October 27, 2008
Study Results Demonstrate More Patients With Early Erosive Rheumatoid Arthritis Treated With ORENCIA(R) (Abatacept) and Methotrexate (MTX) Achieved DAS28 (CRP)-Defined Remission Compared to MTX Alone
Bristol-Myers Squibb Company (NYSE: BMY) today announced results from a Phase IIIb study in adult patients with early moderate-to-severe erosive rheumatoid arthritis (RA) who had never received previous methotrexate (MTX) treatment. This study showed that ORENCIA(R) (abatacept) in combination with MTX had significantly more patients achieve a Disease Activity Score 28 using C-reactive protein (DAS28 (CRP))-defined remission, compared with MTX plus placebo (PBO) (41.4 percent versus 23.3 percent, respectively; p-value less than 0.001). The safety profile of ORENCIA in combination with MTX was similar to that of MTX plus PBO. These results were presented today at the American College of Rheumatology (ACR) Annual Scientific Meeting in San Francisco.
In this randomized, double-blind, Phase IIIb study, patients had moderate-to-severe RA with a mean duration of RA of seven months and existing erosive disease. Additionally, all subjects were positive for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) antibodies, suggestive of a poor prognosis for their RA."The presence of erosions and certain biomarkers, particularly anti-CCP antibodies, early in the course of rheumatoid arthritis indicates a poor prognosis," said study lead investigator Rene Westhovens, M.D., Ph.D., Department of Rheumatology, Katholieke Universiteit Leuven, Belgium. "Identifying therapies that have significant impact early in the disease progression is critical to effectively treating this patient population."
"Bristol-Myers Squibb is committed to advancing treatment options for individuals with rheumatoid arthritis," said Brian Daniels, M.D., rheumatologist and senior vice president, Global Development & Medical Affairs, Bristol-Myers Squibb. "These results provide important insight into ORENCIA and its utility in the treatment of patients with early erosive RA."
Study Design and Findings
In this study, 509 MTX-naive individuals with early erosive RA who were positive for RF (96 percent), anti-CCP antibodies (92 percent) or both (89 percent), and had evidence of joint erosion in hands, wrists or feet, were randomized to receive either combination therapy of ORENCIA(R) (abatacept) plus MTX (n=256) or MTX plus PBO (MTX alone, n=253). ORENCIA was administered at a dose approximating 10 mg/kg based on weight range, and MTX was initiated at 7.5 mg/week and titrated to 20 mg/week by Week 8. The mean dose of MTX was 18.1 and 19.0 mg/week for ORENCIA plus MTX and MTX alone, respectively, at Year 1.
The primary endpoints of this study were DAS28 (CRP)-defined remission (DAS28 (CRP) less than 2.6) and joint damage progression measured using the Genant-modified Total Sharp Score, which uses X-ray to measure change at Year 1. Secondary endpoints included the number of patients who achieved an ACR 50 percent response criteria score and the number of patients who achieved a major clinical response, defined as achieving an ACR 70 percent response criteria score for six consecutive months. Safety was assessed throughout.
At baseline, patients had a mean duration of disease of 6.5 months and a baseline DAS28 (CRP) of 6.3. Of the 256 patients treated with ORENCIA plus MTX and the 253 patients treated with MTX alone, 90.6 percent and 89.7 percent completed Year 1, respectively. At Year 1, significantly more patients receiving ORENCIA plus MTX achieved DAS28 (CRP)-defined remission compared to those receiving MTX alone (41.4 percent versus 23.3 percent, respectively; p-value less than 0.001).
Significantly more patients taking ORENCIA plus MTX reached an ACR 50 score compared to those taking MTX alone (57.4 percent versus 42.3 percent; p-value less than 0.001). In addition, there was a significant difference between the patients taking ORENCIA plus MTX versus those taking MTX alone who achieved a major clinical response (27.3 percent versus 11.9 percent, respectively; p-value less than 0.001). The mean change in the Genant-modified Total Sharp Score from baseline was 0.63 for patients receiving ORENCIA plus MTX, compared to 1.06 for those receiving MTX alone (p-value equal to 0.04).
There were no discontinuations due to lack of efficacy in the ORENCIA plus MTX group compared to 3.2 percent of those taking MTX alone. Discontinuations due to adverse events were 3.1 percent in the ORENCIA plus MTX group versus 4.3 percent of those taking MTX alone. Serious adverse events occurred in 7.8 percent of patients taking ORENCIA plus MTX and 7.9 percent of patients taking MTX alone. Adverse events occurred in 84.8 and 83.4 percent of patients taking ORENCIA(R) (abatacept) plus MTX and MTX alone, respectively. Serious infections occurred in five (2 percent) ORENCIA plus MTX-treated patients and five (2 percent) patients who received MTX alone. Acute infusion reactions, which were mostly mild or moderate, occurred in 16 (6.3 percent) ORENCIA plus MTX-treated patients versus five (2 percent) patients who received MTX alone. One malignancy was reported in the ORENCIA plus MTX group and was considered unlikely to be related to study medication by the investigator.
About ORENCIA(R) (abatacept)
ORENCIA is a prescription medicine that is used to treat adults with moderate to severe RA including those who have not been helped enough by other medicines for RA. ORENCIA may prevent further damage to bones and joints, and may help the individual's ability to perform daily activities. In adults, ORENCIA may be used alone or with disease-modifying anti-rheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists.
ORENCIA also reduces signs and symptoms in children and adolescents six years of age and older with moderate to severe polyarticular juvenile idiopathic arthritis (JIA). In children and adolescents, ORENCIA may be used alone or with MTX.
ORENCIA should not be used with TNF antagonists and is not recommended for use with other biologic RA therapy, such as anakinra.
About Rheumatoid Arthritis
Rheumatoid arthritis is a systemic,(1 )chronic, autoimmune disease characterized by inflammation in the lining of joints (or synovium), causing joint damage with chronic pain, stiffness, swelling and fatigue.(2) RA causes limited range of motion and decreased function as a result of affected joints losing their shape and alignment.(3)
RA affects about one percent of the world's population,(4) including more than one million people in the United States.(1) The condition is more common in women than in men, who account for 75 percent of patients diagnosed with RA.(2) ORENCIA is one treatment option indicated in adult patients with moderately to severely active RA. ORENCIA may be used as monotherapy or concomitantly with DMARDs other than tumor-necrosis factor (TNF) antagonists. ORENCIA is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.
Important Safety Information About ORENCIA(R) (abatacept)
Before receiving treatment with ORENCIA, a lyophilized powder for intravenous infusion, individuals should tell their doctor about all their medical conditions, including if they have any kind of infection even if it is small (such as an open cut or sore) or an infection that is in the whole body (such as the flu) or have an infection that will not go away or a history of infections that keep coming back. People should tell their doctor if they have had tuberculosis (TB), a positive skin test for TB, or recent close contact with someone who has had TB. If symptoms of TB occur (a dry cough that doesn't go away, weight loss, fever, night sweats), they should call their doctor right away. Before starting treatment with ORENCIA, a doctor may examine the person for TB or perform a skin test.
Individuals who have or have had viral hepatitis should tell their doctor. The doctor may want to examine them for hepatitis before using ORENCIA. People should inform their doctor if they have a history of chronic obstructive pulmonary (lung) disease (COPD). In addition, individuals should let their doctor know if they are scheduled to have surgery, or recently received a vaccination or are scheduled for any vaccination.
People should also let their doctor know if they are allergic to any of the following ingredients in ORENCIA: abatacept, maltose, monobasic sodium phosphate, or sodium chloride for administration. People who have diabetes and use a blood glucose monitor to check sugar levels should tell their doctor. The infusion of ORENCIA contains maltose, a sugar that can give falsely high blood glucose readings with some monitors on the day of the infusion. The doctor may tell them to use a different way to monitor their blood sugar levels.
Women who are pregnant, planning to become pregnant, or are thinking about becoming pregnant should tell their doctor. It is not known if ORENCIA can harm your unborn baby. Women who are breast feeding should also inform their doctor. They will need to decide to either breast-feed or receive treatment with ORENCIA, but not both.
People taking ORENCIA should notify their doctor if they are taking any other kinds of medicine, including prescription and nonprescription medicines, vitamins, and herbal supplements. It is also important for individuals to tell their doctor if they are taking other biologic medicines to treat RA or JIA such as: Enbrel(R)(etanercept), Humira(R) (adalimumab), Remicade(R) (infliximab), Kineret(R) (anakinra) or Rituxan(R) (rituximab). You may have a higher chance of getting a serious infection if you take ORENCIA with other biologic medicines.
Possible Side Effects of ORENCIA(R)(abatacept)
ORENCIA can cause serious side effects including serious infections. People receiving ORENCIA have a higher chance of getting infections including pneumonia, and other infections caused by viruses, bacteria, or fungi. Individuals should call their doctor immediately if they feel sick or get any of the following signs of infection: fever, feel very tired, cough, feel flu-like, or warm, red or painful skin.
Allergic reactions can happen on the day of treatment or the day after receiving ORENCIA. People should tell their doctor or get emergency medical help right away if they have hives, swollen face, eyelids, lips, tongue, throat, or trouble breathing.
Certain kinds of cancer (malignancies) have been reported in people receiving ORENCIA. It is not known if ORENCIA increases the chance of getting certain kinds of cancer.
Individuals should not receive ORENCIA with certain types of vaccines. ORENCIA may cause some vaccinations to be less effective.
Respiratory problems in people with COPD. Individuals may get certain respiratory problems more often if they receive ORENCIA and have COPD, including: worsened COPD, pneumonia, cough, or trouble breathing.
The more common side effects with ORENCIA in both adults and children are headache, upper respiratory tract infection, sore throat, and nausea. Other side effects in children may include diarrhea, cough, fever, and abdominal pain.
Please see accompanying Full Prescribing Information, or visit www.ORENCIA.com or www.bms.com.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to extend and enhance human life. For more information visit www.bms.com.
(1) Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, Liang MH, Kremers HM, Mayes MD, Merkel PA, Pillemer SR, Reveille JD, Stone JH; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;Jan;58(1):15-25.
(2) American College of Rheumatology, Patient Education, Rheumatoid Arthritis. Available at: http://www.rheumatology.org/public/factsheets/ra_new.asp?aud=pat2. Accessed May 2006.
(3) National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health. U.S. Department of Health and Human Services. Rheumatoid Arthritis. May 2004.
(4) Lee DM, Weinblatt ME. Rheumatoid Arthritis. The Lancet. 2001;358:903-11.