA and 24.8 percent in patients receiving REMICADE.
Important Safety Information about ORENCIA
Before receiving treatment with ORENCIA, individuals should notify their healthcare providers if they currently are receiving treatment with a TNF antagonist (e.g., Enbrel(R), Humira(R), REMICADE(R)) or Kineret(R) to treat rheumatoid arthritis (RA). These individuals may have a higher risk of experiencing serious infections if they receive treatment with ORENCIA together with other biologic medications for RA. People receiving treatment with ORENCIA also should notify their healthcare providers if they are taking any other medications including hormones, over-the-counter medicines, vitamins, supplements or herbal products.
Individuals should discuss their risks of infection with their healthcare providers. People should inform their healthcare providers of any infections that they may have, including infections in a specific location in or on the body (such as an open cut or sore), or an infection that involves the whole body (such as the flu), as these types of infection could put individuals at risk for serious side effects from ORENCIA. Additionally, individuals should alert their healthcare providers if they have infections that won’t heal or have histories of recurring infections.
People who have had tuberculosis (TB), have had a positive skin test for TB, or who recently have been in close contact with someone who has had TB should inform their healthcare providers. If these individuals develop any of the symptoms of TB (i.e., a dry cough that does not improve, weight loss, fever, night sweats, etc.), they should notify their healthcare providers immediately. Before initiating treatment with ORENCIA, healthcare providers may examine individuals for TB or perform a skin test to determine the presence of TB.
Additionally, individuals should inform their healthcare providers if they are scheduled to have surgery, or if they recently received a vaccination or are scheduled to receive any vaccinations. Before receiving ORENCIA, people should alert their healthcare providers if they have a history of chronic obstructive pulmonary (lung) disease (COPD), as taking ORENCIA may cause their COPD symptoms to worsen.
Pregnant women, women planning to get pregnant or women thinking about becoming pregnant should inform their healthcare providers prior to starting treatment with ORENCIA. It is not known if exposure to ORENCIA(R) (abatacept) poses risks to unborn infants. Women should alert their healthcare providers if they are breastfeeding, as these individuals will need to decide either to breastfeed or to receive treatment with ORENCIA, but not both.
Like all medicines that affect the immune system, ORENCIA can cause serious side effects, including serious infections, allergic reactions and malignancies. Individuals receiving treatment with ORENCIA are at increased risk for developing infections including pneumonia and other infections caused by viruses, bacteria or fungi. Individuals should immediately contact their healthcare providers if they feel sick or experience any infection during treatment with ORENCIA. Allergic reactions to ORENCIA therapy may also occur. These reactions are usually mild or moderate, generally occur within the first 24 hours of an infusion and can include hives, swollen face, eyelids, lips, tongue, throat or difficulty breathing. There have been two serious allergic reactions reported in individuals following ORENCIA infusion. There have also been cases of certain kinds of cancer in individuals receiving ORENCIA. In clinical trials, the frequency of malignancies for ORENCIA was 1.3 percent. The role of ORENCIA in the development of cancer is not known.
The more common side effects with ORENCIA are headache, upper respiratory tract infection, sore throat and nausea.
For full prescribing information, please visit www.ORENCIA.com or www.bms.com.
Dosing and Administration
ORENCIA is administered as a 30-minute intravenous infusion at a fixed dose based on body weight range approximating 10 mg/kg at day 0, 2 weeks, 4 weeks, and every 4 weeks thereafter. Acute infusion-related reactions were experienced in nine percent of people treated with ORENCIA and in six percent of people treated with placebo. According to the full prescribing information, the most frequently reported infusion-related adverse events (1 percent to 2 percent) were dizziness, headache, and hypertension. In pivotal studies, premedications were not required. However, appropriate medical support measures for the treatment of hypersensitivity reactions should be available for immediate use in the event of a reaction.
About ORENCIA
ORENCIA is indicated for reducing signs and symptoms, inducing major clinical response, slowing 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.
ORENCIA, a selective co-stimulation modulator of a signal required for full T cell activation, was discovered and developed by Bristol-Myers Squibb Company.
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 affects about 1 percent of the world’s population, including more than two million people in the United States. The condition is more common in women, who account for 70 percent of patients diagnosed with RA.
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.
REMICADE(R) (infliximab) is a registered trademark of Johnson & Johnson.
Bristol-Myers Squibb Company
CONTACT: Media, Sarah Koenig, +1-609-252-4145, Mobile +1-908-397-5379,sarah.koenig@bms.com, or Tony Plohoros, +1-212-546-4379,tony.plohoros@bms.com; or Investors, John Elicker, +1-212-546-3775,john.elicker@bms.com, or Blaine Davis, +1-212-546-4631,blaine.davis@bms.com
Web site: http://www.bms.com//
